From owner-sci-resources@net.bio.net Sun Aug 01 23:00:00 1993 Path: biosci!NET.BIO.NET!kristoff From: kristoff@NET.BIO.NET (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NSF - Summary of new documents on STIS - 1 August 1993 Message-ID: Date: 2 Aug 93 20:54:54 GMT Sender: kristoff@net.bio.net Distribution: bionet Lines: 82 Approved: sci-resources-moderator@net.bio.net ** NEW DOCUMENTS ON STIS ** Document Type: Dir of Awards Title: NSF 93-59 -- ARCTIC SCIENCE, ENGINEERING, AND EDUCATION File size (bytes): 409276 STIS Filename: nsf9359 Document Type: Program Guideline Title: NSF 93-66 -- Earth Science Research at the National Science Foundation File size (bytes): 48602 STIS Filename: nsf9366 Document Type: Recruit Title: Program Assistant (Office Automation) File size (bytes): 4866 STIS Filename: vgs9381 ------------------------------------------------------------------------ ** UPDATES TO EXISTING STIS DOCUMENTS ** Document Type: Phone Book Title: NSF Alphabetical Listing File size (bytes): 91127 STIS Filename: phnalpha Title: NSF Organizational Directory File size (bytes): 98927 STIS Filename: phnorg Document Type: Recruit Title: Clerical and Administrative Support Positions File size (bytes): 4118 STIS Filename: vgs9373 ------------------------------------------------------------------------ ** FOR YOUR REFERENCE ** ------------------------------------------------------------------------ HOW TO OBTAIN DOCUMENTS The above files can be retrieved in electronic form using the STIS system. If you don't know how to use STIS, send an E-mail message to stisinfo@nsf.gov (Internet) or stisinfo@NSF (BITNET). You will receive a copy of the STIS flyer via E-mail. If you are already using STIS, you can use the information above to retrieve these files: Documents via E-mail: Send a message to stisserv@nsf.gov (Internet) or stisserv@NSF (BITNET). Use the "STIS Filename" shown above in the "get" command. For example, to retrieve vgs9373, the text of your message should be as follows: get vgs9373 Anonymous FTP: FTP to stis.nsf.gov. Use the "STIS Filename" shown above to retrieve a file. For example, to retrieve vgs9373, you would enter: ftp> get vgs9373 WAIS or Gopher: Do a word search on the filename as shown in the summary. If you want a *printed* copy of a document: Send your name and postal mailing address, and the document title and number to "firstop@nsf.gov" (Internet) or "firstop@nsf" (BITNET). If you have problems with the above procedures: Send a message to "stis@nsf.gov" (Internet) or "stis@NSF" (BITNET). From owner-sci-resources@net.bio.net Thu Aug 05 23:00:00 1993 Path: biosci!net.bio.net From: kristoff@net.bio.net (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 22, no. 28, pt. 1, 6 August 1993 Message-ID: Date: 6 Aug 93 03:24:05 GMT Sender: kristoff@net.bio.net Lines: 1187 Approved: biosci-moderator@net.bio.net NOTE: The NIH Guide may be split into more than one mail message to avoid truncation during e-mail distribution. The first message always begins with the RFP/RFA summary sections followed by the appended texts of the full RFP/RFAs. ---------------------------------------------------------------------- $$XID NIHGUIDE 19930806 V22N28 P1O1 ************************************ X-comment: RFAs described: HD-94-006, CA-93-037, AI-93-017, AI-93-012 NIH GUIDE - Vol. 22, No. 28 - August 6, 1993 $$INDEX BEGIN ******************************************************* NOTICES OF AVAILABILITY (RFPs AND RFAs) $$INDEX R1 11/19/93 ************************************************* HUMAN FETAL TISSUE CHARACTERIZATION FOR TRANSPLANTATION (RFA HD-94-006) National Institute of Child Health and Human Development National Institute of Diabetes and Digestive and Kidney Diseases National Institute of Neurological Disorders and Stroke INDEX: CHILD HEALTH, HUMAN DEVELOPMENT; DIABETES, DIGESTIVE, KIDNEY DISEASES; NEUROLOGICAL DISORDERS, STROKE $$INDEX R2 11/23/93 ************************************************* ROLE OF THE MICROENVIRONMENT IN BREAST AND PROSTATE CANCER (RFA CA-93-037) National Cancer Institute INDEX: CANCER $$INDEX R3 11/24/93 ************************************************* MULTICOMPONENT VACCINE DEVELOPMENT (RFA AI-93-017) National Institute of Allergy and Infectious Diseases INDEX: ALLERGY, INFECTIOUS DISEASES $$INDEX R4 12/08/93 ************************************************* IMMUNE RECONSTITUTION OF HIV-INFECTED INDIVIDUALS (RFA AI-93-012) National Institute of Allergy and Infectious Diseases National Institute of Diabetes and Digestive and Kidney Diseases INDEX: ALLERGY, INFECTIOUS DISEASES; DIABETES, DIGESTIVE, KIDNEY DISEASES ERRATUM $$INDEX E1 09/17/93 ************************************************* CENTERS FOR AIDS RESEARCH/CORE SUPPORT GRANT (CFAR/CSG) (RFA AI-93- 014) National Institute of Allergy and Infectious Diseases National Institute of Mental Health INDEX: ALLERGY, INFECTIOUS DISEASES; MENTAL HEALTH This publication is available electronically to institutions via BITNET or INTERNET and is also on the NIH GOPHER. Alternative access is through the NIH Grant Line using a personal computer (data line 301/402-2221). Contact Dr. John James at 301/594-7270 for details. $$INDEX END ********************************************************* NOTICES OF AVAILABILITY (RFPs AND RFAs) $$R1 BEGIN HD-94-006 FULL-TEXT ************************************** HUMAN FETAL TISSUE CHARACTERIZATION FOR TRANSPLANTATION NIH GUIDE, Volume 22, Number 28, August 6, 1993 RFA AVAILABLE: HD-94-006 P.T. 34; K.W. 0705035, 0745065, 0780005 National Institute of Child Health and Human Development National Institute of Diabetes and Digestive and Kidney Diseases National Institute of Neurological Disorders and Stroke Letter of Intent Receipt Date: October 1, 1993 Application Receipt Date: November 19, 1993 THIS IS A NOTICE OF AVAILABILITY OF A REQUEST FOR APPLICATIONS (RFA); IT IS ONLY AN ABSTRACT OF THE RFA. POTENTIAL APPLICANTS MUST REQUEST THE COMPLETE RFA, WHICH CONTAINS ESSENTIAL INFORMATION FOR THE PREPARATION OF AN APPLICATION, FROM THE CONTACT LISTED IN "INQUIRIES," BELOW. FAILURE TO FOLLOW THE INSTRUCTIONS IN THE COMPLETE RFA MAY RESULT IN AN INCOMPLETE APPLICATION, WHICH WILL BE RETURNED TO THE APPLICANT WITHOUT REVIEW. PURPOSE This RFA has been developed to encourage research on the standards and methods for identifying and characterizing optimal human fetal tissue for use in transplantation therapy. Joint funding by the National Institute of Child Health and Human Development (NICHD), the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and the National Institute of Neurological Disorders and Stroke (NINDS) reflects the extent of interest in evaluating human fetal tissues and their biological potentials. Attention should be given to proper collection, processing, culturing and preserving these tissues to assure highest quality control. This research should consider addressing methods for acquisition, establishing morphologic status, determining developmental age and viability, assessing sterility and genetic normality, preserving by cryopreservation, and establishing cell lines. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This RFA, Human Fetal Tissue Characterization for Transplantation, is related to the priority areas of maternal and infant health, and diabetes and chronic disabling conditions. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1), through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories and units of state and local governments. Applications from investigators who are minority individuals and women are encouraged. MECHANISM OF SUPPORT This RFA solicits applications that will be awarded as NIH research project grants (R01s). The duration of these awards is to be four years. This announcement is for a single competition and the application receipt date is November 19, 1993. FUNDS AVAILABLE It is anticipated that up to six grants will be awarded under this program, contingent upon receipt of a sufficient number of meritorious applications and the availability of funds. To fund these awards, $1,000,000 has been set aside for the direct costs in the first year. RESEARCH OBJECTIVES The use of human fetal tissue transplants has been advocated for several years as a means of treating a number of devastating diseases. Fetal tissue transplants may allow replacement of tissues and cell products that have been damaged, destroyed, or that never developed properly due to disease or a genetic disorder. These maladies are life threatening unless intervention is instituted. Childhood diseases such as inborn errors of metabolism, immune deficiencies and other entities are being considered for very early treatment using fetus-to-fetus transplants. Diseases such as insulin-dependent diabetes mellitus (IDDM) and Parkinson's Disease are also prospective candidates for transplantation therapy. The results of the Diabetes Control and Complications Trial demonstrate the profound importance of glucose control in the prevention of Diabetic complications. Thus, transplantation therapy offers new avenue for tighter glucose control in IDDM patients. Initial results of surgical transplantation in Parkinson's Disease for a small number of cases hold considerable promise although more definitive study and evaluation are required. There is currently considerable interest in the therapeutic use of fetal tissues for the treatment of incurable and chronic diseases, both from the medical and the basic science community. Methods should be considered to optimize and standardize the handling and processing of fetal tissues as well as their preservation and storage. It is evident that better characterization of these more immature fetal tissues is required to assure optimal therapeutic results. Improved knowledge of the potential of these cells will define their roles in normal developmental processes based on their developmental age and biological potential, and will improve their usefulness in replacement therapy. Tissue Collection Appropriate collaboration with clinicians will be required to obtain necessary tissue in a timely fashion and collected in a manner suitable for the scheduled tissue processing. Accurate assessment of developmental age, gross examination of tissues, and grading of tissues for viability will also require a pathology/teratology assessment. In obtaining medical histories and serological screening of contributors of the products of conception for this research, appropriate informed consent must be obtained. Evaluation of pathogenic contaminants, cytogenetic studies and assessment of genetic mutations in at-risk specimens are research areas to be included. Applicants should be able to demonstrate immunologic and transplantation expertise and have available established tissue culture facilities with the expertise for growing, characterizing, cryopreserving and maintaining suitable fetal cell lines. Data Collection The data from these studies should be used to address the quality and efficacy of the tissues under investigation for transplantation therapy. This information should be applicable to the establishment of protocols and tissue processing innovations. SPECIAL REQUIREMENTS The fetal tissue acquisition and handling must comply with the regulations for Federal Funding of Fetal Tissue Transplantation Research as set forth in the NIH Guide for Grants and Contracts, Volume 22, Number 11, March 19, 1993. It is expected that at least two meetings per year in the Washington, DC area of the awardees, NIH staff, and NIH consultants, during both the first and subsequent years, will be required to assess progress and workscope. These meetings will be of benefit to the grantees and will allow them to address unforeseen difficulties, establish collaborative efforts and assess the schedule of progress. The grantees will retain primary authority and responsibility for the work. Funds for this travel should be requested in the application. STUDY POPULATIONS SPECIAL INSTRUCTIONS FOR INCLUSION OF MINORITIES IN CLINICAL RESEARCH STUDIES For projects involving clinical research, NIH requires applicants to give special attention to the inclusion of women and minorities in study populations. If women or minorities are not included in the study populations for clinical studies, a specific justification for this exclusion must be provided. Applications without such documentation will not be accepted for review. LETTER OF INTENT Prospective applicants are asked to submit, by October 1, 1993, a letter of intent that includes a descriptive title of the proposed research; the name, address, and telephone number of the Principal Investigator; the identities of other key personnel and participating institutions; and the number and title of the RFA in response to which the application may be submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information that it contains is helpful in planning for the review of applications. It allows NICHD, NIDDK, and NINDS staff to estimate the potential review workload and to avoid conflict of interest in the review. The letter of intent is to be sent to Dr. Delbert H. Dayton at the address listed under INQUIRIES. APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 9/91) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research and from the Office of Grants Information, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone (301) 594-7248. The RFA label available in the PHS 398 application form must be affixed to the bottom of the face page. Failure to use this label could result in delayed processing of an application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2a of the face page of the application form and the YES box checked. Submit a signed, typewritten original of the application, including the Checklist, and three signed, exact photocopies, in one package to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** At the time of submission, two additional copies of the application must also be sent to: Susan Streufert, Ph.D. Division of Scientific Review National Institute of Child Health and Human Development 6100 Executive Boulevard, Room 5E03 Bethesda, MD 20892 REVIEW CONSIDERATIONS Applications will be received by the NIH Division of Research Grants and reviewed for completeness. Incomplete applications will be returned to the applicant. NICHD, NIDDK, and NINDS staff will review the applications for responsiveness to the RFA. Applications judged to be nonresponsive will be returned. Responsive applications may be subjected to a triage by a peer-review group to determine the scientific merit relative to the other applications received in response to this RFA. NIH will withdraw from competition those applications judged to be noncompetitive and will notify the applicant and institutional official. Those applications judged to be competitive will be further evaluated for scientific/technical merit by a review group convened solely for this purpose by the Division of Scientific Review, NICHD. Following review by the Initial Review Group, applications will be evaluated by the appropriate assigned Advisory Councils for program relevance and policy issues before awards for meritorious applications are made. INQUIRIES Written and telephone inquiries concerning this RFA are welcome. Direct inquiries regarding programmatic issues, requests for the RFA, and address the letter of intent to: Delbert H. Dayton, M.D. Center for Research for Mothers and Children National Institute of Child Health and Human Development 6100 Executive Boulevard, Room 4B01 Bethesda, MD 20892 Telephone: (301) 496-5541 Joan T. Harmon, Ph.D. Division of Diabetes, Endocrinology and Metabolic Diseases National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 622 Bethesda, MD 20892 Telephone: (301) 594-7565 Eugene J. Oliver, Ph.D. Division of Demyelinating, Atrophic, and Dementing Disorders National Institute of Neurological Disorders and Stroke 7550 Wisconsin Avenue, Room 806 Bethesda, MD 20892 Telephone: (301) 496-1431 Direct inquiries regarding fiscal matters to: Ms. Mary Ellen Colvin Office of Grants and Contracts National Institute of Child Health and Human Development 6100 Executive Boulevard, Room 8A17 Bethesda, MD 20892 Telephone: (301) 496-1303 Ms. Betty E. Bailey Division of Extramural Activities National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 649 Bethesda, MD 20892 Telephone: (301) 594-7543 Mr. George Tucker Division of Extramural Activities National Institute of Neurological Disorders and Stroke 7550 Wisconsin Avenue, Room 1004 Bethesda, MD 20892 Telephone: (301) 496-9231 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance Nos. 93.847, 93.853, 93.854, and 93.865. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$R1 END ************************************************************ $$R2 BEGIN CA-93-037 FULL-TEXT ************************************** ROLE OF THE MICROENVIRONMENT IN BREAST AND PROSTATE CANCER NIH GUIDE, Volume 22, Number 28, August 6, 1993 RFA AVAILABLE: CA-93-037 P.T. 34; K.W. 0715036, 1002004, 1002008, 0760025 National Cancer Institute Letter of Intent Receipt Date: September 10, 1993 Application Receipt Date: November 23, 1993 THIS IS A NOTICE OF AVAILABILITY OF A REQUEST FOR APPLICATIONS (RFA); IT IS ONLY AN ABSTRACT OF THE RFA. POTENTIAL APPLICANTS MUST REQUEST THE COMPLETE RFA, WHICH CONTAINS ESSENTIAL INFORMATION FOR THE PREPARATION OF AN APPLICATION, FROM THE CONTACT LISTED IN "INQUIRIES," BELOW. FAILURE TO FOLLOW THE INSTRUCTIONS IN THE COMPLETE RFA MAY RESULT IN AN INCOMPLETE APPLICATION, WHICH WILL BE RETURNED TO THE APPLICANT WITHOUT REVIEW. PURPOSE The Cancer Biology Branch, Division of Cancer Biology, Diagnosis and Centers (DCBDC) at the National Cancer institute (NCI), in collaboration with the Chemical and Physical Carcinogenesis Branch, Division of Cancer Etiology (DCE), NCI, invites investigator-initiated research grant applications to elucidate the molecular interactions among the cell populations of human breast and prostatic cancer that contribute to malignant progression. New and experienced investigators in relevant fields and disciplines may apply for funds to pursue this research. The aim of this RFA is to foster application of recent advances in molecular and cellular biology, using appropriate model systems, to study the effects of tumor cell-stroma interactions relevant to tumor development and progression in human breast and prostatic tissues. A multidisciplinary approach involving interactions among basic and clinical scientists is encouraged. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This RFA, Role of the Microenvironment in Breast and Prostate Cancer, is related to the priority area of cancer. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Research grant applications may be submitted by domestic and foreign for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT Support of this RFA will be by National Institutes of Health (NIH) individual research project grants (R01). Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. The total project period for applications submitted in response to the present RFA may not exceed four years. Awards will be administered under PHS grants policy as stated in Public Health Service Grants Policy Statement, DHHS Publication No. (OASH) 90-50,000, revised October 1, 1990. The anticipated award date is July 1, 1994. This RFA is a one-time solicitation. Future unsolicited competing continuation applications will compete with all investigator-initiated applications and be reviewed according to the customary NIH peer review procedures. FUNDS AVAILABLE Approximately $2,000,000 in total costs per year for up to four years will be committed to fund applications submitted in response to this RFA. It is anticipated that up to twelve awards will be made. This level of support is dependent on the receipt of a sufficient number of applications of high scientific merit. Although this program is provided for in the financial plans of the NCI, awards pursuant to this RFA are contingent upon the availability of funds for this purpose. RESEARCH OBJECTIVES This RFA is intended to encourage a variety of investigator-initiated research projects to use appropriate model systems that take into consideration the highly interactive environment of the tumor cells, as well as the contributions of the tumor and host cells to the growth and metastatic spread of breast or prostatic carcinomas. It is also important to delineate the genetic and environmental factors involved in stromal-epithelial interactions which are relevant to malignant progression of hormonally regulated tumors. It may include collaborations among basic and clinical scientists and should embrace an array of molecular and cellular approaches. Evidence of the establishment of reliable tumor cell systems or relevant tumor models should be included in the application. Applications that propose to explore interactions of the stroma with only normal epithelium will not be considered responsive to the RFA. STUDY POPULATIONS SPECIAL INSTRUCTIONS FOR INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDIES For projects involving clinical research, NIH requires applicants to give special attention to the inclusion of minorities in study populations. If minorities are not included in the study populations for clinical studies, a specific justification for this inclusion must be provided. Applications without such documentation will not be accepted for review. LETTER OF INTENT Prospective applicants are asked to submit, by September 10, 1993, a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, the identities of other key personnel and participating institutions, and the number and title of the RFA in response to which the application may be submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information that it contains is helpful in planning for the review of applications. It allows NCI staff to estimate the potential review workload and to avoid conflict of interest in the review. The letter of intent is to be sent to Dr. Suresh Mohla at the address listed under INQUIRIES. APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 9/91) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research and from the Office of Grants Information, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892-9912, telephone 301/594-7248. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed by the Division of Research Grants (DRG) staff for completeness. Incomplete applications will be returned to the applicant without further consideration. Complete applications will be evaluated by NCI program staff to determine if they are responsive to the program requirements and criteria stated in this RFA. Applications may receive a preliminary scientific peer review (triage) by an NCI peer review group on the basis of relative competitiveness. The NIH will withdraw from further competition those applications judged to be non- competitive for award and notify the applicant Principal Investigator and institutional official. Those applications judged to be responsive and competitive will be further evaluated according to the review criteria stated below for scientific and technical merit by an appropriate peer review group convened by the Division of Extramural Activities, NCI. The second level of review by the National Cancer Advisory Board considers the special needs of the Institute and the priorities of the National Cancer Program. Review criteria for evaluating the scientific merit of this RFA include: o extent to which the proposed research addresses the goals of the RFA o scientific and technical significance and originality of proposed research o appropriateness and adequacy of the experimental approach, and potential relevance of the model system to human breast or prostate cancer o qualifications and research experience of the Principal Investigator and staff o appropriateness of the proposed budget and duration in relation to the proposed research INQUIRIES Written and telephone requests for the RFA and the opportunity to clarify any issues or questions from the potential applicants are welcome. Direct requests for the RFA, inquiries regarding programmatic issues, and address the letter of intent to: Dr. Suresh Mohla Division of Cancer Biology, Diagnosis, and Centers National Cancer Institute Executive Plaza North, Room 505 Bethesda, MD 20892 Telephone: (301) 496-7028 Direct inquiries regarding fiscal matters to: Mr. Robert Hawkins Grants Management Branch National Cancer Institute Executive Plaza South, Room 243 Bethesda, MD 20892 Telephone: (301) 496-7800 ext. 13 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.396, Cancer Biology. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health $$R2 END ************************************************************ $$R3 BEGIN AI-93-017 FULL-TEXT ************************************** MULTICOMPONENT VACCINE DEVELOPMENT NIH GUIDE, Volume 22, Number 28, August 6, 1993 RFA AVAILABLE: AI-93-017 P.T. 34; K.W. 0740075, 1002045, 0710070 National Institute of Allergy and Infectious Diseases Letter of Intent Receipt Date: October 1, 1993 Application Receipt Date: November 24, 1993 THIS IS A NOTICE OF AVAILABILITY OF A REQUEST FOR APPLICATIONS (RFA); IT IS ONLY AN ABSTRACT OF THE RFA. POTENTIAL APPLICANTS MUST REQUEST THE COMPLETE RFA, WHICH CONTAINS ESSENTIAL INFORMATION FOR THE PREPARATION OF AN APPLICATION, FROM THE CONTACT LISTED IN "INQUIRIES," BELOW. FAILURE TO FOLLOW THE INSTRUCTIONS IN THE COMPLETE RFA MAY RESULT IN AN INCOMPLETE APPLICATION, WHICH WILL BE RETURNED TO THE APPLICANT WITHOUT REVIEW. PURPOSE The Division of Microbiology and Infectious Diseases of the National Institute of Allergy and Infectious Diseases (NIAID) announces the availability of an RFA for research that will lead to the design of new innovative approaches for the synthesis and development of combination vaccines. The objective of this project is to examine basic research approaches toward the development of multivalent vaccines which would provide safe and long lasting immunity to multiple agents while providing maximum safety, immunogenicity, and efficacy in the fewest doses possible. Multicomponent (multivalent) combination vaccines containing antigens to viral and/or bacterial components provide many distinct advantages over conventional vaccines and allow for the introduction of "disease-specific", "age-specific" and "duration-specific" designer vaccines. The development of combination vaccines will greatly facilitate the implementation of the universal vaccination programs required to bring under control serious infectious diseases worldwide. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This RFA, Multicomponent Vaccine Development, is related to the priority area of immunization and infectious diseases. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT Awards made under this RFA will use the National Institutes of Health (NIH) individual research project grant (R01). Responsibility for the planning, direction and execution of the proposed project will be solely that of the applicant. The total project period for applications submitted by domestic institutions in response to the present RFA may not exceed four years; the total project period for applications submitted by foreign institutions may not exceed three years. The earliest possible award date is July 1, 1994. Applicants are encouraged to coordinate, through the use of consortium arrangements or subcontracts, integrated approaches with individuals or institutions having relevant reagents and expertise in their use, demonstrated ability in a particular area of relevant research, or access to relevant patient populations so as to accelerate technical progress and clinical development of promising therapies. Because the nature and scope of the research proposed in response to this RFA may vary, it is anticipated that the amounts of the awards will vary also. This RFA is a one-time solicitation. Future competing continuation applications will compete with all unsolicited investigator-initiated applications and be reviewed by an appropriate study section according to customary NIH referral and peer review procedures. FUNDS AVAILABLE The estimated level of support (total direct and indirect costs) for the entire program for the first year is $ 1.5 million. The NIAID anticipates making a minimum of four new awards. RESEARCH OBJECTIVES The ability to selectively eradicate various childhood diseases through the development of immunization programs that incorporate new emerging technologies for the creation of improved, safe and efficacious vaccines is a primary aim of NIAID and also the Children's Vaccine Initiative (CVI) Program. A major concept advanced by this program is the idea of providing fewer doses of vaccine to help facilitate delivery and broaden the coverage of immunization. Barriers to the development of multicomponent vaccines are not merely technological, but will require scientific advances in a number of areas in basic science and infectious diseases. One of the most complex, but basic issues that needs to be resolved is the problem of incorporating fundamentally different products or antigens into a single matrix. For example, at this time we are not able to mix attenuated live agents with killed agents such as oral polio vaccine and Haemophilus influenzae type b conjugate vaccines. The current proposed approach for making combination vaccines is restricted to mixing either a series of antigens or other "like" immunogens in a single dose. Additional research is needed to better understand the immunologic basis for incompatibility/compatibility among disparate antigens. Furthermore, the development of vaccines to diseases that produce systemic infection may differ significantly from those in which infection occurs at mucosal or other epithelial surfaces. One of the many new vaccine strategies focuses on the identification of protective epitopes against specific organisms. Often these organisms represent only one of the many pathogens associated with the disease state. One such example is the complex etiology of pneumonia. A significant aspect of this new vaccine strategy would be to develop vaccines composed of relevant portions of multiple pathogens associated with a particular disease (e.g., pneumonia), or a particular need (e.g., children). The development of large vector systems with ability to express multiple foreign genes using a single injection, or newly constructed novel attenuated viruses with defined genetic mutations may provide opportunities to evaluate this strategic approach. Other strategies include the use of viral peptides, which contain several viral specific epitopes, that could be used as carriers for capsular polysaccharide bacterial antigens from various infectious organisms. The overall major objective of this initiative is to encourage basic research in developing new approaches for making combination vaccines that demonstrate the capacity to protect against multiple human pathogens in the fewest doses possible. Efforts are needed to refocus vaccine development strategies toward attaining maximal clinical outcomes for various childhood diseases using new and creative technologies. These advanced technologies will provide, hopefully, new alternatives to current approaches in viral and bacterial vaccine development. Applicants are encouraged to propose innovative approaches to the production of multicomponent vaccines and to consider other relevant issues such as antigenic competition, stability, valence limitations, antigen processing, and immune recognition and lymphocyte activation. SPECIAL REQUIREMENTS NIAID program staff will organize annual meetings in Bethesda that Principal Investigators and other key members (as designated by the Principal Investigators) of the projects are encouraged to attend to discuss progress. Funds for travel to these meetings should be included in the budget. STUDY POPULATIONS SPECIAL INSTRUCTIONS FOR INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDIES For projects involving clinical research, NIH requires applicants to give special attention to the inclusion of women and minorities in study populations. If women or minorities are not included in the study populations for clinical studies, a specific justification for this exclusion must be provided. Applications without such documentation will not be accepted for review. LETTER OF INTENT Prospective applicants are asked to submit, by October 1, 1993, a letter of intent that includes a descriptive title of the proposed research, the names and affiliations of proposed key investigators, and the number and title of the RFA in response to which the application may be submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information that it contains allows NIAID staff to estimate the potential review workload and to avoid possible conflict of interest in the review. The letter of intent is to be sent to Dr. Olivia Preble at the address listed under INQUIRIES. APPLICATION PROCEDURES Applications are to be submitted on form PHS 398 (rev. 9/91), the standard application form for research grants. Application kits are available at most institutional offices of sponsored research and may be obtained from the Office of Grants Information, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone 301/594-7248. Applicants must adhere to the format and requirements specified in the PHS 398 application kit. The receipt date for applications is November 24, 1993. The signed, typewritten original of the application, including the Checklist, and three exact copies must be sent to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** At the time of submission, two additional copies must also be sent to Dr. Olivia Preble at the address listed under INQUIRIES. To ensure their review, applications must be received by both the Division of Research Grants (DRG) and Dr. Olivia Preble by the application receipt date. Applications not received on the receipt date will be considered non-responsive and will be returned to the applicant without review. If the application submitted in response to this RFA is substantially similar to a grant application already submitted to the NIH for review, but which has not yet been reviewed, the applicant will be asked to withdraw either the pending application or the new one. Simultaneous submission of essentially identical applications will not be allowed, nor will essentially identical applications be reviewed by different review committees. Therefore, an application cannot be submitted in response to this RFA that is essentially identical to one that has already been reviewed. This does not preclude the submission of substantial revisions of applications already reviewed, but such applications must include an introduction addressing the previous critique. REVIEW CONSIDERATIONS Applications will be reviewed by DRG staff for completeness and by NIAID staff to determine administrative and programmatic responsiveness to this RFA. Those judged to be incomplete or nonresponsive will be returned to the applicant without review. Those considered complete and responsive may be subjected to a triage review by an NIAID peer review group, before or during the initial review meeting, to determine their scientific merit relative to the other applications submitted in response to this RFA. The NIAID will withdraw from competition those applications judged by the triage peer review group to be noncompetitive for award and will so notify the applicant investigator and the institutional business official. Those applications judged to be competitive for award will be reviewed for scientific and technical merit by a Review Committee convened by the Division of Extramural Activities, NIAID. The second level of review will be provided by the National Advisory Allergy and Infectious Diseases Council. INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues and requests for the RFA to: Dr. David L. Klein Division of Microbiology and Infectious Diseases National Institute of Allergy and Infectious Diseases Solar Building, Room 3A-10 Bethesda, MD 20892 Telephone: (301) 496-5305 FAX: (301) 402-8030 Send the letter of intent and direct any questions regarding review procedures, to: Dr. Olivia Preble Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4C-19 Bethesda, MD 20892 Telephone: (301) 496-8208 FAX: (301) 402-2638 Direct inquiries regarding fiscal matters to: Mr. Todd Ball Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4B-35 Bethesda, MD 20892 Telephone: (301) 496-7075 FAX: (301) 480-3780 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.856, Microbiology and Infectious Disease Research. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$R3 END ************************************************************ $$R4 BEGIN AI-93-012 FULL-TEXT ************************************** IMMUNE RECONSTITUTION OF HIV-INFECTED INDIVIDUALS NIH GUIDE, Volume 22, Number 28, August 6, 1993 RFA AVAILABLE: AI-93-012 P.T. 34; K.W. 0715008, 0710070, 0705040, 0740012, 0745032 National Institute of Allergy and Infectious Diseases National Institute of Diabetes and Digestive and Kidney Diseases Letter of Intent Receipt Date: October 27, 1993 Application Receipt Date: December 8, 1993 THIS IS A NOTICE OF AVAILABILITY OF A REQUEST FOR APPLICATIONS (RFA); IT IS ONLY AN ABSTRACT OF THE RFA. POTENTIAL APPLICANTS MUST REQUEST THE COMPLETE RFA, WHICH CONTAINS ESSENTIAL INFORMATION FOR THE PREPARATION OF AN APPLICATION, FROM THE CONTACT LISTED IN "INQUIRIES," BELOW. FAILURE TO FOLLOW THE INSTRUCTIONS IN THE COMPLETE RFA MAY RESULT IN AN INCOMPLETE APPLICATION, WHICH WILL BE RETURNED TO THE APPLICANT WITHOUT REVIEW. PURPOSE The National Institute of Allergy and Infectious Diseases (NIAID) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) wish to promote research on interactions of the Human Immunodeficiency Virus-1 (HIV-1) with the immune system that may impact on the immunologic reconstitution of infected individuals; cytokines to facilitate stem cell reconstitution of HIV-infected individuals or ameliorate/reverse HIV-related damage to the immune system; and gene-based strategies to counteract detrimental effects of HIV-1 on the immune system, to prevent infection of stem cells transplanted into HIV-infected individuals, and to improve the characteristics of ex vivo expanded lymphocytes to enable them to function more effectively in vivo. Although clinical trials will not be supported under this RFA, the basic and preclinical research accomplished is expected to lay the foundation for future clinical trials. The NIAID and NIDDK request the coordinated submission of related individual research project grant applications from investigators who wish to collaborate on research, but do not require extensive shared physical resources. These applications must share a common theme and describe the objectives and scientific importance of the interchange of ideas, data, and materials among the collaborating investigators. This collaborative research will be supported by investigator- initiated Interactive Research Project Grant (IRPG). For further information, potential applicants should refer to Special Instructions for Preparing Applications for Interactive Research Project Grants, which may be obtained from the program staff listed under INQUIRIES. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This RFA, Immune Reconstitution of HIV-Infected Individuals, is related to the priority area of HIV infection. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign, for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT The support mechanism for this program will be individual research project grants (R01s) which are organized around a common theme into an IRPG. It is the responsibility of the applicants to plan, direct and execute the proposed projects in accord with their interests and perceptions of potential treatment strategies utilizing immune reconstitution. The total project period for applications submitted in response to the present RFA may not exceed four years. IRPG applications considered responsive to this RFA will have at least two components, one proposing research on stem cell or somatic cell therapies and one proposing gene-based therapeutic strategies. Reissuance of this initiative in future years is anticipated but not certain. FUNDS AVAILABLE The NIAID and NIDDK anticipate awarding two to four IRPGs (a total of six to eight R01 awards), for a total cost of $1.9 million for the initial year of funding. The NIAID has set aside $1.2 million for applications received in response to this RFA, and the NIDDK has set aside $0.7 million for this purpose. RESEARCH OBJECTIVES The long term goal of this RFA is to provide an experimental basis for using immune reconstitution as a therapy in individuals whose immune systems are compromised by infectious disease. This RFA focuses on HIV/AIDS. Research responsive to this RFA includes, but is not limited to, the following: o Research to clarify interactions of HIV with the immune system that may bear on the successful reconstitution of infected individuals and gene-based strategies to counter HIV-related damage to the immune system; o Research on antiviral strategies, including the design and evaluation of new gene-based antiviral strategies to be used in stem cells or other sources of immune cells; o Research to discover and/or develop novel sources of multipotent stem cells that can be genetically engineered to resist HIV-1 infection, new cytokines capable of interacting with T cell progenitor cells or their immediate antecedents, new assays to quantitate T cell progenitor cells. STUDY POPULATIONS SPECIAL INSTRUCTIONS CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS For projects involving clinical research, NIH requires applicants to give special attention to the inclusion of minorities and women in study populations. If women and minorities are not included in the study populations for clinical studies, a specific justification for this exclusion must be provided. Applications without such documentation will not be accepted for review. LETTER OF INTENT Prospective applicants are asked to submit, by October 27, 1993, a letter of intent that includes descriptive titles of each proposed research project in the IRPG group, the names and address of the Principal Investigators and other key personnel, the participating institutions, and the number and title of this RFA. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information that it contains allows the NIAID and NIDDK to estimate the potential workload for reviewers and to avoid possible conflict of interest in the review process. The letter of intent is to be sent to Dr. Dianne Tingley at the address indicated in INQUIRIES below. APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 9/91) is to be used in applying for these grants. This form is available at most institutional offices of sponsored research and from the Office of Grants Information, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone (301) 594-7248. Additional instructions for the preparation of interactive project applications will be provided with the RFA. Applications not received by December 8, 1993, will be considered unresponsive and returned to the applicant without review. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed by Division of Research Grants (DRG) for completeness and by NIAID and NIDDK staff to determine responsiveness. Incomplete and non-responsive applications will be returned to the applicant without further consideration or review. Those applications considered responsive to the RFA may be subjected to a triage by a peer review group, before or during the review committee meeting, to determine their scientific merit relative to the other applications submitted in response to this RFA. The NIAID will remove from further competition those applications judged to be noncompetitive for award and will notify the applicant and the institutional business official. Those applications judged to be competitive for award will be further reviewed for scientific and technical merit by an appropriate review committee convened by the Division of Extramural Activities, NIAID. A second level of review will be provided by the NIAID and NIDDK Councils. Factors to be considered in the evaluation of each application will be similar to those used in review of traditional research grant applications and, in addition, will include those addressing overall proposed collaboration. INQUIRIES Written and telephone requests for the RFA and the opportunity to clarify any issues or questions from potential applicants are welcome. It is essential that prospective applicants obtain a copy of the RFA and the Special Instructions for Preparing Applications for IRPGs before preparing an application. Direct requests for the RFA and inquiries regarding scientific issues or responsiveness to: Dr. Sandra Bridges Developmental Therapeutics Branch National Institute of Allergy and Infectious Diseases Solar Building, Room 2C12 Bethesda, MD 20892 Telephone: (301) 496-8197 Dr. Ralph Bain Division of Kidney, Urologic, and Hematologic Diseases National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 3A05 Bethesda, MD 20892 Telephone: (301) 594-7556 Address the letter of intent and questions regarding review of applications to: Dr. Dianne Tingley Scientific Review Program National Institute of Allergy and Infectious Diseases Solar Building, Room 4C16 Bethesda, MD 20892 Telephone: (301) 496-0818 Direct inquiries regarding fiscal matters to: Ms. Jane Unsworth Grants Management Branch National Institute of Allergy and Infectious Diseases Solar Building, Room 4B22 Bethesda, MD 20892 Telephone: (301) 496-7075 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance, 93.856 - Microbiology and Infectious Diseases Research and 93.855 - Immunology, Allergy and Transplantation Research. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR Part 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$R4 END ************************************************************ ERRATUM $$E1 BEGIN R2 19930618 APPEND RFA AI-93-014 BOTH *********************** CENTERS FOR AIDS RESEARCH/CORE SUPPORT GRANT (CFAR/CSG) NIH GUIDE, Volume 22, Number 28, August 6, 1993 RFA: AI-93-014 P.T. 34; K.W. 0715008, 0710030, 0404000, 0745027, 0411005 National Institute of Allergy and Infectious Diseases National Institute of Mental Health Application Receipt Date: September 17, 1993 The following modifications are made to Request for Applications (RFA) AI-93-014, that appeared in the NIH Guide for Grants and Contracts, Vol. 22, No. 22, June 18, 1993. Under the section RESEARCH OBJECTIVES, third paragraph, and item 4 under REVIEW CONSIDERATIONS, it states that "the CFAR Director should currently be a Principal Investigator of one or more peer-reviewed, AIDS or AIDS-related research projects in the CFAR Funded Research Base". This qualification is amended to state that: The CFAR Director should be a recognized leader in the field of AIDS or AIDS-related research. Such leadership can be demonstrated by a combination of AIDS or AIDS-related research activities as exemplified by the following: currently be a Principal Investigator or Co-principal Investigator of one or more peer-reviewed, AIDS or AIDS-related research projects in the CFAR Funded Research Base; membership on AIDS or AIDS-related research study sections or ad hoc review committees; editor of a peer-reviewed AIDS or AIDS-related scientific journal; organizer of national or international meetings in the field of AIDS or AIDS-related research; or author on key scientific publications in the field of AIDS or AIDS-related research. The schedule shown in the NIH Guide, June 18, 1993 is amended: Letter of Intent Receipt Date: July 23, 1993 Final Date for Receipt of Application: September 17, 1993 Under the section Goals and Objectives of the Centers for AIDS Research, o Basic Science Cores - the following additional examples are made to the examples of Basic Science Cores that may be supported by the National Institute of Mental Health: Basic Behavioral Theory relevant to HIV Risk Behavior Initiation, Maintenance and Change; Community and Individual Sampling, Measurement and Assessment; Conceptual and Methodological Model Development for High Risk Behavior; Cultural Diversity; Multiple Informant Strategies to Supplement Self Report; Alternatives to Linear Additive Models; and Generalizability of Validity of Measures Across Subgroups. INQUIRIES Inquiries regarding scientific or programmatic issues may be directed to: Dr. Robert H. Bassin or Dr. Janet M. Young Division of AIDS National Institute of Allergy and Infectious Diseases 6003 Executive Boulevard, Room 2B31 (or 2B28) Bethesda, MD 20892 Telephone: (301) 402-0755 FAX: (301) 480-5703 Inquiries regarding fiscal matters may be addressed to: Ms. Jane Unsworth Division of Extramural Activities National Institute of Allergy and Infectious Diseases 6003 Executive Boulevard, Room 4B22 Bethesda, MD 20892 Telephone: (301) 496-7075 FAX: (301) 480-3780 $$E1 END ************************************************************ From owner-sci-resources@net.bio.net Thu Aug 05 23:00:00 1993 Path: biosci!net.bio.net From: kristoff@net.bio.net (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 22, no. 28, pt. 2, 6 August 1993 Message-ID: Date: 6 Aug 93 03:24:53 GMT Sender: kristoff@net.bio.net Lines: 1038 Approved: biosci-moderator@net.bio.net $$XID RFA HD94006 HD-94-006 P1O1 *************************************** HUMAN FETAL TISSUE CHARACTERIZATION FOR TRANSPLANTATION NIH GUIDE, Volume 22, Number 28, August 6, 1993 RFA: HD-94-006 P.T. 34; K.W. 0705035, 0745065, 0780005 National Institute of Child Health and Human Development National Institute of Diabetes and Digestive and Kidney Diseases National Institute of Neurological Disorders and Stroke Letter of Intent Receipt Date: October 1, 1993 Application Receipt Date: November 19, 1993 PURPOSE This Request for Applications (RFA) has been developed to encourage research on the standards and methods for identifying and characterizing optimal human fetal tissue for use in transplantation therapy. Joint funding by the National Institute of Child Health and Human Development (NICHD), the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and the National Institute of Neurological Disorders and Stroke (NINDS) reflects the extent of interest in evaluating human fetal tissues and their biological potentials. Attention should be given to proper collection, processing, culturing and preserving these tissues to ensure highest quality control. This research should consider addressing methods for acquisition, handling, and processing, establishing morphologic status, determining developmental age and viability, assessing sterility and genetic normality, preserving by cryopreservation, storing and establishing cell lines. President Clinton's directive of January 22 ended the moratorium on Federal funding for use of fetal tissue from induced abortions in human transplantation research. Therefore, human fetal tissues studied under this solicitation may be derived from spontaneous abortion, ectopic pregnancy, or induced abortion. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This RFA, Human Fetal Tissue Characterization for Transplantation, is related to the priority areas of maternal and infant health, and diabetes and chronic disabling conditions. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1), through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories and units of state or local governments. Applications from investigators who are minority individuals and women are encouraged. MECHANISM OF SUPPORT This RFA will use the National Institutes of Health (NIH) research project grant (R01). Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. The total project period for applications submitted in response to the present RFA may not exceed four years. The anticipated award date is July 1, 1994. This RFA is a one time solicitation. Future unsolicited competing continuation applications will compete with all investigator-initiated applications and be reviewed according to the customary peer review procedures. FUNDS AVAILABLE It is anticipated that up to six grants will be awarded under this program, contingent upon receipt of a sufficient number of meritorious applications and the availability of funds. To support these awards, $1,000,000 has been set aside for the direct costs in the first year. The duration of these awards is to be four years and the annual direct costs for the first year are not to exceed $160,000. This announcement is for a single competition with the application receipt deadline of November 19, 1993. Should there be a sufficient continuing program need, this RFA may be reissued. RESEARCH OBJECTIVES Background The use of human fetal tissue transplants has been advocated for several years as a means of treating a number of devastating diseases. Fetal tissue transplants may allow replacement of tissues and cell products that have been damaged, destroyed, or that never developed properly due to disease or a genetic disorder. These maladies are life threatening unless intervention is instituted. Childhood diseases such as inborn errors of metabolism, immune deficiencies and other entities are being considered for very early treatment using fetus-to-fetus transplants. Diseases such as insulin-dependent diabetes mellitus (IDDM) and Parkinson's Disease are also prospective candidates for transplantation therapy. The results of the Diabetes Control and Complications Trial demonstrate the profound importance of glucose control in the prevention of diabetic complications. Thus, transplantation therapy offers new avenues for tighter glucose control in IDDM patients. Initial results of surgical transplantation in Parkinson's Disease for a small number of cases hold considerable promise although more definitive study and evaluation are required. There is currently considerable interest in the therapeutic use of fetal tissues for the treatment of incurable and chronic diseases, both from the medical and the basic science community. Methods should be considered to optimize and standardize the handling and processing of fetal tissues as well as their preservation and storage. It is evident that better characterization of these more immature fetal tissues is required to assure optimal therapeutic results. Improved knowledge of the potential of these cells will define their roles in normal developmental processes based on their developmental age and biological potential, and will improve their usefulness in replacement therapy. Tissue Collection Appropriate collaboration with clinicians will be required to obtain necessary tissue in a timely fashion and collected in a manner suitable for the scheduled tissue processing. Accurate assessment of developmental age, gross examination of tissues, and grading of tissues for viability will also require a pathology/teratology assessment. In obtaining medical histories and serological screening of contributors of the products of conception for this research, appropriate informed consent must be obtained. Evaluation of pathogenic contaminants, cytogenetic studies and assessment of genetic mutations in at-risk specimens are research areas to be included. Applicants should be able to demonstrate immunologic and transplantation expertise and have available established tissue culture facilities with the expertise for growing, characterizing, cryopreserving and maintaining suitable fetal cell lines. Data Collection The data from these studies should be used to address the quality and efficacy of the tissues under investigation for transplantation therapy. This information should be applicable to the establishment of protocols and tissue processing innovations. SPECIAL REQUIREMENTS The fetal tissue acquisition and handling must comply with the regulations for Federal Funding of Fetal Tissue Transplantation Research as set forth in the NIH Guide for Grants and Contracts, Volume 22, Number 11, March 19, 1993. It is expected that at least two meetings per year in the Washington, DC area of the awardees, NIH staff, and NIH consultants, during both the first and subsequent years, will be required to assess progress and workscope. These meetings will be of benefit to the grantees and will allow them to address unforeseen difficulties, establish collaborative efforts and assess the schedule of progress. The grantees will retain primary authority and responsibility for the work. Funds for this travel should be requested in the application. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements will be required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis should be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale should be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues should be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information should be included in the form PHS 398 in Sections 1-4 of the Research Plan AND summarized in Section 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., Native Americans (including American Indians or Alaskan Natives), Asian/Pacific Islanders, Blacks, Hispanics). The rationale for studies on single minority population groups should be provided. For the purpose of this policy, clinical research includes human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including but not limited to clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded. However, every effort should be made to include human tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. For foreign awards, the policy on inclusion of women applies fully; since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. If the required information is not contained within the application, the application will be returned. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and will be reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. LETTER OF INTENT Prospective applicants are asked to submit, by October 1, 1993, a letter of intent that includes a descriptive title of the proposed research; the name, address, and telephone number of the Principal Investigator; the identities of other key personnel and participating institutions; and the number and title of the RFA in response to which the application may be submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information that it contains is helpful in planning for the review of applications. It allows NICHD, NIDDK, and NINDS staff to estimate the potential review workload and to avoid conflict of interest in the review. The letter of intent is to be sent to Dr. Delbert H. Dayton at the address listed under INQUIRIES. APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 9/91) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research and from the Office of Grants Information, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone (301) 594-7248. The RFA label available in the PHS 398 application form must be affixed to the bottom of the face page. Failure to use this label could result in delayed processing of an application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2a of the face page of the application form and the YES box checked. The title can be abridged to "Human Fetal Tissues." Submit a signed, typewritten original of the application, including the Checklist, and three signed, exact photocopies, in one package to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** At the time of submission, two additional copies of the application must also be sent to: Susan Streufert, Ph.D. Division of Scientific Review National Institute of Child Health and Human Development 6100 Executive Boulevard, Room 5E03 Bethesda, MD 20892 REVIEW CONSIDERATIONS Applications will be received by the NIH Division of Research Grants and reviewed for completeness. Incomplete applications will be returned to the applicant. NICHD, NIDDK, and NINDS staff will review the applications for responsiveness to the RFA. Applications judged to be nonresponsive will be returned. Responsive applications may be subjected to a triage by a peer-review group to determine the scientific merit relative to the other applications received in response to this RFA. NICHD will withdraw from competition those applications judged to be noncompetitive and will notify the applicant and institutional official. Those applications judged to be competitive will be further evaluated for scientific and technical merit by a review group convened solely for this purpose by the Division of Scientific Review, NICHD. Following review by the Initial Review Group, applications will be evaluated by the appropriate National Advisory Council for program relevance and policy issues before awards for meritorious applications are made. Review Criteria Applications must contain sufficient information for scientific review based on the following criteria: o Quality of proposed research to determine the optimal methods of tissue evaluation, processing, cryopreservation, maintenance, storage, tissue/cell culturing and quality control for establishment of viable, functional tissue/cells for transplantation o Demonstrated experience of the principal investigator and proposed staff relevant to this RFA, especially in the areas of immunologic and transplantation expertise, pathology/teratology and tissue preparation techniques o Adequacy of access to fetal tissue and confirmed cooperation of the professional clinical obstetric community o Plans for tissue collection to assure a broad population base, maximum access and ascertainment, rapid transport, and support of cooperating institutions o Adequacy of physical facilities for proposed studies o Quality of data analysis systems AWARD CRITERIA Responsiveness to the RFA, scientific merit, and technical proficiency, as described in the application, will be the predominant criteria for determining funding. INQUIRIES Written and telephone inquiries concerning this RFA are encouraged to clarify any issues or questions from potential applicants. Direct inquiries regarding programmatic issues, and address the letter of intent to: Delbert H. Dayton, M.D. Center for Research for Mothers and Children National Institute of Child Health and Human Development 6100 Executive Boulevard, Room 4B01 Bethesda, MD 20892 Telephone: (301) 496-5541 Joan T. Harmon, Ph.D. Division of Diabetes, Endocrinology and Metabolic Diseases National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 622 Bethesda, MD 20892 Telephone: (301) 594-7565 Eugene J. Oliver, Ph.D. Division of Demyelinating, Atrophic, and Dementing Disorders National Institute of Neurological Disorders and Stroke Federal Building, Room 806 7550 Wisconsin Avenue Bethesda, MD 20892 Telephone: (301) 496-1431 Direct inquiries regarding fiscal matters to: Ms. Mary Ellen Colvin Office of Grants and Contracts National Institute of Child Health and Human Development 6100 Executive Boulevard, Room 8A17 Bethesda, MD 20892 Telephone: (301) 496-1303 Ms. Betty E. Bailey Division of Extramural Activities National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 649 Bethesda, MD 20892 Telephone: (301) 594-7543 Mr. George Tucker Division of Extramural Activities National Institute of Neurological Disorders and Stroke Federal Building, Room 1004 7550 Wisconsin Avenue Bethesda, MD 20892 Telephone: (301) 496-9231 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance Nos. 93.847, 93.853, 93.854, and 93.865. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$XID RFA AI93012 AI-93-012 P1O1 *************************************** IMMUNE RECONSTITUTION OF HIV-INFECTED INDIVIDUALS (IRPG) NIH GUIDE, Volume 22, Number 28, August 6, 1993 RFA: AI-93-012 P.T. 34; K.W. 0715008, 0710070, 0705040, 0740012, 0745032 National Institute of Allergy and Infectious Diseases National Institute of Diabetes and Digestive and Kidney Diseases Letter of Intent Receipt Date: October 27, 1993 Application Receipt Date: December 8, 1993 PURPOSE The National Institute of Allergy and Infectious Diseases (NIAID) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) invite Interactive Research Project Grant (IRPG) applications for collaborative research efforts that combine immune reconstitution and gene-based strategies to develop new treatment modalities for HIV-1 infection. The NIAID and NIDDK wish to promote research on: interactions of the Human Immunodeficiency Virus-1 (HIV-1) with the immune system that may impact on the immunologic reconstitution of infected individuals; cytokines to facilitate stem cell reconstitution of HIV-infected individuals or ameliorate/reverse HIV-related damage to the immune system; and gene-based strategies to counteract detrimental effects of HIV-1 on the immune system, to prevent infection of stem cells transplanted into HIV-infected individuals, and to improve the characteristics of ex vivo expanded lymphocytes to enable them to function more effectively in vivo. Although clinical trials will not be supported under this Request for Applications (RFA), the basic and preclinical research accomplished is expected to lay the foundation for future clinical trials. The NIAID and NIDDK request the coordinated submission of related individual research project grant applications from investigators who wish to collaborate on research, but do not require extensive shared physical resources. These applications must share a common theme and describe the objectives and scientific importance of the interchange of ideas, data, and materials among the collaborating investigators. This collaborative research will be supported by investigator-initiated Interactive Research Project Grant (IRPG) awards. For further information, potential applicants should refer to the document, Special Instructions for Preparing Applications for Interactive Research Project Grants. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This RFA, Immune Reconstitution of HIV-Infected Individuals, is related to the priority area of HIV infection. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign, for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Applications from minority individuals and women are encouraged. Applicants for IRPGs may not concurrently submit additional R01 applications (either investigator-initiated or in response to another RFA) that represent significant duplications of the efforts described in the IRPG application. Concurrent submission of program project (P01) or cooperative agreement (U01) applications that request support for essentially similar work is also prohibited. MECHANISM OF SUPPORT The support mechanism for this RFA will be the individual research project grant (R01) from investigators who wish to collaborate on research efforts directed at the development of treatment strategies utilizing immune reconstitution. The independent research projects will be organized into an IRPG that must consist of a minimum of two independent R01 applications. For this RFA, each IRPG group submission should include at least one application proposing research on stem cell or somatic cell therapies and one application proposing gene-based therapeutic strategies. Each application must clearly identify the research that will be carried out independently and that which will be carried out collaboratively and include a succinct description of the scientific relationships among the investigators and plans for collaboration, interaction, and communication. Refer to the document, Special Instructions for the Preparation of Applications for Interactive Research Project Grants. An IRPG Coordinator should be identified from among the participating R01 Principal Investigators. Since the Coordinator will be responsible for facilitating communication and collaboration among the investigators, he/she may request a modest amount of funds for an administrative core to support the time and effort contributed to these activities. See additional instructions on preparation of a IRPG application. All applicable PHS and NIH grants policies will apply to applications received in response to this RFA. Because the nature and scope of the research proposed in response to this RFA may vary, it is anticipated that the size of the awards will vary also. The budget request for the initial year's total costs (direct and indirect) for the R01 applications in the IRPG group may not exceed an average of $250,000 per R01 application. (For example, one application that requests $350,000 might be combined with two applications requesting $200,000.) Any budgets in excess of this amount must be approved by the NIAID prior to submission of the IRPG application. Requests for expensive equipment are not encouraged. Up to four years of support may be requested. Reissuance of this RFA is anticipated but not certain. If by the end of the third year, the NIAID has not announced its intent to re-advertise this RFA, incumbents should prepare unsolicited competing continuation R01 or IRPG applications that will compete with all investigator-initiated applications and will be reviewed by traditional peer review procedures. Those Principal Investigators who wish to continue collaborative efforts should consult NIAID staff before preparing their applications. FUNDS AVAILABLE The NIAID and NIDDK anticipate awarding two to four IRPGs (a total of six to eight R01 awards), for a total cost of $1.9 million for the initial year of funding. The NIAID has set aside $1.2 million for applications received in response to this RFA, and the NIDDK has set aside $0.7 million for this purpose. These funding levels are dependent on the receipt of a sufficient number of applications of high scientific merit. RESEARCH OBJECTIVES Background The mortality and morbidity suffered by HIV-infected individuals is primarily the consequence of immune deficits that become increasingly more severe during the course of the disease. Several immune-based strategies are presently under evaluation for ameliorating and/or reversing immune deficiencies in HIV-infected individuals. Prominent among these are the use of HIV envelope vaccines or therapeutics (e.g., interleukin-2) to augment existing responses to the virus or enhance the immune system as a whole; HIV-specific lymphocytes or antibodies to supplement the response elicited during the natural course of infection; and bone marrow transplantation (BMT) to restore immune cells lost as a result of HIV-1 infection. BMT is currently being used to restore marrow function in cancer patients whose hematopoietic systems have been ablated by chemo- and radiation therapy. The immediate goal is the reconstitution of hematopoietic lineages required for acute survival, i.e., myeloid and megakaryocyte lineages. Less attention has been paid to the restoration of the lymphoid lineage despite the fact that infectious disease is responsible for a significant portion of the mortality in survivors of BMT. The CD4/CD8 T lymphocyte ratio may remain abnormal for prolonged periods after transplantation, and persistent functional deficits are evidenced by various in vitro assays of immune function. Basic information that bears on the feasibility of immune reconstitution as a therapeutic approach for HIV infection is currently incomplete. For example, it is not known with certainty whether or not human multipotent stem cells can be infected by HIV-1 and whether an HIV-1-infected host can provide the proper physiological environment for the maturation of stem cells to their respective differentiated lineages. Further, it is not clear whether a source of stem cells can be identified that meets the minimal criteria for the success of a gene therapy utilizing stem cells, namely the capacity to be maintained in vitro; to be modified to resist HIV-1 infection; to home, differentiate and expand in vivo after modification; and to retain the HIV-resistant phenotype in differentiated lineages, particularly in T lymphocytes. Human and animal model studies are currently assessing the capability of CD34+ bone marrow cells to reconstitute a functional hematopoietic system in appropriately conditioned recipients. Other potential sources of multipotent stem cells have been identified, including fetal liver, yolk sac, and cord blood. There is increasing evidence to support the hypothesis that very primitive stem cells may possess characteristics favorable to engraftment in a nonautologous setting such that they may be able to persist without eliciting either a graft versus host reaction or a host versus graft reaction. Further research is needed to confirm and amplify these findings. Alternatively, the immune system might be temporarily supported in the face of disease-related immunodeficiency by the transfer of antigen-specific, ex vivo expanded lymphocytes. Recent clinical trials suggest that bone marrow transplant patients at risk of cytomegalovirus-related disease might benefit from adoptive immunotherapy with cytotoxic T cells that are capable of killing virus-infected cells. Animal and human studies are exploring a possible role for HIV-specific T cells in controlling the infection. Therefore, research on therapies that utilize cells with limited capacity for in vivo expansion will be supported under this RFA because of their potential utility in controlling HIV-1 in early stage disease and in combatting opportunistic infections. Goals and Objectives The long term goal of this RFA is to provide an experimental basis for using immune reconstitution as a therapy in individuals whose immune systems are compromised by infectious disease. This RFA focuses on HIV/AIDS for which there is need for therapies that can maintain/supplement the immune systems of infected individuals. Since it is unlikely that HIV-1 can be totally eradicated from the body by means presently available, strategies for the immune reconstitution of HIV-infected individuals will require that the transferred cells be genetically engineered to resist infection by, and/or the damaging effects of, HIV-1. Efforts are currently underway to use gene-based strategies and immune reconstitution as independent modalities to treat HIV-1 and associated infections. The objective of this RFA is to encourage preclinical research that combines the two approaches through collaborative efforts among independent investigators. Research Scope Research responsive to this RFA includes, but is not limited to, the following: Research to clarify interactions of HIV with the immune system that may bear on the successful reconstitution of infected individuals o Mechanism(s) of destruction of lymphoid tissue by HIV-1 and gene-based strategies for blocking mediators responsible for the damage. o Effects of HIV infection on thymopoiesis and multilineage engraftment of stem cells and gene-based strategies to counter detrimental effects. o Aberrant T lymphocyte homeostasis in HIV-infected individuals or in relevant animal models and gene-based therapies to normalize the CD4/CD8 ratio. o Abnormal regulation of cytokine gene expression and gene- based strategies for ameliorating the dysfunction of the cytokine network in HIV-infected individuals. Research on antiviral strategies o Design and evaluation of new gene-based antiviral strategies to be used in stem cells or other sources of immune cells. o Effects of specific antiviral strategies on the biological program of engineered multipotent stem cells. o Antiviral gene expression during differentiation of engineered stem cells in vitro and in vivo. o Isolation, modification, and testing of antigen-specific, in vitro expanded lymphocytes. Modification includes the use of genetic engineering to improve the potency, specificity, or other characteristics of the cells to enable them to function more effectively in vivo. Developmental research o Development of novel sources of multipotent stem cells that can be maintained in vitro and modified by genetic engineering techniques to resist subsequent HIV infection and that are capable of differentiating in vivo and retaining the HIV resistant phenotype in the differentiated lineages. Information bearing on the transplantability of multipotent stem cells across allo- and xeno-histocompatibility barriers is needed. o Discovery and characterization of cytokines, growth and/or differentiation factors, particularly those capable of interacting with T cell progenitors or their immediate antecedents. The discovery and development of new soluble factors are needed for the in vitro maintenance of target cells for genetic engineering, to provide sufficient material for evaluating the success and impact of experimental anti-HIV strategies at an early point, and to stimulate in vivo expansion of engineered stem cells. o Development of an in vitro colony forming assay for T cell progenitors similar to those already in use for other hematopoietic cell progenitors. Existing methodologies for quantifying T cell progenitor cells are time and labor intensive and measure progenitors indirectly by quantifying their ability to repopulate the thymus in animal models or to respond to mitogens in vitro. While it is anticipated that complete development of new strategy for immune reconstitution will not occur within the project period for all groups, a rationale for the most likely use of discoveries made or an outline of a plan for eventual clinical trials should be included. Restrictions and Exclusions Clinical trials will not be supported under this RFA. However, proposed analysis of samples acquired from NIAID-sponsored clinical trials is appropriate. Samples from ongoing trials may be made available for specific experiments. Budgetary limitations will prohibit extensive use of primates in these projects (see MECHANISM OF SUPPORT). If a therapeutic strategy is developed to an advanced stage under the RFA, every effort will be made to provide testing through NIAID-supported primate resources. SPECIAL CHARACTERISTICS Meetings Effective communication among IRPG investigators is very important. IRPG investigators should plan to participate in one meeting per year to be held alone or in conjunction with an NIAID-sponsored meeting such as the National Cooperative Drug Discovery Group (NCDDG) meeting. Funds to support attendance at the meeting should be included in each PI's budget. Patent Coverage Inasmuch as the development of effective treatment strategies is the objective of this effort and since the active involvement by industrial laboratories is facilitated by the existence of adequate patent coverage, it is essential that applicants provide a plan, agreed upon by the group, for obtaining patent coverage and for licensing where appropriate. In the event that the need for patent coverage is anticipated, the grantee should contact program staff listed under INQUIRIES well in advance of the application submission deadline, who will provide the details of the patent requirements and relevant regulations. The NIAID will not be a partner in any patents or royalties ensuing from this research. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements are required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis should be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale must be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues should be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information must be included in the form PHS 398 in Items 1-4 of the Research Plan AND summarized in Section 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations [i.e., Native Americans (including American Indians or Alaskan Natives), Asian/Pacific Islanders, African Americans, Hispanics]. The rationale for studies on single minority population groups must be provided. For the purpose of this policy, clinical research is defined as human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including but not limited to clinical trials. The usual NIH policies concerning research involving human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded. Every effort should be made to include tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. For foreign awards, the policy on inclusion of women applies fully; since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in the study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and will be reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. NOTE: Peer review groups need adequate information about the composition of proposed study populations in all applications involving human subjects. To avoid delays in review of such applications, the NIAID therefore requires that, as a minimum, the application must contain demographic data about the clinic and/or in-patient population from which study subjects (including clinical samples, materials, or fluids) will be drawn: average hospital admissions and/or clinic visits per year; percentage distribution of black/hispanic/other minority/non-minority populations; gender; etc. Studies using non-hospital populations, such as community-based studies, should provide similar data about populations in the area or region from which the study subjects will be drawn. In the absence of current data, historical demographic information and/or previous recruitment data for similar studies from the proposed study sites should be provided. LETTER OF INTENT Prospective applicants are asked to submit, by October 27, 1993, a letter of intent that includes descriptive titles of each proposed research project in the IRPG group, the names and address of the Principal Investigators and other key personnel, the participating institutions, and the number and title of this RFA. Although a letter of intent is not required, is not binding, and does not enter into the review of the application, the information that it contains is helpful in planning for the review of expected applications. It allows NIAID staff to estimate the potential workload for reviewers and to avoid possible conflict of interest in the review process. The letter of intent is to be sent to Dr. Dianne Tingley at the address listed under INQUIRIES. APPLICATION PROCEDURES Since applications that do not address the objectives of this RFA will be considered nonresponsive and will be returned without review, potential applicants are strongly encouraged to discuss their research plans with program staff before completing their applications. Applications are to be submitted on the grant application form PHS 398 (rev. 9/91). These forms are available at most institutional offices of sponsored research and from the Office of Grants Information, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone (301) 594-7248. The RFA label available in the PHS 398 application kit must be affixed to the bottom of the face page of the application. To assure the identification of your application with this RFA, the "Yes" box must be marked in item 2a of the face page of the application and the RFA number (RFA AI-93-012) and title IMMUNE RECONSTITUTION OF HIV-1 INFECTED INDIVIDUALS (IRPG) entered in the provided spaces in item 2a. See the attached special instructions for further information on application procedures. The R01 applications constituting the proposed IRPG group must be submitted in a single package, whether or not the applications originate from the same institution. Each application in the package must be clearly identified and a cover letter must list the total number of applications submitted for the IRPG, indicating the Principal Investigator and title of each. The various applications should not be paginated or collated together like a Program Project, since each R01 application will be processed individually and assigned its own grant number by DRG, NIH. For each application, the original, three copies, and the appendix material must be put together in one bundle and clearly identified. Failure to follow the instructions regarding submission date and packaging may lead to a delay in review. The IRPG package must be sent or delivered to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** At the time of submission to the Division of Research Grants (DRG), also submit two additional exact copies of the IRPG applications including appendices directly to Dr. Dianne Tingley at the address listed under INQUIRIES. REVIEW CONSIDERATIONS Applications that have not followed the instructions for preparation or that do not conform to the instructions contained in the PHS 398 (rev. 9/91) application kit will be judged incomplete and will be returned to the applicant. Each R01 application will be reviewed by DRG staff for completeness and by NIAID and NIDDK staff to determine responsiveness to this RFA; those individual or group applications judged to be incomplete or non-responsive will be returned to the applicant without review. To be considered responsive, the application should be directed towards the attainment of the stated programmatic goals (RESEARCH OBJECTIVES). Those applications that are complete and responsive may be subjected to a triage before or during the initial scientific peer review by a peer review group convened by the Division of Extramural Activities (DEA), NIAID to determine their scientific merit relative to the other applications received in response to this RFA. The NIAID will remove from further competition those applications judged to be noncompetitive for award and will notify the applicant and institutional business official. Those applications judged to be competitive for award will be further reviewed for scientific and technical merit by a review committee convened by the Scientific Review Program, DEA, NIAID. A second level of review will be provided by the National Advisory Allergy and Infectious Diseases Council and the National Diabetes and Digestive and Kidney Diseases Advisory Council. In the event of several highly qualified applications, final funding recommendations will be based on Program priorities. Review Criteria The factors considered in evaluating the scientific merit of each application will be: o Scientific and technical merit of each individual R01 application, including originality and feasibility of the approach; o Appropriateness and adequacy of the experimental approach and methodology proposed to carry out the research; o Adequacy of plans for collaboration and communication with other investigators in the IRPG group; o Adequacy of resources and environment (e.g., facilities and equipment, shared interactive resources [cores]); o Experience, training, time commitment, and qualifications of the investigators (a commitment of at least 15 percent is recommended for Principal Investigators). Review Procedures Each R01 application will be reviewed independently for scientific and technical merit. Reviewers will read section 7 and will assess the intended collaborations just as they do the proposed collaborations in any other types of applications. As appropriate, the effectiveness and merit of the collaborations may contribute to the overall assessment of the application. In addition, budget recommendations related to the appropriateness of shared interactive resources (cores) will be reviewed for each application. Recommendations concerning core(s) in an application will be documented in administrative notes in the summary statements. These notes will assist the NIAID and NIDDK in making final decisions on each application in the context of the overall IRPG. AWARD CRITERIA The NIAID and NIDDK anticipate awarding two to four IRPG groups (six to eight R01 awards total) as a result of this RFA. The final number and specific amounts of awards to be made will depend upon consideration of the following: o Results of the initial scientific and technical merit review; o Potential contribution of the proposed research to the goals and objectives of the RFA; o Program balance; o Availability of resources. INQUIRIES It is essential that prospective applicants carefully review the RFA and the Special Insturctions for Preparing Applications for IRPGs (available from program staff listed below). NIAID and NIDDK staff welcome the opportunity to clarify issues or answer questions from potential applicants. Direct inquiries regarding scientific issues or responsiveness to: Dr. Sandra Bridges Division of AIDS National Institute of Allergy and Infectious Diseases Solar Building, Room 2C12 Bethesda, MD 20892 Telephone: (301) 496-8197 Dr. Ralph Bain Division of Kidney, Urologic, and Hematologic Diseases National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 3A05 Bethesda, MD 20892 Telephone: (301) 594-7556 Direct inquiries regarding the scientific review process, format of applications, and address the letter of intent to: Dr. Dianne Tingley Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4C16 Bethesda, MD 20892 Telephone: (301) 496-0818 Direct inquiries regarding fiscal matters and the format of applications to: Ms. Jane Unsworth Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4B22 Bethesda, MD 20892 Telephone: (301) 496-7075 Applicants who wish to use express mail or a courier service are advised to follow the carrier's requirements for showing a street address. The address for the Solar Building is: 6003 Executive Boulevard, Rockville, MD 20852 Schedule Letter of Intent Receipt Date: October 27, 1993 Application Receipt Date: December 8, 1993 Scientific Review Date: March 1994 Advisory Council Date: June 1994 Earliest Award Date: July 1994 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance, 93.856 - Microbiology and Infectious Diseases Research and 93.855 - Immunology, Allergy and Transplantation Research. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR Part 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. From owner-sci-resources@net.bio.net Thu Aug 05 23:00:00 1993 Path: biosci!net.bio.net From: kristoff@net.bio.net (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 22, no. 28, pt. 3, 6 August 1993 Message-ID: Date: 6 Aug 93 03:25:42 GMT Sender: kristoff@net.bio.net Lines: 956 Approved: biosci-moderator@net.bio.net $$XID RFA CA93037 CA-93-037 P1O1 *************************************** ROLE OF THE MICROENVIRONMENT IN BREAST AND PROSTATE CANCER NIH GUIDE, Volume 22, Number 28, August 6, 1993 RFA: CA-93-037 P.T. 34; K.W. 0715036, 1002004, 1002008, 0760025 National Cancer Institute Letter of Intent Receipt Date: September 10, 1993 Application Receipt Date: November 23, 1993 PURPOSE The Cancer Biology Branch, Division of Cancer Biology, Diagnosis and Centers (DCBDC) at the National Cancer institute (NCI), in collaboration with the Chemical and Physical Carcinogenesis Branch, Division of Cancer Etiology (DCE), NCI, invites investigator- initiated research project grant applications to elucidate the molecular interactions among the cell populations of human breast and prostatic cancer that contribute to malignant progression. New and experienced investigators in relevant fields and disciplines may apply for funds to pursue this research. Breast and prostate tissues have a number of characteristics in common; e.g., steroidal sex hormones modulate the growth and differentiation observed during normal neonatal development and at puberty; these same hormones are implicated in the growth of malignancies of each organ; and hormonal intervention remains a key component of treatment of both breast and prostate cancer in patients. In addition, some association between the two neoplasms is suggested by epidemiological data of an increased risk of prostate cancer among relatives of women with breast cancer, as well as a significant increased risk of breast cancer in families with prostate cancer. It is clear that effects of the steroidal hormones on the epithelium are mediated indirectly by interactions with stroma during normal development and differentiation in both organs. Epithelial-stromal interactions may also be influenced by other hormones and growth factors. More importantly, there is good evidence to indicate that aberrations in epithelial-stromal interactions occur during the course of neoplastic progression. Stromal components that might participate in these micro-environmental influences include fibroblasts, endothelial cells, macrophages, the extracellular matrix contributed by both epithelial and stromal cells, and in the case of breast tissue, adipocytes. Little is known of the contribution of this mosaic of cells to the malignant process at the cellular or molecular level. In animal models, a number of carcinogens (naturally occurring and synthetic) have been implicated as potential transforming agents for breast and prostate tissues but virtually nothing is known about the interaction of such carcinogens with stromal components in normal or malignant breast and prostatic tissues. The aim of this Request for Applications (RFA) is to foster application of recent advances in molecular and cellular biology, using appropriate model systems, to study the effects of tumor cell-stroma interactions relevant to tumor development and progression in human breast or prostatic tissues. A multidisciplinary approach involving interactions among basic and clinical scientists is encouraged. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This RFA, Role of the Microenvironment in Breast and Prostate Cancer, is related to the priority area of cancer. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Research grant applications may be submitted by domestic and foreign for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State or local governments, and eligible agencies of the Federal government. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT Support of this RFA will be by National Institutes of Health (NIH) individual research project grants (R01). Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. The total project period for applications submitted in response to the present RFA may not exceed four years. Awards will be administered under PHS grants policy as stated in Public Health Service Grants Policy Statement, DHHS Publication No. (OASH) 90-50,000, revised October 1, 1990. The present RFA announcement is for a single solicitation with a specified deadline of November 23, 1993 for receipt of applications. The NCI anticipates making up to twelve awards for project periods of up to four years, if meritorious proposals and funds are available. The anticipated award date is July 1, 1994. Because the nature and scope of the research proposed in response to this RFA may vary, it is anticipated that the size of an award may vary also. FUNDS AVAILABLE Approximately $2,000,000 in total costs per year for up to four years will be committed to fund applications submitted in response to this RFA. It is anticipated that up to twelve awards will be made. This level of support is dependent on the receipt of a sufficient number of applications of high scientific merit. Although funds to support this program are currently provided for in the financial plans of the NCI, awards pursuant to this RFA are contingent upon the availability of funds for this purpose. RESEARCH OBJECTIVES Background The incidence of breast carcinoma increases with advancing age. About 183,000 new cases and approximately 46,000 deaths due to breast cancer are expected to occur in 1993. It is estimated that in 1993 there will be 165,000 newly diagnosed cases and 35,000 deaths due to prostate cancer. Some association between the two diseases is suggested by epidemiological data. For example, a family history of prostate cancer can have a significant effect on increasing breast cancer risk. Similarly, a significantly higher frequency of prostate cancer has been reported in relatives of breast cancer patients than in relatives of control groups. Breast and prostatic carcinomas originate in epithelial cells; however, the growth and progression of the cancer is intimately related to its microenvironment, i.e., the stroma. Studies on embryological development of the mammary gland and the prostate have indicated that hormonally-induced ductal morphogenesis and epithelial growth is mediated by the interactions between stroma and epithelia. During this neonatal development the carefully timed acquisition of steroid hormone receptors by stromal cells may be responsible for these hormonally-induced events. Studies on the hormonal regulation of differentiation of the mammary gland in vitro indicate that the presence of stromal components can determine the extent and type of functional epithelial maturation. However, the biochemical interactions and molecular communications underlying these events are poorly understood. Breast Cancer Familial clustering of breast cancer indicates that there is a genetic component predisposing individuals to breast cancer. Although it is the epithelial cell which is designated as cancerous, it has been reported that skin fibroblasts derived from breast cancer patients may also be altered and exhibit characteristics associated with a transformed and/or fetal phenotype. Furthermore, these characteristics of fibroblasts may precede the detection of breast cancer. Many growth factors including bFGF, aFGF and TGFa as well as cytokines (e.g., IL-6) may be made available to epithelial cells from the adjacent mammary stroma. Further, recent data indicate that the primary source of the epithelial mitogen IGF is the breast stroma. Analysis of fibroblasts from benign breast showed the production of IGF-I mRNA while fibroblasts from malignant lesions expressed IGF-II mRNA, suggesting a correlation with disease progression. In the mammary tissue, fibroblast stroma has been shown to produce extracellular matrix molecules such as fibronectin and tenascin that influence cell adhesion and proliferation. Tenascin is known to reduce epithelial cell adhesiveness. It is absent in normal breast, its distribution being restricted to embryonic and malignant tissues. A new gene coding for the enzyme stromelysin-3 (ST-3), has been identified, that is expressed specifically in stromal cells surrounding invasive breast carcinomas. ST-3 is a new member of the family of metalloproteinase enzymes which degrades the extracellular matrix. ST-3 is postulated to play an important role in progression of epithelial malignancies. Prostate Cancer Androgens regulate the early growth and morphogenesis of the prostatic epithelium indirectly by their effects on mesenchymal (stromal) tissues. Androgens may also induce the production of andromedins from stromal cells that influence prostatic epithelial growth by paracrine mechanisms. One major family of growth factors for prostatic epithelial cells may be the fibroblast growth factor (FGF). FGF-7, or keratinocyte growth factor, produced by the stromal cells, in the androgen-dependent Dunning rat tumor is a mitogen for those tumor cells that have FGF-7 receptors. In the more malignant androgen-independent tumors both FGF production and the tumor FGF receptor phenotype are modified. Androgen-sensitive LNCaP prostatic tumor cells will form tumors in nude mice only when the inoculum is mixed with bone- or prostate-derived fibroblasts. Other fibroblasts are not permissive for tumor growth. Differences in prostate tumor incidence in different mouse strains or in rat models may also result from characteristics of the stromal compartment. Recent observations indicate that mesenchymal or stromal inductors can impose strong control over the growth of transformed epithelial cells. Rationale for this RFA This RFA is intended to encourage a variety of investigator-initiated research projects to use appropriate model systems that take into consideration the highly interactive environment of the tumor cells, as well as the contributions of the tumor and host cells to the growth and metastatic spread of breast or prostatic carcinomas. It is also important to delineate the genetic and environmental factors involved in stromal-epithelial interactions which are relevant to malignant progression of hormonally regulated tumors. It may include collaborations among basic and clinical scientists and should embrace an array of molecular and cellular approaches. Evidence of the establishment of reliable tumor cell systems or relevant tumor models should be included in the application. Applications that propose to explore interactions of the stroma with only normal epithelium will not be considered responsive to this RFA. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements are required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis must be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale must be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues must be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information must be included in the form PHS 398 in the Research Plan, parts 1-4, AND summarized in part 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., Native Americans [including American Indians or Alaskan Natives], Asian/Pacific Islanders, Blacks, Hispanics). The rationale for studies on single minority population groups should be provided. For the purpose of this policy, clinical research is defined as human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including but not limited to clinical trials. The usual policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are exempt from this requirement. However, every effort should be made to include human tissues from racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. For foreign awards, the policy on inclusion of women applies fully; since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. If the required information is not contained within the application, the application will be returned. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of minorities in a study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. LETTER OF INTENT Prospective applicants are asked to submit, by September 10, 1993, a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, the identities of other key personnel and participating institutions, and the number and title of the RFA in response to which the application may be submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information that it contains is helpful in planning for the review of applications. It allows NCI staff to estimate the potential review workload and to avoid conflict of interest in the review. The letter of intent is to be sent to Dr. Suresh Mohla at the address listed under INQUIRIES. APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 9/91) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research and from the Office of Grants Information, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892-9912, telephone 301/594-7248. The RFA label available in the PHS 398 application form must be affixed to the bottom of the face page of the application. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA number and title, "Role of the Microenvironment in Breast and Prostate Cancer," must be typed on line 2a of the face page of the application form and the YES box must be marked. Submit a signed, typewritten original of the application, including the Checklist, and four signed, exact, clear, single-sided photocopies, in one package with the appendices to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892-9912** At the time of submission, two additional copies of the application must also be sent to: Referral Officer Division of Extramural Activities National Cancer Institute Executive Plaza North, Room 636A Bethesda, MD 20892 Applications must be received by November 23, 1993. If an application is received after that date, it will be returned to the applicant. The Division of Research Grants (DRG) will not accept any application in response to this announcement that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. The DRG will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of substantial revisions of applications already reviewed, but such applications must include an introduction addressing the previous critique. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed by DRG staff for completeness. Incomplete applications will be returned to the applicant without further consideration. Complete applications will be evaluated by NCI program staff to determine if they are responsive to the program requirements and criteria stated in this RFA. If the application is not responsive to the RFA, NCI staff will contact the applicant to determine whether to return the application to the applicant or submit it for review in competition with unsolicited applications at the next review cycle. Applications may receive a preliminary scientific peer review (triage) by an NCI peer review group on the basis of relative competitiveness. The NIH will withdraw from further competition those applications judged to be non- competitive for award and notify the applicant Principal Investigator and institutional official. Those applications judged to be responsive and competitive will be further evaluated according to the review criteria stated below for scientific and technical merit by an appropriate peer review group convened by the Division of Extramural Activities, NCI. The second level of review by the National Cancer Advisory Board considers the special needs of the Institute and the priorities of the National Cancer Program. Review criteria for evaluating the scientific merit of this RFA will be: o extent to which the proposed research addresses the goals of the RFA o scientific and technical significance and originality of proposed research o appropriateness and adequacy of the experimental approach and methodology proposed to carry out the research, and potential relevance of the model system to human breast or prostate cancer o qualifications and research experience of the Principal Investigator and staff o demonstration of availability and access to appropriate resources necessary to perform the research o adequacy of provision for the protection of human subjects and the humane treatment of animals o adequacy of the plans for inclusion of minorities o adequacy of available facilities o appropriateness of the proposed budget and duration in relation to the proposed research AWARD CRITERIA The anticipated date of award is July 1, 1994. In addition to the technical merit of the application, NCI will consider how well the proposed research meets the goals and objectives of the program as described in the RFA. Only highly-rated projects will be funded. INQUIRIES Written and telephone inquiries concerning the objectives and scope of this RFA or inquiries about whether or not specific proposed research would be responsive are strongly encouraged and may be directed to program staff listed below. NCI program staff welcome the opportunity to clarify any issues or questions from potential applicants. Direct inquiries regarding programmatic issues, address the letter of intent to, and send two copies of the PHS 398 to: Dr. Suresh Mohla Division of Cancer Biology, Diagnosis, and Centers National Cancer Institute Executive Plaza North, Room 505 6130 Executive Boulevard Rockville, MD 20892 Telephone: (301) 496-7028 FAX: (301) 402-1037 Direct inquiries regarding fiscal and administrative matters to: Mr. Robert Hawkins Grants Management Branch National Cancer Institute Executive Plaza South, Room 243 Bethesda, MD 20892 Telephone: (301) 496-7800 ext. 13 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.396, Cancer Biology. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health $$XID RFA AI93017 AI-93-017 P1O1 *************************************** MULTICOMPONENT VACCINE DEVELOPMENT NIH GUIDE, Volume 22, Number 28, August 6, 1993 RFA: AI-93-017 P.T. 34; K.W. 0740075, 1002045, 0710070 National Institute of Allergy and Infectious Diseases Letter of Intent Receipt Date: October 1, 1993 Application Receipt Date: November 24, 1993 PURPOSE The National Institute of Allergy and Infectious Diseases (NIAID) invites applications to conduct basic research leading to the design of new innovative approaches for the synthesis and development of combination vaccines. Multicomponent (multivalent) combination vaccines containing antigens to viral and/or bacterial components provide many distinct advantages over conventional vaccines and allow for the introduction of "disease-specific", "age-specific" and "duration-specific" designer vaccines. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This Request for Applications (RFA), Multicomponent Vaccine Development, is related to the priority area of immunization and infectious diseases. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State or local governments, and eligible agencies of the Federal Government. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT Awards made under this RFA will use the National Institutes of Health (NIH) individual research project grant (R01). Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. The total project period for applications submitted by domestic institutions in response to the present RFA may not exceed four years; the total project period for applications submitted by foreign institutions may not exceed three years. The earliest possible award date is July 1, 1994. Applicants are encouraged to coordinate, through the use of consortium arrangements or subcontracts, integrated approaches with individuals or institutions having relevant reagents and expertise in their use, demonstrated ability in a particular area of relevant research, or access to relevant patient populations so as to accelerate technical progress and clinical development of promising therapies. Because the nature and scope of the research proposed in response to this RFA may vary, it is anticipated that the amounts of the awards will vary also. This RFA is a one-time solicitation. Future competing continuation applications will compete with all unsolicited investigator-initiated applications and be reviewed by an appropriate Study Section according to the customary NIH referral and peer review procedures. FUNDS AVAILABLE The estimated level of support (total direct and indirect costs) for the entire program for the first year is $1.5 million. Foreign applications that may be funded under this RFA are not eligible for indirect costs. The NIAID anticipates making a minimum of four new awards. RESEARCH OBJECTIVES Background Immunization is a principal feature of the health care of infants and young children throughout the world. Universal immunization programs, those that deliver vaccines to all children, are responsible for much of the increase in life expectancy in the last half-century. Although most infants receive their first dose of vaccine at an appropriate age, by the third dose of DTP vaccines, immunization of inner city and minority children in the U.S. is significantly delayed and they are, therefore, at risk of disease. Vaccines that would require fewer doses and could be administered orally would facilitate the immunization of all infants. The future impact of combination vaccines on immunization programs must be considered in the context of the Children's Vaccine Initiative (CVI). The ability to selectively eradicate various childhood diseases through the development of immunization programs that incorporate new emerging technologies for the creation of improved, safe and efficacious vaccines is the primary aim of the NIAID and of the CVI program. A major concept advanced by the CVI program is the idea of providing fewer doses of vaccine to help facilitate delivery and broaden the coverage of immunization. The Division of Microbiology and Infectious Diseases (DMID), NIAID has a long standing commitment to study and support the development and evaluation of new generation vaccines against the major childhood infectious diseases. For example, the DMID effort to evaluate new acellular pertussis vaccines for licensure in the United States is an essential component of the development of new multicomponent vaccines, as the success of the latter will depend on incorporation of an acellular pertussis vaccine for infants. Other new approaches to the development of vaccines include attenuated organisms, genetically modified organisms, recombinant viruses, recombinant DNA-derived subunit vaccines, vectors, and novel delivery technologies such as microencapsulation. Progress on the basic areas of research necessary for targeted development of vaccines have enhanced the understanding of infectious diseases and furthered the capability to develop other vaccines. An example of the latter is the development of glycoconjugate technology for the enhancement of infants' immune response, which is now being used in a number of licensed vaccines. Based on available recombinant DNA technology and advanced computer modeling techniques, many new possibilities exist for engineering live attenuated vaccines and developing viral peptides for the construction of vaccines against medically important pathogens. One such example is the development of genetically defined mutations that can be engineered into the genomes of both RNA and DNA viruses to produce safe and effective vaccines for viral diseases. Such an initiative could also result in the acquisition of important information on the mechanisms of pathogenesis. Other long term strategies might include the development of viral peptides containing several viral specific epitopes, that could be used as carriers for capsular polysaccharide bacterial antigens. The use of genetic engineering and protein modeling can maximize the immunogenicity and range of the protective epitopes of the viruses and bacteria under consideration. The construction of bacterial vector systems (e.g., BCG, Salmonella) expressing genes from a number of pathogenic organisms, could provide a model system in which a single injection could provide multiple immunizations at a reduced cost. The insertion of multiple epitopes into a single vector may also help to minimize reactogenicity and may avoid the reduced immunogenicity that can occur when multiple antigens are delivered as mixtures on the same or similar carrier proteins. In the latter situation, the immune system can become overloaded, resulting in an impaired response to any vaccine component. The combination of vaccines or vaccine components into one vector should effectively retain each components optimum performance, stability, and reasonable cost. Scope of Research The objective of this RFA is to evaluate new approaches/concepts for the development of multivalent vaccines to provide safe and long lasting immunity to multiple agents while providing equivalent immunogenicity and efficacy of a single component. Such an approach will greatly facilitate the implementation of the universal vaccination programs required to bring under control serious infectious diseases worldwide. Barriers to the development of multicomponent vaccines are not merely technological, but will require scientific advances in a number of areas in basic science and infectious diseases. One of the most complex, but basic issues that needs to be resolved is the problem of incorporating fundamentally different products or antigens into a single matrix. For example, at this time we are not able to mix attenuated live agents with killed agents such as oral polio vaccine and Haemophilus influenzae type b conjugate vaccines. The current available approach for making combination vaccines is restricted to mixing either a series of antigens or other "like" immunogens in a single dose. Additional research is, therefore, needed to better understand the immunologic basis for incompatibility/compatibility among disparate antigens. Furthermore, it is assumed that the development of vaccines to diseases that produce systemic infection will differ significantly from those in which infection occurs at mucosal or other epithelial surfaces. This area also needs to be addressed. Possible candidates to consider for development into combination vaccines include the following: o Vaccines currently available and licensed (e.g., DTP, hepatitis B, H. influenzae type b, inactivated and oral polio vaccine, and MMR). o Vaccines in Phase III trials, but not yet licensed (e.g., hepatitis A, acellular pertussis, live varicella, live attenuated bivalent influenza). o Vaccines undergoing early Phase I/II trials (e.g., respiratory syncytial virus, herpes virus glycoproteins, Group B streptococcal conjugates, meningococcal A and C conjugates, and pneumococcal conjugates). o Vaccines in the preclinical evaluation or early developmental stage (e.g., cytomegalovirus subunit, malarial merozoite and circumsporozoite antigens, pneumococcal surface proteins). o Vaccines that are still in the conceptual stages of development. The major objective of this initiative is to encourage innovative research on the development of combination vaccines. Applicants are encouraged to propose innovative approaches to this concept and to consider the list that follows as areas of prime, but not exclusive, concern and importance in the development of combination vaccines: (1) antigenic competition; (2) stability in required formulation (i.e., lyophilization); (3) novel delivery systems (i.e., vectors); (4) selection of appropriate serotypes for regional needs; (5) immune interference (i.e., TH1 and TH2 interactions); (6) technical complexity of the manufacturing process (e.g., use of adjuvants and preservatives); (7) valence limitations (number of serotypes in a single package); (8) cost and affordability; (9) lack of animal models for preclinical evaluation; (10) vaccine induced immunosuppression; (11) role of combination vaccines on immunologic memory and priming; (12) equivocal immunogenicity between polyvalent and monovalent vaccines; and (13) oral vaccine formulation. Applications are being sought that incorporate novel and creative ideas and that address many of the perplexing problems now facing investigators interested in developing combination vaccines. Inter- and intra-category mixing of vaccines will also require the rethinking and reshaping of fundamental vaccine strategies, which is encouraged. Furthermore, investigators are encouraged to interact on all levels, especially academia and industry. SPECIAL REQUIREMENTS NIAID program staff will organize annual meetings in Bethesda that Principal Investigators and other key members (as designated by the Principal Investigators) of the projects are encouraged to attend to discuss progress. Funds for travel to these meetings should be included in the budget. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements are required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis must be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale must be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues must be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information must be included in the form PHS 398 (rev. 9/91) in Sections 1-4 of the Research Plan AND summarized in Section 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., Native Americans [including American Indians or Alaskan Natives], Asian/Pacific Islanders, Blacks, Hispanics). The rationale for studies on single minority population groups should be provided. For the purpose of this policy, clinical research is defined as human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including but not limited to clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded. However, every effort should be made to include human tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. For foreign awards, the policy on inclusion of women applies fully; since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. If the required information is not contained within the application, the application will be returned. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. NOTE: Peer review groups need adequate information about the composition of proposed study populations in all applications involving human subjects. To avoid delays in review of such applications, the NIAID advises that, as a minimum, the application should contain demographic data about the clinic and/or in-patient population from which study subjects will be drawn: average hospital admission per year; percentage distribution of Black/Hispanic/other minority/non-minority populations; gender; etc. Studies using non-hospital populations, such as community-based studies, should provide similar data about populations in the area or region from which the study subjects will be drawn. In the absence of current data, historical demographic information and/or previous recruitment data for similar studies from the proposed study sites should be provided. LETTER OF INTENT Prospective applicants are asked to submit, by October 1, 1993, a letter of intent that includes a descriptive title of the proposed research, the names and affiliations of proposed key investigators, and the number and title of the RFA in response to which the application may be submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information that it contains allows NIAID staff to estimate the potential review workload and to avoid possible conflict of interest in the review. The letter of intent is to be sent to Dr. Olivia Preble at the address listed under INQUIRIES. APPLICATION PROCEDURES Applications are to be submitted on form PHS 398 (rev. 9/91), the standard application form for research grants. Application kits are available at most institutional offices of sponsored research and may be obtained from the Office of Grants Information, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone 301/594-7248. Applicants must adhere to the format and requirements specified in the PHS 398 application kit. For purposes of identification and processing, mark "YES" in item 2a on the face page of the application and type in the RFA number AI-93-017 and the title "Multicomponent Vaccine Development." The RFA label available in the form PHS 398 must be affixed to the bottom of the face page of the original application. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. The signed, typewritten original of the application, including the Checklist, and three exact single-sided copies must be sent to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** At the time of submission, two additional copies must also be sent to Dr. Olivia Preble at the address listed under INQUIRIES. To ensure their review, applications must be received by both the Division of Research Grants (DRG) and Dr. Olivia Preble by November 24, 1993. Applications not received this receipt date will be considered non-responsive and will be returned to the applicant without review. If the application submitted in response to this RFA is substantially similar to a grant application already submitted to the NIH for review, but has not yet been reviewed, the applicant will be asked to withdraw either the pending application or the new one. Simultaneous submission of essentially identical applications will not be allowed, nor will essentially identical applications be reviewed by different review committees. Therefore, an application cannot be submitted in response to this RFA that is essentially identical to one that has already been reviewed. This does not preclude the submission of substantial revisions of applications already reviewed, but such applications must include an introduction addressing the previous critique. REVIEW CONSIDERATIONS Review Procedures Applications will be reviewed by DRG staff for completeness and by NIAID staff to determine administrative and programmatic responsiveness to this RFA. Those judged to be incomplete or nonresponsive will be returned to the applicant without review. Those considered complete and responsive may be subjected to a triage review by an NIAID peer review group, before or during the initial review meeting, to determine their scientific merit relative to the other applications submitted in response to this RFA. The NIAID will withdraw from competition those applications judged by the triage peer review group to be noncompetitive for award and will so notify the applicant investigator and the institutional business official. Those applications judged to be competitive for award will be reviewed for scientific and technical merit by a Review Committee convened by the Division of Extramural Activities, NIAID. The second level of review will be provided by the National Advisory Allergy and Infectious Diseases Council. Review Criteria The factors to be considered in scientific review of the application are: 1. Scientific merit of the proposed research approach, design, and methodology as well as the potential scientific, technical or medical significance of the proposed research. 2. Research experience and competence of the Principal Investigator(s) and other staff to conduct the proposed studies. 3. Adequacy of the time (effort) which the Principal Investigator(s) and staff would devote to the proposed studies. 4. Adequacy of facilities, including, if relevant to the proposed research, the clinical facilities and patient availability for clinical studies. AWARD CRITERIA In selecting applications for funding, while scientific merit is of primary consideration, applications will also be evaluated for programmatic relevance and potential for impact on the clinical management of infectious diseases. Particular attention will be paid to studies that assess the basis for non-responsiveness, interference between agents and/or reactogenicity, and the potential public health impact of the proposed multicomponent vaccines. INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Dr. David L. Klein Division of Microbiology and Infectious Diseases National Institute of Allergy and Infectious Diseases Solar Building, Room 3A-10 Bethesda, MD 20892 Telephone: (301) 496-5305 FAX: (301) 496-8030 E-mail: dlk@exec.niaid.pc.niaid.nih.gov Address the letter of intent, two copies of the completed application, and direct any questions regarding review procedures to: Dr. Olivia Preble Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4C-19 Bethesda, MD 20892 Telephone: (301) 496-8208 FAX: (301) 402-2638 Direct inquiries regarding fiscal matters to: Mr. Todd Ball Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4B-35 Bethesda, MD 20892 Telephone: (301) 496-7075 FAX: (301) 480-3780 Schedule Letter of Intent Receipt Date: October 1, 1993 Application Receipt Date: November 24, 1993 Scientific Review Date: March 1994 Council Meeting Date: June 1994 Earliest Award Date: July 1, 1994 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.856, Microbiology and Infectious Disease Research. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. From owner-sci-resources@net.bio.net Sun Aug 08 23:00:00 1993 Path: biosci!NET.BIO.NET!kristoff From: kristoff@NET.BIO.NET (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NSF - Summary of new documents on STIS - 8 August 1993 Message-ID: Date: 9 Aug 93 19:56:54 GMT Sender: kristoff@net.bio.net Distribution: bionet Lines: 87 Approved: sci-resources-moderator@net.bio.net ** NEW DOCUMENTS ON STIS ** Document Type: Program Guideline Title: NSF 93-107 -- CISE Institutional Infrastructure - Research Infrastructure Program File size (bytes): 39846 STIS Filename: nsf93107 Title: NSF 93-112 - Research Experiences for Undergraduates File size (bytes): 42469 STIS Filename: nsf93112 Document Type: SRS Report Title: NSF 92-322--Federal Funds for Research and Development File size (bytes): 61158 STIS Filename: nsf92322 Also available: nsf92322.zip Title: NSF 92-322--Federal Funds for Research and Development File size (bytes): 61158 STIS Filename: nsf92322 Also available: nsf92322.zip Title: NSF 93-323 -- Graduate Enrollment and Support Fall -1991 File size (bytes): 37760 STIS Filename: nsf92323 Also available: nsf92323.zip Title: NSF 93-323 -- Graduate Enrollment and Support Fall -1991 File size (bytes): 37760 STIS Filename: nsf92323 Also available: nsf92323.zip Title: NSF 92-324--Federal Support to Universities, Colleges, and File size (bytes): 32682 STIS Filename: nsf92324 Also available: nsf92324.zip Title: NSF 92-324--Federal Support to Universities, Colleges, and File size (bytes): 32682 STIS Filename: nsf92324 Also available: nsf92324.zip ------------------------------------------------------------------------ ** FOR YOUR REFERENCE ** ------------------------------------------------------------------------ HOW TO OBTAIN DOCUMENTS The above files can be retrieved in electronic form using the STIS system. If you don't know how to use STIS, send an E-mail message to stisinfo@nsf.gov (Internet) or stisinfo@NSF (BITNET). You will receive a copy of the STIS flyer via E-mail. If you are already using STIS, you can use the information above to retrieve these files: Documents via E-mail: Send a message to stisserv@nsf.gov (Internet) or stisserv@NSF (BITNET). Use the "STIS Filename" shown above in the "get" command. For example, to retrieve nsf92324, the text of your message should be as follows: get nsf92324 Anonymous FTP: FTP to stis.nsf.gov. Use the "STIS Filename" shown above to retrieve a file. For example, to retrieve nsf92324, you would enter: ftp> get nsf92324 WAIS or Gopher: Do a word search on the filename as shown in the summary. If you want a *printed* copy of a document: Send your name and postal mailing address, and the document title and number to "firstop@nsf.gov" (Internet) or "firstop@nsf" (BITNET). If you have problems with the above procedures: Send a message to "stis@nsf.gov" (Internet) or "stis@NSF" (BITNET). From owner-sci-resources@net.bio.net Fri Aug 13 23:00:00 1993 Path: biosci!NET.BIO.NET!kristoff From: kristoff@NET.BIO.NET (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 22, no. 29., pt. 1, 13 August 1993 Message-ID: Date: 14 Aug 93 03:34:46 GMT Sender: kristoff@net.bio.net Distribution: bionet Lines: 1142 Approved: sci-resources-moderator@net.bio.net NOTE: The NIH Guide may be split into more than one mail message to avoid truncation during e-mail distribution. The first message always begins with the RFP/RFA summary sections followed by the appended texts of the full RFP/RFAs. ---------------------------------------------------------------------- $$XID NIHGUIDE 19930813 V22N29 P1O1 ************************************ X-comment: RFAs described: AR-94-001, HL-93-018, AI-93-021 NIH GUIDE - Vol. 22, No. 29 - August 13, 1993 $$INDEX BEGIN ******************************************************* NOTICES $$INDEX N1 ********************************************************** ENVIRONMENTAL HEALTH SCIENCES CORE CENTER GRANTS PROGRAM National Institute of Environmental Health Sciences INDEX: ENVIRONMENTAL HEALTH SCIENCES $$INDEX N2 ********************************************************** RESEARCH DEMONSTRATION AND DISSEMINATION PROJECTS National Institute on Drug Abuse INDEX: DRUG ABUSE $$INDEX N3 ********************************************************** NATIONAL ANIMAL WELFARE EDUCATION WORKSHOPS National Institutes of Health INDEX: NATIONAL INSTITUTES OF HEALTH $$INDEX N4 ********************************************************** PROTECTING HUMAN RESEARCH SUBJECTS: INSTITUTIONAL REVIEW BOARD GUIDEBOOK National Institutes of Health INDEX: NATIONAL INSTITUTES OF HEALTH NOTICES OF AVAILABILITY (RFPS AND RFAs) $$INDEX R1 ********************************************************** PREPARATION AND DISTRIBUTION OF RESEARCH DRUG PRODUCTS (RFP N01DA-4- 7403) National Institute on Drug Abuse INDEX: DRUG ABUSE $$INDEX R2 11/30/93 ************************************************* FAILURE TO HEAL: CHRONIC WOUND HEALING IN THE SKIN (RFA AR-94-001) National Institute of Arthritis and Musculoskeletal and Skin Diseases National Institute on Aging National Institute of Child Health and Human Development National Institute of Diabetes and Digestive and Kidney Diseases National Institute of Nursing Research INDEX: ARTHRITIS, MUSCULOSKELETAL, SKIN DISEASES; AGING; CHILD HEALTH, HUMAN DEVELOPMENT, DIABETES, DIGESTIVE, KIDNEY DISEASES; NURSING RESEARCH $$INDEX R3 12/10/93 ************************************************* HEMOGLOBIN-BASED OXYGEN CARRIERS: MECHANISMS OF TOXICITY (RFA HL-93- 018) National Heart, Lung, and Blood Institute INDEX: HEART, LUNG, BLOOD $$INDEX R4 12/22/93 ************************************************* STRATEGIC PROGRAM FOR INNOVATIVE RESEARCH ON AIDS TREATMENT (RFA AI-93-021) National Institute of Allergy and Infectious Diseases INDEX: ALLERGY, INFECTIOUS DISEASES This publication is available electronically to institutions via BITNET or INTERNET and is also on the NIH GOPHER. Alternative access is through the NIH Grant Line using a personal computer (data line 301/402-2221). Contact Dr. John James at 301/594-7270 for details. $$INDEX END ********************************************************* NOTICES $$N1 BEGIN ********************************************************** ENVIRONMENTAL HEALTH SCIENCES CORE CENTER GRANTS PROGRAM NIH GUIDE, Volume 22, Number 29, August 13, 1993 P.T. 04; K.W. 0725005, 0710030, 0403004 National Institute of Environmental Health Sciences This Notice is to remind potential applicants of the single receipt date of February 1 each year for this program. The National Institute of Environmental Health Sciences (NIEHS) uses a variety of award mechanisms to accomplish its mission of studying the mechanisms and effects of environmental agents on human health. Among these are Environmental Health Sciences (EHS) Center Grants, a program of core center support (P30). The objective of this program is to provide core support for an administrative structure, scientific leadership, and shared core equipment to groups of productive scientists with programs in environmental health. The award allows these scientists to: (1) focus their research efforts on issues of relevance to the NIEHS, (2) work in an environment conducive to inter-disciplinary approaches to such research, (3) serve as a resource to the NIEHS in providing scientific expertise on critical public health issues and (4) engage in community outreach and education programs dealing with regional environmental health issues. Direct research support is NOT provided by the grant, except for limited funds for pilot projects or exploratory research. The NIEHS currently supports thirteen EHS centers and five MFBS centers. The funding of additional centers is subject to budget and other limitations. Because of these limitations and the special nature of the program, it is imperative that potential applicants contact NIEHS staff to discuss the scope, content, size, and timing of any applications for this program. In 1994, two extant EHS Centers will be competing for funding. INQUIRIES Guidelines for this program, including fiscal limitations, review criteria, and additional information are available from: Dr. Thorsten A. Fjellstedt Division of Extramural Research and Training National Institute of Environmental Health Sciences P.O. Box 12233, 104 Alexander Drive Research Triangle Park, NC 27709 Telephone: (919) 541-0131 $$N1 END ************************************************************ $$N2 BEGIN ********************************************************** RESEARCH DEMONSTRATION AND DISSEMINATION PROJECTS NIH GUIDE, Volume 22, Number 29, August 13, 1993 P.T. National Institute on Drug Abuse The purpose of this announcement is to alert the research community that effective immediately, applications for support under the R18 mechanism, Research Demonstration and Dissemination Projects, for the National Institute on Drug Abuse will no longer be accepted for review or award. The investigator-initiated traditional research project grant award mechanism (R01) should be used by new applicants who would have considered the research demonstration mechanism. Grantees currently holding R18 awards should contact the NIDA program officer for guidance on submitting competing renewal applications. INQUIRIES Director Office of Extramural Program Review National Institute on Drug Abuse 5600 Fishers Lane Rockville, MD 20857 Telephone: (301) 443-2755 $$N2 END ************************************************************ $$N3 BEGIN ********************************************************** NATIONAL ANIMAL WELFARE EDUCATION WORKSHOPS NIH GUIDE, Volume 22, Number 29, August 13, 1993 P.T. 42; K.W. 0201011, 1014003 National Institutes of Health The National Institutes of Health (NIH), Office for Protection from Research Risks (OPRR), is continuing to sponsor workshops on implementing the Public Health Service Policy on Humane Care and Use of Laboratory Animals. Each of the workshops scheduled for FY 1993 will focus on a specific theme. The workshops are open to institutional administrators, members of Institutional Animal Care and Use Committees, laboratory animal veterinarians, investigators other institutional staff who have responsibility for high-quality management of sound institutional animal care and use programs. Ample opportunities will be provided to exchange ideas and interests, through question and answer sessions and informal discussions. SOUTHWESTERN REGION DATES: September 27-29, 1993 LOCATION Oklahoma City Hilton Northwest 2945 N.W. Expressway Oklahoma City, OK 73112 Telephone: 1-800-445-8667 FAX: (405) 842-4328 SPONSOR University of Oklahoma Health Sciences Center REGISTRATION Ms. Marilyn Perry, Assistant to Director for Compliance Division of Animal Resources BMSB, Room 203 University of Oklahoma Health Sciences Center Oklahoma City, OK 73190 Telephone: (405) 271-5185 FAX: (405) 271-3032 FEE: $140; Graduate Students and Post-Docs $90.00 TOPIC: THE PRESENT AND FUTURE USE OF FARM ANIMALS IN BIOMEDICAL RESEARCH AND EDUCATION DATES: September 28 (Afternoon); September 29 (Morning) LOCATION Oklahoma City Hilton Northwest (Same as above) SPONSOR The University of Oklahoma Health Sciences Center REGISTRATION Ms. Marilyn Perry (address as above) TOPIC: USDA OPEN FORUM ON FARM ANIMAL ISSUES UNDER THE ANIMAL WELFARE ACT INQUIRIES For further information concerning these workshops and future NIH/OPRR Animal Welfare Education workshops, contact: Ms. Roberta Sonneborn Office for Protection from Research Risks National Institutes of Health Building 31, Room 5B59 Bethesda, MD 20892 Telephone: (301) 496-7163 FAX: (301) 402-2803 $$N3 END ************************************************************ $$N4 BEGIN ********************************************************** PROTECTING HUMAN RESEARCH SUBJECTS: INSTITUTIONAL REVIEW BOARD GUIDEBOOK NIH GUIDE, Volume 22, Number 29, August 13, 1993 P.T. 34; K.W. 0783005, 1014006 National Institutes of Health The Office for Protection from Research Risks, Office of Extramural Research, National Institutes of Health announces the availability of the publication, "Protecting Human Research Subjects: Institutional Review Board Guidebook." The "IRB Guidebook" is designed to assist institutional review board (IRB) members, researchers and institutional administrators in fulfilling their responsibilities for protecting the rights and welfare of human subjects as defined in the Department of Health and Human Services regulations ("Protection of Human Subjects;" 45 CFR 46). Copies may be obtained from the U.S. Government Printing Office, Superintendent of Documents, P.O. Box 371954, Pittsburgh, PA 15250 (FAX 202/512-2250; Telephone 202/783-3238) for $31.00. To order the IRB Guidebook, reference GPO Stock No. 017-040-00525-3. $$N4 END ************************************************************ NOTICES OF AVAILABILITY (RFPs AND RFAs) $$R1 BEGIN N01DA-4-7403 ********************************************* PREPARATION AND DISTRIBUTION OF RESEARCH DRUG PRODUCTS NIH GUIDE, Volume 22, Number 29, August 13, 1993 RFP AVAILABLE: N01DA-4-7403 P.T. 34; K.W. 0740021, 1003008, 1003012 National Institute on Drug Abuse The National Institute on Drug Abuse (NIDA) is soliciting proposals from qualified organizations to: develop and produce dosage forms of cannabinoids and other drugs used in basic and clinical research programs; analyze such preparations and cannabis samples for cannabinoid content; and maintain supply and shipment records of these and other research materials. The work may include the manufacture of sterile parenterals, marijuana cigarettes, oral dosage forms, morphine pellets, and other dosage forms as needed; the preparation of analytical standards; and the performance of in vitro smoking studies. Drug Enforcement Administration registrations for manufacturing, distribution, importation, and exportation of Schedule I and II drugs are required. It is anticipated that a five-year incrementally funded contract will be awarded. Estimated issuance date of RFP No. N01DA-4-7403 is August 12, 1993, and responses are due to be received in the Contracting Office 45 calendar days thereafter. This is a follow-on procurement to Contract No. 271-90-7301 with Research Triangle Institute. INQUIRIES Only written or facsimile requests for this RFP will be accepted. Forward all requests to: Ms. Carol Cushing, Contract Specialist National Institute on Drug Abuse Parklawn Building, Room 10-49 5600 Fishers Lane Rockville, MD 20857 FAX: (301) 443-7595 $$R1 END ************************************************************ $$R2 BEGIN AR-94-001 FULL-TEXT ************************************** FAILURE TO HEAL: CHRONIC WOUND HEALING IN THE SKIN NIH GUIDE, Volume 22, Number 29, August 13, 1993 RFA AVAILABLE: AR-94-001 P.T. National Institute of Arthritis and Musculoskeletal and Skin Diseases National Institute on Aging National Institute of Child Health and Human Development National Institute of Diabetes and Digestive and Kidney Diseases National Institute of Nursing Research Letter of Intent Receipt Date: October 15, 1993 Application Receipt Date: November 30, 1993 THIS IS A NOTICE OF AVAILABILITY OF A REQUEST FOR APPLICATIONS (RFA); IT IS ONLY AN ABSTRACT OF THE RFA. POTENTIAL APPLICANTS MUST REQUEST THE COMPLETE RFA, WHICH CONTAINS ESSENTIAL INFORMATION FOR THE PREPARATION OF AN APPLICATION, FROM THE CONTACT LISTED IN "INQUIRIES," BELOW. FAILURE TO FOLLOW THE INSTRUCTIONS IN THE COMPLETE RFA MAY RESULT IN AN INCOMPLETE APPLICATION, WHICH WILL BE RETURNED TO THE APPLICANT WITHOUT REVIEW. PURPOSE The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institute on Aging (NIA), National Institute of Child Health and Human Development (NICHD), National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK), and National Institute of Nursing Research (NINR) invite applications for research on wounds that fail to heal, the prototypic ones being decubitus (pressure) ulcers, venous (stasis) ulcers, and diabetic ulcers. Studies may be both basic and applied. The intent is to apply knowledge rapidly to the prevention and treatment of chronic wounds in a clinical/rehabilitation situation. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This RFA, Failure to Heal: Pathogenesis of Chronic Wound Healing in the Skin, is related to the priority area of chronic disabling conditions. Potential applicants may obtain a copy of "Healthy People 2000" (Summary Report: Stock No. 017-001-00474-0 or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Foreign institutions are not eligible for the First Independent Research Support and Transition (FIRST) (R29) award. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT This RFA will use the National Institutes of Health (NIH) individual research grant (R01), the FIRST award (R29), and the newly described interactive R01 mechanisms. Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. The total project period for applications submitted in response to the present RFA may not exceed five years. The anticipated award date is July 1, 1994. Because the nature and scope of the research proposed in response to this RFA may vary, it is anticipated that the size of an award will also vary. This RFA is a one time solicitation. Future unsolicited competing continuation applications will compete with all investigator initiated applications and be reviewed according to the customary peer review procedures. FUNDS AVAILABLE The estimated funds (total costs) available for the first year of support for the entire program is anticipated to be 1.6 million dollars. The anticipated number of new awards is eight. RESEARCH OBJECTIVES In spite of recent advances in the basic mechanisms of wound healing, knowledge of factors involved in the development and treatment of chronic wounds and their prevention remains limited. Future progress in the treatment of chronic wounds will require greater understanding of their pathogenesis and failure to heal. These two inseparable aspects, pathogenesis and failure to heal, were the subject of a workshop sponsored by the Skin Diseases Interagency Coordinating Committee for the National Institutes of Health held on January 10 and 11, 1993. The workshop brought together a multidisciplinary group of scientists working in the field of wound repair. A summary of this workshop will be published in the Journal of Investigative Dermatology. Identified below is a selection of the areas covered in that workshop that are relevant to this solicitation. This list is illustrative and not exclusive or restrictive. o Cytokines and Growth Factors o Keratinocyte Migration in the Wound Bed o The Chronic Wound Environment o Matrix Degrading Metalloproteinases o Metabolic Abnormalities o Hypoxia o Fibrin Formation and Removal o Aging and Chronic Wound Healing o Clinical Therapeutics STUDY POPULATIONS SPECIAL INSTRUCTIONS FOR INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDIES For projects involving clinical research, NIH requires applicants to give special attention to the inclusion of women and minorities in study populations. If women or minorities are not included in the study populations for clinical studies, a specific justification for this exclusion must be provided. Applications without such documentation will not be accepted for review. Applications from institutions that have a General Clinical Research Center (GCRC) funded by the NIH National Center for Research Resources may wish to identify the GCRC as a resource for conducting the proposed research. If so, a letter of agreement from either the GCRC program director or Principal Investigator could be included with the application. LETTER OF INTENT Prospective applicants are asked to submit, by October 15, 1993, a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, the identities of other key personnel and participating institutions, and the number and title of the RFA in response to which the application may be submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information that it contains allows ICD staff to estimate the potential review workload and to avoid conflict of interest in the review. The letter of intent is to be sent to Dr. Alan N. Moshell at the address listed under INQUIRIES. APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 9/91) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research; from the Office of Grants Information, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone 301/594-7248. The RFA label available in the PHS 398 (rev. 9/91) application form must be affixed to the bottom of the face page of the application. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2a of the face page of the application form and the YES box must be marked. Applications for the FIRST Award (R29) must include at least three sealed letters of reference attached to the face page of the original application. FIRST Award (R29) applications submitted without the required numbered of reference letters will be considered incomplete and will be returned without review. Submit a signed, typewritten original of the application, including the Checklist, and three signed, photocopies, in one package to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** At the time of submission, two additional copies of the application must also be sent to Dr. Alan N. Moshell at the address listed under INQUIRIES. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by the Division of Research Grants (DRG) and responsiveness by the NIAMS. Incomplete applications will be returned to the applicant without further consideration. If the application is not responsive to the RFA, ICD staff will contact the applicant to determine whether to return the application to the applicant or submit it for review in competition with unsolicited applications at the next review cycle. Applications may be triaged by an ICD peer review group on the basis of relative competitiveness. The NIH will withdraw from further competition those applications judged to be non-competitive for award and notify the applicant Principal Investigator and institutional official. Those applications judged to be competitive will undergo further scientific merit review. Those applications that are complete and responsive will be evaluated for scientific/ technical merit by an appropriate peer review group convened by NIAMS. The second level of review will be provided by the appropriate National Advisory Council/Board. Review criteria for this RFA are generally the same as those for unsolicited research grant applications. AWARD CRITERIA The anticipated date of award is July 1, 1994. Awards will be based upon the following criteria: o priority score o availability of funds o programmatic priorities of the funding ICD o responsiveness to the RFA INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues and requests for the RFA to: Alan N. Moshell, M.D. National Institute of Arthritis, and Musculoskeletal and Skin Diseases Westwood Building, Room 752 Bethesda, MD 20892 Telephone: (301) 594-9955 FAX: (301) 594-9673 Hilary D. Sigmon, Ph.D., R.N. National Institute for Nursing Research Westwood Building, Room 405 Bethesda, MD 20892 Telephone: (301) 594-7397 FAX: (301) 594-7603 Dr. David Finkelstein National Institute on Aging Gateway Building, Room 2C231 Bethesda, MD 20892 Telephone: (301) 496-6402 FAX: (301) 402-0010 Dr. Danuta Krotoski National Center for Medical Rehabilitation Research National Institute of Child Health and Human Development Building 61E, Room 2A03 Bethesda, MD 20892 Telephone: (301) 402-2242 FAX: (301) 402-0832 Dr. Charles A. Wells National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 622 Bethesda, MD 20892 Telephone: (301) 594-7505 FAX: (301) 594-9011 Direct inquiries regarding fiscal matters to: Mary Graham National Institute of Arthritis, Musculoskeletal and Skin Diseases Westwood Building, Room 722 Bethesda, MD 20892 Telephone: (301) 594-9974 FAX: (301) 594-9950 Sally A. Nichols Grants Management Office National Institute for Nursing Research Westwood Building, Room 748 Bethesda, MD 20892 Telephone: (301) 594-7498 FAX: (301) 594-7603 Mary Ellen Colvin Grants Management Office National Institute of Child Health and Human Development Building 61E, Room 8A17F Bethesda, MD 20892 Telephone: (301) 496-1303 FAX: (301) 402-0915 Bob Pike Grants Management Office National Institute on Aging Gateway Building, Room 2N212 Bethesda, MD 20892 Telephone: (301) 496-1472 FAX: (301) 402-3672 Betty E. Bailey Division of Extramural Activities National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 649 Bethesda, MD 20892 Telephone: (301) 594-7543 FAX: (301) 594-7594 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.361. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$R2 END ************************************************************ $$R3 BEGIN HL-93-018 FULL-TEXT ************************************** HEMOGLOBIN-BASED OXYGEN CARRIERS: MECHANISMS OF TOXICITY NIH GUIDE, Volume 22, Number 29, August 13, 1993 RFA AVAILABLE: HL-93-018 P.T. National Heart, Lung, and Blood Institute Letter of Intent Receipt Date: October 15, 1993 Application Receipt Date: December 10, 1993 THIS IS A NOTICE OF AVAILABILITY OF A REQUEST FOR APPLICATIONS (RFA); IT IS ONLY AN ABSTRACT OF THE RFA. POTENTIAL APPLICANTS MUST REQUEST THE COMPLETE RFA, WHICH CONTAINS ESSENTIAL INFORMATION FOR THE PREPARATION OF AN APPLICATION, FROM THE CONTACT LISTED IN "INQUIRIES," BELOW. FAILURE TO FOLLOW THE INSTRUCTIONS IN THE COMPLETE RFA MAY RESULT IN AN INCOMPLETE APPLICATION, WHICH WILL BE RETURNED TO THE APPLICANT WITHOUT REVIEW. PURPOSE The Transfusion Medicine Branch, Division of Blood Diseases and Resources, National Heart, Lung, and Blood Institute (NHLBI), announces the availability of an RFA encouraging studies to elucidate the mechanisms of toxicity of hemoglobin-based oxygen carriers. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This RFA, Hemoglobin-Based Oxygen Carriers: Mechanisms of Toxicity, is related to the priority areas of HIV infection, and immunization and infectious diseases. The goal of this program is the development of safe and effective hemoglobin-based oxygen carriers free of infectious disease agents. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-782-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of state or local governments, and eligible agencies of the Federal government. Awards in response to this RFA will be made to foreign institutions only for research of very unusual merit, need, and promise, and in accordance with PHS policy governing such awards. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT This RFA will use the National Institutes of Health (NIH) individual research grant (R01) award and is a one-time solicitation. Applicants, who will plan and execute their own research programs, are requested to furnish their own estimates of the time required to achieve the objectives of the proposed research project. Up to five years of support may be requested. At the end of the official award period, renewal applications may be submitted for peer review and competition for support through the regular grant program of the NHLBI. It is anticipated that support for the present program will begin July 1, 1994. Administrative adjustments in project period or amount of support may be required at the time of the award. Since a variety of approaches would represent valid responses to this announcement, it is anticipated that there will be a range of costs among individual grants awarded. All current policies and requirements that govern the research grant programs of the NIH will apply to grants awarded in connection with this RFA. FUNDS AVAILABLE It is anticipated that for fiscal year 1994, $1,500,000 will be available for this initiative. Approximately $750,000 of that amount will be provided through an initiative of the Advanced Biomaterials Program of the Federal Coordinating Council for Science, Engineering and Technology (FCCSET). It should be noted that award of grants pursuant to this RFA is contingent upon receipt of funds for this purpose. It is anticipated that about six to eight new grants will be awarded under this program. The specific amount to be funded will, however, depend on the merit and scope of the applications received and on the availability of funds. If collaborative arrangements involve sub-contracts with other institutions, the NHLBI Grants Operations Branch (telephone 301-594-7436) should be consulted regarding procedures to be followed. RESEARCH OBJECTIVES The objective of this RFA is to encourage research aimed at providing an understanding of the mechanisms of toxicity of hemoglobin-based oxygen carriers. This program encourages research addressing such fundamental questions as: (1) what are the mechanisms of vasoactivity of hemoglobin solutions, (2) how do protein modifications affect vasoactivity, (3) what are the mechanisms of stimulation of inflammation mediators by hemoglobin-based oxygen carriers, (4) how can this stimulation be prevented; (5) what animal or in vitro models are best used to study toxic effects of oxygen carriers; (6) what are the long-term (metabolic and pharmacologic) effects of oxygen carriers, and (7) what models are best to demonstrate efficacy in terms of oxygen transport to tissue? The ultimate goal is to satisfy a fundamental need in clinical medicine, i.e., development of a safe, economical, and efficacious alternative to allogeneic human red blood cells for transfusion. Examples of promising topics are: o Studies of the interaction of hemoglobin with endothelium and macrophages. o Development of animal models that simulate clinical use, such as trauma, shock, infection, and surgical blood loss. o Studies relating the biochemical modification of hemoglobin to its biological effects. o Studies of encapsulation of hemoglobin into artificial vesicles - biochemical, physical, physiological, and biological effects. o Studies of the tissue distribution and metabolic fate of modified hemoglobins, and artificial vesicles. These are intended as examples only. Investigators are encouraged to consider other innovative approaches. STUDY POPULATIONS SPECIAL INSTRUCTIONS FOR INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDIES For projects involving clinical research, NIH requires applicants to give special attention to the inclusion of women and minorities in study populations. If women or minorities are not included in the study populations for clinical studies, a specific justification for this exclusion must be provided. Applications without such documentation will not be accepted for review. LETTER OF INTENT Prospective applicants are asked to submit, by October 15, 1993, a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, the identities of other key personnel and participating institutions, and the number and title of the RFA in response to which the application may be submitted. Such letters are requested only for the purpose of providing an indication of the number and scope of applications to be received; therefore their receipt is usually not acknowledged. A letter of intent is not binding, will not enter into the review of any application subsequently submitted, and is not a necessary requirement for the application. This letter of intent is to be sent to: Chief, Centers and Special Projects Review Section Division of Extramural Affairs National Heart, Lung, and Blood Institute Westwood Building, Room 553 Bethesda, MD 20892 Telephone: (301) 594-7448 FAX: (301) 594-7407 APPLICATION PROCEDURES Applications must be received by December 10, 1993. Applications are to be submitted on the research grant application form PHS 398 (rev. 9/91). This form is available in an applicant institution's office of sponsored research or business office; and from the Office of Grants Information, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone 301/594-7248. The National Institute of Environmental Health Sciences (NIEHS) also has an interest in the subject matter of this RFA. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by the Division of Research Grants (DRG) and responsiveness by the NHLBI. Incomplete applications will be returned to the applicant without further consideration. If the application is not responsive to the RFA, NHLBI staff will contact the applicant to determine whether to return the application to the applicant or submit it for review in competition with unsolicited applications at the next review cycle. Those applications that are complete and responsive will be evaluated for scientific/technical merit by an appropriate peer review group convened by the Division of Extramural Affairs, NHLBI. The factors to be considered in the evaluation of scientific merit of each application will be similar to those used in the review of traditional research grant applications. The second level of review will be provided by the National Heart, Lung, and Blood Advisory Council. INQUIRIES Written and telephone requests for the RFA and the opportunity to clarify any issues or questions from potential applicants are welcome. Direct requests for the RFA and inquiries regarding programmatic issues to: Dr. George J. Nemo Division of Blood Diseases and Resources National Heart, Lung, and Blood Institute Federal Building, Room 504 Bethesda, MD 20892 Telephone: (301) 496-1537 FAX: (301) 402-4843 Direct inquiries regarding fiscal and administrative matters to: Ms. Jane R. Davis Blood Division Grants Management Section National Heart, Lung, and Blood Institute Westwood Building, Room 4A11 Bethesda, MD 20892 Telephone: (301) 594-7436 AUTHORITY AND REGULATIONS The programs of the Division of Blood Diseases and Resources, NHLBI, are described in the Catalog of Federal Domestic Assistance number 93.839. Awards will be made under the authority of the Public Health Service Act, Section 301 (42 USC 241) and administered under PHS grant policies and Federal regulations, most specifically 42 CFR Part 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372, or to Health Systems Agency review. $$R3 END ************************************************************ $$R4 BEGIN AI-93-021 FULL-TEXT ************************************** STRATEGIC PROGRAM FOR INNOVATIVE RESEARCH ON AIDS TREATMENT NIH GUIDE, Volume 22, Number 29, August 13, 1993 RFA AVAILABLE: AI-93-021 P.T. National Institute of Allergy and Infectious Diseases Letter of Intent Receipt Date: September 23, 1993 Application Receipt Date: December 22, 1993 THIS IS A NOTICE OF AVAILABILITY OF A REQUEST FOR APPLICATIONS (RFA); IT IS ONLY AN ABSTRACT OF THE RFA. POTENTIAL APPLICANTS MUST REQUEST THE COMPLETE RFA, WHICH CONTAINS ESSENTIAL INFORMATION FOR THE PREPARATION OF AN APPLICATION, FROM THE CONTACT LISTED IN "INQUIRIES," BELOW. FAILURE TO FOLLOW THE INSTRUCTIONS IN THE COMPLETE RFA MAY RESULT IN AN INCOMPLETE APPLICATION, WHICH WILL BE RETURNED TO THE APPLICANT WITHOUT REVIEW. PURPOSE This RFA, Strategic Program for Innovative Research on AIDS Treatment (SPIRAT), will support innovative, integrated and inter-related preclinical and clinical research to validate clinical therapeutic concepts for the treatment of HIV-1 infection. A SPIRAT can focus its therapeutic research activities on viral gene(s) or cellular factors required for HIV expression, novel immunotherapeutic approaches, or other approaches with the potential for effective, long-term therapy. Excluded from this RFA are development of drugs and treatment for opportunistic infections, both the subject of other NIAID sponsored programs. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This RFA, Strategic Program for Innovative Research on AIDS Treatment (SPIRAT), is related to the priority area of HIV infection. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325, (202) 783-3238. ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic, private, public, and for-profit organizations such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT Awards will be made as Cooperative Agreements (U19s). The Cooperative Agreement funding mechanism differs from the traditional research grant in that the Government component (NIAID) awarding the Cooperative Agreement anticipates substantial programmatic involvement during performance. The nature of NIAID staff participation is described in the RFA. However, it is the Principal Investigator who defines his/her objectives in accord with his/her interests and perceptions of innovative approaches for the treatment of HIV-1 infection. The applicant institution and the Principal Investigator will be responsible for the Group's application. Awards will be made to the applicant institution on behalf of the group as a whole and not to individual research projects within the Group. Respondents to this RFA may include new applications for a maximum period of four years support. This RFA may be a one-time solicitation. If by the end of the third year of the award, the NIAID has not announced its intent to re-issue the RFA, incumbents should contact NIAID program staff and consider submitting investigator-initiated (R01) applications which will compete with all investigator-initiated applications and be reviewed according to the customary NIH peer review procedures. FUNDS AVAILABLE It is estimated that five to six Groups will be funded for funded under this program as a result of this RFA for a maximum period of years. A total of $6.0 million (including direct and indirect costs) is available for first year funding of this program. A maximum of $25.0 million will be available over the four year period. Awards and level of support are dependent on the receipt of a sufficient number of applications of high scientific merit. Because the nature and scope of the research proposed in response to this RFA may vary, it is anticipated that the size of awards will vary also. Applications with budgets in excess of $1.3 million total costs (direct and indirect) for the first year will be returned without review. Budget requests must be adequately justified and commensurate with the complexity of the project. Although this program is provided for in the financial plans of the NIAID, awards pursuant to this RFA are contingent upon the availability of funds for this purpose. RESEARCH OBJECTIVES The principal goals of this RFA are to (1) interface between innovative, advanced preclinical research of sound scientific rationale and clinical proof-of-concept of an identified HIV therapeutic strategy; and (2) implement pilot clinical studies in HIV-1 infected individuals to validate the therapeutic modality. The following approaches are provided as examples of studies responsive to this RFA and are not intended to be inclusive or restrictive: o Strategies that target HIV gene expression via interference with HIV cis-acting elements, viral regulatory elements, viral structural components, or cellular factors required for HIV expression; o Strategies that interrupt/prevent steps involved in HIV/cell interaction, entry, biochemical processes, virus (or viral components) transport between cellular compartments, assembly, release, maturation; o Intracellular delivery of antagonists to curb critical events in HIV life cycle, such as trans-dominant suppressors, decoys, competitors, catalytic RNA, using viral vectors or other delivery strategies (gene therapy); o Innovative exploitation of the humoral and cellular mechanisms of the immune system for a targeted anti-HIV attack; o Immune system reconstitution, capitalizing on new advanced in restoring immune functions; o Direct DNA transduction ('naked' DNA injection) to augment immune response(s) via intracellular expression of HIV immunogen(s); o Strategies that target non-T cells compartment(s) which may play an essential role in cell-free virus transport, cell-cell transmission, and general dissemination of HIV in the body; o Strategies that prevent the onset of HIV-related neurologic dysfunction, or counteract the neurological damage seen in patients with AIDS-related dementia; o Novel therapeutic interventions that are not affected by emergence of drug-resistant HIV variants, or are insensitive to factors affecting the emergence of drug resistance. SPIRAT applicants from an institution receiving government funds under GCRC, CFAR, DATRI, ACTU, AVEU, and CPCRA, should describe how these programs are integrated with the proposed studies, and ensure that no scientific and budgetary overlap exist with the SPIRAT proposal. SPECIAL REQUIREMENTS A SPIRAT must be composed of a minimum of three projects led by independent investigators with inter-related objectives, and may consist of scientists from a combination of academic, non-profit research, and commercial organizations. For the purpose of this RFA, three (or more) projects within a single company or academic department will not be considered independent. A core component cannot be used toward fulfillment of the requirement for three projects. STUDY POPULATIONS SPECIAL INSTRUCTIONS FOR INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDIES For projects involving clinical research, NIH requires applicants to give special attention to the inclusion of minorities and women in study populations. If women and minorities are not included in the study populations for clinical studies, a specific justification for this exclusion must be provided. Applications without such documentation will not be accepted for review. LETTER OF INTENT Prospective applicants are asked to submit, by September 23, 1993, a letter of intent that includes a descriptive title of the proposed research, brief description of the proposed research, the name, address (including institution), and telephone number of the Principal Investigator, the identity of project leaders and titles of their projects, other key personnel, and their institutions, and the number and title of this RFA. Although a letter of intent is not required, is not binding, and does not enter into the review of the application, the information that it contains allows NIAID to estimate the potential workload for reviewers and to avoid possible conflict of interest in the review progress. The letter of intent is to be sent to Dr. Dianne Tingley at the address listed under INQUIRIES. below. APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 9/91) is to be used in applying for these grants. This form is available at most institutional offices of sponsored research and from the Office of Grants Information, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone 301/594-7248. Additional instructions for the preparation of multi-component applications are provided with the RFA. Applications not received by December 22, 1993 will be considered unresponsive and returned to the applicant without review. REVIEW CONSIDERATIONS Applications will be reviewed by Division of Research Grants (DRG) for completeness and by NIAID staff to determine responsiveness to this RFA. Incomplete and non-responsive applications will be returned to the applicant without further consideration or review. The NIAID will remove from further competition those applications judged to be noncompetitive for award and will notify the applicant and the institutional business official. Those applications judged to be competitive for award will be further reviewed for scientific and technical merit by an appropriate review committee. A second level of review will be provided by the NIAID Council (see SCHEDULE). INQUIRIES Written and telephone requests for the RFA and the opportunity to clarify any issues or questions from potential applicants are welcome. Direct inquiries regarding programmatic or scientific issues and requests for the RFA to: Nava Sarver, Ph.D. Division of AIDS National Institute of Allergy and Infectious Diseases 6003 Executive Boulevard Solar Building, Room 2C11 Bethesda, MD 20892 Telephone: (301) 496-8197 FAX: (301) 402-3211 Address the letter of intent to: Dianne Tingley, Ph.D. Division of Extramural Activities National Institute of Allergy and Infectious Diseases 6003 Executive Boulevard Solar Building, Room 4C16 Bethesda, MD 20892 Telephone: (301) 496-0818 FAX: (301) 402-2638 Inquiries regarding fiscal matters may be directed to: Ms. Jane Unsworth Division of Extramural Activities National Institute of Allergy and Infectious Diseases 6003 Executive Boulevard Solar Building, Room 4B22 Bethesda, MD 20892 Telephone: (301) 496-7075 FAX: (301) 480-3780 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance, 93.856 Microbiology and Infectious Diseases Research and 93.855 Immunology, Allergic and Immunological Diseases Research. Grants are awarded under the authority of the Public Health Service Act, Section 301 (42 USC 241) and administered under the PHS grants policies and Federal Regulations, most specifically at 42 CFR Part 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of the Executive Order 12372 or Health Systems Agency review. $$R4 END ************************************************************ From owner-sci-resources@net.bio.net Fri Aug 13 23:00:00 1993 Path: biosci!NET.BIO.NET!kristoff From: kristoff@NET.BIO.NET (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 22, no. 29., pt. 2, 13 August 1993 Message-ID: Date: 14 Aug 93 03:35:42 GMT Sender: kristoff@net.bio.net Distribution: bionet Lines: 1196 Approved: sci-resources-moderator@net.bio.net $$XID RFA AI93021 AI-93-021 P1O1 *************************************** STRATEGIC PROGRAM FOR INNOVATIVE RESEARCH ON AIDS TREATMENT NIH GUIDE, Volume 22, Number 29, August 13, 1993 RFA: AI-93-021 P.T. National Institute of Allergy and Infectious Diseases Letter of Intent Receipt Date: September 23, 1993 Application Receipt Date: December 22, 1993 PURPOSE The NIAID invites applications for the establishment of Strategic Program for Innovative Research on AIDS Treatment (SPIRAT). This Request for Applications (RFA) will support innovative, integrated preclinical and clinical research to validate clinical therapeutic concepts for the treatment of HIV-1 infection. A SPIRAT can focus its therapeutic research activities on viral gene(s) or cellular factors required for HIV expression, novel immunotherapeutic approaches, or other approaches with the potential for effective therapy. Studies supported by this RFA may have a greater conceptual risk than currently exercised for treating HIV-infected individuals, but also a greater potential for effective, long-term therapeutic returns. The SPIRAT Program thus complements existing, more conservative preclinical and clinical programs for the treatment of HIV infection, managed by the Division of AIDS/NIAID (National Cooperative Drug Discovery Groups for the Treatment of HIV Infection (NCDDG-HIV), AIDS Clinical Trial Groups (ACTG), DAIDS Treatment Research Initiative (DATRI), Community Program for Clinical Research on AIDS (CPCRA)). The development of drugs and treatment for opportunistic infections are the subject of other NIAID sponsored programs and are not responsive to this RFA. Each SPIRAT will form an interdependent collaborative enterprise between preclinical and clinical scientists in the conceptualization and proof of concept of an identified therapeutic strategy. This will entail iterative research and information exchange between preclinical and clinical studies in order to maximally refine and improve upon the therapeutic concept. The Group must, therefore, possess the expertise necessary to (1) evaluate the proposed strategy in preclinical systems, and (2) conduct pilot clinical study(ies) in HIV-infected individuals (and uninfected volunteers, as appropriate) using the proposed therapeutic approach. Information gained from pilot clinical studies will be 'cycled' between preclinical and clinical studies to further refine/revise the therapeutic approach. A SPIRAT should be dedicated to the expedited transition of ground-breaking research from advanced preclinical findings to applied clinical mode in HIV-infected individuals. A SPIRAT is encouraged to include investigators from academic, non-profit, and commercial (pharmaceutical, chemical, or biotechnological companies) organizations. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This RFA, Strategic Program for Innovative Research on AIDS Treatment (SPIRAT), is related to the priority area of HIV infection. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic for-profit and non-profit organizations, private and public, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT Awards will be made as Cooperative Agreements (U19s). The Cooperative Agreement is an assistance mechanism in which substantial NIAID programmatic involvement with the recipient during the performance of the planned activity is anticipated. The nature of NIAID staff participation is described under SPECIAL REQUIREMENTS - Terms and Conditions of Award. The awardee will be responsible for the planning, direction, and execution of the proposed project and interrelated activities. All applications must consist of at least three interrelated projects conducted by at least three independent laboratories. For the purpose of this RFA, two (or more) projects within a single company will not be considered independent. Similarly, two (or more) projects within the same academic department will not be considered independent. This limitation on the number of independent projects from the same academic or private sector organization is intended to increase the diversity and multi disciplinary expertise available to the Group from other than the parent institution or organization. While no maximum number of projects is stipulated, it has been observed that when a multi disciplinary grant or award exceeds six component projects the program becomes less coordinated and more difficult to manage. This RFA is a one-time solicitation. If by the end of the third year of the award, the NIAID has not announced its intent to re-issue the RFA, incumbents should contact NIAID program staff and consider submitting investigator-initiated (R01) applications which will compete with all investigator-initiated applications and be reviewed according to the customary peer review procedures. All policies and requirements that govern the grant program of the U.S. Public Health Service (PHS), and the National Institutes of Health (NIH) apply. FUNDS AVAILABLE The NIAID has set aside $6.0 million total costs for the first year of funding. This level of support is dependent on the receipt of a sufficient number and diversity of applications of high scientific merit. Five to eight awards are anticipated for project periods up to four years. However, recommended support beyond the second year of each SPIRAT is subject to determination by an external ad hoc review committee, convened by the NIAID, that stated goals (milestones) have been sufficiently met. Specifically, the committee will evaluate: accomplishment in executing the proposed studies as outlined in the research proposal; preclinical achievements including quality and substance of findings; transition of such studies to clinical research; and initiation of a clinical pilot study. The committee's recommendation resulting from the second year review will be used by NIAID staff to determine if funding should continue beyond two years for the full term of the award. Because the nature and scope of the research proposed in response to this RFA may vary, it is anticipated that the size of individual awards will vary also. Awards are subject to a first year limit of $1.3 million in total costs (direct plus indirect costs). Budget requests should be carefully justified and commensurate with the complexity of the project. Although this program is provided for in the financial plans of the NIAID, awards pursuant to this RFA are contingent upon the availability of funds for this purpose. Applications in excess of $1.3 million total cost will be returned without review, unless a waiver has been granted by the SPIRAT Program Director, Dr. Nava Sarver (address listed INQUIRIES). RESEARCH OBJECTIVES Background The NIAID and the PHS are currently supporting comprehensive extramural and intramural projects for (2) the study of the etiology, natural history, and demographics of AIDS; (2) determining means of diminishing the risk of infection; (3) screening of high risk individuals; (4) developing prophylactic vaccines; (5) developing therapies to treat those with all stages of HIV disease; and (6) developing therapies that may be useful chemopreventive or prophylactic agents. Notwithstanding these efforts, effective, long-term therapies are lacking, and the number of HIV-infected individuals and AIDS cases is increasing. As of March 31, 1993, 289,320 cases of AIDS had been reported in the U.S. by the Centers for Disease Control (CDC) and more than 182,275 of these patients (63 percent) had died. Recent estimates indicate that 1,000,000 to 1,200,000 individuals in the U.S. may already be infected with HIV. The World Health Organization projection of worldwide HIV infection is placed at 30 to 40 million individuals by the year 2000. Advances in the understanding of the biology and pathogenesis of HIV disease have been made; nonetheless, the disease, which is associated with severe immune dysfunction, remains an intransigent infection with usually fatal consequences. Presently, no treatment that can eradicate or curb HIV infection for extended periods exists. Moreover, FDA approved therapies for HIV infection are associated with toxic side effects and emergence of HIV drug-resistant variants (generally within six to twelve months of treatment), which precludes their long term use. Given the precedence of reverse transcriptase and protease drug resistant variants, it is expected that resistance to inhibitors directed against other viral targets is likely to occur. The search for more effective and innovative therapies that may be less susceptible to the emergence of resistant HIV variants, is one of the highest priorities of the NIAID. In recent years, the scientific information base on HIV has expanded and the number of technological breakthroughs has increased significantly; however, application of developments to clinical and preventive activities has not been commensurate with this expansion. There is a need to apply these research advances to clinical research studies, an effort that requires interdependent research activities between preclinical and clinical investigators in the planning and implementation of studies whose ultimate goal is an effective clinical therapy for HIV+ individuals. Significant scientific and clinical expertise exists throughout the country. A concerted effort to mobilize this expertise through SPIRAT can accelerate advances in the management and ultimately the effective treatment of the disease. The SPIRAT Program is specifically designed to support refinement and proof of concept of innovative molecular intervention and immunotherapy strategies for the treatment of HIV infection. This program complements and balances present efforts pursued under existing NIAID programs, including the AIDS Clinical Trial Groups (ACTG), the Division of AIDS Treatment Research Initiative (DATRI), and the National Cooperative Drug Discovery Groups for the Treatment of HIV Infection (NCDDG-HIV). Research Goals and Objectives of the SPIRAT Program A. The principal goals of this RFA are to (1) interface between innovative, advanced preclinical research of sound scientific rationale and clinical proof of concept of an identified HIV therapeutic strategy; and (2) implement pilot clinical studies of a therapeutic strategy in HIV-infected individuals. In line with this objective, the SPIRAT Program will support projects with a common thematic goal for which advanced preclinical data exist. These efforts are to be implemented through a concerted, interdependent Group effort by components comprising the SPIRAT Group. A SPIRAT can focus its preclinical and clinical research activities on strategies directed against a viral gene or cellular component(s) required for HIV expression, novel cell based immunotherapeutic approaches, or other pioneering approaches. B. Applicants for SPIRAT funding are expected to have an identified strategy based on creative, solid scientific rationale and supported by advanced preclinical data which is proposed for pilot clinical evaluation. Therapeutic strategies that require studies in humans as well as preclinical studies to refine the clinical approach are appropriate for funding under the SPIRAT Program. Each SPIRAT will have a well-defined central research focus consistent with the research objectives of the Program as stated in the RFA. The following approaches are provided as examples and are not intended to be inclusive or restrictive: o Strategies that target HIV gene expression via interference with HIV cis-acting elements, viral regulatory elements, viral structural components, or cellular factors required for HIV expression; o Strategies that interrupt/prevent steps involved in HIV/cell interaction, entry, biochemical processes, virus (or viral components) transport between cellular compartments, assembly, release, maturation; o Intracellular delivery of antagonists to curb critical events in HIV life cycle, such as transdominant suppressors, decoys, competitors, catalytic RNA, using viral vectors or other delivery strategies (gene therapy) o Innovative exploitation of the humoral and cellular mechanisms of the immune system for a targeted anti-HIV attack; o Immune system reconstitution, capitalizing on new advances in restoring immune functions; o Direct DNA transduction ('naked' DNA injection) to augment immune response(s) via intracellular expression of HIV immunogen(s); o Strategies that target non T cell compartment(s) which may play an essential role in cell free virus transport, cell cell transmission, and general dissemination of HIV in the body; o Strategies that prevent the onset of HIV related neurologic dysfunction, or counteract the neurological damage seen in patients with AIDS related dementia; o Novel therapeutic interventions that are not affected by emergence of drug resistant HIV variants, or are insensitive to factors affecting the emergence of drug resistance; C. Applications should address advanced preclinical refinements of the proposed strategy, evaluation and demonstration of therapeutic or immune benefit in laboratory animals, if applicable, and implementation of pilot clinical studies in HIV infected individuals. The cyclic flow of information between preclinical and clinical phases is critical for maximal refinement and optimization of the proposed clinical modality, clinical evaluation of the therapeutic concept, and ultimately, accelerate transition to clinical treatment. Projects or cores with proposed animal models must be integrated into, and required to attain, the Group's objectives. Funds awarded for evaluation in animal models will be withheld (not awarded) until the therapeutic strategy is available for animal efficacy studies. Funds awarded for pilot clinical studies will similarly be withheld (not awarded) until the therapeutic strategy is available for clinical studies. Due to budgetary limitations, primate animal models should not be requested in the original application unless they constitute an integral component of the proposal. Requests for assistance in evaluation studies in primate animals may also be directed to the NIAID for consideration in conducting such studies in its primate model resources. The availability of these models will depend on the nature of the therapeutic approach. In all other cases, should the need for such models become evident during the course of studies under this cooperative agreement, the Principal Investigator may submit a competitive supplement request for the support of primate animal models. Funding of competitive supplements will be from set aside funds allocated to future RFAs for this initiative, and is not guaranteed. Consideration for funding will also depend on the competitive merit and justification of the competitive supplement relative to all other competing applications submitted in response to the RFA. D. Studies required for the IND targeted preclinical development (formulation, toxicology) of proposed treatments are generally beyond the scope of this RFA, but such development through private venture capital is encouraged. Alternatively, a Group may request that the NIH assist in these developmental tasks using existing NIH/NIAID contract resources. The NIAID has several programs for clinical evaluation of therapies for HIV/AIDS. These include the AIDS Clinical Treatment Units (ACTUs) large phase I and Phase II clinical studies, and DATRI. It is envisioned that extended clinical studies of treatments developed by a SPIRAT group can be accommodated under the clinical trial mechanisms available through Division of AIDS. Queries about these programs may be directed to Dr. Nava Sarver, at the address listed under INQUIRIES. E. The Group's objectives and goals should be relevant to and compatible with the NIAID Program's missions and directions as stated in this RFA. Applicants should describe their plans to accommodate the stated SPIRAT Program requirements, criteria, and NIAID involvement. F. Applications on the discovery/development/evaluation of anti HIV drugs or on treatment of opportunistic pathogens associated with AIDS are the subject of other NIAID programs and are excluded from this RFA. G. Relevance to other NIAID programs: This RFA will support innovative, integrated preclinical and clinical studies to validate therapeutic concepts for HIV-1 infection. Other DAIDS/NIAID initiatives involving only preclinical studies for novel intervention strategies address (1) preclinical immune reconstitution, focusing on the basic biology hematopoietic bone marrow and alternative stem cells and genetic modification for future use immune restoration in vivo; (2) preclinical refinement and optimization of gene therapy strategies (including vectors, transcriptional cassettes, anti viral genes) for HIV-1; and (3) early preclinical discovery of new drugs and therapeutic approaches for the treatment of HIV infection (NCDDG-HIV). SPIRAT applicants must ensure that no overlap exists between the specific aims proposed under this RFA and those proposed under any of the three initiatives referenced above, if applicable. SPIRAT applicants from an institution receiving government funds under General Clinical Research Center (GCRC), Center for AIDS Research (CFAR), AIDS Clinical Trial Unit (ACTU), AIDS Vaccine Evaluation Unit (AVEU), DATRI, and CPCRA programs, should describe how these programs are integrated with the proposed studies, and ensure that no scientific and budget overlap exists with the SPIRAT proposal. Definitions ADMINISTRATIVE CORE. An administrative facility that provides central operations and support for the overall management of the cooperative agreement and services shared by the Group as a whole. The Administrative Core should have a budget separate from that of the Principal Investigator's research project, but should be administered by the Principal Investigator's organization. The Administrative Core will have in its budget for each year travel costs for: (1) two required meetings of individual members of the Group; (2) one meeting of representative of all Groups in the SPIRAT Program; and (3) travel expenses for the Scientific Advisory Panel (see below). The Administrative Core will be responsible for allocating required travel expenses to appropriate members of the Group. Only SPIRAT related travel will be supported under this RFA; travel funds to other domestic or foreign meetings is not provided under this RFA. (For additional details of required travel see SPECIAL REQUIREMENTS Terms and Conditions of Award: C. Awardee's Rights and Responsibilities.) ARBITRATION PANEL. An NIAID-convened ad hoc panel that is formed to review scientific or programmatic activity that is impeding progress within a Group. It will be composed of a "Group" designee, one NIAID designee, and a third designee with expertise in the relevant area and chosen by the other two. The Arbitration Panel may help resolve both scientific and programmatic issues that develop during the course of work that restrict progress. COOPERATIVE AGREEMENT. An assistance mechanism in which substantial NIAID programmatic involvement is anticipated with the recipient organization during the performance of the planned activity. CORE COMPONENT. Laboratory facilities for equipment and services that are shared by two or more projects of the SPIRAT. Examples of core components are: biochemical, cell based, virological, and immunological studies; animal model studies; pharmacology/toxicology studies; scale-up synthesis of the therapeutic agent. The core can be defined as a facility laboratory with established techniques and assays which performs a service function resulting in an economy of effort and savings in the overall costs of the Group. The core unit is to be described with the same detail as the research projects to enable evaluation of its scientific merit. (See details for preparation of the budgets under PREPARATION AND ORGANIZATION OF THE APPLICATION). CORE LEADER. The leader of one of the Scientific or Administrative Cores of the SPIRAT. GROUP. see SPIRAT, below. INVENTION. An innovative therapeutic approach that is or may be patentable under Title 35 of the United States Code. STRATEGIC PROGRAM FOR INNOVATIVE RESEARCH ON AIDS TREATMENT (SPIRAT). In this RFA the terms Strategic Program for Innovative Tesearch on AIDS Treatment (SPIRAT) and "Group" are synonymous. Each Group may consist of a number of scientific investigators from academic and/or non profit research institutions as well as scientists from commercial organizations, performing research on interdependent projects whose central focus is development of effective clinical therapy for HIV-infected individuals. A CORE component cannot be used toward fulfillment of the three research projects requirement. NIAID SPIRAT PROGRAM DIRECTOR. A Senior Scientist of the NIAID extramural staff who coordinates NIAID's participation in the SPIRAT Program, oversees the entire SPIRAT Program, maintains the overall scientific balance in the SPIRAT Program commensurate with new research and therapeutic findings and emerging research opportunities, and who ensures that the SPIRAT Program is consistent with the Division of AIDS and NIAID missions and goals. NIAID SCIENTIFIC COORDINATORS. Scientists of the extramural staff of the Division of AIDS, NIAID, who function as peers with the Principal Investigators and Project Leaders and who facilitate the partnership relationship between NIAID and each Group. Two Scientific Coordinators from the Division of AIDS one from the Basic Research and Development Program, and one from the Clinical Research Program will be assigned to each Group by the SPIRAT Program Director. The Scientific Coordinators are the immediate contact persons to the Group. PRINCIPAL INVESTIGATOR. The person who assembles the SPIRAT, who is responsible for the performance of the Group as a whole and for that of each of the Project Leaders, and who is responsible for submitting the single application in response to this RFA. The Principal Investigator will coordinate Group activities scientifically and administratively and should preferably be project leader of one of the Research Projects of the Group. The awardee (Principal Investigator's) institution establishes and operates the Central Operations Office that funds Group members and is legally and fiscally accountable for the disposition of funds awarded. PROJECT LEADER. The leader of one of the scientific research projects of the SPIRAT, who is responsible for the scientific conduct of that project. RESEARCH PROJECT. A discrete, specified, circumscribed project that must relate to the overall theme of the SPIRAT. SCIENTIFIC ADVISORY PANEL. A panel, comprised of two to three peers from the scientific community, whose mission is to provide the Principal Investigator with a comprehensive review of the Group's activities and progress, consult on future goals and strategies, and recommend alternative directions, as appropriate. Selection and appointment of the Panel is the responsibility of the Principal Investigator. SPECIAL REQUIREMENTS Terms and Conditions of Award NOTE: Failure to abide by any of the Terms of Award pertaining to awardee responsibilities stipulated in this Section may result in withholding of funds by the NIAID until compliance with the Terms is restored. A. Working Relationships Within a Cooperative Agreement Under the Cooperative Agreement, a partner relationship exists between the recipient of the award and NIAID. The participation of the Government through the NIAID extramural staff is intended to promote and facilitate a concerted effort by all members of the SPIRAT Program by providing appropriate scientific input and analysis of experimental data, by coordinating efforts among Groups, by providing access to appropriate data bases, by providing ancillary testing and other resources (such as reagents, samples or experimental animals) available under existing Government contracts and, as appropriate, by making available to Groups biological materials for testing. The interaction of academic and non-profit research institutions with commercial organizations and the Government is strongly encouraged and is expected to favor expeditious clinical development of innovative HIV/AIDS therapies. B. Patent Coverage As the discovery of innovative, effective clinical therapies for HIV/AIDS is the goal of this effort, and since active involvement by private sector laboratories is facilitated by the existence of adequate patent coverage, it is essential that applicants provide plans to assure such coverage. Since several institutions may be involved, complex patent situations may arise. Each applicant Group must, therefore, provide a detailed description of the approach to be used for obtaining patent coverage and for licensing where appropriate, in particular where the invention may involve investigators from more than one institution. In addition each Group must provide a detailed description of the procedures to be followed for the resolution of legal problems which potentially may develop. Attention is drawn to the reporting requirements of 35 U.S.C. Parts 200-212 and 37 CFR Part 401 or FAR 55.227-11. Instructions were also published in the NIH GUIDE FOR GRANTS AND CONTRACTS, Vol. 19, No. 23, June 22, 1990. Note that non-profit organizations (including universities) and small business firms retain the rights to any patent resulting from Government contracts, grants or Cooperative Agreements. It is also noted that a Presidential memorandum of February 18, 1983 extended to all business concerns, regardless of size, the first option to the ownership of rights to inventions as provided in P.L. 96-517. As a result of this memorandum, the relationships among industrial organizations and other participants are simplified, since all Group members can now be full partners in the research and in any inventions resulting therefrom. The specific patenting arrangements among the institutions may vary, and could include joint patent ownership, exclusive licensing arrangements, etc. Applicants are encouraged to develop an arrangement that is most suitable for their own particular circumstances. The proposed patent plan among the institutions comprising the Group must be submitted with the application. This patent agreement, signed and dated by the organizational officials authorized to enter into patent arrangements for each Group member and member institution, must be delivered two weeks prior to submission of the application to Dr. Nava Sarver, Targeted Drug Discovery Section, Developmental Therapeutics Branch, Division of AIDS, NIAID, Solar Building Room 2C-11, 6003 Executive Boulevard, Bethesda, MD 20892. (For express mail or courier services, the address is Rockville, MD 20852.) NOTE: Should the Group wish to place all inventions and discoveries resulting from these studies within the public domain, a letter to that effect must be submitted to Dr. Sarver in lieu of the patent agreement two weeks prior to submission of the application. The letter must be co-signed by the Principal Investigator, each of the Project Leaders, and each of the business officials representing the respective institutions. Federal regulation clause 37CFR401 and HHS Inventions regulations at 45 CFR Parts 6 and 8 require that NIH be informed of inventions and licensing occurring under NIH funded research. Invention and licensing reports must be submitted to Extramural Invention Reports office, Office of Extramural Research, Building 31, Room 5B41, NIH, 9000 Rockville Pike, Bethesda, Maryland 20892. C. Awardee Rights and Responsibilities and Nature of NIAID Participation The applying Group must define its objectives and strategies in accord with its own interests and perceptions of novel and exploitable approaches to implementation of effective, innovative HIV/AIDS therapy, and must develop the details of the research design following the guidance given in this RFA. It is the primary responsibility of the Principal Investigator to clearly state the objectives and approaches of the Group, to plan and conduct the research stipulated in the proposal, and to ensure that the results obtained are analyzed and published in a timely manner. The data obtained will be the property of the awardee. Specifically, the Principal Investigator defines the details for the project within the guidelines of the RFA, retains primary responsibility for the performance of the scientific activity, and agrees to accept assistance in coordination, cooperation, and participation of NIAID staff in all aspects of scientific and technical management of the project in accordance with the terms formally and mutually agreed upon prior to the award. The responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. 1. Meetings a. Two mandatory Group meetings. The Principal Investigator and Project Leaders of the Group, and one or both of the NIAID Scientific Coordinators, will meet twice per year to review progress, plan and design research activities, and establish priorities within the Group. The Principal Investigator will be responsible for scheduling the time and place (generally at one of the performance sites), notifying the NIAID at least 30 days prior to the meeting date, and preparing concise proceedings or minutes which will be delivered to the members of the group within thirty days of the meeting. The agenda for this meeting will be determined by agreement between the Principal Investigator and the NIAID Scientific Coordinator. NIAID staff will not chair Group meetings. b. One mandatory meeting will be held annually (SPIRAT Program annual meeting) at a site designated by the NIAID (usually the Washington DC vicinity) during which the Principal Investigators and Project Leaders of all the Groups will present significant findings and progress in symposium format. The NIAID SPIRAT Program Director will consult with the Groups' key personnel in formulating the overall agenda and in identifying key topics for discussion, with specific focus on inter Group interaction and sharing information of general importance to the implementation of clinical studies. It is expected that NIH staff, members of established committees and advisory boards, and others active in the clinical application of innovative therapies for HIV/AIDS will also be invited. Applicants should include requests for travel funds specifically for and restricted to the above meetings when they prepare their budgets. Funds to cover operating costs of the SPIRAT Program annual meeting may be contributed by one or more Groups; NIAID will provide administrative supplements for this purpose, as needed. c. Informal meetings. A critical determinant of Group success will be the degree of communication among its members. Thus, in addition to the three meetings listed above, two additional meetings which may be necessary for coordination of Group activities may be scheduled, and funds should be requested in the budget, with justification. Regular telephone and written communication will be important and are encouraged. NOTE: This RFA will support only SPIRAT-related travel as specified above; no additional travel funds will be provided to attend other domestic or foreign scientific meetings under this RFA. 2. Principal Investigator responsibilities The Principal Investigator will be responsible for the timely submission of all abstracts, manuscripts and reviews (co)authored by members of the Group and supported in part or in total under this Agreement. The Principal Investigator and Project Leaders are requested to submit manuscripts to the Scientific Coordinator within three weeks of acceptance for publication so that an up-to-date summary of program accomplishments can be maintained. 3. Annual Progress Report An annual progress report should be submitted, which should include a complete and cumulative list of all publications (abstracts, manuscripts, reviews) (co)authored by Group members and supported in part or in total under this Agreement. Each Progress Report should also include a brief section outlining intra Group interactions which have augmented activities, citing specific occurrences (e.g., construct X was made under Project 1 and transferred to Project 2 for clinical evaluation). Inter-Group collaboration with other SPIRAT should be specified, where applicable. Interaction with the Scientific Coordinator and the NIAID during the reporting period should be described. The Progress Report should routinely include basic information. Please refer to PHS 2590 (noncompeting continuation application form) which describes the basic information required by NIH for preparation of the progress report. 4. Publications and oral presentations Publications or oral presentations of work done under this Agreement is the responsibility of the Principal Investigator and appropriate Project Leaders and will require appropriate acknowledgement of NIAID support. 5. Acknowledgement of published work All published (abstracts, peer reviewed manuscripts, reviews) and oral presentations of work supported in part or in total by the SPIRAT cooperative agreement must be acknowledged as part of the presentation and will include the mechanism, cooperative agreement number and Institute, e.g., "This work was supported in whole (or in part) by the SPIRAT Program, cooperative agreement number U19-AI-12345, NIAID". 6. Rights to data While the NIAID Scientific Coordinator has a right of access to the data (see NIAID staff responsibilities below) the applicant will retain custody of and rights to the data. Timely publication of major findings is encouraged. The applicant institution and the Principal Investigator will be responsible for the Group's application. The award will be made to the applicant institution on behalf of the Group as a whole and not to individual research projects within the Group. The applicant institution will provide a Central Operations Office for the Group, will be responsible for the performance of the entire Group, and will be accountable for the funds awarded. 7. Group's scientific advisory panel Each Group will designate a Scientific Advisory Panel of two to three investigators within six months of funding. The Panel members will attend one or more of the Group's meetings (see above). The Scientific Coordinator(s) will participate in all meetings of the Panel. The Panel will review the Groups's activities and will advise the Principal Investigator on the Group's progress, including the timeliness of progress in individual projects relative to original projections; progress relative to Group's objectives and needs; continued relevance of a given project to Group's goals; continued coordination of Group's objectives with the objectives of the SPIRAT Program; and recommendations for new directions, as appropriate. The Panel will provide the Principal Investigator with a comprehensive written review of the Group's activity in each year of funding, as specified under Definitions: SCIENTIFIC ADVISORY PANEL. A copy of the Panel's report will be submitted to the NIAID as a supplement to the annual progress report, or within 30 days of the report, whichever is earlier. A Scientific Advisory Panel is required of all Groups. Members of the Panel will not be affiliated with any of the institutions comprising the Group. The composition of the designated Panel will be provided to the NIAID within six months of funding. Funds to cover expenses incurred by the Panel should be included in the Administrative Core component of the application and will be restricted solely for this purpose. D. NIAID Staff Responsibilities: Nature of NIAID Participation Assistance via a Cooperative Agreement differs from the traditional research grant in that, in addition to the normal programmatic and administrative stewardship responsibilities, the awarding component (NIAID) anticipates substantial programmatic involvement during performance of the research program. NIAID shall work with each Group and shall be represented by two NIAID Scientific Coordinators, both members of the professional staff of the Division of AIDS: one coordinator will be from the Basic Research and Development Program (primarily of the Developmental Therapeutics Branch), and one coordinator will be from the Clinical Research Program (primarily of the Medical Branch). During performance of the award, the NIAID SPIRAT Program Director (Dr. Sarver, Chief, Targeted Drug Discovery Section, Developmental Therapeutics Branch) and the Scientific Coordinators will provide appropriate assistance, advice, and guidance by: participating in the design of Group activities; advising in the selection of sources or resources; coordinating or participating in collection and/or analysis of data; advising in management and technical performance; or participating in the preparation of publications. However, the role of NIAID will be to promote and facilitate and not to direct the activities. It is anticipated that decisions in all activities will be reached by consensus of the Group and that NIAID staff will provide input to this process. The manner of reaching this consensus and the final decision-making authority will rest with the Principal Investigator. 1. NIAID Participation in Design of Group Activities, Development of Research Protocols and Evaluation of Results a. The NIAID Scientific Coordinators, like other Group members, may suggest studies within the scope of the Group's objectives and research activities; may present to the Group experimental findings from published sources or from contract projects in support of these suggestions; may participate in the design, but not in the execution, of experiments agreed to by the Group; and may participate in the analysis and publication of results. b. The NIAID Scientific Coordinators may assist the Group or other individual members in research planning, particularly with respect to: i. provision of needed resources and information that otherwise may not be available to the Group (e.g., reference compounds for standardization of test systems or as analytical standards); ii. provision of data from testing conducted in resource contract laboratories when the occasional need arises in Groups whose main research activities do not require these resources on a regular basis (e.g., biochemical, cell based assay, and animal model studies). On occasion, and under mutual agreements, NIAID will arrange for limited preclinical evaluations at other SPIRAT sites. The requesting Group is expected to provide sufficient material for such testing. Groups whose experimental approach involves studies that require testing in animals on a regular basis must budget for costs to be paid from award funding. iii. provision of information concerning work being conducted in other NIAID supported extramural projects, in order to reduce or prevent duplication of efforts. iv. A SPIRAT may also request that further evaluation of the therapeutic strategy under a larger phase I clinical trial be conducted under other clinical programs sponsored by the NIAID. A SPIRAT will be supported by strong commitment by their home institution to the organization and conduct of these programs. NOTE: It is understood that the Government supports studies in the interest of promoting the transition of effective, innovative therapies to the clinic, and that identified therapies that have been derived via government support mechanisms will be offered to the public at reasonable costs. 2. NIAID Participation in Collection and Analysis of Data, Procedures for Submission of Results to NIAID, and Preparation of Group Findings for Presentation and Publication In addition to the special reports and stipulations described below, reporting requirements will be identical to those currently in existence for awardee of traditional NIH research project grants. 1. The principal end product of SPIRAT activities will be the development of an innovative, effective clinical therapy for HIV/AIDS. Transitional preclinical and clinical development through private resources is encouraged. Alternatively, the Group may recommend that further clinical studies be sponsored by NIAID (see item 2, below). In this case, it will be necessary for the Principal Investigator, appropriate Project Leaders and the NIAID Scientific Coordinators to collaborate in the analysis, summary preparation, and subsequent presentation of data to the Division of AIDS and other NIAID staff and NIAID advisory committees, such as the AIDS Clinical Drug Development Committee (ACDDC), DATRI Executive Group, or AIDS Research Advisory Committee (ARAC). 2. NIAID will retain the option to cross-file or independently file an application for investigational clinical trial; e.g., an Investigational New Drug (IND) application to the United States Food and Drug Administration of any invention resulting from these NIAID supported Cooperative Agreements. Reports of data generated by the Group or any of its members required for inclusion in INDs and Clinical Brochures and for cross filing purposes will be submitted by the Principal Investigator to the Scientific Coordinator upon request. Such reports will be in final draft form and include background information, methods, results, and conclusions. They will be subject to approval and revision by NIAID and may be augmented with test results from other Government sponsored projects prior to submission to the appropriate regulatory agency. 3. The NIAID, via the SPIRAT Program Director or the Scientific Coordinator, will have access to data generated under this Cooperative Agreement. Information obtained from the data may be used by the Scientific Coordinator for the preparation of internal reports on the Group's activities. E. Arbitration Process Inasmuch as certain activities require approval by NIAID staff during performance of this Cooperative Agreement specifically, reports intended for inclusion in INDA's and Clinical Brochures, redistribution of materials received from the Government, and dissemination of research findings resulting from the use of these materials NIAID will establish an arbitration process to resolve any differences of opinion between the awardee and NIAID, on scientific and programmatic matters. An arbitration panel, composed of one Group designee, one NIAID designee, and a third designee with expertise in the relevant area and chosen by the other two, will be formed to review any scientific or programmatic issue that is significantly restricting progress. These special arbitration procedures in no way affect the awardee's right to appeal an adverse action in accordance with PHS regulations at 42 CFR Part 50, Subpart D, and HHS regulations at 45 CFR Part 16. The special Terms and Conditions of Award: Nature of NIAID Participation described in this Section are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS grant administration regulations at 45 CFR Parts 74 and 92, and other HHS, PHS, and NIH grant administration policies. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements will be required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis should be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear and compelling rationale should be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group, and related to the prevalence of the condition (e.g. HIV infection) in the catchment area. Gender and racial/ethnic issues should be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information should be included in the form PHS 398 in sections 1-4 of the Research Plan AND summarized in Section 5, Human Subjects. Applicants/offerors are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., Native Americans (including American Indians or Alaskan Natives), Asian/Pacific Islanders, Blacks, Hispanics). The rationale for studies on single minority population groups should be provided. For the purpose of this policy, clinical research includes human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of disease, disorders or conditions, including but not limited to clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded from the clinical research requirements. However, every effort should be made to include human tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. If the required information is not contained within the application, the application will be returned. NOTE: Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific questions(s) addressed and the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and will be reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. Applicants from institutions that have a General Clinical Research Center (GCRC) funded by the NIH National Center for Research Resources are encouraged to respond to this RFA and should identify the GCRC as a resource for conducting the proposed research. If so, a letter of agreement from either the GCRC program director or Principal Investigator could be included with the application. LETTER OF INTENT Prospective applicants are asked to submit, by September 23, 1993, a letter of intent (maximum of three pages) that includes a descriptive title of the overall proposed research; the name, address, telephone number, and institution of the Principal Investigator; names of prospective Project Leaders, other key investigators, and their respective institutions; title, project leader, and institution for each component research project, and the number and title of this RFA in response to which the application may be submitted. Although the letter of intent is not required, is not binding, and is not a factor in the peer review of the application, the information it contains is helpful in planning for the review of applications. It allows NIAID staff to estimate the potential review workload and to avoid conflict of interest in the review process. The letter of intent is to be sent to Dr. Dianne Tingley at the address listed under INQUIRIES. APPLICATION PROCEDURES This RFA requires the submission of a single application for the proposed SPIRAT. Because of the multi institutional nature of a SPIRAT and the special requirements in this RFA, additional instructions regarding format are contained in the Special Instructions for Preparing the Group Application, which are available from the program contacts listed under INQUIRIES. The individual research projects comprising the SPIRAT are subjects to the same format and page limitations as for a research grant application The research grant application form PHS 398 (rev. 9/91) is to be used in applying for these cooperative agreements. These forms are available at most institutional offices of sponsored research and may be obtained from the Office of Grants Information, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone 301/594-7248. The special requirements of this RFA also necessitate certain modification. The Introductory Section should apply to the proposed SPIRAT as a whole with respect to goals, objectives, and overall research plan. The Introductory Section, not to exceed three pages, should contain any additional information about the proposed Principal Investigator or his/her institution as evidence of capability to carry out the scientific and administrative duties required in this RFA and the functions of the Central Operations Office. Refer to the Special Instructions for Preparing the Group Application, for additional instructions how to prepare and assemble the Groups's application. The RFA label available in the PHS 398 (rev. 9/91) application form must be affixed to the bottom of the face page of the application. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, to assure the identification of your application with this RFA the "YES" box must be marked in item 2a of the face page of the application form and the title and number of this RFA typed. Applications that are not received as a single package from the Principal Investigator and that do not conform to the instructions contained in PHS 398 (rev. 9/91) application kit will be judged non-responsive and will be returned to the applicant. Submit a signed, typewritten original of the application, including the Checklist, and three signed, photocopies, in one package to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** At the time of submission, also submit two exact copies of the application directly to: Dr. Dianne Tingley Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4C-16 6003 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-0818 Applications must be received by December 22, 1993. If an application is received after that date, it will be returned to the applicant without review. If the application submitted in response to this RFA is substantially similar to a grant application already submitted to the NIH for review, but has not yet been reviewed, the applicant will be asked to withdraw either the pending application or the new one. Simultaneous submission of identical applications will not be allowed, nor will essentially identical applications be reviewed by different review committees. Therefore, an application cannot be submitted in response to this RFA that is essentially identical to one that has already been reviewed. This does not preclude the submission of substantial revisions of applications already reviewed, but such applications must include an introduction addressing the previous critique. REVIEW CONSIDERATIONS A. Review procedures Applications will be reviewed by the Division of Research Grants for completeness and by NIAID staff to determine administrative and programmatic responsiveness to this RFA; those judged to be incomplete or non-responsive will be returned to the applicant without review. Applications with first year total costs (direct and indirect) in excess of $1.3 million will be returned without review unless the applicant has received a written waiver from the NIAID to exceed this amount (see FUNDS AVAILABLE, above). Those applications that are complete and responsive may be subjected to a triage by an NIAID peer review group to determine their competitiveness relative to the other applications received in response to this RFA. The NIAID will remove from further competition those applications judged to be noncompetitive for award and will notify the applicant (Principal Investigator) and responsible institutional official. Those applications judged to be competitive for award will be further reviewed for scientific and technical merit by a Review Committee convened by the Scientific Review Program, Division of Extramural Activities, NIAID. Second level of review will be provided by the National Advisory Allergy and Infectious Diseases Council. In the event of multiple highly qualified applications, final funding recommendations will be based on highest Program priorities. Review date, Council meeting date, and earliest award date are stated under Schedule, below. B. Review Criteria The application must be directed towards the attainment of the stated programmatic goals (see RESEARCH OBJECTIVES). The following factors are the criteria to be used by peer review groups in the scientific and technical review of these applications: o The scientific merit of the program as a whole, as well as that of each individual project, and the originality and uniqueness of the proposed preclinical and clinical activities. Each project must be supportable on its own merit; o The significance of the overall program goals and the development of a well-defined central research focus, in relation to the research objectives of the SPIRAT Program; o The cohesiveness, multidisciplinary and multifaceted scope of the program and the coordination and interdependence of the individual projects and core(s); plans for effective intra-Group communication and for assuring cohesiveness within the Group as a whole; o Demonstration of experience in the planning, design, and conduct of clinical research with a small number (6 to 10) of HIV-infected individuals (inpatient and outpatient). Relevant prior experience should be noted. The plan for clinical data management and adverse event reporting (AER) should be described; o The likelihood that innovative preclinical therapeutic strategies will be refined and pilot clinical research implemented within two years of award date; o The justification for, and usefulness to the various research projects of the core facilities. The relationship of each core to the central focus of the overall program. Each core unit must provide essential facilities or service for two or more approved individual research projects; o The leadership, scientific ability, and administrative competence of the Principal Investigator for the development, implementation, and management of a comprehensive preclinical and clinical research program; and the Principal Investigator's commitment to devote substantial time and effort to the program; o The qualifications, experience, and commitment of the investigators responsible for the individual research projects or core(s) (Project Leaders) and their contribution to the program, including their ability to devote adequate time and effort to the Group. It is anticipated that, due to the complexity and time required to maintain a well-coordinated and productive research effort, a minimum 20 percent (time) effort by the Principal Investigator and each Project Leader should be devoted to the study, unless there are compelling arguments to the contrary; o Research training, experience and accomplishments of other participating investigators and support personnel in the Group in the research areas outlined in the RFA; o The academic, clinical, and physical environment in which the research will be conducted, including the adequacy of space, equipment, animal facilities, biohazard containment facilities; access to HIV/AIDS patient care; and the potential for interaction with active scientists from other departments and/or institutions in relevant disciplines including infectious diseases, virology, molecular biology, immunology, gene therapy, hematology. The availability of a GCRC (General Clinical Research Center) should be noted. The responsible IRB (Institutional Review Board) should be identified; o Documented commitment of Institutions represented by Group members; documented capability of Principal Investigator's Institution to serve as the Central Operations Office for the Group; o Soundness of the institutional administrative and organizational structure that facilitates attainment of the objective(s) of the program, including fiscal responsibility and management capability to assist the PI and staff in following PHS policy; o Description of the laboratory capabilities in immunology and virology with particular emphasis on ability to detect changes in parameters related to HIV infection. Pharmacological capabilities should also be described, when relevant; o Arrangements for internal quality control of on-going research, allocation of funds, day-to-day management, contractual agreements, and mechanism for selecting and replacing key professional or technical personnel, if required, on an interim or permanent basis; o Management for the ethical and hazardous aspects of the project(s); o Appropriate representation of women and minorities in study design; o Commitment to accept the assistance of NIAID staff in accordance with the guidelines outlined under Terms of Award; o Reasonableness of cost. AWARD CRITERIA Award criteria will be based on scientific merit as reflected in the priority score; on programmatic priorities and relevance; on the overall diversity and balance of proposed therapeutic modalities; and on funds available. INQUIRIES The opportunity to clarify issues or questions about the RFA from potential applicants are welcome. Please send the letter of intent and direct inquiries regarding the RFA and programmatic issues to: Nava Sarver, Ph.D. Division of AIDS National Institute of Allergy and Infectious Diseases Solar Building, Room 2C-11 6003 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-8197 FAX: (301) 402-3211 Direct inquiries regarding application preparation and review to: Dr. Dianne Tingley Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4C-16 6003 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-0818 FAX: (301) 402-2638 Direct inquiries regarding fiscal matters to: Ms. Jane Unsworth Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4B-22 6003 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-7075 FAX: (301 480-3780 Schedule Letter of Intent Receipt Date: September 23, 1993 Application Receipt Date: December 22, 1993 Scientific Review Date: February/March 1994 Council Meeting Date: June 17-19, 1994 Earliest Award Date: August 1, 1994 AUTHORITY AND REGULATIONS This program is described in the catalog of Federal Domestic Assistance, 93.856 Microbiology and Infectious Diseases Research and 93.855 Immunology, Allergy and Transplantation Research. Awards are made under the authority of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92. This program is not subject to the intergovernmental review requirements of Executive Order 122372 or Health Systems Agency review. From owner-sci-resources@net.bio.net Fri Aug 13 23:00:00 1993 Path: biosci!net.bio.net From: kristoff@net.bio.net (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 22, no. 29., pt. 3, 13 August 1993 Message-ID: Date: 14 Aug 93 03:37:21 GMT Sender: kristoff@net.bio.net Lines: 1033 Approved: biosci-moderator@net.bio.net $$XID RFA AR94001 AR-94-001 P1O1 *************************************** FAILURE TO HEAL: CHRONIC WOUND HEALING IN THE SKIN NIH GUIDE, Volume 22, Number 29, August 13, 1993 RFA: AR-94-001 P.T. National Institute of Arthritis and Musculoskeletal and Skin Diseases National Institute on Aging National Institute of Child Health and Human Development National Institute of Diabetes and Digestive and Kidney Diseases National Institute of Nursing Research Letter of Intent Receipt Date: October 15, 1993 Application Receipt Date: November 30, 1993 PURPOSE The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institute on Aging (NIA), National Institute of Child Health and Human Development (NICHD), National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK), and National Institute of Nursing Research (NINR) invite applications for research on wounds that fail to heal, the prototypic ones being decubitus (pressure) ulcers, venous (stasis) ulcers and diabetic ulcers. Studies may be both basic and applied. The intent is to apply knowledge rapidly to the prevention and treatment of chronic wounds in a clinical/rehabilitation situation. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This Request for Applications (RFA), Failure to Heal: Pathogenesis of Chronic Wound Healing in the Skin, is related to the priority area of chronic disabling conditions. Potential applicants may obtain a copy of "Healthy People 2000" (Summary Report: Stock No. 017-001-00474-0 or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Applications from minority individuals and women are encouraged. Foreign institutions are not eligible for the First Independent Research Support and Transition (FIRST) (R29) award. MECHANISM OF SUPPORT This RFA will use the National Institutes of Health (NIH) individual research grant (R01) and FIRST award (R29) and the newly described interactive R01 mechanism. Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. The total project period for applications submitted in response to the present RFA may not exceed five years. The anticipated award date is July 1, 1994. Because the nature and scope of the research proposed in response to this RFA may vary, it is anticipated that the size of an award will also vary. This RFA is a one time solicitation. Future unsolicitated competing continuation applications will compete with all investigator initiated applications and be reviewed according to the customary peer review procedures. FUNDS AVAILABLE The estimated funds (total costs) available for the first year of support for the entire program is anticipated to be 1.6 million dollars. The anticipated number of new awards is eight. RESEARCH OBJECTIVES Background In spite of recent advances in the basic mechanisms of wound healing, knowledge of factors involved in the development and treatment of chronic wounds and their prevention remains limited. Future progress in the treatment of chronic wounds will require greater understanding of their pathogenesis and failure to heal. These two inseparable aspects, pathogenesis and failure to heal, were the subject of a Workshop sponsored by the Skin Diseases Interagency Coordinating Committee for the National Institutes of Health held on January 10th and 11, 1993. The Workshop brought together a multidisciplinary group of scientists working in the field of wound repair. A summary of this Workshop will be published in the Journal of Investigative Dermatology. Identified below is a selection of the areas covered in that workshop that are relevant to this solicitation. This list is illustrative and not exclusive or restrictive. Cytokines and Growth Factors A number of reports have established that the application of growth factors to acute experimental wounds in animals enhances healing. However, it is unclear what role growth factors play in chronic wounds. Indeed, recent clinical trials of topical application of single growth factors to pressure, venous and diabetic wounds have not been very encouraging. It should be appreciated that growth factors are multifunctional with both stimulatory and inhibitory actions depending upon cellular context. Among the areas of interest relative to cytokines and growth factors are: o What is the normal sequence of growth factors in acute wounds and how are these altered in the chronic wound situation? o Are growth factors being trapped by macromolecules present in chronic wounds? o Are growth factors released by cultured cells, both allogeneic and autologous, that are applied to chronic wounds? Keratinocyte Migration in the Wound Bed In normal skin, the basal cells are attached to the basement membrane and lose anchorage upon skin injury. The signals responsible for epidermal migration after wounding are unknown, but keratinocytes begin to migrate toward the site of injury. The "tractor tread" hypothesis, whereby keratinocytes stop at the wound bed with progressive climbing of proximal cells over the now resting cells has gained wide acceptance as a model of keratinocyte migration. Investigations of the epidermal edge of venous ulcers has shown that the epidermis displays mitotic activity, resulting in increased epidermal thickness at the edges of chronic wounds. This has led to the hypothesis that a fundamental defect exists in the chronic wound situation, perhaps a failure of cells to adhere to one another or their substrates. There has been substantial recent information on the signals for keratinocyte movement and substrate requirements at least in the context of acute injury. The concept that the extracellular matrix is an integral part of keratinocyte migration has also received experimental support. Migration enhancing and inhibiting molecules found in extracellular matrix and/or in wound beds have been described. Areas of research within this topic include: o Investigations of specific cytokine and growth factor actions in relation to keratinoctye migration; o Specific elucidation of the stimulatory and/or inhibitory effects of the extracellular matrix molecules on keratinocyte migration; o Specific investigation of the basis for the failure of keratinocytes to migrate across the bed of chronic wounds. The Chronic Wound Environment For the last several years, evidence has suggested that chronic wounds may be growth factor deficient or represent a microenvironment hostile to the repair process. More recently, however, there is new evidence suggesting that wounds may not necessarily be deficient in growth factors, but that the stimulatory action of the peptides may be prevented from being expressed. Areas of inquiry in this subject include: o Investigations of wound fluids from acute and chronic wounds to establish whether or not there is a difference in regard to stimulation and/or inhibition of the wound healing process; o Investigations designed to determine whether or not macromolecules present in the chronic wound bed act as a trap for endogenous growth factors, making them unavailable to the maintenance of tissue integrity and the repair process at the wound site. Matrix Degrading Metalloproteinases Matrix degrading proteinases are proenzymes that need to be activated and are considered to be the physiologic mediators of matrix degradation. The prototypic one is interstitial collagenase, but there are at least ten of these enzymes that are secreted as zymogens. Stimulated by growth factors and by extracellular matrix, they all utilize zinc with a zinc atom binding at the center of the molecule at a conserved sequence. They are stabilized by calcium and inhibited by various chelators such as the tissue inhibitor of metalloproteinase. It is clear that collagenases are present in acute wounds, but little or nothing is known about their possible role in chronic wounds. Within this area, research topics might include: o Investigations of the source of metalloproteinases in acute and chronic wounds; o Identification of which members of the metalloproteinase family are present and in what sequence in both acute and chronic wounds; o Investigations of the role of the inhibitors of the metalloproteinases in the wound healing process. Metabolic Abnormalities The incidence of chronic wounds appears to be higher in persons suffering from disease conditions such as diabetes or physical disabilities due to mobility impairments such as those that result from spinal cord injury (SCI). Little is known about how changes in the homeostatic mechanisms of persons having either of these conditions predispose them to wounds, or how they affect wound repair. Though the categories of chronic wounds that are prevalent in both conditions vary, there may be similar etiologies. For diabetic wounds, both neurological abnormalities and vasculopathy have been postulated in explaining the pathogenesis of the diabetic ulcer. In persons with SCI, changes in sensory innervation and circulation provide a spectrum of metabolic changes that can predispose to the development of chronic wounds. In this area, further research could include: o Investigations of small vessel abnormalities as a contributor to diabetic ulceration; o Investigations of the effect of neurotransmitters and neuropeptides for their effect upon the inflammatory and wound healing process; o Investigations of the effects of excess glucose or sorbitol on cell metabolism in the context of wound repair. Hypoxia Oxygen plays a major role in wound repair and probably is a fundamental aspect of chronic wound pathogenesis. For the most part, the biology of oxygen in wound healing has been studied in the context of connective tissue synthesis. Oxygen also has important effects on a number of enzyme systems that can alter cell behavior. In this subject area, further investigation would be possible in: o Effect of oxygen or lactate in the stimulation of extracellular matrix and/or in the fibrotic reaction observed in some chronic wounds; o The interaction of low oxygen tension with the release of various growth factors and cytokines and their effect on the wound healing process. Fibrin Formation and Removal Chronic wounds, including pressure ulcers and venous ulcers, are characterized by the presence of fibrin within the wound bed and surrounding tissues. Fibrin accumulation in acute wounds is removed within days, but it is not degraded in chronic wounds. Knowledge of the process of fibrin formation and polymerization that has accumulated in recent years may provide the basis for understanding the persistence of fibrin in chronic wounds. The role of fibrin retention and the adherence of other molecules to it in interacting with cytokines and growth factors in the wound healing process have just begun to be investigated. In this area, new research approaches could include: o Investigations of the process of fibrin accumulation in chronic wounds; o Investigations of specific macromolecules that bind to fibrin in the chronic wound bed and their influence on wound healing; o Investigations of the fibrin polymers seen in chronic wounds and their comparison to that seen in acute wounds. Aging and Chronic Wound Healing It has been noted by many investigators that wound healing is slower in older individuals, but the underlying cause and mechanism is not understood. Areas of interest include: o Changes in composition of extracellular matrix with advancing age; o Alterations in wound healing with advancing age. Clinical Therapeutics An important focus of wound healing research is the improvement of patient care through the interdisciplinary collaboration between clinicians and basic scientists. Restoration of physical integrity and function of the injured or diseased tissue can best be accomplished by integrating bio/molecular technology with clinical treatments as clinicians and basic scientists work together. Examples to encourage opportunities for clinicians to collaborate with basic scientists include: o Investigations designed to determine the biological or molecular reason for successful wound healing with currently used clinical therapies, such as electrical stimulation, laser, or nutritional regimens. For example, clinicians have reported faster healing of pressure sores with patients on high protein diets. In order to identify the pivotal amino acid, methionine, cysteine, or arginine might be studied. Because zinc is a necessary cofactor of DNA polymerase and reverse transcriptase, studies could be pursued to determine whether or not the healing impairment associated with zinc deficiency is due to an inhibition of cellular proliferation o Investigations designed to identify specific biological/molecular markers that could be used to define standardized outcome measures. For example, various dressings such as hydrocolloid, polyvinyldiene, polyethylene, polyurethane, and human skin are used in health care facilities to increase the rate of epithelial healing. Can serum protease inhibitors or tissue inhibitors be identified in the fluid of chronic wounds to standardize use of specific wound cleansers and dressings in the treatment of pressure sores/venous leg ulcers? STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements are required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis must be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale must be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues must be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information must be included in the form PHS 398 (rev. 9/91) in Sections 1-4 of the Research Plan AND summarized in Section 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., Native Americans [including American Indians or Alaskan Natives], Asian/Pacific Islanders, Blacks, Hispanics). The rationale for studies on single minority population groups should be provided. For the purpose of this policy, clinical research is defined as human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including, but not limited to, clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded. However, every effort should be made to include human tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. For foreign awards, the policy on inclusion of women applies fully; since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. If the required information is not contained within the application, the application will be returned. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. GENERAL CLINICAL RESEARCH CENTERS Applicants from institutions that have a General Clinical Research Center (GCRC) funded by the NIH National Center for Research Resources may wish to identify the GCRC as a resource for conducting the proposed research. If so, a letter of agreement from either the GCRC program director or Principal Investigator could be included with the application. LETTER OF INTENT Prospective applicants are asked to submit, by October 15, 1993, a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, the identities of other key personnel and participating institutions, and the number and title of the RFA in response to which the application may be submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information that it contains allows ICD staff to estimate the potential review workload and to avoid conflict of interest in the review. The letter of intent is to be sent to Dr. Alan N. Moshell at the address listed under INQUIRIES. APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 9/91) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research; from the Office of Grants Information, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone 301/594-7248. The RFA label available in the PHS 398 (rev. 9/91) application form must be affixed to the bottom of the face page of the application. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2a of the face page of the application form and the YES box must be marked. Applications for the FIRST Award (R29) must include at least three sealed letters of reference attached to the face page of the original application. FIRST Award (R29) applications submitted without the required number of reference letters will be considered incomplete and will be returned without review. Submit a signed, typewritten original of the application, including the Checklist, and three signed, photocopies, in one package to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** At the time of submission, two additional copies of the application must also be sent to Dr. Alan N. Moshell at the address listed under INQUIRIES. Applications must be received by November 30, 1993. If an application is received after that date, it will be returned to the applicant without review. The Division of Research Grants (DRG) will not accept any application in response to this announcement that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. The DRG will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of substantial revisions of applications already reviewed, but such applications must include an introduction addressing the previous critique. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by the DRG and responsiveness by the NIAMS. Incomplete applications will be returned to the applicant without further consideration. If the application is not responsive to the RFA, ICD staff will contact the applicant to determine whether to return the application to the applicant or submit it for review in competition with unsolicited applications at the next review cycle. Applications may be triaged by an ICD peer review group on the basis of relative competitiveness. The NIH will withdraw from further competition those applications judged to be non-competitive for award and notify the applicant Principal Investigator and institutional official. Those applications judged to be competitive will undergo further scientific merit review. Those applications that are complete and responsive will be evaluated in accordance with the criteria stated below for scientific/technical merit by an appropriate peer review group convened by NIAMS. The second level of review will be provided by the National Advisory ICD Council/Board. Review criteria for this RFA are generally the same as those for unsolicited research grant applications and include: o scientific, technical, or clinical significance and originality of proposed research; o appropriateness and adequacy of the experimental approach and methodology proposed to carry out the research; o qualifications and research experience of the Principal Investigator and staff, particularly, but not exclusively, in the area of the proposed research; o availability of the resources necessary to perform the research; o appropriateness of the proposed budget and duration in relation to the proposed research; o responsiveness to the RFA objectives. AWARD CRITERIA The anticipated date of award is July 1, 1994. Awards will be based upon the following criteria: o priority score o availability of funds o programmatic priorities of the funding ICD o responsiveness to the RFA INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Address the letter of intent and send two copies of the completed application to: Alan N. Moshell, M.D. National Institute of Arthritis and Musculoskeletal and Skin Diseases Westwood Building, Room 752 Bethesda, MD 20892 Telephone: (301) 594-9955 FAX: (301) 594-9673 Direct inquiries regarding programmatic issues to: Hilary D. Sigmon, Ph.D., R.N. National Institute for Nursing Research Westwood Building, Room 405 Bethesda, MD 20892 Telephone: (301) 594-7397 FAX: (301) 594-7603 Dr. David Finkelstein National Institute on Aging Gateway Building, Room 2C231 Bethesda, MD 20892 Telephone: (301) 496-6402 FAX: (301) 402-0010 Dr. Danuta Krotoski National Center for Medical Rehabilitation Research National Institute of Child Health and Human Development Building 61E, Room 2A03 Bethesda, MD 20892 Telephone: (301) 402-2242 FAX: (301) 402-0832 Dr. Charles A. Wells National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 622 Bethesda, MD 20892 Telephone: (301) 594-7505 FAX: (301) 594-9011 Direct inquiries regarding fiscal matters to: Mary Graham National Institute of Arthritis, Musculoskeletal and Skin Diseases Westwood Building, Room 722 Bethesda, MD 20892 Telephone: (301) 594-9974 FAX: (301) 594-9950 Sally A. Nichols Grants Management Office National Institute for Nursing Research Westwood Building, Room 748 Bethesda, MD 20892 Telephone: (301) 594-7498 FAX: (301) 594-7603 Mary Ellen Colvin Grants Management Office National Institute of Child Health and Human Development Building 61E, Room 8A17F Bethesda, MD 20892 Telephone: (301) 496-1303 FAX: (301) 402-0915 Bob Pike Grants Management Office National Institute on Aging Gateway Building, Room 2N212 Bethesda, MD 20892 Telephone: (301) 496-1472 FAX: (301) 402-3672 Betty E. Bailey Division of Extramural Activities National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 649 Bethesda, MD 20892 Telephone: (301) 594-7543 FAX: (301) 594-7594 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.361. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$XID RFA HL93018 HL-93-018 P1O1 *************************************** HEMOGLOBIN-BASED OXYGEN CARRIERS: MECHANISMS OF TOXICITY NIH GUIDE, Volume 22, Number 29, August 13, 1993 RFA: HL-93-018 P.T. National Heart, Lung, and Blood Institute Letter of Intent Receipt Date: October 15, 1993 Application Receipt Date: December 10, 1993 PURPOSE The Transfusion Medicine Branch, Division of Blood Diseases and Resources, National Heart, Lung, and Blood Institute (NHLBI), invites grant applications for studies to elucidate the mechanisms of toxicity of hemoglobin-based oxygen carriers. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This Request for Applications (RFA), Hemoglobin-Based Oxygen Carriers: Mechanisms of Toxicity, is related to the priority areas of HIV infection, and immunization and infectious diseases. The goal of this program is the development of safe and effective hemoglobin-based oxygen carriers free of infectious disease agents. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-782-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of state or local governments, and eligible agencies of the Federal government. Awards in response to this RFA will be made to foreign institutions only for research of very unusual merit, need, and promise, and in accordance with PHS policy governing such awards. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT This RFA will use the National Institutes of Health (NIH) individual research grant award (R01) and is a one-time solicitation. Applicants, who will plan and execute their own research programs, are requested to furnish their own estimates of the time required to achieve the objectives of the proposed research project. Up to five years of support may be requested. At the end of the official award period, renewal applications may be submitted for peer review and competition for support through the regular grant program of the NHLBI. It is anticipated that support for the present program will begin July 1, 1994. Administrative adjustments in project period or amount of support may be required at the time of the award. Since a variety of approaches would represent valid responses to this announcement, it is anticipated that there will be a range of costs among individual grants awarded. All current policies and requirements that govern the research grant programs of the NIH will apply to grants awarded in connection with this RFA. FUNDS AVAILABLE It is anticipated that for fiscal year 1994, $1,500,000 will be available for this initiative. Approximately $750,000 of that amount will be provided through an initiative of the Advanced Biomaterials Program of the Federal Coordinating Council for Science, Engineering and Technology (FCCSET). It should be noted that award of grants pursuant to this RFA is contingent upon receipt of such funds for this purpose. It is anticipated that about six to eight new grants will be awarded under this program. The specific amount to be funded will, however, depend on the merit and scope of the applications received and on the availability of funds. If collaborative arrangements involve sub-contracts with other institutions, the NHLBI Grants Operations Branch (telephone 301/594-7436) should be consulted regarding procedures to be followed. RESEARCH OBJECTIVES Background An alternative to red blood cells for transfusion has been sought unsuccessfully for over one hundred years. In recent years, the NHLBI and other government agencies have supported research on the development of stable oxygen carriers that do not need to be cross-matched and that can be stored for extended periods of time. During the past decade, awareness of the dangers inherent in transfusion of allogeneic red blood cells has heightened. These include transmission of infectious agents such as HIV, hepatitis viruses and other microorganisms. Consequently, physicians are increasingly reluctant to transfuse their patients and patients are increasingly reluctant to receive blood. Although testing of units of blood is becoming more comprehensive and efficient, there is no question that products that are free of infectious agents that could be used in place of red cells would have wide clinical application. In spite of this promise, studies of hemoglobin-based oxygen carriers have been disappointing as unpredictable toxicities have thwarted development of clinically useful products. Infusion of hemoglobin-based oxygen carriers into the circulation can result in a variety of outcomes. Carrier molecules may leave the circulation by a number of routes including endothelial transcytosis, phagocytic uptake, and diffusion. The effects of these materials may be as diverse as the range of properties of the various tissues they bathe. Their interaction with endothelium-derived relaxing factors, stimulation of other vasoactive materials, and stimulation of mediators of inflammation may add to the complex biological reactions noted in research to date. Furthermore, much of the previous work in this field is clouded by differences in species, so that, at present, there are no animal or in vitro models that will reliably predict human reactions. In addition to federal support, research and development of artificial oxygen carriers has been carried out by industry. Indeed, industry has contributed valuable knowledge in the area of product and quality control. Sophisticated high technology systems have been developed to produce products in large quantities. However, in recent clinical trials with hemoglobin-based oxygen carriers, unexpected toxicities were observed, suggesting the need for more basic research to address fundamental questions concerning interactions with the immune system and endothelium in particular. Research Objectives and Experimental Approaches The purpose of this RFA is to encourage research aimed at providing an understanding of the mechanisms of toxicity of hemoglobin-based oxygen carriers. This program encourages research addressing such fundamental questions as: (1) what are the mechanisms of vasoactivity of hemoglobin solutions, (2) how do protein modifications affect vasoactivity, (3) what are the mechanisms of stimulation of inflammation mediators by hemoglobin-based oxygen carriers, (4) how can this stimulation be prevented, (5) what animal or in vitro models are best used to study toxic effects of oxygen carriers, (6) what are the long-term (metabolic and pharmacologic) effects of oxygen carriers, and (7) what models are best to demonstrate efficacy in terms of oxygen transport to tissue? Particular encouragement is offered to investigators possessing modern tools, who are well-trained, and who are currently pursuing other research interests to devote time and resources to this area. It is hoped that interdisciplinary and collaborative approaches may be developed which will complement the efforts of workers in the field. The ultimate goal is to satisfy a fundamental need in clinical medicine, i.e., development of a safe, economical and efficacious alternative to allogeneic human red blood cells for transfusion. Examples of promising topics are: o Studies of the interaction of hemoglobin with endothelium and macrophages. o Development of animal models that simulate clinical use, such as trauma, shock, infection, and surgical blood loss. o Studies relating the biochemical modification of hemoglobin to its biological effects. o Studies of encapsulation of hemoglobin into artificial vesicles - biochemical, physical, physiological, and biological effects. o Studies of the tissue distribution and metabolic fate of modified hemoglobins, and artificial vesicles. These are intended as examples only. Investigators are encouraged to consider other innovative approaches. Applications may address one or several issues, but should retain a common theme and focus on addressing those issues. Because issues involving hematology, biochemistry, physiology, cell biology, pharmacology or molecular biology may need to be addressed in a coordinated manner, collaboration among investigators having expertise in these and other appropriate disciplines is encouraged. When individuals are at different institutions, individual R01 applications may include consortium arrangements. While the main focus of this RFA is on basic or fundamental research studies to elucidate the mechanisms of toxicity of hemoglobin-based oxygen carriers, clinical studies, but not clinical trials, are also appropriate. Collaborative arrangements with ongoing clinical studies or trials that provide patient material at little or no cost to the applicant are also encouraged. Such arrangements should be clearly delineated in the application. The description should include sufficient information to permit scientific evaluation of the studies proposed. Among issues to include are the number and type of specimens/patients, patient population characteristics (including gender and minority composition; see STUDY POPULATIONS below), overall goals of the collaborative project, remaining term of the project, and IRB approval of the project. If substantial interactions and costs with ongoing projects are proposed, a consortium agreement can be developed and submitted to support this additional research aspect. If statistical analysis is anticipated, the methodologies and personnel involved should be described in the application and evident in the study design. Exclusions: Epidemiological studies, large-scale clinical trials, and large multi-project grant applications (program project grants) are specifically excluded from this RFA. SPECIAL REQUIREMENTS Upon initiation of the program, the NHLBI will sponsor annual meetings to encourage the exchange of information among investigators who participate in this program. In the preparation of the budget for the grant application, applicants should request additional travel funds for one meeting each year to be held in Bethesda, Maryland. Applicants should also include a statement in the applications indicating their willingness to participate in such meetings. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements will be required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis should be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population- based studies, a clear compelling rationale should be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues should be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information must be included in the form PHS 398 (rev. 9/91) in Sections 1-4 of the Research Plan AND summarized in Section 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., Native Americans, Blacks, and Hispanics). The rationale for studies on single minority population groups should be provided. For the purpose of this policy, clinical research includes human biomedical and behavioral studies of etiology, epidemiology, (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including but not limited to clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded. However, every effort should be made to include human tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. For foreign awards, the policy on inclusion of women applies fully; since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. If the required information is not contained within the application, the application will be deferred until the information is provided. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and will be reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. LETTER OF INTENT Prospective applicants are asked to submit, by October 15, 1993, a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, the identities of other key personnel and participating institutions, and the number and title of the RFA in response to which the application may be submitted. Such letters are requested only for the purpose of providing an indication of the number and scope of applications to be received; therefore their receipt is usually not acknowledged. A letter of intent is not binding, and it will not enter into the review of any application subsequently submitted, nor is it a necessary requirement for the application. This letter of intent is to be sent to: Chief, Centers and Special Projects Review Section Division of Extramural Affairs Natinal Heart, Lung, and Blood Institute Westwood Building, Room 553 Bethesda, MD 20892 Telephone: (301) 594-7448 FAX: (301) 594-7407 APPLICATION PROCEDURES Applications are to be submitted on the research grant application form PHS 398 (rev. 9/91). This form is available in an applicant institution's office of sponsored research or business office and from the Office of Grants Information, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone (301) 594-7248. Use the conventional format for research grant applications and ensure that the points identified in the section on REVIEW CONSIDERATIONS are fulfilled. To identify the application as a response to this RFA, check "YES" on Item 2a of page 1 of the application and enter the title and RFA number: HEMOGLOBIN-BASED OXYGEN CARRIERS: MECHANISMS OF TOXICITY: NHLBI RFA HL-93-018-B. The RFA label available in the PHS 398 application kit must be affixed to the bottom of the face page of the original copy of the application. Failure to use this label could result in delayed processing of the application. Send or deliver the completed application and three signed, exact photocopies to the following, making sure that the original application with the RFA label attached is on top: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** Send an additional two copies of the application to the Chief, Centers and Special Projects Review Section at the address listed under LETTER OF INTENT. It is important to send these two copies at the same time as the original and three copies are sent to the Division of Research Grants. Otherwise the NHLBI cannot guarantee that the application will be reviewed in competition for this RFA. Applications must be received by December 10, 1993. If an application is received after that date, it will be returned to the applicant without review. The DRG will not accept any application in response to this announcement that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. The DRG will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of substantial revisions of applications already reviewed, but such applications must include an introduction addressing the previous critique. This is a National Heart, Lung, and Blood Institute Request for Applications. the National Institute of Environmental Health Sciences (NIEHS) also has an interest in the subject matter of this announcement and therefore, may be given a secondary institute assignment, if appropriate. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by the DRG and responsiveness by the NHLBI. Incomplete applications will be returned to the applicant without further consideration. If the application is not responsive to the RFA, NHLBI staff will contact the applicant to determine whether to return the application to the applicant or submit it for review in competition with unsolicited applications at the next review cycle. Applications may be triaged by an NHLBI peer review group on the basis of relative competitiveness. The NIH will withdraw from further competition those applications judged to be non-competitive for award and notify the applicant Principal Investigator and institutional official. Those applications judged to be competitive will undergo further scientific merit review. Those applications that are complete and responsive will be evaluated in accordance with the criteria stated below for scientific/technical merit by an appropriate peer review group convened by the Division of Extramural Affairs, NHLBI. The second level of review will be provided by the National Heart, Lung, and Blood Advisory Council. Review Criteria The factors to be considered in the evaluation of scientific merit of each application will be similar to those used in the review of traditional research grant applications, including the novelty, originality, and feasibility of the approach; the training, experience and research competence of the investigator(s); the adequacy of the experimental design; the suitability of the facilities; and the appropriateness of the requested budget to the work proposed. AWARD CRITERIA The anticipated date of award is July 1, 1994. Funding decisions will be made on the basis of scientific and technical merit as determined by peer review, program needs and balance, and the availability of funds. Awards in response to this RFA will be made to foreign institutions only for research of very unusual merit, need, and promise, and in accordance with PHS policy governing such awards. INQUIRIES Written and telephone inquiries concernint htis RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Inquiries regarding programmatic issues may be directed to: Dr. George J. Nemo Division of Blood Diseases and Resources National Heart, Lung, and Blood Institute Federal Building, Room 504 Bethesda, MD 20892 Telephone: (301) 496-1537 FAX: (301) 402-4843 Inquiries regarding fiscal and administrative matters may be directed to: Ms. Jane R. Davis Blood Division Grants Management Section National Heart, Lung, and Blood Institute Westwood Building, Room 4A11 Bethesda, MD 20892 Telephone: (301) 594-7436 AUTHORITY AND REGULATIONS The programs of the Division of Blood Diseases and Resources, NHLBI, are described in the Catalog of Federal Domestic Assistance number 93.839. Awards will be made under the authority of the Public Health Service Act, Section 301 (42 USC 241) and administered under PHS grant policies and Federal regulations, most specifically 42 CFR Part 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372, or to Health Systems Agency review. From owner-sci-resources@net.bio.net Tue Aug 17 23:00:00 1993 Path: biosci!NET.BIO.NET!kristoff From: kristoff@NET.BIO.NET (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NSF - Summary of new documents on STIS - 15 August 1993 Message-ID: Date: 18 Aug 93 04:52:09 GMT Sender: kristoff@net.bio.net Distribution: bionet Lines: 130 Approved: sci-resources-moderator@net.bio.net ** NEW DOCUMENTS ON STIS ** Document Type: Antarctic EAM Title: OPP 93106-Antarctic waste regulations File size (bytes): 23386 STIS Filename: opp93106 Title: OPP 93107-Black Island telecommunications upgrade File size (bytes): 19579 STIS Filename: opp93107 Title: OPP-93108 Sea water intake, McMurdo File size (bytes): 23405 STIS Filename: opp93108 Title: OPP 93109-AMANDA science project at South Pole File size (bytes): 27382 STIS Filename: opp93109 Title: OPP 93110-Radarsat power plan File size (bytes): 34412 STIS Filename: opp93110 Title: OPP 93111-Ice core drilling at McMurdo Dome File size (bytes): 25004 STIS Filename: opp93111 Title: OPP 93112-Snow-removal melt areas at McMurdo File size (bytes): 35321 STIS Filename: opp93112 Title: OPP 93113-Freon change in ASR-8 radar < File size (bytes): 11840 STIS Filename: opp93113 Title: OPP 93114-Tunnel at South Pole Station File size (bytes): 22440 STIS Filename: opp93114 Document Type: Letter Title: NSF 93-109 -- OCE Dear Colleague Letter File size (bytes): 15222 STIS Filename: nsf93109 Document Type: Program Guideline Title: NSF 93-101 - Coastal Ocean Processes (CoOOP), Coastal Air-Sea Chemical Fluxes File size (bytes): 16812 STIS Filename: nsf93101 Title: NSF 93-105 -- Mathematical Sciences Postdoctoral Research Fellowships File size (bytes): 44835 STIS Filename: nsf93105 Title: NSF 93-113 Postdoctoral Research Fellowships in Plant Biology File size (bytes): 34317 STIS Filename: nsf93113 Title: NSF 93-96 -- Cooperative Agreements for Environmental Research in Support of U.S. Antarctic Program Environmental Management File size (bytes): 26740 STIS Filename: nsf9396 ------------------------------------------------------------------------ ** UPDATES TO EXISTING STIS DOCUMENTS ** Document Type: Antarctic EAM Title: OPP 93000-USAP environmental documents list File size (bytes): 13802 STIS Filename: opp93000 Document Type: Phone Book Title: NSF Alphabetical Listing File size (bytes): 91378 STIS Filename: phnalpha Title: NSF Organizational Directory File size (bytes): 98935 STIS Filename: phnorg ------------------------------------------------------------------------ ** FOR YOUR REFERENCE ** ------------------------------------------------------------------------ HOW TO OBTAIN DOCUMENTS The above files can be retrieved in electronic form using the STIS system. If you don't know how to use STIS, send an E-mail message to stisinfo@nsf.gov (Internet) or stisinfo@NSF (BITNET). You will receive a copy of the STIS flyer via E-mail. If you are already using STIS, you can use the information above to retrieve these files: Documents via E-mail: Send a message to stisserv@nsf.gov (Internet) or stisserv@NSF (BITNET). Use the "STIS Filename" shown above in the "get" command. For example, to retrieve phnorg, the text of your message should be as follows: get phnorg Anonymous FTP: FTP to stis.nsf.gov. Use the "STIS Filename" shown above to retrieve a file. For example, to retrieve phnorg, you would enter: ftp> get phnorg WAIS or Gopher: Do a word search on the filename as shown in the summary. If you want a *printed* copy of a document: Send your name and postal mailing address, and the document title and number to "firstop@nsf.gov" (Internet) or "firstop@nsf" (BITNET). If you have problems with the above procedures: Send a message to "stis@nsf.gov" (Internet) or "stis@NSF" (BITNET). From owner-sci-resources@net.bio.net Fri Aug 20 23:00:00 1993 Path: biosci!NET.BIO.NET!kristoff From: kristoff@NET.BIO.NET (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 22, no. 30, pt. 1, 20 August 1993 Message-ID: Date: 21 Aug 93 14:54:55 GMT Sender: kristoff@net.bio.net Distribution: bionet Lines: 1598 Approved: sci-resources-moderator@net.bio.net NOTE: The NIH Guide may be split into more than one mail message to avoid truncation during e-mail distribution. The first message always begins with the RFP/RFA summary sections followed by the appended texts of the full RFP/RFAs. ---------------------------------------------------------------------- $$XID NIHGUIDE 19930820 V22N30 P1O2 ************************************ X-comment: RFAs described: HD-94-007 NIH GUIDE - Vol. 22, No. 30 - August 20, 1993 $$INDEX BEGIN ******************************************************* NOTICES OF AVAILABILITY (RFPs AND RFAs) $$INDEX R1 ********************************************************** SPEECH AND LANGUAGE DEVELOPMENT IN THE DEAF CHILD OF HEARING PARENTS: APPROACHES TO INTERVENTION (RFP NIH-DC-93-05) National Institutes on Deafness and Other Communications Disorders INDEX: DEAFNESS, OTHER COMMUNICATIONS DISORDERS $$INDEX R2 ********************************************************** RESYNTHESIS OF COMPOUNDS FOR SCREENING (RFP NCI-CM-47007-29) National Cancer Institute INDEX: CANCER $$INDEX R3 01/18/94 ************************************************* BEHAVIORAL DEVELOPMENT IN MIDDLE CHILDHOOD (RFA HD-94-007) National Institute of Child Health and Human Development National Institute of Mental Health INDEX: CHILD HEALTH, HUMAN DEVELOPMENT; MENTAL HEALTH ONGOING PROGRAM ANNOUNCEMENTS $$INDEX P1 ********************************************************** RESEARCH PROGRAM TO IMPROVE DRUG ABUSE TREATMENT (PA-93-100) National Institute on Drug Abuse INDEX: DRUG ABUSE $$INDEX P2 ********************************************************** NUTRITION IN CYSTIC FIBROSIS (PA-93-103) National Institute of Diabetes and Digestive and Kidney Diseases INDEX: DIABETES, DIGESTIVE, KIDNEY DISEASES $$INDEX P3 ********************************************************** RESEARCH ON ORAL BONE LOSS AND OSTEOPOROSIS (PA-93-104) National Institute of Dental Research National Institute of Arthritis and Musculoskeletal and Skin Diseases INDEX: DENTAL RESEARCH; ARTHRITIS, MUSCULOSKELETAL, SKIN DISEASES ERRATUM $$INDEX E1 11/10/93 ************************************************* AID/NIAID PROGRAM: FUNDAMENTAL MALARIA VACCINE STUDIES (RFA AI-93- 016) National Institute of Allergy and Infectious Diseases INDEX: ALLERGY, INFECTIOUS DISEASES $$INDEX E2 11/17/93 ************************************************* IN UTERO STEM CELL TRANSPLANTATION FOR GENETIC DISEASES (RFA HL-93-014) National Heart, Lung and Blood Institute National Institute of Diabetes and Digestive and Kidney Diseases INDEX: HEART, LUNG, BLOOD; DIABETES, DIGESTIVE, KIDNEY DISEASES This publication is available electronically to institutions via BITNET or INTERNET and is also on the NIH GOPHER. Alternative access is through the NIH Grant Line using a personal computer (data line 301/402-2221). Contact Dr. John James at 301/594-7270 for details. $$INDEX END ********************************************************* NOTICES OF AVAILABILITY (RFPs AND RFAs) $$R1 BEGIN NIH-DC-93-05 ********************************************* SPEECH AND LANGUAGE DEVELOPMENT IN THE DEAF CHILD OF HEARING PARENTS: APPROACHES TO INTERVENTION NIH GUIDE, Volume 22, Number 30, August 20, 1993 RFP AVAILABLE: NIH-DC-93-05 P.T. 34; K.W. 0715050, 0715055, 0410001, 0710120 National Institutes on Deafness and Other Communications Disorders The National Institute on Deafness and Other Communication Disorders, National Institutes of Health, has a requirement to identify and evaluate factors associated with successful developmental progress within a variety of treatment approaches for deaf children of hearing parents. The Contractor will specifically evaluate the variables that are associated with communicative, cognitive, social, and academic progress. In addition, profiles of individual performance will be examined across treatment approaches and factors influencing initial placement and validity of these factors, based on outcome data, will be examined. These findings will be of assistance to parents, speech-language pathologists, audiologists, teachers of deaf children, and others involved in the selection of a communication approach and the management of the developing deaf child of hearing parents. A six-year cost-reimbursement type contract is anticipated. The solicitation is scheduled to be issued on or about September 3, 1993. Proposals will be due 45 days after the date of issuance of the solicitation. All responsible sources may submit a proposal that will be considered by the Government. INQUIRIES Copies of the solicitation may be obtained by sending a written request to: John P. DeCenzo, Contracting Officer Division of Contracts and Grants National Institutes of Health Building 31, Room 1B44 Bethesda, MD 20892 Telephone: (301) 496-4487 $$R1 END ************************************************************ $$R2 BEGIN NCI-CM-47007-29 ****************************************** RESYNTHESIS OF COMPOUNDS FOR SCREENING NIH GUIDE, Volume 22, Number 30, August 20, 1993 RFP AVAILABLE: NCI-CM-47007-29 P.T. 34; K.W. 0740012, 0715008, 1003012, 1003006 National Cancer Institute The Drug Synthesis and Chemistry Branch (DS&CB) of the Developmental Therapeutics Program (DTP) of the Division of Cancer Treatment (DCT) of the National Cancer Institute (NCI) is seeking Contractors with established expertise in the field of synthesis of organic and inorganic compounds to prepare those deemed of interest to the program for evaluation as antitumor and AIDS-antiviral agents. The primary focus will be to synthesize samples of compounds, generally identified from literature sources, that have been designated of interest to the DTP drug development program and which are not available from the original sources. Compounds may be required for either primary screening or follow-up testing in the anticancer and/or anti-HIV programs. Compounds assigned for synthesis will include, but not be limited to, carbocycles, heterocycles typically containing nitrogen, oxygen, and sulfur, carbohydrates, nucleosides, and metal coordination complexes. Detailed experimental procedures obtained from the literature will be available for the majority of the assignments. Some development on synthetic methods may be required in those cases where no such procedures are available or when the published methods prove unreliable in practice. The quantities of compounds to be prepared will vary widely, but will usually be in the range from 0.1 to 5 grams. All synthesized compounds submitted to the DS&CB (at least 15 to 20 target compounds per year per contract) will be characterized as to identity and purity. Each Contractor must have available a fully operational facility including all necessary equipment and instrumentation needed to perform for all aspects of the contract. The NCI signs legally binding agreements with some suppliers (often pharmaceutical or chemical companies) which state that all information on compounds donated by those suppliers will be held confidential. The occasion may arise whereby the successful offeror will be assigned such a confidential compound as a synthesis or modification target. If the Contractor were a chemical pharmaceutical company, they could gain valuable data on confidential new lead compounds. The NCI believes that in order to honor the confidentiality agreement with suppliers and in order to avoid any chance of transmitting privileged data to a competitor, pharmaceutical and chemical companies must be excluded from the competition. A pharmaceutical or chemical company is defined as an organization which sells drugs and/or chemicals to the general public for profit. NOTE: Two related RFPs are currently available. It is anticipated that multiple incrementally funded contracts will be awarded for a period of five years beginning on or about September 1, 1994. RFP No. NCI-CM-47007-29, Resynthesis of Compounds for Screening, is an open competition. RFP No. NCI-CM-47015-29, Resynthesis of Compounds for Screening by Small Business, is a 100% set-aside for small business. The Standard Industrial Code (SIC) for the small business set-aside is 8731 (500 employees). Offerors who qualify as a small business are encouraged to submit proposals under both RFPs; however, not more than one award of the available awards (under both RFPs) will be made to any single offering organization. INQUIRIES These projects represent a recompetition of contracts with New Mexico State University, N01-CM-17528, Research Triangle Institute, N01-CM-17568, and Starks Associates, N01-CM-17517. Both RFPs will be issued on or about September 20, 1993. Proposals will be due on November 5, 1993. Requests for the RFP may be made by written request to: Clyde Williams, Contracting Officer Research Contracts Branch, TCS National Cancer Institute Executive Plaza South, Room 603 Bethesda, MD 20892 Telephone: (301) 496-8620 Collect calls will not be accepted. $$R2 END ************************************************************ $$R3 BEGIN HD-94-007 FULL-TEXT ************************************** BEHAVIORAL DEVELOPMENT IN MIDDLE CHILDHOOD NIH GUIDE, Volume 22, Number 30, August 20, 1993 RFA AVAILABLE: HD-94-007 P.T. 34, AA; K.W. 0404000, 0404004 National Institute of Child Health and Human Development National Institute of Mental Health Application Receipt Date: January 18, 1994 THIS IS A NOTICE OF AVAILABILITY OF A REQUEST FOR APPLICATIONS (RFA); IT IS ONLY AN ABSTRACT OF THE RFA. POTENTIAL APPLICANTS MUST REQUEST THE COMPLETE RFA, WHICH CONTAINS ESSENTIAL INFORMATION FOR THE PREPARATION OF AN APPLICATION, FROM THE CONTACT LISTED IN "INQUIRIES," BELOW. FAILURE TO FOLLOW THE INSTRUCTIONS IN THE COMPLETE RFA MAY RESULT IN AN INCOMPLETE APPLICATION, WHICH WILL BE RETURNED TO THE APPLICANT WITHOUT REVIEW. PURPOSE The Human Learning and Behavior Branch, Center for Research for Mothers and Children, National Institute of Child Health and Human Development (NICHD) and the Division of Neuroscience and Behavioral Science, National Institute of Mental Health (NIMH) invite applications for the support of research on behavioral development during middle childhood. The purpose of this RFA is to stimulate the submission of high quality research applications for scientific studies designed to characterize psychological and behavioral aspects of development of American children during their middle childhood period. More specifically, the investigations should center on gaining a deep understanding of social, emotional and cognitive processes that develop and help to uniquely define that period that is termed middle childhood (the period that includes the age range among children in grades K-6). Research focusing on normative development is particularly encouraged. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority goals. This RFA, Behavioral Development in Middle Childhood, relates to the priority area of psychological, behavioral, familial and cultural factors associated with variations in development of American boys and girls during their middle childhood years. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic for-profit and non-profit organizations, public and private, such as universities, colleges, units of state and local governments, and eligible agencies of the Federal government. Applications from minority individuals and women are encouraged. Foreign institutions are not eligible for the First Independent Research Support and Transition (FIRST) (R29) award. MECHANISMS OF SUPPORT Research support will be provided through the individual research project grant (R01) and the FIRST award (R29). FUNDS AVAILABLE The support of grants in connection with this RFA is contingent on the availability of funds for this purpose. The number of grants awarded will be influenced by the total amount of funds available to the NICHD and NIMH, the overall number of meritorious applications received, and the relevance of the applications to stated program goals. It is anticipated that up to $1 million direct costs ($750,000 NICHD; $250,000 NIMH) will be available to fund six to eight meritorious applications under this RFA. RESEARCH OBJECTIVES This RFA was initiated in response to requests made by the Congress of the United States to the NICHD. Report #102-397 (FY 1993) of the U.S. Senate Appropriations Committee (p. 114) encourages the NICHD: "...to embark on a long term planning process to investigate psychological and behavioral processes of the middle childhood years, ages 5-11 years." A similar request was made in report #102-708 (FY 1993) by the Committee on Appropriations of the U.S. House of Representatives (p. 77) encourages: "the NICHD in collaboration with the NIMH to consider development of a new general behavioral science initiative in the area of middle childhood development." Our expectation is that a strong program of basic research conducted under the auspices of this RFA may provide key information about social, cognitive and emotional factors that could influence development of appropriate decision-making skills. The results from such research may help provide relevant information on how peer pressure emerges and how it can be used to foster health promoting behaviors or lead to behavioral problems. Similarly, data from to-be supported investigations of social, emotional and cognitive development may inform scholars, educators and parents concerning factors that may enhance and maintain motivation related to self-confidence and academic functioning beyond the years of middle childhood. In short, the results of the to-be supported research can help to illuminate the roots of critical behaviors that uniquely define middle childhood and lead to healthy development, or start children on the paths to behavioral problems that appear in the teenage years. STUDY POPULATION SPECIAL INSTRUCTIONS FOR INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDIES The research subjects will be boys and girls who attend grades K-6 in the United States. Investigators are encouraged to study male and female children varying in their racial and socio-economic background. NIH policy requires research grants to include minorities and women. If women and minorities are excluded or inadequately represented in the proposed research, a clear and compelling rationale must be provided. Applicants are encouraged to carefully assess the feasibility of, including the broadest possible representation, of minority groups. APPLICATION PROCEDURES Applications are to be submitted on form PHS 398 (rev. 9/91). The application kit may be obtained from the office of sponsored research at your university/research institution and from the Office of Grants Information, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, Md 20892, telephone 301/594-7248. Applications for the FIRST Award (R29) must include at least three sealed letters of reference attached to the face page of the original application. First Award (R29) applications submitted without the required number of reference letters will be considered incomplete and will be returned without review. REVIEW CONSIDERATIONS Applications will be reviewed upon receipt by NIH staff for completeness and responsiveness to the RFA. Incomplete or non-responsive applications will be returned to the applicant. Those applications judged to be competitive will undergo review for scientific merit by a Special Review Committee (SRC) convened by the NICHD. The second level of review will be conducted by the respective National Advisory Councils of the NICHD and the NIMH. The anticipated date of the award is July 1, 1994. INQUIRIES Potential applicants are welcome to make inquiries concerning this RFA. Questions related to programmatic issues and requests for the RFA may be directed to: Norman A. Krasnegor, Ph.D. Center for Research for Mothers and Children National Institute of Child Health and Human Development 6100 Building, Room 4B05 Bethesda, MD 20892 Telephone: (301) 496-6591 Mary Ellen Oliveri, Ph.D. Division of Neuroscience and Behavioral Science National Institute of Mental Health 5600 Fishers Lane, Room 11C-10 Rockville, MD 20857 Telephone: (301) 443-3942 Direct inquiries concerning fiscal matters to: Edgar D. Shawver Office of Grants and Contracts National Institute of Child Health and Human Development 6100 Building, Room 8A17E Bethesda, MD 20892 Telephone: (301) 496-1303 Diana Trunnell Assistant Chief, Grants Management Branch National Institute of Mental Health 5600 Fishers Lane, Room 7C-15 Rockville, MD 20857 Telephone: (301) 443-3065 AUTHORITY AND REGULATIONS This program is described in the Catalogue of Federal Assistance No. 93.865 for Mothers and Children and 93.242, Mental Health Research Projects. Awards are made under the authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR part 74. Awards are also made under authorization of PHS Title V, Part B. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$R3 END ************************************************************ ONGOING PROGRAM ANNOUNCEMENTS $$P1 BEGIN PA-93-100 ************************************************ RESEARCH PROGRAM TO IMPROVE DRUG ABUSE TREATMENT NIH GUIDE, Volume 22, Number 30, August 20, 1993 PA NUMBER: PA-93-100 P.T. 34; K.W. 0404009, 0745070 National Institute on Drug Abuse PURPOSE The purpose of this Program Announcement is to encourage research on interventions to improve drug abuse treatment. The aim of the grant program is to demonstrate improvements in drug abuse and dependence treatment, resulting in a greater range of effective, standard treatments enabling treatment systems to operate with greater effectiveness and efficiency. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This Program Announcement, Research Program to Improve Drug Abuse Treatment, is primarily related to the priority area of alcohol and other drugs. Potential applicants may obtain a copy of Healthy People 2000 (Full Report: Stock No. 017-001-00474-0, or Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign for-profit and non-profit organizations, public and private such as universities, colleges, hospitals, laboratories, units of State or local governments, and eligible agencies of the Federal Government. Women and minority investigators are encouraged to apply. MECHANISM OF SUPPORT The mechanism available for support of this program announcement is the research project grant (R01). In fiscal year 1994, it is estimated that $10 million will be available from the National Institute on Drug Abuse (NIDA) to support approximately 15 new grants under this announcement. RESEARCH OBJECTIVES Increasing the effectiveness of drug abuse treatment through research is one of the primary goals of NIDA. Effective treatment is essential to efforts to reduce the demand for illicit drugs. The importance of this goal has been underscored by the Acquired Immunodeficiency Syndrome (AIDS) epidemic, since effective treatment is critical to preventing the spread of the Human Immunodeficiency Virus (HIV) among injecting drug users. This program announcement establishes a research program to improve drug abuse treatment in accord with recommendations from the five-year treatment research planning process. The intent of the research grant program is to improve existing treatment strategies. Description of the Program. Applications submitted under this announcement should focus on improving existing treatment approaches, developing new treatment approaches, or addressing important clinical questions impacting on treatment outcome. Interventions may be based in a variety of settings (e.g., hospitals, residential programs, outpatient programs, correctional settings). Investigation into all types of treatment modalities is encouraged. Research projects that investigate the effectiveness of different service components and service strategies are of particular interest. Additionally, programs testing the independent and joint effects of marketed drug dependence pharmacotherapies and psychobehavioral treatment components for particular populations of drug addicts, such as the dually diagnosed, are encouraged. Applicants may establish new treatment slots with the funds requested, in support of their research objectives. In addition, funds may be used to support service components to enhance treatment outcomes (e.g., vocational rehabilitation as part of the treatment provided), but the provision of services must be clearly related to research objectives. Research Projects. Investigators are encouraged to use the most rigorous methodology consistent with the purposes of the research. Some research proposals may appropriately be studied through experimental designs involving random assignment of subjects to treatments, yet, such strategies may not be appropriate for all circumstances. Examples of research areas to be studied include, but are not limited to, the following: o More effective outreach and recruitment strategies for treatment entry and engagement. Community-based interventions that forge therapeutic alliances with families, social networks, and community organizations need to be formulated and tested, especially for the substantial minority of drug users who will not enter drug abuse treatment. o Research to improve treatment engagement and retention. o Therapy-specific diagnostic methods of defining drug abuse syndromes that assess problems addressed by specific therapeutic alternatives and matching individual patient characteristics with treatment techniques. o Research on outpatient treatment retention and compliance, addressing the serious problem of continued use of alcohol, marijuana, cocaine, and benzodiazepines by patients in treatment for other drugs of abuse. o Research to investigate and maximize the efficacy of individual and group, behavioral, cognitive-behavioral, psychodynamic, family therapy, brief interventions, and interpersonal therapies. o Use of existing behavior modification methods to compensate for cognitive deficits in drug addicts is of particular interest. o Drug counseling techniques, operationally defined, to permit the investigation of their efficacy. o Outreach strategies to encourage treatment reentry and/or provide alternative community-based interventions for patients who drop out of treatment. o The impact of ancillary and specialized services, such as literacy training, vocational training and employment services, housing assistance, primary health care, reproductive counseling, parenting training, and case management on treatment engagement, retention, and drug abuse treatment outcomes. o AIDS-related treatment research within existing programs, including medical and case management services for infected and ill clients, grief counseling for clients and staff, AIDS prevention counseling, sexual and perinatal transmission, etc. o Considering the danger of HIV infection with relapse to drug use, new extended treatment programs or aftercare strategies for maintaining prolonged therapeutic interventions, supervision, and support for clients need to be established to prevent relapse and protect individuals. o Means of linking primary medical care with drug abuse treatment in improving drug treatment outcomes especially for drug dependent persons who have serious concomitant medical problems. o Research on models for integrating treatment of drug abuse and other co-occurring psychiatric and neurological disorders. o Psychosocial and behavioral treatments for use in combination with pharmacotherapies to address the problem of continued drug dependence and that interfere with treatment engagement and compliance with medication regimes. o Adaptation and assessment of existing treatments that have been found generally effective, for specific racial and ethnic groups. o Studies of interventions that specifically address the unique needs of women (e.g., interventions that emphasize interpersonal relationships, that address sexual abuse or other forms of victimization). o Treatment research on youth who begin drug use at an early age, are school dropouts, and are at risk for later drug dependence. o Intensive and multi-component interventions for difficult-to-treat clients, low-income persons caught in the cycle of poverty, poorly educated clients who may be functionally illiterate, psychiatrically impaired or lacking in vocational skills. All applicants are strongly encouraged to address issues of project feasibility, implementation of the intervention, study design, sampling procedure, instrumentation and measurement, data collection, tracking of clients, follow-up, and data analysis, as appropriate. The applicant also may wish to include an information dissemination plan, to assure that research findings are communicated to the treatment field in a timely, efficient fashion. Applicants are advised to provide adequate information regarding available facilities and staff, as well as plans to acquire new staff. Investigators are encouraged to offer HIV testing and counseling in accordance with current guidelines to subjects identified during the course of the research as being at risk for HIV acquisition or transmission. In high-risk populations, investigators are encouraged to assess the effects of new interventions on the acquisition and transmission of infectious diseases, including HIV. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements will be required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis should be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale should be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues should be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information should be included in the form PHS 398 in Sections 1-4 of the Research Plan AND summarized in Section 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., Native Americans (including American Indians or Alaskan Natives), Asian/Pacific Islanders, Blacks, Hispanics). The rationale for studies on single minority population groups should be provided. For the purpose of this policy, clinical research includes human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including but not limited to clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded. However, every effort should be made to include human tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. For foreign awards, the policy on inclusion of women applies fully; since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. If the required information is not contained within the application, the application will be returned. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and will be reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. APPLICATION PROCEDURES Applications are to be submitted on the grant application form PHS 398 (rev. 9/91) and will be accepted at the standard application deadlines as indicated in the application kit. The receipt dates for applications for AIDS-related research are found in the PHS 398 instructions. Applicants who are currently supported under the NIDA research demonstration program (R18) will be considered competing continuation (type 2) R01 and may submit their applications for the competing continuation receipt dates of November 1, March 1, or July 1. Application kits are available at most institutional offices of sponsored research and from the Office of Grants Information, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone 301/594-7248. The title and number of the announcement must be typed in item 2a of face page of the application. The completed original application and five legible copies must be sent or delivered to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, Maryland 20892** REVIEW CONSIDERATIONS The Division of Research Grants (DRG), NIH, serves as a central point for receipt of applications for most discretionary DHHS grant programs. Applications received under this announcement will be assigned to an initial review group (IRG) in accordance with established PHS referral guidelines. The IRGs, consisting primarily of non-Federal scientific and technical experts, will review the applications for scientific and technical merit in accordance with the standard NIH peer review procedures. Notification of the review recommendations will be sent to the applicant after the initial review. Applications will receive a second-level review by an appropriate National Advisory Council, whose review may be based on policy considerations as well as scientific merit. Only applications recommended for further consideration by the Council may be considered for funding. AWARD CRITERIA Applications recommended for further consideration by an appropriate National Advisory Council will compete for available funds with all other approved applications assigned to the appropriate Institute. The following will be considered in making funding decisions: o Quality of the proposed project as determined by peer review o Availability of funds o Institute program needs and balance INQUIRIES Written and telephone inquiries are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Frank M. Tims, Ph.D. Division of Clinical Research National Institute on Drug Abuse 5600 Fishers Lane, Room 10A-30 Rockville, MD 20857 Telephone: (301) 443-4060 Direct inquiries regarding fiscal issues to: Chief, Grants Management Branch National Institute on Drug Abuse 5600 Fishers Lane, Room 8A-54 Rockville, MD 20857 Telephone: (301) 443-6710 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.279. Awards are made under authorization of Section 301 of the Public Health Service Act (42 USC 241) and administered under PHS policies and Federal Regulations at Title 42 CFR 52 "Grants for Research Projects," Title 45 CFR Part 74 and 92, "Administration of Grants" and 45 CFR Part 46, "Protection of Human Subjects". Title 42 CFR Part 2, "Confidentiality of Alcohol and Drug Abuse Patient Records," may also be applicable to these awards. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. Sections of the Code of Federal Regulations are available in booklet form from the U.S. Government Printing Office. Grants must be administered in accordance with the PHS Grants Policy Statement, (revised 10/90), which may be available from your office of sponsored research. $$P1 END ************************************************************ $$P2 BEGIN PA-93-103 ************************************************ NUTRITION IN CYSTIC FIBROSIS NIH GUIDE, Volume 22, Number 30, August 20, 1993 PA NUMBER: PA-93-103 P.T. 34; K.W. 0715165, 0710095, 0765035 National Institute of Diabetes and Digestive and Kidney Diseases PURPOSE The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) invites applications for research to assess nutritional status in cystic fibrosis (CF), the pathophysiology underlying the nutritional problems associated with cystic fibrosis, and the contribution of nutritional disorders to morbidity and mortality of cystic fibrosis, and to develop and/or test interventions to improve nutritional status, growth and development in cystic fibrosis. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This Program Announcement, Nutrition in Cystic Fibrosis, is related to the priority area of chronic diseases. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by foreign and domestic, for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Applications from minority individuals and women are encouraged. Foreign institutions are not eligible for the First Independent Research Support and Transition (FIRST) (R29) award. MECHANISM OF SUPPORT The mechanisms of support for this program will be the research project grant (R01), and FIRST awards (R29). Although the sizes of awards may vary considerably from one project to another, it is anticipated that the average size of an award will be approximately $220,000 in total costs for the first budget period. RESEARCH OBJECTIVES The purpose of this initiative is to stimulate research in characterizing the nutritional status of children and adults with CF, improve methods for evaluating nutritional status in CF, understand the causes of malnutrition in CF, examine the molecular and cellular consequences of nutritional alterations in CF, define the relationship of nutritional status to mortality and morbidity in CF, examine whether or not improved nutritional status will influence progression of pulmonary disease, and develop strategies to improve nutritional status, growth and development in CF. Background Despite dramatic improvements in lifespan of patients with CF, the median survival in 1992 was 29 years. Malnutrition contributes significantly toward morbidity in CF. Although malnutrition due to pancreatic enzyme insufficiency is correctable and 92 percent of U.S. CF patients take pancreatic enzyme supplements, the majority of CF patients are underweight and have short stature with half below the tenth percentiles for height and weight, based on data from nearly 19,000 patients in the Cystic Fibrosis Foundation (CFF) National Patient Registry, 1991. Mortality rate and decline in pulmonary function correlate with poorer weight status after adjusting for age, sex, and pulmonary function in longitudinal analyses from this database. The relationship between pulmonary function and nutritional status is complex and the extent to which achievement of normal nutrition and growth might ameliorate the rate of progression of lung disease and improve survival remains to be determined. Longitudinal analysis of CF patients is warranted to answer causal questions. Improved nutritional status may improve exercise tolerance and muscle function, possibly improving respiratory muscle strength, and may have important implications for resistance to infection. A variety of methods are now available for assessing body composition in CF, including bioelectric impedance analysis, dual photon and dual x-ray absorptiometry, and total body electrical conductivity. Assessment of energy expenditure and substrate utilization will permit exploration of questions about the relative contributions of altered energy needs and intake to malnutrition and growth failure in CF. There is evidence that resting energy expenditure is increased in CF, but the mechanism by which this occurs and the contributions of lung disease, the genetic defect itself, medications and inflammation, infection, and other potential factors influencing metabolism must be elucidated. In addition to identifying the mechanisms of altered energy balance, improved methods are needed to detect patients requiring improved nutritional support, monitor prospectively the response to nutritional intervention, and assess the impact of nutritional status on anticipated new therapeutic strategies. Moreover, assessment of the impact on nutritional status of anticipated new therapeutic strategies for CF, including pharmacologic therapy targeted to the molecular basis of the disease and gene therapy, will require simple, validated and cost effective techniques for evaluation of nutritional status. Areas of opportunity and new directions for research were identified at a recent NIDDK/CFF conference on Nutrition in CF and are summarized in this Program Announcement. Scope Some examples of research topics that would be considered responsive to this solicitation include the following: 1. The relationship of nutritional status to mortality and morbidity in CF: o how to use anthropometric indices, including height, weight and skinfold data, parental height, and pubertal stage, most effectively in longitudinal investigation of CF mortality and morbidity; o the nature and basis of male/female discrepancies in CF morbidity and mortality and of clinical worsening at adolescence in CF; o the impact of critical periods of growth, e.g., infancy and adolescence, on nutritional status and response to nutritional intervention in CF; o how fitness and nutritional status are related to mortality and morbidity in CF; 2. Methods to evaluate nutritional status and identify functional correlates in CF: o validation over the age and disease spectrum of nutritional assessment tools ultimately of use in the clinical setting in CF, including both sophisticated methodology and simpler measures; o development and analysis of functional correlates of nutritional status in CF, including exercise tolerance and static and dynamic muscle function; o establish which body composition methods are most useful for assessment of CF and development of dynamic measures of body composition change; o definition of body compartments of nutritional significance and correlation with function in CF; 3. Nutrient absorption and utilization and energy expenditure in CF: o evaluation of energy expenditure methods in CF, i.e., for energy costs of specific activities; o evaluation of substrate utilization methods in CF, e.g., protein and lipid turnover; o novel methods to evaluate nutrient absorption and losses in CF; o evaluation of methods to assess micronutrient homeostasis in CF; o the relative contributions of altered energy loss, energy expenditure, and energy intake to energy imbalance in CF; 4. Combined effects of CF and other conditions: o the impact of other factors including early screening, socio-economic status, liver disease, transplantation and pregnancy on nutritional status in CF; o the etiology of insulin deficiency in CF, its effects on protein metabolism and growth, and optimal methods to assess and manage diabetes mellitus in CF; 5. Relationship of respiratory disease to malnutrition: o relationship of respiratory muscle strength to malnutrition and to specific nutrient deficiencies; o longitudinal data on respiratory muscle strength in CF with and without intervention; o methods to assess muscle function versus mass in malnutrition; o effects of malnutrition on anatomic and functional lung growth; o longitudinal analysis of whether prevention of malnutrition and growth failure ameliorates the rate of progression of lung disease; 6. Longitudinal analysis of the relationship between malnutrition and chronic infection in CF: o does repeated or chronic infection accelerate malnutrition? o are metabolic changes or failure to replete markers for inadequate treatment of infection? o are micronutrient changes a cause or a consequence of susceptibility to infection? o at what level of malnutrition does immunological function deteriorate? o what is the relationship of nutritional status and inflammatory response, acute phase response, and prostaglandin release causing vasoconstriction? o how does infection influence energy expended? 7. Strategies to improve nutritional status in CF: o prospective evaluation of the effectiveness of interventions ranging from education to total parenteral nutrition; o the risks, benefits and role of growth factors and anabolic agents; o improved enzyme formulations that are acid resistant or without pH inhibition; o the role of micronutrients as pharmacologic agents; o specific nutritional supplements such as omega 3 fatty acids or structured lipids; o use of transgenic CF animal models and CF cell lines to explore the impact of nutritional factors and interventions. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements are required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis must be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale must be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues should be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information must be included in the form PHS 398 (rev. 9/91) in Item 4 (Research Design and Methods) of the Research Plan AND summarized in Item 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., Native Americans (including American Indians or Alaskan Natives), Asian/Pacific Islanders, Blacks, Hispanics). The rationale for studies on single minority population groups must be provided. For the purpose of this policy, clinical research is defined as human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including but not limited to clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded. However, every effort should be made to include human tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. For foreign awards, the policy on inclusion of women applies fully; since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. If the required information is not contained within the application, the review will be deferred until the information is provided. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and will be reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. APPLICATION PROCEDURES Applications are to be submitted on the grant application form PHS 398 (rev. 9/91) and will be accepted at the regular application deadlines as indicated in the application kit. Application kits are available at most institutional offices of sponsored research and may be obtained from the Office of Grants Information, Division of Research Grants, National Institutes of Health, Westwood Building Room 449, Bethesda, MD 20892, telephone 301/594-7248. The title and number of this announcement must be typed in Section 2a on the face page of the application. Applications for the FIRST Award (R29) must include at least three sealed letters of reference attached to the face page of the original application. FIRST Award (R29) applications submitted without the required numbered of reference letters will be considered incomplete and will be returned without review. The completed original application and five legible copies must be sent or delivered to: Division of Research Grants National Institutes of Health Westwood Building Room 240 Bethesda, MD 20892** REVIEW PROCEDURES Applications will be assigned on the basis of established PHS referral guidelines. Applications will be reviewed for scientific and technical merit by study sections of the Division of Research Grants, NIH, in accordance with the standard NIH peer review procedures. Following scientific-technical review, the applications will receive a second-level review by the appropriate Institute's national advisory council. AWARD CRITERIA Applications will compete for available funds with all other approved applications. The following will be considered in making funding decisions: o Quality of the proposed project as determined by peer review o Availability of funds o Program balance among research areas of the announcement INQUIRIES Written and telephone inquiries are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Judith E. Fradkin, M.D. Division of Diabetes, Endocrinology and Metabolic Diseases National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 621 Bethesda, MD 20892 Telephone: (301) 594-7567 Direct inquiries regarding fiscal matters to: Linda M. Stecklein Division of Extramural Activities National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 653 Bethesda, MD 20892 Telephone: (301) 594-7543 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.847. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$P2 END ************************************************************ $$P3 BEGIN PA-93-104 ************************************************ RESEARCH ON ORAL BONE LOSS AND OSTEOPOROSIS NIH GUIDE, Volume 22, Number 30, August 20, 1993 PA NUMBER: PA-93-104 P.T. 34; K.W. 0715031, 0715148 National Institute of Dental Research National Institute of Arthritis and Musculoskeletal and Skin Diseases PURPOSE The National Institute of Dental Research (NIDR) and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) invite grant applications to conduct multidisciplinary research, both basic and clinical, with emphasis on genetic and epidemiological aspects of the link between osteoporosis and oral bone loss. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This Program Announcement, Osteoporosis and Oral Bone Loss, is related to the priority area of oral health. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign, non-profit and for-profit, public and private organizations, such as dental or medical schools, universities and research institutions. Foreign institutions are not eligible for the First Independent Research Support and Transition (FIRST) Award (R29). Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT The mechanisms available for the support of this program include the research project grant (R01), First Independent Research Support and Transition (FIRST) Award (R29), small grant (R03) (NIDR only), and Interactive Research Project Grants (IRPG). Applications from institutions that have an Osteoporosis Research Center funded by the NIAMS may wish to identify the center as a resource for conducting the proposed research. If so, a letter of agreement from both the center director and program director should be included with the application. RESEARCH OBJECTIVES Osteoporosis is a major health problem in the United States affecting an estimated 20 million people, many of whom are women. The disease is implicated in 1.5 million fractures each year and accounts for medical care expenditures of at least $10 billion annually. In addition, there is evidence of significant mortality and morbidity associated with osteoporosis. While little is known about the possible relationship between oral bone loss and osteoporosis, the scientific literature suggests that skeletal osteopenia, in concert with underlying factors, may create an environment conducive to accelerated loss of oral bone. In the dentate this may be manifested as a loss of tooth support. In toothless (edentulous) individuals, osteopenia may augment local anatomic, biological, and mechanical factors resulting in extensive ridge atrophy. Thus, skeletal osteopenia may influence the need for and outcome of periodontal, pre-prosthetic, and implant procedures. There is also evidence in the literature to suggest that therapeutic measures that control or have an effect on osteoporosis could have a favorable impact on oral bone retention. An NIH workshop titled "Osteoporosis and Oral Bone Loss" was sponsored by the National Institute of Dental Research, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Office of Research on Women's Health, to bring together experts from various disciplines to focus attention on the possible relationship between osteoporosis and oral bone loss. The goal of the workshop was to summarize the state of the science on this relationship, to identify gaps in knowledge regarding possible linkages underlying the relationship, and to develop specific research recommendations for the future. The complete proceedings of the workshop and the research recommendations will be published in an upcoming supplement to the Journal of Bone and Mineral Research. While craniofacial bone may provide measurable features indicative of skeletal bone health, studies specifically designed to examine the relationship between craniofacial bone mass and osteoporosis have had mixed results and have been plagued by methodological deficiencies that cloud interpretation and prohibit comparison of results. Thus, many of our concepts are based on anecdotal information, clinical impressions, and studies on small sample sizes. Recognizing these limitations, the literature shows that there is: (1) a positive correlation between tooth loss, edentulism, and osteoporosis; (2) a relationship between skeletal, maxillary, and mandibular bone mass; (3) annual decrease in jaw bone of elderly individuals, the rate of decrease being greater in women than in men; (4) a significant difference between younger and older women in maxillary and mandibular alveolar bone; and (5) a significant difference in osseous fractal dimensions in premenopausal and postmenopausal women. Thus, despite the limited data available, it was the consensus of the workshop that the rate and severity of oral bone loss might be accelerated by the presence of various forms of osteoporosis. These data as well as our knowledge of basic bone biology suggest a strong rationale for a relationship between oral bone loss and osteoporosis. The participants in the workshop on Osteoporosis and Oral Bone Loss described the need for continued integration of insights from collaborative studies carried out by specialists in oral biology and medicine and experts in skeletal osteoporosis. Some recommended research directions include, but are not limited to: o Development of new and improved methods for quantitatively assessing oral bone volume, density, structural and mechanical properties, quality and turnover applicable to both dentate and edentate individuals. These methods should be suitable for large scale population studies. o Development of in vitro and in vivo models for studying oral bone loss and remodelling. Models that investigate the effect of mechanical, biophysical and metabolic influences on oral bone are encouraged. o Identification and development of molecular markers present in the oral cavity that can be used for the diagnosis of oral and non-oral bone loss. o Development of basic knowledge on the similarities and differences between oral and non-oral bone in health and disease and investigate possible relationships between osteoporosis and oral bone loss. o Design of epidemiological and genetic studies to elucidate possible linkages between oral bone loss and osteoporosis. o Development of simple, cost-effective, accurate and safe diagnostic tests to ascertain individuals at risk for oral bone loss. o Conducting studies to clarify the role of fluorides in the possible prevention of osteoporosis and, specifically, oral bone loss. o Identification and characterization of association between osteoporosis and periodontal diseases. These areas of research are neither prioritized nor meant to be restrictive. Investigators are encouraged to submit scientifically meritorious applications in any area of research responsive to the general research objectives of this Program Announcement. Research applications should be of high scientific quality. The project should be founded on a strong hypothesis as evidenced by preliminary data collected by the investigator or others. Prior experience of the investigative team is an important element in proving the likely success of the research proposed. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for clinical research grants and cooperative agreements are required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis should be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale must be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues should be addressed in developing a research design and sample site appropriate for the scientific objectives of the study. This information should be included in form PHS 398 (rev. 9/91) in items 1-4 of the Research Plan and summarized in item 5, Human Subjects. Applicants are urged to carefully assess the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all such projects to include representation of the full array of United States racial, ethnic minority populations (i.e., Native Americans [including American Indians or Alaskan Natives], Asian/Pacific Islanders, Blacks, Hispanics). The rationale for studies on single minority population groups should be provided. For the purpose of this policy, clinical research is defined as human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including but not limited to clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded. However, every effort should be made to include human tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. For foreign awards, the policy on inclusion of women applies fully; since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. If the required information is not contained within the application, the application will be returned. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question(s) addressed or the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and will be reflected in assigning the priority score to the application. All applications for clinical research submitted to the NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. APPLICATION PROCEDURES Applications are to be submitted on grant application form PHS 398 (rev. 9/91), which may be obtained from the Office of Grants Information, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone 301/594-7248 and from the institution's office of sponsored research. To identify the application as a response to this PA, check "yes" on item 2a of face page of the application and enter PA-93-104 "Osteoporosis and Oral Bone Loss". Applications for the R01 and R29 mechanisms will be accepted at the standard applications receipt dates indicated in the application kit. The application receipt date for R03s is April, August, and December 3. The receipt dates for the IRPG mechanism (which was announced in the NIH Guide, Vol. 22, No. 16, April 23, 1993) are February, June, and October 15. Submit a signed, typewritten original of the application, and five signed photocopies, in one package to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** REVIEW CONSIDERATIONS Applications will be assigned on the basis of established Public Health Service referral guidelines. Applications will be reviewed for scientific and technical merit by initial review groups of the Division of Research Grants, NIH or by the review group of the relevant Institute in accordance with the standard NIH peer review procedures. Following scientific-technical review, applications will receive a second level review by the appropriate national advisory council or board. AWARD CRITERIA Applications will compete for available funds with all other approved applications assigned to that ICD. The following will be considered in making funding decisions: o Quality of the proposed project as determined by peer review o Availability of funds o Program balance among research areas of the announcement. INQUIRIES Written and telephone inquiries concerning this PA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Mohandas Bhat, M.D.S., Dr.P.H. Craniofacial Development and Disorders Program National Institute of Dental Research Westwood Building, Room 509 Bethesda, MD 20892 Telephone: (301) 594-7648 Joan A. McGowan, M.N.S., Ph.D. Bone Biology and Bone Diseases Branch National Institute of Arthritis and Musculoskeletal and Skin Diseases Westwood Building, Room 403 Bethesda, MD 20892 Telephone: (301) 594-9957 E-mail: McGowanJ@occshost.NLM.NIH.GOV Direct inquiries regarding fiscal matters to: Ms. Theresa Ringler Grants Management Office National Institute of Dental Research Westwood Building, Room 510 Bethesda, MD 20892 Telephone: (301) 594-7629 Ms. G. Carol Clearfield Grants Management Branch National Institute of Arthritis and Musculoskeletal and Skin Diseases Westwood Building, Room 726B Bethesda, MD 20892 Telephone: (301) 594-9973 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.121. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158,(42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$P3 END ************************************************************ ERRATA $$E1 BEGIN R1 19930730 APPEND RFA AI-93-016 BOTH *********************** AID/NIAID PROGRAM: FUNDAMENTAL MALARIA VACCINE STUDIES RFA: AI-93-016 P.T. 34; K.W. 0740075, 0715151 National Institute of Allergy and Infectious Diseases Letter of Intent Receipt Date: September 1, 1993 Application Receipt Date: November 10, 1993 The following changes are made to Request for Applications AI-93-016, which was printed in the NIH Guide for Grants and Contracts, Vol. 22, No. 27, July 30, 1993. LETTERS OF INTENT The letter is to be sent to Dr. B. Fenton Hall at the address listed under INQUIRIES. APPLICATION PROCEDURES At the time of submission, two additional copies of the grant applications must be sent to Dr. B. Fenton Hall at the address listed under INQUIRIES. Applications must be received by the Division of Research Grants and Dr. Hall by November 10, 1993. REVIEW CONSIDERATIONS A Review Committee will be convened by the Division of Research Grants, NOT by the Division of Extramural Activities, NIAID. INQUIRIES Letters of Intent, Requests for the RFA, and inquiries regarding programmatic issues may be directed to Dr. B. Fenton Hall Inquiries on review procedures may be directed to: Sami Mayyasi, Ph.D. Immunology, Virology and Pathology Review Section Division of Research Grants Westwood Building, Room A-10 Bethesda, MD 20816 $$E1 END ************************************************************ $$E2 BEGIN R2 19930409 APPEND RFA HL-93-014 BOTH *********************** IN UTERO STEM CELL TRANSPLANTATION FOR GENETIC DISEASES NIH GUIDE, Volume 22, Number 30, August 20, 1993 RFA: HL-93-014 P.T. 34; K.W. 0715032, 0745065, 0755020, 1002019, 0715135 National Heart, Lung and Blood Institute National Institute of Diabetes and Digestive and Kidney Diseases Letter of Intent Receipt Date: October 1, 1993 Application Receipt Date: November 17, 1993 The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) will join with the National, Heart, Lung and Blood Institute (NHLBI) to co-sponsor the Request for Applications (RFA) HL-93-014 entitled "In Utero Stem Cell Transplantation for Genetic Disease," published in the NIH Guide for Grants and Contracts, Vol. 22, No. 14, April 9, 1993. The NIDDK has a continuing interest in the support of research on the development of in utero stem cell transplantation for the treatment of genetic metabolic diseases with particular emphasis on lysosomal storage diseases and mucopolysaccharidoses. Since these metabolic diseases have been shown to be ameliorated by postnatal bone marrow transplants, they would make appropriate model systems for the development of in utero stem cell transplantation. Applications received in response to this RFA that propose to treat genetic metabolic diseases will be considered for funding by both the NHLBI and the NIDDK. Interested investigators are encouraged to contact Program Staff to discuss potential applications and to obtain the full text of the amended RFA. Inquiries may be addressed to: Dr. Catherine McKeon Division of Diabetes, Endocrinology and Metabolic Diseases National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 621 Bethesda, MD 20892 Telephone: (301) 594-7582 FAX: (301) 594-9011 $$E2 END ************************************************************ From owner-sci-resources@net.bio.net Fri Aug 20 23:00:00 1993 Path: biosci!NET.BIO.NET!kristoff From: kristoff@NET.BIO.NET (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 22, no. 30, pt. 2, 20 August 1993 Message-ID: Date: 21 Aug 93 14:56:31 GMT Sender: kristoff@net.bio.net Distribution: bionet Lines: 491 Approved: sci-resources-moderator@net.bio.net $$XID RFA HD94007 HD-94-007 P1O1 *************************************** BEHAVIORAL DEVELOPMENT IN MIDDLE CHILDHOOD NIH GUIDE, Volume 22, Number 30, August 20, 1993 RFA: HD-94-007 P.T. 34, AA; K.W. 0404000, 0404004 National Institute of Child Health and Human Development National Institute of Mental Health Application Receipt Date: January 18, 1994 PURPOSE The Human Learning and Behavior Branch (HLB) of the Center for Research for Mothers and Children (CRMC), National Institute of Child Health and Human Development (NICHD) and the Division of Neuroscience and Behavioral Science (DNBS), National Institute of Mental Health (NIMH) invite applications for the support of research on behavioral development during middle childhood. The purpose of this Request for Applications (RFA) is to stimulate the submission of high quality research applications for scientific studies designed to characterize psychological and behavioral aspects of the development of American children during their middle childhood period. More specifically, the investigations should center upon gaining a deep understanding of social, emotional and cognitive processes that develop and help to uniquely define that period in development that is termed middle childhood (the period that includes the age range among children in grades K-6). Research focusing on normative development is particularly encouraged. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority goals. This RFA, Behavioral Development in Middle Childhood, relates to the priority area of psychological, behavioral, familial and cultural factors associated with variations in development of American boys and girls during their middle childhood years. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic for-profit and non-profit organizations, public and private, such as universities, colleges, units of state and local governments, and eligible agencies of the Federal government. Applications from minority individuals and women are encouraged. Foreign institutions are not eligible for the First Independent Research Support and Transition (FIRST) (R29) award. MECHANISMS OF SUPPORT Research support will be provided through the individual research project grant (R01) and FIRST (R29) awards. Policies that the govern grant programs of the Public Health Service will prevail. Responsibility for the planning, direction, and execution of the proposed projects will be solely that of the applicant. The total period of support for any application submitted in response to this RFA may not exceed five years. This RFA is a one-time solicitation. Future unsolicited applications or those submitted as continuations to any funded application in connection with this RFA will be reviewed by Division of Research Grants (DRG) Initial Review Groups (IRGs) according to the customary peer review procedures. FUNDS AVAILABLE The support of grants in connection with this RFA is contingent on the availability of funds for this purpose. The number of grants awarded will be influenced by the total amount of funds available to the NICHD and NIMH, by the overall number of meritorious applications received, and the relevance of the applications to stated program goals. It is anticipated that up to $1 million direct costs ($750,000, NICHD; $250,000, NIMH) will be available to fund six to eight meritorious applications under this RFA (a maximum of four to six, NICHD; two, NIMH). RESEARCH OBJECTIVES Background This RFA was initiated in response to requests made by the Congress of the United States to the NICHD. Report #102-397 (FY 1993) of the U.S. Senate Appropriations Committee (p.114) encourages the NICHD: "...to embark on a long-term planning process to investigate psychological and behavioral processes of the middle childhood years, ages 5-11 years." Similarly, in report #102-708 (FY 1993) by The Committee on Appropriations of the U.S. House of Representatives (p.77) encourages: " the NICHD in collaboration with the NIMH to consider development of a new general behavioral science initiative in the area of middle childhood development." While the scope of child behavior development research spans the years between birth to the beginning of adulthood, scientists working in this domain have by and large focused their research interests on two periods, infancy and adolescence. For example, during the past three decades scientists have made many discoveries about a baby's normative capacities for learning, knowing and remembering, the forming of social and emotional relationships within the family, psychomotor competency, and the acquisition of speech and language. During the past ten years there has also been an upsurge of interest in the study of adolescence. Much of this research on American teenagers has dealt with risk taking behaviors that are deleterious to the health of the individual or present dangers of relevance to the public health. By comparison with the research efforts devoted to infants and adolescents, the scientific investigation and thus our basic understanding of middle childhood has not been as broad or as deep. This knowledge gap on behavioral development in middle childhood was highlighted in a report by the National Academy of Sciences (NAS) (Collins, 1984). While the NAS panel members agreed that many studies on social, emotional, and cognitive processes had been undertaken in middle childhood-aged children, they concluded that much additional basic research was needed to gain a deeper understanding of this important period. This conclusion still remains valid. Although research during the past decade has continued to investigate aspects of social, emotional, cognitive and general psychological functioning in children from the age cohort of interest (Collins and Gunnar, 1990), investigations of middle childhood per se were not the main focus. Rather, researchers have been studying aspects of psychological and behavioral functioning and the children they employed as subjects happened to be in the elementary school age range. This generalization further reinforces the need to address the knowledge gap and explore psychological and behavioral processes uniquely associated with middle childhood. Scientists who have studied middle childhood have gained important general insights about the uniqueness of this period. Students of development recognize that middle childhood is a time of significant change in the lives of children. For example, the expanding capacities for thinking, abstracting, and self-management differentiate K-6th grade children from infants and toddlers. Their ability and skill to interact with others, form friendships, and socialize outside of the family structure are defining features of the middle childhood years. The capacity and motivation for learning and acquiring knowledge, both in formal educational settings and on their own, helps to set children's middle childhood years apart from their earlier developmental periods. Physical development during this period progresses along a trajectory that transforms a child into an adolescent. An important conclusion of the NAS report was that the behavior and performance of children during their middle childhood are much more predictive of adolescent and adult status than is their behavior earlier in life. The panel also asserted that the prediction of later status improves as a child develops during this period of life (Collins, 1984). This latter point is highly relevant for the rationale to issue an RFA. The period of adolescence in America is most often brought to the public consciousness due to the headlines that teenagers as individuals or as a group generate with respect to negative behaviors. Consider, for example, the problems of teenagers associated with peer pressure, unintentional injuries, dropping out of school, teenage pregnancy, depression, suicide and experimentation with and dependence upon licit and illicit substances (e.g., cigarettes, alcohol, marijuana, etc.). One could argue that the concerns raised and the intervention programs under way and/or being considered to deal with these and other problems of adolescents are too late, since the roots of the problems start earlier in development. Are such behavioral problems predictable? Could a better understanding of development during the middle childhood years provide relevant clues about the initiation of healthy behaviors or when behavior is going to go awry? It is the jointly held view of both NICHD and NIMH that a basic research emphasis on behavioral development in middle childhood will provide necessary information for aiding public health officials, community groups, and parents to design meaningful prevention programs that could start at a period in life before problem behaviors emerge. The focus of this RFA is therefore on the development of psychological and behavioral factors that emerge in the context of the various environments in which children live (e.g., family, peer group, school class, etc.) during their middle childhood years. While there are many processes that could be studied in relation to middle childhood, the focus of this RFA is on social, emotional and cognitive development. In the area of social development, for example, an important question relates to the beginnings and intensification of peer relationships. That is, what are the factors, during middle childhood, that shift children's interests such that they begin to affiliate with others, beyond the family, and develop social relationships with acquaintances and friends? How do such peer relationships affect children's behavioral and psychological development? How do experiences and relationships within the family enhance or impede psychological growth and adaptive functioning? In the area of emotion, studies of development of affect during middle childhood are needed. Some relevant questions concerning emotion relate to the ways children develop and express anger and sadness. How do peer, family, and school environmental factors help to shape, modulate, or exacerbate the development and expression of normal emotions? In the area of cognitive development, questions of interest relate to how children expand their capacities to think, plan, reason, and abstract. How do elementary school aged children differ from toddlers on the one hand and adolescents on the other in these key areas of cognitive development? How, too, does the concept of self develop to help children to manage and discipline themselves? (Eccles, J., 1993) These questions are not exhaustive but are meant to be illustrative of ones the answers to which can be useful in gaining a deep understanding of middle childhood developmental mechanisms that could have critical bearings upon adolescent and possibly adult behaviors of public health relevance. Both cross-sectional and prospective longitudinal designs are encouraged. Research designed to gain an understanding of social, emotional, and cognitive developmental transitions from pre-schoolers to elementary school aged children or elementary schoolers to middle school aged children (Gunnar and Collins, 1988) are of great interest in so far as they help to demarcate the psychological and behavioral boundaries of middle childhood. Studies that focus on normative behavioral development in the domains listed are encouraged. The Institutes encourage theoretically-based research and empirical designs in which hypotheses are tested. Investigators are encouraged to highlight the relevance of their proposed research for an understanding and prediction of both healthy development and behavioral development that goes awry (e.g., risk taking, substance abuse, unintentional injury, violence, etc.). Investigators are also encouraged to incorporate setting factor(s) in which development occurs (e.g., the family, peer group, school, etc.) as a major independent variable(s) into their research design. Our expectation is that a strong program of basic research conducted under the auspices of this RFA may provide key information on social, cognitive, and emotional factors that could influence development of appropriate decision making skills. The results from such research may help provide relevant information on how peer pressure emerges and how it can be used to foster health-promoting behaviors or lead to behavioral problems. Similarly, data from proposed investigations of social, emotional, and cognitive development may inform scholars, educators and parents concerning factors that may enhance and maintain motivation related to self-confidence and academic functioning beyond the years of middle childhood. The knowledge gathered from this initiative may also be of critical aid in developing future treatment or prevention programs in the areas of mental and behavioral disorders that have their origins in the childhood years of development. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements will be required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis should be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale should be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues should be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information should be included in the form PHS 398 in Sections 1-4 of the Research Plan AND summarized in Section 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., Native Americans (including American Indians or Alaskan Natives), Asian/Pacific Islanders, Blacks, Hispanics). The rationale for studies on single minority population groups should be provided. For the purpose of this policy, clinical research includes human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including but not limited to clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded. However, every effort should be made to include human tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. For foreign awards, the policy on inclusion of women applies fully; since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. If the required information is not contained within the application, the application will be returned. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and will be reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. SPECIAL REQUIREMENTS In order to maximize the impact of research on this topic the NICHD and NIMH will jointly sponsor yearly meetings at the NIH of the funded Principal Investigators. At these meetings, grantees will have the opportunity to meet each other and their project officers, share methodological information, and provide updates on progress. Applicants should therefore include funds in their proposed budget for a two day visit each year with NIH officials at the two sponsoring Institutes. APPLICATION PROCEDURES Applications are to be submitted on form PHS 398 (rev. 9/91). The application kit may be obtained from the office of sponsored research at your university/research institution and from the Office of Grants Information, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, Md 20892, telephone 301/594-7248. Applications for the FIRST Award (R29) must include at least three sealed letters of reference attached to the face page f the original application. First Award (R29) applications submitted without the required number of reference letters will be considered incomplete and will be returned without review. The RFA label available in the PHS 398 kit must be affixed to the bottom of the face page of the application. Failure to use this label could result in delayed processing and therefore cause the application to not reach the Initial Review Group (IRG) in time for review. In addition, the RFA title and number must be typed on line 2a of the face page and the YES box must be marked with an X. Submit a signed, typewritten original of the application, including the checklist, and three signed, photocopies, in one package to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** At the time of submission, two additional copies of the application must also be sent to: Susan Streufert, Ph.D. Division of Scientific Review National Institute of Child Health and Human Development 6100 Building, Room 5E03F Bethesda, MD 20892 Telephone: (301) 496-1485 Applications must be received by January 18, 1994. Applications received after that date will be returned to the applicant. If the application submitted in response to this RFA is substantially similar to a grant application already submitted to the NIH for review, but has not yet been reviewed, the applicant will be asked to withdraw either the pending application or the new one. Simultaneous submission of identical applications will not be allowed, nor will essentially identical applications be reviewed by different review committees. Therefore, an application cannot be submitted in response to this RFA that is essentially identical to one that has already been reviewed. This does not preclude the submission of substantial revisions of applications already reviewed, but such applications must include an introduction addressing the previous critique. REVIEW CONSIDERATIONS Applications will be reviewed by NIH staff for completeness and responsiveness to the RFA. Incomplete applications will be returned to the applicant without further consideration. If the application is not responsive to the RFA, it will be returned to the applicant. The applicant will then have the option of submitting it to the DRG for review by a standing IRG at the next review cycle. Applications may be triaged by a peer review committee on the basis of relative competitiveness. The NIH will withdraw from further consideration those applications deemed to be non-competitive for award and will notify the Principal Investigator and institutional official of this fact. Those applications judged to be competitive will undergo review for scientific merit by a Special Review Committee (SRC) convened by the NICHD. The second level of review will be conducted by the respective National Advisory Councils of the NICHD and the NIMH. REVIEW CRITERIA The review criteria to be employed are as follows: o scientific significance, technical excellence, and originality of the proposed research. o appropriateness and adequacy of the approach and methodology proposed to carry out the research. o qualifications and research experience of the Principal Investigator, collaborating investigators and staff, in the area of the proposed research. o availability of resources necessary to carry out the research. o appropriateness of the budget and time in relation to the proposed specific aims and scientific goals. The anticipated date of award is July 1, 1994. INQUIRIES Potential applicants are welcome to make inquiries concerning this RFA. Questions related to programmatic issues may be directed to: Norman A. Krasnegor, Ph.D. Center for Research for Mothers and Children National Institute of Child Health and Human Development 6100 Building, Room 4B05 Bethesda, MD 20892 Telephone: (301) 496-6591 Mary Ellen Oliveri, Ph.D. Division of Neuroscience and Behavioral Science National Institute of Mental Health 5600 Fishers Lane, Room 11C-10 Rockville, MD 20857 Telephone: (301) 443-3942 Direct inquiries concerning fiscal matters to: Edgar D. Shawver Office of Grants and Contracts National Institute of Child Health and Human Development 6100 Building, Room 8A17E Bethesda, MD 20892 Telephone: (301) 496-1303 Diana Trunnell Assistant Chief, Grants Management Branch National Institute of Mental Health 5600 Fishers Lane, Room 7C-15 Rockville, MD 20857 Telephone: (301) 443-3065 AUTHORITY AND REGULATIONS This program is described in the Catalogue of Federal Domestic Assistance No. 93.865, Research for Mothers and Children and 93.242 Mental Health Research projects. Awards are made under the authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR part 74. Awards are also made under authorization of PHS Act Title V, Part B. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. References Collins, W.A. (Ed.) (1984), Development during middle childhood, the years from 6-12. Washington, D.C.: National Academy Press. Collins, W.A. and Gunnar, M.R. (1990), Social and personality development. Annual Review of Psychology, 41, 387-416. Eccles, J.S. (1993), Age and gender differences in children's self-and task-perceptions during elementary school. Child Development, 64, 830. Gunnar, M.R. and Collins, W.A. (Eds.) (1988), Development during the transition to adolescence. Minnesota Symposium on Child Psychology, 21, Hillsdale, N.J.: Lawrence Erlbaum Associates. From owner-sci-resources@net.bio.net Sun Aug 22 23:00:00 1993 Path: biosci!NET.BIO.NET!kristoff From: kristoff@NET.BIO.NET (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NSF - Summary of new documents on STIS - 22 August 1993 Message-ID: Date: 23 Aug 93 22:22:37 GMT Sender: kristoff@net.bio.net Distribution: bionet Lines: 105 Approved: sci-resources-moderator@net.bio.net ** NEW DOCUMENTS ON STIS ** Document Type: Press Release Title: NSF 93-58 NSF FACILITY USING FOSSIL MOLLUSCS TO DATE "CLIMATIC OPTIMUM" File size (bytes): 5487 STIS Filename: pr9358 Title: NSF 93-59 NSF-FUNDED RESEARCHERS FIND RODENT "POPULATIONEXPLOSION" MAY BE BEHIND HANTAVIRUS EPIDEMIC IN SOUTHWEST File size (bytes): 5254 STIS Filename: pr9359 Title: NSF 93-60 NEW REPORT OFFERS 20-YEAR LOOK AT MATH AND SCIENCE EDUCATION IN U.S. File size (bytes): 6022 STIS Filename: pr9360 Title: NSF 93-61 NSF AWARDS MATHEMATICAL SCIENCES POSTDOCTORAL RESEARCH FELLOWSHIPS File size (bytes): 2923 STIS Filename: pr9361 Title: NSF 93-62 NSFNET TO BOOST NETWORK ACCESS AS IT ENTERS NEW REALM File size (bytes): 8504 STIS Filename: pr9362 Title: NSF 93-63 SBIR-FUNDED ALTERNATIVE KEYBOARD EASES COMPUTER USAGE FOR DISABLED, CHILDREN File size (bytes): 7227 STIS Filename: pr9363 Title: NSF 93-64 NSF ASSISTANT DIRECTOR, LEADING COMPUTER SCIENTIST, DEAD OF APPARENT HEART ATTACK File size (bytes): 3283 STIS Filename: pr9364 Title: NSF 93-65 SCIENTISTS TO PRESENT RESULTS OF LONG-TERM ECOLOGICAL RESEARCH AT TRIENNIAL MEETING File size (bytes): 8404 STIS Filename: pr9365 Document Type: Recruit Title: Oceanographer (Associate Program Director) File size (bytes): 3543 STIS Filename: vex9327 ------------------------------------------------------------------------ ** UPDATES TO EXISTING STIS DOCUMENTS ** Document Type: Phone Book Title: NSF Alphabetical Listing File size (bytes): 91304 STIS Filename: phnalpha Title: NSF Organizational Directory File size (bytes): 98952 STIS Filename: phnorg ------------------------------------------------------------------------ ** FOR YOUR REFERENCE ** ------------------------------------------------------------------------ HOW TO OBTAIN DOCUMENTS The above files can be retrieved in electronic form using the STIS system. If you don't know how to use STIS, send an E-mail message to stisinfo@nsf.gov (Internet) or stisinfo@NSF (BITNET). You will receive a copy of the STIS flyer via E-mail. If you are already using STIS, you can use the information above to retrieve these files: Documents via E-mail: Send a message to stisserv@nsf.gov (Internet) or stisserv@NSF (BITNET). Use the "STIS Filename" shown above in the "get" command. For example, to retrieve phnorg, the text of your message should be as follows: get phnorg Anonymous FTP: FTP to stis.nsf.gov. Use the "STIS Filename" shown above to retrieve a file. For example, to retrieve phnorg, you would enter: ftp> get phnorg WAIS or Gopher: Do a word search on the filename as shown in the summary. If you want a *printed* copy of a document: Send your name and postal mailing address, and the document title and number to "firstop@nsf.gov" (Internet) or "firstop@nsf" (BITNET). If you have problems with the above procedures: Send a message to "stis@nsf.gov" (Internet) or "stis@NSF" (BITNET). From owner-sci-resources@net.bio.net Thu Aug 26 23:00:00 1993 Path: biosci!net.bio.net From: kristoff@net.bio.net (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 22, no. 31, pt. 2, 27 August 1993 Message-ID: Date: 27 Aug 93 03:25:47 GMT Sender: kristoff@net.bio.net Lines: 1472 Approved: biosci-moderator@net.bio.net $$XID NIHGUIDE 19930827 V22N31 P2O2 ************************************ during the grant period must inform AHCPR immediately in writing. The AHCPR may suspend or terminate the grant as requested by the Principal Investigator or on its own initiative. o The dissertation constitutes the final report of the grant. The dissertation must be officially accepted by the faculty committee or university official responsible for the candidate's dissertation and must be signed by the responsible officials. Three copies of the dissertation must be submitted to AHCPR. o The dissertation and all financial status reports must be submitted in English. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS CONCERNING INCLUSION OF WOMEN AND MINORITIES IN RESEARCH STUDY POPULATIONS The AHCPR requires applicants to include minorities and women in study populations so that research findings can be of benefit to all persons. If women or minorities are excluded or inadequately represented in research, a clear and compelling rationale must be provided. Applications without such documentation will not be accepted for review. APPLICATION PROCEDURES The RFA contains important information on application procedures, including special instructions for health services dissertation research applications, and may be obtained from the AHCPR staff listed under INQUIRIES. The application receipt date is January 24, 1994. The research grant application form PHS 398 (rev. 9/91) is to be used in applying for these grants, in accordance with the instructions described in the RFA and the instructions in the application. The application form PHS 398 is available at most institutional offices of sponsored research and the Office of Grants Information, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone 301-594-7248. In addition, a packet containing both a Grant Announcement based upon the RFA and the research grant application form PHS 398 will be available after September 15 from the AHCPR Publications Clearinghouse/DISS, P.O. Box 8547, Silver Spring, MD 20907, telephone: 1-800-358-9295. Also, a letter from the faculty committee or university official directly responsible for supervising the development and progress of the dissertation research must be submitted with the application. Details of the requirements for the letter are given in the RFA. REVIEW CONSIDERATIONS Applications will be reviewed initially by the Referral Office at Division of Research Grants, NIH, for completeness and by the AHCPR for responsiveness to the RFA. Incomplete and nonresponsive applications will be returned to applicants without further consideration. Applications will be evaluated in accordance with the criteria stated in the RFA for scientific/technical merit by an appropriate peer review group. Review considerations and special review criteria are listed in the RFA. INQUIRIES Applicants may discuss programmatic issues with and request the RFA by letter or phone from: Julius Pellegrino, M.B.A., M.P.H. Center for General Health Services Extramural Research Agency for Health Care Policy and Research 2101 E. Jefferson Street, Suite 502 Rockville, MD 20852 Telephone: (301) 594-1357 ext.138 Direct inquiries regarding fiscal matters to: Ralph L. Sloat, Grants Management Officer Agency for Health Care Policy and Research 2101 East Jefferson Street Rockville, MD 20852 Telephone: (301) 594-1447 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance, No. 93.180. Awards are made under authorization of the Public Health Service Act, Title IX, as amended by Public Laws 101-239 and 102-410, (42 U.S.C. 299-299c-6) and Section 1142 of the Social Security Act (42 U.S.C. 1320b-12). Awards are administered under the PHS Grants Policy Statement; and Federal Regulations 42 CFR Part 67, Subpart A, and 45 CFR Part 74 (45 CFR Part 93 for State and local governments). This program is not subject to the intergovernmental review requirements of Executive Order 12372. $$R5 END ************************************************************ $$R6 BEGIN HS-94-003 FULL-TEXT ************************************** HIV COST AND SERVICES UTILIZATION STUDY NIH GUIDE, Volume 22, Number 31, August 27, 1993 RFA AVAILABLE: HS-94-003 P.T. 34; K.W. 0730050, 0408006, 0715008 Agency for Health Care Policy and Research Letter of Intent Receipt Date: December 22, 1993 Application Receipt Date: February 22, 1994 THIS IS A NOTICE OF AVAILABILITY OF A REQUEST FOR APPLICATIONS (RFA); IT IS ONLY AN ABSTRACT OF THE RFA. POTENTIAL APPLICANTS MUST REQUEST THE COMPLETE RFA, WHICH CONTAINS ESSENTIAL INFORMATION FOR THE PREPARATION OF AN APPLICATION, FROM THE CONTACT LISTED IN "INQUIRIES," BELOW. FAILURE TO FOLLOW THE INSTRUCTIONS IN THE COMPLETE RFA MAY RESULT IN AN INCOMPLETE APPLICATION, WHICH WILL BE RETURNED TO THE APPLICANT WITHOUT REVIEW. PURPOSE The Agency for Health Care Policy and Research (AHCPR) supports and conducts health services research, including evaluations of health care systems. The purpose of this RFA is to invite applications for cooperative agreements with the AHCPR to conduct a study of utilization, cost, financing, access to, and quality of health care services for persons infected with the Human Immunodeficiency Virus (HIV). This HIV Cost and Services Utilization Study (HCSUS) is to provide policy-relevant information on the delivery of health care and associated social services to people with HIV infection in a variety of health care settings and geographic areas. HEALTHY PEOPLE 2000 The Public Health Services (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This RFA, HIV Cost and Services Utilization Study, is related to the priority areas of HIV infection, sexually transmitted diseases, immunization and infectious diseases, and clinical preventive services. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0 or Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic, non-profit organizations, public or private, including universities, clinics, State and local governments, and non-profit foundations; or consortia of organizations, if the application is submitted by a domestic, non-profit, public or private organization. A consortium may include other types of organizations such as for-profit. Applications from minority and women investigators are encouraged. MECHANISM OF SUPPORT The administrative and funding instrument to be used for this program will be the cooperative agreement (U01), an assistance mechanism in which substantial AHCPR scientific and programmatic involvement with the awardee is anticipated during the performance of the activity. The total project period for applications submitted in response to this RFA may not exceed four years. The anticipated award date is July 1, 1994. Award of funding beyond the initial budget period will depend upon annual progress reviews by AHCPR. FUNDS AVAILABLE The AHCPR expects to award a total of $15 million over four years to one or more applicants under this RFA during Fiscal Years (FYs) 1994-1997. Up to $3 million will be available in FY 1994. RESEARCH OBJECTIVES Background. Rapid changes have occurred in the treatment of persons with HIV infection and in the population of persons newly infected with HIV. There is a need for current information about patterns of service delivery across regions of the country, socioeconomic groups, and systems of health care. The HCSUS will extend and refine the base of knowledge developed by prior studies of health care delivery to people with HIV infection. The HCSUS will build upon the AHCPR-supported "AIDS Costs and Services Utilization Survey (ACSUS)." While the principal audience for the HCSUS findings will be policy-makers at the Federal, State and local levels, the HCSUS also should furnish information of interest to health care providers, researchers, and consumers of HIV-related services. Because the HCSUS will provide information relevant to the formulation of public policy, mechanisms to assure timely analyses of relevant policy issues will be essential. Objectives and Scope. The first goal of the HCSUS is to compare the experiences of people receiving health care from different health care delivery settings. The HCSUS will study how delivery settings vary in patterns of utilization, costs of care, quality of care, access to care, meeting service needs, quality of life, and patient satisfaction. Because one person's usual source of care may change over time, a second goal of the HCSUS is to examine factors related to transitions between provider types and to changes in utilization over time at the level of the individual. People with HIV infection may use multiple providers of different types of service concurrently. The third goal of the HCSUS is to provide information on factors that affect utilization and costs of the full range of HIV-related services and to assess how use of one service type affects use of other types. Study Design: Core Study. The HCSUS will provide information about the delivery of services to persons with HIV infection as a function of: provider setting (encompassing the major types of providers of HIV-related health care); sociodemographic characteristics, including a sample that is diverse in terms of gender, race/ethnicity, and exposure group; geographic region of the U.S.; and stage of HIV infection, such as asymptomatic, symptomatic non-AIDS, and AIDS). The HCSUS also will obtain information about the characteristics of the care setting, in order to describe different provider types and to address questions about the organizational context of service delivery. Study Design: Special Studies. In addition to the project core, applications may include one or more special, focused studies that examine key research questions in greater depth than in the project core. The design and methodology of the special studies may differ from the project core and from each other, but should be coordinated with the core study. Research issues that may be more appropriately considered within the context of a special study include: care of HIV-infected patients in rural areas; early intervention and linkage; and alternative sample for bias assessment. A report of a public meeting, "HIV Cost and Services Utilization Study: Technical Issues," provides additional examples of research issues that may be appropriate for inclusion as special studies, discusses research questions that may be considered for inclusion in the core study, and notes technical issues for the project's research design. To obtain this report, see INQUIRIES below. Timetable. Allowing for start-up and close-out, the HCSUS should, at a minimum, describe health care utilization experiences during 1995 and 1996. SPECIAL REQUIREMENTS To promote the development of this multi-site collaborative project, a number of additional issues should be addressed in applications responding to the RFA, including Site Selection and Project Organization; Confidentiality of Data; Community Involvement; and Rapid Response Capability. Terms and Conditions of Award This cooperative agreement anticipates substantial AHCPR scientific and programmatic involvement with the awardee(s) throughout the implementation of the HCSUS. The awardee(s) will have primary responsibility for all tasks and activities, including sampling, protocol development, data collection, data analysis, preparation of publications, community involvement, and liaison with users of findings. The AHCPR role in the cooperative agreement will include providing advice in study development; priority setting; gaining access to related data bases; establishing collaboration with other Federal programs; and disseminating research findings. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS CONCERNING INCLUSION OF WOMEN AND MINORITIES IN RESEARCH STUDY POPULATIONS The AHCPR requires applicants to include minorities and women in study populations. If women or minorities are excluded or inadequately represented in research, a clear and compelling rationale must be provided. Applications without such documentation will not be accepted for review. LETTER OF INTENT Prospective applicants are asked to submit, by December 22, 1993, a letter of intent that includes the name, address, and telephone number of the Principal Investigator, co-investigators and other key personnel; member institutions, including any other participating organizations or institutions; and the number and title of the RFA. Although a letter of intent is not required, is not binding, and does not enter into the consideration of any subsequent applications, the information allows AHCPR staff to estimate the potential review workload and avoid conflict of interest in the review. The letter of intent is to be sent to the HCSUS Project Officer at the address listed under INQUIRIES. APPLICATION PROCEDURES The RFA contains important information for applicants and may be obtained from the Project Officer or the AHCPR Clearinghouse, see INQUIRIES. The application receipt date is February 22, 1994. The research grant application form PHS 398 (rev. 9/91) is to be used. These forms are available at most institutional offices of sponsored research and the Office of Grants Information, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone 301/594-7248. Conference for Prospective Applicants The AHCPR plans to convene a conference for prospective applicants in Rockville, Maryland on October 1, 1993. Attendance is not a prerequisite to applying. Attendees must pay for their own travel costs. For information, contact Ms. Ruth Ann Celtnieks, telephone (301) 594-1354, ext. 118, FAX (301) 594-2155. REVIEW CONSIDERATIONS Applications will be reviewed initially by the Division of Research Grants, NIH, for completeness and by AHCPR staff for responsiveness to the RFA. Incomplete and nonresponsive applications will be returned to applicants without further consideration. Applications will be evaluated in accordance with the criteria stated in the RFA for scientific/technical merit by an appropriate AHCPR peer review group. Review considerations and special review criteria are listed in the RFA. INQUIRIES Copies of the RFA and background documents will be available from the AHCPR Publications Clearinghouse, P.O. Box 8547, Silver Spring, MD 20907, (800-358-9295). Direct inquiries regarding programmatic issues and requests for the RFA to: HCSUS Project Officer Center for General Health Services Extramural Research Agency for Health Care Policy and Research 2101 East Jefferson Street, Suite 502 Rockville, MD 20852-4908 Telephone: (301) 594-1354, ext. 131 or 118 Direct inquiries regarding fiscal matters to: Ralph Sloat, Grants Management Officer Agency for Health Care Policy and Research 2101 East Jefferson Street, Suite 601 Rockville, MD 20852-4908 Telephone: (301) 594-1447 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.226. Awards are made under authorization of the Public Health Service Act, Title IX, as amended by Public Laws 101-239 and 102-410, (42 U.S.C. 299-299C-6). Awards are administered under the PHS Grants Policy Statement; and Federal Regulations 42 CFR 67, Subpart A, and 45 CFR Part 74 (45 CFR Part 92 for State and local governments). This program is not subject to the intergovernmental review requirements of Executive Order 12372. $$R6 END ************************************************************ ONGOING PROGRAM ANNOUNCEMENTS $$P1 BEGIN PA-93-105 ************************************************ HELICOBACTER PYLORI PATHOGENESIS NIH GUIDE, Volume 22, Number 31, August 27, 1993 PA NUMBER: PA-93-105 P.T. 34; K.W. 0715125, 0765033 National Institute of Allergy and Infectious Diseases National Institute of Diabetes and Digestive and Kidney Diseases PURPOSE The National Institute of Allergy and Infectious Diseases (NIAID) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) invite submission of investigator-initiated research applications for support of basic and clinical studies needed to establish the role of bacterial and host factors in the pathogenesis of the various forms of Helicobacter pylori disease, including infection, gastritis, and duodenal ulceration. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This program announcement, Helicobacter Pylori Pathogenesis, is related to the priority areas of immunization and infectious diseases and diabetes and chronic disabling conditions. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-0325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign, for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State or local governments, and eligible agencies of the Federal government. Applications from minority individuals and women are encouraged. Foreign institutions are not eligible for the First Independent Research Support and Transition (FIRST) award (R29). MECHANISMS OF SUPPORT Traditional research project grant (R01) and the FIRST award (R29) applications may be submitted in response to this announcement. RESEARCH OBJECTIVES AND SCOPE Background Although it was only discovered in 1982, H. pylori has already been shown to be associated with several gastroduodenal diseases, including active and chronic gastritis and duodenal ulcers. Epidemiologic studies have shown that H. pylori colonizes the gastric mucosa in more that 50 percent of persons and is associated with disease of the upper gastrointestinal tract in one out of every two people in the world. Indeed, these conditions, including gastric and duodenal ulcer disease, are among the most common human ailments requiring medical attention. An estimated 10 percent of people in the United States will develop peptic ulcer disease, and it is estimated that there will be 300,000 new cases, 3.2 million recurrences, and 3,000 deaths due to duodenal ulcer disease each year. Most research in this area has focused on seroepidemiological studies and clinical studies to define the role of H. pylori in various syndromes and the effect of antibiotic treatment on resolution of disease. While these studies have been important in defining the importance of H. pylori in causing a wide variety of diseases, there has not been a concomitant emphasis on understanding the pathogenesis and natural history of these infections. Research Objectives and Experimental Approaches The overall goal of this program announcement is to stimulate innovative research to define the host and bacterial factors involved in the various phases of H. pylori infection excluding gastric carcinoma and lymphoma. These studies may include animal model studies as well as carefully controlled clinical and epidemiological studies that could lead to intervention strategies to control and prevent these infections. Applicants are encouraged to address the areas mentioned below. The list is not all inclusive and applicants may wish to pursue other areas. Examples include, but are not limited to, the following: o Definition of the virulence determinants of H. pylori. These studies may require development of genetic systems to identify the role of specific bacterial genes such as adhesins, enzymes, cytotoxins, and other bacterial components in pathogenesis and virulence. Use of relevant animal models is especially encouraged. o Description of the pathophysiology of H. pylori infection. Efforts to determine the role of hormones and cytokines in the aberrations seen in gastric physiology throughout the spectrum of disease are strongly encouraged. o Description of the immunopathology of H. pylori infection. Efforts to determine the nature of inflammatory and other immune responses, including the role of specific lymphocyte classes in the regulation of the host response to infection are strongly encouraged. o Definition of the epidemiology of disease in various settings. These efforts may include population-based studies as well as detailed clinical studies of the natural history of infection and disease progression. Multidisciplinary studies having collaboration among investigators with expertise in appropriate disciplines is encouraged. When individuals are at different institutions, individual R01 applications may include consortium arrangements or utilize the Interactive Research Project Grant (IRPG) mechanism (NIH Guide, Vol. 22, No. 16, April 23, 1993). Collaborative arrangements with on-going clinical studies or trials that provide patient material and data are encouraged. Such arrangements should be clearly delineated in the application. Where statistical analysis is anticipated, the methodologies and personnel involved should be described in the application and evident in the study design. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements are required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis must be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions that disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale must be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues should be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information must be included in the form PHS 398 (rev. 9/91) in Sections 1-4 of the Research Plan AND summarized in Section 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., Native Americans (including American Indians or Alaskan Natives), Asian/Pacific Islanders, Blacks, Hispanics). The rationale for studies on single minority population groups must be provided. For the purpose of this policy, clinical research is defined as human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including but not limited to clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded. However, every effort should be made to include human tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. For foreign awards, the policy on inclusion of women applies fully; since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. If the required information is not contained within the application, the review will be deferred until the information is provided. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and will be reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. APPLICATION PROCEDURES Applications are to be submitted on the grant application form PHS 398 (rev. 9/91) and will be accepted on the standard application deadlines as indicated in the application kit. Application kits are available at most institutional offices of sponsored research and may be obtained from the Office of Grants Information, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone (301) 594-7248. The title and number of the announcement must be typed in Section 2a on the face page of the application. The completed original and five legible, single-sided copies of the application must be sent or delivered to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** FIRST (R29) applications must include at least three sealed letters of reference attached to the face page of the original application. FIRST applications submitted without the required number of reference letters will be considered incomplete and will be returned without review. Applicants from institutions that have a General Clinical Research Center (GCRC) funded by the NIH National Center for Research Resources may wish to identify the Center as a resource for conducting the proposed research. If so, a letter of agreement from the GCRC Program Director must be included in the application material. REVIEW CONSIDERATIONS Applications will be assigned to appropriate Institutes, Centers, or Divisions (ICDs) within NIH on the basis of established PHS referral guidelines. Applications will be reviewed for scientific and technical merit by study sections of the Division of Research Grants, NIH, in accordance with the standard NIH peer review procedures. Following scientific/technical review, the applications will receive secondary review by the appropriate national advisory council. AWARD CRITERIA Applications will compete for available funds with all other favorably recommended applications assigned to that ICD. The following will be considered when making funding decisions: quality of the proposed project as determined by peer review, program balance among research areas of the announcement, availability of funds. INQUIRIES Written and telephone inquiries are encouraged. The opportunity to clarify any issues from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Leslye D. Johnson, Ph.D. Division of Microbiology and Infectious Diseases National Institute of Allergy and Infectious Diseases Solar Building, Room 3A-06 6006 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-7051 FAX: (301) 402-2508 Frank Hamilton, M.D., M.P.H. Division of Digestive Diseases National Institute of Digestive Diseases and Kidney Westwood Building, Room 3A-16 Bethesda, MD 20892 Telephone: (301) 594-7571 Direct inquiries regarding fiscal matters to: Mr. Todd Ball Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4B35 6003 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-7075 Ms. Thelma Jones Grants Management Branch National Institute of Digestive Diseases and Kidney Westwood Building, Room 649C Bethesda, MD 20892 Telephone: (301) 594-7543 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.856, Microbiology and Infectious Disease Research; Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grant policies and Federal Regulations at 42 CFR Part 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$P1 END ************************************************************ $$XID RFA HD94009 HD-94-009 P1O1 *************************************** DEVELOPMENT OF BIOCHEMICAL AND GENETIC MARKERS FOR PREMATURE ATHEROGENESIS NIH GUIDE, Volume 22, Number 31, August 27, 1993 RFA: HD-94-009 P.T. 34; K.W. 0715040, 0760002, 1002019 National Institute of Child Health and Human Development National Heart, Lung, and Blood Institute Application Receipt Date: December 9, 1993 PURPOSE The Endocrinology, Nutrition and Growth (ENG) Branch of the Center for Research for Mothers and Children, National Institute of Child Health and Human Development (NICHD) and the Lipid Metabolism-Atherogenesis (LA) Branch, National Heart, Lung, and Blood Institute (NHLBI) issue a Request for Applications (RFA) on Development of Biochemical and Genetic Markers for Premature Atherogenesis. Coronary atherosclerosis remains a major killer disease, often causing deaths during prime productive years. It has been shown that the pathological process of coronary atherosclerosis often begins in adolescence, and it is known that profound changes occur in the lipoprotein system during infancy and adolescence that may predispose to atherogenesis. Preventive measures could be effective in mitigating the ravages of coronary atherosclerosis if markers of the atherogenic process were available in susceptible children and adolescents. The purpose of this RFA is to ascertain biochemical and genetic markers of the atherosclerotic process in order to identify those children at high risk. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This RFA, Development of Biochemical and Genetic Markers for Premature Atherogenesis, is related to the priority area of childhood nutrition. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT Applications in response to this RFA will be funded through the research project grant (R01) program of the NIH. This announcement is for a single competition with the application receipt deadline of December 9, 1993. Future unsolicited competing continuation applications will compete with all investigator-initiated applications and be reviewed by a Division of Research Grants (DRG) study section. However, if the NICHD and the NHLBI determine that there is a sufficient continuing program need, these Institutes may announce a request for competitive continuation applications. The total project period for applications submitted in response to the present RFA should not exceed five years. The earliest anticipated award date is September 1, 1994. FUNDS AVAILABLE It is anticipated that six grants will be awarded under this program, contingent upon receipt of a sufficient number of meritorious applications and the availability of funds. To fund these awards the NICHD has set aside $750,000 and the NHLBI has set aside $250,000 for direct costs in the first year. RESEARCH OBJECTIVES Background The major emphasis of preventive research in this area is currently placed on control of hypercholesterolemia. However, lipoproteins other than LDL-cholesterol may be important in atherogenesis and might serve as robust predictors once they are identified. The purpose of this RFA is to stimulate investigators to move beyond cholesterol in exploring biochemical and genetic predictors of atherogenesis and to encourage investigators to ascertain differences in lipoprotein profiles and other metabolic, hormonal, or genetic factors between offspring of families prone to premature coronary atherosclerosis and offspring of families not so afflicted. Such differences may be useful as markers to identify those children at high risk of developing atherosclerosis later in life. Objectives and Scope The NICHD and the NHLBI are devoted to uncovering predictors of chronic disease during childhood. This RFA is aimed at identifying genetic and biochemical precursors in childhood and adolescence of atherosclerosis later in life. The prevention of chronic disease in adulthood is best achieved by attacking these problems in children. To maximize the probability of success in developing childhood markers for atherogenesis, studies should focus on changes in lipoprotein profiles during childhood and adolescence in offspring of coronary-prone parents, especially mothers, in comparison to a matched group of offspring of parents unaffected by coronary atherosclerosis. Studies of several generations and studies of affected twins should also be informative. Investigators are also encouraged to develop epidemiologic techniques to permit the correlation of genetic or metabolic markers measurable in childhood with a familial tendency to premature atherosclerosis. It is known that high serum levels of LDL-cholesterol predispose to coronary atherosclerosis. Children who are homozygous for familial hypercholesterolemia have very high levels of this serum lipid fraction and are at risk of clinically significant coronary pathology in their second and third decades. The molecular basis for this hereditary condition is known to be absent or dysfunctional cellular LDL receptors. However, the majority of coronary artery occlusions occur in individuals who have only mild-to-moderate elevations of LDL-cholesterol. Therefore, changes in other lipoprotein fractions need to be explored as possible harbingers of atherosclerosis in addition to elevations of LDL-cholesterol. Examples of putative lipoprotein markers include elevated levels of LDL- apolipoprotein B; low levels of HDL cholesterol (hypo HDL) and low levels of apolipoprotein AI; isoforms of apolipoprotein E; elevated levels of Lp(a) lipoproteins; elevated serum triglycerides; and high levels of oxidized LDL. Ratios and functional measures, such as delayed clearing of dietary fat or these or other lipids and lipoproteins might also serve as markers in childhood for atherosclerosis later in life. Factors other than lipoproteins and their receptors that may also contribute to the process of coronary atherosclerosis in an ancillary manner include homocysteine, peptide hormones, sex steroids, growth factors, endothelin-1, thromboxane, fibrinogen, fibrin, fibrin split products, tissue plasminogen activator, and other components of the coagulation cascade. In addition to uncovering markers of atherosclerosis in offspring of affected parents, evaluating the segregation of such markers in several generations of coronary-prone families is also encouraged to ascertain the heritability and penetrance of possible metabolic and genetic markers. Studies designed to ascertain how putative markers track prospectively are also needed. Genetic studies of individuals who are heterozygotes or compound heterozygotes for genes that control the metabolism and transport of lipoproteins are encouraged as well. This RFA is designed to study lipoproteins and other putative biochemical and genetic markers of premature atherosclerosis. The scope of the RFA includes infants, children, and adolescents as well as animal models if they can be shown to be relevant. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements will be required to include minorities in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis should be placed on the need for inclusion of minorities in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear and compelling rationale should be provided. The racial/ethnic composition of the proposed study population must be described. In addition, racial/ethnic issues should be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information should be included in the form PHS 398 (rev. 9/91) in Sections 1-4 of the Research Plan and summarized in Section 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., Native Americans (including American Indians or Alaskan Natives), Asian/Pacific Islanders, Blacks, Hispanics). The rationale for studies on single minority population groups should be provided. For the purpose of this policy, clinical research includes human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including but not limited to clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded. However, every effort should be made to include human tissues from racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. For foreign awards, since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. If the required information is not contained within the application, the application will be returned. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of minorities in a study design is inadequate to answer the scientific question(s) addressed and the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and will be reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 9/91) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research and from the Office of Grants Information, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone 301-594-7248. The RFA label available in the PHS 398 application form must be affixed to the bottom of the face page. Failure to use this label could result in delayed processing of an application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2a of the face page of the application form and the YES box checked. Submit a signed, typewritten original of the application, including the Checklist, and three signed, exact photocopies, in one package to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** At the time of submission, two additional copies of the application must also be sent to: Susan Streufert, Ph.D. Division of Scientific Review National Institute of Child Health and Human Development 6100 Building, Room 5E01 Bethesda, MD 20892 Applications must be received by December 9, 1993. If an application is received after that date, it will be returned to the applicant. The Division of Research Grants (DRG) will not accept any application in response to this announcement that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. If the application submitted in response to this RFA is substantially similar to a research grant application already submitted to the NIH for review, that has not yet been reviewed, the applicant will be asked to withdraw either the pending application or the new one. Simultaneous submission of identical applications will not be allowed, nor will essentially identical applications be reviewed by different review committees. Therefore, an application cannot be submitted in response to this RFA that is essentially identical to one that has already been reviewed. This does not preclude the submission of substantial revisions of applications already reviewed, but such applications must include an introduction addressing the previous critique. REVIEW CONSIDERATIONS Applications will be reviewed by NICHD and NHLBI staff for responsiveness to the RFA. Applications judged to be nonresponsive will be returned. The applicant may resubmit the application and have it assigned for review in the same manner as unsolicited grant applications. Responsive applications may be subjected to a triage by a peer-review group to determine their scientific merit relative to the other applications received in response to this RFA. NIH will withdraw from competition those applications judged to be noncompetitive and notify the applicant and institutional business official. Those applications judged to be competitive will be further evaluated for scientific/technical merit by a review group convened solely for this purpose by the Division of Scientific Review, NICHD. Criteria for the initial review will include the significance and originality of research goals and approaches; the feasibility of research and adequacy of the experimental design; the research experience and competence of the investigator(s) to conduct the proposed work; the adequacy of investigator effort devoted to the project; and the appropriateness of the project duration and cost relative to the work proposed. Following review by the Initial Review Group, applications will be evaluated by the National Advisory Child Health and Human Development Council and by the National Heart, Lung, and Blood Advisory Council for program relevance and policy issues before awards for meritorious proposals are made. AWARD CRITERIA The anticipated award date is September 1, 1994. Scientific merit and technical proficiency, based on the demonstrated and projected capabilities described in the application in response to the RFA, will be the predominant criteria for determining funding priorities. INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Gilman D. Grave, M.D. Center for Research for Mothers and Children National Institute of Child Health and Human Development 6100 Building, Room 4B11 Bethesda, MD 20892 Telephone: (301) 496-5593 Direct inquiries regarding fiscal matters to: Mr. E. Douglas Shawver Office of Grants and Contracts National Institute of Child Health and Human Development 6100 Building, Room 8A17 Bethesda, MD 20892 Telephone: (301) 496-1303 AUTHORITY AND REGULATIONS This program is described in the catalog of Federal Domestic Assistance No. 93.865, Research for Mothers and Children. Awards will be made under the authority of the Public Health Service Act, Section 301 (42 USC 241), and administered under PHS grants policies and Federal Regulations 42 CFR Part 52 and 45 CFR Part 74. This program is not subject to review by a Health Systems Agency. $$XID RFA HS94001 HS-94-001 P1O1 *************************************** GRANTS FOR HEALTH SERVICES DISSERTATION RESEARCH NIH GUIDE, Volume 22, Number 31, August 27, 1993 RFA: HS-94-001 P.T. 34; K.W. 0730050 Agency for Health Care Policy and Research Application Receipt Date: January 24, 1994 PURPOSE The Agency for Health Care Policy and Research (AHCPR) announces the availability of a Request for Applications (RFA) for grants for health services dissertation research. The AHCPR conducts and supports research that will enhance the quality, appropriateness, and effectiveness of health care services, and access to such services. The provision of dissertation grant support is part of AHCPR's effort to stimulate the development of innovative and timely research on issues related to the delivery of health care services. Grant support is designed to aid the career development of new health services researchers and to encourage individuals from a variety of academic disciplines and programs to study complex issues with respect to health care services. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. The AHCPR urges applicants to submit grant applications with relevance to the specific health services research objectives of this initiative. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0 or Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS A student applying for a dissertation research grant (the Principal Investigator) must be enrolled in an accredited doctoral degree program in the social, management, medical, or health sciences. The student also must be conducting or intending to conduct dissertation research on issues related to the delivery of health care services as described below. The proposed principal investigator must be a registered doctoral candidate in resident or nonresident status. All requirements for the doctoral degree other than the dissertation must be completed by the time of the award. Prior to submission of the application, the dissertation proposal must be approved by the dissertation faculty committee and certified by the faculty advisor. This information must be verified in a letter of certification from the thesis chairperson and submitted with the grant application (see APPLICATION PROCEDURES). The applicant may be either the institution that will administer the grant on behalf of the proposed Principal Investigator or the proposed Principal Investigator applying as an individual. Applications from minority and women investigators are encouraged. A proposed Principal Investigator for dissertation research grant support need not be a citizen of the United States. However, an investigator who is not a U.S. citizen and does not have a permanent resident visa must apply through an institution. Also, an application from a student enrolled in a foreign institution will be accepted if the application is in English and the investigator applies through an institution. The proposed investigator who receives support for dissertation research under a grant from the AHCPR may not at the same time receive support under a predoctoral training grant or fellowship grant awarded by any other agency of the U.S. Department of Health and Human Services. MECHANISM OF SUPPORT This RFA will use the small grant (R03) mechanism. Responsibility for the planning, direction, and execution of the proposed project will be solely that of the proposed principal investigator. The total direct costs must not exceed $20,000 for the entire project period. An application that exceeds this amount will be returned to the applicant. The proposed principal investigator may request support only for the amount of time necessary to complete the dissertation. A dissertation research grant usually is awarded for a period of 12 months or less, but may be awarded for up to 17 months. FUNDS AVAILABLE The AHCPR expects to award up to $500,000 in fiscal year 1994 to support about 20 dissertation research projects. The number of awards will be contingent on the availability of funds and the quality of the applications. RESEARCH OBJECTIVES Only applications that propose studies in areas identified in section 902 of the Public Health Service Act are eligible for support. Areas of health services research authorized under section 902 in which AHCPR is interested in dissertation grants include: o Effectiveness, efficiency, and quality of health care services; o Outcomes of health care services and procedures; o Clinical practice, including primary care and practice-oriented research; o Health care costs, productivity, and market forces; o Health care technologies, facilities, and equipment; o Health promotion and disease prevention; o Medical liability; o AIDS/HIV infection with respect to issues of access and delivery of health care services; o Rural health services; and o Health of low-income, minority, elderly, and other underserved populations. Applicants are encouraged to discuss the general policy priority of their research topics by letter or by telephone with AHCPR staff listed under INQUIRIES. SPECIAL REQUIREMENTS Allowable Costs Expenses usually allowed under PHS research grants will be covered by AHCPR dissertation research grants. Allowable costs include: the investigator's salary; direct project expenses such as travel, data processing, and supplies; and, for institutional applicants only, indirect costs. Fees for maintaining matriculation or other fees imposed on those preparing dissertations are allowable costs, provided the fees are required of all students of similar standing, regardless of the source of funding. Applicants are expected to work full time on the project. Any level of effort that is less than full time must be fully justified. For the purpose of calculating indirect costs, dissertation research grants are considered to be training grants. Therefore, in accordance with PHS policy, indirect costs, payable only when the applicant is an institution, are limited to eight percent of total allowable direct costs exclusive of tuition and related fees and expenditures for equipment, or at the institution's actual indirect cost rate, whichever results in a lesser dollar amount. Other Conditions The following conditions apply to dissertation grants: o A Principal Investigator who discontinues or suspends a project during the grant period must inform the AHCPR immediately in writing. The AHCPR may suspend or terminate the grant as requested by the Principal Investigator or on its own initiative. o The dissertation constitutes the final report of the grant. The dissertation must be officially accepted by the faculty committee or university official responsible for the candidate's dissertation and must be signed by the responsible officials. Three copies of the dissertation must be submitted to the AHCPR. o The dissertation and all financial status reports must be submitted in English. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS CONCERNING INCLUSION OF WOMEN AND MINORITIES IN RESEARCH STUDY POPULATIONS The AHCPR requires all applicants for research grants to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder, or condition under study. Special emphasis must be placed on including minorities and women in studies of diseases, disorders, and conditions which disproportionately affect them. This policy applies to males and females of all ages. If women or minorities are excluded or inadequately represented in research, a clear and compelling rationale must be provided. This policy applies to all AHCPR research grants. The AHCPR will not award grants for applications which do not comply. If the application does not contain the required information, it will be returned without review. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues should be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information should be included in the form PHS 398 in Sections 1 to 4 of the Research Plan and summarized in Section 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, AHCPR recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., American Indians/Alaskan Natives, Asian/Pacific Islanders, African Americans, Hispanics). Where appropriate, the applicant must provide the rationale for studies on single minority population groups. For foreign awards, the policy on inclusion of women applies fully. Since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. Peer reviewers will address specifically whether the applicant's research plan conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question(s) addressed and the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and will be reflected in the priority score assigned to the application. APPLICATION PROCEDURES The application receipt date is January 24, 1994. The research grant application form PHS 398 (revised 9/91) is to be used in applying for these grants, in accordance with the instructions described here and the instructions in the application. These forms are available at most institutional offices of sponsored research; the Office of Grants Information, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone 301-594-7248; and the Scientific Review Branch, Agency for Health Care Policy and Research, 2101 East Jefferson Street, Suite 602, Rockville, MD 20852, telephone 301-594-1449. In addition, a packet containing both a Grant Announcement based upon this RFA and the research grant application form PHS 398 will be available after September 15 from: AHCPR Publications Clearinghouse/DISS P.O. Box 8547 Silver Spring, MD 20907 Telephone: 1-800-358-9295 The RFA label available in the PHS 398 application form must be affixed to the bottom of the face page of the application. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2a of the face page of the application form and the YES box in 2a must be marked. The completed, signed, original application and five legible copies of form PHS 398 and the letter from the faculty committee must be sent or delivered to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** Completed applications must be received by the Division of Research Grants by January 24, 1994. If an application is received after that date, it will be returned to the applicant. An application that does not conform to the instructions in this RFA will be returned. Resubmitted applications are seldom funded. Therefore, individuals considering resubmissions are strongly encouraged to contact the Dissertation Program Coordinator, at the address listed in INQUIRIES below, prior to resubmitting revised applications. Special Instructions Whenever feasible, the proposed Principal Investigator for a dissertation grant is encouraged to have the application administered through an institution. This may be either the degree-granting institution or another non-profit institution with which the proposed Principal Investigator is professionally affiliated. In determining which institution is more appropriate, the student must consider the extent to which the resources of the designated institution are capable of supporting the proposed research effort. A letter from the faculty committee or university official directly responsible for supervising the development and progress of the dissertation research must be submitted with the application. The letter must (1) certify approval of the dissertation proposal, (2) certify that all requirements for the doctoral degree except the dissertation are completed (or will be completed by the time of the grant award), and (3) note that the faculty committee expects the doctoral candidate to proceed with the approved dissertation proposal with or without AHCPR support. The application must identify all members of the faculty advisory committee, by listing the information in form 398, page 2, and providing a brief separate biographical sketch for each on form 398, page 6. Applicants for a dissertation grant should take special care in reading the instructions in the research grant application form PHS 398. Special care should be taken to thoroughly understand and carefully address the matters of human subject certifications and assurances, including issues related to gender and minority representation, as described in the application form PHS 398 (especially pages 11-13, 21-23, and 25-26). In the instructions for the PHS 398, "human subject" is defined by regulations as "a living individual about whom an investigator (whether professional or student) conducting research obtains (1) data through intervention or interaction with the individual or (2) identifiable private information." The human subject regulations encompass graphic, written, or recorded information derived from individually identifiable human subjects. REVIEW CONSIDERATIONS Applications will be reviewed initially by the Referral Office at the Division of Research Grants, NIH, for completeness and by AHCPR for responsiveness to the RFA. Incomplete and nonresponsive applications will be returned to applicants without further consideration. Review criteria for AHCPR grant applications are significance and originality from a scientific and technical viewpoint; adequacy of the methodology to carry out the proposed project; availability of data or proposed plan to collect data required for the project; qualifications and experience of the Principal Investigator and proposed staff; adequacy of the plan for organizing and carrying out the project; reasonableness of the proposed budget; and adequacy of the facilities and resources available to the applicant. Dissertation research grant applications will be reviewed under AHCPR review procedures by non-Federal or Federal experts. Reviewers will be selected on the basis of their health services research accomplishments and knowledge and their experience in research career development. Because reviews are rigorous, considerable methodological detail is important in the narrative of the application. All elements of the application will be considered in the review process. Primary emphasis will be given to the significance, scientific merit, and feasibility of the project. Applications may be subject to triage to determine their scientific merit relative to other applications received in response to this RFA. The AHCPR will withdraw from further competition those applications judged by triage to be noncompetitive for award and notify the Principal Investigator and institutional official. Those applications judged to be competitive will undergo further scientific merit review. Review results and funding decisions will be announced approximately six months after the submission date. Special review criteria, funding decisions, and continuation of support are described below. Applications will be evaluated in accordance with the criteria stated above for scientific/technical merit and the special review criteria listed below by an appropriate peer review group. Special Review Criteria Applications are reviewed to determine their suitability in four major areas: problem or policy significance, research design, investigator's qualifications and support structure, and budgetary appropriateness. Problem Significance o The project is focused on a significant problem or policy in the delivery of health care. o The methodology or anticipated results of the project have national interest, provide a basis for generalized conclusions, or have important practical applicability. Research Design o The problem to be addressed by the research is clearly defined. o The application reflects an adequate knowledge of other research related to the problem. o Questions to be answered or hypotheses to be tested are well formulated and clearly stated. o Research methodology is fully described, including, where applicable, explanation of sampling procedures, description of types and sources of data to be gathered, discussion of methodological problems expected to be encountered, and description of specific analyses to be undertaken. o The application adequately describes the plans for managing the project, including a tentative schedule for the main steps of the investigation within the project period requested. Investigator's Qualifications and Support Structure o The applicant shows promise as a health services research investigator. o The applicant's experience and training are sufficient to carry out the research. o The available facilities and organizational arrangements are appropriate to the research. o Faculty advice, composition of dissertation committee, and support are suitable to the research being undertaken, as evidenced by the letter of support. Budgetary Appropriateness o The allocation of time and money reflects an understanding of the research tasks to be accomplished and of the problems likely to arise. o Where appropriate and feasible, the proposed approach uses data available or being collected through government and other sources. AWARD CRITERIA Applications will compete for available funds with all other applications for this RFA. The following will be considered in making funding decisions: quality of the proposed project as determined by peer review, and availability of funds. The earliest anticipated date of award for applications will be August 1, 1994. INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. Applicants are encouraged to discuss programmatic issues, such as the suitability of their research topics, with and request the RFA by letter or telephone from: Julius Pellegrino, M.B.A., M.P.H. Center for General Health Services Extramural Research Agency for Health Care Policy and Research Executive Office Center, Suite 502 2101 East Jefferson Street Rockville, MD 20852 Telephone: (301) 594-1357 ext.138 Direct inquiries regarding fiscal and administrative matters to: Ralph L. Sloat, Grants Management Officer Agency for Health Care Policy and Research 2101 East Jefferson Street Rockville, MD 20852 Telephone: (301) 594-1447 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance, No. 93.180. Awards are made under authorization of the Public Health Service Act, Title IX, as amended by Public Laws 101-239 and 102-410, (42 U.S.C. 299-299c-6) and Section 1142 of the Social Security Act (42 U.S.C. 1320b-12). Awards are administered under the PHS Grants Policy Statement; and Federal Regulations 42 CFR Part 67, Subpart A, and 45 CFR Part 74 (45 CFR Part 92 for State and local governments). This program is not subject to the intergovernmental review requirements of Executive Order 12372. From owner-sci-resources@net.bio.net Thu Aug 26 23:00:00 1993 Path: biosci!NET.BIO.NET!kristoff From: kristoff@NET.BIO.NET (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 22, no. 31, pt. 1, 27 August 1993 Message-ID: Date: 27 Aug 93 03:22:22 GMT Sender: kristoff@net.bio.net Distribution: bionet Lines: 1499 Approved: sci-resources-moderator@net.bio.net $$XID NIHGUIDE 19930827 V22N31 P1O2 ************************************ X-comment: RFAS described: HD-94-009, HD-94-008, HL-93-021, HS-94-001, HS-94- 003 NIH GUIDE - Vol. 22, No. 31 - August 27, 1993 $$INDEX BEGIN ******************************************************* NOTICES $$INDEX N1 ********************************************************** MINORITY ACCESS TO RESEARCH CAREERS PROGRAM National Institute of Mental Health National Institute on Alcohol Abuse and Alcoholism National Institute on Drug Abuse INDEX: MENTAL HEALTH; ALCOHOL ABUSE, ALCOHOLISM; DRUG ABUSE $$INDEX N2 ********************************************************** THE HUMAN BRAIN PROJECT: PHASE I FEASIBILITY STUDIES (PA-93-068) National Institute of Mental Health National Institute on Drug Abuse National Science Foundation National Institute on Aging National Institute of Child Health and Human Development National Institute on Deafness and Other Communication Disorders National Center for Research Resources National Library of Medicine Office of Naval Research National Aeronautics and Space Administration Department of Energy Fogarty International Center INDEX: MENTAL HEALTH; DRUG ABUSE; NATIONAL SCIENCE FOUNDATION; AGING; CHILD HEALTH, HUMAN DEVELOPMENT; DEAFNESS, COMMUNICATION DISORDERS; RESEARCH RESOURCES; NATIONAL LIBRARY OF MEDICINE; NAVAL RESEARCH; AERONAUTICS, SPACE ADMINISTRATION; ENERGY; FOGARTY INTERNATIONAL CENTER $$INDEX N3 ********************************************************** INTERACTIVE RESEARCH PROJECT GRANT APPLICATION RECEIPT AND FUNDING POLICIES National Cancer Institute INDEX: CANCER $$INDEX N4 ********************************************************** HUMAN TISSUE AVAILABLE FOR RESEARCH INTO DEVELOPMENTAL DISORDERS National Institute of Child Health and Human Development INDEX: CHILD HEALTH, HUMAN DEVELOPMENT $$INDEX N5 ********************************************************** FOOD AND DRUG ADMINISTRATION GUIDELINE FOR THE STUDY AND EVALUATION OF GENDER DIFFERENCES IN THE CLINICAL EVALUATION OF DRUGS Food and Drug Administration INDEX: FOOD AND DRUG ADMINISTRATION NOTICES OF AVAILABILITY (RFPs AND RFAs) $$INDEX R1 ********************************************************** FERTILITY DRUGS AND OVARIAN CANCER (RFP NICHD-CRE-93-12) National Institute of Child Health and Human Development INDEX: CHILD HEALTH, HUMAN DEVELOPMENT $$INDEX R2 12/09/93 ************************************************* DEVELOPMENT OF BIOCHEMICAL AND GENETIC MARKERS FOR PREMATURE ATHEROGENESIS (RFA HD-94-009) National Institute of Child Health and Human Development National Heart, Lung, and Blood Institute INDEX: CHILD HEALTH, HUMAN DEVELOPMENT; HEART, LUNG, BLOOD $$INDEX R3 01/07/94 ************************************************* HISPANIC CHILD HEALTH: SOCIAL, BEHAVIORAL, AND CULTURAL FACTORS (RFA HD-94-008) National Institute of Child Health and Human Development INDEX: CHILD HEALTH, HUMAN DEVELOPMENT $$INDEX R4 01/14/94 ************************************************* HIV AND CELLULAR INFILTRATIVE DISEASE IN THE LUNG (RFA HL-93-021) National Heart, Lung, and Blood Institute INDEX: HEART, LUNG, BLOOD $$INDEX R5 01/24/94 ************************************************* GRANTS FOR HEALTH SERVICES DISSERTATION RESEARCH (RFA HS-94-001) Agency for Health Care Policy and Research INDEX: HEALTH CARE POLICY, RESEARCH $$INDEX R6 02/22/94 ************************************************* HIV COST AND SERVICES UTILIZATION STUDY (RFA HS-94-003) Agency for Health Care Policy and Research INDEX: HEALTH CARE POLICY, RESEARCH ONGOING PROGRAM ANNOUNCEMENTS $$INDEX P1 ********************************************************** HELICOBACTER PYLORI PATHOGENESIS (PA-93-105) National Institute of Allergy and Infectious Diseases National Institute of Diabetes and Digestive and Kidney Diseases INDEX: ALLERGY, INFECTIOUS DISEASES; DIABETES, DIGESTIVE, KIDNEY DISEASES This publication is available electronically to institutions via BITNET or INTERNET and is also on the NIH GOPHER. Alternative access is through the NIH Grant Line using a personal computer (data line 301/402-2221). Contact Dr. John James at 301/594-7270 for details. $$INDEX END ********************************************************* NOTICES $$N1 BEGIN ********************************************************** MINORITY ACCESS TO RESEARCH CAREERS PROGRAM NIH GUIDE, Volume 22, Number 31, August 27, 1993 P.T. 34; K.W. 1014006 National Institute of Mental Health National Institute on Alcohol Abuse and Alcoholism National Institute on Drug Abuse The Program Announcement "Minority Access to Research Careers Program (MARC)" was published by the Alcohol, Drug Abuse, and Mental Health Administration (ADAMHA) in 1987 and has been supported by the three former ADAMHA institutes, the National Institute of Mental Health (NIMH), the National Institute on Alcohol Abuse and Alcoholism (NIAAA), and the National Institute on Drug Abuse (NIDA). The MARC program at the National Institutes of Health (NIH) has been administered primarily by the National Institute of General Medical Sciences (NIGMS) and the other NIH institutes have provided funding for some aspects of selected MARC grants. The merger of the ADAMHA institutes with the NIH has led to a reorganization of the former ADAMHA MARC Program. The NIMH will continue and further develop this program in the area of mental health. The name of this program has been changed to "Career Opportunities in Research Education and Training (COR)." The NIDA and NIAAA will honor commitments for continuation of awards made under the former ADAMHA MARC, but will no longer accept assignment of new applications submitted to this program. The NIDA and NIAAA will participate in the NIGMS-administered MARC program. INQUIRIES For further information regarding this announcement, contact: Ernestine Vanderveen, Ph.D. Minority Research Coordinator National Institute on Alcohol Abuse and Alcoholism Parklawn Building, Room 16C-06 Rockville, MD 20857 Telephone: (301) 443-1273 Timothy P. Condon, Ph.D. Office of Science Policy, Education, and Legislation National Institute on Drug Abuse Parklawn Building, Room 10A55 Rockville, MD 20857 Telephone: (301) 443-6071 Yvonne T. Maddox. Ph.D. Minority Access to Research Careers Program National Institute of General Medical Sciences Westwood Building, Room 950 Bethesda, MD 20892 Telephone: (301) 594-7823 Sherman L. Ragland Office for Special Populations National Institute of Mental Health Parklawn Building, Room 17C-16 Rockville, MD 20857 Telephone: (301) 443-2847 FAX: (301) 443-1328 $$N1 END ************************************************************ $$N2 BEGIN ********************************************************** THE HUMAN BRAIN PROJECT: PHASE I FEASIBILITY STUDIES NIH GUIDE, Volume 22, Number 31, August 27, 1993 PA NUMBER: PA-93-068 P.T. 34; K.W. 0705010, 1002030, 1004017 National Institute of Mental Health National Institute on Drug Abuse National Science Foundation National Institute on Aging National Institute of Child Health and Human Development National Institute on Deafness and Other Communication Disorders National Center for Research Resources National Library of Medicine Office of Naval Research National Aeronautics and Space Administration Department of Energy Fogarty International Center As indicated above, the Department of Energy and the Fogarty International Center have joined the Federal organizations supporting the Human Brain Project. For the information of those intending to apply in response to the program announcement of The Human Brain Project (PA-93-068; NIH GUIDE, Vol. 22, No. 13, April 2, 1993), it is important that the special purpose of this program is considered when applications are prepared. The following excerpts from the program announcement emphasize the need for each application to include both an informatics research component and a neuroscience research component: o This initiative will incorporate cutting-edge informatics research with neuroscience research in order to facilitate the integration of neuroscience information and to promote communication and collaboration across scientific disciplines and geographic locations. o The Human Brain Project encourages informatics research carried out in concert with neuroscience research. Since informatics solutions will likely include computer-based tools such as databases, computer networks and associated software to acquire, store, manage, analyze, integrate, and transmit neuroscience information, it is probable that key personnel on successful applications will include not only neuroscientists, but also those engaged in research in computer science, information science, engineering, mathematics, and/or statistics. Applicants are reminded that applications considered to be inappropriate for this program announcement will be assigned to the appropriate agencies, institutes and centers according to their goals and designs and in accordance with standard referral guidelines. Applicants are notified that applications for P20 grant mechanisms will not be accepted from organizations outside of the United States. $$N2 END ************************************************************ $$N3 BEGIN ********************************************************** INTERACTIVE RESEARCH PROJECT GRANT APPLICATION RECEIPT AND FUNDING POLICIES NIH GUIDE, Volume 22, Number 31, August 27, 1993 P.T. 34; K.W. 0715035, 1014006 National Cancer Institute The National Cancer Institute (NCI) initiated the concept of the interactive research project grant (IRPG) in January 1992 with the publication of NIH Program Announcement PA-92-29 (NIH Guide for Grants and Contracts, Vol. 21, No. 1, January 10, 1992). This was followed by Program Announcements in Digital Mammography (PA-92-57, NIH Guide for Grants and Contracts, Vol. 21, No. 12, March 27, 1992), and Magnetic Resonance Spectroscopy and Cancer Treatment (PA-92-86, NIH Guide for Grants and Contracts, Vol. 21, No. 22, June 12, 1992). Policies pertaining to these and all subsequent IRPG solicitations, whether initiated by the NCI or another NIH Institute or Center, are now subsumed under the NIH-wide program announcement PA-93-078, entitled "Investigator Initiated Interactive Research Project Grants" (NIH Guide for Grants and Contracts, Vol. 22, No. 16, April 23, 1993). The items that differ from the previous NCI IRPG solicitations as specified in the NIH-wide announcement are: (a) to reduce the minimum number of required projects from three to two; and (b) clarification of the nature and content of the information to be provided under Section 7 (Consultants/Collaborators) of the form PHS 398 application kit. It is the policy of the NCI to accept unsolicited IRPG applications in all areas of cancer research appropriate to the mission of the NCI as delineated in the PHS referral guidelines. Applications received in response to IRPG program announcements normally will be assigned to the appropriate Institute and study sections of the Division of Research Grants according to the PHS referral guidelines. AWARD CRITERIA The general principles to be employed by the NCI in consideration of funding individual components of IRPGs received in response to program announcements will be those that apply to all R01 awards; that is, applications must fall within the R01 payline to be ranked for immediate funding. In addition, however, if any individual application within an IRPG set falls within the natural R01 payline at the time of review, the NCI will consider selected additional applications within the set with scores better than the 35th percentile as possible candidates for funding as exceptions, especially if such applications fall within scientific areas designated as high priority by the NCI. Currently, these high priority areas include cancer of the breast, prostate, and ovary. Continuing commitments and current limitations on available research project grant (RPG) funds have affected the success rates of IRPGs, as they have with all other RPG mechanisms. Experience to date with IRPGs indicates that, as for new (Type 1) R01 applications in general, few original Type 1 applications submitted as components of IRPG sets are likely to be scored within the established payline of the NCI; it is consequently far less likely that more than one application in any IRPG set will be scored within that payline. If one or more, but not all, applications within an IRPG group receive initial funding, and unfunded applications within that group are subsequently amended and submitted on later receipt dates, the awarded IRPG component(s) should be identified and may be cited in the amended applications. This situation will be considered as forming a basis for subsequent exception funding for the resubmitted amended applications should their percentile ranking place them outside the then-current payline. In such cases, those amended R01 applications must make reference to being part of a partially funded IRPG. They may, however, request support to extend beyond the end date of the already awarded component R01(s), consistent with the scientific goals of the application. The National Cancer Institute intends to publish annually a list of updated high priority areas for Interactive Research Project Grants. While all IRPG applications outside these areas will be fully considered for regular funding under current paradigms, the extreme stringency of success rates for NCI R01 awards in general suggests that potential IRPG applicants proposing to conduct research in lower priority areas should be cautioned, therefore, to limit submission of interactive projects to those that are most fully conceptualized and integrated and that are felt to have the best chance of receiving funding as independent research efforts. INQUIRIES Applicants with questions regarding NCI policies pertaining to these awards are encouraged to contact an NCI program director or: Deputy Director Division of Extramural Activities National Cancer Institute Telephone: (301) 496-4218 FAX: (301) 402-0956 $$N3 END ************************************************************ $$N4 BEGIN ********************************************************** HUMAN TISSUE AVAILABLE FOR RESEARCH INTO DEVELOPMENTAL DISORDERS NIH GUIDE, Volume 22, Number 31, August 27, 1993 P.T. 34; K.W. 0780020, 0780005 National Institute of Child Health and Human Development The National Institute of Child Health and Human Development (NICHD) has contracted for the collection of tissues to further research into human developmental disorders such as chromosomal disorders, encephalopathies, aminoacidopathies, leukodystrophies, lysosomal disorders, neurological disorders, sudden infant death syndrome (SIDS), unexplained mental retardation, and autism. Currently tissue is available for distribution from over 140 cases including SIDS infants, chromosomal disorders (primarily fetal tissue), non-affected cases, accidental deaths, deaths from known causes (primarily infection and congenital abnormalities), anencephaly, depression, hydrocephalus, seizure disorders, spina bifida, etc. Tissues are stored at -85 degrees Celsius or fixed in 20 percent formalin. Tissues collected include cerebral coronal hemisections, medulla, brainstem, cerebellum, dura, cranial and peripheral nerves, CSF, vitreous humor, whole blood, and various tissues from the cardiovascular, endocrine, gastrointestinal, genital, hematopoietic system, integumentary, musculoskeletal, respiratory, and urinary systems. The contract also provides for a collaboration with investigators who have access to tissue from patients with the above disorders. This collaboration may include recovery of tissue, storage, publicizing the availability of tissue, and the distribution of tissues to qualified investigators. INQUIRIES Direct inquiries regarding this research resource to: Felix de la Cruz, M.D. Center for Research for Mothers and Children National Institute of Child Health and Human Development 6100 Building, Room 4B09 Bethesda, MD 20892 Telephone: (301) 496-1383 Marian Willinger, Ph.D. Center for Research for Mothers and Children National Institute of Child Health and Human Development 6100 Building, Room 4B03 Bethesda, MD 20892 Telephone: (301) 496-5575 $$N4 END ************************************************************ $$N5 BEGIN ********************************************************** FOOD AND DRUG ADMINISTRATION GUIDELINE FOR THE STUDY AND EVALUATION OF GENDER DIFFERENCES IN THE CLINICAL EVALUATION OF DRUGS NIH GUIDE, Volume 22, Number 31, August 27, 1993 P.T. 34; K.W. 0710100 Food and Drug Administration The Food and Drug Administration (FDA) "Guideline for the Study and Evaluation of Gender Differences in the Clinical Evaluation" was published in the Federal Register as a Notice on July 22, 1993 (56FR39406). This guideline sets forth the expectations regarding the inclusion of both genders in drug development and revises the section "Women of Childbearing Potential" in the 1977 guideline entitled, "General Consideration for the Clinical Evaluation of Drugs [HEW Publication No. (FDA) 77-3040]. There are two major changes addressed in this guidance. First, the FDA is withdrawing the restriction on the participation of women of childbearing potential in early clinical trials, including clinical pharmacology studies and early therapeutic studies. Second, FDA is formalizing expectations regarding inclusion of subjects of both genders in drug development; analyses of clinical data by gender; assessment of potential pharmacokinetic differences between genders; and, where appropriate, assessment of pharmacodynamic differences and the conduct of specific additional studies in women. A major effect of the new guideline is to give more flexibility to IRBs, investigators, and subjects in determining how best to ensure the safe participation of women of childbearing potential in clinical studies. FDA policy in the new guideline reflects the importance of the IRB deliberative process, the informed consent document and process, and the necessity for attention to the completeness and accuracy of information conveyed to potential and enrolled subjects. Women must receive adequate information and opportunity for discussion regarding, for example, potential risks to their fertility and possible teratogenic potential of the drugs and biologics. INQUIRIES For futher information contact: Patrick J. Savino CDER Executive Secretariat Staff (HFD-8) Food and Drug Administration 5600 Fishers Lane Rockville, MD 20857 Telephone: (301) 594-1012 $$N5 END ************************************************************ NOTICES OF AVAILABILITY (RFPs AND RFAs) $$R1 BEGIN NICHD-CRE-93-12 ****************************************** FERTILITY DRUGS AND OVARIAN CANCER NIH GUIDE, Volume 22, Number 31, August 27, 1993 RFP AVAILABLE: NICHD-CRE-93-12 P.T. 34; K.W. 0413002, 0740025, 0715035 National Institute of Child Health and Human Development The Contraceptive and Reproductive Evaluation Branch, National Institute of Child Health and Human Development (NICHD), seeks sources for a study of the long-term sequelae of exposure to fertility drugs. The primary objective is to determine whether and, if so, to what degree, exposure to ovulation-inducing drugs increases the risk of ovarian cancer. The secondary objective is to shed light on other potentially serious adverse effects of ovulation induction. The proposed cohort study would involve subjects from one or more well-defined historic cohorts with data already collected on reproductive, personal, familial, and any other relevant risk factors, including complete fertility drug history (dosage and duration of usage), as well as histological diagnoses of any malignancies occurring among the participants. Enough women must have been already enrolled to ensure sufficient statistical power to test hypotheses in subsets of the data, such as anovulatory versus other forms of infertility and women of different parity and gravidity. Due to the relative rarity of ovarian cancer, all interested parties must be able to document the existence of an historic cohort currently providing at least 30,000 woman-years of follow-up after exposure. This requirement is based on available incidence data to detect a three-fold difference in risk of ovarian cancer. Offerors should have expertise in the field of reproductive epidemiology, particularly with regard to ovulation induction and ovarian cancer. Offerors should also have experience in assembling and obtaining adequate follow-up of large cohorts and in collecting, managing, and analyzing large epidemiologic data bases. The Government estimates the effort to be approximately 4.5 technical staff-years. It is anticipated that one cost-reimbursement incrementally funded type contract will be awarded for a period of 54 months. INQUIRIES This announcement is not a request for proposals (RFP). RFP No. NICHD-CRE-93-12 is now available. Copies of the RFP may be obtained by sending a written request, with a self-addressed label, or a FAX request to: Charles W. Grewe, Contracting Officer Office of Grants and Contracts National Institute of Child Health and Human Development 6100 Building, Room 7A07 Bethesda, MD 20892 FAX: (301) 402-3676 $$R1 END ************************************************************ $$R2 BEGIN HD-94-009 FULL-TEXT ************************************** DEVELOPMENT OF BIOCHEMICAL AND GENETIC MARKERS FOR PREMATURE ATHEROGENESIS NIH GUIDE, Volume 22, Number 31, August 27, 1993 RFA AVAILABLE: HD-94-009 P.T. 34; K.W. 0715040, 0760002, 1002019 National Institute of Child Health and Human Development National Heart, Lung, and Blood Institute Application Receipt Date: December 9, 1993 THIS IS A NOTICE OF AVAILABILITY OF A REQUEST FOR APPLICATIONS (RFA); IT IS ONLY AN ABSTRACT OF THE RFA. POTENTIAL APPLICANTS MUST REQUEST THE COMPLETE RFA, WHICH CONTAINS ESSENTIAL INFORMATION FOR THE PREPARATION OF AN APPLICATION, FROM THE CONTACT LISTED IN "INQUIRIES," BELOW. FAILURE TO FOLLOW THE INSTRUCTIONS IN THE COMPLETE RFA MAY RESULT IN AN INCOMPLETE APPLICATION, WHICH WILL BE RETURNED TO THE APPLICANT WITHOUT REVIEW. PURPOSE The Endocrinology, Nutrition and Growth (ENG) Branch of the Center for Research for Mothers and Children, National Institute of Child Health and Human Development (NICHD) and the Lipid Metabolism-Atherogenesis (LA) Branch, National Heart, Lung, and Blood Institute (NHLBI) issue an RFA on Development of Biochemical and Genetic Markers for Premature Atherogenesis. Coronary atherosclerosis remains a major killer disease, often causing deaths during prime productive years. It has been shown that the pathological process of coronary atherosclerosis often begins in adolescence, and it is known that profound changes occur in the lipoprotein system during infancy and adolescence that may predispose to atherogenesis. Preventive measures could be effective in mitigating the ravages of coronary atherosclerosis if markers of the atherogenic process were available in susceptible children and adolescents. This RFA encourages investigators to ascertain biochemical and genetic markers of the atherosclerotic process in order to identify those children at high risk. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This RFA, Development of Biochemical and Genetic Markers for Premature Atherogenesis, is related to the priority area of childhood nutrition. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT Applications in response to this RFA will be funded through the individual research grant (R01) program of the NIH. This announcement is for a single competition with the application receipt deadline of December 9, 1993. Future unsolicited competing continuation applications will compete with all investigator-initiated applications and be reviewed by a Division of Research Grants (DRG) study section. However, if the NICHD and the NHLBI determine that there is a sufficient continuing program need, these Institutes may announce a request for competitive continuation applications. The total project period for applications submitted in response to the present RFA should not exceed five years. The earliest anticipated award date is September 1, 1994. FUNDS AVAILABLE It is anticipated that six grants will be awarded under this program, contingent upon receipt of a sufficient number of meritorious applications and the availability of funds. To fund these awards the NICHD has set aside $750,000 and the NHLBI has set aside $250,000 for direct costs in the first year. RESEARCH OBJECTIVES Background The major emphasis of preventive research in this area is currently placed on control of hypercholesterolemia. However, lipoproteins other than LDL-cholesterol may be important in atherogenesis and might serve as robust predictors once they are identified. The purpose of this RFA is to stimulate investigators to move beyond cholesterol in exploring biochemical and genetic predictors of atherogenesis and to encourage investigators to ascertain differences in lipoprotein profiles and other metabolic, hormonal, or genetic factors between offspring of families prone to premature coronary atherosclerosis and offspring of families not so afflicted. Such differences may be useful as markers to identify those children at high risk of developing atherosclerosis later in life. Objectives and Scope The NICHD and the NHLBI are devoted to uncovering predictors of chronic disease during childhood. This RFA is aimed at identifying genetic and biochemical precursors in childhood and adolescence of atherosclerosis later in life. The prevention of chronic disease in adulthood is best achieved by attacking these problems in children. In order to maximize the probability of success in developing childhood markers for atherogenesis, studies should focus on changes in lipoprotein profiles during childhood and adolescence in offspring of coronary-prone parents, especially mothers, in comparison to a matched group of offspring of parents unaffected by coronary atherosclerosis. Studies of multiple generations and studies of affected twins should also be informative. Investigators are also encouraged to develop epidemiologic techniques to permit the correlation of genetic or metabolic markers measurable in childhood with a familial tendency to premature atherosclerosis. It is known that high serum levels of LDL-cholesterol predispose to coronary atherosclerosis. Children who are homozygous for familial hyper-cholesterolemia have very high levels of this serum lipid fraction and are at risk of clinically significant coronary pathology in their second and third decades. The molecular basis for this hereditary condition is known to be absent or dysfunctional cellular LDL receptors. However, the majority of coronary artery occlusions occur in individuals who have only mild-to-moderate elevations of LDL-cholesterol. Therefore, changes in other lipoprotein fractions need to be explored as possible harbingers of atherosclerosis in addition to elevations of LDL-cholesterol. Examples of putative lipoprotein markers include elevated levels of LDL- apolipoprotein B; low levels of HDL cholesterol (hypo HDL) and low levels of apolipoprotein AI; isoforms of apolipoprotein E; elevated levels of Lp(a) lipoproteins; elevated serum triglycerides; and high levels of oxidized LDL. Ratios and functional measures, such as delayed clearing of dietary fat, of these or other lipids and lipoproteins might also serve as markers in childhood for atherosclerosis later in life. Factors other than lipoproteins and their receptors that may also contribute to the process of coronary atherosclerosis in an ancillary manner include homocysteine, peptide hormones, sex steroids, growth factors, endothelin-1, thromboxane, fibrinogen, fibrin, fibrin split products, tissue plasminogen activator, and other components of the coagulation cascade. In addition to uncovering markers of atherosclerosis in offspring of affected parents, evaluating the segregation of such markers in multiple generations of coronary-prone families is also encouraged in order to ascertain the heritability and penetrance of possible metabolic and genetic markers. Studies designed to ascertain how putative markers track prospectively are also needed. Genetic studies of individuals who are heterozygotes or compound heterozygotes for genes that control the metabolism and transport of lipoproteins are encouraged as well. This RFA is designed to study lipoproteins and other putative biochemical and genetic markers of premature atherosclerosis. The scope of the RFA includes infants, children, and adolescents as well as animal models if they can be shown to be relevant. STUDY POPULATIONS SPECIAL INSTRUCTIONS FOR INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDIES For projects involving clinical research, NIH requires applicants to give special attention to the inclusion of women and minorities in study populations. If women or minorities are not included in the study populations for clinical studies, a specific justification for this exclusion must be provided. Applications without such documentation will not be accepted for review. APPLICATION PROCEDURES Applications are to be submitted on form PHS 398 (rev. 9/91). These forms are available at most institutional offices of sponsored research and from the Office of Grants Information, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone 301-594-7248. Applications must be received by December 9, 1993. Potential applicants must request the detailed information included in the RFA before preparing an application. REVIEW CONSIDERATIONS Applications will be reviewed by NICHD staff for responsiveness to the RFA. Applications judged to be nonresponsive will be returned. Responsive applications may be subjected to a triage by a peer-review group to determine their scientific merit relative to the other applications received in response to this RFA. NIH will withdraw from competition those applications judged to be noncompetitive and notify the applicant and institutional business official. Those applications judged to be competitive will be further evaluated for scientific/technical merit by a review group convened solely for this purpose by the Division of Scientific Review, NICHD. Criteria for the initial review are described in the RFA. Following review by the Initial Review Group, applications will be evaluated by the National Advisory Child Health and Human Development Council and by the National Heart, Lung, and Blood Advisory Council for program relevance and policy issues before awards for meritorious proposals are made. AWARD CRITERIA The anticipated award date is September 1, 1994. Scientific merit and technical proficiency, based on the demonstrated and projected capabilities described in the application in response to the RFA, will be the predominant criteria for determining funding priorities. INQUIRIES Written and telephone inquiries concerning the RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues and requests for the RFA to: Gilman D. Grave, M.D. Center for Research for Mothers and Children National Institute of Child Health and Human Development 6100 Building, Room 4B11 Bethesda, MD 20892 Telephone: (301) 496-5593 Direct inquiries regarding fiscal matters to: Mr. E. Douglas Shawver Office of Grants and Contracts National Institute of Child Health and Human Development 6100 Building, Room 8A17 Bethesda, MD 20892 Telephone: (301) 496-1303 AUTHORITY AND REGULATIONS This program is described in the catalog of Federal Domestic Assistance No. 93.865, Research for Mothers and Children. Awards will be made under the authority of the Public Health Service Act, Section 301 (42 USC 241), and administered under PHS grants policies and Federal Regulations 42 CFR Part 52 and 45 CFR Part 74. This program is not subject to review by a Health Systems Agency. $$R2 END ************************************************************ $$R3 BEGIN HD-94-008 FULL-TEXT ************************************** HISPANIC CHILD HEALTH: SOCIAL, BEHAVIORAL, AND CULTURAL FACTORS NIH GUIDE, Volume 22, Number 31, August 27, 1993 RFA AVAILABLE: HD-94-008 P.T. 34, FD; K.W. 0404000, 0417000, 0413001, 0413003 National Institute of Child Health and Human Development Application Receipt Date: January 7, 1994 THIS IS A NOTICE OF AVAILABILITY OF A REQUEST FOR APPLICATIONS (RFA); IT IS ONLY AN ABSTRACT OF THE RFA. POTENTIAL APPLICANTS MUST REQUEST THE COMPLETE RFA, WHICH CONTAINS ESSENTIAL INFORMATION FOR THE PREPARATION OF AN APPLICATION, FROM THE CONTACT LISTED IN "INQUIRIES," BELOW. FAILURE TO FOLLOW THE INSTRUCTIONS IN THE COMPLETE RFA MAY RESULT IN AN INCOMPLETE APPLICATION, WHICH WILL BE RETURNED TO THE APPLICANT WITHOUT REVIEW. PURPOSE The Demographic and Behavioral Sciences Branch (DBS) of the Center for Population Research, National Institute of Child Health and Human Development (NICHD) is inviting grant applications for the support of research on social, demographic, behavioral, and cultural factors in Hispanic child health. The purpose of the RFA is to encourage theoretically and methodologically innovative research to address scientific issues among the Hispanic population and to better address the needs of its children. Issues of interest are (a) factors that promote low rates of infant mortality and chronic disease in some Hispanic subgroups, despite the experience of racism and poverty by this population; (b) how the experience of migration, its antecedents and consequences, affects the health of Hispanic subgroups and their children; (c) how trends in fertility and mortality may change over time and space in response to changing characteristics of the population; and (d) factors that have led to different health outcomes among different Hispanic subpopulations, and to differences in the social, demographic, behavioral, and biological predictors of those outcomes. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This RFA, Hispanic Child Health: Sociodemographic, Behavioral and Cultural Factors, is encouraging research that has implications for the objectives targeting Hispanics. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-004734-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of States or local government and eligible agencies of the Federal government. Applications from minority individuals and women are encouraged. Domestic applications may include an international component. MECHANISM OF SUPPORT This RFA will use the National Institutes of Health (NIH) individual research grant (R01) and the First Independent Research Support and Transition (FIRST) (R29) awards. Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. The total project period for applications submitted in response to the present RFA may not exceed five years. This announcement is for a single competition with the application receipt deadline of January 7, 1994. The anticipated award date is August 1, 1994. Because the nature and scope of the research proposed in response to this RFA may vary, it is anticipated that the size of an award will vary also. This RFA is a one time solicitation. Future unsolicited competing continuation applications will compete with all investigator-initiated applications and be reviewed according to the customary peer review procedures. FUNDS AVAILABLE $900,000 in direct costs are set aside for the first year of support. It is anticipated that six grants will be made from NICHD funds. It is anticipated that only new applications will be received. The level of support is dependent on the receipt of a sufficient number of applications of high scientific merit. Although this program is provided for in the financial plans of the NICHD, awards pursuant to this RFA are contingent upon the availability of funds for this purpose. RESEARCH OBJECTIVES Background This RFA is a response to a request the U.S. Congress addressed to NICHD. In Report No. 102-708, the House of Representatives Committee on Appropriations expressed concern about the health of Hispanic children in the United States. The Committee urged NICHD to increase research in this area. This RFA also responds to the report, "One Voice, One Vision -- Recommendations to the Surgeon General to Improve Hispanic Health." The Research Agenda of the Surgeon General's National Hispanic/Latino Health Initiative identified the need for culturally appropriate theoretical frameworks and research methodologies to address the unique research needs of the diverse Hispanic/Latino population groups. Copies of the report may be obtained from the Office of the Surgeon General, Department of Health and Human Services, 200 Independence Avenue, SW, Washington, DC 20201 (telephone 202-690-7163). This RFA is also partially an outgrowth of a 1987 initiative by the NICHD, titled "Social and Demographic Research on Infant Mortality and Low Birthweight." Research conducted under that RFA has addressed some of the demographic, social, and behavioral issues related to the health of Hispanic, particularly Mexican-American, women and children. Objectives The purpose of this RFA is to address the sociodemographic, behavioral, and cultural factors that affect child health among Hispanic subpopulations in the United States. Individuals of Central or South American, Cuban, Mexican, Puerto Rican, or some other Spanish origin are considered to be Hispanic, regardless of race. Variations within subgroups may be as important as variations among them. Contrasts may also be drawn between U.S. groups and those in the countries of origin if doing so would shed light on the experience of U.S. populations. Child health refers to characteristics of children ages 0-17 that can affect the likelihood of attaining full growth, optimal development, and well-being. In so far as reproductive or family health and behavior, including fertility or maternal or paternal behavior, may affect child health, it is within the scope of this RFA. The intent of the RFA is to direct attention to the social, behavioral, and cultural factors that affect child health rather than to pathological or clinical conditions, per se. SPECIAL REQUIREMENTS Annual meetings will be held to foster the sharing of information, data, and other experiences. Principal Investigators are encouraged to attend these meetings, and funds must be included in the application budget for one two-day meeting per year in Bethesda, Maryland to discuss the research with other investigators. A statement about the willingness to engage in annual meetings should be included with the application. STUDY POPULATIONS Research should focus primarily on U.S. populations although non-U.S. populations may be used to the extent that they increase our understanding of U.S. Hispanics. The ultimate objective of this RFA is to improve our understanding of child health in the U.S. Children are considered to be age 17 years and under; thus young and middle adolescents are included. The study population may be adults since many of the research issues pertinent to child health and well-being require an understanding of the adult population. Non-Hispanics may be included for comparative purposes. SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS For projects involving clinical research, NIH requires applicants to give special attention to the inclusion of women and minorities in study populations. The focus of this RFA is one U.S. minority group, Hispanic-Americans. Other minorities may be included for comparison purposes but should not be the focus of the application. If women are not included in the study population, a specific justification for the exclusion must be provided. Applications without such documentation will not be accepted for review. APPLICATION PROCEDURES Applications are to be submitted on form PHS 398 (rev. 9/91) that is available in most institutional offices of sponsored research and from the Office of Grants Information, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449 Bethesda MD 20892, telephone (301) 594-7248. FIRST (R29) award applications must include at least three sealed letters of reference attached to the face page of the original application. FIRST (R29) award applications submitted without the required number of reference letters will be considered incomplete and will be returned without review. Applications must be identified by checking the "YES" box in Item 2a on the face page of the application and by typing the words, "In Response to RFA HD-94-008." The RFA label in form PHS 398 must be affixed to the bottom of the face page of the original application. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. The signed typewritten original (topmost), including the Checklist, and three signed copies of the applications must be sent or delivered in one package to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** It is extremely important for the timely review of your application that two additional copies of the application be sent under separate cover to: Susan Streufert, Ph.D. Division of Scientific Review National Institute of Child Health and Human Development 6100 Executive Boulevard, Room 5E03 Bethesda, MD 20892 Telephone: (301) 496-1485 Applications must be received by January 7, 1994. Late applications will not be accepted. If an application is received after that date, it will be returned to the applicant without review. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed by NIH staff for completeness and responsiveness to the RFA. Incomplete applications will be returned to the applicant without further consideration. If the application is judged to be non-responsive to the RFA, NIH staff will return the application to the applicant. The applicant may resubmit the application and have it assigned for review in the same manner as an unsolicited grant applications during the next review cycle. The review criteria for the research projects submitted in response to this RFA are generally the same as those for unsolicited research grant applications: o scientific and technical significance of proposed research; o appropriateness and adequacy of the research approach and methodology proposed to carry out the research; o qualifications and research experience of the Principal Investigator and staff, particularly, but not exclusively, in the area of the proposed research; o availability of resources necessary to perform the research; o appropriateness of the proposed budget and duration in relation to the proposed research. In addition, applications will be judged on the significance and appropriateness of the research problem and methods to the Hispanic population of the U.S. AWARD CRITERIA The anticipated date of award is August 1, 1994. Responsiveness to the RFA, scientific merit, and technical proficiency, as described in the application, will be the predominant criteria for determining funding. An attempt will be made to assure that different Hispanic sub-groups and a diversity of subject matter will be represented in the applications receiving awards. INQUIRIES Written and telephone inquiries and the opportunity to clarify any issues or questions from potential applicants are welcome. Direct inquiries regarding programmatic issues to: Nancy E. Moss, Ph.D. Center for Population Research National Institute of Child Health and Human Development 6100 Executive Boulevard, Room 8B13 Bethesda, MD 20892 Telephone: (301) 496-1174 Direct inquiries regarding fiscal matters to: Melinda B. Nelson Office of Grants and Contracts 6100 Executive Boulevard, Room 8A17 National Institute of Child Health and Human Development Bethesda, MD 20892 Telephone: (301) 496-5481 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.864 and No. 93.866. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$R3 END ************************************************************ $$R4 BEGIN HL-93-021 FULL-TEXT ************************************** HIV AND CELLULAR INFILTRATIVE DISEASE IN THE LUNG NIH GUIDE, Volume 22, Number 31, August 27, 1993 RFA AVAILABLE: HL-93-021 P.T. 34; K.W. 0715008, 0715165, 0755030, 1002004, 1002008 National Heart, Lung, and Blood Institute Letter of Intent Receipt Date: December 10, 1993 Application Receipt Date: January 14, 1994 THIS IS A NOTICE OF AVAILABILITY OF A REQUEST FOR APPLICATIONS (RFA); IT IS ONLY AN ABSTRACT OF THE RFA. POTENTIAL APPLICANTS MUST REQUEST THE COMPLETE RFA, WHICH CONTAINS ESSENTIAL INFORMATION FOR THE PREPARATION OF AN APPLICATION, FROM THE CONTACT LISTED IN "INQUIRIES," BELOW. FAILURE TO FOLLOW THE INSTRUCTIONS IN THE COMPLETE RFA MAY RESULT IN AN INCOMPLETE APPLICATION, WHICH WILL BE RETURNED TO THE APPLICANT WITHOUT REVIEW. PURPOSE The National Heart, Lung, and Blood Institute (NHLBI) invites grant applications for support of research on understanding cellular infiltrative disease in the lung associated with infection by the human immunodeficiency virus (HIV). The primary objectives of this special grant program are to determine the etiology of inflammatory cell infiltration and proliferation in the lung and to understand the cellular and molecular mechanisms involved in the development of lymphoid and nonspecific interstitial pneumonitis associated with HIV infection. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This RFA, HIV and Cellular Infiltrative Disease in the Lung, is related to the priority areas of maternal and infant health, HIV infection, sexually transmitted diseases, and immunization and infectious diseases. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Foreign institutions are not eligible for the First Independent Research Support and Transition (FIRST) award (R29). Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT This RFA solicits applications for the National Institutes of Health (NIH) research project grant (R01) and the FIRST award (R29). Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. The total project period for applications submitted in response to this RFA may not exceed five years. This RFA is a one-time solicitation. Future unsolicited competing continuation applications will compete with all investigator-initiated applications and be reviewed according to the customary peer review procedures. FUNDS AVAILABLE The estimated funds (total costs) available for the first year of support for the entire program is $1.5 million. The expected number of new awards is six to eight. The specific number to be funded will, however, depend on the merit and scope of the applications received and the availability of funds. Since a variety of approaches would represent valid responses to this announcement, it is anticipated that there will be a range of costs among individual grants awarded. Although this program is provided for in the financial plans of the NHLBI, awards pursuant to this RFA are contingent upon the availability of funds for this purpose. RESEARCH OBJECTIVES Two prominent types of interstitial processes distinguished by their clinical and pathologic features have been recognized in association with HIV infection. The first disorder is lymphoid interstitial pneumonitis/pulmonary lymphoid hyperplasia complex (LIP/PLH) which is more commonly associated with chronic pulmonary infiltrates in HIV-infected children than it is in HIV-infected adults. Lymphoid interstitial pneumonitis is characterized by infiltration of the lung by a pleomorphic mixture of lymphocytes, plasma cells, and immunoblasts. Although the etiology of the process is unknown, it is postulated that it involves recognition of a specific antigen by host lymphocytes, the activation of T-cells, increased production of lymphokines, and a rapid increase in effector cells that is responsible for tissue damage. A second frequently occurring infiltrative disorder associated with HIV infection is nonspecific interstitial pneumonitis (NIP) which is less well characterized than LIP/PLH and occurs with equal frequency in children and adults. Nonspecific interstitial pneumonitis in HIV-infected persons is characterized by lymphocyte infiltration, interstitial edema, mononuclear cell infiltration, alveolar type II cell proliferation, and loose interstitial fibrosis. Lymphocytes can be found in the bronchoalveolar lavage (BAL) fluid in 70 to 80 percent of HIV-infected individuals without evidence of lung tumors or infection. It has been suggested that lymphocytic alveolitis in HIV-infected adults may represent an early stage of LIP/PLH or NIP, but this needs to be verified and the mechanism for this process needs to be investigated. The overall objective of this initiative is to encourage basic research on the etiology, mechanisms of pathogenesis, and the host determinants that are involved in the initiation and progression of interstitial infiltrative disease in the lung associated with HIV infection. Applications are invited for innovative multidisciplinary approaches to identify the cause of these disorders and to delineate cellular and molecular mechanisms involved in their pathogenesis. Applications submitted in response to this RFA should clearly define the rationale, background, and specific aims of the proposed studies, and should provide a succinct description of the methods and procedures to be used. Among the topics that would be relevant to the objectives of this RFA are studies of lymphocyte recruitment, replication, and trafficking in the lung as a consequence of HIV infection; identification of cytokines involved and their regulatory pathways; comparisons of infiltrative processes in the lungs of HIV-infected individuals with infiltrative processes seen in the lungs of other immunosuppressed hosts; and the development and use of animal models to study HIV-associated infiltrative disorders of the lung. SPECIAL REQUIREMENTS Applications that propose descriptive studies in humans only and do not contain studies directed at uncovering mechanisms of disease or supporting hypotheses related to mechanisms of disease will not be acceptable. This program will not support studies directed at development of animal models alone. Models must be applied to the study of disease mechanisms associated with cellular infiltration in the lung. Applications that focus on the molecular biology and molecular immunology of these disorders are of particular interest. STUDY POPULATIONS SPECIAL INSTRUCTIONS FOR INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDIES For projects involving clinical research, NIH requires applicants to give special attention to the inclusion of women and minorities in study populations. If women and minorities are not included in the study populations for clinical studies, a specific justification for this exclusion must be provided. Applications without such documentation will not be accepted for review. LETTER OF INTENT Prospective applicants are asked to submit a letter of intent and include the names of any other participating institutions or investigators. A letter of intent is not binding, and it will not enter into the review of any application subsequently submitted, nor is it a requirement for application. Such letters are requested for the purpose of obtaining an indication of the number of applications to be received. The NHLBI staff will not provide a response to a letter of intent. This letter is to be received no later than December 10, 1993 and sent to: Chief, Centers and Special Projects Review Section Division of Extramural Affairs National Heart, Lung, and Blood Institute Westwood Building, Room 553 Bethesda, MD 20892 Telephone: (301) 594-7448 FAX: (301) 594-7407 or 594-7424 APPLICATION PROCEDURES Applications must be received by January 14, 1994. The research grant application form PHS 398 (rev. 9/91) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research and from the Office of Grants Information, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone (301) 594-7248. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by the DRG and responsiveness to the objectives of this RFA by the NHLBI. Incomplete applications will be returned without further consideration. If an application is judged unresponsive, the applicant will be contacted and given an opportunity to withdraw the application or to have it considered for the regular, investigator-initiated grant program of the NIH. Applications judged to be responsive will be reviewed for scientific and technical merit by an initial review group, which will be convened by the Division of Extramural Affairs, NHLBI, solely to review these applications. INQUIRIES Written and telephone inquiries regarding this RFA are encouraged. The opportunity to clarify any issues or questions from the potential applicants is welcome. Direct inquiries regarding programmatic issues to: Hannah H. Peavy, M.D. Division of Lung Diseases National Heart, Lung, and Blood Institute Westwood Building, Room 6A09 Bethesda, MD 20892 Telephone: (301) 594-7425 FAX: (301) 594-7487 Direct inquiries regarding review matters to: Chief, Centers and Special Projects Review Section Division of Extramural Affairs National Heart, Lung, and Blood Institute Westwood Building, Room 553 Bethesda, MD 20892 Telephone: (301) 594-7448 FAX: (301) 594-7407 or 594-7424 Direct inquiries regarding fiscal matters to: Raymond L. Zimmerman Division of Extramural Affairs National Heart, Lung, and Blood Institute Westwood Building, Room 4A17 Bethesda, MD 20892 Telephone: (301) 594-7420 FAX: (301) 594-7492 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance, No. 93.838. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or to review by a Health Systems Agency. $$R4 END ************************************************************ $$R5 BEGIN HS-94-001 FULL-TEXT ************************************** GRANTS FOR HEALTH SERVICES DISSERTATION RESEARCH NIH GUIDE, Volume 22, Number 31, August 27, 1993 RFA AVAILABLE: HS-94-001 P.T. 34; K.W. 0730050 Agency for Health Care Policy and Research Application Receipt Date: January 24, 1994 THIS IS A NOTICE OF AVAILABILITY OF A REQUEST FOR APPLICATIONS (RFA); IT IS ONLY AN ABSTRACT OF THE RFA. POTENTIAL APPLICANTS MUST REQUEST THE COMPLETE RFA, WHICH CONTAINS ESSENTIAL INFORMATION FOR THE PREPARATION OF AN APPLICATION, FROM THE CONTACT LISTED IN "INQUIRIES," BELOW. FAILURE TO FOLLOW THE INSTRUCTIONS IN THE COMPLETE RFA MAY RESULT IN AN INCOMPLETE APPLICATION, WHICH WILL BE RETURNED TO THE APPLICANT WITHOUT REVIEW. PURPOSE The Agency for Health Care Policy and Research (AHCPR) announces the availability of an RFA for grants for health services dissertation research. The AHCPR conducts and supports research that will enhance the quality, appropriateness, and effectiveness of health care services and access to such services. The provision of dissertation grant support is part of the effort of the AHCPR to stimulate the development of innovative and timely research on issues related to the delivery of health care services. Grant support is designed to aid the career development of new health services researchers and to encourage individuals from a variety of academic disciplines and programs to study complex issues with respect to health care services. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. The AHCPR urges applicants to submit grant applications with relevance to the specific health services research objectives of this initiative. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0 or Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS A student applying for a dissertation research grant, the Principal Investigator (PI), must be enrolled in an accredited doctoral degree program in the social, management, medical, or health sciences. The PI also must be conducting or intending to conduct dissertation research on issues related to the delivery of health care services as described below. The proposed PI must be a registered doctoral candidate in resident or nonresident status. All requirements for the doctoral degree other than the dissertation must be completed by the time of the award. Prior to submission of the application, the dissertation proposal must be approved by the dissertation faculty committee and certified by the faculty advisor. The applicant may be either the institution that will administer the grant on behalf of the proposed PI or the proposed PI applying as an individual. Applications from women and minority investigators are encouraged. A proposed PI for dissertation research grant support need not be a U.S. citizen. However, a PI who is not a U.S. citizen and does not have a permanent resident visa must apply through an institution. Also, an application from a student enrolled in a foreign institution will be accepted provided that the application is in English and the investigator applies through an institution. A PI who receives support for dissertation research under a grant from AHCPR may not at the same time receive support under a predoctoral training grant or fellowship grant awarded by any other agency of the U.S. Department of Health and Human Services. MECHANISM OF SUPPORT This RFA will use the small grant (R03) mechanism. Responsibility for the planning, direction, and execution of the proposed project will be solely that of the proposed Principal Investigator. The total direct costs must not exceed $20,000 for the entire project period. An application that exceeds this amount will be returned to the applicant. The proposed PI may request support only for the amount of time necessary to complete the dissertation. A dissertation research grant usually is awarded for a period of 12 months or less, but may be awarded for up to 17 months. FUNDS AVAILABLE The AHCPR expects to award up to $500,000 in Fiscal Year 1994 to support about 20 dissertation research projects. The number of awards will be contingent on the availability of funds and the quality of the applications. RESEARCH OBJECTIVES Only applications that propose studies in areas identified in section 902 of the Public Health Service Act are eligible for support. Areas of health services research authorized under section 902 in which AHCPR is interested in dissertation grants include: o Effectiveness, efficiency, and quality of health care services; o Outcomes of health care services and procedures; o Clinical practice, including primary care and practice-oriented research; o Health care costs, productivity, and market forces; o Health care technologies, facilities, and equipment; o Health promotion and disease prevention; o Medical liability; o AIDS/HIV infection with respect to issues of access and delivery of health care services; o Rural health services; and o Health of low-income, minority, elderly, and other underserved populations. Applicants are encouraged to discuss the general policy priority of their research topics by letter or by phone with AHCPR staff listed under INQUIRIES. SPECIAL REQUIREMENTS Allowable Costs Expenses usually allowed under PHS research grants will be covered by AHCPR dissertation research grants. Allowable costs include: the investigator's salary; direct project expenses such as travel, data processing, and supplies; and, for institutional applicants only, indirect costs. Fees for maintaining matriculation or other fees imposed on those preparing dissertations are allowable costs, provided the fees are required of all students of similar standing regardless of the source of funding. Applicants are expected to work full time on the project. Any level of effort that is less than full time must be fully justified. For the purpose of calculating indirect costs, dissertation research grants are considered to be training grants. Therefore, in accordance with PHS policy, indirect costs, payable only when the applicant is an institution, are limited to eight percent of total allowable direct costs exclusive of tuition and related fees and expenditures for equipment, or at the institution's actual indirect cost rate, whichever results in a lesser dollar amount. Other Conditions The following conditions apply to dissertation grants: o A Principal Investigator who discontinues or suspends a project From owner-sci-resources@net.bio.net Thu Aug 26 23:00:00 1993 Path: biosci!NET.BIO.NET!kristoff From: kristoff@NET.BIO.NET (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: IMPORTANT BIOSCI INFORMATION Message-ID: Date: 27 Aug 93 02:46:54 GMT Sender: kristoff@net.bio.net Distribution: bionet Lines: 244 Approved: sci-resources-moderator@net.bio.net Three important items follow: BIOSCI archive searching by e-mail, the BIOSCI FAQ, and the BIOSCI User Address Directory form. If you have not yet listed yourself in our e-mail address directory, please take a few minutes to complete and return the form below. If your address information has changed since you listed yourself, please send us an updated form. Sincerely, Dave Kristofferson BIOSCI/bionet Manager kristoff@net.bio.net **** SEARCHING BIOSCI ARCHIVES WITH WAISMAIL **** E-mail users can search the BIOSCI archives by using our waismail e-mail server. For instructions send the message help to waismail@net.bio.net. Leave the Subject: line blank. Other methods of searching the archives via WAIS and gopher are described in the BIOSCI FAQ. **** BIOSCI FREQUENTLY ASKED QUESTIONS (FAQ) SHEET **** New users of BIOSCI/bionet may want to read the "Frequently Asked Questions" or "FAQ" sheet for BIOSCI. The FAQ provides details on how to participate in these forums and is available for anonymous FTP from net.bio.net [134.172.2.69] in pub/BIOSCI/biosci.FAQ. It may also be requested by sending e-mail to biosci@net.bio.net (use plain English for your request). The FAQ is also posted on the first of each month to the newsgroup BIONEWS/bionet.announce immediately following the posting of the BIOSCI information sheet. **** BIOSCI USER ADDRESS DIRECTORY **** Please take this opportunity to add your name and address information to the BIOSCI User Address Database if you have not already done so. Below is the address form that we would like each reader of the BIOSCI/bionet newsgroups to complete and return if you would like to be listed in our database. The database serves as a directory that enables biologists, who are currently using (or even just reading) the BIOSCI newsgroups, to look up e-mail addresses and other information about our users. The address database is reindexed nightly for WAIS and waismail access (waismail is our WAIS e-mail server, more below) and will also be available for access via other gopher sites if they wish to permit it. The raw unindexed data is available for FTP from net.bio.net and is atomized sufficiently to allow import into your local RDBMS should you so desire. Please carefully follow the instructions for completing the form below and return it to either of the following two addresses (whichever is more convenient for you). Thanks in advance for taking the time to complete and return the form. Addresses for returning forms Location Network ----------------------------- -------- ------- biovote@net.bio.net U.S.A. Internet/BITNET biovote@daresbury.ac.uk U.K. JANET MAKING SURE THAT YOUR INFORMATION IS CURRENT This notice will be mailed bimonthly to each newsgroup. You should check our WAIS source or waismail e-mail server from time-to-time to see if your address information is still up-to-date. Send the message help to waismail@net.bio.net for instructions on using waismail. Leave the Subject: line in your message blank. Using Gopher to complete the form --------------------------------- If you don't want to use a text editor, you can also use Dan Jacobson's gopher site to fill out the address database form as follows. Otherwise skip this section on gopher and proceed to the instructions for filling out the form below. > To add yourself to the database just point your > gopher client at merlot.welch.jhu.edu and select the following: > > --> 15. Searching For Biologists/ > > --> 9. E-mail Addresses of Biosci-Bionet Users/ > > --> 1. Add (or Correct) Your Address to the BIOSCI User Address > Data.. > > > And fill out the form. or Rob Harper's gopher site in Europe as follows: > Europeans can point their gopher client at gopher.csc.fi and add their > information to the database. All entries will be mailed directly to > Dave for incorporation in a wais source. > > The path to the questionare is as follows. > > ---> 10. Finnish EMBnet BioBox/ > > ---> 8. FAQ Files/ > > FAQ Files > > 1. EMBnet: Information. > 2. EMBnet: Internet resources guide. > 3. A Biologist's Guide to Internet Resources/ > 4. All FAQs (Frequently Asked Questions) Searches and Archives/ > --->5. Bionauts Address Database (questionaire) IMPORTANT INSTRUCTIONS - PLEASE READ CAREFULLY Please enter all responses after the : on each line, leaving one (1) blank space after the : (i.e., before the start of your text). Please do NOT extend your responses past the end of each line (80 characters) or alter any of the field identifiers such as "first name: ". Several lines are provided at the end of the form for comments, but, please adhere to the line length restriction. On the date: line, please enter the date in the DD-MM-YY format, e.g., 05-05-93 for 5 May 1993. This line will tell others when the information was last updated. Please be sure to include the 0's for single digit days or months, e.g., 05-05-93, not 5-5-93. Note that the "e-mail network: " line below is for specifying, e.g., "Internet," "BITNET," "EARN," "JANET," or whatever other network that your computer may be on. If you are uncertain about any field, please feel free to leave it blank, but please DO NOT DELETE the field identifier from the form! In the first field below, "New information or Update ...", please enter "N" if this is the first time that you have registered in the directory or "U" if you are correcting a listing that you sent to us previously. The comment: lines may be used for anything that you like but PLEASE DO NOT DELETE THEM FROM THE FORM OR ALTER THEM. One suggested use is to list the names of the newsgroups in which you participate. Please use the MAILING LIST name (see below - the latest version of the list can be requested from biosci@net.bio.net) instead of the USENET name even if you don't participate by e-mail. WAIS might get confused by the periods in the USENET names. This allows one to retrieve via WAIS or waismail the list of participants in a particular group. For example: comment: ARABIDOPSIS PLANT-BIOLOGY BIONEWS On the comment: lines use these names below ---- NOT the USENET names below MAILING LIST NAME USENET Newsgroup Name ----------------- --------------------- ACEDB-SOFT bionet.software.acedb AGEING bionet.molbio.ageing AGROFORESTRY bionet.agroforestry ARABIDOPSIS bionet.genome.arabidopsis BIOFORUM bionet.general BIO-INFORMATION-THEORY bionet.info-theory BIONAUTS bionet.users.addresses BIONEWS bionet.announce BIO-JOURNALS bionet.journals.contents BIO-MATRIX bionet.molbio.bio-matrix BIO-SOFTWARE bionet.software CHROMOSOMES bionet.genome.chromosomes COMPUTATIONAL-BIOLOGY bionet.biology.computational DROSOPHILA bionet.drosophila EMBL-DATABANK bionet.molbio.embldatabank EMPLOYMENT bionet.jobs GDB bionet.molbio.gdb GENBANK-BB bionet.molbio.genbank GENETIC-LINKAGE bionet.molbio.gene-linkage HIV-MOLECULAR-BIOLOGY bionet.molbio.hiv HUMAN-GENOME-PROGRAM bionet.molbio.genome-program IMMUNOLOGY bionet.immunology INFO-GCG bionet.software.gcg JOURNAL-NOTES bionet.journals.note METHODS-AND-REAGENTS bionet.molbio.methds-reagnts MOLECULAR-EVOLUTION bionet.molbio.evolution NEUROSCIENCE bionet.neuroscience N2-FIXATION bionet.biology.n2-fixation PHOTOSYNTHESIS bionet.photosynthesis PLANT-BIOLOGY bionet.plants POPULATION-BIOLOGY bionet.population-bio PROTEIN-ANALYSIS bionet.molbio.proteins PROTEIN-CRYSTALLOGRAPHY bionet.xtallography RAPD bionet.molbio.rapd SCIENCE-RESOURCES bionet.sci-resources TROPICAL-BIOLOGY bionet.biology.tropical VIROLOGY bionet.virology WOMEN-IN-BIOLOGY bionet.women-in-bio YEAST bionet.molbio.yeast Listing newsgroups on the comment: line is optional, of course. Thanks again for your cooperation! --------------- please cut here and return portion below --------------- New information or Update to old record (enter N or U): date (DD-MM-YY): first name: middle initial: family name: job title: e-mail address: e-mail network: phone number: FAX number: institution: address1: address2: address3: city: state/province: country: postal code: research interest: research interest: comment: comment: comment: comment: comment: From owner-sci-resources@net.bio.net Thu Aug 26 23:00:00 1993 Path: biosci!net.bio.net From: kristoff@net.bio.net (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 22, no. 31, pt. 3, 27 August 1993 Message-ID: Date: 27 Aug 93 03:26:36 GMT Sender: kristoff@net.bio.net Lines: 1041 Approved: biosci-moderator@net.bio.net $$XID RFA HD94008 HD-94-008 P1O1 *************************************** HISPANIC CHILD HEALTH: SOCIAL, BEHAVIORAL, AND CULTURAL FACTORS NIH GUIDE, Volume 22, Number 31, August 27, 1993 RFA: HD-94-008 P.T. 34, FD; K.W. 0404000, 0417000, 0413001, 0413003 National Institute of Child Health and Human Development Application Receipt Date: January 7, 1994 PURPOSE The Demographic and Behavioral Sciences Branch (DBS) of the Center for Population Research, National Institute of Child Health and Human Development (NICHD) is inviting grant applications for the support of research on social, demographic, behavioral, and cultural factors in Hispanic child health. The purpose of the Request for Applications (RFA) is to encourage theoretically and methodologically innovative research to address scientific issues among the Hispanic population and to better address the needs of its children. Issues of interest are (a) factors that promote low rates of infant mortality and chronic disease in some Hispanic subgroups, despite the experience of racism and poverty by this population; (b) how the experience of migration, its antecedents and consequences, affects the health of Hispanic subgroups and their children; (c) how trends in fertility and mortality may change over time and space in response to changing characteristics of the population; and (d) factors that have led to different health outcomes among different Hispanic subpopulations, and to differences in the social, demographic, behavioral, and biological predictors of those outcomes. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy people 2000", a PHS-led national activity for setting priority areas. The RFA, Hispanic Child Health: Sociodemographic, Behavioral and Cultural Factors, is encouraging research that has implications for the objectives targeting Hispanics. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-004734-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of States or local government and eligible agencies of the Federal government. Applications from minority individuals and women are encouraged. Domestic applications may include an international component. MECHANISM OF SUPPORT This RFA will use the National Institutes of Health (NIH) individual research grant (R01) and the FIRST (R29) awards. Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. The total project period for applications submitted in response to the present RFA may not exceed five years. This announcement is for a single competition with the application receipt deadline of January 7, 1994. The anticipated award date is August 1, 1994. Because the nature and scope of the research proposed in response to this RFA may vary, it is anticipated that the size of an award will vary also. This RFA is a one time solicitation. Future unsolicited competing continuation applications will compete with all investigator-initiated applications and be reviewed according to the customary peer review procedures. FUNDS AVAILABLE $900,000 in direct costs are set aside for the first year of support. It is anticipated that six grants will be made from NICHD funds. It is anticipated that only new applications will be received. The level of support is dependent on the receipt of a sufficient number of applications of high scientific merit. Although this program is provided for in the financial plans of the NICHD, awards pursuant to this RFA are contingent upon the availability of funds for this purpose. RESEARCH OBJECTIVES Background This RFA is a response to a request the U.S. Congress addressed to the NICHD. In Report No. 102-708, the House of Representatives Committee on Appropriations expressed concern about the health of Hispanic children in the United States. The Committee urged NICHD to increase research in this area. The report language stated the rationale for this research effort as follows: "Hispanics differ from other groups in rates of infant mortality, adolescent pregnancy, risk-taking behavior, chronic childhood illness, and childhood obesity. The high rates of poverty experienced by many Hispanic mothers and children may contribute to these problems. The duration of time living in the U.S. also appears to be a problem related to the incidence of poor health." This RFA also responds to the report, "One Voice, One Vision -- Recommendations to the Surgeon General to Improve Hispanic Health." The Research Agenda of the Surgeon General's National Hispanic/Latino Health Initiative identified the need for culturally appropriate theoretical frameworks and research methodologies to address the unique research needs of the diverse Hispanic/Latino population groups. Copies of the report may be obtained from the Office of the Surgeon General, Department of Health and Human Services, 200 Independence Avenue, SW, Washington, DC 20201 (telephone 202-690-7163). This RFA is also partially an outgrowth of a 1987 initiative by the NICHD, titled "Social and Demographic Research on Infant Mortality and Low Birthweight." Research conducted under that RFA has addressed some of the demographic, social, and behavioral issues related to the health of Hispanic, particularly Mexican-American, women and children. Other The purpose of this RFA is to address the sociodemographic, behavioral, and cultural factors that affect child health among Hispanic subpopulations in the United States. Individuals of Central or South American, Cuban, Mexican, Puerto Rican, or some other Spanish origin are considered to be Hispanic, regardless of race. Variations within subgroups may be as important as variations among them. Contrasts may also be drawn between U.S. groups and those in the countries of origin if they shed light on the experience of U.S. populations. Child health refers to characteristics of children ages 0-17 that can affect the likelihood of attaining full growth, optimal development and well-being. In so far as reproductive or family health and behavior, including fertility or maternal or paternal behavior, may affect child health, it is within the scope of this RFA. The intent of the RFA is to direct attention to the social, behavioral, and cultural factors that affect child health rather than to pathological or clinical conditions, per se. The Hispanic population in the U.S. is characterized by a relatively young age structure, high fertility, and a diversity of culture, economic well-being, and educational and labor market experience. While the experiences of some subgroups, such as the Hispanics of New Mexico, are deeply rooted, others have experienced rapid change. The majority of U.S. Hispanics have long been concentrated in the Southwestern states, but the composition of this population has changed in recent years with a new influx of immigrants from Central America as well as from Mexico. Other major Hispanic communities, in South Florida, and in the Northeastern states, have also altered in composition with the addition of new immigrants. Rapid population growth in some areas has strained social, health, and educational resources. While the majority of Hispanics in the U.S. are urban, background factors for child health may operate differently for rural or migrant populations. Populations who live along the U.S.-Mexico border experience a unique constellation of economic, legal, ecologic, and cultural factors which can affect child health. Proximity to the border may affect a range of choices (e.g., health care, jobs, family responsibilities) that individuals make, as well as the structural factors that condition those choices. In addition to geographic variation, there is evidence that the culture, behavior, demographic and health characteristics of Hispanic origin populations change with duration of residence in the United States. It has been suggested that the health conditions of some immigrants may worsen over time as they adopt the behaviors of people born in the United States. There is also evidence that the fertility of Hispanic women changes by generation in the U.S. Some changes and adaptations to United States culture and norms may be beneficial (increased positive valuation of education for women), but countervailing changes may worsen health outcomes (e.g., increase in substance use). Research is needed that describes how and why duration of residence in the U.S. is related to health outcomes. Until fairly recently, the unique historical, migratory, and cultural experience of each Hispanic subpopulation has been ignored, but recognition of these is a central focus of this RFA. An important way to advance our understanding of the health of the Hispanic population is to move away from using ethnicity as a simple identifier to a multi-dimensional characterization. Improvements in conceptualizations of ethnic identity, as they affect health outcomes, are called for. To achieve a deeper understanding of Hispanic subpopulation characteristics and how they affect child health, a range of methods may be used, either singly or in combination. These can be demographic, econometric, or epidemiological, and/or they may be triangulated with ethnographic methods or historical or archival data. The use of ethnographic methods may be particularly appropriate for an improved understanding of the cultural factors that contribute to Hispanic child health. Interdisciplinary research is encouraged. Additional examples of relevant research topics include, but are not limited to: o Household and kinship structures among Hispanics have long interested U.S. sociologists and epidemiologists because of the presumed positive effect of these structures on health and mortality. Recent evidence suggests that extended households may be formed by need as well as preference. Additional research is needed to determine to what extent these structures represent economic or cultural choices, and how they are affected by changes in age structures, labor markets, and internal and external migration. How do different types of household and kin structures affect child health? o Some, but not all, U.S. Hispanics are involved in cyclical migration, for example between Puerto Rico and the mainland, or between Mexico and the U.S. Other Hispanics are involved in internal migration, as agricultural laborers or as labor markets form and reform. How do these different types of migration affect health, particularly children's health, either indirectly through parental health and demographic behavior, or directly? How does access to education and health services modify the effects of migration on health? o Many researchers have identified the paradox that, despite their relative poverty and lower educational attainment, infants born to mothers of Mexican descent have low birth weight and infant mortality rates that are similar to those of non-Hispanic whites. These rates increase for Mexican-origin mothers born in the U.S. This pattern parallels that for chronic disease mortality, and may be related to transcultural changes in maternal nutrition and/or substance use. Insightful research is needed to explore the separate and joint effects of socioeconomic, behavioral, cultural, and biological factors on the perinatal and infant outcomes of Hispanic infants. o Patterns of residential segregation in the U.S. by race and ethnicity have been well documented. At the same time, a new array of conceptual and methodological tools are encouraging researchers to address other contextual influences on demographic behavior and health. Family structure and health practices may mediate these contextual influences on children's health and well-being, or they may have direct effects. Contextual influences may be sociodemographic, such as percentage of households in poverty, or degree of residential segregation; they may be behavioral, such as proportion who attend church regularly; they may be cultural, such as shared understanding of gender roles, or valuation of parenthood. Research is needed that addresses these relationships for U.S. Hispanics, and takes into account some of the unique characteristics of Hispanic subgroups and their neighborhoods. o Among Hispanic adolescents there is an excess of behaviorally related morbidity and mortality, including sexually transmitted disease, and injuries and deaths due to violence and accidents. Since 1988 there has been a large percentage increase in births to Hispanic females ages 15-19; early childbearing carries a somewhat greater medical risk for the infant, and limits the educational, marital, and occupational opportunities of the young parents. Research is needed on the cultural and behavioral antecedents of these outcomes. How do concepts of gender-appropriate roles and behaviors influence the choices and constraints experienced by Hispanic adolescents? To what extent are they influenced by family structure and relationships, or by features of the adolescent's community? o Many Hispanics enter the U.S. with lower levels of education than other immigrants. Once in the United States, Hispanics are less likely to graduate from secondary school or college than African-Americans or non-Hispanic whites. Research is needed to clarify the role of schooling, particularly in relation to adolescent health. What are the factors affecting transitions from school to work to family formation among Hispanics? Are there other life course orderings or transitions that are normative for Hispanics, and how do these affect health? Are there specific aspects of schooling, such as language barriers, that facilitate or impede the health of Hispanic children? o Family centeredness or "familism" is often identified as a health-protective factor among Hispanics. Research is needed to identify the factors that facilitate or constrain familism. These could range from policies (governmental supports and programs) to regional or local geopolitical or economic conditions, or neighborhood features, as well as the structures and characteristics of families themselves. In these contexts, how do men and women balance family roles and make choices about the use of time and other resources? In turn, how do these factors affect child health? One of the major issues in conducting research on Hispanic subpopulations is the problem of sample size. While there may be sufficient numbers of Mexican- or Puerto Rican-Americans in some data sets, there may be insufficient numbers of Central Americans or Cubans. The following data sets have been supported by the NICHD and contain Hispanic samples of varying sizes: the National Longitudinal Survey of Youth, the 1988 National Maternal and Infant Health Survey, the National Survey of Families and Households, the National Survey of Family Growth, and the Hispanic Health and Nutrition Survey. Other possible data sets are the 1988 Puerto Rico Fertility and Family Planning Assessment, the 1985-86 New York Fertility, Employment, and Migration Survey, the National Educational Longitudinal Survey, or Bureau of the Census data sets such as the Survey of Income and Program Participation and the Current Population Survey. Respondents to this RFA may want to consider use of one or more of these data sets alone or in combination with other forms of data collection. They may propose collecting their own data, performing secondary analysis of other data sets, or using ethnographic data. SPECIAL REQUIREMENTS Annual meetings will be held to foster the sharing of information, data, and other research experiences. Principal Investigators are encouraged to attend these meetings, and funds must be included in the application budget for one two-day meeting per year in Bethesda, Maryland to discuss the research with other investigators. A statement about the willingness to engage in annual meetings should be included with the application. STUDY POPULATIONS Research should focus primarily on U.S. populations although non-U.S. populations may be used to the extent that they increase our understanding of U.S. Hispanics. The ultimate objective of this RFA is to improve our understanding of child health in the U.S. Children are considered to be age 17 years and under; thus young and middle adolescents are included. The study population may be adults since many of the research issues pertinent to child health and well-being require an understanding of the adult population. Non-Hispanics may be included for comparative purposes. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS For projects involving clinical research, NIH requires applicants to give special attention to the inclusion of women and minorities in study populations. The focus of this RFA is one U.S. minority group, Hispanic-Americans. Other minorities may be included for comparison purposes but should not be the focus of the application. If women are not included in the study population, a specific justification for the exclusion must be provided. Applications without such documentation will not be accepted for review. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues must be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information must be included in the form PHS 398 (rev. 9/91) in Sections 1-4 of the Research Plan AND summarized in Section 5, Human Subjects. For the purpose of this policy, clinical research is defined as human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including, but not limited to, clinical trials. If the required information is not contained within the application, the application will be returned. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. APPLICATION PROCEDURES Applications are to be submitted on form PHS 398 (rev. 9/91) that is available in most institutional offices of sponsored research and from the Office of Grants Information, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449 Bethesda MD 20892, telephone (301) 594-7250. FIRST (R29) award applications must include at least three sealed letters of reference attached to the face page of the original application. FIRST (R29) award applications submitted without the required number of reference letters will be considered incomplete and will be returned without review. Applications must be identified by checking the "YES" box in Item 2a on the face page of the application and by typing the words, "In Response to RFA HD-94-008." The RFA label in form PHS 398 must be affixed to the bottom of the face page of the original application. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. The signed typewritten original (topmost), including the Checklist, and three signed copies of the applications must be sent or delivered in one package to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** It is extremely important for the timely review of your application that two additional be sent under separate cover to: Susan Streufert, Ph.D. Division of Scientific Review National Institute of Child Health and Human Development 6100 Executive Boulevard, Room 5E03 Bethesda, MD 20892 Telephone: (301) 496-1485 Applications must be received by January 7, 1994. Late applications will not be accepted. If an application is received after that date, it will be returned to the applicant without review. Review Considerations Upon receipt, applications will be reviewed by NICHD staff for completeness and responsiveness to the RFA. Incomplete applications will be returned to the applicant without further consideration. If the application is judged to be non-responsive to the RFA, NIH staff will return the application to the applicant. The applicant may resubmit the application and have it assigned for review in the same manner as unsolicited grant applications during the next review cycle. If the application submitted in response to this RFA is substantially similar to a grant application already submitted to the NIH for review, but has not yet been reviewed, the applicant will be asked to withdraw either the pending application or the new one. Simultaneous submission of identical applications will not be allowed, nor will essentially identical applications be reviewed by different review committees. Therefore, an application cannot be submitted in response to this RFA that is essentially identical to one that has already been reviewed. This does not preclude the submission of substantial revisions of applications already reviewed, but such applications must include an introduction addressing the previous critique. Applications may be triaged by an NICHD peer review group on the basis of relative competitiveness. The NIH will withdraw from further competition those applications judged to be non-competitive for award and notify the applicant Principal Investigator and institutional official. Those applications judged to be competitive will undergo further scientific merit review by a special study section convened by NICHD in accordance with the criteria stated below. The second level of review will be provided by the NICHD National Advisory Council. The review criteria for the research projects are generally the same as those for unsolicited research grant applications: o scientific and technical significance of proposed research; o appropriateness and adequacy of the research approach and methodology proposed to carry out the research; o qualifications and research experience of the Principal Investigator and staff, particularly, but not exclusively, in the area of the proposed research; o availability of resources necessary to perform the research; o appropriateness of the proposed budget and duration in relation to the proposed research. In addition, applications will be judged on the significance and appropriateness of the research problem and methods to the Hispanic population of the U.S. AWARD CRITERIA The anticipated date of award is August 1, 1994. Responsiveness to the RFA, scientific merit, and technical proficiency, as described in the application, will be the predominant criteria for determining funding. An attempt will be made to ensure that different Hispanic sub-groups and a diversity of subject matter will be represented in the applications receiving awards. INQUIRIES Written and telephone inquiries are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Nancy E. Moss, Ph.D. Center for Population Research National Institute of Child Health and Human Development 6100 Executive Boulevard, Room 8B13 Bethesda, MD 20892 Telephone: (301) 496-1174 Direct Inquiries regarding fiscal matters to: Melinda B. Nelson Office of Grants and Contracts National Institute of Child Health and Human Development 6100 Executive Boulevard, Room 8A17 Bethesda, MD 20892 Telephone: (301) 496-5481 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.864 and No. 93.866. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$XID RFA HL93021 HL-93-021 P1O1 *************************************** HIV AND CELLULAR INFILTRATIVE DISEASE IN THE LUNG NIH GUIDE, Volume 22, Number 31, August 27, 1993 RFA: HL-93-021 P.T. 34; K.W. 0715008, 0715165, 0755030, 1002004, 1002008 National Heart, Lung, and Blood Institute Letter of Intent Receipt Date: December 10, 1993 Application Receipt Date: January 14, 1994 PURPOSE The National Heart, Lung, and Blood Institute (NHLBI) invites grant applications for support of research on understanding cellular infiltrative disease in the lung associated with infection by the human immunodeficiency virus (HIV). The primary objectives of this special grant program are to determine the etiology of inflammatory cell infiltration and proliferation in the lung and to understand the cellular and molecular mechanisms involved in the development of lymphoid and nonspecific interstitial pneumonitis associated with HIV infection. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This Request for Applications (RFA), HIV and Cellular Infiltrative Disease in the Lung, is related to the priority areas of maternal and infant health, HIV infection, sexually transmitted diseases, and immunization and infectious diseases. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Among the disciplines and expertise that may be appropriate for this research program are cell biology, virology, molecular biology, immunology, molecular immunology, infectious diseases, pathology, and pulmonary medicine. Applications may be submitted by domestic and foreign for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Foreign institutions are not eligible for the First Independent Research Support and Transition (FIRST) (R29) award. Applications from minority individuals and women are encouraged. All current policies and requirements that govern the research grant programs of the National Institutes of Health (NIH) will apply to grants awarded under this RFA. Awards under this announcement to foreign institutions will be made only for research of very unusual merit, need, and promise, and in accordance with PHS policy governing such awards. MECHANISM OF SUPPORT The support mechanism for this program will be the NIH individual research project grant (R01) and the FIRST award (R29). While multidisciplinary approaches are encouraged, it is not the intent of this announcement to solicit applications for large studies encompassing a variety of individual subprojects, i.e., program projects. If collaborative arrangements through subcontracts with other institutions are planned, consult the program staff listed under INQUIRIES. Upon initiation of the program, the NHLBI will sponsor periodic meetings to encourage exchange of information among investigators who participate in this program. In the budget for the grant application, applicants should request travel funds for a one-day meeting each year, most likely to held in Bethesda, MD. Applicants should also include a statement in their applications indicating their willingness to participate in these meetings. Applicants (who will plan and execute their own research programs) are expected to furnish their own estimates of time required to achieve the objectives of the proposed research project. Up to five years of support may be requested for R01s; five years are required for FIRST awards. Requested budgets for FIRST awards may not exceed those specified in the FIRST award guidelines. Since a variety of approaches would represent valid responses to this announcement, it is anticipated that there will be a range of costs among individual grants awarded. This RFA is a one-time solicitation. Future unsolicited competing continuation applications may be submitted for peer review and competition for support through the regular grant program of the NIH. It is anticipated that support for this program will begin in July 1994. Administrative adjustments in project period and/or amount may be required at the time of the award. Applicants from institutions that have a General Clinical Research Center (GCRC) funded by the National Center for Research Resources may wish to identify the GCRC as a resource for conducting the proposed research. If so, a letter of agreement from either the GCRC program director or Principal Investigator should be included with the application. FUNDS AVAILABLE Although approximately $1,500,000 for this program is included in the financial plans for fiscal year 1994, award of grants pursuant to this RFA is contingent upon receipt of funds for this purpose. It is anticipated that six to eight new grants will be awarded under this program. The specific number to be funded will, however, depend on the merit and scope of the applications received and the availability of funds. RESEARCH OBJECTIVES Background Pulmonary disorders continue to be one of the most frequent medical consequences of infection with HIV. Although pulmonary infections such as Pneumocystis carinii pneumonia, bacterial pneumonia, and viral pneumonia represent the major portion of these disorders, a number of interstitial infiltrative processes that cannot be directly linked to a known infectious agent also occur frequently in HIV-infected individuals. Two prominent types of interstitial processes distinguished by their clinical and pathologic features have been recognized in association with HIV infection. The first disorder is lymphoid interstitial pneumonitis/pulmonary lymphoid hyperplasia complex (LIP/PLH), which is much more commonly associated with chronic pulmonary infiltrates in HIV-infected children than it is in HIV-infected adults. Lymphoid interstitial pneumonitis is characterized by infiltration of the lung by a pleomorphic mixture of lymphocytes, plasma cells, and immunoblasts. Although the etiology of the process is unknown, it is postulated that it involves recognition of a specific antigen by host lymphocytes, the activation of T-cells, increased production of lymphokines, and a rapid increase in effector cells that is responsible for tissue damage. This type of lymphocytic interstitial pneumonitis, known sometimes to accompany other disorders of the immune system such as dysproteinemias and autoimmune diseases, was identified early in the HIV epidemic as a common finding in HIV-infected individuals, especially children. Information on the frequency with which LIP/PLH occurs is limited. In early reports, lymphoid interstitial pneumonitis, which is an AIDS defining condition in children under 13 years of age, was associated with 50 to 78 percent of pulmonary complications in children with HIV infection. In more recent studies, LIP/PLH has been identified in 20 to 30 percent of pediatric AIDS patients. Although benign in individuals without HIV infection, LIP/PLH in HIV-infected individuals may result in progressive pulmonary disease, characterized clinically by dyspnea, cough, abnormal chest films, hypoxemia and a restrictive defect in lung function. Some HIV-infected patients with LIP/PLH eventually develop lymphoid malignancies involving the lung. A second frequently occurring infiltrative disorder associated with HIV infection is nonspecific interstitial pneumonitis (NIP), which is less well characterized than LIP/PLH and occurs with equal frequency in children and adults. Nonspecific interstitial pneumonitis in HIV-infected persons is characterized by lymphocyte infiltration, interstitial edema, mononuclear cell infiltration, alveolar type II cell proliferation, and loose interstitial fibrosis. The prevalence of NIP in HIV-infected individuals with pulmonary disease has been reported to vary from 11 to 38 percent. The lymphocytic infiltrates characteristic of NIP are comprised mainly of CD8+ T-cells with less than normal levels of CD4+ T-cells. It is unclear if the latter reflects the general diminution of CD4+ T-cells in HIV-infected individuals or is indicative of other factors involved in its pathogenesis. The infiltrates of NIP are similar to those seen in graft versus host disease and autoimmune disorders, where CD8+ T-cells also are prevalent in infiltrates. Lymphocytes can be found in the bronchoalveolar lavage (BAL) fluid in 70 to 80 percent of HIV-infected individuals without evidence of lung tumors or infection. The majority of these lymphocytes are CD8+ cytotoxic T-cells which may be active against virus-infected CD4+ T-cells and thereby contribute to the depletion of CD4+ T-cells and macrophages in the lung. Furthermore, the CD8+ cytotoxic lymphocytes contain significant amounts of serine protease which when released may contribute significantly to lung tissue destruction and subsequent morbidity. It has been suggested that lymphocytic alveolitis in HIV-infected adults may represent an early stage of LIP/PLH or NIP, but this needs to be documented and the mechanism for this process needs to be investigated. Other Objectives and Scope The overall objective of this initiative is to encourage basic research on the etiology, mechanisms of pathogenesis, and the host determinants that are involved in the initiation and progression of interstitial infiltrative diseases in the lung associated with HIV infection. Applications are invited for innovative multidisciplinary approaches to identify the cause of these disorders and to delineate cellular and molecular mechanisms involved in their pathogenesis. Applications submitted in response to this announcement should clearly define the rationale, background, and specific aims of the proposed studies, and should provide a succinct description of the methods and procedures to be used. Several topics relevant to the objectives of this RFA are cited below in order to provide a perspective of the scope of the research that would meet the goals of the program. Investigators are also encouraged to consider other approaches that meet the goals of this program in addition to those cited below. A. Pathogenesis The finding of HIV reverse transcriptase activity in bronchoalveolar lavage fluid from HIV positive patients with LIP/PLH and correlation of HIV activity and the presence of anti-HIV antibodies in lavage fluid with cytopathic effects in human lung tissue from LIP/PLH patients suggest that the infiltrative processes may be initiated by an immunologic response to HIV infection of the lung itself. Whether or not HIV infection initiates these processes and how much of their pathogenesis results from HIV infection remain to be determined. Some investigators have suggested an interaction of HIV with other infectious agents acting as cofactors as a major determinant in the development and progression of the infiltrative process seen in these disorders. Experimental evidence for this so-called "co-factor hypothesis" and its bearing on the pathogenesis of LIP/PLH or NIP would be an appropriate area of study in response to this initiative. Whether an as yet unrecognized infectious agent is responsible for these disorders could be considered and might be pursued by application of new approaches for identifying such agents. For example, electron microscopic studies of viral particles associated with infiltrating lymphoid cells might provide insights into the type of agent(s) which may be present. Electron microscopy combined with immunologic techniques (immuno-EM), which have proven useful with other infectious diseases, could enhance such an approach. Investigations that employ in vitro or animal models aimed at uncovering the molecular mechanisms and pathogenesis of these disorders are of particular interest. It has been hypothesized that the infiltrative processes begin as a lymphocytic alveolitis which then progresses to either LIP/PLH or NIP. However, there are little or no data to support this concept. Thus, it is of interest to determine the relationship of lymphocytic alveolitis to these more advanced forms of infiltrative disease and to identify the factors that are involved in the progression to LIP/PLH and NIP. Studies on lymphocyte recruitment, replication, and trafficking in the lung as a consequence of HIV infection with or without cofactors present are needed. Details about the types of cells that infiltrate the lung and their state of activation relevant to the development of these conditions are essential to understanding the mechanisms involved. For example, does local proliferation of immune cells already present in the lung contribute to the pathogenesis? Identification of the cytokines involved and their regulatory pathways in the context of HIV infection is also needed to define the immunopathogenesis. Investigation of the similarities and differences of infiltrative processes in the lung in HIV-infected individuals compared to infiltrates in other immunosuppressed states, such as graft versus host disease, might also help to further delineate the role of HIV in pathogenesis. The lack of knowledge about the mechanisms contributing to the pediatric predominance of LIP/PLH suggests a number of approaches that could provide much needed basic information and could have important implications for the management and treatment of children who develop this complication. A number of studies suggest that the immaturity of the immune system is a factor in disease expression. Studies are needed to provide detail about the impact of HIV infection on the developing immune response of the lung. Does increased pediatric immune cell sensitivity to HIV infection which has been demonstrated in vitro contribute to increased susceptibility and more severe disease in these young patients? Do growth factors or other developmental factors which are present at higher levels in the body during development play a role in the pathogenesis? Are nutritional factors important determinants in the increased occurrence of LIP/PLH in children? The limited clinical data available on these infiltrative processes in the lung suggest that the course and prognosis of these diseases is quite variable. In several early studies, HIV-infected patients who developed LIP/PLH or NIP were seen to progress to either end stage fibrosis or malignancies in the lung. It has also been noted that black patients may be more predisposed to developing LIP/PLH than are white patients. Basic studies on host factors, either acquired or genetic, that affect the expression of disease or contribute to progression to more severe disease would be of interest in response to this initiative. B. Animal Models The ability to make significant progress in understanding the basic mechanisms involved in these diseases would be greatly enhanced by adaptation of this condition to animal models, especially small laboratory animals. While a sheep/lentivirus model is available, it may be of limited value for studying these disorders since it does not produce the profound immunodeficiency found in HIV infection of humans. Likewise the use of nonhuman primates for the mechanistic studies sought by this initiative would likely not provide a significant advantage over human studies. A mouse AIDS model (MAIDS) and rodent models for the study of opportunistic infections associated with HIV infection have been developed and could possibly be adapted to the study of infiltrative disease in the lung. In addition, the various immunologically defective laboratory animal models that are already available might be considered for adaptation to these studies. Clearly, additional animal models need to be developed and/or adapted to the study of these diseases if new information is to be obtained about the mechanisms involved in initiation and progression of disease. SPECIAL REQUIREMENTS Applications that propose descriptive studies and do not contain studies directed at elucidating mechanisms of disease or supporting hypotheses related to mechanisms of disease will not be acceptable. This program will not support studies directed at development of animal models alone. Models must be applied to the study of disease mechanisms associated with cellular infiltration in the lung. Applications that focus on molecular biology and molecular immunology of these disorders are of particular interest. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements will be required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis should be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale should be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues should be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information should be included in the form PHS-398 in Sections 1-4 of the Research Plan AND summarized in Section 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., Native Americans [including American Indians or Alaskan Natives], Asian/Pacific Islanders, Blacks, Hispanics). The rationale for studies on single minority population groups should be provided. For the purpose of this policy, clinical research includes human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including but not limited to clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are not subject to these policies. However, every effort should be made to include human tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. If the required information is not contained within the application, the application will be returned. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and will be reflected in assigning the priority score to the application. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. LETTER OF INTENT Prospective applicants are asked to submit, by December 10, 1993, a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, the identities of other key personnel and participating institutions, and the number and title of the RFA in response to which the application may be submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information that it contains allows NHLBI staff to estimate the potential review workload and to avoid conflict of interest in the review. Chief, Centers and Special Projects Review Section Division of Extramural Affairs National Heart, Lung, and Blood Institute Westwood Building, Room 553 Bethesda, MD 20892 Telephone: (301) 594-7448 FAX: (301) 594-7407 or 594-7424 APPLICATION PROCEDURES Submit applications on form PHS 398, (rev. 9/91), the application form for the traditional research project grant. This form is available in an applicant institution's office of sponsored research and from the Office of Grants Information, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone (301) 594-7248. Use the conventional format for research project grant applications and ensure the points identified in the section, "Review Procedures and Criteria" are fulfilled. To identify the application as a response to this RFA, check "yes" on item 2a of page 1 of the application and enter the title "HIV and Cellular Infiltrative Disease in the Lung," HL-93-021-L. The RFA label found in form PHS 398 application kit must be affixed to the bottom of the face page of the original completed application form PHS 398. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. Send or deliver the completed application and three signed photocopies in one package to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** Send two additional copies of the application to the Chief, Centers and Special Projects Review Section at the address listed under LETTER OF INTENT. It is important to send these two copies at the same time as the original and three copies are sent to the Division of Research Grants. Otherwise the NHLBI cannot guarantee that the application will be reviewed in competition for this RFA. Applications must be received by January 14, 1994. If an application is received after this date, it will be returned to the applicant without review. The DRG will not accept any application in response to this announcement that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. The DRG will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of substantial revisions of applications already reviewed, but such applications must include an introduction addressing the previous critique. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by the DRG and responsiveness to this RFA by the NHLBI. Incomplete applications will be returned without further consideration. If an application is judged unresponsive, the applicant will be contacted and given an opportunity to withdraw the application or to have it considered for the regular, investigator-initiated grant program of the NIH. Applications judged to be responsive will be reviewed for scientific and technical merit by an initial review group, which will be convened by the Division of Extramural Affairs, NHLBI, solely to review these applications. This initial review will include a preliminary evaluation to determine scientific merit relative to the other applications received in response to this RFA (triage); the NIH will withdraw from further consideration applications judged to be noncompetitive and promptly notify the principal investigator and the official signing for the applicant organization. Those applications judged to be competitive will be further evaluated for scientific/technical merit by the usual peer review procedures. Review Criteria. The factors to be considered in the evaluation of scientific merit of each application will be similar to those used in the review of traditional research project grant applications including the novelty, originality, and feasibility of the approach; the training, experience, and research competence of the investigator(s); the adequacy of the experimental design; the suitability of the facilities; and the appropriateness of the requested budget to the work proposed. AWARD CRITERIA The anticipated date of award is July 1, 1994. In addition to the scientific merit of the applications, awards will be based on responsiveness to the RFA and the availability of resources. INQUIRIES Direct inquiries regarding programmatic issues to: Hannah H. Peavy, M.D. Division of Lung Diseases National Heart, Lung, and Blood Institute Westwood Building, Room 6A09 Bethesda, MD 20892 Telephone: (301) 594-7425 FAX: (301) 594-7487 Direct inquiries regarding review matters to: Chief, Centers and Special Projects Review Section Division of Extramural Affairs National Heart, Lung, and Blood Institute Westwood Building, Room 553 Bethesda, MD 20892 Telephone: (301) 594-7448 FAX: (301) 594-7407 or 594-7424 Direct inquiries regarding fiscal matters to: Raymond L. Zimmerman Division of Extramural Affairs National Heart, Lung, and Blood Institute Westwood Building, Room 4A17 Bethesda, MD 20892 Telephone: (301) 594-7420 FAX: (301) 594-7492 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance, No. 93.838. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or to review by a Health Systems Agency. From owner-sci-resources@net.bio.net Thu Aug 26 23:00:00 1993 Path: biosci!net.bio.net From: kristoff@net.bio.net (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 22, no. 31, pt. 4, 27 August 1993 Message-ID: Date: 27 Aug 93 03:27:15 GMT Sender: kristoff@net.bio.net Lines: 899 Approved: biosci-moderator@net.bio.net $$XID RFA HS94003 HS-94-003 P1O1 *************************************** HIV COST AND SERVICES UTILIZATION STUDY NIH GUIDE, Volume 22, Number 31, August 27, 1993 RFA: HS-94-003 P.T. 34; K.W. 0730050, 0408006, 0715008 Agency for Health Care Policy and Research Letter of Intent Receipt Date: December 22, 1993 Application Receipt Date: February 22, 1994 PURPOSE The Agency for Health Care Policy and Research (AHCPR) supports and conducts health services research, including evaluations of health care systems. The purpose of this Request for Applications (RFA) is to invite applications for cooperative agreements with the AHCPR to conduct a study of utilization, cost, financing, access to, and quality of health care services for persons infected with the Human Immunodeficiency Virus (HIV). This HIV Cost and Services Utilization Study (HCSUS) is intended to provide up-to-date, policy-relevant information on the delivery of health care and associated social services to people with HIV infection. This study will develop and analyze information on the delivery of health care to persons with HIV infection in a variety of health care settings and geographic areas. In addition to the conduct of research and report of findings in the scientific literature, this project will provide analyses that have utility for meeting short-term needs for policy-relevant information. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This RFA, HIV Cost and Services Utilization Study, is related to the priority areas of HIV infection, sexually transmitted diseases, immunization and infectious diseases, and clinical preventive services. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0 or Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic, non-profit organizations, public and private, including universities, clinics, units of State and local governments, non-profit firms and foundations; or consortia of organizations, if the application is submitted by a domestic, non-profit, public or private organization. A consortium may include other types of organizations, such as for-profits. Applications from minority and women investigators are encouraged. MECHANISM OF SUPPORT The administrative and funding instrument to be used for this program will be the cooperative agreement (U01), an assistance mechanism (rather than an acquisition mechanism), in which substantial AHCPR scientific and programmatic involvement with the awardee(s) is anticipated during the performance of the activity. Under this cooperative agreement, the AHCPR seeks to support and stimulate the awardee's activity by collaborating and otherwise facilitating the activity in a partner role, while avoiding a dominant role, direction, or prime responsibility. Details of the responsibilities, relationships, and governance of the project to be funded under this cooperative agreement are listed under Terms and Conditions of Award. The total project period for applications submitted in response to this RFA may not exceed four years. The anticipated award date is July 1, 1994. Although this project is provided for in the financial plans of the AHCPR, any award(s) pursuant to this RFA is contingent upon the availability of funds for this purpose. Award of continuation funding beyond the initial budget period will depend upon availability of funds, satisfactory progress, and annual progress reviews according to customary AHCPR administrative procedures. FUNDS AVAILABLE The AHCPR expects to award a total of $15 million over four years under this RFA to one or more applicants. Up to $3 million will be available in Fiscal Year (FY) 1994 and an average of $4 million for each of the next three fiscal years. RESEARCH OBJECTIVES Background Over the preceding decade, rapid changes have occurred in the availability of services for, and the treatment of, persons with HIV infection, and in the characteristics of the population of persons newly infected with HIV. The swift pace of change means that existing data on health care services to people with HIV infection quickly become dated. Policy-makers involved in funding, establishing, developing, and managing health care programs for persons with HIV infection, as well as health care providers, their patients, and the patients' families, have a need for current information about patterns of service delivery. The ability of health care policy-makers to stay well-informed about HIV-related services delivery is limited by the rapidity with which the epidemic has evolved and complicated by wide variations in patterns of treatment across regions of the country, socioeconomic groups, and systems of health care. Most studies of health care delivery to persons with HIV infection have gathered data from a homogeneous patient group, in a single community, receiving services from a single provider; and thus do not reflect the spectrum of health care delivery systems that provide services to persons with HIV infection. Because of differences in methodology, aggregating these narrowly focused studies is rarely feasible. While the principal audience for the findings from the HCSUS will be policy-makers at the Federal, State, and local levels, HCSUS also should furnish information of interest to health care providers, health services researchers, and consumers of HIV-related health care and support services. The needs of the principal audience for timely, policy-relevant information require that the HCSUS focus on services utilization and financing, and the factors affecting them. The HCSUS is not intended to include program evaluation, community intervention, laboratory experiments, controlled trials, clinical research or efficacy studies, epidemiology, or prevention research. This project will provide information relevant to the formulation of legislation, regulation, and program administration. Mechanisms to ensure timely analyses of relevant health care policy issues are considered critical for success of the project developed under this RFA, and are discussed below in the section, SPECIAL REQUIREMENTS. The HCSUS is conceived as extending and refining the base of knowledge developed by prior studies of health care delivery to people with HIV infection. The HCSUS builds upon, but does not replicate the "AIDS Costs and Services Utilization Survey (ACSUS)" supported by the AHCPR. The ACSUS collected data about the use of health care services by HIV-infected persons during an eighteen month period. Under AHCPR auspices, Westat, Inc., the ACSUS contractor, recruited a diverse cohort of 2,090 persons with HIV infection at 26 participating sites in 10 selected cities; surveyed their quarterly use of services on six occasions between April 1991 and December 1992; and obtained supplementary data from billing, medical, and Medicaid records. Analysis of the ACSUS interview data has begun. The National Technical Information Service (NTIS) has received a public use data set containing information from the screener questionnaire administered to over 5,000 patients; persons wishing to obtain these data can call the NTIS at (703) 487-4650 and ask for "AIDS Cost and Services Utilization Survey I" (Order Number: PB93-505899GEI). An AHCPR publication describing the ACSUS study design in greater detail, (ACSUS Report 1: "Research Design and Analysis Objectives"), is available from the AHCPR Clearinghouse, (see INQUIRIES). Additional public use data sets and reports will become available in the future. Prior to the development of this RFA, the AHCPR conducted a series of discussions with public and private organizations and individuals concerned with the delivery of health care and support services to people with HIV infection. Comments and information concerning the focus and technical aspects of the proposed project were solicited. In collaboration with the Health Resources and Services Administration (HRSA), PHS, and the National Community AIDS Partnership, the AHCPR sponsored a conference in November 1992, to discuss a national agenda for HIV service delivery research and evaluation. Copies of the report of this conference, "Creating an Agenda for Research and Evaluation: HIV Service Delivery, the Ryan White CARE Act, and Beyond," are available from the AHCPR. On June 24-25, 1993, the AHCPR conducted a public meeting to solicit further advice on technical aspects of the research design of this RFA. The report of the meeting, entitled "HIV Cost and Services Utilization Study: Technical Issues," will be available to applicants. Information on obtaining the written materials noted above is provided under the section INQUIRIES. Objectives and Scope Questions concerning differences among various systems of health care delivery continue to arise and will grow in salience as proposals for health care reform are advanced. Throughout the course of the HIV epidemic, questions have been posed concerning the utilization, costs, and outcomes of care provided by different types of providers. Answers to these questions will provide decision-makers at Federal, State, and local levels with important information for the planning, development, and implementation of health care services and programs. The goals of the HCSUS are directed toward providing answers to these policy-relevant questions. The first goal of the HCSUS will be to compare the experiences of people receiving health care from different care delivery settings or systems. The HCSUS will address the question: how do health care delivery settings vary in terms of patterns of utilization, costs of care, quality of care, access to care, meeting service needs, quality of life, and patient satisfaction? The HCSUS will provide comparable data on patients receiving services from different types of care providers. Applicants should provide their own conceptualization or typology of health care settings or systems. One approach is to consider locations of care. Important settings include, but are not limited to: ambulatory HIV clinics affiliated with hospitals; health maintenance organizations (HMOs), especially Medicaid HMOs; free-standing clinics, including specialized HIV clinics, as well as community or neighborhood health centers; and community-based health care providers, including private practices. Other types of settings, such as community-based AIDS service organizations, substance abuse treatment centers, sexually transmitted disease (STD) clinics, or providers of mental health care, also may be included. Other conceptualizations of service delivery systems are possible and justifiable. Various other factors are correlated with provider type and may directly affect service utilization. These include case-mix factors: gender; race/ethnicity; HIV exposure group, such as gay and bisexual men, injecting drug users; age; and insurance status. Data on these characteristics are necessary when developing statistical models to estimate differences by type of care setting. The relationships of such characteristics to service utilization, costs, access, and quality of care also are of interest. In addition, the major or usual source of care for a given person may change over time as a result of changes in employment, insurance, or severity of illness. A second goal of the HCSUS is to investigate factors related to transitions between provider types and examine changes in utilization over time and by disease severity at the level of the individual patient. This goal includes more specific issues, such as the extent to which loss of private insurance leads to a shift from the private to the public sector, and the extent to which (and the point at which) people with symptomatic HIV infection seek and/or are referred to care provided by a specialist, rather than a generalist. People with HIV infection may use several providers of different types concurrently. Public policy has focused on expanding community-based services with the goal of reducing institutional and emergency room care. The third goal of the HCSUS is to provide information on factors that affect utilization and costs of the full array of services related to care for HIV infection and examine the degree to which the use of one service type affects use of other types. Relevant services include, but are not limited to: inpatient, emergency room, and ambulatory clinical care and health-related support services; home health care; long-term care; psychosocial support; housing; and other community-based services. A related question that the HCSUS will address is the degree to which some services act as substitutes for others. In particular, the study should be designed so as to examine the degree to which, and the conditions under which, community-based services, including home health care and other forms of supportive care, affect the utilization and costs of institutional care, such as inpatient hospital use, nursing home use, and "inappropriate" emergency room use. Study Design The choice of study design is intimately connected to the nature of the research questions to be studied and the intended audience(s) for the findings. A large-scale project such as HCSUS must accommodate several goals and audiences. In discussions with various organizations and individuals prior to the development of this RFA, it became apparent that there is no clearly optimum study design that will achieve all objectives. In particular, choice of study design will depend upon how one chooses to balance (1) a descriptive versus analytic emphasis, and (2) investigating focused hypotheses versus developing a multi-purpose data set for answering questions that may arise in the future. Applicants are encouraged to propose a position on these continua and to justify the suitability of their study design to that balance. As noted in the report of the public meeting, "HIV Cost and Services Utilization Study: Technical Issues," there is debate concerning the advantages of longitudinal versus cross-sectional designs. Applicants have the latitude to propose either type of design, or some combination of both; applicants should justify their design choice in terms of its suitability for providing credible information on the three major issues outlined above. Accordingly, applicants have significant freedom in developing their study design. They are encouraged to design new research strategies, use new combinations of methods, or tailor existing methods to their research questions. Attendees of the public meeting on technical aspects of research design for this RFA noted that it would be useful to organize presentation of the study design in terms of two components: core and special studies. Study Design: Core Study The methodology and data collection activities proposed by the applicant to address the goals noted above will establish the central core of the project's design. The project core should be capable of addressing a broad range of health care policy issues using uniform data collection procedures across all sites. The successful applicant will be expected to provide information about the delivery of health care services to persons with HIV infection as a function of: o Provider Setting: Information should encompass the major types of providers of HIV-related health care, including (but not limited to) public hospitals, health maintenance organizations, community health centers, community-based physicians, and other health care and support services providers; o Geographic Region of the United States: Service delivery patterns vary in different areas of the country. A major virtue of a large-scale study such as the HCSUS is its ability to gather data in a uniform manner from several geographical areas. HCSUS should provide information from several geographically diverse areas. Applicants may wish to consider including, and provide justification for, areas with moderate, as well as high, levels of HIV seroprevalence; o Sociodemographic Characteristics: Information should include a sample that represents different populations, defined by gender, race or ethnicity, and exposure group. Ideally, the sample would be large enough to permit separate analyses to be conducted within these different groups; and o Stages of HIV infection: This would include persons at different stages of HIV infection, such as asymptomatic, symptomatic non-AIDS, and AIDS. The HCSUS will obtain information about the characteristics of the care setting in order to describe characteristics of different provider types, and address questions about the organizational context in which services are delivered to persons with HIV infection. Applicants should explicitly discuss the particular organizational characteristics to be measured and the procedures for measuring them. The HCSUS will provide information on factors that affect service delivery. Important aspects of service delivery include: rates of service utilization, financing and costs of care, access barriers and unmet service needs, and quality of care. Other factors of interest are patient satisfaction, quality of life, and survival. In addition, measures of continuity and coordination of care, especially as people move between different care systems such as clinical health care and substance abuse treatment systems, are of interest. The core component of the HCSUS will sample people receiving services related to their HIV infection. Although such a sample cannot provide definitive information on access barriers, since those outside the care system are not included, it is appropriate to obtain information concerning current barriers or obstacles to care and, retrospectively, factors that may have impeded access to services at earlier stages of the disease. As noted above, the HCSUS sample will be heterogeneous in terms of usual source of care, gender, race/ethnicity, geographical location, and exposure group. Applications that present a detailed and feasible probability sampling procedure of these populations are of special interest. The AHCPR, however, does not mandate probability sampling procedures for the HCSUS. If probability sampling is not used in the core study, the applicant may propose to develop a special study (see section "Study Design: Special Studies"), to supplement the core study for the purpose of estimating the extent of bias in the core sample. Certain information, such as a comprehensive enumeration of all providers of different services, financing, or measures of quality of life, may have to be obtained from patients themselves. Measures of quality of care and of disease stage may require review of medical records. Measures of provider characteristics may be obtained from organization personnel and documents. The applicant, however, may propose other sources of data. The AHCPR is interested in applications that present creative and innovative methods for data collection. The applicant will be expected to impose relevant uniform data collection procedures at each data collection site. Methods for assuring data quality and uniformity should be described. The applicant also should describe procedures for minimizing nonresponse bias and for reducing loss to follow-up. As reflected in the report of the public meeting, "HIV Cost and Services Utilization Study: Technical Issues," there is no consensus on the proper method for measuring costs. One approach is to obtain detailed information on charges from billing data and then to adjust those charges in some manner. An alternate approach would focus on units of service received and impute a cost per unit of service. This approach would not necessarily require that resources be expended to obtain billing data. Each approach has its benefits and drawbacks, and other approaches are possible. The applicant should describe and justify procedures for cost estimation in detail. Moreover, the applicant should assure that the HCSUS data can be used for relevant cost-effectiveness analyses. At a minimum, the core data set should include: measures of service utilization; health-related quality of life, including well-being and functional status; satisfaction with care; perceived barriers to accessing care; unmet service needs; health insurance; employment status; income both personal and household; type of residence and household composition; and other sociodemographic characteristics. In addition, sufficient clinical data should be collected to stage study participants in terms of disease progression at periodic points in time; such clinical data might include CD4 cell data, HIV-related symptoms, comorbid conditions, and current use of alcohol or illicit drugs. In addition, the data set developed by the core study should be sufficiently comprehensive to address future policy issues that may arise. The applicant should describe and justify the specific measures to be included in the core data set. As part of the core study, applicants may wish to consider the inclusion of supplementary approaches to the study of health services for persons with HIV infection such as use of secondary data, provider studies, case-control methods, cross-sectional analyses, supplementation of and integration with existing data sources, and case studies. Links to and comparability with other data sources may enhance the ability to respond effectively to policy issues using the HCSUS data. Study Design: Special Studies In addition to the project core, the response to this RFA may include proposals for one or more special, focused studies that examine key research questions in greater depth than is possible in the project core. The design and methodology of these special studies may differ from that of the project core and from each other, but should be coordinated with the core study. Research issues that may be more appropriately considered within the context of a special study include: o Care of HIV-infected Patients in Rural Areas: Obtaining a sample of rural residents infected with HIV infection may be difficult to integrate with the general sampling scheme for the core study. This special study would obtain information on relevant problems in HIV service delivery for residents of several different rural areas; o Early Intervention and Linkage: One special study could obtain a supplemental sample of individuals who are at an early point in the disease course, and who may or may not be in care. This study could address issues of access to care, early intervention and management, and factors that facilitate linking people between HIV counseling and testing sites, and other service providers; and o Probability Sample: If a probability sample is not proposed for the core study, applicants may consider obtaining a probability sample of people with HIV infection receiving treatment in order to assess the extent of bias within the core sample. The "HIV Cost and Services Utilization Study: Technical Issues" Report, noted earlier, provides additional examples of research issues that may be appropriate for inclusion as special studies. It also discusses research questions that may be considered for inclusion in the core design and suggests technical considerations for the project's research design. Timetable Allowing for start-up and close-out, the HCSUS should, at a minimum, describe health care utilization experiences during 1995 and 1996. Applicants should allow time for inter-site coordination in any proposed schedules. SPECIAL REQUIREMENTS To promote the development of this multi-site collaborative project, a number of additional issues should be addressed in applications responding to this RFA, as discussed below. Site Selection and Project Organization In describing the selection of sites and the organization of the project, applicants should: o discuss the reasons for their choice of study locations/sites; o describe and document their ability to recruit and retain a sufficient number of study participants; o describe potential biases in the sample and discuss the degree to which findings will be generalizable; o justify their selection of collaborating institutions and investigators, and describe the complementary capacities each site/collaborator would bring to the HCSUS; o describe, in detail, a mechanism to ensure that effective collaboration will occur among sites, and, if the applicant(s) proposes a consortium, among institutions and investigators, on issues such as use of common protocols, facilitating the conduct and monitoring of the study, uniform data collection and access to data, reporting of results, and development of publications; and o demonstrate their ability to interact effectively with collaborators and representatives of study sites, including Persons Living with AIDS (PLWA) groups, community-based organizations, and other service providers. The AHCPR recommends that the applicant establish a Steering Committee to provide advice and guidance, and to assist in governance of the study and in conflict resolution. The membership of the Steering Committee may include, in addition to the Principal and Co-Investigators, experts in HIV-related service delivery, research, and policy development; HIV-infected persons and their representatives; community-based organizations; and local and national health service providers and institutions. If a consortium of institutions responds to this RFA, the application should describe a practical structure for consortium decision-making and governance. Unanticipated disagreements about methods, resource allocation, standardization, authorship, etc., may arise during the course of any project. The consortium must be able to make unified decisions on the issues' merits, without dissolving or routinely relying upon outside arbitration. Confidentiality of Data Data from persons with HIV infection must be treated as highly sensitive information. The applicant must describe procedures for ensuring confidentiality of data. This should include a discussion of who will be permitted access to the data, both the raw data and machine-readable files, and how personal identifiers will be safeguarded. Community Involvement The cooperation and participation of HIV-infected persons and their representatives, community-based organizations, and local and national health service providers and institutions will be critical to the success of the HCSUS. Accordingly, applications should describe in detail the level of involvement in this project of the community of people with HIV infection. Involvement can occur both at particular data collection sites and/or at the level of overall project administration. Participation may entail research partnership, approval, advice, information, or other degrees of involvement. Rapid Response Capability A principal purpose of the HCSUS is to conduct analyses and provide rapid responses to expressed needs for health policy-relevant information. Applicants should describe procedures for producing focused analyses in an expeditious manner, on demand. A rapid response capability will require cleaning and processing small batches of data as soon as they are received from the field, updating data files on a continuous basis, and maintaining sufficient staff to conduct analyses of data on a short timetable. Rapid response mechanisms also are related to plans for uniform data collection and may be facilitated by establishment of a data coordination center. Applicants are encouraged to describe their proposed mechanisms for ensuring such timely responses, including plans for: o collecting and maintaining at a central location a wide range of updated and "cleaned" data in such a way that numerous policy-relevant analyses may be conducted rapidly; o assuring flexibility, throughout the course of the study, in collection of additional data necessary to inform emerging policy issues; o identifying evolving policy issues and disseminating relevant findings thorough periodic and continuing collaboration with decision-makers and other data users representing, at a minimum, the public policy sector, including Federal, State, and local officials. Applicants should include plans and budgets for meetings at which exchange with such groups may occur. (At least one meeting should take place annually in the Washington, DC, area.); o maintaining project staff capable of producing a rapid response to unanticipated requests for analyses of policy issues, or for analyses identified through collaboration with public sector decision-makers and the AHCPR; and o describing plans for timely dissemination of research findings through a rapid response mechanism, as well as publication in the scientific literature. Terms and Conditions of Award This cooperative agreement anticipates substantial AHCPR scientific and programmatic involvement with the awardee(s) throughout the planning, implementation, termination, and close out of the HCSUS. 1. Awardee Responsibilities The awardee(s) will have primary and lead responsibility for all tasks and activities including: sampling, stratification, protocol development, study organization, participant recruitment and follow-up, data collection, quality control, data analysis and interpretation, preparation of publications, community involvement, collaboration among participating organizations, and liaison with information users and policy-makers and other programs of related research. The awardee(s) also will have responsibility for providing rapid response to requests for policy analyses, but may request the AHCPR to assist in establishing priority in responding to requests for such analyses. The AHCPR is committed to disseminating the products of the HCSUS as rapidly as possible. In this context, products include both written reports of findings and the data themselves. The AHCPR will have access to data from the HCSUS upon request. All rights of access to the data will be consistent with current Public Health Service policies and Federal Regulations 42 CFR 67, as well as with section 903(c) of the PHS Act and other statutes listed under AUTHORITY AND REGULATIONS. 2. AHCPR Staff Responsibilities The AHCPR Project Officer and other AHCPR staff will have substantial scientific and programmatic involvement during the conduct of this activity, through technical assistance, advice, and coordination beyond the normal program stewardship for grants. Collaboration on study design and protocol development will occur after the award(s) is made. Specifically, AHCPR's role in the cooperative agreement will include providing technical assistance, advice, and support to the Principal Investigator in: o developing the program and setting priorities, including sampling, design and protocol development, recruitment methods, data analysis and interpretation, prioritization of policy issues requiring rapid response, and preparation of research publications; o gaining access to related data bases; o establishing collaboration with other Federal agencies and programs; and o disseminating research findings through the AHCPR's publication program. In addition, the AHCPR Project Officer will participate in or coordinate strategy sessions with the awardee(s) on three occasions in the first year and up to every six months thereafter to review progress, discuss data collection and analysis, and assess collaboration across sites. The AHCPR will require prior written approval for the addition or deletion of a participating or collaborating institution, site, or other organizational component. The AHCPR reserves the right to terminate or curtail the study in the event of: o substantial shortfall in participant recruitment, follow- up, data reporting, quality control, or other major breech of the protocol; or o substantive changes in the agreed-upon protocol with which the AHCPR does not agree. These special Terms of Award apply in addition to and not in lieu of otherwise applicable PHS grants policies and Federal regulations. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS CONCERNING INCLUSION OF WOMEN AND MINORITIES IN RESEARCH STUDY POPULATIONS The AHCPR requires all applicants for research grants to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder, or condition under study. Special emphasis must be placed on including minorities and women in studies of diseases, disorders, and conditions which disproportionately affect them. This policy applies to males and females of all ages. If women or minorities are excluded or inadequately represented in research, a clear and compelling rationale should be provided. The AHCPR will not award grants for applications which do not comply. If the application does not contain the required information, it will be returned without review. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues should be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information should be included in the form PHS 398 in Sections 1 to 4 of the Research Plan and summarized in Section 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, AHCPR recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., American Indians/Alaskan Natives, Asian/Pacific Islanders, African Americans, Hispanics). Where appropriate, the applicant must provide the rationale for studies on single minority population groups. Peer reviewers will address specifically whether the applicant's research plan conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific questions(s) addressed and the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and will be reflected in assigning the priority score to the application. LETTER OF INTENT Prospective applicants are asked to submit, by December 22, 1993, a letter of intent that includes the name, address, and telephone number of the Principal Investigator; identifies co-investigators and other key personnel and member institutions, community-based organizations, and any other participating organizations or institutions; and states the number and title of the RFA in response to which the application may be submitted. Although a letter of intent is not required, is not binding, and does not enter into the consideration of any subsequent applications, the information allows AHCPR staff to estimate the potential review workload and avoid conflict of interest in the review. The letter of intent is to be sent to the HCSUS Project Officer at the address listed under INQUIRIES. APPLICATION PROCEDURES Applications are to be submitted on the grant application form PHS 398 (rev. 9/91). State and local government applicants may use form PHS 5161. These forms are available at most institutional offices of sponsored research; the Office of Grants Information, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone (301) 594-7248; and from the Scientific Review Branch, Agency for Health Care Policy and Research, 2101 East Jefferson Street, Suite 602, Rockville, MD 20852, telephone (301) 594-1449. The RFA label available in the PHS 398 application form must be affixed to the bottom of the face page of the application. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the title and number of the RFA must be typed in Section 2a on the face page of the application form and the YES box must be marked. The page limitations described in the instructions for the PHS 398 have been modified for this RFA. The application must not exceed 40 pages, (rather than the customary 25 pages), for Items 1-4 of the Research Plan. The completed original application, including the Checklist, and four legible copies (two copies when using the PHS 5161) must be sent or delivered to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** Applications submitted under this RFA must be received by the Division of Research Grants, NIH, by February 22, 1994. If an application is received after that date, it will be returned to the applicant. One copy, labeled "Advance Copy," must be submitted simultaneously to: HCSUS Project Officer Center for General Health Services Extramural Research Agency for Health Care Policy and Research 2101 East Jefferson Street, Suite 502 Rockville, MD 20852 Conference for Prospective Applicants The AHCPR plans to convene a conference for prospective applicants in Rockville, Maryland on October 1, 1993. Attendance is not a prerequisite to applying. Attendees must pay for their own travel and accommodation costs. For additional information, contact Ms. Ruth Ann Celtnieks, telephone (301) 594-1354, extension 118, FAX (301) 594-2155. REVIEW CONSIDERATIONS All applications will be judged on the basis of the scientific merit of the proposed project and the documented ability of the investigator to meet the RESEARCH OBJECTIVES of the RFA. Upon receipt, applications will be reviewed by the Referral Office, Division of Research Grants, NIH, for completeness, and by AHCPR staff for responsiveness to the RFA. Incomplete and nonresponsive applications will be returned to the applicant without further consideration. All accepted applications will undergo peer review for scientific merit by a special study section. Applications also will be reviewed by AHCPR's National Advisory Council for Health Care Policy, Research, and Evaluation. Review criteria for AHCPR grant applications are significance and originality from a scientific and technical viewpoint; adequacy of the method; availability of data or proposed plan to collect data required for the project; qualifications and experience of the principal investigator and proposed staff; adequacy of the plan for organizing and carrying out the project; reasonableness of the proposed budget; and adequacy of the facilities and resources available to the applicant. Although the technical merit of the proposed protocol is important, it is not the sole criterion for selection of the awardee(s). Other considerations, such as the timeliness of the proposed data collection and analyses, access to subjects, and potential for strong collaboration, will be part of the evaluation criteria. Special Review Criteria In addition to the review criteria noted above, the review committee will independently evaluate each application in response to this RFA against the following special scientific and technical review criteria: o the degree to which the study focuses on assessing issues of health policy relevance; and issues of service utilization, financing, access barriers and unmet service needs, and costs and quality of care; o inclusion of a variety of study sites representing diverse organizational configurations and geography; o assurance of the demographic and socioeconomic diversity of the sample, especially the representation of women and members of communities of color, across the spectrum of HIV-related disease stages; o the scientific and technical merit of the application, including for example, the adequacy of the plan and the rationale for the core study; the adequacy of the rationale for inclusion/exclusion of special studies; sampling, including sampling site selection, sample size, minimization of nonresponse bias; longitudinal versus other designs; data collection, including type and quality of data to be collected from patients and organizations; length of observation period; and links with other data sources; o the appropriateness of the mechanism proposed for rapid response to requests for provision of information and analyses of HIV-related policy issues; o the quality of the organizational and institutional arrangements to ensure adequate internal collaboration. Also, in the case of a consortium, the degree of clarity in the specification of activities and in the description of coordination efforts among organizational participants. This description should include the role and extent of any collateral or supplemental support provided to the applicant organization by the other consortium members; o the prior demonstrated ability of the applicant to cooperate with governmental and other groups such as consortium members, subgrantees, subcontractors, community-based organizations, data supplying organizations, respondents, and site representatives; o the degree of community involvement and the nature of the involvement; o the composition of the research team, including evidence of necessary experience and expertise, and appropriateness of relative time commitments; o the appropriateness of the proposed budget and the extent to which the fiscal plan provides assurance that effective use is likely to be made of the funds awarded; and o adequacy of plans for protecting human subjects and for maintaining data confidentiality. AWARD CRITERIA Applications will compete for available funds with all other applications for this RFA. The following will be considered in making funding decisions: quality of the proposed project as determined by peer review, and availability of funds. The earliest anticipated date of award for applications will be July 1, 1994. The AHCPR will determine funding based on recommendations from peer review and AHCPR's Council, the likelihood of successful collaboration based upon sufficient compatibility of features, and availability of funds. INQUIRIES Those considering an application in response to this RFA are encouraged strongly to discuss their project with AHCPR program administrators before formal submission. The AHCPR welcomes the opportunity to clarify any issues or questions from potential applicants. Copies of this RFA and background documents, including the "HIV Cost and Services Utilization Study: Technical Issues" Report, will be available from the AHCPR Publications Clearinghouse, P.O. Box 8547, Silver Spring, MD 20907, (1-800-358-9295). Direct inquiries regarding programmatic issues and address the letter intent to: HCSUS Project Officer Center for General Health Services Extramural Research Agency for Health Care Policy and Research 2101 East Jefferson Street, Suite 502 Rockville, MD 20852-4908 Telephone: (301) 594-1354, ext. 131 or 118 Direct inquiries regarding fiscal matters to: Mr. Ralph L. Sloat Grants Management Officer, Office of Management Agency for Health Care Policy and Research 2101 East Jefferson Street, Suite 601 Rockville, MD 20852-4908 Telephone: (301) 594-1447 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.226. Awards are made under authorization of the Public Health Service Act, Title IX, as amended by Public Laws 101-239 and 102-410 (42 U.S.C. 299-299c-6). Awards are administered under the PHS Grants Policy Statement and Federal Regulations 42 CFR 67, Subpart A, and 45 CFR Part 74 (45 CFR Part 92 for State and local governments). This program is not subject to the intergovernmental review requirements of Executive Order 12372. From owner-sci-resources@net.bio.net Mon Aug 30 23:00:00 1993 Path: biosci!NET.BIO.NET!kristoff From: kristoff@NET.BIO.NET (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NSF - Summary of new documents on STIS - 29 August 1993 Message-ID: Date: 31 Aug 93 07:34:18 GMT Sender: kristoff@net.bio.net Distribution: bionet Lines: 101 Approved: sci-resources-moderator@net.bio.net ** NEW DOCUMENTS ON STIS ** Document Type: Dir of Awards Title: NSF 91-103 Presidential Faculty Fellows FY 1991 File size (bytes): 4717 STIS Filename: nsf91103 Title: PRESIDENTIAL FACULTY FELLOWS FOR FISCAL YEAR 1993 File size (bytes): 5256 STIS Filename: nsf9284 Document Type: Program Guideline Title: NSF 93-104 - Proposal Solicitation- NSF-INRIA Collaborative Research File size (bytes): 16401 STIS Filename: nsf93104 Title: NSF 93-114 -- Presidential Faculty Fellows Awards File size (bytes): 44244 STIS Filename: nsf93114 Title: NSF 93-130 -- Research Planning Grants and Career Advancement Awards for Women Scientists and Engineers File size (bytes): 28544 STIS Filename: nsf93130 Document Type: Recruit Title: Secretary (Office Automation) File size (bytes): 5123 STIS Filename: vgs9385 ------------------------------------------------------------------------ ** UPDATES TO EXISTING STIS DOCUMENTS ** Document Type: Phone Book Title: NSF Alphabetical Listing File size (bytes): 91806 STIS Filename: phnalpha Title: NSF Organizational Directory File size (bytes): 99468 STIS Filename: phnorg Document Type: Program Guideline Title: NSF 93-41 - Engineering Research Centers (Centers for Cross-Disciplinary Research in Engineering) File size (bytes): 48641 STIS Filename: nsf9341 Title: NSF 93-41 - Engineering Research Centers (Centers for Cross-Disciplinary Research in Engineering) File size (bytes): 48641 STIS Filename: nsf9341 ------------------------------------------------------------------------ ** FOR YOUR REFERENCE ** ------------------------------------------------------------------------ HOW TO OBTAIN DOCUMENTS The above files can be retrieved in electronic form using the STIS system. If you don't know how to use STIS, send an E-mail message to stisinfo@nsf.gov (Internet) or stisinfo@NSF (BITNET). You will receive a copy of the STIS flyer via E-mail. If you are already using STIS, you can use the information above to retrieve these files: Documents via E-mail: Send a message to stisserv@nsf.gov (Internet) or stisserv@NSF (BITNET). Use the "STIS Filename" shown above in the "get" command. For example, to retrieve nsf9341, the text of your message should be as follows: get nsf9341 Anonymous FTP: FTP to stis.nsf.gov. Use the "STIS Filename" shown above to retrieve a file. For example, to retrieve nsf9341, you would enter: ftp> get nsf9341 WAIS or Gopher: Do a word search on the filename as shown in the summary. If you want a *printed* copy of a document: Send your name and postal mailing address, and the document title and number to "firstop@nsf.gov" (Internet) or "firstop@nsf" (BITNET). If you have problems with the above procedures: Send a message to "stis@nsf.gov" (Internet) or "stis@NSF" (BITNET).