From owner-sci-resources@net.bio.net Sun Nov 07 22:00:00 1993 Path: biosci!net.bio.net From: kristoff@net.bio.net (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NSF - Summary of new documents on STIS - 7 November 1993 Message-ID: Date: 8 Nov 93 22:54:25 GMT Sender: kristoff@net.bio.net Lines: 65 Approved: biosci-moderator@net.bio.net This message contains a summary of the documents added to the NSF STIS system in the previous week. Reference material concerning STIS follows the summary. ------------------------------------------------------------------------ ** UPDATES TO EXISTING STIS DOCUMENTS ** Document Type: Phone Book Title: NSF Alpha Telephone Directory File size (bytes): 92040 STIS Filename: phnalpha Title: NSF Alpha Telephone Directory File size (bytes): 92040 STIS Filename: phnalpha Document Type: Program Guideline Title: NSF 93-150 Postdoctoral Research Associates in Computational Science and Engineering File size (bytes): 16295 STIS Filename: nsf93150 ------------------------------------------------------------------------ ** 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 nsf93150, the text of your message should be as follows: get nsf93150 Anonymous FTP: FTP to stis.nsf.gov. Use the "STIS Filename" shown above to retrieve a file. For example, to retrieve nsf93150, you would enter: ftp> get nsf93150 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 Mon Nov 15 22:00:00 1993 Path: biosci!nsf.gov From: parzberg@nsf.gov (Peter Arzberger) Newsgroups: bionet.sci-resources Subject: nsf93141 - NSF 93-141 - Research on Digital Libraries Message-ID: Date: 15 Nov 93 12:14:42 GMT Sender: kristoff@net.bio.net Lines: 76 Approved: biosci-moderator@net.bio.net The following is extracted from the new program announcement on the NSF-ARPA-NASA Research on Digital Libraries. Complete copies of the program announcement should be attainable at local Sponsored Project Offices or over the network on STIS or the NSF gopher (under CISE, program announcements). Title : NSF 93-141 - Research on Digital Libraries Type : Program Guideline NSF Org: CISE / IRI Date : September 16, 1993 File : nsf93141 RESEARCH ON DIGITAL LIBRARIES A JOINT INITIATIVE OF: NATIONAL SCIENCE FOUNDATION COMPUTER AND INFORMATION SCIENCE AND ENGINEERING DIRECTORATE ADVANCED RESEARCH PROJECTS AGENCY COMPUTING SYSTEMS TECHNOLOGY OFFICE and the SOFTWARE AND INTELLIGENT SYSTEMS TECHNOLOGY OFFICE National Aeronautics and Space Administration PROPOSALS MUST BE RECEIVED AT NSF NO LATER THAN FEBRUARY 4, 1994 Digital Library Initiative, FY 1994 INTRODUCTION The past decade has seen a remarkable expansion in digital networks within the U.S. research and education community from a state where networking was the purview of the privileged few to one where it is considered an essential tool by millions of researcher and educators. Since the mid-1980's with the advent of NSFNET the volume of traffic, the number of interconnected networks and the functionality of the networks has grown and continues to grow exponentially. The entire assemblage of linked networks using the IP communications protocol throughout the world is now referred to as the Internet. It is a network of networks, which within the U.S., links one third of all two year and four year colleges and universities, many primary and secondary schools, public and private institutions, commercial enterprises, individuals in their homes, and foreign institutions in sixty countries. Information sources accessed via the Internet are the ingredients of a digital library. Today, the network connects some information sources that are a mixture of publicly available (with or without charge) information and private information shared by collaborators. They include reference volumes, books, journals, newspapers, national phone directories, sound and voice recordings, images, video clips, scientific data (raw data streams from instruments and processed information), and private information services such as stock market reports and private newsletters. These information sources, when connected electronically through a network, represent important components of an emerging,universally accessable, digital library. To explore the full benefits of such digital libraries, the problem for research and development is not merely how to connect everyone and everything together in the network. Rather, it is to achieve an economically feasible capability to digitize massive corpora of extant and new information from heterogeneous and distributed sources; then store, search, process and retrieve information from them in a user friendly way. Among other things, this will require both fundamental research and the development of ~intelligent~ software. It is the purpose of this announcement to support such research and development by combining the complementary strengths of the participating agencies in basic research, advanced development and applications, and academic/industry linkage. NSF 93-141 (new) From owner-sci-resources@net.bio.net Mon Nov 15 22:00:00 1993 Path: biosci!nsf.gov From: parzberg@nsf.gov (Peter Arzberger) Newsgroups: bionet.sci-resources Subject: NSF-Sloan Postdoctoral Research Fellowships in Molecular Evolution Message-ID: Date: 13 Nov 93 14:42:20 GMT Sender: kristoff@net.bio.net Lines: 73 Approved: biosci-moderator@net.bio.net The following is extracted from the new program announcement on the NSF-Sloan Postdoctoral Research Fellowships in Molecular Evolution. Complete copies of the program announcement should be attainable at local Sponsored Project Offices or over the network on STIS or the NSF gopher. Please note the deadline and eligibility requirements. Title : NSF 93-151 -- Postdoctoral Research Fellowships in Molecular Evolution Type : Program Guideline NATIONAL SCIENCE FOUNDATION ALFRED P. SLOAN FOUNDATION 1994 ANNOUNCEMENT DEADLINE FOR APPLICATIONS: JANUARY 17, 1994 The National Science Foundation and the Alfred P. Sloan Foundation announce a special program of Postdoctoral Research Fellowships in Molecular Evolution as part of an effort by both foundations to increase support for basic research in Molecular Evolution. Within the NSF, both the Directorates for Biological Sciences and for Social, Behavioral and Economic Sciences are participating in this program. In this first year of the joint program, approximately 18 two-year awards of $80,000 will be offered. The deadline for submission of application materials is January 17, 1994, with awards to be announced in April, 1994. Contingent upon availability of funds, a competition for approximately the same number of fellowships will be held in each of the next 4 years. Molecular evolutionary studies involve the theoretical, comparative, computational, and/or experimental analyses of biological patterns and processes at the molecular level, within the framework of organismic evolutionary change and adaptation. The NSF and the Sloan Foundation believe that the experimental tools and intellectual discoveries of molecular biology have generated exciting possibilities for expanding the scientific understanding of evolution. Moreover, NSF and the Sloan Foundation envision molecular evolution studies involving the biological sciences in concert with other disciplines, both in concepts and techniques, and encourage applications that reflect a broad scientific spectrum. The NSF/Sloan Postdoctoral Research Fellowship in Molecular Evolution will provide recipients the freedom to define and pursue their own research programs while developing relevant interdisciplinary knowledge and skills in a host laboratory or field station. Applicants are expected to take full advantage of this important feature of the award by identifying opportunities to broaden their scientific training and experience, both conceptually and technically, so that they may approach problems in molecular evolution with sound concepts and the most appropriate tools. Because of this essential aspect of the program, applicants are expected to submit research and training plans that differ from the plans followed during their doctoral training or, for applicants who have been postdoctoral fellows for more than one year at the time of award initiation, plans that differ from their current postdoctoral research. Eligibility Applicants for a National Science Foundation/Alfred P.Sloan Foundation Molecular Evolution Postdoctoral Research Fellowship must have earned the Ph.D. after January 1, 1989, or must expect to receive it no later than June 30, 1994. Applicants can be considered only from nationals or permanent resident aliens of the United States. The term "national of the United States" denotes a citizen of the United States or a native resident of the possesion of the United States such as American Samoa. Only one application per applicant will be considered. From owner-sci-resources@net.bio.net Mon Nov 15 22:00:00 1993 Path: biosci!net.bio.net From: kristoff@net.bio.net (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NSF - Summary of new documents on STIS - 14 November 1993 Message-ID: Date: 16 Nov 93 01:02:30 GMT Sender: kristoff@net.bio.net Lines: 110 Approved: biosci-moderator@net.bio.net ** NEW DOCUMENTS ON STIS ** Document Type: Antarctic EAM Title: Automated surface observing systems File size (bytes): 2206 STIS Filename: opp94004 Title: Berthing at McMurdo for Williams FIeld File size (bytes): 44200 STIS Filename: opp94005 Title: Conservation of Antarctic Animals and Plants; Waste Regulation; Enforcement and Hearing Procedures File size (bytes): 34155 STIS Filename: opp94006 Title: Ice core drilling at Vostok File size (bytes): 16609 STIS Filename: opp94007 Document Type: Bulletin Title: NSF Bulletin November 1993, Vol. 21; No.3 File size (bytes): 43935 STIS Filename: bul9311 Document Type: Program Guideline Title: NSF 93-149 - Grant Opportunities for Academic Liaison with Industry (GOALI) File size (bytes): 22994 STIS Filename: nsf93149 Title: NSF 93-151 -- Postdoctoral Research Fellowships in Molecular Evolution File size (bytes): 29416 STIS Filename: nsf93151 Title: NSF 93-155 -- Research Equipment Grant Program File size (bytes): 28515 STIS Filename: nsf93155 Document Type: Recruit Title: Contract Specialist File size (bytes): 5385 STIS Filename: vgs9415 Title: Secretary (Office Automation) File size (bytes): 4906 STIS Filename: vgs9418 ------------------------------------------------------------------------ ** UPDATES TO EXISTING STIS DOCUMENTS ** Document Type: Antarctic EAM Title: USAP environmental documents list File size (bytes): 14223 STIS Filename: opp93000 Document Type: Phone Book Title: NSF Alpha Telephone Directory File size (bytes): 100809 STIS Filename: phnalpha ------------------------------------------------------------------------ ** 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 phnalpha, the text of your message should be as follows: get phnalpha Anonymous FTP: FTP to stis.nsf.gov. Use the "STIS Filename" shown above to retrieve a file. For example, to retrieve phnalpha, you would enter: ftp> get phnalpha 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 Nov 18 22:00:00 1993 Path: biosci!NET.BIO.NET!kristoff From: kristoff@NET.BIO.NET (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: Three NIH Guides coming! Message-ID: Date: 19 Nov 93 04:29:52 GMT Sender: kristoff@net.bio.net Distribution: bionet Lines: 12 Approved: sci-resources-moderator@net.bio.net After returning from my trip to DC earlier this month I had several new items dropped in my lap which I had not anticipated last month. I'm finally getting caught up on BIOSCI this evening, and my apologies for the late postings of the Guide. Sincerely, Dave Kristofferson BIOSCI/bionet Manager biosci-help@net.bio.net From owner-sci-resources@net.bio.net Thu Nov 18 22:00:00 1993 Path: biosci!net.bio.net From: kristoff@net.bio.net (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 22, no. 40, pt. 3, 5 November 1993 Message-ID: Date: 19 Nov 93 04:44:29 GMT Sender: kristoff@net.bio.net Lines: 837 Approved: biosci-moderator@net.bio.net $$XID RFA CA94006 CA-94-006 P1O1 *************************************** PATTERNS OF CARE IN RADIATION ONCOLOGY NIH GUIDE, Volume 22, Number 40, November 5, 1993 RFA: CA-94-006 P.T. 34; K.W. 0785140, 0725015, 0730050 National Cancer Institute Letter of Intent Receipt Date: December 1, 1993 Application Receipt Date: January 24, 1994 PURPOSE The Radiation Research Program (RRP), Division of Cancer Treatment (DCT), National Cancer Institute (NCI) invites applications for Patterns of Care Studies in Radiation Oncology. The objective of this Request for Applications (RFA) is to focus on those factors in radiation oncology that are most likely to affect patient outcome, such as failure to control local-regional neoplastic disease, treatment related morbidity that negatively impacts a patient's quality of life, or failure to implement new methods and new treatment strategies that have been shown to be advantageous for the patient. While patterns of care studies in the past have focused on retrospective data, the new concept should address prospective studies that document patterns of diagnostic methodology, treatment workup and followup for a variety of tumors. The purpose of this research is to identify those variables associated with maximizing local control, with the goal of increasing survival and minimizing complications of normal tissues. An interdisciplinary activity involving diagnostic imaging, pathology, medical oncology, surgery and radiation oncology is essential to the goals of this RFA. New research projects are likely to result from these studies, such as new findings that are useful in the design of therapeutic protocols and in the formulation of clinical and reimbursement policy. 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, Patterns of Care in Radiation Oncology, 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 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. In order to participate in this program, applicant institutions must demonstrate or meet the following requirements: Requirements 1. Expertise in the design and coordination of multi-disciplinary, multi-modality clinical studies. 2. Capacity to develop and implement a methodology for investigating patterns of care studies that respond to the objectives of this RFA. 3. Demonstrated experience and expertise in the appropriate statistical methodology and design of clinical studies so that statistically valid results are obtained that accurately represent radiation oncology practice throughout the U.S. 4. Availability of facilities and professional personnel with expertise in data collection, management and analysis and the ability to participate in patterns of care studies to provide centralized statistical services. 5. Demonstrated capabilities for monitoring the quality assurance of the data collection procedures. 6. Demonstrated capabilities for developing reports, presentations, scientific manuscripts, workshops, short courses, newsletters and other methods for the educational and informational objectives of this RFA. MECHANISM OF SUPPORT The administrative and funding instrument to be used for this program will be the investigator-initiated research project grant (R01). The NCI anticipates awarding one to two grants, with total costs not to exceed $650,000 for the first year. This RFA is a one-time solicitation. Generally, future unsolicited competitive continuation applications will compete as research project applications with all other investigator-initiated applications and be reviewed by the Division of Research Grants (DRG). However, if there is sufficient programmatic need, the NCI will invite recipients of awards under this RFA to submit competitive continuation grant applications for review according to the procedures of the DRG. Except as otherwise stated in this RFA, awards will be administered under PHS grants policy as stated in the PHS Grants Policy Statement, DHHS Publication No. (OASH) 90-05,000, revised October 1, 1990. FUNDS AVAILABLE Approximately $650,000 in total costs per year for three years will be committed specifically to fund applications that are submitted in response to this RFA. The NCI anticipates that one or two awards will be made. Although this program is provided for in the financial plans of the NCI, the award of a grant in response to this RFA is also contingent upon the availability of funds for this purpose. The earliest feasible start date for the initial award will be September 30, 1994. RESEARCH OBJECTIVES The major goal of this research initiative is to support clinical investigations that (1) document and evaluate patient survival and outcome as a function of radiation oncology practice and methodology, (2) coordinate with the leadership of the Cooperative Groups conducting clinical trials for the optimal design of protocols and clinical research based on data received from patterns of care studies, (3) examine the patterns of care for minorities vs non-minorities, and (4) present the findings of the patterns of care studies to the radiation oncology community to achieve both the goals of information and education. The evaluation and documentation of the acceptance and implementation of new treatment strategies in the radiation oncology community where a benefit for the cancer patients has been shown is also of interest. New studies of interest are prospective patterns of care and/or patterns of fractionation that will support and enhance on-going protocols for cancers of the prostate and cervix. Prospective studies that show patterns of total care for breast cancer are of special interest. Background The National Cancer Institute has supported patterns of care studies in radiation oncology since 1973. The first Patterns of Care Study (PCS) was accomplished through a grant to the American College of Radiology (ACR) and was the first nationwide evaluation of a medical specialty. A pioneering effort, the PCS has served as a model for other oncology-related disciplines. The PCS was again funded as a grant in 1978 and 1983. Data from these earlier studies provided the foundation for long-term follow-up of patients treated for cancer of the prostate, cervix, and Hodgkin's disease. Significantly, these studies have shown that the quality of care and the survival of cancer patients treated with radiation therapy was statistically related to the treatment "process" (e.g., equipment, personnel, and diagnostic workup). By identifying those pretreatment and treatment factors that are significant to patient survival and outcome in disease sites where local control and patient outcome could be improved, previous patterns of care studies have facilitated a gradual, but significant, improvement in the management of several cancers, including prostate and cervical cancer and Hodgkin's disease. New Study The objective of this RFA is to focus on those factors that are most likely to affect patient outcome and quality of life, such as failure to treat and control local-regional neoplastic disease and the incidence of treatment related morbidity. Although studies in the past have focused on retrospective data, prospective studies that document patterns of diagnostic methodology, treatment workup, and followup for a variety of anatomical sites with neoplastic disease are of interest, with a goal of identifying those variables associated with maximizing local control and minimizing complications of normal tissues. Specific projects of interest include prospective patterns of care studies that coordinate with active protocols of the cooperative groups in cancers of the prostate and cervix, as well as studies that show patterns of total care for early stage breast cancer. Patterns of care that document differences between minorities and non-minorities are also of interest, as well as documentation of the penetration of the results of clinical trials into routine clinical practice. Applicants should describe how they plan to coordinate with active protocols and how they will assess the impact of results of clinical trials on routine clinical practice. 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 applications for NIH clinical research grants 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 the clinical research of this RFA, particularly in proposed population-based studies, a clear and compelling rationale must be provided. The composition of the proposed study population must be described in terms of the racial/ethnic group, together with a rationale for its choice. 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 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 tissue 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 minorities and women in the study design is inadequate to answer the scientific question 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 that do not comply with these policies. LETTER OF INTENT Prospective applicants are asked to submit, by December 1, 1993, a letter of intent that includes a descriptive title of the proposed research, the name and address of the Principal Investigator, the names of other key personnel, the 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, it is requested in order to provide an indication of the number and scope of applications to be reviewed and to avoid conflict of interest in the review. The letter of intent is to be sent to Dr. Sandra Zink at the address listed under INQUIRIES. APPLICATION PROCEDURES Applications are to be submitted on form PHS 398 (rev. 9/91). Application kits are available from 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 RFA label available in the form PHS 398 must be affixed to the bottom of the face page. 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 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 three signed, exact, clear and single-sided photocopies, in one package to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 5333 Westbard Avenue Bethesda, MD 20892** At the time of submission, send two additional copies of the application to: Ms. Toby Friedberg Referral Officer Division of Extramural Activities National Cancer Institute Executive Plaza North, Room 636 6130 Executive Boulevard Bethesda, MD 20892 Applications must be received by January 24, 1994. If an application is received after that date, it will be returned. 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 Review Procedure Upon receipt, applications will be reviewed (initially) by the Division of Research Grants (DRG) for completeness and responsiveness by the NCI. Incomplete applications will be returned to the applicant without further consideration. Those applications judged to be both competitive and responsive will be further evaluated according to the review criteria stated in the RFA 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 1. Extent to which the application addresses the goals and objectives of this RFA; 2. scientific, technical or clinical significance and originality of the proposed research; 3. appropriateness and adequacy of the experimental approach and methodology proposed to carry out the research; 4. the leadership ability of the Principal Investigator and documented experience in clinical studies; 5. documented ability of the staff to carry out all the procedures of data collection, evaluation of evaluability, and quality assurance; 6. statistical support necessary to design, monitor, analyze and report on the patterns of care studies; and 7. adequacy of appropriate facilities and resources to support the research objectives of this RFA. Reviewers will examine the budget request critically and recommend an appropriate budget. AWARD CRITERIA The earliest feasible start date for the initial award will be September 30, 1994, and will be made solely on the basis of peer review. Only the most meritorious will be considered, contingent upon the availability of funds. Although this program is provided for in the financial plans of the NCI, a grant award pursuant to this RFA is contingent upon the availability of funds for this purpose. 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 encouraged. The NCI welcomes the opportunity to clarify any issues or questions from potential applicants. Direct inquiries regarding programmatic issues to: Dr. Sandra Zink Radiation Research Program National Cancer Institute Executive Plaza North, Suite 800 Bethesda, MD 20892 Telephone: (301) 496-9360 FAX: (301) 480-5785 Direct inquiries regarding fiscal matters to: Ms. Barbara Fisher Grants Administration Branch Executive Plaza South, Room 242 6120 Executive Boulevard Bethesda, MD 20852 Telephone: (301) 496-7800, Ext. 29 FAX: (301) 496-8601 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.395 (Cancer Treatment Research). Awards are made under the authorization of Public Health Service Act, Title IV, Sections 301, 410 and 411, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285 (a.)) and administered under the PHS grants policies and Federal Regulations 42 CFR Part 52 and 45 CFR Part 74 and 92. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$XID RFA AI94002 AI-94-002 P1O1 *************************************** MECHANISM OF RESPIRATORY SYNCYTIAL VIRUS VACCINE IMMUNOPOTENTIATION NIH GUIDE, Volume 22, Number 40, November 5, 1993 RFA: AI-94-002 P.T. 34; K.W. 0705048, 0740075, 0710070 National Institute of Allergy and Infectious Diseases Letter of Intent Receipt Date: January 14, 1994 Application Receipt Date: March 17, 1994 PURPOSE The National Institute of Allergy and Infectious Diseases (NIAID) invites applications to conduct basic research on the immunology of Respiratory Syncytial Virus (RSV) protection and disease. Specifically, the NIAID is interested in addressing the immune responses associated with the exacerbation of disease in children who had previously received formalin-inactivated RSV vaccine. 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), Mechanism of RSV Vaccine Immunopotentiation, 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. Successful applications from foreign institutions, however, are limited to three years of support without indirect costs. 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 grant (R01) award 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 by domestic institutions may not exceed four years; the total project period for applications submitted by foreign institutions may not exceed three years. The anticipated earliest possible award date is September 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 animal or patient populations to accelerate technical progress and clinical development of promising prophylactics. Because the nature and scope of the research proposed in response to this RFA may vary, it is anticipated that the amounts awarded will also vary. 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 funds available for the total (direct and indirect) first year cost of all awards under this RFA is $1.0 million. Foreign applications that may be funded under this RFA are not eligible for indirect costs. The NIAID anticipates making a minimum of three new awards. RESEARCH OBJECTIVES Background Acute respiratory infections represent a significant cause of death, worldwide. The most serious acute respiratory condition, pneumonia, is the cause of four million deaths per year in children under the age of five. The etiology of pneumonia has been assessed in both developed and developing countries and has been found to be strikingly similar. Worldwide, it has been estimated that, for children under the age of five, over half of pneumonia deaths are of viral or bacterial/viral origin. Of all the respiratory viruses associated with death due to childhood pneumonia, over 62 percent were associated with RSV. Within the U.S., the impact of RSV infection is primarily through increased morbidity (hospitalization due to pneumonia) in both normal and high risk children including low birth weight infants and children with bronchopulmonary dysplasia (BPD), congenital heart disease (CHD) and immunodeficiencies. For example, in a prospective study conducted at the University of Colorado Hospital, BPD infants infected with RSV accounted for 10 percent of total pediatric hospital days. Thus, the development of successful vaccines for RSV could significantly alleviate the excess infant morbidity and mortality. Presently, there are no licensed RSV vaccines and only limited efforts in the development of vaccine candidates because attempts to develop a safe and effective vaccine have met with continued frustration. In the mid-1960's, a formalin inactivated RSV vaccine was evaluated in previously unprimed (seronegative) infants. When these children were subsequently exposed during an RSV outbreak, the resulting illnesses were very severe. Specifically, children under two years of age who received the vaccine had a much higher incidence of pneumonia (60 percent) and hospitalization (21 percent) compared to the children who received placebo (8 percent and 1.5 percent, respectively). Attempts to understand the nature of this immunopotentiation event have relied primarily on data generated using the cotton-rat model. In this system, RSV challenge of animals immunized with a formalin-inactivated RSV vaccine has been associated with changes in lung histology. The equation of this altered histology in animals with the exacerbated disease in humans has been widely debated. Nonetheless, in the absence of definitive data to the contrary, the cotton-rat model has been widely used to define the preclinical safety of potential new vaccine candidates. At a recent NIAID/WHO/CDC RSV Workshop (May 1993) use of alternative animal model systems for detailed studies of the immunologic mechanism of immunopotentiation (eg., mouse model) and development of animal models with clinical disease patterns/immunologic responses similar to those seen in humans (eg., lamb/bovine models) were encouraged. It was also clear that continued use of the cotton-rat model to define safety of new experimental vaccines requires additional knowledge as to the basis of the histologic changes observed following challenge. Until then, a significant barrier would remain in the development of RSV vaccines. Scope of Research The long-term goal of the NIAID is to facilitate the development of an effective RSV vaccine. However, interim objectives must be met before candidate vaccines can be entered into clinical trials involving seronegative infants and children. The goal of this RFA is to stimulate innovative new research on the complex immunology associated with RSV disease immunopotentiation and within that context to develop in vitro and/or in vivo assays that accurately reflect the potential safety of RSV vaccine candidates. Examples of projects that might be responsive to this RFA include, but are not limited to: 1. Detailed analysis of the immune pathways stimulated following: o immunization with experimental RSV vaccines that have been previously associated with immunopotentiation; o immunization with experimental RSV vaccines that have been associated with protection but not immunopotentiation; o natural infection; 2. Development of in vivo models that closely mimic the clinical disease/immunopotentiation event seen in humans; 3. Development of immunologically defined reagents for valid in vivo models; 4. Development of in vitro models to assess the immunopotentiation effect of candidate RSV vaccines; 5. Definition of the properties of vaccine preparations which have been associated with immunopotentiation. 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 will be requested to attend to discuss progress. At the discretion of the Program Staff, clinical researchers and members of the vaccine industry may also be invited to attend. 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 January 14, 1994, 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-94-002 and the title "MECHANISM of RSV VACCINE IMMUNOPOTENTIATION." 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 and Dr. Olivia Preble by March 17, 1994. Applications not received by 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 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 NIH 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) that the Principal Investigator(s) and staff would devote to the proposed studies. 4. Adequacy of facilities, including, if relevant to the proposed research, adequacy of 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 development of RSV 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. Carole Heilman Division of Microbiology and Infectious Diseases National Institute of Allergy and Infectious Diseases Solar Building, Room 3B-06 Bethesda, MD 20892 Telephone: (301) 496-5305 FAX: (301) 496-8030 E-mail: hck@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 4C19 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: January 14, 1993 Application Receipt Date: March 17, 1994 Scientific Review Date: June 1994 Council Meeting Date: September 1994 Earliest Award Date: September 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 Thu Nov 18 22:00:00 1993 Path: biosci!net.bio.net From: kristoff@net.bio.net (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 22, no. 40, pt. 2, 5 November 1993 Message-ID: Date: 19 Nov 93 04:43:36 GMT Sender: kristoff@net.bio.net Lines: 837 Approved: biosci-moderator@net.bio.net $$XID NIHGUIDE 19931105 V22N40 P2O2 ************************************ Direct inquiries regarding fiscal matters to: Gary Fleming, J.D., M.A. Grants Management Branch National Institute on Drug Abuse 5600 Fishers Lane, Room 8A-54 Rockville, MD 20857 Telephone: (301) 443-6710 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.279. Awards are made under authorization of the Public Health Service Act, Section 301 and administered under PHS grants policies and Federal Regulations of Title 42 CFR 52 "Grants for Research Projects", Title 45 CFR Part 74 and 92, "Administration of Grants" and 45 CFR Part 46, "Protection of Human Subjects". Title 42 CFR Part 2, "Confidentiality of Alcohol and Drug Abuse Patient Records" may be applicable to these awards. Title 42 Part 241(d) "Certificates of Confidentiality and Communicable Disease Reporting" will also apply. Program is not subject to the intergovernmental review requirements of Executive Order 12372. $$P1 END ************************************************************ $$P2 BEGIN PA-94-011 ************************************************ ECONOMIC STUDIES IN CANCER PREVENTION, SCREENING AND CARE NIH GUIDE, Volume 22, Number 40, November 5, 1993 PA NUMBER: PA-94-011 P.T. 34; K.W. 0408006, 0715035, 0745027, 0730050 National Cancer Institute Agency for Health Care Policy and Research PURPOSE The Division of Cancer Prevention and Control (DCPC), National Cancer Institute (NCI) and the Agency for Health Care Policy and Research (AHCPR) invite investigator-initiated grant applications for research directed at increasing the knowledge base in the area of the economic aspects of cancer prevention, screening and care. The goal of this program announcement is to generate new economic knowledge that will promote the optimal design of cancer prevention and control trial studies and interventions and will facilitate the formulation of effective health care policy related to cancer prevention and control. This initiative requests research applications on new methods development, the synthesis and extension of existing methods, and innovative data gathering strategies. Applications that propose to implement actual data collection on a pilot or full-scale basis as well as analytical studies that use existing data and methodology will be entertained. The focus of this Program Announcement (PA) relates to the general health services and medical treatment effectiveness research supported by the AHCPR for a wide range of clinical conditions, including cancer. For example, AHCPR is presently supporting, and continues to be interested in, research on the analysis of health care costs, the measurement of patient outcomes, the cost effectiveness of health care services and procedures, and the development of methods used in studies of the quality and outcomes of care. Related research priorities for AHCPR are described in: PA-93-045 "Cost and Financing Issues in Health Care Reform", PA-93-063 "Primary Care and Health Care Reform", and RFA HS-94-002 "Medical Treatment Effectiveness Research." 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, Economic Studies in Cancer Prevention, Screening, and Care, 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 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, public and private organizations, such as universities, colleges, hospitals, laboratories, units of state or local governments, and eligible agencies of the Federal government. Applications from minority and women investigators are encouraged. MECHANISM OF SUPPORT Support of this program will be through the National Institutes of Health (NIH) research project grant (R01). Applicants will be responsible for the planning, direction, and execution of the proposed project. Except as otherwise stated in this PA, awards will be administered under PHS grants policy as stated in the Public Health Service Grants Policy Statement, DHHS Publication No. (OASH) 90-50,000. Because the nature and scope of research proposed in response to this PA may vary, it is anticipated that the size of award will vary also. The anticipated amount of the direct costs per award will vary from $50,000 to $500,000 per year. Expenses incurred in development and implementation of the proposed research, including baseline and follow-up surveys, design of materials, and professional education are allowable costs. RESEARCH OBJECTIVES This initiative supports research directed at increasing our understanding of economic aspects of cancer prevention, screening and care. Cancer is a heterogeneous chronic disease characterized by innovation in treatment and care approaches. Studies that cover the national population of all ages on an episodic basis fail to capture an adequate sample of cancer patients or the full scope and duration of cancer costs. Studies that focus on a convenience sample of cancer patients in a single health care delivery setting or community can be criticized as lacking external validity. Studies proposed in response to this PA will be expected to address these issues and propose innovative methods of overcoming these limitations. Three broad topics are included in this PA: o The cost of cancer treatment and care in various organizational settings. o Collection of economic data in the context of clinical trials and the use of economic data and analysis in the design of trials. o Cost-effectiveness of cancer prevention and screening trials and cancer prevention and control interventions. The purpose of this PA is to solicit collaborative research between academics in the fields of health economics and health services research and clinical researchers in cancer. The specific research goals of this PA are: 1. The cost of cancer treatment and care in various organizational settings To develop and validate methods for collecting reliable and representative data on longitudinal patterns of health care resource use, expenditures and costs for cancer prevention, screening, diagnostic, treatment, and care in various organizational settings. To develop and validate methods for collecting reliable and representative data on the cost of continuing care for cancer patients. These costs include not only out-of-pocket costs for medical treatment and related expenses but also other monetary and non-monetary disease and treatment costs to the cancer patient and the family of the cancer patient. To explore alternative proposed and existing models of out-patient and home-based continuing care for cancer patients in order to determine efficient modes of organization that provide access to and meet the continuing care needs of cancer patients and their families. 2. Collection of economic data in the context of clinical trials and the use of economic data and analysis in the design of trials To determine the cost of the health care intervention (e.g., cancer prevention, control, treatment or rehabilitation) in NCI sponsored trial settings compared to standard cancer control and treatment settings. To determine the feasibility of collecting data on direct and indirect lifetime costs in the context of clinical trials. To collect data on direct and/or indirect lifetime cost in the context of a clinical trial. 3. Cost-effectiveness of cancer prevention and screening trials and cancer prevention and control interventions To review and evaluate the existing conceptual basis, methodology and application of cost effectiveness analysis to cancer related interventions. Studies should identify conceptual, methodological and data collection problems unique to cancer related interventions and propose solutions to these problems. Studies should also include an evaluation of the appropriate role of cost effectiveness analysis in policy formulation related to cancer and how this role relates, or should relate, to medical ethics, equity and fairness, and community values. To determine the cost effectiveness of NCI sponsored cancer prevention and screening trials. Studies should include an analysis of the important determinates of cost effectiveness, the level of uncertainty of these determinates, and how these determinates might be effected by alternative trial designs. To determine the cost effectiveness of cancer prevention and control interventions as implemented through the health care system. Studies should include an analysis of the important determinates of cost effectiveness, the level of uncertainty of these determinates, and how these determinates might be effected by alternative health care delivery settings and health care policies. The relevance of cost effectiveness analysis for the particular question studied should be demonstrated by showing that it contributes additional information to the health care decision making process than would be available from clinical trial efficacy information alone. 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 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 and 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 (revised 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, the 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 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. In cases where the proposed study involves collaboration with an ongoing NCI sponsored trial the application must include a letter from the principal investigators of that trial indicating the latter's endorsement of the proposed study and willingness to collaborate. Any grant proposing association with an existing NCI trial would, of course, have to be approved by NCI grants or contracts administration and by the project officer to the existing trial before submission. All regulations involving human subjects and release of data applicable to the original trial would apply to the supplemental grant. APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 9/91) is to be used in applying for these grants. The application package 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. The title and number of the announcement must be typed in line 2a on the 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, MD 20892** REVIEW CONSIDERATIONS Applications will be assigned to the appropriate PHS study section, by the Division of Research Grants on the basis of established Public Health Service referral guidelines. Applications will be reviewed by the study section for scientific and technical merit in accordance with standard PHS peer review procedures. The following criteria will be considered when assessing the merit of a research grant application: 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 resources necessary for the research; o appropriateness of the proposed budget and timetable in relation to the scope of the proposed research; o adequacy of the proposed means for protecting against or minimizing potential adverse effects upon humans, vertebrate animals, and/or the environment; and o for studies involving minorities and both genders subjects in research, the adequacy of plans to include minorities and both genders in the study design, and the potential of that design to address the scientific question(s) addressed. 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 the objectives and scope of this PA, or inquiries about whether or not specific proposed research would be responsive, are encouraged. The Program Director welcomes the opportunity to clarify any issues or questions from potential applicants. Martin L. Brown Division of Cancer Prevention and Control National Cancer Institute Executive Plaza North, Suite 300 Bethesda, MD 20892 Telephone: (301) 496-8500 FAX: (301) 496-8667 Michael Hagen Program Officer Agency for Health Care Policy and Research 2101 East Jefferson Street, Suite 502 Rockville, MD 20852-4908 Telephone: 301/594-1354 Direct inquiries regarding budgetary, administrative, and/or policy issues to: Mrs. Eileen M. Natoli Grants Administration Branch National Cancer Institute Executive Plaza South, Suite 242 Bethesda, MD 20892 Telephone: (301) 496-7800 FAX: (301) 496-8601 Ralph Sloat, Grants Management Officer Agency for Health Care Policy and Research 2101 East Jefferson Street, Suite 601 Rockville, MD 20852 Telephone: (301) 594-1447 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.399, Cancer Control Research. 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 and 92. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$P2 END ************************************************************ $$XID RFA HS94004 HS-94-004 P1O1 *************************************** FIRST INDEPENDENT RESEARCH SUPPORT AND TRANSITION AWARD NIH GUIDE, Volume 22, Number 40, November 5, 1993 RFA: HS-94-004 P.T. 34; K.W. 0730050 Agency for Health Care Policy and Research Application Receipt Date: March 11, 1994 PURPOSE The Agency for Health Care Policy and Research (AHCPR) announces the availability of the First Independent Research Support and Transition (FIRST) Award (R29) in health services research. The purpose of the FIRST Award is to provide a sufficient period of research support for newly independent health services researchers to initiate their own research and demonstrate independent investigative efforts; to provide a reasonable opportunity to demonstrate creativity, productivity, and further promise; and to help in the transition to traditional types of AHCPR research project grants. The award is not intended for established investigators who may be in transition to another endeavor. A FIRST Award is for a distinct research endeavor and may not be used merely to supplement or broaden an ongoing project at the applicant institution. FIRST Awards are intended to provide funds for newly independent investigators for five years during which time they can establish their own research program and make significant and innovative contributions to health services research. 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 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 To be eligible for a FIRST Award, the proposed Principal Investigator (PI) must be genuinely independent of a mentor yet at the same time must be at the beginning stages of his or her research career with, in most instances, no more than five years research experience since completing postdoctoral research training or its equivalent. If the applicant is in the final stages of such training, it is permissible to apply, but no FIRST Award will be made to persons in training status. In addition, the proposed PI must otherwise be eligible to serve in the same capacity on a traditional research project grant (R01) awarded to the applicant institution. Only non-profit domestic institutions and organizations are eligible to receive FIRST Awards. The applicant investigator must never have been designated previously as PI on any PHS-supported research project OTHER THAN a PHS small grant (R03), an Academic Research Enhancement Award (R15), or certain career development awards (K series) directed principally to physicians, dentists, or other clinicians with little research experience. (Current or past Research Career Development Awardees are not eligible.) Subproject leaders on multicomponent PHS awards such as Program Project grants (P01), Center grants (P50), or Minority Biomedical Research Support grants (S06) may also be eligible, depending on their stage of career development; however, potential applicants in these categories are urged to contact AHCPR prior to filing an application. MECHANISM OF SUPPORT This Request for Applications (RFA) represents the initial use of the First Independent Research Support and Transition (FIRST) Award (R29) by AHCPR. See SPECIAL REQUIREMENTS, below, for details of this mechanism. FUNDS AVAILABLE The AHCPR expects to fund approximately three FIRST Awards in Fiscal Year (FY) 1994. The actual number awarded in FY 94 will depend on availability of funds as will the number in future years. RESEARCH OBJECTIVES The AHCPR conducts and supports research on the quality, appropriateness, efficiency, and effectiveness of health care services and the systems for delivery of these services. Research areas of interest for FIRST applications are as follows: o Health care reform issues; o Health care costs and financing; o Relationship between primary care and health care costs, access, and quality; o Rural health including access to services, supply of health professionals, delivery systems issues, primary health care, health promotion and disease prevention, technology diffusion, and special populations; o Health care quality improvement and quality assurance including methods and measures; o Information technologies and factors affecting their use; o Costs and quality of alternative delivery systems and managed care; o Health care technologies, facilities, and equipment; o Medical effectiveness and patient outcomes research; o Medical liability and malpractice; o Access, medical effectiveness, and patient outcomes research in low-income, minority, elderly, and other underserved populations; o Dissemination of health and clinical information and research findings to practitioners, consumers, and patients for use in improved health care decisionmaking; o Services for persons with human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS); and o Evaluation of outcomes associated with the use of clinical practice guidelines. The following announcements, which were published in the NIH Guide for Grants and Contracts, provide more detailed information on selected areas of interest: "Health Services for Persons with HIV Infection" (PA-93-110), Vol. 22, No. 33, September 17, 1993; "Health Care Quality Improvement and Quality Assurance Research" (PA-93-084), Vol. 22, No. 19, May 21, 1993; "Primary Care and Health Care Reform" (PA-93-063), Vol. 22, No. 10, March 12, 1993; "Cost and Financing Issues in Health Care Reform" (PA-93-45), Vol. 22, No. 4, Jan. 29, 1993; "Health Services Research on Rural Health" (PA-92-71), Vol. 21, No. 16, May 1, 1992; and "Effective Dissemination of Health and Clinical Information and Research Findings" (PA-92-51), Vol 21, No. 10, March 13, 1992. STUDY POPULATIONS SPECIAL INSTRUCTION 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 the need to include 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 research, a clear and compelling rationale should be provided. AHCPR will not award grants for applications which do not comply. 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 the 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 (or in the Program Narrative section of form PHS 5161 for State and local governments). 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 U.S. racial/ethnic minority populations (i.e., Native Americans, Asian/Pacific Islanders, African Americans, and Hispanics). Where appropriate, the applicant must provide the rationale for studies on single minority population groups. 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. This policy applies to all AHCPR research grants. The AHCPR will not award grants for applications that do not comply. If the application does not contain the required information, it will be returned without review. SPECIAL REQUIREMENTS An individual may submit only one FIRST Award application to the Public Health Service (PHS) for the receipt date and may not submit any other type of research grant application (including research career applications), to the PHS during the applicable review cycle. However, applications for an R03 and an R15 may be submitted to the PHS simultaneously with a FIRST application provided they are on separate topics. Applications for other projects may be submitted during the FIRST Award period, if the time and effort on the FIRST Award are less than 100 percent. FIRST Award applications must request five years of research support. Applications submitted to AHCPR in which the request is for fewer than five years of support will be designated R01s and so reviewed unless the applicant withdraws the application. The Principal Investigator must make a commitment of no less than 50 percent effort to the proposed project. Up to 100 percent effort may be requested if a greater commitment of the principal investigator is required to do the research. The request for effort of the applicant investigator will be reviewed and modifications may be recommended. The total direct cost award for the five-year period may not exceed $350,000. The direct cost award in any yearly budget period should not exceed $100,000. Indirect costs will be paid to the grantee institution in accord with applicable policy of the Department of Health and Human Services (DHHS). FIRST Awards are not renewable. Replacement of the PI on a FIRST Award will not be approved. Transfer of the FIRST Award with the Principal Investigator to another institution for the remaining performance period may be requested. APPLICATION PROCEDURES The application receipt date is March 11, 1994. The research grant application form PHS 398 (rev. 9/91) is to be used, and the applicants must provide relevant information on eligibility. 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. Application page limitations apply to the Research Plan section of the PHS 398 application form. Sections 1-4 of the Research Plan, as described on page 20 of the instructions for the PHS 398 (rev. 9/91), are limited to a total of 25 pages, including tables and figures. Applications exceeding the 25-page limitation will be returned. If appendix material is submitted, five collated sets must be included with the application package. Identify each of the five sets with the name of the principal investigator and the project title. This material will not be routinely duplicated and will be used in a limited way by members of the initial review group. 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. 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. The following is to be addressed in a letter or memorandum from a suitable department head or dean and submitted with the application: (1) eligibility of the proposed Principal Investigator to independently lead a research project at the applicant institution, is this person otherwise qualified to be the PI on a traditional research project grant (R01)?; and (2) details of the intended commitment of the institution to the project for the five-year period. In addition, three letters of reference for the proposed PI are needed. Reference letters must be submitted with the application. Such letters are critically important and should reflect the investigator's research originality and potential for independent investigation. When the application is from the institution where the proposed PI received postdoctoral research training, it must be made absolutely clear that the FIRST Award would be to support a research endeavor independent of that conducted in the former training environment. FIRST applicants are to request the letters of reference well in advance of the application submission, advising the referees to return the reference letters to the applicant in sealed envelopes as soon as possible. To protect the utility and confidentiality of reference letters, applicants should not open envelopes. The sealed envelopes must be attached to the front of the original applications. Applications received without the three reference letters will be returned to the applicant. A list of individuals providing letters of reference must be included in Section 10 of the Research Plan. Provide the name, title, and institutional affiliation for each person. The completed, signed, original application and five legible copies of form PHS 398; the letter or memorandum from the department head or dean; and the three letters of reference 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 March 11, 1994. If an application is received after that date, it will be returned to the applicant. The following is the review schedule for FIRST applications: Application Receipt Date: March 11, 1994 Initial Review Date: May/June 1994 Council Review Date: September 1994 Earliest Possible Start Date: September 30, 1994 REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed 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 the applicant without further consideration. 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. Review criteria are described below. Review Criteria Applications will be evaluated by an appropriate peer review group convened by AHCPR in accordance with the criteria for scientific and technical merit stated below, taking into consideration the investigator's stage of development, merit of the proposed research, the resources and environment, and the appropriateness of the proposed budget. Applications may be reviewed by the National Advisory Council for Health Care Policy, Research, and Evaluation for policy relevance and research value. For a FIRST application, it is recognized that an investigator with limited experience is less likely to be able to submit an application with the breadth and depth of that submitted by an experienced investigator. Reviewers are expected to recognize that, in general, less detail will be expected with regard to work planned for the later years of the project, but the Principal Investigator should outline the general plans for these years. A FIRST application must provide clear evidence of the investigator's ability to develop a plan for the research project. The following criteria will be used in evaluating the application for scientific and technical merit: Principal Investigator o Potential to carry out independent research; o Quality and extent of education, scientific training, and research experience; o Evidence of research productivity, appropriate to the level of experience; o Quality of any research publications; and o Commitment to a research career. Research Design o Originality and significance of the research goals; o Appropriateness and significance of the research hypotheses; o Feasibility and adequacy of design and methodology; and o Availability of data and appropriateness of plans for organizing the project and carrying out the data collection and analysis. Resources and Environment o Availability of essential facilities and equipment, subject populations, computer time, or other resources, as appropriate; and o Evidence of institutional commitment to the project. Budget Appropriateness o Appropriateness of budget estimates in relation to aims and methods; and o Appropriateness of period of support for carrying out the research and for demonstrating the investigator's scientific abilities. AWARD CRITERIA The decision to fund an application will depend on the overall scientific and technical merit of the proposal as determined by peer review, program balance and relevance, and availability of funds. In very unusual circumstances, FIRST awards may be recommended by the initial review group or the awarding component for periods of fewer than five years. INQUIRIES Inquiries regarding programmatic issues may be directed to the appropriate office listed below: For applied dissemination research: Center for Research Dissemination and Liaison Agency for Health Care Policy and Research 2101 East Jefferson Street, Suite 501 Rockville, MD 20852 Telephone: (301) 594-1362 For medical effectiveness and outcomes research: Center for Medical Effectiveness Research Agency for Health Care Policy and Research 2101 East Jefferson Street, Suite 605 Rockville, MD 20852 Telephone: (301) 594-1485 For other AHCPR health services research: Center for General Health Services Extramural Research Agency for Health Care Policy and Research 2101 East Jefferson Street, Suite 502 Rockville, MD 20852 Telephone: (301) 594-1349, Ext. 104 Direct inquiries regarding fiscal/administrative matters to: Ralph Sloat, Grants Management Officer Agency for Health Care Policy and Research 2101 East Jefferson Street, Suite 601 Rockville, MD 20852 Telephone: (301) 594-1447 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.180 and 93.226. Awards are authorized under 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. This program is not subject to the intergovernmental review requirements of Executive Order 12372. From owner-sci-resources@net.bio.net Thu Nov 18 22:00:00 1993 Path: biosci!net.bio.net From: kristoff@net.bio.net (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 22, no. 40, pt. 1, 5 November 1993 Message-ID: Date: 19 Nov 93 04:42:47 GMT Sender: kristoff@net.bio.net Lines: 1505 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 19931105 V22N40 P1O2 ************************************ X-comment: RFAs described: CA-94-006, HS-94-004, AI-94-002 NIH GUIDE - Vol. 22, No. 40 - November 5, 1993 $$INDEX BEGIN ******************************************************* NOTICES $$INDEX N1 ********************************************************** NATIONAL HUMAN SUBJECTS PROTECTION WORKSHOPS National Institutes of Health Food and Drug Administration INDEX: NATIONAL INSTITUTES OF HEALTH; FOOD AND DRUG ADMINISTRATION $$INDEX N2 ********************************************************** WORLD AIDS FOUNDATION Fogarty International Center INDEX: FOGARTY INTERNATIONAL CENTER NOTICES OF AVAILABILITY (RFPs AND RFAs) $$INDEX R1 01/24/94 ************************************************* PATTERNS OF CARE IN RADIATION ONCOLOGY (RFA CA-94-006) National Cancer Institute INDEX: CANCER $$INDEX R2 03/11/94 ************************************************* FIRST INDEPENDENT RESEARCH SUPPORT AND TRANSITION AWARD (RFA HS-94-004) Agency for Health Care Policy and Research INDEX: HEALTH CARE POLICY, RESEARCH $$INDEX R3 03/17/94 ************************************************* MECHANISM of RESPIRATORY SYNCYTIAL VIRUS VACCINE IMMUNOPOTENTIATION (RFA AI-94-002) National Institute of Allergy and Infectious Diseases INDEX: ALLERGY, INFECTIOUS DISEASES ONGOING PROGRAM ANNOUNCEMENTS $$INDEX P1 ********************************************************** RESEARCH ON NEEDLE HYGIENE AND NEEDLE EXCHANGE PROGRAMS (PA-94-010) National Institute on Drug Abuse INDEX: DRUG ABUSE $$INDEX P2 ********************************************************** ECONOMIC STUDIES IN CANCER PREVENTION, SCREENING AND CARE (PA-94-011) National Cancer Institute Agency for Health Care Policy and Research INDEX: CANCER; HEALTH CARE POLICY, RESEARCH 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 ********************************************************** NATIONAL HUMAN SUBJECTS PROTECTION WORKSHOPS NIH GUIDE, Volume 22, Number 40, November 5, 1993 P.T. 42; K.W. 0783005 National Institutes of Health Food and Drug Administration The National Institutes of Health (NIH) and the Food and Drug Administration (FDA) are continuing to sponsor a series of workshops on responsibilities of researchers, Institutional Review Boards (IRBs), and institutional officials for the protection of human subjects in research. The workshops are open to everyone with an interest in research involving human persons and those currently serving or about to begin serving as a member of an IRB. Issues discussed at these workshops are relevant to all other Public Health Service agencies. The current schedule includes: WESTERN WORKSHOP DATES: November 4-5, 1993 LOCATION Radisson Hotel Denver South, Denver, CO SPONSORS University of Colorado Health Sciences Center, Denver, CO University of Southern Colorado, Pueblo, CO REGISTRATION Ms. Mary Peratt, Secretary IRB University of Colorado Health Sciences Center 4200 East Ninth Avenue (Box C-290) Denver, CO 80262 Telephone: (303) 270-7960 TITLE: Medical Research: Protection of Vulnerable Subjects DESCRIPTION: IRBs are confronted with a complexity of questions and ethical issues that seldom have defined answers or ready resolve. Some of the more perplexing clinical research protocols presented for review are studies involving human subjects in overt, at-risk groups. This human subjects workshop will address protections of highly vulnerable and protected human populations. Discussions will focus on the ethical principles, protective measures, and definitions of criteria for informed consent that are tantamount for IRB reviews when members of these vulnerable groups are subjects of research studies. Subject groups and protocols to be covered will be focused on prisoners, children, mentally compromised, AIDS and HIV-infected, geriatric, and emergency room. The conference program is designed to be of value to physicians, nurses, pharmacists, scientific investigators, pharmaceutical and medical device company representatives, and other health care professionals. All IRB members, faculty, and students in health care areas and administrators will benefit from the conference. Critical attention will be given to Federal regulations governing these special groups, professional judgment, real and perceived elements of "implied," "second," and "third" party consents. Conference emphasis will be placed on the assessment of risks and protection of the vulnerable subject with the application of medical, legal, psychosocial and ethical standards and principles. The conference format is structured to promote the optimum exchange of ideas and discussion through small and large group, topic-defined, informal, and provocative sessions. WEST COAST WORKSHOP DATES: January 23-24, 1994 LOCATION Doubletree Hotel, Pasadena, CA SPONSORS City of Hope National Medical Center, Duarte, CA Charles R. Drew University of Medicine and Science, Los Angeles, CA REGISTRATION Ms. Donna Pearce Administrative Secretary, IRB City of Hope National Medical Center Beckman Research Institute Duarte, CA 91010 Telephone: (818) 359-8111, ext. 2700 TITLE: Ethical Issues in Human Subject Research: Catastrophic Diseases and Minorities DESCRIPTION: This workshop is intended for physicians, nurses, pharmacists, and other health care professionals as well as administrators, members of Institutional Review Boards, students, ethicists and legal experts, and lay persons with interest and concern for human subject research. The program will address the following issues: (1) new governmental policies on human subject research; (2) resolving ethical principles in clinical research on AIDS, gene transfer, and cancer prevention trials involving catastrophic illnesses; (3) drug trials and parallel track protocols; (4) minorities as research subjects; and (5) the uncertain fate of clinical research in the current era of health care reform. SOUTH COAST CENTRAL WORKSHOP DATES: February 17-18, 1994 LOCATION Fairmont Hotel, New Orleans, LA SPONSORS University of New Orleans - Lakefront, New Orleans, LA Xavier University of Louisiana, New Orleans, LA REGISTRATION Ms. Anne O'Hearn Jakob Office of Conference Services University of New Orleans - Lakefront New Orleans, LA 70148 Telephone: (504) 286-7118 TITLE: Recent Trends in Human Subjects Research DESCRIPTION: The purpose of this conference is to explore recent issues and trends related to the protection of human subjects in research. It will provide discussions and opportunities among participants to share views on NIH's new guidelines on fetal research, the inclusion of women and minorities in research, and FDA's recent policy on enrolling women of childbearing age in drug trials. Workshops and meetings will be conducted by faculty of more than 25 national experts whose research interests include alzheimer's disease, environmental research, women's health, human genome research, biomedical research, and others. INQUIRIES For further information regarding these workshop and future NIH/FDA National Human Subject Protections Workshops, contact: Ms. Darlene Marie Ross Office for Protection from Research Risks National Institutes of Health Building 31, Room 5B63 Bethesda, MD 20892 Telephone: (301) 496-8101 $$N1 END ************************************************************ $$N2 BEGIN ********************************************************** WORLD AIDS FOUNDATION NIH GUIDE, Volume 22, Number 40, November 5, 1993 P.T. 34, 42; K.W. 0715008, 0502017 Fogarty International Center The World AIDS Foundation (WAF) announces its intent to support research and education relating to Acquired Immunodeficiency Syndrome (AIDS) in the developing world. The goal of the WAF is to facilitate information exchange and assist developing countries in responding to the AIDS pandemic. The WAF is particularly interested in projects that are catalytic and once in place could have a multiplicative effect. Projects that involve collaboration with the WHO Global Programme on AIDS are of particular interest. The WAF is also interested in supporting applications that originate from developing countries and that emphasize collaboration between and among scientists, physicians, and public health workers from developed and developing countries. Of special interest are projects that respond to the anticipated increase in HIV infection in South-East Asia and the Western Pacific. The limit of any single funding request to the WAF is $200,000. APPLICATION PROCEDURES Concept letters and applications may be prepared in either English or French. Applicants should submit concept letters for initial consideration. Following review of concept letters, applicants may be invited to submit complete proposals. The annual deadline for receipt of concept letters is February 1. INQUIRIES Concept letters and inquiries concerning the programs of the World AIDS Foundation may be directed by mail or by FAX to: World AIDS Foundation Assistant Secretary for Health c/o Director, Fogarty International Center National Institutes of Health Building 31, Room B2C02 Bethesda, MD 20892, U.S.A. FAX: (301) 402-2056 or Fondation Mondiale SIDA c/o Directeur de l'Institut Pasteur 28 rue du Docteur Roux 75724 Paris, Cedex 15, FRANCE FAX: 0033-1-45688938 $$N2 END ************************************************************ NOTICES OF AVAILABILITY (RFPs AND RFAs) $$R1 BEGIN CA-94-006 FULL-TEXT ************************************** PATTERNS OF CARE IN RADIATION ONCOLOGY NIH GUIDE, Volume 22, Number 40, November 5, 1993 RFA AVAILABLE: CA-94-006 P.T. 34; K.W. 0785140, 0725015, 0730050 National Cancer Institute Letter of Intent Receipt Date: December 1, 1993 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 Radiation Research Program (RRP), Division of Cancer Treatment (DCT), National Cancer Institute (NCI) invites applications for Patterns of Care Studies in Radiation Oncology. The objective of this RFA is to focus on those factors in radiation oncology that are most likely to affect patient outcome, such as failure to control local-regional neoplastic disease, treatment related morbidity that negatively impacts a patient's quality of life, or failure to implement new methods and treatment strategies that have been shown to be advantageous for the patient. 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, Patterns of Care in Radiation Oncology, 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 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 administrative and funding instrument to be used for this program will be the investigator-initiated research project grant (R01). The NCI anticipates awarding one to two grants, with total costs not to exceed $650,000 for the first year. This RFA is a one-time solicitation. Generally, future unsolicited competitive continuation applications will compete as research project applications with all other investigator-initiated applications and be reviewed by the Division of Research Grants (DRG). However, if it is determined that there is sufficient programmatic need, the NCI will invite recipients of awards under this RFA to submit competitive continuation grant applications for review according to the procedures of the DRG. FUNDS AVAILABLE Approximately $650,000 in total costs per year for three years will be committed specifically to fund grants that are awarded in response to this RFA. The NCI anticipates that one to two awards will be made. Although this program is provided for in the financial plans of the NCI, the award of a grant in response to this RFA is also contingent upon the availability of funds for this purpose. The earliest feasible start date for the initial award will be September 30, 1994. RESEARCH OBJECTIVES The major goal of this research initiative is to support clinical investigations that (1) document and evaluate patient survival and outcome as a function of radiation oncology practice and methodology, (2) coordinate with the leadership of the Cooperative Groups for the optimal design of protocols and clinical trials based on data received from patterns of care studies, (3) examine the patterns of care for minorities vs non-minorities, and (4) present the findings of the patterns of care studies to the radiation oncology community to achieve both the goals of information and education. The evaluation and documentation of the acceptance and implementation of new treatment strategies in the radiation oncology community where a benefit for the cancer patients has been shown is also of interest. New studies of interest are prospective patterns of care and/or patterns of fractionation studies that will support and enhance on-going protocols for cancers of the prostate and cervix. Prospective studies that show patterns of total care for breast cancer are of special interest. STUDY POPULATIONS SPECIAL INSTRUCTIONS FOR INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDIES NIH policy is that applications for NIH clinical research grants 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 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 persons of all ages. If minorities and women are excluded or inadequately represented in the clinical research of this RFA, a clear and compelling rationale must be provided. NIH funding components will not award grants that do not comply with these policies. LETTER OF INTENT Prospective applicants are asked to submit, by December 1, 1993, a letter of intent that includes a descriptive title of the proposed research, the name and address of the Principal Investigator, the names of other key personnel, the participating institutions, and the number and title of the RFA in response to which the application may be submitted. A letter of intent is not required, is not binding and does not enter into the review of subsequent applications. The letter of intent is to be sent to the Program Director at the address listed under INQUIRIES. APPLICATION PROCEDURES Application are to be submitted on form PHS 398 (rev. 9/91). Application kits are available from 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 RFA label available in the application form PHS 398 must be affixed to the bottom of the face page. Detailed instructions on submission procedures are described in the RFA. REVIEW CONSIDERATIONS Applications that are complete and responsive to the RFA will be evaluated by an appropriate peer review group convened by the NCI in accordance with the usual NIH peer review procedures. See RFA for review criteria to be used in initial review. Following initial review, applications will be given a secondary review by the National Cancer Advisory Board unless not recommended for further consideration by the initial review group. Applications that are incomplete or unresponsive to the RFA will be returned to the applicant. Questions concerning the responsiveness of proposed research to the RFA may be directed to program staff listed under INQUIRIES. 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 encouraged. The NCI welcomes the opportunity to clarify any issues or questions from potential applicants. Direct inquiries regarding programmatic issues and requests for the RFA to: Dr. Sandra Zink Radiation Research Program National Cancer Institute Executive Plaza North, Suite 800 Bethesda, MD 20892 Telephone: (301) 496-9360 FAX: (301) 480-5785 Direct inquiries regarding fiscal matters to: Ms. Barbara Fisher Grants Administration Branch Executive Plaza South, Room 242 6120 Executive Boulevard Rockville, MD 20852 Telephone: (301) 496-7800, Ext. 29 FAX: (301) 496-8601 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.395 (Cancer Treatment Research). Awards are made under the authorization of Public Health Service Act, Title IV, Sections 301, 410 and 411, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285 (a.)) and administered under the PHS grants policies and Federal Regulations 42 CFR Part 52 and 45 CFR Part 74 and 92. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$R1 END ************************************************************ $$R2 BEGIN HS-94-004 FULL-TEXT ************************************** FIRST INDEPENDENT RESEARCH SUPPORT AND TRANSITION AWARD NIH GUIDE, Volume 22, Number 40, November 5, 1993 RFA AVAILABLE: HS-94-004 P.T. 34; K.W. 0730050 Agency for Health Care Policy and Research Application Receipt Date: March 11, 1994 THIS IS A NOTICE OF THE 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 the First Independent Research Support and Transition (FIRST) Award (R29) in health services research. The purpose of the FIRST Award is to provide a sufficient period of research support for newly independent health services researchers to initiate their own research and demonstrate independent investigative efforts; provide a reasonable opportunity to demonstrate creativity, productivity, and further promise; and to help in the transition to traditional types of AHCPR research project grants. The award is not intended for established investigators who may be in transition to another endeavor. A FIRST Award is for a distinct research endeavor and may not be used merely to supplement or broaden an ongoing project at the applicant institution. FIRST Awards are intended to provide funds for newly independent investigators for five years during which time they can establish their own research program and make significant and innovative contributions to health services research. 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 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 To be eligible for a FIRST Award, the proposed Principal Investigator (PI) must be genuinely independent of a mentor, yet at the beginning stages of his or her research career with, in most instances, no more than five years research experience since completing postdoctoral research training or its equivalent. If the applicant is in the final stages of such training, it is permissible to apply, but no FIRST Award will be made to persons in training status. In addition, the proposed PI must otherwise be eligible to serve in the same capacity on a traditional research project grant (R01) awarded to the applicant institution. Only non-profit domestic institutions and organizations are eligible to receive FIRST Awards. Further information on eligibility is contained in the RFA. MECHANISM OF SUPPORT This RFA represents the initial use of the First Independent Research Support and Transition (FIRST) Award (R29) by AHCPR. See SPECIAL REQUIREMENTS, below, for details of this mechanism. FUNDS AVAILABLE The AHCPR expects to fund approximately three FIRST Awards in Fiscal Year (FY) 1994. The actual number awarded in FY 94 will depend on availability of funds as will the number in future years. RESEARCH OBJECTIVES The AHCPR conducts and supports research on the quality, appropriateness, efficiency, and effectiveness of health care services and the systems for delivery of these services. Research areas of interest for FIRST applications are as follows: o Health care reform issues; o Health care costs and financing; o Relationship between primary care and health care costs, access, and quality; o Rural health including access to services, supply of health professionals, delivery systems issues, primary health care, health promotion and disease prevention, technology diffusion, and special populations; o Health care quality improvement and quality assurance including methods and measures; o Information technologies and factors affecting their use; o Costs and quality of alternative delivery systems and managed care; o Health care technologies, facilities, and equipment; o Medical effectiveness and patient outcomes research; o Medical liability and malpractice; o Access, medical effectiveness, and patient outcomes research in low-income, minority, elderly, and other underserved populations; o Dissemination of health and clinical information and research findings to practitioners, consumers, and patients for use in improved health care decisionmaking; o Services for persons with human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS); and o Evaluation of outcomes associated with the use of clinical practice guidelines. The following program announcements, which were published in the NIH Guide for Grants and Contracts, provide more detailed information on selected areas of interest: "Health Services for Persons with HIV Infection" (PA-93-110), Vol. 22, No. 33, September 17, 1993; "Health Care Quality Improvement and Quality Assurance Research" (PA-93-084), Vol. 22, No. 19, May 21, 1993; "Primary Care and Health Care Reform" (PA-93-063), Vol. 22, No. 10, March 12, 1993; "Cost and Financing Issues in Health Care Reform" (PA-93-45), Vol. 22, No. 4, Jan. 29, 1993; "Health Services Research on Rural Health" (PA-92-71), Vol. 21, No. 16, May 1, 1992; and "Effective Dissemination of Health and Clinical Information and Research Findings" (PA-92-51), Vol 21, No. 10, March 13, 1992. SPECIAL REQUIREMENTS An individual may submit only one FIRST Award application to the Public Health Service for this receipt date. FIRST Award applications must request five years of research support. Applications submitted to AHCPR in which the request is for fewer than five years of support will be returned to the applicant. The PI must make a commitment of no less than 50 percent effort to the proposed project. Up to 100 percent effort may be requested if a greater commitment of the PI is required to do the research. The request for effort of the applicant investigator will be reviewed and modifications may be recommended. The total direct cost award for the five-year period may not exceed $350,000. The direct cost award in any yearly budget period should not exceed $100,000. Indirect costs will be paid to the grantee institution in accord with applicable policy of the Department of Health and Human Services (DHHS). FIRST Awards are not renewable. Further special requirements are provided in the RFA. STUDY POPULATIONS SPECIAL INSTRUCTION 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. All applications without such documentation will not be accepted for review. APPLICATION PROCEDURES The RFA contains important information for applicants, including the application and review schedule for FIRST Awards, and may be obtained from the Center for Research and Dissemination Liaison, see INQUIRIES. The application receipt date is March 11, 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. In addition, a letter or memorandum from a suitable department head or dean is to be submitted with the application, that addresses: (1) eligibility of proposed Principal Investigator to independently lead a research project at the applicant institution (i.e., is this person otherwise qualified to be the PI on a traditional research project grant (R01)?) and (2) details of the intended commitment of the institution to the project for the five-year period. Also, three letters of reference for the proposed PI are to be submitted with the application. Further details on letters of reference are provided in the RFA. 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. Further review considerations and review criteria are listed in the RFA. Review results and funding decisions will be announced approximately six months after the submission date. INQUIRIES A copy of the RFA may be obtained from the Center for Research Dissemination and Liaison at the address below. In addition, inquiries regarding programmatic issues may be directed to the appropriate office listed below: Applied Dissemination Research: Center for Research Dissemination and Liaison Suite 501, telephone (301) 594-1362 Medical Effectiveness and Outcomes Research: Center for Medical Effectiveness Research Suite 605, telephone (301) 594-1485 Other AHCPR Health Services Research: Center for General Health Services Extramural Research Suite 502, telephone (301) 594-1349, Ext. 104 Direct inquiries regarding fiscal/administrative matters to: Ralph Sloat, Grants Management Officer Agency for Health Care Policy and Research 2101 East Jefferson Street, Suite 601 Rockville, MD 20852 Telephone: (301) 594-1447 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.180 and 93.226. Awards are authorized under 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. This program is not subject to the intergovernmental review requirements of Executive Order 12372. $$R2 END ************************************************************ $$R3 BEGIN AI-94-002 FULL-TEXT ************************************** MECHANISM of RESPIRATORY SYNCYTIAL VIRUS VACCINE IMMUNOPOTENTIATION NIH GUIDE, Volume 22, Number 40, November 5, 1993 RFA AVAILABLE: AI-94-002 P.T. 34; K.W. 0705048, 0740075, 0710070 National Institute of Allergy and Infectious Diseases Letter of Intent Receipt Date: January 14, 1994 Application Receipt Date: March 17, 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 Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID) announces the availability of an RFA for research on the immunology of Respiratory Syncytial Virus (RSV) protection and disease. Specifically, the NIAID is interested in addressing the immune responses associated with the exacerbation of disease in children who had previously received formalin-inactivated RSV vaccine. 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, Mechanism of Respiratory Syncytial Virus (RSV) Vaccine Immunopotentiation, 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 grant (R01) award 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 by domestic institutions may not exceed four years; the total project period for applications submitted by foreign institutions may not exceed three years. The anticipated earliest possible award date is September, 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 animal or patient populations so as to accelerate technical progress and clinical development of promising prophylactics. 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 funds available for the total (direct and indirect) first year cost of all awards under this RFA is $ 1.0 million. The NIAID anticipates making a minimum of three new awards. RESEARCH OBJECTIVES Presently, there are no licensed Respiratory Syncytial Virus (RSV) vaccines and only limited efforts in the development of vaccine candidates because attempts to develop a safe and effective vaccine have met with continued frustration. In the mid-1960s, a formalin inactivated RSV vaccine was evaluated in previously unprimed (seronegative) infants. When these children were subsequently exposed during an RSV outbreak, the resulting illnesses were very severe. Specifically, children under two years of age who received the vaccine had a much higher incidence of pneumonia (60 percent) and hospitalization (21 percent) compared to the children who received placebo (8 percent and 1.5 percent, respectively). Attempts to understand the nature of this immunopotentiation event have relied primarily on data generated using the cotton-rat model. In this system, RSV challenge of animals immunized with a formalin-inactivated RSV vaccine has been associated with changes in lung histology. The equation of this altered histology in animals with the exacerbated disease in humans has been widely debated. Nonetheless, in the absence of definitive data to the contrary, the cotton-rat model has been widely used to define the preclinical safety of potential new vaccine candidates. At a recent NIAID/WHO/CDC RSV Workshop (May 1993) use of alternative animal model systems for detailed studies of the immunologic mechanism of immunopotentiation (eg., mouse model) and development of animal models with clinical disease patterns/immunologic responses similar to those seen in humans (eg., lamb/bovine models) were encouraged. It was also clear that continued use of the cotton rat model to define safety of new experimental vaccines requires additional knowledge as to the basis of the histologic changes observed following challenge. Until then, a significant barrier would remain in the development of RSV vaccines. The long-term goal of the NIAID is to facilitate the development of an effective RSV vaccine. However, interim objectives must be met before candidate vaccines can be entered into clinical trials involving seronegative infants and children. The goal of this RFA is to stimulate innovative new research on the complex immunology associated with RSV disease immunopotentiation and within that context to develop in vitro and/or in vivo assays that accurately reflect the potential safety of RSV vaccine candidates. Examples of projects that might be responsive to this RFA include, but are not limited to: 1. Detailed analysis of the immune pathways stimulated following: o immunization with experimental RSV vaccines that have been previously associated with immunopotentiation; o immunization with experimental RSV vaccines that have been associated with protection but not immunopotentiation; o natural infection; 2. Development of in vivo models that closely mimic the clinical disease/immunopotentiation event seen in humans; 3. Development of immunologically defined reagents for valid in vivo models; 4. Development of in vitro models to assess the immunopotentiation effect of candidate RSV vaccines; 5. Definition of the properties of vaccine preparations which have been associated with immunopotentiation. 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 will be requested to attend to discuss progress. At the discretion of the Program Staff, clinical researchers and members of the vaccine industry may also be invited to attend. 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 January 14, 1994, 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), which is 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 date for receipt of applications is March 17, 1994. 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 and Dr. Olivia Preble by the application receipt date. Applications not received on this 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 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 to determine their scientific merit relative to the other applications submitted in response to this RFA. The NIH 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. Carole Heilman Division of Microbiology and Infectious Diseases National Institute of Allergy and Infectious Diseases Solar Building, Room 3B-06 Bethesda, MD 20892 Telephone: (301) 496-5305 FAX: (301) 496-8030 Address 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 4C19 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. $$R3 END ************************************************************ ONGOING PROGRAM ANNOUNCEMENTS $$P1 BEGIN PA-94-010 ************************************************ RESEARCH ON NEEDLE HYGIENE AND NEEDLE EXCHANGE PROGRAMS NIH GUIDE, Volume 22, Number 40, November 5, 1993 PA NUMBER: PA-94-010 P.T. 34; K.W. 0404009, 0411005, 0715008 National Institute on Drug Abuse PURPOSE The purpose of this program announcement is to encourage research on comprehensive needle hygiene activities in two areas: (1) intervention studies related to the adoption of NIDA's newly proposed recommendations to prevent HIV transmission by not sharing drug injection equipment (directly or indirectly), including new research findings on efficacy of disinfection of cleaning needles and syringes and (2) the evaluation of needle exchange programs (NEP) in combination with other HIV risk reduction strategies. These two interrelated research initiatives have great implications for creating and reformulating comprehensive prevention programs in the midyears of the second decade of the HIV epidemic. The goal of research on needle hygiene and NEPs is to develop, implement, and evaluate strategies that reduce HIV risk behaviors and decrease the probability of HIV exposure. 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 announcement, Research on Needle Hygiene and Needle Exchange Programs, is 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 of 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 Applicants may be submitted by foreign and domestic, for-profit and non-profit, public and private organizations such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Women and minority investigators are encouraged to apply. Applicants are encouraged from State and municipal governments with outreach units and/or State and municipal governments collaborating with university-based research units. MECHANISM OF SUPPORT This program announcement will use the National Institutes of Health (NIH) individual research project grant (R01). Because the nature and scope of the research proposed in response to this program announcement may vary, it is anticipated that the size of an award will vary also. RESEARCH OBJECTIVES Summary The NIDA initiated the Cooperative Agreement for AIDS Community-Based Outreach/Intervention Program in 1990. Since that time, NIDA, the Centers for Disease Control and Prevention (CDC), and other agencies' grantees have been monitoring the HIV/AIDS epidemic in a population of out-of-treatment drug users and developing, implementing, and assessing the effectiveness of selected interventions. During this period, considerable changes have occurred in community ecologies (social and biological environments) related to HIV and drug use (e.g., dramatic increase in tuberculosis and heterosexual transmission, male heterosexual increase in incidence of HIV of 114 percent; female heterosexual increase 108 percent) as well as in the behavioral dynamics of at-risk populations and the science of prevention. More than 300,000 cases of AIDS were reported to the CDC as of July 1993; of these, 20 percent of the males and 49 percent of the females were exposed to the virus via injecting drug use. Changes such as these dictate the need to promote new study activities. Fortunately, during this time, knowledge has been gathered about preventing the spread of HIV through behavioral change interventions designed to reduce an individual's risk of transmission. In addition, selected interventions have been effective in facilitating risk reduction behavioral change among injection drug users (IDUs). Nonetheless, preliminary findings from NIDA sponsored research programs suggest that there is room for improvement and expansion of community-based behavioral change strategies to reduce the spread of HIV. For example, many IDUs who have tested HIV positive report that they lend their "works" to others, while many who have tested negative report borrowing needles and not practicing adequate needle hygiene. Recent ethnographic observation has uncovered the finding that injectors are unaware that indirect exposure (i.e., using potentially contaminated syringes to prepare and divide drug solutions) may place them at risk for the transmission of HIV. Although many drug users do make positive behavioral changes, a large percentage require additional assistance to maintain their lower risk behavioral profiles. Whereas behavioral interventions are the most promising prevention strategy available (near-term prospects for a vaccine or cure are not favorable), challenges such as those mentioned above suggest that our research efforts now need to expand their focus by phasing in and evaluating third generation innovative community-based behavioral change projects. These new research endeavors should include populations that have adopted change to facilitate the maintenance of these safer behaviors and/or those that have yet to adopt lower risk needle sharing behaviors. Two particular areas deserve special attention: (1) updated research data on the efficacy of cleaning needles and syringes with bleach make it incumbent upon us to examine the extent to which drug users are able to comply with revised disinfection recommendations (HIV/AIDS Prevention Bulletin, April 19, 1993); (2) an increasing national interest in needle exchange as an AIDS prevention strategy (GAO/HRD 93-60 and CDC, unpublished report) raises the need to evaluate the full range of effects of programs that provide access to unused injection equipment. It is of critical importance to understand the social context of these behaviors, the extent to which needles are available and accessible, and the impact of local laws and regulations concerning needle/syringe availability and paraphernalia possession on HIV risk behaviors and behavioral change. In light of the preliminary findings, proposed bleach disinfection recommendations, and a growing interest in needle exchange, we are calling for expanded research designs that will extend ongoing research activities. There is a need for targeted interventions focusing specifically on current risk behavior in demographic, geographic and behavioral subgroups of the at-risk populations to permit a better understanding of the behavioral dynamics of drug users in social context and the spread of HIV. For research strategies to be effective and interpretable, they should be guided theoretically and should target selective risk behaviors of individuals and/or networks. Interventions on behavioral norms that facilitate or discourage behavior change within communities and the development of strategies for specific subgroups of at-risk populations are encouraged. Attention should be paid to developing operationalized definitions and measures that describe the behavioral dynamics and intervention process. The foci of this research activity are epidemiologic/ethnographic observations of needle sharing practices (indirect and direct), use/nonuse of needle exchange, and evaluation of the efficacy of the interventions. Methodological problems associated with research related to the efficacy of needle exchange programs must be addressed if the findings can prove helpful in developing policy options. NIDA and CDC have collaborated, and will continue to collaborate, in the development and implementation of this program announcement. Program Description Needle/Syringe Sharing and Needle Hygiene Studies. Studies are needed to evaluate the impact of proposed recommendations on the disinfection of injection equipment, the impact of these changes on members of the injecting drug user community, and the diffusion of information about needle cleaning procedures. To date, our knowledge base contains limited information on the sequence and procedures related to disinfection practices acquired from a few quantitative surveys and even fewer qualitative studies. Thus, both qualitative and quantitative data on previous and current needle sharing and cleaning practices are desired to identify factors that facilitate and/or inhibit the adoption of recently proposed needle hygiene practices. Applicants are encouraged to design and evaluate interventions that specifically focus on changing behavior in accordance with the proposed guidelines for needle cleaning. In order to plan potentially efficacious prevention activities, it will be critical to assess and evaluate how needle use, needle cleaning, and disease avoidance behaviors currently vary at the individual/network level as well as by communities with different prevalence rates of HIV/AIDS. We anticipate that several intervention strategies will be needed to take into account the behavioral heterogeneity of groups and individuals as well as the varying HIV seroprevalence of different communities. Race/ethnicity, and gender-related factors must be addressed in the design, implementation, and evaluation of the interventions. It is hoped that, in addition to the above, innovative research studies will obtain new data/information about drug injectors and practices (e.g., injection settings and situations, how and from whom users learn to inject, how they understand needle-sharing $direct sharing via actual use and indirect sharing via drug solution, cookers, cotton, rinse water, and the relation to HIV infection) that can be used to maximize the effectiveness of cleaning drug equipment. While not limited in scope, three methodologies are encouraged: (1) overt, passive participant field observation of needle-sharing/cleaning practices by trained ethnographers across diverse settings; (2) life-history interviews that incorporate a guided interview with respect to past and current needle sharing/cleaning practices; and (3) biological (e.g., HIV, hepatitis B virus, amount of blood, blood type, antibody, DNA "fingerprint") testing of needles/syringes, cotton, cookers, rinse water, etc., to measure levels of infectivity and sharing. These methodologies will form the basis for designing the interventions and should be derived theoretically from the social and behavioral science literature on behavioral change. Needle Exchange Programs (NEPs). A relatively new prevention strategy undergoing extensive review is that of needle exchange programs, which generally involve the exchange of new, sterile syringes for used ones. NEPs currently exist and are beginning in a number of communities across the country. Given the proliferation of NEPs, it is important to prepare for the possible inclusion of needle exchange as an intervention strategy to reduce risk behavior associated with HIV transmission in the future. Applicants are encouraged to obtain the report of the recent CDC funded study on needle exchange prepared by the University of California, San Francisco (Lurie and Reingold, 1993). The NIDA will not support needle exchange programs, per se, but will support the evaluation of the efficacy of currently operating needle exchange programs on drug use, HIV risk behaviors, and HIV serostatus. Ethnography, epidemiology, and evaluation perspectives must guide the research activities around needle exchange. Baseline epidemiologic data are urgently needed, as are efficacy studies of NEP as part of HIV risk reduction. Such epidemiological data should be based on longitudinal information and should include data on risk behaviors and serostatus of identifiable subgroups as a function of gender, race/ethnicity, and drug using characteristics. Cross-sectional information may be collected as part of a well-defined strategy. Efficacy data should focus on NEPs impact on HIV risk reduction as well as other health-related and economic consequences of such programs. These data may be qualitative in nature or may derive from observational studies that attempt to control for diverse factors related to risk reduction. Studies using a social network perspective are encouraged. Research should focus on the comparative effectiveness of existing needle exchange programs in relation to the more standard needle cleaning practices and other behavioral risk reduction programs. Comparison of communities with NEP currently in place is encouraged to evaluate the impact of such programs on relative risk reduction in their communities and compare the rate of risk to communities currently without such programs, taking into account differing HIV prevalence rates, needle availability in the communities, and the legality of accessing needles. Such studies, particularly those that attempt to control as many potentially confounding factors as possible, will enhance our understanding about the relative consequence of various community-based intervention strategies. It is critical to overcome some of the methodological limitations surrounding the interpretation of data from previous research related to evaluation of syringe exchange programs. For example, methodologic issues often cloud the task of collapsing client characteristics across studies (e.g., convenience sampling is only adequate if it is a representative sample; random sampling avoids the potential bias associated with convenience sampling). Careful attention must be given to design, management, analyses, and overwhelming limitations in implementing controlled random trials in community based settings. Interpretation of some studies is complicated by the choice of central tendency measures, with most studies choosing to report the value of the median (without descriptive qualifiers), which makes it impossible to access information about the statistical 'outliers' (those clients who are younger, or who inject more or less frequently). Additionally, there would be an important advantage in comparing groups who have access to needle exchange versus those who have no access as studies that include comparison group(s) are able to provide a referent for describing characteristics of clients. Where feasible, enhancing ongoing studies focusing on the issues of needle hygiene and/or needle/syringe exchange, is encouraged. Investigators are required to offer HIV testing and counseling in accordance with current guidelines to subjects identified 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. Methodology Independent information can include, but need not be limited to: 1. Macro Level Factors/Social Environment. Needle availability, accessibility, and laws and regulations governing access to and possession of paraphernalia in regards to both bleach distribution and needle exchange programs and the effects of these factors on needle sharing (direct and indirect), bleach distribution, disinfecting equipment. 2. Social Context of Drug Using Behaviors. Characteristics of injection locations (e.g., access to running water, bathrooms, etc), types and amounts of drugs used, drug preparation techniques, types of injection equipment used, factors that appear to limit or enhance needle sharing and disinfection. 3. Social Network Factors. Research on the structural characteristics of drug user networks are encouraged and norms that govern these behaviors, characteristics of individuals present in the injection situation (participants and nonparticipants); others with whom the respondent injects (race/ethnicity, gender, relationships that may affect the order of who injects first); cleaning or disinfectant behavior if equipment is shared; conversations that include discussions of HIV, AIDS, HIV prevention. 4. Micro Level/Individual Factors. Behavioral data on how respondents usually acquire needles (access), and with what difficulty (barriers); respondents' participation in an HIV intervention program and what is recalled; individual changes in drug use, injection, and disinfection behaviors over time; subgroup changes in these behaviors; and intervention components, if any, that account for the change. 5. Efficacy of Interventions. Evaluation of different behavior change interventions and identifying subgroup characteristics as a function of which intervention produces risk reduction, analyzing changes in behavioral risk as a function of intervention, evaluating the extent (with a special focus on the duration) of change as it relates to type of intervention employed. 6. Demand for and Utilization of Risk Reduction Services. Bleach distribution, impact of preventive services on adoption of preventive behaviors. Cost associated with providing services to various at risk populations. 7. Interface with Drug/Medical Treatment System. Evaluation of effective methods of referral to medical and drug treatment; evaluation of participation in the NEP on medical treatment adherence; effects on probability and duration of drug relapse and maintenance of risk reduction during relapse; effects of NEP sites located close to drug treatment programs (methadone or drug free programs), hospitals, psychiatric facilities, homeless shelters or other facilities that attract concentrations of individuals who are vulnerable to initiating drug injection, relapsing to drug use or injection, having sex with injection users or becoming victims of crime associated with injection users, effects on treatment seeking and retention into treatment. 8. Program Design Issues. Influence on NEP program effectiveness of hours of operation, distribution of bleach and condoms, distribution of other paraphernalia, (e.g., cotton, cookers), access to HIV testing and counseling and medical care on site, availability of other social services, additional educational efforts, forms of assurance of confidentiality/anonymity. 9. Equipment Infectivity and Sharing Issues. Use of a syringe tracking and biological (e.g., HIV, hepatitis B virus, amount of blood, blood type, antibody, DNA "fingerprint") testing system to measure the effects of the NEP on levels of infectivity and sharing as well as circulation times of syringes and effectiveness of cleaning. Consistent NEP participants may be compared with samples of inconsistent participants and non-participants with respect to these parameters; sharing networks may be identified and tracked; needle/syringe dynamics may be elucidated and equipment from community sites may be compared with that distributed by the NEP. Conceptual and methodological research from a social network perspective is encouraged, and not only relying on the index subject, but linked data to his or her drug user contact and other network members will help to address unanswered questions. In summary, qualitative and quantitative evaluations of NEPs should contribute to our understanding about what works (intervention components), in which communities does it work (given varying epidemiological and social demographic characteristics), with whom does it work (subgroups), and how much does it cost. 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 AIDS-related 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 Grant Information, Division of Research Grants, National Institutes of Health, Westwood Building, Room 240, Bethesda, MD 20892, telephone 301-594-7248. The title and number of the program announcement must be typed in Item 2a on the face page of the application. The completed original and five permanent, legible copies of the PHS 398 form must be submitted to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** REVIEW CONSIDERATIONS The Division of Research Grants, NIH, serves as a central point for receipt of applications for most discretionary DHHS grant programs. Applications received under this program 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 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 Advisory Council will be considered for funding on the basis of overall scientific, clinical and technical merit of the application as determined by peer review, appropriateness of budget estimates, program needs and balance, policy considerations, adequacy of provisions for the protection of human subjects, and availability of funds. 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: Richard Needle, Ph.D., M.P.H. Community Research Branch National Institute on Drug Abuse 5600 Fishers Lane, Room 9A-30 Rockville, MD 20857 Telephone: (301) 443-6720 From owner-sci-resources@net.bio.net Thu Nov 18 22:00:00 1993 Path: biosci!net.bio.net From: kristoff@net.bio.net (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 22, no. 41, 12 November 1993 Message-ID: Date: 19 Nov 93 04:46:13 GMT Sender: kristoff@net.bio.net Lines: 1404 Approved: biosci-moderator@net.bio.net $$XID NIHGUIDE 19931112 V22N41 P1O1 ************************************ X-comment: RFAs described: DA-94-002 NIH GUIDE - Vol. 22, No. 41 - November 12, 1993 $$INDEX BEGIN ******************************************************* NOTICES $$INDEX N1 ********************************************************** REVISED CRITERIA FOR EVALUATING PRE- AND POSTDOCTORAL INDIVIDUAL NATIONAL RESEARCH SERVICE AWARDS National Institute of Nursing Research INDEX: NURSING RESEARCH NOTICES OF AVAILABILITY (RFPs AND RFAs) $$INDEX R1 ********************************************************** TERRY BEIRN COMMUNITY PROGRAMS FOR CLINICAL RESEARCH ON AIDS STATISTICAL CENTER (RFP NIH-NIAID-DAIDS-95-01) National Institute of Allergy and Infectious Diseases INDEX: ALLERGY, INFECTIOUS DISEASES $$INDEX R2 ********************************************************** DEVELOPMENT AND MANUFACTURE OF DOSAGE FORMS OF COMPOUNDS W/POTENTIAL FOR TREATMENT OF INFECTIOUS DISEASES (RFP NIH-NIAID-DAIDS-95-03) National Institute of Allergy and Infectious Diseases INDEX: ALLERGY, INFECTIOUS DISEASES $$INDEX R3 ********************************************************** PHARMACEUTICAL SUPPORT FOR PRE-CLINICAL EVALUATION OF ANTIRETROVIRAL AND ANTI-INFECTIVE AGENTS (RFP NIH-NIAID-DAIDS-95-04) National Institute of Allergy and Infectious Diseases INDEX: ALLERGY, INFECTIOUS DISEASES $$INDEX R4 ********************************************************** RESYNTHESIS OF POTENTIAL THERAPEUTIC AGENTS FOR TREATMENT OF INFECTIOUS DISEASES (RFP NIH-NIAID-DAIDS-95-05) National Institute of Allergy and Infectious Diseases INDEX: ALLERGY, INFECTIOUS DISEASES $$INDEX R5 ********************************************************** TUBERCULOSIS PREVENTION AND CONTROL RESEARCH (RFP NIH-NIAID-DMID-94- 22) National Institute of Allergy and Infectious Diseases INDEX: ALLERGY, INFECTIOUS DISEASES $$INDEX R6 03/11/94 ************************************************* BEHAVIORAL THERAPIES DEVELOPMENT PROGRAM (RFA DA-94-002) National Institute on Drug Abuse INDEX: DRUG ABUSE This publication is available electronically to institutions via BITNET or INTERNET and is also on the NIH GOPHER. Alternative access is through the NIH Grant Line using a personal computer (data line 301/402-2221). Contact Dr. John James at 301/594-7270 for details. $$INDEX END ********************************************************* NOTICES $$N1 BEGIN ********************************************************** REVISED CRITERIA FOR EVALUATING PRE- AND POSTDOCTORAL INDIVIDUAL NATIONAL RESEARCH SERVICE AWARDS NIH GUIDE, Volume 22, Number 41, November 12, 1993 P.T. 22; K.W. 0720005, 1014006 National Institute of Nursing Research The National Institute of Nursing Research (NINR) has revised the criteria for evaluating Predoctoral and Postdoctoral Individual National Research Service Awards (F31 and F32). Copies of new guidelines are being mailed to schools and colleges of nursing, but faculty and potential applicants may request a copy from: Ms. Anissa Nash National Institute of Nursing Research Building 31, Room 5B03 Bethesda, MD 20892 $$N1 END ************************************************************ NOTICES OF AVAILABILITY (RFPs AND RFAs) $$R1 BEGIN NIH-NIAID-DAIDS-94-01 ************************************ TERRY BEIRN COMMUNITY PROGRAMS FOR CLINICAL RESEARCH ON AIDS STATISTICAL CENTER NIH GUIDE, Volume 22, Number 41, November 12, 1993 RFP AVAILABLE: NIH-NIAID-DAIDS-95-01 P.T. 34; K.W. 0715008, 0755018 National Institute of Allergy and Infectious Diseases The Division of AIDS (DAIDS), National Institute of Allergy and Infectious Diseases (NIAID), has a requirement for the continuation of the Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA) Statistical Center to work in partnership with a series of CPCRA research units awarded to community-based health organizations. The objective of this contract is to bring statistical expertise to the design and analysis of community-based clinical research and provide central data management of research data, thus contributing to improving the clinical management of persons with HIV disease. This Request for Proposals (RFP) represents the recompetition of the CPCRA Statistical Center, with an October 1994 award date. Necessary functions relevant to this activity include: providing leadership with regard to experimental design, sample size, protocol feasibility, data analysis, and other statistical issues involving protocol development, implementation, and analysis; performing interim and final statistical analyses and being substantially involved in the writing of scientific papers; conducting methodological research on the efficient design, conduct, and analysis of community-based clinical research studies; performing cross-study analyses to identify new leads regarding prognostic factors and late treatment effects; designing and implementing a program to provide training to CPCRA participants with respect to statistical and data management issues, including protocol-specific training; serving on relevant CPCRA committees; providing for central registration of patients and for randomization where appropriate; identifying information to be included in protocol-specific research records, developing study forms, and defining the computerized database; providing for centralized data entry for all research studies as well as computer processing, storage, and retrieval of data at a central data management facility using a commercial (nonproprietary) database management system; designing and implementing quality assurance procedures to evaluate the validity and completeness of data collected; and preparing and distributing a variety of reports, operation manuals, and related material. To perform the required work, the Contractor must be able to provide: experience as a statistical and data management center for multicenter clinical trials research efforts; Ph.D.-level statisticians with experience and expertise in statistical techniques required for the analysis of clinical trials; experience in active collaborations with clinicians in the design, conduct, and analysis of clinical trials; access to large-capacity computer facility; and experience in the various activities described above. This is an announcement for an anticipated RFP. The issuance of RFP NIH-NIAID-DAIDS-95-01 will be available on or about November 22, 1993, and proposals will be due by 4:30 p.m., local time, on February 15, 1994. It is anticipated that one contract will be awarded as a result of this solicitation. It is expected that the contract will have a seven-year period of performance, and a completion cost- reimbursement type contract is anticipated. INQUIRIES Provide this office with five self-addressed mailing labels. Telephone inquiries will not be honored, and all inquiries must be in writing. A short-form version of the RFP will be provided first, which includes only the Statement of Work, Reporting Requirements, and the Evaluation Criteria to be used for selection of the awardees. After examining this, a full-text version of the RFP must be requested, in writing, for those offerors interested in responding. FAX requests are acceptable for full text versions of the RFP only. All proposals from responsible sources will be considered by the NIAID. This advertisement does not commit the Government to award a contract. No collect calls will be accepted. Requests for the RFP are to be directed in writing to: Ms. Nancy M. Hershey Contract Management Branch National Institute of Allergy and Infectious Diseases Solar Building, Room 3C07 6003 Executive Boulevard Bethesda, MD 20892 FAX: (301) 402-0972 $$R1 END ************************************************************ $$R2 BEGIN NIH-NIAID-DAIDS-95-03 ************************************ DEVELOPMENT AND MANUFACTURE OF DOSAGE FORMS OF COMPOUNDS WITH POTENTIAL FOR TREATMENT OF INFECTIOUS DISEASES NIH GUIDE, Volume 22, Number 41, November 12, 1993 RFP AVAILABLE: NIH-NIAID-DAIDS-95-03 P.T. 34; K.W. 0715125, 0740021 National Institute of Allergy and Infectious Diseases The Developmental Therapeutics Branch, Basic Research and Development Program, Division of AIDS of the National Institute of Allergy and Infectious Diseases (NIAID) has a requirement for the development and manufacture of dosage forms of potential therapeutic agents that are intended for evaluation in Phase I and Phase II clinical protocols. The contractor will be required to: determine suitable formulations for therapeutic agents, evaluate new formulation compositions and technologies, manufacture dosage formulations, evaluate bulk drug substances using appropriate analytical assays, and conduct quality control testing of manufactured dosage forms. The Request for Proposals (RFP) contains two mandatory qualification criteria: (1) pharmaceutical companies are excluded from participating as a prime contractor or subcontractor and (2) at the time of the Best and Final Offers, the Offeror must be capable of manufacturing pharmaceutical materials in compliance with current Good Manufacturing Practice (GMP) regulations (21 CFR 210-211). This announcement is for the recompetition of a current contract the ended October 25, 1993. RFP NIH-NIAID-DAIDS-95-03 was issued November 1, 1993, and proposals will be due by COB February 15, 1994. It is anticipated that one level- of-effort type cost reimbursement contract will be awarded and the period of performance for this contract will be five years. A short-form version of the RFP will be available, for informational purposes, which includes the background information, the full Statement of Work, Evaluation Criteria, and the Reporting Requirements. There is sufficient information in this document to enable prospective offerors to determine if they have the expertise/capability to meet the Government's requirements. A full- text version is also available, which includes all the necessary information, business forms, etc., to submit a proposal. There are a limited number of full-text versions available. Therefore, request the short-form RFP first, then the full-text version only if you intend to submit a proposal. All requests must be in writing. Specify if you are requesting the short-version or full-text version of the RFP (if no distinction is made, the short-form version will be sent). Fax responses are acceptable, but it is preferred that requests be submitted in writing with two self-addressed mailing labels attached to ensure proper delivery. All proposals from responsible sources will be considered by the NIAID. This advertisement does not commit the Government to award a contract. INQUIRIES Requests for the RFP are to be directed in writing to: Mr. Ross Kelley Contract Management Branch National Institute of Allergy and Infectious Diseases Solar Building, Room 3C07 6003 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-2509 FAX: (301) 402-0972 $$R2 END ************************************************************ $$R3 BEGIN NIH-NIAID-DAIDS-95-04 ************************************ PHARMACEUTICAL SUPPORT FOR PRE-CLINICAL EVALUATION OF ANTIRETROVIRAL AND ANTI-INFECTIVE AGENTS NIH GUIDE, Volume 22, Number 41, November 12, 1993 RFP AVAILABLE: NIH-NIAID-DAIDS-95-04 P.T. 34; K.W. 0740012, 0740025 National Institute of Allergy and Infectious Diseases The National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), supports the discovery, preclinical, and clinical development of compounds to treat infectious diseases. The purpose of this solicitation is to provide analytical and pharmaceutical support to the drug discovery effort in the areas of analytical method development and quality control of chemicals and pharmaceuticals. Responsibilities of the contractor will include: characterization of the identity and purity of the drug substance, preformulation determinations of compound solubility and stability, analysis of pharmaceutical dosage forms, and extensions of the analytical methodologies to the detection of the drug in selected biological fluids. The current contract will expire on October 25, 1994. This solicitation is to re-compete this effort. A portion of the work under this contract may require use of a laboratory in compliance with current Good Laboratory Practice (GLP) regulations, issued by the Federal Drug Administration (FDA). In order to qualify for an award, the offeror must either have a laboratory facility in compliance with GLP regulations or must propose a subcontract with such a laboratory facility. This is an announcement for an anticipated Request for Proposal (RFP). RFP NIH- NIAID-DAIDS-95-04 was issued on November 1, 1993, and proposals will be due by the close-of-business February 15, 1994. It is anticipated that one level-of-effort type cost-reimbursement contract will be awarded for a five year period to carry out analytical method development and pharmaceutical analysis of therapeutic agents and dosage forms as a result of this solicitation. A short-form version of the RFP will be available for informational purposes, which includes the background information, full Statement of Work and Evaluation Criteria, and the Reporting Requirements. There is sufficient information in this document to enable prospective offerors to determine if they have the expertise/capability to meet the Government's requirements. A full- text version is also available, which includes all the necessary information, business forms, etc., to submit a proposal. There are a limited number of full-text versions available. Therefore, request the short form RFP first, then the full-text version only if you intend to submit a proposal. Telephone inquiries will not be honored. Specify if you are requesting the short-form or full-text version of the RFP (if no distinction is made, the short-form version will be sent). FAX responses are acceptable, but it is preferred that requests be submitted in writing with two self-addressed mailing labels attached to ensure proper delivery. All proposals from responsible sources will be considered by the NIAID. This advertisement does not commit the Government to award a contract. INQUIRIES Requests for the RFP are to be directed in writing to: Mr. Bruce E. Anderson Contract Management Branch National Institute of Allergy and Infectious Diseases Solar Building, Room 3C07 6003 Executive Boulevard Bethesda, MD 20892 FAX: (301) 402-0972 $$R3 END ************************************************************ $$R4 BEGIN NIH-NIAID-DAIDS-95-05 ************************************ RESYNTHESIS OF POTENTIAL THERAPEUTIC AGENTS FOR TREATMENT OF INFECTIOUS DISEASES NIH GUIDE, Volume 22, Number 41, November 12, 1993 RFP AVAILABLE: NIH-NIAID-DAIDS-95-05 P.T. 34; K.W. 0740020, 1003006, 0715125 National Institute of Allergy and Infectious Diseases The National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), supports a number of programs designed to identify and develop promising therapeutic agents active against a wide spectrum of infectious agents, including HIV, tuberculosis, and viral and non-viral opportunistic infections associated with the Acquired Immune Deficiency Syndrome (AIDS). Many of these research endeavors require pharmaceutical research and development resources such as chemical resynthesis, pharmaceutical analysis, and preparation of pharmaceutical dosage forms to provide therapeutic agents of sufficient quantity and quality to permit a proper evaluation of their efficacy and safety. The purpose of this solicitation is to provide a contract for resynthesis and acquisition of chemicals for testing as anti-infective agents. These chemicals will be used to prepare dosage forms for clinical evaluation and for use in animal models of infectious diseases, toxicological studies, as required to support the Government's ongoing evaluation of these agents. The Division of AIDS (DAIDS), NIAID previously awarded a contract to provide a chemical resynthesis capability on a scale of 1-1000g to support the drug discovery effort for infectious diseases. The current contract will expire in October 1994. The anticipated contract will be a set-aside for small business concerns. The Government's requirements specify the following two mandatory qualification criteria that must be met: (1) Neither the Offeror nor a proposed subcontractor may be a pharmaceutical company, defined as an organization that sells drugs or other therapeutic agents to the general public for profit and (2) The Offeror must be able to manufacture pharmaceutical materials in compliance with current Good Manufacturing Practice regulations (21 CFR 210-211) at time of Best and Final Offers. Documentation of this capability is required. This is an announcement for an anticipated Request for Proposals (RFP). RFP NIH-NIAID-DAIDS-95-05 was issued on November 1, 1993 and proposals will be due the close-of-business February 15, 1994. It is anticipated that one (1) level-of-effort type cost-reimbursement contract will be awarded for a five year period to carry out requested scale up and/or modify the synthetic procedure to yield increasingly larger batches as required for the further evaluation on new agents. A short-form version of the RFP will be available, for informational purposes, which includes the background information, full Statement of Work and Evaluation Criteria, and the Reporting Requirements. There is sufficient information in this document to enable prospective offerors to determine if they have the experience/capability to meet the Government's requirements. A full- text version is also available, which includes all the necessary information, business forms, etc., to submit a proposal. There are a limited number of full-text versions available. Therefore, request the short-form RFP first, then the full-text version only if you intend to submit a proposal. Telephone inquiries will not be honored. Specify if you are requesting the short-form or full-text version of the RFP (if no distinction is made, the short-form version will be sent). FAX responses are acceptable, but it is preferred that requests be submitted in writing with two self-addressed mailing labels attached to ensure proper delivery. All proposals from responsible sources will be considered by the NIAID. This advertisement does not commit the Government to award a contract. INQUIRIES Requests for the RFP are to be directed in writing to: Ms. Merilee Rahe-Stoline Contract Management Branch National Institute of Allergy and Infectious Diseases Solar Building, Room 3C07 6003 Executive Boulevard Bethesda, MD 20892 FAX: (301) 402-0972 $$R4 END ************************************************************ $$R5 BEGIN NIH-NIAID-DMID-94-22 ************************************* TUBERCULOSIS PREVENTION AND CONTROL RESEARCH NIH GUIDE, Volume 22, Number 41, November 12, 1993 RFP AVAILABLE: NIH-NIAID-DMID-94-22 P.T. 34; K.W. 0715165, 1002027 National Institute of Allergy and Infectious Diseases The Respiratory Diseases Branch, Division of Microbiology and Infectious Diseases (DMID), National Institute of Allergy and Infectious Diseases (NIAID), has a requirement for a multifaceted, prevention-focused, clinical and basic research effort on Mycobacterium tuberculosis and associated infections. The program is aimed at understanding disease pathogenesis and prevention of infection. The Contractor must have demonstrated experience in clinical and basic research associated with Mycobacterium tuberculosis. Request for Proposals (RFP) NIH-NIAID-DMID-94-22 is now available. Responses are due by January 14, 1994. It is anticipated that two level of effort contracts will be awarded with incremental funding over a period of five years. Any responsible offeror may submit a proposal that will be considered by the Government. INQUIRIES Interested organizations may request either a streamlined or full RFP package. If no selection is made, a streamlined version of the RFP will be provided, which includes only the Statement of Work, deliverable and reporting requirements, special requirements, and mandatory qualifications, if any, and technical evaluation criteria. After examination of these documents, any organization interested in responding to the RFP must request the entire RFP in writing, by telephone, or by FAX request. This advertisement does not commit the Government to award a contract. To receive a copy of this RFP, supply this office with two self- addressed mailing labels. Telephone inquiries will not be honored and all inquiries must be in writing and addressed to: Carl Henn Contract Management Branch National Institute of Allergy and Infectious Diseases Solar Building, Room 3C07 6003 Executive Boulevard Bethesda, MD 20892 $$R5 END ************************************************************ $$R6 BEGIN DA-94-002 FULL-TEXT ************************************** BEHAVIORAL THERAPIES DEVELOPMENT PROGRAM NIH GUIDE, Volume 22, Number 41, November 12, 1993 RFA AVAILABLE: DA-94-002 P.T. 34; K.W. 0404009, 0404000 National Institute on Drug Abuse Letter of Intent Receipt Date: February 11, 1994 Application Receipt Date: March 11, 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 purpose of this RFA is to introduce a major research effort on behavioral therapies for drug abuse and dependence. Behavioral therapy research has been conceptualized, for the purposes of this initiative, to consist of three phases. For the Behavioral Therapies Development Program to succeed, it is essential that all three phases of behavioral therapy research receive appropriate support. Therefore, it is the intention of the National Institute on Drug Abuse (NIDA) to support: (1) Phase I research (including the development, refinement, and pilot efficacy testing of behavioral interventions for drug dependence); (2) Phase II research (efficacy testing and replication of promising piloted behavioral therapies; and (3) Phase III research (studies to test the generalizability and transferability of behavioral therapies proven efficacious in Phase II studies). 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, Behavioral Therapies Development Program for Drug Abuse and Dependence, is 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 foreign and domestic, for-profit and non-profit organization, 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 First Independent Research Support and Transition (FIRST) (R29) Awards. MECHANISM OF SUPPORT Support mechanisms include: Research projects grants (R01), small grants (R03), and FIRST Awards (R29). Investigators may also respond to this RFA under the Interactive Research Project Grant (IRPG) mechanism. Additional requirements for the IRPG mechanism are described in PA-93-078. Most investigator-initiated research is supported by regular research grants. Research grants are awarded to institutions on behalf of Principal Investigators who have designed and will direct a specific project or set of projects. Because the nature and scope of the research proposed in response to this RFA may vary, it is anticipated the size of the award will vary also. FUNDS AVAILABLE It is anticipated that approximately $3 million will be available to support the first year of the behavioral therapies research program. It is anticipated that approximately eight new awards will be made under this announcement. RESEARCH OBJECTIVES While considerable progress has been made, engagement and retention in treatment and relapse following treatment remain concerns. The NIDA is undertaking the Behavioral Therapies Development Program with the goal of addressing these concerns and substantially improving the efficacy of behavioral treatments for drug abuse. NIDA's Behavioral Therapies Development Program delineates three phases of behavioral therapy research. Phase I, the earliest phase of behavioral therapy research, therapy development, is viewed as a multi-stage process. It involves identifying promising clinical and research findings relevant to drug abuse treatment, generating and formulating new behavioral therapies, operationally defining the therapies in manuals, and pilot testing and refining the therapies. With the Behavioral Therapies Development Program, support for Phase I research is intended to continue and intensify. Phase II research consists of small-scale efficacy testing of promising therapies identified in Phase I, as well as studies examining the efficacy of components of therapies. Most of the behavioral treatment research that NIDA has supported in the past has been of this type. Phase II also involves the replication, at other sites, of efficacy studies with positive results. Under the Behavioral Therapies Development Program, Phase II clinical trials and component analysis studies will be emphasized more strongly, as is the case for replication studies. Phase III entails the testing of therapies that have been shown to be efficacious in more than one controlled Phase II clinical trial. This involves establishing the generalizability and transferability of these therapies and determining their usefulness within community-based treatment programs. For drug abuse treatment to succeed, it is essential that all phases of behavioral therapy research receive sufficient emphasis and support. Through the Behavioral Therapies Development Program, NIDA will greatly increase its support of the early phases of behavioral therapy development, small-scale controlled clinical trials of fully developed therapies (including replications), and studies in community-based treatment programs of the most promising therapies identified in the Phase II clinical trials. This RFA is intended to introduce this initiative by encouraging research grant applications in any one of the three phases of behavioral therapy research. 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 February 11, 1994, 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 NIDA 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: Director, Office of Extramural Program Review National Institute on Drug Abuse 5600 Fishers Lane, Room 10-42 Rockville, MD 20857 Telephone: (301) 443-2755 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 may be obtained from the Office of Grant Information, Division of Research Grants, National Institutes of Health, Westwood Building, Room 240, Bethesda, MD 20892, telephone 301/594-7248. The RFA label in the PHS 398 (rev. 9/91) application form must be affixed to the bottom of the original face page. Failure to use the RFA label and to follow instructions 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 in Item 2a on the face page of the application form and the YES box must be marked. Submit a signed, typewritten original of the application 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: Director, Office of Extramural Program Review National Institute on Drug Abuse 5600 Fishers Lane, Room 10-42 Rockville, MD 20857 Applications must be received by March 11, 1994, and will be reviewed according to the following review schedule: Application Receipt Date: March 11, 1994 Initial Review: June 1994 Advisory Council: September 1994 Earliest Date of Award: September 1994 REVIEW CONSIDERATIONS Applications received under this RFA will be assigned to an initial review group (IRG) convened by the NIDA in accordance with established PHS referral guidelines. Notification of the review recommendations will be sent to the applicant after the initial review. Applications will receive a second-level review by the National Advisory Drug Abuse 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 The anticipated date of award is September 30, 1994. 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: Lisa Onken, Ph.D. National Institute on Drug Abuse 5600 Fishers Lane, Room 10A-30 Rockville, MD 20857 Telephone: (301) 443-0108 Direct inquiries regarding fiscal matters to: Gary Fleming, J.D., M.A. 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 the Public Health Service Act, Section 301, and administered under PHS policies and Federal Regulations at Title 42 CFR 52 "Grants for Research Projects", Title 45 CFR Part 74 & 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. $$R6 END ************************************************************ $$XID RFA DA94002 DA-94-002 P1O1 *************************************** BEHAVIORAL THERAPIES DEVELOPMENT PROGRAM NIH GUIDE, Volume 22, Number 41, November 12, 1993 RFA: DA-94-002 P.T. 34; K.W. 0404009, 0404000 National Institute on Drug Abuse Letter of Intent Receipt Date: February 11, 1994 Application Receipt Date: March 11, 1994 PURPOSE Behavioral therapies are frequently the only treatments available to drug-dependent individuals. (The term, "behavioral therapies," is used here in a broad sense and includes various forms of psychotherapy, behavior therapy, skills training, counseling, and other rehabilitative therapies.) Even where medications are available, behavioral therapies are an integral component of treatment. Considerable progress has been made over the past decade in developing effective behavioral therapies for drug abuse and dependence. These recent research advances suggest that the field is ready to move ahead with a major initiative in this area. Recognizing the importance of behavioral therapies for drug abuse and dependence, the National Institute on Drug Abuse (NIDA) is launching a Behavioral Therapies Development Program. It is intended to: (1) complement and dramatically expand work underway within the Clinical and Experimental Therapeutics Research Branch, Division of Clinical Research, NIDA and (2) parallel NIDA's Medications Development Program. The release of this Request for Applications (RFA) coincides with the commencement of NIDA's Behavioral Therapies Development Program and represents NIDA's ongoing commitment to support behavioral therapy drug abuse and dependence research. It is NIDA's intention to support scientifically sound and clinically relevant behavioral therapy research that will potentially have a meaningful impact on the efficacy of drug abuse/dependence treatment. Through the Behavioral Therapies Development Program, support may be sought to identify, evaluate, and standardize behavioral therapies for the treatment of drug abuse and dependence. Ultimately, therapies found to be efficacious through rigorous testing, will be disseminated to clinicians. Although substantial work has already been done, this initiative will target for funding, in a systematic way, essential research on behavioral therapies for drug abuse and dependence. This will include, in particular, critical areas of research that have been overlooked in the past. The purpose of this RFA is to introduce a major research effort on behavioral therapies for drug abuse and dependence. Behavioral therapy research has been conceptualized, for the purposes of this initiative, to consist of three phases. For the Behavioral Therapies Development Program to succeed, it is essential that all three phases of behavioral therapy research receive appropriate support. Therefore, it is NIDA's intention to support: (1) Phase I research (including the development, refinement, and pilot efficacy testing of behavioral interventions for drug dependence); (2) Phase II research (efficacy testing and replication of promising piloted behavioral therapies; and (3) Phase III research (studies to test the generalizability and transferability of behavioral therapies proven efficacious in Phase II studies). 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, Behavioral Therapies Development Program for Drug Abuse and Dependence, is 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 foreign and domestic, for-profit and non-profit organization, 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 First Independent Research Support and Transition (FIRST) (R29) Awards. MECHANISM OF SUPPORT Support mechanisms include: Research projects grants (R01), small grants (R03), and FIRST awards (R29). Investigators may also respond to this RFA under the Interactive Research Project Grant (IRPG) mechanism. Additional requirements for the IRPG mechanism are described in PA-93-078. Most investigator-initiated research is supported by regular research grants. Research grants are awarded to institutions on behalf of Principal Investigators who have designed and will direct a specific project or set of projects. FUNDS AVAILABLE It is anticipated that approximately $3 million will be available to support the first year of the behavioral therapies research program. Because the nature and scope of the research proposed in response to this RFA may vary, the size of an award will also vary. However, it is anticipated that approximately eight new awards will be made under this announcement. RESEARCH OBJECTIVES Background and Rationale Recent results from research studies indicate great promise for the efficacy of behavioral therapies for drug dependence. For example, Higgins and Budney (1993) reported using the community reinforcement approach (Hunt and Azrin, 1973; Azrin, 1976) to treat cocaine-dependent individuals. Their results were extremely encouraging, with a large number of subjects achieving initial abstinence from cocaine. Carroll et al. (1993) found evidence that while a behavioral therapy (as compared to standard treatment without the behavioral therapy) does not always increase an individual's ability to maintain abstinence from drugs while the patient is in treatment, behavioral interventions may, indeed, help patients maintain the gains that they have made after they are out of treatment. Specifically, they found that whether cocaine abusers were provided relapse prevention or clinical management, they all improved during treatment. However, at 6 and 12-month followup, only those who had received the relapse prevention were able to maintain the gains they made in treatment. While considerable progress has been made, engagement and retention in treatment and relapse following treatment remain concerns. NIDA is undertaking the Behavioral Therapies Development Program with the goal of addressing these concerns and substantially improving the efficacy of behavioral treatments for drug abuse. NIDA's Behavioral Therapies Development Program delineates three phases of behavioral therapy research. Phase I, the earliest phase of behavioral therapy research, therapy development, is viewed as a multi-stage process. It involves identifying promising clinical and research findings relevant to drug abuse treatment, generating and formulating new behavioral therapies, operationally defining the therapies in manuals, and pilot testing and refining the therapies. With the Behavioral Therapies Development Program, support for Phase I research is intended to continue and intensify. Phase II research consists of small-scale efficacy testing of promising therapies identified in Phase I, as well as studies examining the efficacy of components of therapies. Most of the behavioral treatment research that NIDA has supported in the past has been of this type. Phase II also involves the replication, at other sites, of efficacy studies with positive results. Under the Behavioral Therapies Development Program, Phase II clinical trials and component analysis studies will be emphasized more strongly, as is the case for replication studies. Phase III entails the testing of therapies that have been shown to be efficacious in more than one controlled Phase II clinical trial. This involves establishing the generalizability and transferability of these therapies, and determining their usefulness within community-based treatment programs. For drug abuse treatment to succeed, it is essential that all phases of behavioral therapy research receive sufficient emphasis and support. Through the Behavioral Therapies Development Program, NIDA will greatly increase its support of the early phases of behavioral therapy development, small-scale controlled clinical trials of fully developed therapies (including replications), and studies in community-based treatment programs of the most promising therapies identified in the Phase II clinical trials. This RFA is intended to introduce this initiative by encouraging research grant applications in any one of the three phases of behavioral therapy research. Specific Areas of Interest Areas of interest include, but are not limited to, the following: Phase I Research: Investigators are encouraged to submit applications to develop new or modify existing behavioral therapies that: (1) appear promising for the treatment of drug-dependent and abusing individuals; and (2) have a convincing rationale or theoretical basis. Therapies of interest include but are not limited to the following: 1. Discrete therapy modules that address specific problems common among drug-dependent individuals, and that can be implemented in conjunction with other therapeutic services. For example, an investigator may wish to develop a four-session, highly focused, job-seeking skills module that can be easily implemented by a wide range of practitioners, to effectively increase appropriate job-seeking behavior. Other examples include, but are not limited to, modules to engage ambivalent drug- dependent individuals in treatment, to address "denial," or to increase assertiveness in female drug addicts who feel pressured by others to use drugs. 2. Therapies designed specifically to engage and retain individuals in treatment. An example could be a therapy that: (1) is sensitive to the motivational level of the client, (2) is specifically designed to respond to the needs of the individual, whatever his or her motivational level might be, and (3) actively works to increase an individual's desire to remain in treatment. 3. Therapies to impact specific client characteristics. Such therapies are based upon theories regarding measurable psychological, behavioral, or interpersonal constructs. Examples include therapies to overcome cognitive deficits, family dysfunction, or social skill deficiencies, where these constructs are hypothesized to be causally related to drug abuse and where they may be quantified. Investigators may propose the development of measures where relevant to the development and assessment of the therapy. 4. Therapies for abusers of specific drugs. This may include, but is not limited to, therapies to treat cocaine, heroin, benzodiazepine dependence, or dependence upon several drugs. 5. Therapies to treat comorbid populations. This may include therapies to treat drug abuse/dependence in individuals who have, for example, psychotic, mood, anxiety, personality disorders, or one of the disruptive behavior disorders of childhood and adolescence such as an attention-deficit/hyperactivity, conduct, or oppositional defiant disorder. This may also include behavioral therapies aimed at integrating drug dependence and mental health treatment approaches in dually diagnosed populations, where the ultimate goal of the therapy is to decrease drug use. 6. Therapies for specific ethnic, racial, or cultural groups. This includes therapies that are culturally sensitive and address the unique needs and perspectives of minorities or cultural groups. 7. Therapies for women. Such therapies may be aimed, for example, at meeting the emotional and cognitive needs of drug-abusing pregnant or parenting women, or of women who have or are experiencing physical/sexual abuse. 8. Therapies for adolescents. Such therapies may be aimed, for example, at addressing the problems associated with active drug abuse or dependence on the part of the youth during the early, middle, and/or late adolescent stages of development. 9. Therapies for families. Such therapies should address drug abuse from the perspective of the whole family rather than from the viewpoint of an individual family member. 10. Therapies for use in community settings. Therapies need to be developed for use in outreach programs and other non-traditional settings that access drug abusers who avoid the formal drug abuse treatment system. An application for a grant to develop a therapy should include an explicit, logical, consistent, and coherent statement describing the theoretical basis for that therapy, and the population for whom it is intended. A thorough literature review documenting relevant research and clinical findings should also be included. Although, of course, a manual for a therapy will not exist prior to an application to develop such a manual, the nature of the therapy to be developed should be described in as much detail as possible in the application. Components of the psychotherapy, behavior therapy, or drug counseling approach to be developed should be operationally defined wherever possible. Applicants proposing client characteristic specific therapies, should address the issue of whether theoretically based diagnostic systems or client assessment scales tailored to their therapy need development. If one theorizes, for example, that certain heroin addicts either began or maintained heroin use due to interpersonal conflicts, and that the resolution of these conflicts will decrease drug use, a measure of interpersonal conflicts should either exist, or be developed with a therapy based upon treating these conflicts. The development of a theoretically based therapy should include measures of client attributes directly related to that therapy. Where necessary, investigators may develop new or refine existing client assessment scales to measure the impact of the proposed theoretically-based therapy. Methods that will be used to develop these instruments should be described in detail. Close attention should be paid to the psychometric characteristics of these measures (i.e., validity, internal consistency, inter-rater and test-retest reliability). Applicants should also address the issue of how they intend to measure what is actually occurring in the therapy they are proposing to develop. The credibility of any treatment research depends on the ability to determine the extent to which that treatment was actually administered, and administered correctly. In the development of any therapy, therefore, emphasis should be placed upon the development of psychometrically sound therapist competence and adherence scales, process measures, and instruments measuring the integrity and fidelity of the therapy. Applicants should describe the instruments they intend to develop, and the methods that they will use to ensure they are developing valid and reliable measures. In the development of a new therapy for drug dependence, a broad range of issues relevant to efficacy and safety must be addressed. Pilot efficacy testing of newly developed/modified therapies, therefore, should be considered an integral part of any therapy development process. The applicant should describe, in detail, the nature of any pilot testing intended. Any pilot testing proposed should be based upon sound, scientific methods. Phase II Research Phase II research establishes the efficacy of therapies, and the efficacious components of therapies. In Phase II research control and comparison groups are operationally defined, standardized, and manualized. However, early in Phase II, it may be appropriate to compare a therapy with "treatment as usual." Investigators should have clearly delineated research questions, and should carefully choose their control/comparison groups to answer those questions. It is appropriate, but not required, that investigators design studies to answer not only if their therapy works, but why it works. Specific areas of Phase II research include, but are not limited to: 1. Comparative Behavioral Therapy Research. Controlled clinical trials that examine the relative efficacy of behavioral therapies and attempt to determine which therapies are best for which individuals, and under what conditions, are encouraged. Studies that investigate the relative efficacy of individual, group, or family psychotherapy; behavior therapy; skills training; drug abuse counseling; or other rehabilitative approaches in various special populations are also encouraged. Applicants proposing comparative behavioral therapy research studies are encouraged to examine the interactions of relevant therapist/patient characteristics with therapy type and to assess the relative contribution of therapist, patient, and type of therapy to outcome. For example, contingency management has been shown to be efficacious for some individuals, but not for others (Stitzer et al., 1993). Investigators proposing a clinical trial using contingency management in one group may wish, therefore, to design the study such that they may determine the characteristics of patients for whom this intervention is or is not helpful. (This type of study may be done, of course, within or outside the context of a comparative clinical trial). Another example of a study examining client characteristics is a study which attempts to determine the relative efficacy of a cognitive therapy in individuals with varying levels of cognitive ability. For these studies, it is imperative that investigators accurately measure and control for the psychiatric diagnosis and problem severity level of the patients. It is also necessary that clear definitions of outcome variables be specified, and that valid and reliable measures of outcome be used. It is important that therapists/counselors providing the therapy be systematically trained, that manuals be used to guide the therapies, that valid and reliable therapist competence and adherence scales be used, and that the treatment process be measured accurately. For all efficacy studies, it is expected that adequate followup assessments be planned. It is also important that these studies use procedures and methods that can be replicated. It is strongly suggested that pilot data showing that a counseling or psychotherapy strategy is promising be provided when proposing comparative research involving this therapy. These pilot data should indicate that the utilization of the therapy approach shows promise in its ability to produce a decrease in drug use, dropout rate, or psychiatric symptoms. 2. Research To Integrate Behavioral Therapies with Pharmacotherapies. Where effective pharmacotherapies are available, research projects that attempt to maximize the efficacy of that pharmacotherapy through integration with behavioral therapy, or vice versa, are encouraged. 3. Component Analysis Research. Knowing the effective components of treatment can greatly aid in improving the quality of treatment. Theoretically based research that attempts to determine the effective components or combination of components in drug dependence psychotherapies, behavior therapies, or counseling strategies is encouraged. 4. Replications. Applications that propose to replicate a behavioral therapy for drug abuse/dependence study that has positive findings are strongly encouraged. Applications that propose to generalize the efficacy of a promising therapy in another population are also encouraged. Where the investigator believes that significant modification of the therapy is needed before it can be tested in another population, investigators are referred to the section of this RFA entitled, "Phase I Research." It is recognized that for many research questions asked in the field of psychotherapy, behavior therapy, and counseling, no perfect research design may exist. Where there is more than one way to answer a proposed research question, investigators are urged to state their theoretical, ethical, and practical reasons for choosing one control group or one research design over another (see Borkovec, 1990, 1993). Investigators are also encouraged to address the issues of selection bias and attrition (Howard et al., 1990; Howard et al., 1993), and any other pertinent methodological issues. Phase III Research. Where behavioral therapies have been shown to be efficacious in a clinical trial, and where replication has borne out the contention that the therapy is, indeed, efficacious, investigators may propose to carry out a study to address the therapy's transferability, generalizability to other populations, and applicability in community-based drug abuse treatment programs. It is incumbent upon the applicant proposing any Phase III research to review the relevant literature on the behavioral therapy to be researched, and to clearly delineate the reasons that it is ready for a Phase III study. An example of a Phase III study might involve an investigator using a therapy that has been rigorously tested in a replicated controlled clinical trial, packaging that therapy, including development of training manuals and other training materials, to be used in a community setting. The investigator might then pilot the therapy in the community clinic, refine the therapy package, and ultimately test the usefulness of the packaged therapy in the community setting. Applicants are expected to develop applications that are focused on one phase; that is, investigators may choose to focus on either Phase I, Phase II or Phase III research. However, where it is justifiable, investigators may develop proposals to include a research component consistent with another phase (e.g., a Phase II research application may include a small Phase I component). If a subject is identified as being at risk for HIV acquisition and/or transmission, HIV testing and counseling should be offered to the subject in accordance with current guidelines. Furthermore, in high-risk populations, investigators are encouraged to assess the effect of the new therapy on the acquisition/transmission of associated infectious disease, 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. LETTER OF INTENT Prospective applicants are asked to submit, by February 11, 1994, 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 NIDA 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: Director, Office of Extramural Program Review National Institute on Drug Abuse 5600 Fishers Lane, Room 10-42 Rockville, MD 20857 Telephone: (301) 443-2755 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 may be obtained from the Office of Grant Information, Division of Research Grants, National Institutes of Health, Westwood Building, Room 240, Bethesda, MD 20892, telephone 301/594-7248. The RFA label in the PHS 398 (rev. 9/91) application form must be affixed to the bottom of the original face page. Failure to use the RFA label and to follow instructions 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 in Item 2a on 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 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: Director, Office of Extramural Program Review National Institute on Drug Abuse 5600 Fishers Lane, Room 10-42 Rockville, MD 20857 Applications must be received by March 11, 1994, and will be reviewed according to the following review schedule: Application Receipt Date: March 11, 1994 Initial Review: June 1994 Advisory Council: September 1994 Earliest Date of Award: September 1994 Applications received after the above receipt date will be held for the next regular receipt date and reviewed under standard circumstances. However, such applications may not be considered for the Fiscal Year 1994 funding set aside under this RFA. REVIEW CONSIDERATIONS The Division of Research Grants, 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) convened by the NIDA 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 the National Advisory Drug Abuse 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 The anticipated date of award is September 30, 1994. Applications recommended for further consideration by an appropriate Advisory Council will be considered for funding on the basis of overall scientific and technical merit of the application as determined by peer review, appropriateness of budget estimates, program needs and balance, policy considerations, adequacy of provisions for the protection of human subjects, and availability of funds. Upon completion of the project's period of award made under this RFA, grantees may submit competitive renewal applications. 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: Lisa Onken, Ph.D. National Institute on Drug Abuse 5600 Fishers Lane, Room 10A-30 Rockville, MD 20857 Telephone: (301) 443-0108 Direct inquiries regarding fiscal matters to: Gary Fleming, J.D., M.A. 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 the Public Health Service Act, Section 301, and administered under PHS policies and Federal Regulations at Title 42 CFR 52 "Grants for Research Projects", Title 45 CFR Part 74 & 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. References Azrin, N. "Improvements in the community reinforcement approach to alcoholism," Behavior Research and Therapy, 14: 339-348, 1976. Borkovec, T.D. "Control groups and comparison groups in psychotherapy outcome research," In Onken, L. Simon and Blaine, J.D. (Eds.) Psychotherapy and counseling in the treatment of drug abuse, NIDA Research Monograph #104, Department of Health and Human Services Publication Number (ADM)90-1722, 1990. Borkovec, T.D. "Between-group therapy outcome research: Design and methodology," In Onken, L. Simon, Blaine, J.D., and Boren, J.J. (Eds.) Behavioral Treatments for Drug Abuse and Dependence, NIDA Research Monograph, Department of Health and Human Services, 1993. Carroll, K.M., Rounsaville, B.J., Nich, C., Gordon, L.T., Wirtz, P.W., and Gawin, F.H. "One year follow-up of psychotherapy and pharmacotherapy for cocaine dependence: Delayed emergence of psychotherapy effects." Submitted for publication. Higgins, S.T. and Budney, A.J. "Treatment of cocaine dependence via the principles of behavior analysis and behavioral pharmacology," In Onken, L. Simon, Blaine, J.D., and Boren, J.J. (Eds.) Behavioral Treatments for Drug Abuse and Dependence, NIDA Research Monograph, Department of Health and Human Services, 1993. Howard, K.I., Cox, M., and Saunders, S.M. "Attrition in substance abuse comparative treatment research: The illusion of randomization," In Onken, L. Simon and Blaine, J.D. (Eds.) Psychotherapy and counseling in the treatment of drug abuse, NIDA Research Monograph #104, Department of Health and Human Services Publication Number (ADM)90-1722, 1990. Howard, K.I., Krause, M.S. and Lyons, J. "When clinical trials fail: A guide to disaggregation," In Onken, L. Simon, Blaine, J.D., and Boren, J.J. (Eds.) Behavioral Treatments for Drug Abuse and Dependence, NIDA Research Monograph, Department of Health and Human Services, 1993. Hunt, G.M., and Azrin, N. A community reinforcement approach to alcoholism. Behavior Research and Therapy, 11: 91-104, 1973. Stitzer, M.L., Iguchi, M.Y., Kidors, M., and Bigelow, G.E. "Contingency management in methadone treatment: The case for positive incentives," In Onken, L. Simon, Blaine, J.D., and Boren, J.J. (Eds.) Behavioral Treatments for Drug Abuse and Dependence, NIDA Research Monograph, Department of Health and Human Services, 1993. From owner-sci-resources@net.bio.net Thu Nov 18 22:00:00 1993 Path: biosci!net.bio.net From: kristoff@net.bio.net (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 22, no. 42, pt. 1, 19 November 1993 Message-ID: Date: 19 Nov 93 04:48:32 GMT Sender: kristoff@net.bio.net Lines: 1504 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. ---------------------------------------------------------------------- X-comment: RFAS described: HL-94-005-B, AI-94-003, AI-94-001, AI-93-020, HL-9 4-003-B NIH GUIDE - Vol. 22, No. 42 - November 19, 1993 $$INDEX BEGIN ******************************************************* NOTICES $$INDEX N1 ********************************************************** "FAILURE TO THRIVE" SYNDROME AMONG OLDER PERSONS (PA-93-022) National Institute on Aging INDEX: AGING NOTICES OF AVAILABILITY (RFPs AND RFAs) $$INDEX R1 ********************************************************** INFANT SLEEP POSITION AND SUDDEN INFANT DEATH SYNDROME RISK (BAA NICHD-CRMC-94-01) National Institute of Child Health and Human Development INDEX: CHILD HEALTH, HUMAN DEVELOPMENT $$INDEX R2 ********************************************************** PHARMACOKINETIC AND PHARMACODYNAMIC STUDIES FOR MEDICATIONS DEVELOPMENT (RFP N01DA-4-8306) National Institute on Drug Abuse INDEX: DRUG ABUSE $$INDEX R3 ********************************************************** IN VITRO OPIOID DETERMINATIONS FOR MEDICATIONS DEVELOPMENT (RFP N01DA-4-8307) National Institute on Drug Abuse INDEX: DRUG ABUSE $$INDEX R4 02/10/94 ************************************************* IN VITRO INACTIVATION OF VIRUSES IN BLOOD COMPONENTS (RFA HL-94-005-B) National Heart, Lung, and Blood Institute INDEX: HEART, LUNG, BLOOD $$INDEX R5 03/10/94 ************************************************* NEONATAL IMMUNITY FOR VACCINES (RFA AI-94-003) National Institute of Allergy and Infectious Diseases INDEX: ALLERGY, INFECTIOUS DISEASES $$INDEX R6 03/15/94 ************************************************* IMMUNOLOGIC ENHANCEMENT OF VACCINE IMMUNOGENICITY (RFA AI-94-001) National Institute of Allergy and Infectious Diseases INDEX: ALLERGY, INFECTIOUS DISEASES $$INDEX R7 03/15/94 ************************************************* COOPERATIVE CLINICAL TRIAL IN PEDIATRIC TRANSPLANTATION (RFA AI-93-020) National Institute of Allergy and Infectious Diseases INDEX: ALLERGY, INFECTIOUS DISEASES $$INDEX R8 03/15/94 ************************************************* GENE THERAPY FOR SICKLE CELL DISEASE (RFA HL-94-003-B) National Heart, Lung, and Blood Institute INDEX: HEART, LUNG, BLOOD ONGOING PROGRAM ANNOUNCEMENTS $$INDEX P1 02/16/94 ************************************************* SMALL INSTRUMENTATION GRANTS PROGRAM (PA-94-012) National Institutes of Health INDEX: NATIONAL INSTITUTES OF HEALTH $$INDEX P2 ********************************************************** MECHANOTRANSDUCTION IN THE VESTIBULAR LABYRINTH (PA-94-013) National Institute on Deafness and Other Communication Disorders INDEX: DEAFNESS, OTHER COMMUNICATIONS DISORDERS This publication is available electronically to institutions via BITNET or INTERNET and is also on the NIH GOPHER. Alternative access is through the NIH Grant Line using a personal computer (data line 301/402-2221). Contact Dr. John James at 301/594-7270 for details. $$INDEX END ********************************************************* NOTICES $$N1 BEGIN ********************************************************** "FAILURE TO THRIVE" SYNDROME AMONG OLDER PERSONS NIH GUIDE, Volume 22, Number 42, November 19, 1993 PA NUMBER: PA-93-022 P.T. 34; K.W. 0710010, 0710095, 0715072, 0710070, 0765035 National Institute on Aging Effective immediately, the limits on annual budgets for applications submitted in response to this Program Announcement (published in the NIH Guide Vol. 21, No. 42, November 20, 1992) ($175,000 for first-year budgets and analogous limits for future years) are no longer in effect. INQUIRIES Inquiries regarding this program announcement may be directed to: Geriatrics Program National Institute on Aging Gateway Building, Suite 3E327 Bethesda, MD 20892 Telephone: (301) 496-6761 $$NI END ************************************************************ NOTICES OF AVAILABILITY (RFPs AND RFAs) $$R1 BEGIN NICHD-CRMC-94-01 ***************************************** INFANT SLEEP POSITION AND SUDDEN INFANT DEATH SYNDROME RISK NIH GUIDE, Volume 22, Number 42, November 19, 1993 BAA AVAILABLE: NICHD-CRMC-94-01 P.T. 34; K.W. 0715205, 0715187 National Institute of Child Health and Human Development The National Institute of Child Health and Human Development (NICHD) is conducting a study of sleep positions in Sudden Infant Death Syndrome (SIDS) cases. Research is to be conducted into current infant sleep practices so that NICHD may evaluate (1) whether and to what extent sleep practices change as a result of the American Academy of Pediatrics recommendation, which recommended that normal term infants be placed on their side or back to sleep; (2) to what extent changes in sleep practice may have positive or adverse effects on infant mortality in the United States; and (3) what are the relative risks for those infants sleeping in various positions to succumb to SIDS. To answer these research questions, the NICHD plans to issue a Broad Agency Announcement (BAA) for proposals that address one or more of the research questions proposed. This BAA for an infant's sleep position study and SIDS risks is a new acquisition. The issuance of the BAA will be on or about November 19, 1993 and proposals are due by 4:00 p.m. (Local Time), January 21, 1994. INQUIRIES Organizations desiring a copy of the above BAA may send their written request to: Mrs. Lynn Salo Office of Grants and Contracts National Institute of Child Health and Human Development 6100 Building, Room 7A07 Bethesda, MD 20892 All requests must cite the BAA No. NICHD-CRMC-94-01 and include two self-addressed mailing labels. All sources that consider themselves qualified are encouraged to submit a proposal. This advertisement does not commit the government to award a contract. $$R1 END ************************************************************ $$R2 BEGIN N01DA-4-8306 ********************************************* PHARMACOKINETIC AND PHARMACODYNAMIC STUDIES FOR MEDICATIONS DEVELOPMENT NIH GUIDE, Volume 22, Number 42, November 19, 1993 RFP AVAILABLE: N01DA-4-8306 P.T. 34; K.W. 0710100, 0740025, 0755010 National Institute on Drug Abuse The National Institute on Drug Abuse (NIDA) is soliciting proposals from qualified organizations having in-house capability to carry out clinical research on the pharmacokinetics and pharmacodynamics of psychoactive drugs. These studies involve the monitoring of pharmacological responses, collection of biological samples, development and validation of analytical methods, identification of metabolites, quantification of drug/metabolite in biological samples, and performing statistical and pharmacokinetic analysis of the data. The correlation of pharmacological responses with pharmacokinetic parameters will be made. The offeror must also indicate possession of current DEA registration for Schedule II-V substances prior to award and apply for Schedule I registration, if necessary. It is estimated that a three-year contract, which will include options for additional studies as well as options for two additional years, will result from this procurement. Estimated issuance date of Request for Proposals (RFP) No. N01DA-4-8306 is November 22, 1993 and responses are due to be received in the Contracting Office 45 calendar days thereafter. INQUIRIES Written requests are to be forwarded to: Kenneth E. Goodling, Contract Specialist National Institute on Drug Abuse Parklawn Building, Room 10-49 5600 Fishers Lane Rockville, MD 20857 This advertisement does not commit the Government to make an award. $$R2 END ************************************************************ $$R3 BEGIN N01DA-4-8307 ********************************************* IN VITRO OPIOID DETERMINATIONS FOR MEDICATIONS DEVELOPMENT NIH GUIDE, Volume 22, Number 42, November 19, 1993 RFP AVAILABLE: N01DA-4-8307 P.T. 34; K.W. 0760055, 0760075, 0755010 National Institute on Drug Abuse The National Institute on Drug Abuse (NIDA) is soliciting proposals from qualified organizations having in-house capability to perform in vitro opioid receptor binding and functional activity assays. Proprietary test compounds will be evaluated in established assays, and the resulting data will be utilized by the Opiate Treatment Discovery Program of the NIDA Medications Development Division. In addition, the successful offeror will devote a substantial number of person hours to the development of new opioid receptor binding and functional activity assays. Offerors must indicate possession of current DEA registration for Schedule II-V substances prior to award and apply for Schedule I registration at the time of award. It is estimated that a three-year contract, which will include options for additional studies, will result from this procurement. Estimated issuance date of Request for Proposals (RFP) No. N01DA-4-8307 is November 22, 1993, and responses are due to be received in the Contracting Office 45 calendar days thereafter. INQUIRIES Written requests are to be forwarded to: Jeffrey Weiner, Contract Specialist National Institute on Drug Abuse Parklawn Building, Room 10-49 5600 Fishers Lane Rockville, MD 20857 This advertisement does not commit the Government to make an award. $$R3 END ************************************************************ $$R4 BEGIN HL-94-005-B FULL-TEXT ************************************ IN VITRO INACTIVATION OF VIRUSES IN BLOOD COMPONENTS NIH GUIDE, Volume 22, Number 42, November 19, 1993 RFA AVAILABLE: HL-94-005-B P.T. 34; K.W. 0750010, 1002045 National Heart, Lung, and Blood Institute Letter of Intent Receipt Date: December 10, 1993 Application Receipt Date: February 10, 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 Transfusion Medicine Branch, Division of Blood Diseases and Resources, National Heart, Lung, and Blood Institute (NHLBI), announces the availability of an RFA encouraging basic and applied research on the development of simple, cost-effective inactivation procedures to destroy the infectivity of transfusion-transmitted viruses in blood and blood components while maintaining the therapeutic effectiveness of these preparations. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Heathy People 2000", a PHS-led national activity for setting priority areas. This RFA, In Vitro Inactivation of Viruses in Blood Components, is related to the priority areas of HIV infection, 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 202-782-3238). 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 Recent progress in inactivating viruses in plasma derivatives has been highly successful. Safe and efficient inactivation procedures have been developed and are now widely available. One of these methods, which was developed under NHLBI support, involves treatment of material with organic solvent and detergent. Conversely, attempts to develop inactivation procedures to destroy the infectivity of viruses in blood and blood components have been uniformly unsuccessful despite considerable research activity in this area. The fragile nature of cellular components, particularly plasma membranes, make them extremely susceptible to disruption by virucidal procedures. As a result, the destruction of viral activity is often accompanied by loss of cellular function. Consequently, whole blood and cellular components including red blood cell concentrates, platelet concentrates, and leukocyte concentrates, continue to carry a risk of virus transmission. Current risks of being infected with a unit of screened blood are 1 in 3,000 for HCV, 1 in 200,000 for HBV, and 1 in 225,000 for HIV. Over the past five years, investigators supported under an NHLBI RFA program have explored a number of different approaches to inactivate or remove viruses from blood and blood components including the use of UV-C irradiation, filtration, hydrolyzed diol epoxides, ozone, halogenated oxidizing agents, and photoactive dyes for viral sterilization of fresh frozen plasma, red blood cell concentrates, and platelet concentrates. While significant progress has been made under the previous RFA program toward the development of inactivation procedures, additional research is urgently needed to better understand the mode of action of these as well as other virucidal reagents and procedures so as to apply and optimize their use in a blood banking environment. Furthermore, studies on the removal of viruses from biological materials in ways that permit the treated products to be used clinically are also needed and are an important goal of this RFA. Possible approaches include viral adherence to affinity columns, use of monoclonal antibodies for in vitro neutralization, absorption-filtration procedures, centrifugal removal of viruses, and use of filters for leukodepletion. In summary, transfusion practices continue to carry a small but unacceptable risk of infection from transfusion-transmitted viruses. The solution to this problem is the development of inactivation or virus removal procedures that do not destroy the functional integrity of blood or blood components. Some procedures are currently available such as the use of photochemicals that inactivate nucleic acids and destroy virus infectivity with minimal effects on nucleic acid-free red cells and platelets. What is needed are technological advances that would permit the use of photochemicals and inactivation procedures in an efficient cost-effective fashion that is compatible with the operation of a large-scale blood center. Other forms of viral inactivation that maintain the functional integrity of blood components also need to be pursued. This program encourages basic and applied research on the development and evaluation of procedures to remove or destroy the infectivity of transfusion-transmitted viruses in blood and blood components while maintaining the therapeutic effectiveness of these preparations. 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 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. 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: Acting 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 February 10, 1994. 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. 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. Luiz H. Barbosa 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 Diseases and Resources Grants Management Section National Heart, Lung, and Blood Institute Westwood Building, Room 4A11 Bethesda, MD 20892 Telephone: (301) 594-7436 FAX: (301) 594-7492 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 grants policies and Federal regulations, most specifically 42 CFR Part 52 and CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372, or to Health Systems Agency review. $$R4 END ************************************************************ $$R5 BEGIN AI-94-003 FULL-TEXT ************************************** NEONATAL IMMUNITY FOR VACCINES NIH GUIDE, Volume 22, Number 42, November 19, 1993 RFA AVAILABLE: AI-94-003 P.T. 34; K.W. 0705040, 0740075, 0403020 National Institute of Allergy and Infectious Diseases Letter of Intent Receipt Date: January 15, 1994 Application Receipt Date: March 10, 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 Division of Allergy, Immunology and Transplantation (DAIT) and the Division of Microbiology and Infectious Diseases (DMID) of the National Institute of Allergy and Infectious Diseases (NIAID) invite applications for basic and preclinical studies to increase knowledge of the development and function of the immune system in the neonate. Applications are especially solicited that address the utilization of this information for the development of new anti-pathogen vaccines effective in this age group. The knowledge developed through this initiative would also be applicable to the development of vaccines for autoimmune and allergic diseases. 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, Neonatal Immunity for Vaccines, is related to the priority areas of diabetes and chronic disabling diseases, and to 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 202-782-3238). ELIGIBILITY REQUIREMENTS Research grant applications may be submitted by domestic and foreign, for-profit and non-profit organizations, public and private institutions, such as universities, colleges, hospitals, laboratories, units of State or local governments, and eligible agencies of the Federal government. Foreign institutions are not eligible to apply for First Independent Research Support and Transition (FIRST) (R29) Awards. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT The mechanisms of support will be the individual 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 may not exceed five years; foreign awards may not exceed three years. FUNDS AVAILABLE The estimated funds available for the total (direct and indirect) first year costs of all awards made under this RFA will be $1,500,000. In Fiscal Year 1994, the NIAID plans to fund approximately seven R01s/R29s. Applications should not request more than four percent annual inflationary increases for future years. 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 NIAID, awards pursuant to this RFA are contingent upon the availability of funds for this purpose. Funding beyond the first and subsequent years of the grant will be contingent upon satisfactory progress during the preceding years and availability of funds. RESEARCH OBJECTIVES Background Infant mortality worldwide and in our inner cities is a continuing problem. Infants are at risk for overwhelming bacterial and viral infections. In order to meet the Childhood Vaccine Initiative goal of immunizing infants as early in life as possible, greater understanding of the neonatal immune system is necessary. A Blue Ribbon Panel convened by the NIAID in March of 1993 was charged with developing priorities for research in the area of vaccines. One of the areas highlighted by the panel was the need for basic research in immunology as it relates to vaccine research. In particular, the panel emphasized the need for basic research in the area of neonatal immunity. The immune system of the infant is functionally immature. Neonates do not produce much immunoglobulin. Maternal antibodies are transferred late in gestation to the fetus. This maternal antibody offers short term protection for the neonate. The role of this maternal antibody in the decreased response of the neonate's own immune system is unclear. The neonate's immune response to challenge from infectious agents is also deficient. Enhanced understanding of the neonatal response to pathogens and the potential for interference by maternal antibody in the function of the neonatal immune system is needed. Research Objectives and Scope The goal of this RFA is to increase knowledge of the development and function of the neonatal immune system and to use this knowledge to develop new and more effective vaccine strategies for this age group. Studies involving human tissues and cells are especially encouraged. Examples of relevant research topics are given below. These examples, however, are not intended to be all inclusive or limiting: o role of natural or vaccine-induced maternal antibodies, or of in utero antigen exposure, in the development of and regulation of the immune response of the neonate o mechanisms of immunosuppression/immunopotentiation in neonates exposed to pathogens or pathogen-derived antigens, and the long-term consequence of this neonatal exposure for development of the immunologic repertoire o ontogeny of the immune response in neonates and infants o characterization of antigens that elicit protective immune responses against pathogens in neonates, and methods to enhance such responses 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 research, 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 January 15, 1994, a letter of intent that includes a descriptive title of the overall proposed research, the name, address and telephone number of the Principal Investigator (Program Director), and the number and title of this RFA. Although the letter of intent is not required, is not binding, does not commit the sender to submit an application, 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 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 the standard research grant application form PHS 398 (rev. 09/91). These application forms may be obtained from the institution's office for sponsored research or its equivalent 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 March 10, 1994. 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. For purposes of identification and processing, item 2a on the face page of the application must be marked "YES" and the RFA number and the words "NEONATAL IMMUNITY FOR VACCINES" must be typed in. REVIEW CONSIDERATIONS The general criteria for applications are the review criteria used for traditional research project grant applications. AWARD CRITERIA Funding decisions will be made on the basis of scientific and technical merit as determined by peer review, program priorities, and the availability of funds. INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Requests for the RFA, as well as inquiries regarding programmatic issues, may be directed to: Elaine Collier, M.D. Division of Allergy, Immunology & Transplantation National Institute of Allergy and Infectious Diseases Solar Building, Room 4A20 6003 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-7985 FAX: (301) 402-2571 Direct inquiries regarding review issues, address the letter of intent to, and mail two copies of the application and the five sets of appendices to: Olivia Preble, Ph.D. Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4C19 6003 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-8208 FAX: (301) 402-2638 Direct inquiries regarding fiscal matters to: Mr. Jeffrey Carow Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4B29 6003 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-7075 Schedule Letter of Intent Receipt Date: January 15, 1994 Application Receipt Date: March 10, 1994 Scientific Review Date: July 1994 Advisory Council Date: September 1994 Earliest Award Date: September 1994 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance, No. 93.855 - Immunology, Allergy and Transplantation Research. Awards will be made under the authority of the Public Health Service Act, Title III, Section 301 (Public Law 78-410, as amended; 42 USC 241) and administered under PHS grants policies and Federal Regulations 42 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$R5 END ************************************************************ $$R6 BEGIN AI-94-001 FULL-TEXT ************************************** IMMUNOLOGIC ENHANCEMENT OF VACCINE IMMUNOGENICITY NIH GUIDE, Volume 22, Number 42, November 19, 1993 RFA AVAILABLE: AI-94-001 P.T. 34; K.W. 0710065, 0740075 National Institute of Allergy and Infectious Diseases Letter of Intent Receipt Date: January 15, 1994 Application Receipt Date: March 15, 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 Division of Allergy, Immunology and Transplantation (DAIT) and the Division of Microbiology and Infectious Diseases (DMID) of the National Institute of Allergy and Infectious Diseases (NIAID) invite applications for basic, applied, or preclinical studies of molecular immunologic methods to enhance protective responses to the antigens of infectious pathogens of man to develop new and improved vaccines. The NIAID seeks studies that utilize advances in immunology to develop new targeting molecules, immunologic adjuvants, or other technology to improve existing vaccines by making them safer or more immunogenic, and to develop new vaccines where none exist for microbial pathogens. Of special interest are those studies that demonstrate the feasibility of new ideas or novel approaches and show promise for clinical application. 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, Immunologic Enhancement of Vaccine Immunogenicity, is related to the priority areas of diabetes and chronic disabling 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 202-782-3238). ELIGIBILITY REQUIREMENTS Research grant applications may be submitted by domestic and foreign, for-profit and non-profit organizations, public and private institutions, such as universities, colleges, hospitals, laboratories, units of State or local governments, and eligible agencies of the Federal government. Foreign institutions are not eligible to apply for First Independent Research Support and Transition (FIRST) (R29) Awards. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT The mechanisms of support will be the individual research project (R01) grant and the FIRST (R29) grant. Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. The total project period may not exceed five years. FUNDS AVAILABLE The estimated total funds (direct and indirect costs) available for the first year of support for all awards under this RFA will be $2,000,000. In Fiscal Year 1994, the NIAID plans to fund approximately 10 R01s/R29s. Applications may not request more than four percent annual inflationary increases for future years. 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 NIAID, awards pursuant to this RFA are contingent upon the availability of funds for this purpose. Funding beyond the first and subsequent years of the grant will be contingent upon satisfactory progress during the preceding years and availability of funds. RESEARCH OBJECTIVES Background The area of vaccine research and development has been and continues to be a major priority for the NIAID, and it is the lead agency within the National Institutes of Health for such efforts. Vaccines are probably the best tools ever developed for the prevention of disease, and they are important for both disease control and control of health care costs. A Blue Ribbon Panel on Vaccine Research convened by NIAID in 1993 emphasized the priorities of improving the safety and effectiveness of current vaccines, as well as the development of new vaccines for diseases where none exist including emerging infectious diseases. Major advances in our understanding of the immune system and its response to infectious agents have occurred in recent years. These advances include: characterization of the structure and function of the T lymphocyte receptor for antigen and the numerous accessory molecules involved in the initial signal transduction events; identification and characterization of the numerous cytokines that regulate immune responses; delineation of the steps involved in antigen processing and presentation; definition and characterization of adhesion molecules and their roles in interactions between cells of the immune system; identification of genes that regulate the expression and function of many immune system molecules; and, in several infectious diseases, elucidation of the role (protective vs. pathogenic) played by different arms of the immune response. Research Objectives and Scope The goal of this initiative is to increase knowledge of the cellular, molecular, and immunologic basis of immunogenicity and to promote the application of this knowledge to the development of new approaches not only to improve existing vaccines (e.g., render them safer, more immunogenic) but also to develop new vaccines for pathogens or diseases for which no vaccines currently exist. Studies that involve relevant animal models of human diseases, including appropriate in vivo testing of immunoenhancers, and studies that involve human tissues and cells are especially encouraged. Some examples of relevant research topics are given below; these examples, however, are not intended to be all-encompassing or limiting. o Incorporation of antigen or antigenic peptides into targeting molecules that will more efficiently deliver them to antigen presenting cells and/or specific lymphoid tissue o Manipulation of antigen processing and presentation pathways to enhance immunogenicity o Modification of cytokine structure to enhance potency of the adjuvant properties and/or to reduce undesirable or deleterious aspects of cytokine function(s) o Concomitant administration of appropriate cytokines and antigens to elicit specific effector arms (e.g., TH1 vs. TH2 lymphocytes, immunoglobulin isotypes) of the immune system o Prolongation of antigen exposure by immunization with cells into which microbial genes have been transferred. 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 research, 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 January 15, 1994, a letter of intent that includes a descriptive title of the overall proposed research, the name, address and telephone number of the Principal Investigator, and the number and title of this RFA. Although the letter of intent is not required, is not binding, does not commit the sender to submit an application, 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 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 the standard research grant application form PHS 398 (Rev. 09/91). Application forms may be obtained from the institution's office for sponsored research or its equivalent 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 March 15, 1994. 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. For purposes of identification and processing, item 2a on the face page of the application must be marked "YES" and the RFA number and the words "IMMUNOLOGIC ENHANCEMENT OF VACCINE IMMUNOGENICITY" must be typed in. REVIEW CONSIDERATIONS The usual review criteria for R01/R29 applications will be used to evaluate applications submitted in response to this RFA. AWARD CRITERIA Funding decisions will be made on the basis of scientific and technical merit as determined by peer review, program priorities, and the availability of funds. INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Requests for the RFA as well as inquiries regarding programmatic issues may be directed to: Howard B. Dickler, M.D. Division of Allergy, Immunology and Transplantation National Institute of Allergy and Infectious Diseases Solar Building, Room 4A19 6003 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-7104 FAX: (301) 402-2571 Direct inquiries regarding review issues, address the letter of intent to, and mail two copies of the application and the five sets of appendices to: Olivia Preble, Ph.D. Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4C19 6003 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-8208 FAX: (301) 402-2638 Direct inquiries regarding fiscal matters to: Mr. Jeffrey Carow Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4B29 6003 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-7075 Schedule Letter of Intent Receipt Date: January 15, 1994 Application Receipt Date: March 15, 1994 Scientific Review Date: July 1994 Advisory Council Date: September 1994 Earliest Award Date: September 1994 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance, No. 93.855 - Immunology, Allergy and Transplantation Research. Awards will be made under the authority of the Public Health Service Act, Title III, Section 301 (Public Law 78-410, as amended; 42 USC 241) and administered under PHS grants policies and Federal Regulations 42 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$R6 END ************************************************************ $$R7 BEGIN AI-93-020 FULL-TEXT ************************************** COOPERATIVE CLINICAL TRIAL IN PEDIATRIC TRANSPLANTATION NIH GUIDE, Volume 22, Number 42, November 19, 1993 RFA AVAILABLE: AI-93-020 P.T. 34; K.W. 0745065, 0755015, 0770005 National Institute of Allergy and Infectious Diseases Letter of Intent Receipt Date: December 1, 1993 Application Receipt Date: March 15, 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 Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases (NIAID), invites applications from single institutions or consortia of institutions wishing to participate in a multi-center, cooperative clinical trial to improve the outcome of kidney and/or liver transplants in pediatric populations. The goal of this study is to evaluate therapeutic approaches for enhancing graft and patient survival among kidney and/or liver transplant recipients up to 16 years of age. Because of the importance of the immune system in graft acceptance/survival, this RFA also seeks to enhance basic knowledge about aspects of the pediatric immune system relevant to transplantation and to foster the application of such knowledge in the clinical setting. 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, Cooperative Clinical Trial in Pediatric Transplantation, is related to the priority area of diabetes and chronic disabling 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 for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State or local government, and eligible agencies of the Federal government. Foreign organizations are not eligible to apply. Domestic applications may not include international components. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT The administrative and funding mechanism to be used to undertake this program will be the Cooperative Agreement (U01). Details of the responsibilities, relationships, and governance of a study funded under a cooperative agreement are discussed in the RFA under the section Terms and Conditions of Award. FUNDS AVAILABLE The estimated total funds (direct and indirect costs) available for the first year of support for awards under this RFA will be $1,000,000. In Fiscal Year 1994, the NIAID plans to fund at least two Pediatric Transplant Units (PTUs) either as individual projects or as a consortium. This level of support is dependent on the receipt of a sufficient number of applications of high scientific merit. RESEARCH OBJECTIVES The purpose of this RFA is to provide support for a prospective, multi-center, cooperative clinical trial in pediatric transplant recipients. The primary objectives of this study may include, but are not limited to, the following: o design and implement a common protocol to evaluate, in a controlled setting, therapeutic approaches for enhancing graft and patient survival in pediatric kidney and/or liver transplant recipients up to 16 years of age; o evaluate new and innovative therapeutic approaches, including modifications of existing therapeutic approaches, as a means of improving outcome; and o conduct appropriate correlative laboratory studies in support of the common protocol. A secondary objective of this study is to enhance basic understanding of the pediatric immune system. Specific questions to be addressed in this area may include, but are not limited to, the following: o What qualitative and quantitative differences in immune response to transplantation exist between pediatric and adult transplant recipients? To what extent are these differences the result of other factors, e.g., the size and volume of the pediatric patient? o What is the nature of the apparent "enhanced" immune state of the pediatric transplant patient and to what extent does it account for/contribute to differences in outcome relative to adults? o What are the major mediators of graft rejection? o What impact, if any, does the immune system have on growth and development in pediatric transplant recipients? o What immunologic differences exist among various pediatric age groups with respect to immune system function/activity? Although it is recognized that many factors play a role in enhancing outcome, such as compliance, socioeconomic factors, and other systems (e.g., the endocrine system), the limited funds available for this RFA may preclude study of each and every such factor. Emphasis will be focused on the immune system. Study Design: In order to accumulate sufficient sample size for the study, a collaborative effort will be required by at least two Pediatric Transplant Units (PTUs), funded as either individual projects or as a consortium. The PTUs will follow a uniform study protocol with standardized data collection procedures. The protocol may focus on pediatric kidney transplant recipients alone, pediatric liver transplant recipients alone, or both. Combined kidney/liver transplantation is not within the scope of this RFA. Pediatric transplant recipients up to 16 years of age may be studied. The specific age groups to be studied will be determined by the design of the common protocol. The protocol should include a proposed controlled clinical trial designed to evaluate new and innovative therapeutic approaches, including modifications in existing therapeutic approaches, to enhance graft and patient survival. Although the actual protocol to be conducted will be designed by the Steering Committee for this project, applications must include a proposed protocol that meets the objectives and scope of this 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 women and minorities in study populations. If women and minorities are not included in the study populations for clinical research, 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 December 1, 1993, a letter of intent that includes a descriptive title of the overall proposed research, the name, address and telephone number of the Principal Investigator, the number and title of this RFA, and a list of the key investigators and their institution(s). The letter of intent is to be sent to Dr. Mark Rohrbaugh at the address listed under INQUIRIES. APPLICATION PROCEDURES Applications are to be submitted on the standard research grant application form PHS 398 (rev. 9/91). For purposes of identification and processing, item 2a on the face page of the application must be marked "YES" and the RFA number and the words "COOPERATIVE CLINICAL TRIAL IN PEDIATRIC TRANSPLANTATION" must be typed in. 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. These application forms may be obtained from the institution's office of sponsored research or its equivalent 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 March 15, 1994. REVIEW CONSIDERATIONS The required standard review criteria for RFAs are the same as those for unsolicited research project grant applications. In addition, applicants are expected to address the issues identified in the RFA under SPECIAL REQUIREMENTS. AWARD CRITERIA 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. 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: Andrea A. Zachary, Ph.D. Division of Allergy, Immunology and Transplantation National Institute of Allergy and Infectious Diseases Solar Building, Room 4A13 Bethesda, MD 20892 Telephone: (301) 496-5598 FAX: (301) 402-2571 Direct inquiries regarding review issues, address the letter of intent to, and mail two copies of the application and all five sets of appendices to: Mark Rohrbaugh, Ph.D. Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4C22 Bethesda, MD 20892 Telephone: (301) 496-8424 FAX: (301) 402-2638 Direct inquiries regarding fiscal matters to: Mr. Jeffrey Carow Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4B29 Bethesda, MD 20892 Telephone: (301) 496-7075 Schedule Letter of Intent Receipt Date: December 1, 1993 Application Receipt Date: March 15, 1994 Scientific Review Date: June 1994 Advisory Council Date: September 1994 Earliest Award Date: September 1994 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance, No. 93.855 - Immunology, Allergy and Transplantation Research. Awards will be made under the authority of the Public Health Service Act, Title III, Section 301 (Public Law 78-410, as amended; 42 USC 241) and administered under PHS grants policies and Federal Regulations 42 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$R7 END ************************************************************ $$R8 BEGIN HL-94-003-B FULL-TEXT ************************************ GENE THERAPY FOR SICKLE CELL DISEASE NIH GUIDE, Volume 22, Number 42, November 19, 1993 RFA AVAILABLE: HL-94-003-B P.T. 34; K.W. 0715032, 0745032 National Heart, Lung, and Blood Institute Letter of Intent Receipt Date: January 15, 1994 Application Receipt Date: March 15, 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 Sickle Cell Disease Branch, Division of Blood Diseases and Resources, National Heart, Lung, and Blood Institute (NHLBI), invites research grant applications for the support of basic and applied research leading to the development of strategies to correct and/or replace the endogenous defective gene in sickle cell anemia. 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, Gene Therapy for Sickle Cell Disease, is related to the priority areas of clinical prevention services, chronic disabling conditions, and maternal and infant 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 202-782-3238). 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 state or local governments, and eligible agencies of the federal government. Awards in response to this RFA will be made to domestic institutions only. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT This RFA will use the National Institutes of Health (NIH) program project grant (P01) and is a one-time solicitation. A program project grant accommodates the support of a research program in which a multidisciplinary team of investigators works collaboratively in a clearly defined area of mutual scientific interest. In a program project, achievement of the objectives of the research effort is facilitated by the sharing of ideas, data, and specialized resources. An important goal of this program is to attract new and established investigators into the field of gene therapy for sickle cell disease by providing access to critical technologies in the form of shared facilities and funds to pursue innovative pilot/feasibility studies. Five years of support must 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 September 30, 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. All applications submitted in response to this RFA should conform to the policies and format described in Program Project Grant - Preparation of the Application, NHLBI (Revised). A copy of this publication may be obtained from Dr. Junius Adams at the address listed under INQUIRIES. FUNDS AVAILABLE It is anticipated that for fiscal year 1994, up to two new program project grants of up to $1,000,000 will be awarded under this program. It should be noted that award of grants pursuant to this RFA is contingent upon receipt of such funds for this purpose. 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 Sickle cell disease is a worldwide health problem and is one of the most common inherited disorders of man. A rational approach for the cure of sickle cell disease would be the replacement of the abnormal beta-globin gene with a normal beta-globin gene or to repair the sickle mutation in DNA. Either approach would use bone marrow stem cells manipulated in vitro to alter their genetic makeup and subsequently reintroduce them into the patient. Molecular studies and recent advances made at the level of the genome that have enhanced our understanding of gene regulation and expression, along with rapidly developing techniques of gene transfer, have opened new avenues for the potential treatment of genetic diseases. The ability to insert copies of normal genes into cells, with the production of new genes producing proteins to correct this biochemical defect, would be a major advance in treating this disease. Adequate expression of the normal beta-globin gene in patients with sickle cell anemia would be curative. The following are examples of the type of research approaches that would be responsive to the program: o Improvement of the efficiency of transfection of hematopoietic stem cells by augmenting the number of stem cells available for transfection and increasing the efficiency of the vector. o Introduction of a selective advantage to stem cells that allow successful competition with endogenous stem cell for proliferation, self-renewal, and differentiation in vivo o Development of new strategies for the introduction of exogenous genes into stem cells with the goal of obtaining therapeutically useful levels of expression and stability of the transferred gene. o Development of more efficient methods for gene insertion by homologous recombination. o Development of methods to silence or attenuate the expression of the endogenous beta-S-globin gene o Development of improved animal models to assess the efficacy of approaches o An important goal of this program is to attract new and established investigators into the field of gene therapy for sickle cell disease by providing access to critical technologies (in the form of shared core facilities described above) and funds to pursue innovative pilot/feasibility studies. Pilot/feasibility studies will enable established investigators who did not previously work in gene therapy and new investigators with state-of-the-art core technologies that will enable them to be competitive in the field. In addition, pilot/feasibility studies will allow investigators to pursue promising but untested innovative research in gene therapy. These approaches are meant to serve only as examples of the types of research projects that would be responsive to the goals of this solicitation. Investigators are encouraged to develop and propose their own 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 January 15, 1994, 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. The letter of intent is to be sent to: Acting 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 March 15, 1994. 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 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. Applicants from institutions that have a General Clinical Research Center (GCRC) funded by the NIH Center for Research Resources may From owner-sci-resources@net.bio.net Thu Nov 18 22:00:00 1993 Path: biosci!net.bio.net From: kristoff@net.bio.net (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 22, no. 42, pt. 4, 19 November 1993 Message-ID: Date: 19 Nov 93 04:52:34 GMT Sender: kristoff@net.bio.net Lines: 1014 Approved: biosci-moderator@net.bio.net $$XID RFA AI93020 AI-93-020 P1O1 *************************************** COOPERATIVE CLINICAL TRIAL IN PEDIATRIC TRANSPLANTATION NIH GUIDE, Volume 22, Number 42, November 19, 1993 RFA: AI-93-020 P.T. 34; K.W. 0745065, 0755015, 0770005 National Institute of Allergy and Infectious Diseases Letter of Intent Receipt Date: December 1, 1993 Application Receipt Date: March 15, 1994 PURPOSE The Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases (NIAID), invites applications from single institutions or consortia of institutions wishing to participate in a multi-center, cooperative clinical trial to improve the outcome of kidney and/or liver transplants in pediatric populations. The goal of this study is to evaluate new and innovative therapeutic approaches, including evaluation of modifications in existing therapeutic approaches, for enhancing graft acceptance and patient/graft survival among kidney and/or liver transplant recipients up to 16 years of age. Because of the importance of the immune system in graft acceptance/survival, this study also seeks to enhance basic knowledge about the pediatric immune system and foster the application of such knowledge in the clinical setting. HEALTHY PEOPLE 2000 The Public Health Service 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), Cooperative Clinical Trial in Pediatric Transplantation, is related to the priority area of diabetes and chronic disabiling 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 for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State or local government, and eligible agencies of the Federal government. Foreign organizations are not eligible to apply. Domestic applications may not include international components. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT The administrative and funding mechanism to be used to undertake this program will be the Cooperative Agreement (U01), an "assistance" mechanism, rather than an "acquisition" mechanism, in which substantial NIH scientific and/or programmatic involvement with the awardee is anticipated during the performance of the activity. Under the cooperative agreement, the NIH purpose is to support and/or stimulate the recipient's activity by involvement in and otherwise working jointly with the award recipient in a partner role, but it is not to assume direction, prime responsibility, or a dominant role in the activity. Details of the responsibilities, relationships, and governance of a study funded under cooperative agreement(s) are discussed later in this document under the section Terms and Conditions of Award. The total project period for applications submitted in response to this RFA may not exceed five years. At present, the NIAID is administratively limiting the duration of U01 cooperative agreements to four years; this administrative limitation may change in the future. At this time, the NIAID has not determined whether and how this solicitation will be continued beyond the present RFA. FUNDS AVAILABLE The estimated total funds (direct and indirect costs) available for the first year of support for awards under this RFA will be $1,000,000. In Fiscal Year 1994, the NIAID plans to fund at least two Pediatric Transplant Units (PTUs) either as individual projects or as a consortium. It is anticipated that the size of awards will vary depending on the number of participating institutions and the number of potential study participants. The usual PHS policies governing grants administration and management will apply. 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 NIAID, awards pursuant to this RFA are contingent upon the availability of funds for this purpose. Funding beyond the first and subsequent years of the grant will be contingent upon satisfactory progress during the preceding years and availability of funds. RESEARCH OBJECTIVES Background Kidney and liver transplantation remains the therapy of choice for children with end-stage renal or hepatic failure. There are no alternative therapies for hepatic failure and, although dialysis offers an alternative treatment for children with renal failure, the morbidity and side effects remain significant. Unfortunately, the improvements seen in renal allograft survival in adults which have occurred during the last decade have not been seen in pediatric patients. Children have significantly poorer one-year graft survival rates for both kidney and liver transplantation than adults. Although many factors have been implicated, the most important appears to be the pediatric immune system. For example, in contrast to adults, children apparently exhibit an "enhanced" immune state and require higher doses of immunosupressive therapy. Although it appears that end-stage organ disease produces a generalized immunosuppression, children are less affected than adults. The concept of the pediatric patient being less immunocompromised than adults is further supported by the results of non-specific assays, such as total T lymphocyte counts and response to mitogen stimulation. This, in turn, is associated with more frequent and more vigorous graft rejection episodes and a high frequency of graft loss due to rejection. Also problematic are the immunosuppressive drugs currently used, both in the inability to readily determine optimal regimens and exacerbation of side effects. For example, cyclosporin A (CsA) needs to be delivered in greater doses because the intestinal length of children apparently results in reduced absorption, and more frequently because children metabolize CsA faster. Further, increased doses of either CsA or corticosteroids increase hyperlipidemia which, in turn, increases the risk of atherosclerotic cardiovascular disease. Other side effects of corticosteroids include growth retardation. However, attempts to reduce or eliminate corticosteroids from the treatment regimen lead to rejection episodes in 50 percent of pediatric patients. Such episodes reduce glomerular filtration rates in renal transplants and this diminishes the growth improvement achieved by steroid removal. Thus, several important questions can be addressed in children that are relevant to both renal and hepatic transplantation. These include: the causes of the poor patient and graft survival rates, the effects of therapy on growth and development, and how best to optimize treatment regimens. Objectives and Scope The purpose of this RFA is to provide support for a prospective, multi-center, cooperative clinical trial in pediatric transplant recipients. The primary objectives of this study may include, but are not limited to, the following: o design and implement a common protocol to evaluate, in a controlled setting, therapeutic approaches for enhancing graft and patient survival in pediatric kidney and/or liver transplant recipients up to 16 years of age; o evaluate new and innovative therapeutic approaches, including modifications in existing therapeutic approaches, as a means of improving outcome; and o conduct appropriate correlative laboratory studies in support of the common protocol. A secondary objective of this study is to enhance basic understanding of the pediatric immune system, i.e., differences between children and adults that are essential to understanding graft rejection. Specific questions to be addressed in this area may include, but are not limited to, the following: o What qualitative and quantitative differences in immune response to transplantation exist between pediatric and adult transplant recipients? To what extent are these differences the result of other factors, e.g., the size and volume of the pediatric patient? o What is the nature of the apparent "enhanced" immune state of the pediatric patient and to what extent does it account for/contribute to differences in outcome relative to adults? o What are the major mediators of graft rejection? o What impact, if any, does the immune system have on growth and development in pediatric transplant recipients? o What immunologic differences exist among various pediatric age groups with respect to immune system function/activity? Although it is recognized that many factors may play a role in enhancing outcome, such as compliance, socioeconomic factors, and other systems (e.g., the endocrine system), the limited funds available for this RFA may preclude study of each and every such factor. Emphasis will be focused on the immune system. Study Design In order to accumulate sufficient sample size for the study, a collaborative effort will be required by at least two PTUs, funded as either individual projects or as a consortium. In this collaborative effort, the PTUs will follow a uniform study protocol with standardized data collection procedures. The protocol may focus on pediatric kidney transplant recipients alone, pediatric liver transplant recipients alone, or both. Combined kidney/liver transplantation is not within the scope of this RFA. Pediatric transplant recipients up to 16 years of age may be studied. The specific age groups to be studied will be determined by the design of the consensus protocol. The protocol should include a controlled clinical trial designed to evaluate new and innovative therapeutic approaches, including modifications in existing therapeutic approaches, to enhance graft and patient survival. SPECIAL REQUIREMENTS A. Study Organization 1. Steering Committee A Steering Committee will be established to serve as the main governing body of the study. At a minimum, the Steering Committee will be composed of the NIAID Pediatric Transplantation Research Coordinator (PTRC) and one representative from each participating institution as follows: the Principal Investigator of each PTU whether a single institution or a consortium of institutions, and a Senior Investigator from each additional institution participating in a consortium arrangement. The Senior Investigator is the person responsible for on-site scientific direction and implementation of the consensus protocol at institutions participating in a consortium arrangement. Senior Investigators must be physicians with substantial experience in (1) pediatric kidney and/or liver transplantation; (2) immunosuppression; and (3) the design, implementation and evaluation of clinical trials. All major scientific decisions will be determined by the Steering Committee, with each Principal Investigator, Senior Investigator, and the NIAID PTRC having one vote. The Chairperson will be selected by the Steering Committee from among the non-Federal members during the first meeting of the Committee, to be convened by the NIAID PTRC. The Committee will meet at least three times during the first 12 months of the study and at least semi-annually thereafter. This Committee will have primary responsibility for developing the consensus protocol, facilitating the conduct and monitoring of the study, analyzing and interpreting study data, and reporting study results. The study will proceed into the implementation stage only with the concurrence of both the awardees and the NIAID PTRC. Topics for the protocols will be proposed and prioritized by the Steering Committee. Each Principal Investigator and Senior Investigator (or his/her designee) will be expected to participate in all other Steering Committee activities, e.g., conference calls, special subcommittees as may be necessary, etc. Subcommittees of the Steering Committee may be established as necessary. At a minimum, the Steering Committee will establish an Immunology Research Advisory Subcommittee to provide advice to the Steering Committee with respect to research on the peditric immune system, as described under the section "RESEARCH OBJECTIVES." The Immunology Research Advisory Subcommittee will be composed of one representative selected by each member of the Steering Committee, as well as the NIAID PTRC. This Subcommittee will meet annually in conjunction with one of the Steering Committee meetings. 2. Data and Safety Monitoring Board An independent Data and Safety Monitoring Board, to be appointed by the NIAID, will review progress at least annually and report to the NIAID PTRC. Protocols will be subject to review by the Data and Safety Monitoring Board in an advisory capacity. 3. Data Coordination and Management The NIAID will be responsible for ensuring the provision of centralized data management and coordination assistance. Under the direction of the Steering Committee, the NIAID will provide technical assistance and data management services to the PTUs with respect to quality control, uniformity of data collection, management of the collective data base, and data analysis. PTUs will submit data to the NIAID; specific data analyses to be carried out will be determined by the Steering Committee and the results of those analyses will be delivered to the Steering Committee as the group responsible for determining which further analyses should be done, how the results are interpreted, whether the results should influence ongoing data collection, and how the findings should be disseminated. Although the PTUs will be closely involved with these centralized data collection and management services, applicants should not include in their budget requests support for any of these functions. B. Minimum Requirements for Application To promote the development of a collaborative program among the award recipients, a minimum number of issues need to be addressed in the applications, as outlined below. 1. The application should include a proposed protocol that meets the objectives and scope of this RFA, as well as a discussion of the rationale for the patient population, the study design and the therapeutic approach(es) selected for study, and an assessment of how anticipated study results can be expected to contribute to improvements in patient/graft survival. Award of the Cooperative Agreement does not imply that the proposed protocol will be implemented. Since the actual study will be designed by the Steering Committee, the final study may not reflect any single protocol submitted in response to this RFA. 2. The applicant institution and each participating institution associated with an applicant consortium must document their experience and capacity to recruit and retain pediatric study participants, provide a description of the population currently available for the proposed protocol, and describe proposed mechanisms for monitoring accrual performance and criteria for continued participation by each participating institution. 3. The application must identify the single applicant organization that will be legally and financially respnsible and accountable for the use and disposition of funds awarded on the basis of this RFA to other institutions and/or individual components of the PTU, and show availability of personnel and facilities capable of performing and supporting the administrative functions of the PTU. 4. The application must name a single Principal Investigator (PI) who will have scientific responsibility for the application as a whole including all PTU-related research activities included under it. The PI must be a physician with substantial experience in (1) pediatric kidney and/or liver transplantation; (2) immunosuppression; and (3) the design, implementation and evaluation of clinical trials. In addition, applications from consortia of institutions must name a single Senior Investigator for each participating institution (other than the applicant institution) who will be responsible for on-site scientific direction and implementation of the consensus protocol. Senior Investigators must also be physicians with substantial experience in (1) pediatric kidney and/or liver transplantation; (2) immunosuppression; and (3) the design, implementation and evaluation of clinical trials. 5. The application must name a Project Coordinator who is an individual with substantial technical/administrative experience in managing patient enrollment, patient follow-up, and multi-source data collection for clinical studies. Each participating institution associated with an applicant consortium much also name such a Project Coordinator. 6. The application must provide: a clear, concise plan in narrative and diagrammatic form that depicts the interrelationships among the members of the PTU, their relevant experience/expertise, and the contribution of each to fulfillment of the objectives of this RFA; an organizational chart of the PTU showing the name, organization, and scientific discipline of the PI and of all key scientific, technical and administrative personnel; and a mechanism for selecting and replacing key professional or technical personnel. 7. The application must provide a plan to assure the maintenance of close cooperation and effective communication among members of the PTU, whether a single institution or a consortium of institutions, including letters of commitment to this plan from all participating institutions. 8. The application should discuss the capability of the applicant organization and each institution in an applicant consortium to participate and interact effectively in cooperative, multi-center clinical trials. 9. The application must include a written commitment to accept the participation and assistance of NIAID staff in accordance with the guidelines outlined under "Terms and Conditions of Award: NIAID Staff Responsibilities." The application must also include a written commitment to the cooperative organization and willingness to serve on the Steering Committee and adhere to the decisions reached by that Committee, including following the consensus protocol. 10. All costs required for the proposed protocol must be included in the application and must be fully justified. These include the additional costs of clinical research associated with the proposed protocol, costs for patient recruitment and follow-up, laboratory studies, data collection, and participation in on-site quality assurance audits. Requested budgets should also include: (1) travel to the Chicago, Illinois area for three two-day Steering Committee meetings during the first 12 months of the study and semi-annual Steering Committee meetings thereafter for the Principal Investigator and Senior Investigator(s) of each institution participating in an applicant consortium, and (2) travel to the Chicago, Illinois area for annual one-day meetings of the Immunology Research Advisory Subcommittee for one representative from each PTU and each institution participating in a consortium arrangement. C. Terms and Conditions of Award The following terms and conditions will be incorporated into the award statement and provided to the Principal Investigator as well as the institutional official at the time of award. These special Terms of Award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS Grant Administration Regulations at 45 CFR part 74 and 92, and other HHS, PHS, and NIH Grant Administration policy statements. The administrative and funding instrument used for this program is the cooperative agreement (U01), an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH scientific and/or programmatic involvement with the awardee is anticipated during the performance of the activity. Under the cooperative agreement, the NIH purpose is to support and/or stimulate the recipient's activity by involvement in and otherwise working jointly with the award recipient in a partner role, but it is not to assume direction, prime responsibility, or a dominant role in the activity. Consistent with this concept, the dominant role and prime responsibility for the activity resides with the awardees for the project as a whole, although specific tasks and activities in carrying out the study will be shared among the awardees and the NIAID PTRC. 1. Awardee Rights and Responsibilities Awardees will have primary responsibility for defining the details for the project within the guidelines of the RFA and for performing the scientific activity, and agree to accept close coordination, cooperation, and participation of NIAID staff in all aspects of scientific and technical management of the project. Specifically, awardees have primary responsibilities as described below. Steering Committee Membership and Meeting Attendance Each Principal Investigator and Senior Investigator will serve as a voting member of the Steering Committee and will participate in all scientific decisions. Each Principal Investigator and Senior Investigator (or his/her designee) will be responsible for attending all Steering Committee meetings, including not less than three meetings during the first 12 months of the study and two per year thereafter. The Steering Committee shall be responsible for determining the frequency of meetings and scheduling the time and location. Each Principal Investigator and Senior Investigator (or his/her designee) will be expected to participate in all other Steering Committee activities, e.g., conference calls, special subcommittees as may be necessary, etc. Subcommittees of the Steering Committee may be established as necessary. At a minimum, the Steering Committee will establish an Immunology Research Advisory Subcommittee to provide advice to the Steering Committee with respect to research on the peditric immune system, as described under the section "RESEARCH OBJECTIVES." The Immunology Research Advisory Subcommittee will be composed of one representative selected by each member of the Steering Committee, as well as the NIAID PTRC. This Subcommittee will meet annually in conjunction with one of the Steering Committee meetings. Protocol Development and Conduct The Steering Committee will define protocol objectives and approaches and design the consensus protocol. Each awardee will follow the procedures required by the consensus protocol generated by the Steering Committee regarding study conduct and monitoring, patient management, data collection and quality control. Data Coordination and Management Each awardee will be responsible for providing the NIAID with all primary study data for management, quality control and analysis, using procedures and standards determined by the Steering Committee. All data will be available to all awardees. Specific analyses to be performed by NIAID will be directed by the Steering Committee. The awardees will retain custody of and have primary rights to all data developed under these awards, subject to Government rights of access consistent with HHS, PHS, and NIH policies. Publication and Presentation of Study Findings Early publication of major findings is encouraged. Publications and oral presentations of work performed under this agreement will require appropriate acknowledgement of both the PTUs and NIAID support. Analyses to be performed using the collective data from all PTUs will be determined and directed by the Steering Committee. PTUs wishing to perform analyses of local data will inform the Steering Committee of any such analyses prior to initiation in order to avoid duplication. Review and approval by the Steering Committee will be required for all analyses prior to publication or presentation according to criteria that will be developed by the Committee. Monitoring Study Progress The Steering Committee will establish mechanisms for assessing performance of the PTUs, including institutions participating in consortia arrangements, with particular attention to accrual of adequate numbers of eligible patients, timely submission and quality of required data and conscientious observance of protocol requirements. Federally Mandated Regulatory Requirements Each PTU, and each institution participating in a consortium arrangement, is required to meet the DHHS/PHS regulations for the protection of human subjects and FDA requirements for the conduct of research using investigational agents. At a minimum, these include: o methods for assuring that each institution at which PTU investigators are conducting clinical studies has a current, approved assurance on file with the Office of Protection from Research Risks (OPRR); that study protocols are reviewed and approved by the responsible Institutional Review Board (IRB) prior to patient entry; that active protocols are reviewed at least annually by the IRB; and that amendments are approved by the IRB. o methods for assuring or documenting that each patient, or patient's parent/legal guardian, gives fully informed consent to participation in a research protocol prior to the initiation of the experimental intervention. 2. NIAID Staff Responsibilities The NIAID PTRC will have substantial scientific/programmatic involvement during the conduct of this activity, through technical assistance, advice and coordination above and beyond normal program stewardship for grants, as described below. Steering Committee Membership and Meeting Attendance The NIAID PTRC will serve as a voting member of the Steering Committee, will attend all Steering Committee meetings, and will participate in other Committee activities, e.g., conference calls, special subcommittees. The NIAID PTRC will also serve on the Immunology Research Advisory Subcommittee. Protocol Development As a member of the Steering Committee, the NIAID PTRC will serve as a resource with respect to the design of the protocol and will assist the Steering Committee in protocol development. Study Materials The NIAID will be responsible for the acquisition and distribution of those study materials involved in the protocol developed by the consensus of the Steering Committee. The NIAID will also arrange for the appropriate approvals (when necessary) from the Food and Drug Administration (FDA) and the Bureau of Biologics (BOB) with respect to the use investigational drugs. Monitoring Study Performance The NIAID PTRC will provide assistance to the Steering Committee in the development of mechanisms and procedures for monitoring study performance. This includes participation in periodic on-site monitoring with respect to compliance with protocol specifications, quality control and accuracy of data recording, and accrual. Data Coordination and Management The NIAID will be responsible for ensuring the provision of centralized data management and coordination assistance. Under the direction of the Steering Committee, the NIAID will provide technical assistance and data management services to the PTUs with respect to quality control, uniformity of data collection, management of the collective data base, and data analysis. The Government, via the NIAID PTRC, will have access to data generated under this Cooperative Agreement and may periodically review the data and progress reports. Information obtained from the data may be used by NIAID Staff for the preparation of internal reports on the activities of the study. However, awardees will retain custody of and have primary rights to all data developed under these awards. Publication and Presentation of Study Findings The NIAID PTRC may contribute, through review, comment, analysis, and/or co-authorship, to reporting results of the study to the investigator community and other interested scientific and lay organizations. Co-authorship by the NIAID PTRC will be subject to approval in accordance with NIH policies regarding staff authorship of publications resulting from extramural awards. Organizational Changes Certain organizational changes require the prior written approval of the NIAID PTRC. These changes include the addition/deletion of a physician, scientific investigator, affiliate, component, or research base that is associated with this study. A change in the Principal Investigator, or in any key personnel identified on the Notice of Award, must have the prior written approval of the NIAID Grants Management Specialist in consultation with the NIAID PTRC. Program Review The NIAID PTRC will review the progress of each PTU through consideration of the annual reports, site visits, patient logs, etc. This review may include, but is not limited to, compliance with the study protocol, meeting patient enrollment targets, adherence to uniform data collection procedures, and the timeliness and quality of data reporting. The NIAID reserves the right to terminate or curtail the study (or any individual award) in the event of (a) substantial shortfall in participant recruitment, follow-up, data reporting, quality control, or other major breech of the protocol, (b) substantive changes in the agreed-upon protocol to which the NIAID does not agree, (c) reaching a major study endpoint substantially before schedule with persuasive statistical significance, or (d) human subject ethical issues that may dictate a premature termination. 3. Collaborative Responsibilities A Steering Committee, composed of the Principal Investigators, Senior Investigators of institutions participating in a consortium, and the NIAID PTRC, will be the main governing body of the study and will have primary responsibility for all scientific decisions, including: defining protocol objectives and approaches; designing and implementing the protocol; developing procedures for data collection, management and quality control; establishing procedures for assessing performance with respect to accrual, timely submission and quality of data, and conscientious observance of protocol requirements; analyzing and interpreting study data; and publishing/presenting study findings. Each member of the Steering Committee will have one vote. The chairperson will be selected by the Steering Committee from among the non-Federal members. Subcommittees will be established by the Steering Committee, as it deems appropriate. At a minimum, the Steering Committee will establish an Immunology Research Advisory Subcommittee to provide advice with respect to research on the pediatric immune system as described under the section "RESEARCH OBJECTIVES." The Immunology Research Advisory Subcommittee will be composed of one representative selected by each member of the Steering Committee, as well as the NIAID PTRC. This Subcommittee will meet annually in conjunction with one of the Steering Committee meetings. An independent Data and Safety Monitoring Board, to be appointed by the NIAID, will review progress at least annually and report to the NIAID PTRC. The protocol will be subject to review by this Board in an advisory capacity. Awardees will be required to accept and implement the common protocol and procedures approved by the Steering Committee. The study will proceed into the implementation stage only with the concurrence of the awardees and the NIAID PTRC. 4. Arbitration Any disagreement that may arise on scientific/programmatic matters (within the scope of the award) between award recipients and the NIAID may be brought to arbitration. An arbitration panel will be composed of three members -- one selected by the Steering Committee (with the NIAID member not voting) or by the individual awardee in the event of an individual disagreement, a second member selected by the NIAID, and the third member selected by the two prior members. This special arbitration procedure in no way affects the awardee's rights to appeal an adverse action that is otherwise appealable in accordance with the PHS regulations at 42 CFR part 50, subpart D and HHS regulation at 45 CFR part 16. 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 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. 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. 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 will be drawn: average hospital admissions 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 sites should be provided. LETTER OF INTENT Prospective applicants are asked to submit, by December 1, 1993, a letter of intent that includes a descriptive title of the overall proposed research, the name, address and telephone number of the Principal Investigator, the number and title of this RFA, and a list of the key investigators and their institution(s). Although the letter of intent is not required, is not binding, does not commit the sender to submit an application, 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 conflict of interest in the review. The letter of intent is to be sent to Dr. Mark Rohrbaugh at the address listed under INQUIRIES. APPLICATION PROCEDURES Applications are to be submitted on the standard research grant application form PHS 398 (rev. 9/91). For purposes of identification and processing, item 2 on the face page of the application must be marked "YES" and the RFA number and the words "COOPERATIVE CLINICAL TRIAL IN PEDIATRIC TRANSPLANTATION" must be typed in. Applications from multi-component consortia must contain a single face page and additional face pages for each institution involved, an overall budget page, and separate budget pages for each institution involved. Each consortium institution is allowed 25 pages for the research plan if different plans are proposed by the different member institutions. For additional information, refer to page 8 of the PHS 398 application form. These application forms may be obtained from the institution's office of sponsored research or its equivalent 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 address the requirements below as outlined in the section "SPECIAL REQUIREMENTS: Minimum Requirements for Application." 1. Applications should include a proposed protocol that meets the objectives and scope of this RFA, as well as a discussion of the rationale for the patient population, the study design and the therapeutic approach selected for study, and an assessment of how anticipated study results can be expected to contribute to improvements in patient/graft survival. 2. The applicant institution and each participating institution associated with an applicant consortium must document their experience and capacity to recruit and retain pediatric study participants, provide a description of the population currently available for the proposed protocol, and describe proposed mechanisms for monitoring accrual performance and criteria for continued participation. 3. Applications must name a single Principal Investigator (PI) who will have scientific responsibility for the application as a whole including all PTU-related research activities included under it. The PI must be a physician with substantial experience in (1) pediatric kidney and/or liver transplantation; (2) immunosuppression; and (3) the design, implementation and evaluation of clinical trials. In addition, applications from consortia of institutions must name a single Senior Investigator for each participating institution (other than the applicant institution) who will be responsible for on-site scientific direction and implementation of the consensus protocol. Senior Investigators must also be physicians with substantial experience in (1) pediatric kidney and/or liver transplantation; (2) immunosuppression; and (3) the design, implementation and evaluation of clinical trials. 4. The application must name a Project Coordinator who is an individual with substantial technical/administrative experience in managing patient enrollment, patient follow-up, and multi-source data collection for clinical studies. Each participating institution associated with an applicant consortium much also name such a Project Coordinator. 5. The application must provide: a clear, concise plan in narrative and diagrammatic form that depicts the interrelationships among the members of the PTU, their relevant experience/expertise, and the contribution of each to fulfillment of the objectives of this RFA; an organizational chart of the PTU showing the name, organization, and scientific discipline of the PI and of all key scientific, technical and administrative personnel; and a mechanism for selecting and replacing key professional or technical personnel. 6. The application must provide a plan to assure the maintenance of close cooperation and effective communication among members of the PTU, whether a single institution or a consortium of institutions, including letters of commitment to this plan from all participating institutions. 7. The application should discuss the capability of the applicant organization and each institution in an applicant consortium to participate and interact effectively in cooperative, multi-center clinical trials. 8. The application must include a written commitment to accept the participation and assistance of NIAID staff in accordance with the guidelines outlined under "Terms and Conditions of Award: NIAID Staff Responsibilities." The application must also include a written commitment to the cooperative organization and willingness to serve on the Steering Committee and adhere to the decisions reached by that Committee, including following the consensus protocol. 9. All costs required for the proposed protocol must be included in the application and must be fully justified. These include the additional costs of clinical research associated with the proposed protocol, costs for patient recruitment and follow-up, laboratory studies, data collection, and participation in on-site quality assurance audits. Requested budgets should also include: (1) travel to the Chicago, Illinois area for three 2-day Steering Committee meetings during the first 12 months of the study and semi-annual Steering Committee meetings thereafter for the Principal Investigator and Senior Investigator(s) of each institution participating in an applicant consortium, and (2) travel to the Chicago, Illinois area for annual one-day meetings of the Immunology Research Advisory Subcommittee for one representative from each PTU and each institution participating in a consortium arrangement. It is highly recommended that the Chief of the Transplantation Section, Genetics and Transplantation Branch, NIAID Division of Allergy, Immunology and Transplantation, be contacted in the early stages of preparation of the application. (See program contact in "INQUIRIES" below.) Applications must be received by March 15, 1994. Applications that are not received by the receipt date or 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. The RFA label in the application form PHS 398 must be affixed to the bottom of the face page. 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. Submit a signed, typewritten original of the application, including the checklist, and three signed, exact, single-spaced photocopies, in one package to; Division of Research Grants National Institutes of Health Westwood Guilding, Room 240 Bethesda, MD 20892** At the time of submission, two additional exact copies of the grant application and all five sets of appendix material must also be sent to Dr. Mark Rohrbaugh at the address listed under INQUIRIES. 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. The Division of Research Grants (DRG) will not accept any application in response to this RFA 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 a substantial revision of an application already reviewed, but such applications must include an introduction addressing the previous critique. REVIEW CONSIDERATIONS Review Method Upon receipt, applications will be reviewed for completeness by the NIH Division of Research Grants (DRG) and for responsiveness by NIAID staff. Incomplete applications will be returned to the applicant without further consideration. If the application is not responsive to the RFA, it will be returned without further consideration. Those applications that are complete and responsive may be subjected to a triage by a peer review group to determine their scientific merit relative to other applications received in response to this RFA. The NIAID will withdraw from competition those applications judged to be non-competitive for award and will notify the Principal Investigator and institutional business official. Those applications judged by the reviewers to be competitive for award will be further reviewed for scientific and technical merit by a review committee convened by the Division of Extramural Activities, NIAID. The second level of reivew will be provided by the National Advisory Allergy and Infectious Diseases Council. Review Criteria The review criteria for this RFA are the same as those for unsolicited research project grant applications. In addition, applicants are expected to address the issues identified under SPECIAL REQUIREMENTS as well as criteria specific to the objectives of this RFA. These criteria include: 1. The scientific and technical significance, merit and originality of the proposed protocol and its anticipated contributions to improved graft/patient survival. 2. The scientific expertise and experience of the Principal Investigator, the Senior Investigators for an applicant consortium, and key technical personnel in the fields of pediatric transplantation, immunosuppression and clinical trial design, conduct and analysis. 3. Documentation of the availability of adequate pediatric patient populations and experience and expertise of the applicant institution(s) and key personnel in recruitment, retention and follow-up of pediatric study participants. 4. Documentation of the sponsoring institution's commitment to the cooperative program, including support for membership of the proposed Principal Investigator and Senior Investigator on the Steering Committee; willingness to abide by the scientific decisions made via consensus of Steering Committee members; and willingness to accept the participation and assistance of NIAID staff. 5. Adequacy of the proposed plan for coordination and communication within the applicant institution and with institutions participating in consortia-type arrangements, particularly with respect to multi-center clinical trials. 6. Adequacy of available laboratory and clinical facilities, including information on the institution's present patient load and access to and projections for patient involvement in clinical investigations. AWARD CRITERIA 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. 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: Andrea A. Zachary, Ph.D. Division of Allergy, Immunology and Transplantation National Institute of Allergy and Infectious Diseases Solar Building, Room 4A13 Bethesda, MD 20892 Telephone: (301) 496-5598 FAX: (301) 402-2571 Direct inquiries regarding review issues, address the letter of intent to, and mail two copies of the application and all five sets of appendices to: Mark Rohrbaugh, Ph.D. Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4C22 Bethesda, MD 20892 Telephone: (301) 496-8424 FAX: (301) 402-2638 Direct inquiries regarding fiscal matters to: Mr. Jeffrey Carow Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4B29 Bethesda, MD 20892 Telephone: (301) 496-7075 Schedule Letter of Intent Receipt Date: December 1, 1993 Application Receipt Date: March 15, 1994 Scientific Review Date: June 1994 Advisory Council Date: September 1994 Earliest Award Date: September 1994 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance, No. 93.855 - Immunology, Allergy and Transplantation Research. Awards will be made under the authority of the Public Health Service Act, Title III, Section 301 (Public Law 78-410, as amended; 42 USC 241) and administered under PHS grants policies and Federal Regulations 42 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 Nov 18 22:00:00 1993 Path: biosci!net.bio.net From: kristoff@net.bio.net (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 22, no. 42, pt. 3, 19 November 1993 Message-ID: Date: 19 Nov 93 04:51:42 GMT Sender: kristoff@net.bio.net Lines: 1157 Approved: biosci-moderator@net.bio.net $$XID RFA HL94005B HL-94-005-B P1O1 ************************************ IN VITRO INACTIVATION OF VIRUSES IN BLOOD COMPONENTS NIH GUIDE, Volume 22, Number 42, November 19, 1993 RFA: HL-94-005-B P.T. 34; K.W. 0750010, 1002045 National Heart, Lung, and Blood Institute Letter of Intent Receipt Date: December 10, 1993 Application Receipt Date: February 10, 1994 PURPOSE The Transfusion Medicine Branch, Division of Blood Diseases and Resources, National Heart, Lung, and Blood Institute (NHLBI), invites grant applications to conduct basic and applied research on the development of simple, cost-effective inactivation procedures to destroy the infectivity of transfusion-transmitted viruses in blood and blood components while maintaining the therapeutic effectiveness of these preparations. 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), In Vitro Inactivation of Transfusion-transmitted Viruses in Cellular Blood Components, is related to the priority areas of HIV infection, 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 202-782-3238). 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 for new applications. 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 Background Recent progress in inactivating viruses in plasma derivatives has been highly successful. Safe and efficient inactivation procedures have been developed and are now widely available. One of these methods, which was developed under NHLBI support, involves treatment of material with organic solvent and detergent. This approach has been applied successfully to coagulation factor concentrates, immune globulins, lymphokines and other growth factors. Plasma derivatives treated with solvent/detergent mixtures are now prepared in over 14 countries around the world. Derivatives that are manufactured using this method have shown no evidence of transmission of hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) in studies designed to monitor the transmission of these agents. Conversely, attempts to develop inactivation procedures to destroy the infectivity of viruses in blood and blood components have been uniformly unsuccessful despite considerable research activity in this area. The fragile nature of cellular components, particularly plasma membranes, make them extremely susceptible to disruption by virucidal procedures. As a result, the destruction of viral activity is often accompanied by loss of cellular function. Consequently, whole blood and cellular components including red blood cell concentrates, platelet concentrates, and leukocyte concentrates, continue to carry a risk of virus transmission. Current risks of being infected with a unit of screened blood are 1 in 3,000 for HCV, 1 in 200,000 for HBV, and 1 in 225,000 for HIV. In addition, viruses such as the human T-cell lymphotropic viruses (HTLV) types I and II, and cytomegalovirus (CMV), also pose potential risks following the transfusion of blood or blood components. Despite advances in donor selection and blood donor screening, it is unlikely that the risk of transmission of these viruses will be completely eliminated without the introduction of efficient virucidal or virus-removal procedures that maintain cellular function. Over the past five years, investigators supported under an NHLBI RFA program have explored a number of different approaches to inactivate or remove viruses from blood and blood components including the use of UV-C irradiation, filtration, hydrolyzed diol epoxides, ozone, halogenated oxidizing agents, and photoactive dyes for viral sterilization of fresh frozen plasma, red blood cell concentrates, and platelet concentrates. Removal of leukocytes by filtration was shown to reduce CMV transmission to susceptible patients; however, elimination of HIV-infected cells by this method was incomplete, and filtration could not be expected to remove cell-free virus. The use of UV or ionizing irradiation is attractive because of its simplicity; however, the dose of gamma-irradiation used to inactivate lymphocytes is not sufficiently virucidal, and the virucidal doses are generally cell-destructive. UV irradiation was found to inactivate HIV under conditions generally favorable to platelets. However, important caveats on the use of UV remain; viral sensitivity to UV treatment seems to depend on the size of the viral genome and whether it is single or double stranded and, apparently, suboptimal doses for viral inactivation induce virus activation and/or replication. Hydrolyzable compounds such as beta-propriolactone have proved highly virucidal but failed to destroy sufficient virus under conditions tolerated by cellular components. The use of ozone has been shown to inactivate HIV but virucidal doses often cause hemolysis. Promising results have been obtained with the treatment of whole blood and red blood cells with photodynamically active dyes. Cell-associated virus has been known to be inactivated by these procedures under conditions where uninfected cells maintain their functional integrity. Techniques need to be developed to allow ultraviolet light or other energy sources to penetrate to all circulating elements. This approach will require methods to move blood through narrow pathways and perhaps the development of new plastics that facilitate the penetration of light. There is also a need to evaluate and contrast the advantages of continuous flow irradiation with batch irradiation of intact red blood cell concentrates and platelet concentrates. This evaluation should include the extent of viral inactivation and the impact of irradiation on cellular integrity immediately following treatment and during storage under standard blood bank conditions. While significant progress has been made under the previous RFA program toward the development of inactivation procedures, additional research is urgently needed to better understand the mode of action of these as well as other virucidal reagents and procedures so as to apply and optimize their use in a blood banking environment. Furthermore, studies on the removal of viruses from biological materials in ways that permit the treated products to be used clinically are also needed and are an important goal of this RFA. Possible approaches include viral adherence to affinity columns; use of monoclonal antibodies for in vitro neutralization; absorption-filtration procedures; centrifugal removal of viruses; and use of filters for leukodepletion. In summary, transfusion practices continue to carry a small but unacceptable risk of infection from transfusion-transmitted viruses. The solution to this problem is the development of inactivation or virus removal procedures that do not destroy the functional integrity of blood or blood components. Some procedures are currently available such as the use of photochemicals that inactivate nucleic acids and destroy virus infectivity with minimal effects on nucleic acid-free red cells and platelets. What is needed are technological advances that would permit the use of photochemicals and inactivation procedures in an efficient cost-effective fashion that is compatible with the operation of a large-scale blood center. Other forms of viral inactivation that maintain the functional integrity of blood components also need to be pursued. This program encourages basic and applied research on the development and evaluation of procedures to remove or destroy the infectivity of transfusion-transmitted viruses in blood and blood components while maintaining the therapeutic effectiveness of these preparations. 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 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. 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: Acting 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 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 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 RFA number and title: IN VITRO INACTIVATION OF VIRUSES IN BLOOD COMPONENTS: HL 94-005-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 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. 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 February 10, 1994. 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 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 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 concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Inquiries regarding this Request for Applications may be directed to: Dr. Luiz H. Barbosa 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 For fiscal and administrative matters, contact: Ms. Jane R. Davis Blood Diseases and Resources Grants Management Section National Heart, Lung, and Blood Institute Westwood Building, Room 4A11 Bethesda, MD 20892 Telephone: (301) 594-7436 FAX: (301) 594-7492 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 grants policies and Federal regulations, most specifically 42 CFR Part 52 and CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372, or to Health Systems Agency review. $$XID RFA HL94003B HL-94-003-B P1O1 ************************************ GENE THERAPY FOR SICKLE CELL DISEASE NIH GUIDE, Volume 22, Number 42, November 19, 1993 RFA: HL-94-003-B National Heart, Lung, and Blood Institute P.T. 34; K.W. 0715032, 0745032 Letter of Intent Receipt Date: January 15, 1994 Application Receipt Date: March 15, 1994 PURPOSE The Division of Blood Diseases and Resources (DBDR) of the National Heart, Lung, and Blood Institute (NHLBI), invites research grant applications for the support of basic and applied research leading to the development of strategies to correct and/or replace the endogenous defective gene in sickle cell anemia. 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), Gene Therapy for Sickle Cell Disease, is related to the priority areas of clinical prevention services, chronic disabling conditions, and maternal and infant 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 202-782-3238). 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 state or local governments, and eligible agencies of the federal government. Awards in response to this RFA will be made to domestic institutions only. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT This RFA will use the National Institutes of Health (NIH) program project grant (P01) and is a one-time solicitation. A program project grant accommodates the support of a research program in which a multidisciplinary team of investigators works collaboratively in a clearly defined area of mutual scientific interest. In a program project, achievement of the objectives of the research effort is facilitated by the sharing of ideas, data, and specialized resources such as equipment, laboratories, and clinical facilities. An essential requirement is the central theme toward which the total scientific effort is directed and to which each research project relates. The NHLBI expects the applicant to develop the approaches that would be used to accomplish the objectives of the proposed research program. The interrelated research projects included in the program should be conducted by experienced scientists who have a variety of disciplinary and specialty backgrounds and who are willing and able to relate to each other so that new scientific information may be freely exchanged and effectively utilized by others in the research program. The program director must be an established leader in scientific research with demonstrated capabilities in administration. The director is expected to demonstrate exemplary leadership by presenting a cohesive program, focusing research efforts on the central theme. The quality of the written grant application and its cohesiveness serve as an indicator of the leadership capabilities of the director. Meetings of participating investigators, who share and evaluate results and new ideas, are essential to the consolidation of the research projects into a cohesive program. An internal advisory committee selected from the participating investigators in the program can be effective in assisting the program director in making scientific and administrative decisions. An advisory committee composed of outside consultants can be helpful in providing scientific and organizational advice and assisting the Principal Investigator in maintaining and monitoring scientific progress. The size of the program project should be carefully considered. The awarded program project must be composed of at least three scientifically meritorious research projects to permit an efficacious collaborative efforts among the participating investigators. In addition, no more than $1 million in direct costs in the first year with a maximum increase of four percent in each additional year may be requested. An important goal of this program is to attract new and established investigators into the field of gene therapy for sickle cell disease by providing access to critical technologies in the form of shared facilities and funds to pursue innovative pilot/feasibility studies. Pilot/feasibility studies, when combined with appropriate core support, will provide established investigators who have not previously worked in gene therapy and new young investigators with state-of-the-art core technologies that will enable them to be competitive in the field. In addition, pilot/feasibility studies will allow investigators to pursue promising by untested methodologies or highly novel, innovative research avenues that offer significant results and insight. It is anticipated that by providing preliminary results and establishing feasibility data, these pilot studies will lead to new R01 grant applications in the area of gene therapy research for sickle cell disease. Each pilot/feasibility project may request up to $60,000 in total costs per year for a maximum of two years. New pilot/feasibility studies may be proposed to replace those that terminate. If awarded, these new pilot/feasibility studies will be subjected to the same dollar/time limits. 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. Five years of support must 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 September 30, 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. All applications submitted in response to this RFA should conform to the policies and format described in Program Project Grant - Preparation of the Application, NHLBI, (Revised). A copy of this publication may be obtained from Dr. Junius Adams at the address listed under INQUIRIES. FUNDS AVAILABLE It is anticipated that for fiscal year 1994, up to two new program project grants of up to $1,000,000 will be awarded under this program. 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 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 Sickle cell disease is a worldwide health problem and is one of the most common inherited disorders of man. This genetic blood disorder is probably the best understood disease at the molecular level and Linus Pauling coined the term "molecular disease" over forty years ago in ascribing the abnormality to the globin portion of the hemoglobin molecule. Almost ten years later, the specific molecular defect was identified as a single amino acid substitution of valine for glutamic acid at position 6 of the beta-globin polypeptide chain. With the advent of recombinant DNA technology, investigators were able to further define this genetic mutation in the globin gene as a change in the codon GAG to GTG. The substitution of glutamic acid by valine results in a loss of two negative charges on the surface of the molecule making sickle hemoglobin less soluble than normal hemoglobin upon deoxygenation. This abnormal hemoglobin aggregates and forms fibers within the red cells, leading to morphological changes that subsequently affect the ability of the cells to traverse the microvasculature, causing occlusion of these small vessels that results in acute pain, and acute as well as chronic organ damage. In addition, sickle red cells are less resilient than normal cells, leading to their early destruction and thus a chronic anemia. This cascade of events caused by the abnormal cell morphology affects the structure and function of the red cells, blood flow through tissues and organs throughout the body, and abnormal interaction of these cells with the microvasculature. The complex pathophysiology of this disorder is a direct consequence of the change in morphology of red cells containing sickle hemoglobin. Despite the distinction of being the first described molecular disease, there is no cure or effective treatment currently available. A rational therapeutic approach to this disorder would be the replacement of the sickle beta-globin gene with a normal beta-globin gene or to repair the sickle mutation in DNA. Either approach would use bone marrow stem cells manipulated in vitro to alter their genetic makeup and subsequently reintroduce them into the patient. Molecular studies and recent advances made at the level of the genome that have enhanced our understanding of gene regulation and expression, along with rapidly developing techniques of gene transfer, have opened new avenues for the potential treatment of genetic diseases. The ability to insert copies of normal genes into cells, with the production of new genes producing proteins to correct this biochemical defect, would be a major advance in treating this disease. Adequate expression of the normal beta-globin gene in patients with sickle cell anemia would be curative. The molecular biology of globin gene expression and regulation has supplied sufficient knowledge to make gene therapy feasible. The adult hemoglobin tetramer is composed of two pairs of unlike globin chains (2 alpha and 2 beta) that are the products of distinct loci on different chromosomes. The alpha-globin gene cluster is located on chromosome 16 and the beta-globin gene cluster on chromosome 11. For proper tetramer formation, it is essential that the alpha- and beta-globin genes are expressed equally. An excess or deficit of either chain produces a thalassemia-like condition that results in chronic anemia. In addition to equimolar expression of alpha- and beta-globin, control of globin gene expression is manifested in the ontogenic changes in hemoglobin type. Embryonic hemoglobin is the first hemoglobin produced in the developing fetus. It is rapidly replaced by fetal hemoglobin (Hb F). At birth, Hb F is already being replaced by adult hemoglobin (Hb A), and Hb A predominates by 6 months of age. The control of globin gene expression has been studied in great detail. Within and surrounding each globin gene are groups of nucleotides that have been conserved during evolution and are essential for proper gene expression. Conserved DNA sequences that are remote from the expressed genes have also been shown to play a critical role in globin gene expression. The most important of these is the locus control region (LCR) that is located 3~ to the globin genes. The LCR is characterized by at least four Dnase hypersensitive sites containing tissue specific consensus sequences. In addition to the LCR, there are other consensus sequences located throughout the globin gene clusters that are known to bind trans acting protein factors that are critical for globin gene expression. The best characterized erythroid-specific transcription factor, GATA-1, is named for the tetranucleotide to which it binds. The discovery of the LCR had great impact on the possibility of achieving tissue specific, high level expression of globin genes introduced ex vivo. When "mini gene" constructs containing either the human beta- or gamma-globin genes ligated to a portion of the LCR were introduced into fertilized mouse ova, transgenic mice were produced that expressed the human beta-globin gene at normal levels only in erythroid cells and only in adults. Similarly, the exogenous gamma-globin gene was expressed with similar tissue specificity, but only in the fetus. Thus, it is possible for inserted globin genes to be expressed normally with correct tissue and developmental specificity independent of the site of integration of these genes. Although normal expression of globin genes is achievable that is independent of the site of integration, there remain two major obstacles to being able to insert a normal globin gene in the position of beta-S-globin gene. (1) A mechanism is needed to down-regulate or ablate the expression of the beta-S-globin gene. If the endogenous gene and the exogenous gene are co-expressed, there would be an excess of beta-globin synthesis and an alpha-thalassemia would ensue. (2) If beta-globin genes are randomly inserted into the genome, it is possible that the exogenous gene will integrate into an unrelated gene that is critical and inactivate it. A method of site specific recombination has been developed in which the exogenous gene can only insert into its endogenous counterpart. This procedure inactivates the endogenous gene and effectively removes any possibility of insertional mutagenesis. This method is currently very inefficient and further research and development is necessary for application to gene therapy for sickle cell disease. Another area that needs further research is the production of a safe and efficient vector for gene transfer. At present, modified retrovirus vectors appear to be the most efficacious method for delivering gene to the target cell. These vectors have been used with great success in mice, but successful gene transfer and persistent expression has been difficult to accomplish in larger animals. However, longer co-culture of the bone marrow with vector producing cells has allowed the successful transfer of genes into primate bone marrow. Another problem has been recombination events that return the vectors to replication competent viruses. This problem has been largely overcome by more refined packaging techniques. The use of adeno associated virus (AAV) is also of interest. The findings that AAV is not pathogenic to humans, has wide host range, and integrates easily into the host genome make this vector potentially attractive for gene therapy. Another promising approach to the amelioration of the clinical expression of sickle cell disease by gene therapy involves the augmentation of fetal hemoglobin synthesis. Since it is adult hemoglobin that is affected in sickle cell disease, its replacement by fetal hemoglobin would be of obvious clinical benefit. Furthermore, fetal hemoglobin inhibits the polymerization of sickle hemoglobin, the essence of the pathophysiology of sickle cell disease. It has long been known that replacement of adult hemoglobin by fetal hemoglobin would not have any adverse effects, because individuals with hereditary persistence of fetal hemoglobin, where fetal hemoglobin persists into adult life, are clinically normal. Since the discovery that the chemotherapeutic agent 5-azacytidine could dramatically increase the levels of fetal hemoglobin in anemic individuals, several other compounds without the undesirable side effects of 5-azacytidine have also been shown empirically to augment fetal hemoglobin synthesis. These agents are not universally applicable and they require lifelong treatment. However, the impressive advances in basic research discussed above on globin gene regulation have suggested other means to achieve this goal with a higher degree of efficiency. The discovery of the DNA sequences and protein factors that are responsible for the switch from fetal to adult hemoglobin strongly suggest that this switch can be almost completely reversed, resulting in the replacement of sickle hemoglobin with fetal hemoglobin, which would cure the disease. An area of research that would benefit all aspects of gene therapy for sickle cell disease is the development of an improved animal model of sickle cell disease. Various strategies have been employed to create a transgenic mouse model of sickle cell disease including the crossing of mice carrying the human beta-S-globin gene with mice with beta+-thalassemia, the inclusion of the human alpha-globin gene, and the design of "super sickling" globin genes that contain the mutations for Hb S as well as those for Hb Antilles and/or D Punjab. Although these approaches have improved the transgenic mouse model, further work is necessary to duplicate sickle cell disease in the mouse. Improved animal models would be useful for testing strategies of homologous recombination, increasing fetal hemoglobin synthesis, and determining the amount of synthesis from the transfected globin gene that is necessary to ameliorate sickling. >From the preceding discussion, it is obvious that much effort is directed toward development of strategies for gene insertion into hematopoietic progenitor cells in human bone marrow that may be directly applicable to the treatment of sickle cell disease. The genetic elements necessary for high level globin gene expression in erythroid cells have now been identified so that tissue specific expression at a level adequate to alter hemoglobin composition is achievable. Currently, the major difficulty in achieving gene transfer is that vectors capable of transferring globin genes with the required regulatory elements into sufficient numbers of hemopoietic progenitor cells have yet to be developed. However, advances in this direction continue to occur, and the replacement of the sickle hemoglobin gene by gene transfer continues to offer the most promising cure for all sickle cell disease patients. Other modalities such as bone marrow transplantation may be applicable to a proportion of patients with variable risks. Long term pharmacological manipulation of fetal hemoglobin synthesis may also be of benefit to a large proportion of patients. Nonetheless, successful gene transfer would be more broadly applicable. Sickle cell disease is an excellent candidate for gene therapy for several reasons: (1) the human hemoglobin molecule and the globin gene complex that is responsible for its production represent the best known and most studied molecular system in man; (2) the gene for sickle hemoglobin is only active in hematopoietic tissue, and this tissue is easily accessible as bone marrow for treatment outside of the body; (3) the current state of technology is such that gene therapy for sickle cell disease is attainable; (4) although the development of gene therapy for sickle cell disease would require a significant initial investment, it would provide a cure for this debilitating, chronic disease that consumes a significant portion of health care costs in the United States; (5) the development of a cure for sickle cell disease would represent a significant improvement of health care to an underserved minority population in this country. The following are examples of the type of research approaches that would be responsive to the program: o Improvement of the efficiency of transfection of hematopoietic stem cells by augmenting the number of stem cells available for transfection and increasing the efficiency of the vector. o Introduction of a selective advantage to stem cells that allow successful competition with endogenous stem cell for proliferation, self-renewal, and differentiation in vivo o Development of new strategies for the introduction of exogenous genes into stem cells with the goal of obtaining therapeutically useful levels of expression and stability of the transferred gene. o Development of more efficient methods for gene insertion by homologous recombination. o Development of methods to silence or attenuate the expression of the endogenous beta-S-globin gene o Development of improved animal models to assess the efficacy of approaches o An important goal of this program is to attract new and established investigators into the field of gene therapy for sickle cell disease by providing access to critical technologies (in the form of shared core facilities described above) and funds to pursue innovative pilot/feasibility studies. Pilot/feasibility studies will enable established investigators who did not previously work in gene therapy and new investigators with state-of-the-art core technologies that will enable them to be competitive in the field. In addition, pilot/feasibility studies will allow investigators to pursue promising but untested innovative research in gene therapy. These approaches are meant to serve only as examples of the types of research projects that would be responsive to the goals of this solicitation. Investigators are encouraged to develop and propose their own innovative approaches. 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 by submit, by January 15, 1994, 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: Acting 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 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 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. All applications must conform to the format and policies described in Program Project Grant - Preparation of the Application NHLBI (revised). In addition, ensure that the points identified in the section on REVIEW CONSIDERATIONS are fulfilled. 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. 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 such that it may not reach the review committee in time for review. 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: GENE THERAPY FOR SICKLE CELL DISEASE: NHLBI RFA HL-94-003-B. Send or deliver the completed application and three signed, exact photocopies of it 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 Acting 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 March 15, 1994. 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 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 investigators; the adequacy of the experimental design; the suitability of the facilities; and the appropriateness of the requested budget to the work proposed. The major factors to be considered in the evaluation of program project applications will include: o The significance of the proposed program including its potential for successfully addressing the primary goal of gene therapy for sickle cell disease. o The proposed program must adhere to the clearly defined central theme of gene therapy for sickle cell disease to which each component project relates and to which each investigator contributes. o The proposed research should represent new directions and opportunities and demonstrate the development of significant key alliances among investigators in the diverse areas of scientific expertise (e.g., molecular biology, virology, cell biology, animal models, stem cell biology, and pathology) required for further advancement of sickle cell gene therapy research. This RFA will also provide the infrastructure necessary to foster such collaborative efforts by establishing appropriate cores, such as microbiology, vector development, cell biology, and animal model facilities. In addition to stimulating collaboration, these core facilities must be designed to enhance and extend the effectiveness of the gene therapy program by ensuring access to new biomedical research services and specialized instrumentation, avoiding duplication of expensive effort and increasing quality control. o The scientific merit of the proposed component projects, including the originality and feasibility of the approach, the adequacy of the experimental design, and the relevance to the central theme of the program. o The quality and commitment of senior scientific leadership and their experience and ability to successfully integrate basic, applied, and clinical research. o The quality and commitment of a qualified group of project investigators from several scientific disciplines with the experience, training, and abilities to successfully direct each project and core unit. o The physical and intellectual resources and environment in which the participating laboratories will operate and interact, as well as the supportive nature and commitment of the sponsoring institution(s). o Scientific merit of any proposed pilot/feasibility studies and the quality of the internal and external review mechanisms established by the parent institution to evaluate the scientific merit of the initial and subsequently selected pilot/feasibility studies, including a detailed plan for maintaining oversight and review of on-going pilot/feasibility studies and for providing written documentation of these actions, copies of which will be forwarded to the NHLBI program official. o The proposed program must include a plan to ensure close interaction among all participants and the communication of ideas and results. o The appropriateness of the requested budget for the proposed program. AWARD CRITERIA The anticipated date of award is September 30, 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. INQUIRIES Written and telephone inquiries concerning this 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. Junius G. Adams, III Division of Blood Diseases and Resources National Heart, Lung, and Blood Institute Federal Building, Room 508 Bethesda, MD 20892 Telephone: (301) 496-6931 FAX: (301) 402-4843 For fiscal and administrative matters, contact: Ms. Jane R. Davis Blood Diseases and Resources Grants Management Section National Heart, Lung, and Blood Institute Westwood Building, Room 4A11 Bethesda, MD 20892 Telephone: (301) 594-7436 FAX: (301) 594-7492 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 grants 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. Bibliography Bank A, Markowitz D, Lerner N: Gene transfer: A potential approach to gene therapy for sickle cell disease. Ann NY Acad Sci 565:37-43, 1989. Bender MA, Gelinas RE, Miller AD: A majority of mice show long-term expression of a human beta-globin gene after retroviral transfer into hematopoietic stem cells. Mol Cell Biol 9:1426-1434, 1989. Bodine DM, McDonagh KT, Brandt SI, Ney PA, Agricola B, Byrne E, Nienhuis AW: Development of a high-titer retrovirus producer cell line capable of gene transfer into rhesus monkey hematopoietic stem cells. Proc Natl Acad Sci USA 87:3738-3742, 1990. Culliton B.: Gene therapy begins. Science 249:1372, 1990 Dzieriak EA, Papayannopoulou T, Mulligan RC: Lineage-specific expression of a human beta-globin gene in a murine bone marrow transplant recipients reconstituted with retrovirus-transduced stem cells. Nature 33:35-41, 1988. Karlsson S: Treatment of genetic defects in hematopoietic cell function by gene transfer. Blood 78:2481-2488, 1991. Koller B, Smithies O: Inactivation of the beta2-microglobulin locus in mouse embryonic stem cells by homologous recombination. Science 246:799-803, 1989. Miller AD: Progress toward human gene therapy. Blood 76:271-278, 1990. Novak U, Harris EAS, Forrester W, Groudine M, Gelinas R: High-level beta-globin gene expression after retroviral transfer of locus activation region-containing human beta-globin gene derivatives into murine erythroleukemia cells. Proc Natl Acad Sci USA 87:3386-3390, 1990. Smithies O, Gregg RG, Boggs SS, Koralewski MA, Kucherlaputi RS: Insertion of DNA sequences into the human chromosomal beta-globin locus by homologous recombination. Nature 317:230-234, 1985. Sorrento B, Ney P, Bodine D, Nienhuis AW: A 46 base pair enhancer sequence within the locus activating region is required for induced expression of the gamma-globin gene during erythroid differentiation. Nucleic Acids Res 18:2721-2731, 1990. Steinberg MH: Prospects of gene therapy for hemoglobinopathies. Am J Med Sci 302:298-303, 1991. From owner-sci-resources@net.bio.net Thu Nov 18 22:00:00 1993 Path: biosci!net.bio.net From: kristoff@net.bio.net (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 22, no. 42, pt. 2, 19 November 1993 Message-ID: Date: 19 Nov 93 04:49:38 GMT Sender: kristoff@net.bio.net Lines: 1272 Approved: biosci-moderator@net.bio.net $$XID NIHGUIDE 19931119 V22N42 P2O2 ************************************ 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. 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. 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 program project grant applications. The major factors to be considered in the evaluation of applications will include the significance of the proposed program and its potential for successfully addressing the primary goal of the RFA, the scientific merit and cohesiveness of the proposed component projects, the quality and commitment of the project director and the principal investigators of the proposed component projects, the research environment, the scientific merit of any proposed pilot/feasibility studies, and the appropriateness of the requested budget. 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. Junius G. Adams, III Division of Blood Diseases and Resources National Heart, Lung, and Blood Institute Federal Building, Room 504 Bethesda, MD 20892 Telephone: (301) 496-6931 FAX: (301) 402-4843 Direct inquiries regarding fiscal and administrative matters to: Ms. Jane R. Davis Blood Diseases and Resources Grants Management Section National Heart, Lung, and Blood Institute Westwood Building, Room 4A11 Bethesda, MD 20892 Telephone: (301) 594-7436 FAX: (301) 594-7492 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 grants 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. $$R8 END ************************************************************ ONGOING PROGRAM ANNOUNCEMENTS $$P1 BEGIN PA-94-012 ************************************************ SMALL INSTRUMENTATION GRANTS PROGRAM NIH GUIDE, Volume 22, Number 42, November 19, 1993 PA NUMBER: PA-94-012 P.T. 34; K.W. 0735000, 1002024, 0735015, 1014001 National Institutes of Health Application Receipt Date: February 16, 1994 PURPOSE The National Institutes of Health (NIH) has supported a Small Instrumentation Grants Program (SIP) since FY 1987 in response to several studies that indicated that the state of biomedical research instrumentation had seriously eroded and was retarding the progress of biomedical research. The most significant need identified in these studies was for the relatively low-cost pieces of equipment in the price range of approximately $5,000 to $60,000. Approximately $5.3 million will be available from the NIH in FY 1994 for the SIP. ELIGIBILITY REQUIREMENTS Eligible organizations or organizational components are those domestic, non-profit organizations that: (1) received at least three NIH research grants in the research grants base (defined below) totaling between $200,000 and $3,208,000 in FY 1993; and (2) have active NIH research grant support. The "research grants base" is defined as those grants awarded with the following activity codes: K01, K02, K04, K05, K06, K08, K11, K12, K14, K15, K16, K20, K21, P01, P40, P41, P42, P50, P60, R01, R03, R10, R21, R22, R23, R24, R29, R35, R37, R55, S06, S14, U01, U10, U24, U41, U42, and U54. Organizations or organizational components that received awards totaling MORE THAN $3,208,000 in FY 1993 are NOT eligible. MECHANISM OF SUPPORT The mechanism of support for this program will be the small instrumentation grant (S15). Applicants will be responsible for identifying and purchasing the equipment requested for use on active NIH research grants. APPLICATION PROCEDURES Only those organizations or organizational components receiving a LETTER OF INVITATION TO APPLY are eligible for a SIP award. These letters, which contain application instructions, will be mailed on or about November 24, 1993. Only one application may be submitted from each eligible organization or organizational component, which may establish its own procedures for identifying equipment requests. Investigators interested in participating in their organization's or organizational component's application should contact the official responsible for completing the application. Those officials who expect to be involved in preparing an application should publicize the availability of SIP funds, so that investigators in need of small research instruments are provided the opportunity to indicate their needs for such equipment. The SIP award will be restricted to the purchase of equipment costing between $5,000 and $60,000. Awards will be made on or before September 1, 1994. The amount of the award will be based on a percentage of the organization's or organizational component's research grants base for FY 1993 or $5,000, whichever is greater. Organizations or organizational components will be notified of the maximum amount for which they may apply. Completed applications must be received by February 16, 1994. REVIEW CONSIDERATIONS Applications will be assigned to individual NIH awarding components for administrative review of the completeness of the application in accordance with the application instructions. Incomplete applications will be returned to the applicant without further consideration. Specific funding decisions will depend on available funds and the appropriateness of the request in relation to active NIH grant support. INQUIRIES All eligible organizations or organizational components will receive a letter of invitation to apply for a SIP award. Therefore, only those issues NOT ADDRESSED in the application instructions may be addressed to: Research Training and Special Programs Office Office of Extramural Research National Institutes of Health Building 31, Room 5B44 Bethesda, MD 20892 Telephone: (301) 496-1968 FAX: (301) 496-0166 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance, No. 93.337, Biomedical Research Support. Grants will be available under the authority of and administered in accordance with the PHS Grants Policy Statement and Federal regulations at 42 CFR 52 and 42 USC 241. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$P1 END ************************************************************ $$P2 BEGIN PA-94-013 ************************************************ MECHANOTRANSDUCTION IN THE VESTIBULAR LABYRINTH NIH GUIDE, Volume 22, Number 42, November 19, 1993 PA NUMBER: PA-94-013 P.T. 34; K.W. 0715050, 0710020, 0710050 National Institute on Deafness and Other Communication Disorders PURPOSE The National Institute on Deafness and Other Communication Disorders (NIDCD) of the National Institutes of Health (NIH) invites grant applications for the support of basic studies of mechanotransduction in the vestibular labyrinth. It is expected that research in this area will advance our understanding of the mechanisms of vestibular dysfunction arising from disease of the inner ear. 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 (PA), Mechanotransduction in the Vestibular Labyrinth, is related to the priority areas of physical activity fitness, unintentional injuries, occupational safety and health, diabetes and chronic disabling diseases, and clinical prevention services. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-11474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-11473-1) 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. Domestic applications may include international components. Foreign institutions are not eligible to apply for the First Independent Research Support and Transition (FIRST) (R29) award. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT The mechanisms available for support of this program are the NIH individual research project grant (R01) and the FIRST (R29) award. Applicants from institutions that have a General Clinical Research Center (GCRC) funded by the NIH National Center for Research Resources (NCRR) 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. RESEARCH OBJECTIVES In vestibular transduction, an adequate physical stimulus results in a displacement of the endorgan accessory structures, the cupula and the otolithic membrane, overlying the vestibular hair cells, deflecting the hair bundles of the latter. The deflection of a hair cell's bundle towards its tallest stereocilia opens specialized transduction channels in the stereocilia. This increases the flow of positive ions into the hair cell, leading to calcium entry and the release of neurotransmitter to afferent fibers synapsing with the hair cell. Research on vestibular mechanotransduction may be conducted at three levels: (1) macromechanics- the motion, deformation and coupling of the endorgan accessory structures in relation to the vestibular receptor organs; (2) micromechanics- the motion, deformation and coupling of sensory hair bundles in relation to the overlying accessory structures; and (3) the internal mechanics of ciliary bundles. This initiative seeks to encourage research on the mechanical and molecular aspects of the vestibular transduction process at these three levels in animal models and/or computer simulation models. Based on the early pioneering work of Steinhausen and others, it has been thought that the macromechanics of the semicircular canals could be modeled as a pendulum moving in a viscous medium. On the basis of this model, cupular displacement in the frequency range of physiologic head movement is proportional to angular velocity. Along the same lines, the otolithic organs have been described as uniform structures with the mechanical behavior of an overdamped, second-order system whose displacement is proportional to applied linear force. These models have shaped the field of vestibular physiology for many years. Indeed, any discrepancies from the models' predictions and the observed response dynamics of afferent discharge have been assumed to result from filtering by later stages of the transduction process. Recent experimental observations, however, have cast considerable doubt on the validity of these models. In vivo experimental observations suggest that the cupula is deformed like a diaphragm while adhering firmly to the ampular wall during physiologic stimulation. The otolithic organs have been shown to have complex curved surfaces appropriately modeled as a viscoelastic material. The development of enhanced video microscopy and other imaging techniques provide new opportunities to describe cupular and otolithic motion more accurately. Recent anatomic and electrophysiologic studies of the bullfrog utricular macula have identified four categories of type II hair cells with hair bundle morphologies that differ systematically with macular location. These bundle categories have, in turn, been correlated with afferent function. More regional mapping studies of hair bundle morphology and mechanics are needed. In particular, it is important to determine whether regional variations in micromechanics underlie afferent response diversity. Contemporary imaging techniques offer the opportunity to visualize simultaneously the displacement, deformation and coupling of the hair bundles and the accessory structures. The prevailing view that the mechanics of the vestibular end organs are entirely determined by their passive mechanical properties has recently been challenged by two important findings: (1) motile responses in vestibular hair cells; and, (2) the influence of adaptation of the mechanoelectric transducer channel on hair bundle stiffness. The shortening of isolated mammalian type I vestibular hair cells has been demonstrated following exposure to a potassium-rich medium. In addition, voltage-dependent active hair bundle motions have been observed in mechanically displaced saccular hair cells. If present in vivo, hair cell motility might directly influence the mechanosensitivity of the vestibular receptor organs. Neurotransmission in auditory, vestibular and lateral line systems is triggered by a series of events that follow the opening of mechanically sensitive transduction channels in the hair cell stereocilia. Evidence has accumulated suggesting that the opening of a channel results from increased mechanical tension on the channel protein imposed by fine filaments (tip links) linking each adjacent taller stereocilium in a hair bundle. An adaptation mechanism, dynamically modulating transducer currents and afferent response by adjustments in the tension of these tip links, has been postulated on the basis of observations in some isolated amphibian vestibular hair cells. Whenever possible, the functional significance of experimental observations and the validity of models of vestibular mechanotransduction should be established by relating these events to consequent neural function. Research studies may include, but are not limited to, the topics listed below: o application of advanced imaging techniques to describe vestibular mechanics in situ; o development of in vitro epithelial preparations for studies of labyrinthine mechanics; o development of data-driven models of vestibular mechanics; o determination of the micromechanics of the different vestibular receptor subtypes, type I and type II hair cells; o determination of the role of regional variations of vestibular micromechanics in afferent response diversity; o determination of the role of the internal mechanics of the ciliary bundles in vestibular mechanotransduction; o determination of the role of active hair cell processes in vestibular mechanotransduction. 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. 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 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 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 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 national advisory council. 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: Daniel A. Sklare, Ph.D. Division of Communication Sciences and Disorders National Institute on Deafness and Other Communication Disorders Executive Plaza South, Room 400-C 6120 Executive Boulevard Rockville, MD 20892 Telephone: (301) 496-1804 FAX: (301) 402-6251 Direct inquiries regarding fiscal matters to: Sharon Hunt Division of Extramural Activities National Institute on Deafness and Other Communication Disorders Executive Plaza South, Room 400-B 6120 Executive Boulevard Rockville, MD 20892 Telephone: (301) 402-0909 FAX: (301) 402-1758 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.173. 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 ************************************************************ $$XID RFA AI94001 AI-94-001 P1O1 *************************************** IMMUNOLOGIC ENHANCEMENT OF VACCINE IMMUNOGENICITY NIH GUIDE, Volume 22, Number 42, November 19, 1993 RFA: AI-94-001 P.T. 34; K.W. 0710065, 0740075 National Institute of Allergy and Infectious Diseases Letter of Intent Receipt Date: January 15, 1994 Application Receipt Date: March 15, 1994 PURPOSE The Division of Allergy, Immunology and Transplantation (DAIT) and the Division of Microbiology and Infectious Diseases (DMID) of the National Institute of Allergy and Infectious Diseases (NIAID) invite applications for basic, applied, or preclinical studies of molecular immunologic methods to enhance protective responses to the antigens of infectious pathogens of man to develop new and improved vaccines. The NIAID seeks studies that utilize advances in immunology to develop new targeting molecules, immunologic adjuvants, or other technology to improve existing vaccines by making them safer or more immunogenic and to develop new vaccines where none exist for microbial pathogens. Of special interest are those studies that demonstrate the feasibility of new ideas or novel approaches and show promise for clinical application. 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), Immunologic Enhancement of Vaccine Immunogenicity, is related to the priority areas of diabetes and chronic disabling 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 202-782-3238). ELIGIBILITY REQUIREMENTS Research grant applications may be submitted by domestic and foreign, for-profit and non-profit organizations, public and private institutions, such as universities, colleges, hospitals, laboratories, units of State or local governments, and eligible agencies of the Federal government. Foreign institutions are not eligible to apply for First Independent Research Support and Transition (FIRST) (R29) Awards. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT The mechanisms of support will be the individual research project grant (R01) and the FIRST (R29) grant. Multidisciplinary approaches that involve collaborative efforts among investigators in the fields of basic immunology, molecular biology, cell biology, biochemistry, and infectious disease are strongly encouraged. 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 competing renewal applications will compete with all investigator-initiated applications and will be reviewed according to customary referral and review procedures. FUNDS AVAILABLE The estimated total funds (direct and indirect costs) available for the first year of support for all awards made under this RFA will be $2,000,000. In Fiscal Year 1994, the NIAID plans to fund approximately 10 R01s/R29s. Applications may not request more than four percent annual inflationary increases for future years. The usual PHS policies governing grants administration and management will apply. 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 NIAID, awards pursuant to this RFA are contingent upon the availability of funds for this purpose. Funding beyond the first and subsequent years of the grant will be contingent upon satisfactory progress during the preceding years and availability of funds. RESEARCH OBJECTIVES Background The area of vaccine research and development has been, and continues to be, a major priority for the NIAID, and it is the lead agency within the National Institutes of Health (NIH) for such efforts. Vaccines are probably the best tools ever developed for the prevention of disease, and they are important for both disease control and control of health care costs. A Blue Ribbon Panel on Vaccine Research convened by the NIAID in 1993 emphasized the priorities of improving the safety and effectiveness of current vaccines, as well as the development of new vaccines for diseases where none exist including emerging infectious diseases. Major advances in our understanding of the immune system and its response to infectious agents have occurred in recent years. These advances include: characterization of the structure and function of the T lymphocyte receptor for antigen and the numerous accessory molecules involved in the initial signal transduction events; identification and characterization of the numerous cytokines that regulate immune responses; delineation of the steps involved in antigen processing and presentation; definition and characterization of adhesion molecules and their roles in interactions between cells of the immune system; identification of genes that regulate the expression and function of many immune system molecules; and, in several infectious diseases, elucidation of the role (protective vs. pathogenic) played by different arms of the immune response. Research Objectives and Scope The goal of this initiative is to increase knowledge of the cellular, molecular, and immunologic basis of immunogenicity and to promote the application of this knowledge to the development of new approaches, not only to improve existing vaccines (e.g., render them safer, more immunogenic), but also to develop new vaccines for pathogens or diseases for which no vaccines currently exist. Studies that involve relevant animal models of human diseases, including appropriate in vivo testing of immunoenhancers, and studies that involve human tissues and cells are especially encouraged. Some examples of relevant research topics are given below; these examples, however, are not intended to be all-encompassing or limiting. o Incorporation of antigen or antigenic peptides into targeting molecules that will more efficiently deliver them to antigen presenting cells and/or specific lymphoid tissue o Manipulation of antigen processing and presentation pathways to enhance immunogenicity o Modification of cytokine structure to enhance potency of the adjuvant properties and/or to reduce undesirable or deleterious aspects of cytokine function(s) o Concomitant administration of appropriate cytokines and antigens to elicit specific effector arms (e.g., TH1 vs. TH2 lymphocytes, immunoglobulin isotypes) of the immune system o Prolongation of antigen exposure by immunization with cells into which microbial genes have been transferred. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy requires that applicants for NIH clinical research grants and cooperative agreements 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, together with a rationale for its choice. 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 items 1-4 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 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, clinical samples which may be coded for use by the applicant but could be identified by another source are not excluded. Every effort should be made and documented 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 U.S. 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. 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, at a minimum, the application must contain demographic data about the clinic and/or in-patient population from which study subjects will be drawn: average hospital admissions 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 sites should be provided. LETTER OF INTENT Prospective applicants are asked to submit, by January 15, 1994, a letter of intent that includes a descriptive title of the overall proposed research, the name, address and telephone number of the Principal Investigator, and the number and title of this RFA. Although the letter of intent is not required, is not binding, does not commit the sender to submit an application, 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 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 the standard research grant application form PHS 398 (rev. 09/91). For purposes of identification and processing, item 2a on the face page of the application must be marked "YES" and the RFA number and the words "IMMUNOLOGIC ENHANCEMENT OF VACCINE IMMUNOGENICITY" must be typed in. Application forms may be obtained from the institution's office for sponsored research or its equivalent 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. It is highly recommended that the Chief of the Clinical Immunology Branch be contacted in the early stages of preparation of the application. (See program contact in INQUIRIES below.) Applications must be received by March 15, 1994. indicated in the RFA heading and in "SCHEDULE" below. Applications that are not received as a single package on the receipt date or that do not conform to the instructions contained in PHS 398 (rev. 09/91) Application kit, will be judged non-responsive and will be returned to the applicant. The RFA label available in the application form PHS 398 must be affixed to the bottom of the face page. 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. FIRST (R29) applications must include at least three sealed letters of reference attached to the face page of the original application. FIRST (R29) applications submitted without the required number of reference letters will be considered incomplete and will be returned 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. Submit a signed, typewritten original of the application, including the checklist, and three signed, exact, single-sided 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 exact copies of the grant application must also be sent to Dr. Olivia Preble at the address listed under INQUIRIES. 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. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by the NIH DRG and for responsiveness by NIAID staff; those judged to be incomplete will be returned to the applicant without review. Those considered to be non-responsive will be either returned without review or will be referred to the DRG as unsolicited applications, to be scheduled for initial review at the next DRG review cycle. Those applications that are complete and responsive may be subjected to a triage by an NIAID peer review group to determine their scientific merit relative to other applications received in response to this RFA. The NIAID will withdraw from competition those applications judged to be non-competitive for award and will notify the applicant and institutional business officials. Those applications judged by the reviewers to be competitive for award will be further 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. The factors to be considered in the evaluation of scientific merit of each application will be 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; and the adequacy and suitability of the facilities. While the following review factors do not usually influence the priority score, they are nonetheless carefully considered by the initial review group: the appropriateness of the requested budget to the work proposed; the adequacy of protection of human subjects and/or animals in research; and the adherence, whenever appropriate, to NIH guidelines concerning adequate representation of women and minorities in clinical research. Any documented concerns expressed by the initial review group about any of these factors on a given application may influence the recommendation of the Advisory Council concerning funding of that application. AWARD CRITERIA Funding decisions will be made on the basis of scientific and technical merit as determined by peer review, program priorities, and the availability of funds. 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: Howard B. Dickler, M.D. Division of Allergy, Immunology & Transplantation National Institute of Allergy and Infectious Diseases Solar Building, Room 4A19 6003 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-7104 FAX: (301) 402-2571 Direct inquiries regarding review issues; address the letter of intent to; and mail two copies of the application and all five sets of appendices to: Olivia Preble, Ph.D. Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4C19 6003 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-8208 FAX: (301) 402-2638 Direct inquiries regarding fiscal matters to: Mr. Jeffrey Carow Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4B29 6003 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-7075 Schedule Letter of Intent Receipt Date: January 15, 1994 Application Receipt Date: March 15, 1994 Scientific Review Date: July 1994 Advisory Council Date: September 1994 Earliest Award Date: September 1994 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance, No. 93.855 - Immunology, Allergy and Transplantation Research. Awards will be made under the authority of the Public Health Service Act, Title III, Section 301 (Public Law 78-410, as amended; 42 USC 241) and administered under PHS grants policies and Federal Regulations 42 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$XID RFA AI94003 AI-94-003 P1O1 *************************************** NEONATAL IMMUNITY FOR VACCINES NIH GUIDE, Volume 22, Number 42, November 19, 1993 RFA: AI-94-003 P.T. 34; K.W. 0705040, 0740075, 0403020 National Institute of Allergy and Infectious Diseases Letter of Intent Receipt Date: January 15, 1994 Application Receipt Date: March 10, 1994 PURPOSE The Division of Allergy, Immunology and Transplantation (DAIT) and the Division of Microbiology and Infectious Diseases (DMID) of the National Institute of Allergy and Infectious Diseases (NIAID) invite applications for basic and preclinical studies to increase knowledge of the development and function of the immune system in the neonate. Applications are especially solicited that address the utilization of this information for the development of new anti-pathogen vaccines effective in this age group. The knowledge developed through this initiative would also be applicable to the development of vaccines for autoimmune and allergic diseases. 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), Neonatal Immunity for Vaccines, is related to the priority areas of diabetes and chronic disabling 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 202-782-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign, for-profit and non-profit organizations, public and private institutions, such as universities, colleges, hospitals, laboratories, units of State or local governments, and eligible agencies of the Federal government. Foreign institutions are not eligible to apply for First Independent Research Support and Transition (FIRST) (R29) Awards. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT The mechanisms of support will be the individual research project grant (R01) and the FIRST (R29) award. Multidisciplinary approaches that involve collaborative efforts among investigators in the fields of basic immunology, molecular biology, cell biology, biochemistry, and infectious disease are strongly encouraged. The total project period for applications submitted in response to this RFA may not exceed five years; foreign applications may not request more than three years of support. This RFA is a one-time solicitation. Future competing renewal applications will compete with all investigator-initiated applications and will be reviewed according to customary referral and review procedures. FUNDS AVAILABLE The estimated funds available for the total (direct and indirect) first year costs of all awards made under this RFA will be $1,500,000. In Fiscal Year 1994, the NIAID plans to fund approximately seven R01s/R29s. Applications should not request more than four percent annual inflationary increases for future years. The usual PHS policies governing grants administration and management will apply. 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 NIAID, awards pursuant to this RFA are contingent upon the availability of funds for this purpose. Funding beyond the first and subsequent years of the grant will be contingent upon satisfactory progress during the preceding years and availability of funds. RESEARCH OBJECTIVES Background Infant mortality worldwide and in our inner cities is a continuing problem. Infants are at risk for overwhelming bacterial and viral infections. In order to meet the Childhood Vaccine Initiative goal of immunizing infants as early in life as possible, greater understanding of the neonatal immune system is necessary. A Blue Ribbon Panel convened by the NIAID in March of 1993 was charged with developing priorities for research in the area of vaccines. One of the areas highlighted by the panel was the need for basic research in immunology as it relates to vaccine research. In particular, the panel emphasized the need for basic research in the area of neonatal immunity. The immune system of the infant is functionally immature. Neonates do not produce much immunoglobulin. Maternal antibodies are transferred late in gestation to the fetus. This maternal antibody offers short term protection for the neonate. The role of this maternal antibody in the decreased response of the neonate's own immune system is unclear. The neonate's immune response to challenge from infectious agents is also deficient. Enhanced understanding of the neonatal response to pathogens and the potential for interference by maternal antibody in the function of the neonatal immune system is needed. Research Objectives and Scope The goal of this RFA is to increase knowledge of the development and function of the neonatal immune system and to use this knowledge to develop new and more effective vaccine strategies for this age group. Studies involving human tissues and cells are especially encouraged. Examples of relevant research topics are given below. These examples, however, are not intended to be all inclusive or limiting: o role of natural or vaccine-induced maternal antibodies, or in utero antigen exposure, in the development of and regulation of the immune response of the neonate o mechanisms of immunosuppression/immunopotentiation in neonates exposed to pathogens or pathogen-derived antigens, and the long-term consequence of this neonatal exposure for development of the immunologic repertoire o ontogeny of the immune response in neonates and infants o characterization of antigens that elicit protective immune responses against pathogens in neonates, and methods to enhance such responses In preparing an application in response to this RFA, the applicant should bear in mind the research objectives of this RFA. Applications must be prepared according to the instructions in form PHS 398 (rev. 9/91). STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy requires that applicants for NIH clinical research grants and cooperative agreements 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, together with a rationale for its choice. 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 items 1-4 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 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, clinical samples which may be coded for use by the applicant but could be identified by another source are not excluded. Every effort should be made and documented 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 U.S. 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. 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 will be drawn: average hospital admissions 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 sites should be provided. LETTER OF INTENT Prospective applicants are asked to submit, by January 15, 1994, a letter of intent that includes a descriptive title of the overall proposed research, the name, address and telephone number of the Principal Investigator (Program Director), and the number and title of this RFA. Although the letter of intent is not required, is not binding, does not commit the sender to submit an application, 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 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 the standard research grant application form PHS 398 (rev. 09/91). For purposes of identification and processing, item 2a on the face page of the application must be marked "YES" and the RFA number and the words "NEONATAL IMMUNITY FOR VACCINES" must be typed in. These application forms may be obtained from the institution's office for sponsored research or its equivalent 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. It is highly recommended that the Chief of the Autoimmunity Section, Clinical Immunology Branch be contacted in the early stages of preparation of the application. (See program contact in INQUIRIES below.) Applications must be received by March 10, 1994. Applications that are not received as a single package on the receipt date or 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. The RFA label available in the application form PHS 398 must be affixed to the bottom of the face page. 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. First (R29) applications must include at least three sealed letters of reference attached to the face page of the original application. First (R29) applications submitted without the required number of reference letters will be considered incomplete and will be returned without review. Applications received after the receipt date will be returned 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. Submit a signed, typewritten original of the application, including the checklist, and three signed, exact, single-sided 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 exact copies of the grant application must also be sent to Dr. Olivia Preble at the address provided below in INQUIRIES. 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. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by the NIH Division of Research Grants (DRG) and for responsiveness by NIAID staff; those judged to be incomplete will be returned to the applicant without review. Those considered to be non-responsive will be either returned without review or will be referred to the DRG as unsolicited applications, to be scheduled for initial review at the next DRG review cycle. Those applications that are complete and responsive may be subjected to a triage by an NIAID peer review group to determine their scientific merit relative to other applications received in response to this RFA. The NIAID will withdraw from competition those applications judged to be non-competitive for award and will notify the applicant and institutional business officials. Those applications judged by the reviewers to be competitive for award will be further reviewed for scientific and technical merit by a review committee convened by the Division of Extramural Activities, NIAID. Applicants may receive an abbreviated summary statement together with essentially unedited reviewers' comments. The second level of review will be provided by the National Advisory Allergy and Infectious Diseases Council. The factors to be considered in the evaluation of scientific merit of each application will be 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; and the adequacy and suitability of the facilities. While the following review factors do not usually influence the priority score, they are nonetheless carefully considered by the initial review group: the appropriateness of the requested budget to the work proposed; the adequacy of protection of human subjects and/or animals in research; and the adherence, whenever appropriate, to NIH guidelines concerning adequate representation of women and minorities in clinical research. Any documented concerns expressed by the initial review group about any of these factors on a given application may influence the recommendation of the Advisory Council concerning funding of that application. AWARD CRITERIA Funding decisions will be made on the basis of scientific and technical merit as determined by peer review, program priorities, and the availability of funds. 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: Elaine Collier, M.D. Division of Allergy, Immunology and Transplantation National Institute of Allergy and Infectious Diseases Solar Building, Room 4A20 6003 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-7985 FAX: (301) 402-2571 Direct inquiries regarding review issues; address the letter of intent to; and mail two copies of the application and all five sets of appendices to: Olivia Preble, Ph.D. Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4C19 6003 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-8208 FAX: (301) 402-2638 Direct inquiries regarding fiscal matters to: Mr. Jeffrey Carow Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4B29 6003 Executive Boulevard Bethesda, MD 20892*** Telephone: (301) 496-7075 Schedule Letter of Intent Receipt Date: January 15, 1994 Application Receipt Date: March 10, 1994 Scientific Review Date: July 1994 Advisory Council Date: September 1994 Earliest Award Date: September 1994 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance, No. 93.855 - Immunology, Allergy and Transplantation Research. Awards will be made under the authority of the Public Health Service Act, Title III, Section 301 (Public Law 78-410, as amended; 42 USC 241) and administered under PHS grants policies and Federal Regulations 42 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 Nov 21 22:00:00 1993 Path: biosci!net.bio.net From: kristoff@net.bio.net (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NSF - Summary of new documents on STIS - 21 November 1993 Message-ID: Date: 22 Nov 93 20:30:01 GMT Sender: kristoff@net.bio.net Lines: 82 Approved: biosci-moderator@net.bio.net This message contains a summary of the documents added to the NSF STIS system in the previous week. Reference material concerning STIS follows the summary. ------------------------------------------------------------------------ ** NEW DOCUMENTS ON STIS ** Document Type: Antarctic EAM Title: SO2, NOx, and CO in air at McMurdo File size (bytes): 2256 STIS Filename: opp94001 Title: PM10 and TSP in air at McMurdo File size (bytes): 2345 STIS Filename: opp94002 Title: PCDDs and PCDFs in air at McMurdo File size (bytes): 2496 STIS Filename: opp94003 Document Type: Program Guideline Title: NSF 93-151 -- Postdoctoral Research Fellowships in Molecular Evolution File size (bytes): 29416 STIS Filename: ns93151a Title: Nsf93-158 Jt International Research Opportunities in Biodiversity File size (bytes): 15108 STIS Filename: nsf93158 ------------------------------------------------------------------------ ** UPDATES TO EXISTING STIS DOCUMENTS ** Document Type: Phone Book Title: NSF Alpha Telephone Directory File size (bytes): 112526 STIS Filename: phnalpha ------------------------------------------------------------------------ ** 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 phnalpha, the text of your message should be as follows: get phnalpha Anonymous FTP: FTP to stis.nsf.gov. Use the "STIS Filename" shown above to retrieve a file. For example, to retrieve phnalpha, you would enter: ftp> get phnalpha 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 Sun Nov 28 22:00:00 1993 Path: biosci!net.bio.net From: kristoff@net.bio.net (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 22, no. 43, pt. 2, 26 November 1993 Message-ID: Date: 29 Nov 93 19:39:40 GMT Sender: kristoff@net.bio.net Lines: 1420 Approved: biosci-moderator@net.bio.net $$XID NIHGUIDE 19931126 V22N43 P2O2 ************************************ o Institutional commitment to providing a quality training environment, including availability of space and facilities, curriculum time, and research support; o Demonstration of cooperation by any collaborating facilities or institutions in providing experience and research training sites for trainees and mechanisms for integration of trainees; o Proposed methods for monitoring and evaluating performance of trainees and of the overall program, including tracking of graduates after completion of training and record of trainees in obtaining individual research awards or fellowships following training and in establishing careers in health services research; o Record of the training program in retaining health professional postdoctoral trainees for more than 1 year of research training; and o Reasonableness of the proposed budget, including number and levels of trainees, in relation to the research training. In addition, applicant institutions will be evaluated on the acceptability of their proposed plans for instruction in the responsible conduct of research and for recruiting individuals from underrepresented minority groups into the proposed training program. Prospective applicants should consult the NIH Guide for Grants and Contracts, Vol. 21, No. 43, November 27, 1992, and Vol. 22, No. 25, July 16, 1993, for information on these two issues. INQUIRIES Written and telephone requests for the RFA are encouraged and the opportunity to clarify any issues or questions from potential applicants are welcome. Inquiries regarding programmatic issues and requests for the RFA may be directed to: DonnaRae Castillo NRSA Project Officer Agency for Health Care Policy and Research 2101 East Jefferson Street, Suite 501 Rockville, MD 20852 Telephone: (301) 594-1362 Direct inquiries regarding fiscal/administrative matters to: Ralph Sloat Grants Management Branch Agency for Health Care Policy and Research 2101 East Jefferson Street, Suite 601 Rockville, MD 20852 Telephone: (301) 594-1447 AUTHORITY AND REGULATIONS NRSA institutional training grants are made under authority of Section 487 of the Public Health Service (PHS) Act as amended (42 USC 288). Title 42 of the Code of Federal Regulations, Part 66, is applicable to this program. The program is described under Catalog of Federal Domestic Assistance No. 93.225. This program is not subject to the intergovernmental review requirements of Executive Order 12372. $$R3 END ************************************************************ $$R4 BEGIN CA/ES/AG-94-005 FULL-TEXT ******************************** BREAST CANCER RESEARCH PROGRAMS IN NCI-DESIGNATED CANCER CENTERS NIH GUIDE, Volume 22, Number 43, November 26, 1993 RFA AVAILABLE: CA/ES/AG-94-005 P.T. 34; K.W. 0715036, 0710030 National Cancer Institute National Institute of Environmental Health Sciences National Institute on Aging Letter of Intent Receipt Date: January 12, 1994 Application Receipt Date: February 17, 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 This RFA is sponsored by the Cancer Centers Branch, Division of Cancer Biology, Diagnosis and Centers (DCBDC) of the National Cancer Institute (NCI); the Chemical Exposures and Molecular Biology Branch, Division of Extramural Research and Training of the National Institute of Environmental Health Sciences (NIEHS); and the Extramural Research Programs of the National Institute on Aging (NIA). The co-sponsoring Institutes announce the availability of planning and development grants for the purpose of developing and establishing broad, multidisciplinary research programs in breast cancer within existing NCI-designated cancer centers (i.e., those institutions currently awarded a Cancer Center Support Grant, P30). The primary purpose of this RFA is to encourage Cancer Centers that do not currently have a formal breast cancer research "program" to develop and establish the research infrastructure for an organized, interactive activity within the center. A secondary purpose is to encourage cancer centers with established breast cancer research programs to expand their competitive research base by focusing on breast cancer in the elderly and/or on environmental factors affecting the incidence, morbidity, and mortality of breast cancer. In the primary area, emphasis should be placed on developing "programs" that will involve a broad array of research approaches in basic, clinical, and prevention and control research and that will have the potential for medical application and impact on reducing the incidence and mortality of breast cancer on a local, regional, and/or national level. In the secondary area, the center should already have a strong, broadly-based research "program" in place with potential for medical application, and emphasis should be placed on expanding the existing "program" to take advantage of research opportunities related to the elderly and/or to environmental factors. Under both purposes, the sponsoring Institutes will be particularly receptive to applications that include or involve a focus on the problem of breast cancer in underserved minority populations and populations of women that have disproportionately high death rates due to cancer. Upon completion of these planning and development grants, it is anticipated that recipient institutions will either have a formal breast cancer research "program" in place or an expanded "program" addressing breast cancer in the elderly and/or environmental factors contributing to breast cancer. It is also expected that those "programs" will be sustained in the future through the same types of competitive funding sources that support other established programs in the Cancer Center. 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, Breast Cancer Research Programs in NCI-designated Cancer Centers, 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 Only institutions that are current recipients of Cancer Center Support Grants (CCSG) (P30) awards from the NCI are eligible to apply for a planning and development grant in response to this RFA. Two different levels of eligibility are as follows: Option A 1. Eligibility. Cancer Centers that currently have neither: (a) an existing breast cancer research "program" or substantial breast cancer research activity equivalent to a program that is part of the CCSG-supported Cancer Center; or (b) a Specialized Program of Research Excellence (SPORE) (P50) grant in breast cancer. 2. Purpose/Funds. These institutions may apply for up to $400,000 in total costs per year for up to four years for the purpose of developing a broadly based research program in breast cancer (see FUNDS AVAILABLE). Option B 1. Eligibility. Cancer Centers that currently already have either: (a) an existing research "program" or substantial breast cancer research activity equivalent to a "program" that is part of the CCSG-supported Cancer Center; or (b) a Specialized Program of Research Excellence (SPORE) (P50) grant in breast cancer. 2. Purpose/Funds. These institutions may apply for up to $150,000 in total costs per year to develop research activities focused on breast cancer in elderly women or on environmental factors influencing breast cancer. An Institution may apply for both of these expansion components, but must provide separate applications for each. The maximum period of support will be four years. (see FUNDS AVAILABLE) MECHANISM OF SUPPORT This RFA is a one-time solicitation. Support of this program will be through the National Institutes of Health (NIH) exploratory grant mechanism (P20). Applicants will be responsible for the planning, direction, and execution of the proposed project. Awards will be administered under PHS grants policy as stated in the Public Health Service Grants Policy Statement, DHHS Publication No. OASH 90-50,000 (rev. October 1, 1990) and this RFA. The P20 Planning and Development Grant will support: (1) the partial salary of the Program Development Director; (2) funds for special retreats and meetings; (3) developmental funds for recruitment of new scientists; (4) developmental funds for pilot projects; and (5) expansion of an existing shared resource or development of a new shared resource. FUNDS AVAILABLE Approximately $4.9 million is anticipated for availability in Fiscal Year 1994 to fund applications submitted in response to this RFA. Up to eight awards for the development of new breast cancer programs could be made for approximately $400,000 total costs per year. For those Centers applying for expansion of their existing programs, up to 12 subcomponents could be awarded at $150,000 total costs each per year. The funding level is dependent on the receipt of a sufficient number of applications of high merit. The sponsoring Institutes could fund more or fewer grants than the numbers estimated above depending on the scientific merit of the applications received. The total project period is limited to not more than four years. The earliest possible start date for the initial awards will be September 30, 1994. Although this program is provided for in the financial plans of the NCI, NIEHS and NIA, the award of grants pursuant to this RFA is also contingent upon the availability of funds for this purpose. RESEARCH OBJECTIVES Breast cancer is the most common cancer among U.S. females and the incidence of breast cancer has increased at a rate of approximately two percent per year since 1980. This RFA is to encourage research that draws from expertise in many disciplines to focus on the problem of breast cancer in the basic, clinical and prevention and control research arenas, and in research that bridges basic science with clinical research. Significant scientific and clinical expertise in breast cancer exists in many of the NCI-designated Cancer Centers throughout the country. Cancer Centers have well-established interactive research environments, and they have the leadership, space, equipment, structure and resources already available to take advantage of new research directions as opportunities arise. This RFA is designed to provide a significant part of the developmental resources necessary to establish the program in order to encourage qualified institutions to make the long term commitment necessary to sustain the program as a ongoing part of the Cancer Center. The goal of this RFA is to establish a solid, broad-based infrastructure for the conduct and continued development of breast cancer research. The planning effort should result in an integrated, interactive research capability with a significant base of externally funded, peer reviewed research projects, focused on the problem of breast cancer. The functions of the Cancer Center Support Grant and the definitions of and requirements for formal cancer research "programs," are described in "Guidelines: Cancer Center Support Grants." This document is available from the NCI program staff listed under INQUIRIES. STUDY POPULATIONS SPECIAL INSTRUCTIONS FOR INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDIES Clinical research conducted under this RFA is likely to accrue women predominantly. However, applicants should also ensure that special attention is given to the inclusion of minorities in study populations. If minorities are not included in the study population for any clinical study, a specific justification for the exclusion from the study must be provided. Applications without such documentation will not be accepted for review. LETTER OF INTENT Prospective applicants are asked to submit, by January 12, 1994, a letter of intent that includes a descriptive title of the proposed application; the name, address, and telephone number of the Principal Investigator; the names of other key personnel; the participating institution(s); 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 a subsequent application, the information that it contains allows Institute staff to estimate the potential review workload, to establish the peer review group as soon as possible, and to avoid conflict of interest in the review. The letter of intent is to be sent to Dr. Margaret E. Holmes 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 the P20 Planning Grant. 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; and the program administrators listed under INQUIRIES. Supplemental instructions for preparing the application are provided in the RFA. The receipt date for applications under this RFA is February 17, 1994. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed initially for completeness and responsiveness. Incomplete or non-responsive applications will be returned to the applicant without further consideration. Applications will be assessed on: (1) the technical merit of the proposed plans and all scientific elements critical to the development of a strong research program; (2) the contributions of other resources from the cancer center and the institution to the successful development of a research program; and (3) the potential of the cancer center to develop a successful, broad-based, interactive research program with clinical application capability over the period of the planning process. The final priority score will be based on how well the cancer center is expected to build upon its current research capabilities to establish or expand a breast cancer research program with a competitively funded research base that is multidisciplinary, interactive, and collaborative and that has the potential for generating results that may have effective applications. The specific criteria that will be used by the peer review group in its evaluation of each application are outlined in the RFA. Only highly meritorious applications will be funded. The earliest anticipated date of award is September 30, 1994. 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: Margaret E. Holmes, Ph.D. Division of Cancer Biology, Diagnosis, and Centers National Cancer Institute Executive Plaza North, Room 502 Bethesda, MD 20892 Telephone: (301) 496-8531 FAX: (301) 402-0181 William Suk, Ph.D. Division of Extramural Research and Training National Institute of Environmental Health Sciences P.O. Box 12233 Research Triangle Park, NC 27709 Telephone: (919) 541-0797 FAX: (919) 541-2843 Rosemary Yancik, Ph.D. Assistant Director for Liaison and Applied Research National Institute on Aging Building 31, Room 5C05 Bethesda, MD 20892 Telephone: (301) 496-5278 FAX: (301) 496-2793 Direct inquiries regarding fiscal matters to: Ms. Crystal Elliot Grants Administration Branch National Cancer Institute Executive Plaza South, Room 242 Bethesda, MD 20892 Telephone: (301) 496-7800, ext. 19 Mr. David Mineo Grants Management Branch National Institute of Environmental Health Sciences Building 2, Mail Drop 2-01 P.O. Box 12233 Research Triangle Park, NC 27709 Telephone: (919) 541-7628 Joseph Ellis Grants and Contracts Management Office National Institute on Aging Gateway Building, Room 2N212 Bethesda, MD 20892 Telephone: (301) 496-1472 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance Number 93.397, Cancer Centers Support. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 100-607) 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 ************************************************************ $$R5 BEGIN DK-94-013 FULL-TEXT ************************************** CENTERS OF EXCELLENCE IN MOLECULAR HEMATOLOGY NIH GUIDE, Volume 22, Number 43, November 26, 1993 RFA AVAILABLE: DK-94-013 P.T. 04; K.W. 0785070, 1002004, 1002008, 0710030, 0715132 National Institute of Diabetes and Digestive and Kidney Diseases Letter of Intent Receipt Date: February 4, 1994 Application Receipt Date: March 17, 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 This RFA invites investigators to submit research applications for Centers of Excellence in Molecular Hematology. The Centers are intended to create a focus for multidisciplinary investigations into the cellular and molecular bases of genetic diseases of the blood; encourage the efficient assembly of the needed expertise, equipment, and technologies to generate advances in molecular hematology; attract new scientific expertise into the study of the molecular mechanisms of hematologic diseases and disorders; and utilize cellular and molecular biology techniques to develop methods to characterize, identify, treat, and cure inherited diseases of the blood and genetic diseases of other systems. 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, Centers of Excellence in Molecular Hematology, is related to the priority area of 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, units of State or local governments, and eligible agencies of the Federal government. Foreign institutions are ineligible. Minority individuals and women are encouraged to submit as Principal Investigators. MECHANISM OF SUPPORT Support of this program will be through the National Institutes of Health (NIH) specialized center (P50) award. Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. Except as otherwise stated in this announcement, awards will be administered under PHS grants policy as stated in the PHS Grants Policy Statement. FUNDS AVAILABLE The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) expects to award up to three (3) center grants (P50) for molecular hematology research in fiscal year 1994. The anticipated awards are for five years and are contingent upon the availability of appropriated funds. The total amount of available funds to support this program is anticipated to be no more than $2.25 million per year. No applicant may request more than $750,000 in total costs (including both direct and indirect costs) in the initial budget period. A standard escalation factor may be used for subsequent budget periods. The award date for these grants will be September 30, 1994. RESEARCH OBJECTIVES During the past two decades, major advances have been made in understanding the molecular basis for inherited diseases, including the genes for Cooley's anemia, sickle cell disease, and hemophilia. The Centers of Excellence in Molecular Hematology are intended to promote the development of the broad range of scientific expertise and technologies needed for investigation of genetic diseases and genetic therapy. The Centers will emphasize the study of gene structure and function, the structural biology of proteins and the complex biochemistry of protein interactions, the mechanisms of hematopoietic gene regulation and of differential gene expression during hematopoietic cell maturation and differentiation. They will have as their ultimate goal the development of preventive, curative, or intervention strategies in the treatment of genetic diseases. Areas addressed by the NIDDK Centers of Excellence in Molecular Hematology should relate to announced research emphases of the NIDDK in hematologic research. The program's areas of emphasis include the molecular and cellular biology of hematopoiesis; hematopoietic stem cell biology; erythropoietin and other hematopoietic growth factors; erythrocyte metabolism and ion transport; hematopoietic membrane biology; hemoglobin biosynthesis and regulation; and iron absorption and metabolism. Administrative guidelines describing the Centers of Excellence in Molecular Hematology (P50) and the application process for the Centers are available from the NIDDK. These guidelines should be requested before applying. 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 may be included with the application. STUDY POPULATIONS SPECIAL INSTRUCTIONS FOR INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDIES For projects involving clinical research, the NIH requires applicants to give special attention to the inclusion of women and minorities in study populations. 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. Applications without such documentation will not be accepted for review. LETTER OF INTENT Prospective applicants are asked to submit, by February 4, 1994, 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. The letter of intent is not required, is not binding, and does not enter into the review of subsequent applications. The letter of intent is to be sent to: Chief, Review Branch Division of Extramural Activities National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 605 Bethesda, MD 20892 APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 9/91) is to be used in applying, and is available from 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 March 17, 1994. If an application is received after that date, it will be returned to the applicant. REVIEW CONSIDERATIONS Upon receipt, applications will be examined for completeness and responsiveness. Incomplete applications or non-responsive applications will be returned to the applicant without further consideration. Those applications that are complete and responsive will be evaluated by an appropriate peer review group convened by the NIDDK. Where the number of applications is large compared to the number of awards to be made, a preliminary scientific peer review may be conducted and applications withdrawn from further competition when they are not competitive for the award. Applications judged to be competitive will be reviewed for scientific and technical merit in accordance with the usual NIH peer review procedures. The applications will be given a secondary review by the NIDDK Advisory Council. INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. Copies of the RFA, and the Administrative Guidelines for NIDDK Centers of Excellence in Molecular Hematology may be obtained from: David G. Badman, Ph.D. Division of Kidney, Urologic and Hematologic Diseases National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 5A-04 Bethesda, MD 20892 Telephone: (301) 594-7541 FAX: (301) 594-7501 Inquiries regarding fiscal matters may be directed to: Aretina D. Perry Division of Extramural Activities National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 649 Bethesda, MD 20892 Telephone: (301) 594-7543 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.849. 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. $$R5 END ************************************************************ $$R6 BEGIN HD-94-010 FULL-TEXT ************************************** GENE THERAPY FOR DISORDERS CAUSING MENTAL RETARDATION NIH GUIDE, Volume 22, Number 43, November 26, 1993 RFA AVAILABLE: HD-94-010 P.T. 34; K.W. 0745032, 0715130, 0715135, 1002019 National Institute of Child Health and Human Development Letter of Intent Receipt Date: December 30, 1993 Application Receipt Date: March 25, 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 Mental Retardation and Developmental Disabilities Branch (MRDD), Center for Research for Mothers and Children (CRMC), National Institute of Child Health and Human Development (NICHD) invites program project grant applications to develop new technologies, or improve existing ones, for gene therapy targeted toward disorders causing mental retardation. For the purpose of this RFA, the diseases of interest are restricted to genetic conditions in which mental retardation is the primary clinical manifestation. Genetic disorders causing mental retardation include defects of amino acid metabolism, urea cycle defects, organic acidemia, carbohydrate metabolism (e.g., galactosemia), peroxisomal disorders, trace metal defects, lysosomal storage diseases, and disorders of purine metabolism (e.g., Lesch-Nyhan syndrome). Whatever organs are necessary to target for gene transfer to correct or prevent mental retardation could be considered in response to this RFA. 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, Gene Therapy for Disorders Causing Mental Retardation, is related to the priority area of 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, and eligible agencies of the Federal government. Applicants may collaborate, through consultation or contractual arrangements, with foreign investigators. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT This RFA will use the NIH program project grant mechanism (P01). The applications should be prepared in a manner consistent with the information presented in the publication, P01 Program Project Guidelines, Division of Scientific Review, NICHD that is available from NICHD staff listed under INQUIRIES. 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. The anticipated award date is September 30, 1994. This RFA is a one-time solicitation. Future unsolicited competing continuation applications will compete with all investigator-initiated applications and will be reviewed according to the customary NIH peer review procedures. FUNDS AVAILABLE It is estimated that program project applications submitted in response to this announcement will compete for approximately $3 million in direct costs that will be made available for the first year of support. It is anticipated that four to five awards will be made. The number of awards depends on the overall scientific merit of the applications and the availability of funds in fiscal year 1994. Four to five P01s may be funded under this grant solicitation. Assignment of grants to appropriate Institutes will be based on current National Institutes of Health (NIH) referral guidelines. RESEARCH OBJECTIVES The MRDD Branch supports research that relates to the biological, behavioral, and social processes that contribute to, or influence the development of, mental retardation and developmental disabilities. Prevention of MRDD and amelioration of the clinical manifestations of those afflicted constitute areas of special emphasis within the Branch. To accomplish its mission, the Branch uses the mechanisms of research grants, supports special core facilities in the Mental Retardation Research Centers, provides contract support for development of new research resources, and disseminates information to the scientific community and the public. Genetic disorders have become increasingly prominent in the etiology of mental retardation, particularly in severe cases, i.e., I.Q. <50. In a survey of 122 severely mentally retarded children in Sweden, 36 percent were found to have demonstrable chromosome abnormalities, and five percent were caused by mutant genes. In addition, 20 percent had multiple congenital anomaly syndromes and 16 percent had perinatal or unidentified prenatal causes. Since a large proportion of the multiple congenital anomaly syndromes, especially those that affect the central nervous system, and some of the unidentified prenatal causes are genetically determined, it is likely that genetic causes accounted for more than 50 percent of the total. With aggressive use of antimicrobial agents to treat infectious diseases, widespread immunization programs to protect against bacterial and viral infectious agents, better nutrition, and surgical correction of congenital defects, increasing numbers of mentally retarded children who otherwise would have succumbed are able to survive and live longer. Significant progress has been made in several areas of research relevant to gene therapy. The concepts have evolved quite rapidly from in vitro cellular and molecular studies, preclinical studies on an expanding list of animal models for human genetic disorders, to actual clinical gene therapy involving human subjects. The number of cloned and characterized genes is increasing rapidly; we now have a better understanding of the nature of disease-producing mutations, and gene regulation; a much improved and growing list of gene delivery systems are available; and various methods can now be applied to develop animal models for genetic disorders. In addition, the limited number of approaches that are currently available such as dietary restriction, and enzyme replacement, to treat a number of genetic disorders, are not completely successful and require life-long treatment. This RFA solicits applications that will address methods to efficiently transfer foreign genes into human and other mammalian systems, including transfer of genetically modified cells to recipient tissues, organs, or animal models; develop methods for sustained survival, and controlled expression of transferred foreign genes in vivo by developing and using appropriate enhancers and other regulatory sequences; develop genetic animal models of human diseases by homologous recombination, gene knockout, and other methods; and initiate human clinical trials for conditions that cause mental retardation. Proposed projects should evaluate the efficacy, long-term effects, safety and, in human trials, neuropsychological outcomes. 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 December 30, 1993, a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, titles of the component subprojects and the Principal Investigator, core facilities when applicable, and the director of each core, names 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 NICHD 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. Felix F. de la Cruz at the address listed under INQUIRIES. APPLICATION PROCEDURES The applicant is to submit the application using PHS 398 (rev. 9/91). Application kits containing this form and the necessary instructions are available in 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 application must be submitted to the Division of Research Grants by March 25, 1994. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by DRG and responsiveness to the RFA by NICHD staff. Incomplete applications will be returned to the applicant without further consideration. If the application is not responsive to the RFA, Institute 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. Under certain circumstances, applications may be triaged by a peer review group on the basis of relative competitiveness. In that case, the NIH will withdraw from further competition those applications judged to be non-competitive for an award and notify the applicant Principal Investigator and institutional official. Applications judged to be competitive will undergo further scientific merit review. Applications that are complete and responsive will be evaluated for scientific and technical merit by a review panel convened solely for this purpose by the Division of Scientific Review, NICHD. The second level of review will be provided by the National Advisory Child Health and Human Development Council. Review criteria for this RFA are generally the same as those for unsolicited research grant applications and are described in the RFA. AWARD CRITERIA In addition to the scientific and technical merit of the application, other factors will be considered in making the awards. Among these are relevance to mental retardation; access to unique populations; and institutional commitment and support. The anticipated date of award is September 30, 1994. INQUIRIES Written and telephone requests for the RFA, and the opportunity to clarify any issues or questions from potential applicants are welcome. Requests for the RFA and program project guidelines, and inquiries regarding programmatic and scientific issues may be directed to: Felix F. de la Cruz, M.D., M.P.H. Mental Retardation and Developmental Disabilities Branch National Institute of Child Health and Human Development 6100 Executive Boulevard, Room 4B-09 Bethesda, MD 20892 Telephone: (301) 496-1383 Fiscal and administrative inquiries may be directed to: Mr. E. Douglas Shawver Office of Grants and Contracts National Institute of Child Health and Human Development 6100 Executive Boulevard, Room 8A-17 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 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. $$R6 END ************************************************************ ONGOING PROGRAM ANNOUNCEMENTS $$P1 BEGIN PA-94-014 ************************************************ BASIC RESEARCH IN SUPPORT OF TREATMENTS FOR AIDS NIH GUIDE, Volume 22, Number 43, November 26, 1993 PA NUMBER: PA-94-014 P.T. 34; K.W. 0715008, 0710030 National Institute of General Medical Sciences National Institute of Diabetes and Digestive and Kidney Diseases National Institute of Allergy and Infectious Diseases PURPOSE The purpose of this program announcement (PA) is to encourage research in areas fundamental to the development of treatments for AIDS and associated opportunistic infections. 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 PA, Basic Research in Support of Treatments for AIDS, 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 foreign and domestic, 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 eligible for First Independent Research Support and Transition (FIRST) (R29) awards and program project (P01) grants. MECHANISM OF SUPPORT Support of this program will be through the individual research project grant (R01), and the FIRST Award (R29). Individuals desiring to apply for support under one of these mechanisms are specifically encouraged to apply for grants citing this program announcement. The National Institute of General Medical Sciences (NIGMS) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) will also support this program through the program project grant (P01) mechanisms. However, the National Institute of Allergy and Infectious Diseases (NIAID) will NOT accept investigator initiated program project (P01) applications. Potential applicants are advised to contact the program staff listed under INQUIRIES for guidance in the areas appropriate for program project grant applications and the preparation of the application itself. Investigators holding active P01 (NIGMS and NIDDK only), R01, or Method to Extend Research in Time (MERIT) (R37) grants to study fundamental processes associated with interaction of proteins with ligands, bioavailability of drugs, crystallization of proteins, macromolecular engineering, or evolutionary adaptation, with at least one year of support remaining at the time of the anticipated award, are also encouraged to apply through competing supplemental awards. RESEARCH OBJECTIVES Despite all that is known about fundamental biological processes, particularly at the molecular level, and the application of this knowledge to understanding the structure and replication of HIV, there are still fundamental gaps in our understanding of basic biology that must be filled before a rational approach to the treatment of HIV infection and associated secondary infections can be accomplished. These gaps include: o A basic understanding of the factors that govern the interaction of proteins with ligands--especially with respect to the flexibility of both the binding site of the protein and binding ligand. Such an understanding is essential for the de novo design of drugs to inhibit specific proteins necessary for the HIV life cycle and antibiotics to treat opportunistic infections. o A basic understanding of the factors that govern the availability of a drug at its site of action. Potential new drug candidates frequently fail due to poor bioavailability, i.e., the compounds show high receptor affinity, but fail to get to their targets in sufficient quantity. Recently, efforts to develop HIV protease inhibitors as new drugs to treat HIV infection have foundered because of a failure to achieve adequate intracellular drug concentrations. The reasons why these new drug candidates fail is not well understood, and thus, cannot be accounted for in the design stage. o A basic understanding of the principles that underlie the crystallization of proteins--especially membrane and/or glycosylated proteins. The inability to routinely crystallize a given protein is a serious roadblock in the determination of the three-dimensional structure of, for example, the envelope protein of HIV, and other proteins necessary for the HIV life cycle or proteins important in the life cycle of organisms that cause opportunistic infections. The determination of the structures of these proteins at high resolution is an essential first step in the design of drugs to inhibit the processes for which these proteins are essential. o A basic understanding of the principles of macromolecular engineering. A promising approach in the treatment of AIDS is to alter genetically HIV infected lymphocytes so that they produce proteins or nucleic acids that inhibit either the production or escape of HIV, misdirect specific components of HIV, or are toxic to infected cells. A significant limitation in this approach is the inability to engineer reliably specific functionality into an existing protein or nucleic acid scaffold or, at a more basic level, to design a protein or nucleic acid de novo to perform a specific function. o An understanding of basic evolutionary processes by which organisms adapt to complex environments. The rapid evolution of the HIV, even within a single host, is a major obstacle to vaccine and drug development and underlies the phenomenon of multiple drug resistance. Knowledge about the general features which govern adaptation and evolution is an essential step to understanding the relationship between viral diversity and the course of infection, and the evolution of multiple drug resistance. These are factors that must be considered in developing vaccines and designing drugs to make them effective. The purpose of this program announcement is to solicit applications that address one or more of these key issues in ways that not only take advantage of an investigator's existing expertise in these areas but also encourages the investigator to recognize the implications of his or her research to AIDS and AIDS-associated opportunistic infections. The expectation is that the investigator will remain focused on the central question of AIDS during the course of the project. For investigators already funded by NIGMS, NIDDK, or NIAID for basic research in these areas, a competitive supplement to provide key links to AIDS research is encouraged. In addition to the information described in the application kit (PHS 398) required for a supplemental application, the request should detail how the requested funds will enable the investigator to enhance significantly the applicability of the research project to AIDS and AIDS-associated opportunistic infections. APPLICATION PROCEDURES Applications for regular and supplemental awards for regular research (R01), FIRST, and MERIT grants are to be submitted on the grant application form PHS 398 (rev. 9/91) and will be accepted at the receipt dates for applications for AIDS-related research: January 2, May 1, and September 1. Applications for regular and supplemental awards for program project grants (P01) have receipt dates of February 1, June 1, and October 1. 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. On the first (face) page, item 2a, of the application, the word "YES" must be checked and the title and number of the program announcement typed in the space provided: "Basic Research in Support of Treatments for AIDS, PA-94-014." 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. 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 CONSIDERATIONS Applications will be assigned to a funding component (Institute or Center) and an Initial Review Group (IRG) on the basis of established Public Health Service referral guidelines. The IRGs will review applications for scientific and technical merit in accordance with standard NIH peer review procedures. Following the IRG review, the applications will receive a second-level review by the appropriate national advisory council. AWARD CRITERIA Applications will compete for available funds with all other approved applications. The following will be considered making funding decisions: o Quality of the proposed project as determined by peer review o Availability of funds o The implications of the project for AIDS and an intellectual environment that focuses on AIDS research 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: James Cassatt, Ph.D. Biophysics and Physiological Sciences Program National Institute of General Medical Sciences Westwood Building, Room 907 Bethesda, MD 20892 Telephone: (301) 594-7800 FAX: (301) 594-7700 Carl W. Dieffenbach, Ph.D. Division of AIDS National Institute of Allergy and Infectious Diseases Solar Building, Room 2C05 Bethesda, MD 20892 Telephone: (301) 496-8199 FAX: (301) 402-3211 Eliezar Dawidowicz, Ph.D. Metabolism and Structural Biology Research Program National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 621 Bethesda, MD 20892 Telephone: (301) 594-7582 FAX: (301) 594-9011 Direct inquiries regarding fiscal matters to: Ms. Ruth Monaghan Grants Management Office National Institute of General Medical Sciences Westwood Building, Room 9A03 Bethesda, MD 20892 Telephone: (301) 594-7813 Ms. Donna A. Huggins Division of Extramural Activities National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 649 Bethesda, MD 20892 Telephone: (301) 594-7543 Ms. Carol B. Alderson Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4B27 Bethesda, MD 20892 Telephone: (301) 496-7075 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance Nos. 93.821, 93.859, 93.862, and 93.863. Awards are authorized by sections 301 and 405 of the Public Health Service Act, as amended, and administered under PHS grants policies and Federal Regulations 45 CFR Part 74 and 45 CFR Part 92. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$P1 END ************************************************************ $$P2 BEGIN PA-94-015 ************************************************ BASIC RESEARCH ON HEMATOPOIETIC GENE REGULATION NIH GUIDE, Volume 22, Number 43, November 26, 1993 PA NUMBER: PA-94-015 P.T. 34; K.W. 0785070, 0765015, 1002004 National Institute of Diabetes and Digestive and Kidney Diseases PURPOSE The purpose of this Program Announcement (PA) is to encourage research grant applications related to the mechanisms of hemopoietic gene regulation and of differential gene expression during hematopoietic cell maturation and differentiation. 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 PA, Basic Research on Hemopoietic Gene Regulation, is related to the priority area of diabetes and other chronic disorders. 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 First Independent Research Support and Transition (FIRST) (R29) awards. Applications from minority individuals and women are encouraged. MECHANISMS OF SUPPORT Support of this program will be primarily by research project grants (R01) and FIRST awards (R29). Deadlines for new grants are February 1, June 1, and October 1, and for competing and revised grants are March 1, July 1, and November 1. Because the nature and scope of the research applications submitted in response to this Program Announcement may vary, it is anticipated that the size of award will vary also; however, the average size is estimated to be approximately $200,000 total costs. RESEARCH OBJECTIVES The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) supports basic and clinical studies related to hematopoiesis and the process of lineage-specific differentiation of the hematopoietic stem cell. These processes are central to the maintenance of normal blood cell counts, and to the reconstitution of blood counts following bone marrow insults, such as infections, radiation and chemotherapy. An increased understanding of the specific molecular mechanisms underlying lineage-specific differentiation processes could enhance our ability to combat selective cytopenias, and facilitate bone marrow reconstitution following bone marrow transplantation. Areas of research interest under this announcement include, but are not limited to, investigations into the mechanisms of hematopoietic gene regulation and of differential gene expression during hematopoietic cell maturation and differentiation. Of particular interest is the elucidation of factors such as DNA elements, DNA binding proteins, nuclear matrix, signal transduction mechanisms, stromal or cell-surface protein interactions that may contribute to lineage-specific differentiation by modulation of gene expression. The alpha- and beta-globin gene clusters serve as examples of an area of hematopoiesis that has developed greatly in the past few years. Most of the regions of the human chromosomes containing the genes for hemoglobin, defective in Cooley's anemia and sickle cell disease patients, have been sequenced. The characterization of relevant DNA regions and DNA-binding proteins is well along. The role of the DNA within the genes, as well as in the genetic regions that control the DNA, is now understood to a considerable extent. This information has been of considerable value in explaining the normal developmental control of these genes, as well as the abnormal states that exist in the hemoglobin disorders. Regions of DNA linked to both clusters of hemoglobin genes determine developmental expression, and may be intimately involved in the switch in hemoglobin formation which occurs at the time of birth in humans and in many animals. Other regulatory factors, either closely linked to genes or on other chromosomes, have been found to control the expression of the genes. Much still remains to be learned about gene regulation and switching of expression from one gene to another at various stages of human development, including the mechanism of action of drugs such as hydroxyurea and butyrate, which have been shown to enhance fetal hemoglobin formation, thus lending themselves as possible therapeutic agents for the globin gene disorders. The recent cloning of the gene for the hormone erythropoietin and the gene for the erythropoietin receptor, for humans and other species, has opened up the study of this aspect of the erythroid component of hematopoiesis. The cloning of other cytokines and their receptors continues rapidly, as well, promising clarification of many aspects of hematopoiesis, as well as providing other drugs for clinical use. The molecular mechanisms of these hormone-cell interactions are being studied at the level of receptor binding, internalization, signal transduction, and apoptosis. Similarly, new techniques using cell surface molecules and monoclonal antibodies, are allowing identification of various precursor cell populations, including cells which may constitute the hypothetical totipotent hematopoietic stem cell. Characterization and preparation of these stem cell and precursor cells in large quantities would be of major importance in the application of this new knowledge to clinical situations. New techniques including transgenic animal expression systems, "knock out" animal models (frequently using embryonal cells), PCR assays, homologous genetic recombination, transient and stable cell expression systems, and YAC and other large DNA cloning vectors, are allowing the field of molecular hematopoiesis to develop very rapidly. Whereas much of the previous work has used mouse and other animal models, these new techniques are facilitating more direct analyses of human genes and cells. This Program Announcement is intended to stimulate a broad range of new research programs in the general area of regulation of genetic processes involved in hematopoietic cell differentiation. 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 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 re