From owner-sci-resources@net.bio.net Sun Oct 04 23:00:00 1992 Path: biosci!NET.BIO.NET!kristoff From: kristoff@NET.BIO.NET (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NSF - Summary of new documents on STIS - 4 October 1992 Message-ID: Date: 5 Oct 92 16:27:30 GMT Sender: kristoff@net.bio.net Distribution: bionet Lines: 92 This message contains a summary of the documents added to the NSF STIS system in the previous week. Reference material concerning STIS and this message follows the summary. ------------------------------------------------------------------------ ** NEW DOCUMENTS ON STIS ** Document Type: Issuance Title: SUMMARY OF THE FIRST MEETING OF THE NSB COMMISSION ON THE FUTURE OF THE NSF File size (bytes): 24459 STIS Filename: ilpa925 Document Type: Recruit Title: Dir. Division of Polar Programs, GEO File size (bytes): 6763 STIS Filename: vep9216 Document Type: Report Title: NSF 92-109 Research Priorities in Networking and Communications Research (Workshop Report) File size (bytes): 84735 STIS Filename: nsf92109 ------------------------------------------------------------------------ ** UPDATES TO EXISTING STIS DOCUMENTS ** Document Type: General Publication Title: NSF9119 - STIS User's Guide File size (bytes): 58851 STIS Filename: nsf9119 Document Type: Phone Book Title: NSF Phone Book - Alphabetical File size (bytes): 71757 STIS Filename: phnalpha Title: NSF Phone Book - Organizational File size (bytes): 106186 STIS Filename: phnorg Document Type: STIS Title: Document Types on STIS File size (bytes): 2679 STIS Filename: stistype ------------------------------------------------------------------------ ** 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 stistype, the text of your message should be as follows: get stistype Anonymous FTP: FTP to stis.nsf.gov. Use the "STIS Filename" shown above to retrieve a file. For example, to retrieve stistype, you would enter: ftp> get stistype 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 "pubs@nsf.gov" (Internet) or "pubs@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 Wed Oct 07 23:00:00 1992 Path: biosci!NET.BIO.NET!kristoff From: kristoff@NET.BIO.NET (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide vol. 21, no. 35 delayed; no. 36 follows Message-ID: Date: 8 Oct 92 23:51:27 GMT Sender: kristoff@net.bio.net Distribution: bionet Lines: 12 Apparently the NIH Guide, vol. 21, no. 35 was sent while we were off-line for a few hours last week. I am trying to retrieve another copy for posting. No. 36 arrived this afternoon and follows this posting. Sincerely, Dave Kristofferson BIOSCI/bionet Manager kristoff@net.bio.net From owner-sci-resources@net.bio.net Wed Oct 07 23:00:00 1992 Path: biosci!NET.BIO.NET!kristoff From: kristoff@NET.BIO.NET (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 21, no. 36, pt. 3, 9 October 1992 Message-ID: Date: 8 Oct 92 23:57:23 GMT Sender: kristoff@net.bio.net Distribution: bionet Lines: 1105 $$XID RFA HL9303B HL-93-03-B P1O1 ************************************** CELL AND MOLECULAR BIOLOGY OF MEGAKARYOCYTOPOIESIS NIH GUIDE, Volume 21, Number 36, October 9, 1992 RFA: HL-93-03-B P.T. 34; K.W. 0780015, 0780020, 0760003, 0760020, 1002008, 1002019 National Heart, Lung, and Blood Institute Letter of Intent Receipt Date: January 15, 1993 Application Receipt Date: March 15, 1993 PURPOSE The Division of Blood Diseases and Resources (DBDR), of the National Heart, Lung, and Blood Institute (NHLBI) invites applications for studies that may contribute to better understanding of regulation of the proliferation and maturation of megakaryocytes and the control of platelet production. The knowledge gained may allow manipulation of megakaryocytopoiesis and platelet level in patient populations. 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, Cell and Molecular Biology of Megakaryocytopoiesis, is related to the priority area of platelet disorders and bone marrow transplantation. 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 202-782-3238). 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 and 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. Foreign institutions are not eligible for First Independent Research Support and Transition (FIRST) Awards (R29). Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT This RFA solicits applications for the National Institutes of Health (NIH) individual research grant (R01) and FIRST Award (R29) 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 in September 1993. Administrative adjustments in project period and/or amount of support may be required at the time of the award. 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 Although the financial plans for fiscal year 1994 include $1.5 million for this program, award of grants pursuant to this RFA is contingent upon receipt of funds for this purpose. It is anticipated that about six 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. 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. If collaborative arrangements involve sub-contracts with other institutions, the NHLBI Grants Operations Branch (telephone 301-496-7257) may be consulted regarding procedures to be followed. RESEARCH OBJECTIVES The bone marrow megakaryocytes are the cells that produce the blood platelets. The number of platelets and their biochemical integrity are important for normal hemostasis, and both of these parameters are dependent upon the normal development of the parent cells, the megakaryocytes. The megakaryocyte is the least understood hematopoietic cell of the bone marrow. It possesses features unlike those of the other hematopoietic cells: the megakaryocyte nuclei are highly polyploid, and several thousand platelets are formed from a remarkable process of synthesis and organization of the cytoplasmic compartment of each megakaryocyte. The factors which regulate the process of endomitosis, the extent of polyploidy, and the ultrastructural changes which occur in the nucleus during maturation are not understood. Likewise, the factors which regulate cytoplasmic development are not known. Specific growth and maturation factors which trigger endomitosis and cytoplasmic maturation of megakaryocytes are not yet defined, in contrast to the considerable knowledge that has been obtained concerning factors specific for red and white cells. The in vivo location of platelet production needs to be defined; although it is generally thought that the megakaryocytes release their platelets in the marrow, it has also been suggested that the megakaryocytes travel to the lung and release platelets in the lung. Optimal methods for assessing the rate of production of platelets have not been established. The feedback mechanisms by which thrombocytopenia signals an increase in production of platelets have not been characterized. Thus considerable work remains to be done in understanding the developmental regulation of megakaryocytes and the factors which lead to platelet release. Disorders of megakaryocytopoiesis can lead to serious clinical problems. The loss of normal regulation of the production of platelets and abnormal platelet function are seen in myeloproliferative disorders and leukemias. In myeloproliferative disorders, this can result paradoxically in hemorrhage in the presence of thrombocytosis. It is reasonable to suspect that the biochemical development of the megakaryocyte is abnormal in these circumstances. However, no consistent abnormalities have been defined in studies of proteins of platelets obtained from patients with these disorders. An understanding of the biochemical abnormalities which cause the thrombopathies would be very important, and would depend on definition of abnormalities in platelets and on an improved understanding of factors that influence megakaryocyte biochemistry. A rapidly growing clinical area in which the understanding of megakaryocytopoiesis is critical is bone marrow transplantation, since patients undergoing transplantation suffer from a prolonged loss of platelet production. Approximately 15 percent of bone marrow transplant recipients die due to primary or secondary hemorrhagic complications, mainly due to thrombocytopenia. On the average, each patient requires about 100 to 150 units of platelet transfusion until recovery of marrow function occurs, usually after 40 to 50 days. Some patients remain thrombocytopenic for a prolonged period and may become refractory to platelet transfusion therapy. An understanding of megakaryocytopoiesis and platelet production is likely to be beneficial for the support of bone marrow recipients. If appropriate growth factors could be isolated and cloned, they will find ready application not only in these patients but also in other cases where thrombocytopenia is a concern, e.g., patients with AIDS or cancer. Similarly, although probably by a different mechanism, sepsis in neonates is associated with prolonged thrombocytopenia. Another clinically relevant area which is poorly understood is the frequent occurrence of megakaryoblastic leukemias in children with Down's syndrome; this phenomenon is found as a transient leukemia in neonates and often develops into a full-blown leukemia later in childhood. The characterization of the genetics and biochemistry of this disorder may be very useful in elucidating the process of megakaryocytopoiesis. It is important to develop an understanding of growth factors and other factors influencing hematopoiesis in order to maintain normal blood cell production and thus be able to improve treatment for the bleeding problems. A major area of interest has been the interaction of proliferation and growth factors with megakaryoblasts and megakaryocytes, both at the progenitor level and at the level of cytoplasmic maturation. Thus far, this work has largely depended on a mixed population of progenitor cells for the starting assay, and a major obstacle to understanding the effects of growth factors has been the inability to isolate a pure normal megakaryoblastic cell line. Studies at the single cell level or with a pure cell population with newer techniques (e.g., cell sorter or polymerase chain reaction) could be productive. Several cell lines derived from megakaryocytic leukemias have been described recently, some of which contain a fraction of cells capable of achieving a ploidy of 8N. These cells may be useful in elucidating some of the early stages of polyploidy. However, they all appear to have multiple trisomies and chromosomal rearrangements and deletions, and the contribution of these factors to the lack of normal development is not understood. The chromosomal abnormalities may restrict the usefulness of these cell lines in understanding the normal dynamics of both development of polyploidy and cytoplasmic maturation. The availability of megakaryocytic cell lines which behave in a normal manner will significantly help to answer some of the outstanding questions in this area. These questions include identification of lineage-specific factors involved in stem cell commitment to the megakaryocytic lineage, nuclear transcription factors which may be unique to megakaryocytes, factors which stimulate DNA and protein synthesis in megakaryocytes, and factors which lead to cytoplasmic maturation and finally to platelet production from the mature megakaryocyte cytoplasm. New technology, such as the use of transgenic animals, provides the potential for manipulating megakaryocytopoiesis in vivo. For example, a portion of the regulatory region of the gene for a platelet-specific protein, platelet factor 4 (PF4) was used to insert foreign genes into the germ cells of mice and to obtain megakaryocyte-specific expression of the foreign proteins. The transgene expression occurred earliest in the 2N megakaryocytes, the construct was expressed in a developmentally accurate fashion, and there were no major positional effects between two cell lines with regard to transgene expression. The selective expression of the transgene in bone marrow progenitors and peripheral blood cells can be employed to devise simple bone marrow assays to monitor the transition and commitment of hemopoietic stell cells to megakaryocyte precursors. This may allow the identification, isolation and cloning of the elusive megakaryocyte maturation and growth factors. The transgenic mouse can be utilized to selectively target gene products to megakaryocytes and platelets and then study their effects in vivo. Examples of Areas of Interest The following are only examples and prospective applicants are urged to use their own ideas as to the area of research. Development of Cell Lines and Culture Systems The critical molecular events which lead to commitment of progenitor cells to the megakaryocytic lineage and to complete maturation of megakaryocytes to platelet production have not been identified. These studies require the development of cell lines which can enter and complete the normal maturation cycle. Immortalized cell lines could be generated which can be triggered to undergo differentiation under restricted conditions. Another approach would be to develop bone marrow culture systems which allow the transition of stem cells to megakaryocytes to be specifically monitored. This approach could employ precursor cells isolated from transgenic mice that possess megakaryocyte-specific promotors coupled to reporter molecules in conjunction with purified hematopoietic growth factors. The role of known oncogenes, growth factor receptors, and other signaling proteins could be investigated in the above systems with dominant negative suppressor techniques, antisense approaches, or injection of specific neutralizing antibodies. The function of previously unidentified components might be sought by somatic cell genetic techniques coupled to expression cloning methods. Nuclear and Cytoplasmic Development The biochemical steps which are responsible for the development and extent of polyploidy and for maturation of the cytoplasm and the formation of granule and membrane systems are not defined. The molecules that are specific to megakaryocytes and to different stages of development must be defined; new markers other than those currently used in studies of platelets should be sought. The cis acting regions and transacting factors of genes specifically expressed in megakaryocytes should be determined, and the effects of hematopoietic growth factors and cytokines on these events should be assessed. Specific areas of study which might elucidate nuclear development include the role of cyclins, kinases, phosphatases, and contractile proteins in endomitosis. Specific areas of study regarding cytoplasmic development include stage-specific events in granule formation and synthesis of membrane and cytoskeletal components, including targeting of proteins to specific structures. The mechanism by which the cytoplasm becomes organized into the mature platelets is unknown, and studies which could address this question would be useful. It would also be important to identify the specific growth factors which control nuclear and cytoplasmic development and platelet formation. Sensors and Signals Investigations are needed to clarify the sensors and molecular signals which modulate the plasma levels of the megakaryocyte specific growth factors and thereby regulate megakaryocytopoiesis. Platelet Production Newly available techniques might be used to clarify questions related to platelet production. For example, megakaryocytes that have been genetically labeled with short-lived reporter molecules might serve as in vivo markers for quantitating platelet production. The site of megakaryocyte fragmentation might be determined by injecting the labeled cells and measuring the formation of the circulating platelets. Genetic Defects in Megakaryocytopoiesis Chromosomal abnormalities have been associated with megakaryocytic leukemias, notably in Down syndrome and in adult leukemias in otherwise genetically normal individuals. Other congenital syndromes which include defects in megakaryocytopoiesis have been identified, such as TAR syndrome and Epstein's syndrome. In addition, a number of animal models of defective megakaryocytopoiesis have been described. Characterization of the genetic abnormalities in these various conditions could provide useful information on the factors regulating megakaryocytopoiesis. Disciplines and Expertise Among the disciplines and expertise that may be appropriate for this program are hematology, biochemistry, cell biology, medicine, and molecular biology. Exclusions Epidemiological studies and large-scale clinical trials are specifically excluded from this RFA. SPECIAL REQUIREMENTS Upon initiation of the program, the NHLBI will sponsor annual meetings to encourage and exchange of information among investigators who participate in this program. In the preparation of the budget for the grant application, applicants must request additional travel funds for one meeting each year to be held in Bethesda, MD. Applicants must 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 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, 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 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 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 The NHLBI requests that prospective applicants submit, by January 15, 1993, a letter of intent that includes a brief synopsis of the proposed research and identification of any other participating institutions. 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 publication. This letter of intent is to be sent to: Dr. Charles L. Turbyfill Division of Extramural Affairs National Heart, Lung, and Blood Institute Westwood Building, Room 553 Bethesda, MD 20892 Telephone: (301) 496-7351 FAX: (301) 496-7033 APPLICATION PROCEDURES Applications are to be submitted on the research grant application form PHS 398 (rev. 9/91). This form is available in most applicant institution's offices of sponsored research or business offices; and from the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone 301/496-7441. Use the conventional format for research-project grant applications and ensure that the points identified in the Section on Review Considerations are fulfilled. FIRST Award applications must include at least three sealed letters of reference attached to the face page of the original application. FIRST Award applications submitted without the required number of reference letters will be considered incomplete and will be returned without 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 number of the RFA, Cell and Molecular Biology of Megakaryocytopoiesis, HL- 93-03-B. The RFA label available in application form PHS 398 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 your application. Send or deliver the completed application and three signed, exact photocopies of it to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** At the same time, send two additional copies of the completed PHS 398 application to Dr. Charles Turbyfill 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, 1993. An application received after this date will be considered ineligible. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by the DRG and for 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 NHLBI 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 NHLBI. The second level of review will be provided by the National Advisory NHLBI Council/Board. 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 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. The second level review will be by the National Heart, Lung, and Blood Advisory Council. AWARD CRITERIA The anticipated date of award is September 1993. 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 Inquiries regarding this request for applications to: Dr. Pankaj Ganguly Chief, Thrombosis and Hemostasis Branch Division of Blood Diseases and Resources National Heart, Lung, and Blood Institute Federal Building, Room 5C14 Bethesda, MD 20892 Telephone: (301) 402-2237 FAX: (301) 402-1622 Fiscal and administrative matters to: Ms. Jane R. Davis Chief, Blood Division Grants Management Section Division of Extramural Affairs National Heart, Lung, and Blood Institute Westwood Building, Room 4A15 Bethesda, MD 20892 Telephone: (301) 496-7257 FAX: (301) 402-1200 AUTHORITY AND REGULATIONS The programs of the Division of Blood Diseases and Resources, NHLBI, are described in the Catalog of Federal Domestic Assistance No. 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 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. $$XID RFA AI9208 AI-92-08 P1O1 ***************************************** PAPILLOMAVIRUS IN VITRO CELL CULTURE SYSTEMS NIH GUIDE, Volume 21, Number 36, October 9, 1992 RFA: AI-92-08 P.T. 34; K.W. 1002045, 0780015, 0740020 National Institute of Allergy and Infectious Diseases Letter of Intent Receipt Date: November 6, 1992 Application Receipt Date: December 10, 1992 PURPOSE The Antiviral Research Branch of the Division of Microbiology and Infectious Diseases (DMID), National Institute of Allergy and Infectious Diseases (NIAID), invites Cooperative Agreement applications from organizational entities willing to participate, with the assistance of the NIAID, in furthering innovative in vitro approaches to the study of papillomavirus infections and their therapeutic control. The goals of this solicitation are to stimulate the use of in vitro papillomavirus replication systems for research on (1) the events of papillomavirus replication and pathogenesis and (2) the antiviral potential of experimental therapeutic agents. 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), Papillomavirus In Vitro Cell Culture Systems, is related to the priority area of sexually transmitted 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 or nonprofit organizations, public and private, such as universities, medical colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government having adequate resources or access to resources to support papillomavirus in vitro cell culture research. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT Support for this program will be through the cooperative agreement (U01) funding instrument. The U01 is an assistance mechanism in which NIAID programmatic involvement with the recipient during the performance of the planned activity is anticipated. The nature of NIAID program involvement is described under SPECIAL REQUIREMENTS. The awardee will be responsible for the planning, direction, and execution of the proposed project and interrelated activities. Except as otherwise stated in this RFA, the award will be administered under PHS grants policy as stated in the Public Health Service Grants Policy Statement, DHHS Publication No. (OASH) 90-50,000, revised October 1, 1991. The total project period for applications submitted in response to the present RFA may not exceed four years. This RFA is a one-time solicitation. NIAID has no plans to reissue this announcement at any future date. Future competing continuation applications will compete under the R01 mechanism with all investigator-initiated applications and will be reviewed by an appropriate DRG study section according to the customary peer review procedures for unsolicited applications. FUNDS AVAILABLE The NIAID anticipates making at least one award as a result of this request. However, the number of awards to be made is dependent upon receipt of a sufficient number of applications of high scientific merit and upon availability of funds. Although this program is provided for in the financial plans of NIAID, awards pursuant to this RFA are contingent upon the availability of funds for this purpose. If appropriate, collaboration with other investigators or institutions is permissible. It is expected that the total direct costs for the first year for successful applications will be around $175,000. However, individual awards may be higher or lower. In general, awards will be made for a project period of up to four years. The earliest possible award date is July 1, 1993. Specific selections for awards will be made by a NIAID/DMID senior staff committee. Criteria will be scientific excellence, expertise, program balance, and cost. RESEARCH OBJECTIVES Background Papillomavirus infections are the most rapidly spreading viral sexually transmitted disease today. It is estimated that as many as 24 million people in the United States are infected with HPV. This infection not only has a serious detrimental impact on the infected individual's quality of life, but several types of the etiologic agent are almost certainly a cofactor in the development of cervical carcinoma which kills 7000 American women annually. In immunocompromised patients, warts may grow exuberantly and cause serious morbidity. In addition, recurrent respiratory papillomatosis (RRP), a fortunately rare disease believed to be acquired during passage through the birth canal of an infected mother, can be life-threatening. None of the currently available therapies, including interferon, 5-fluorouracil, cryotherapy, laser surgery and podophyllotoxin are adequate. Therefore, the NIAID made two awards in 1988 to investigators to utilize rabbit, nude mouse, and primate models of papillomavirus infections for the evaluation of experimental therapies. As a result of these studies, several compounds have been identified which appear to warrant clinical evaluation. Phase I studies of one of these, ribavirin, as a therapy for RRP have recently begun. Further preclinical study of the others, PMEG and HPMPC, members of the phosphonate family of nucleotides, are targeted for clinical studies in the near future. Although preliminary evaluations of experimental agents are performed in vitro prior to in vivo evaluation for all other DMID-supported animal models, until recently there has not been a suitable in vitro system for evaluation of anti- HPV agents. In the past few years, several research groups have developed in vitro systems in which many of the events of papillomavirus replication have been reported to occur. The availability of these systems provides an unparalleled opportunity to investigate the mechanisms of papillomavirus replication and pathogenesis at a molecular level. This basic research may also result in the identification of viral genes which are promising targets for therapeutic intervention. In addition, these systems should provide a means to evaluate the potential anti-papillomavirus activity of experimental agents and provide a rational basis for selecting agents whose activity warrants further study in the animal models. RESEARCH OBJECTIVES The research to be supported by this RFA will be focussed on the use of in vitro culture systems for studies of the multiple events of virus replication including viral DNA replication and preferably expression of late genes. The culture systems will also be used to study the effect of experimental therapeutic agents on these events. Research applications should propose an in vitro system of studying multiple replication events of papillomaviruses such as early gene expression, viral DNA replication and preferably also the expression of late genes. Applicants should also provide a description of research plans for study of compounds with therapeutic potential. SPECIAL REQUIREMENTS Terms and Conditions of Award The Cooperative Agreement mechanism involves a partnership between the recipient of the award and the NIAID. The role of the NIAID is to provide technical assistance and guidance to the Principal Investigator. The following terms and conditions pertaining to the scope and nature of the interaction will be incorporated in the Notice of Award. These agreements will be in addition to the customary programmatic and financial negotiations which occur in the administration of grants. The Terms of Award described in this section are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines; DHHS Grant Administration Regulations at 45 CFR 74; other DHHS, PHS Grant Administration Policy Statement and other NIAID administrative terms of award. Decisions regarding a change of scope of the originally funded application must be reviewed and approved by the NIAID Scientific Coordinator in accord with the PHS Grants Policy Statement. Such changes may occur due to emerging research findings of other investigators. In the event of a dispute, the decision of a three member arbitration team, described under Arbitration Procedures, will be binding. Although the NIAID Scientific Coordinator may participate in discussions on research planning and data analysis, the recipient(s) of these award(s) will be responsible entirely for the design, conduct, and analysis of their research findings. The NIAID Scientific Coordinator will not direct, nor be liable for, the awardee's research activities. The awardee will be responsible for publishing and disseminating research results. Responsibilities of the Awardee Under Cooperative Agreement assistance mechanisms, the NIH identifies general or specific program areas for support, and the performers define and implement the specific aims, objectives and approaches for their awarded project activities. The Principal Investigator defines the details for the project within the guidelines of the RFA, retains primary responsibility for the performance of the scientific activity, and agrees to accept close assistance of NIAID staff in the aspects of scientific and technical management of the project as specified in the Terms and Conditions of Award. The data obtained will be the property of the awardee who will retain custody of and primary rights to the data. The awardee will be responsible for: a. Project Implementation and Management The Principal Investigator is to define and implement the specific aims, objectives, and approaches for in vitro research on papillomaviruses. Specifically, the awardee will be responsible for: Defining research objectives and approaches in accord with his/her own interests and perceptions of novel and feasible approaches to conducting in vitro research on papillomavirus replication and the effects of experimental antiviral agents on the events of replication; Designing, planning, and conducting the necessary research protocols stipulated in the application; Ensuring that the results obtained are analyzed, interpreted, and published in a timely manner; Modifying research protocols as appropriate; and Providing information to the NIAID Scientific Coordinator concerning progress. b. Budget The Principal Investigator should adequately justify the requested budget for each twelve month segment. Budget planning must include such line items as personnel, major equipment, travel, etc. Trips to the NIAID must be projected once a year for the Principal Investigator and possibly one or two other key personnel, if appropriate. Meetings will be for the purpose of maintaining project cohesiveness, program and product standards, providing technical assistance and other expertise. The NIAID Scientific Coordinator will attend each meeting. Additional communications will be made by telephone or telephone conference call. c. Reporting Requirements An annual progress report is required. In addition, the awardee will keep the Scientific Coordinator apprised of experimental results on a more frequent basis when the research involves the evaluation of an experimental compound's anti-papillomavirus activity. d. Publications The Government, via the Scientific Coordinator, 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 the Scientific Coordinator for the preparation of internal reports on the awardee(s)' activities. However, the awardee will retain rights to the data and timely publication is encouraged. Publication or oral presentation of work done under this agreement is the responsibility of the Principal Investigator and will require appropriate acknowledgement of NIAID support. Responsibilities of the NIAID Assistance via U01s differs from the traditional research grant. In addition to the normal programmatic and administrative stewardship responsibilities, the awarding component anticipates substantial programmatic involvement during performance of the project. Under the U01 mechanism, NIAID staff will facilitate and participate in, but not direct, the research in order to ensure that research priorities for papillomaviruses are addressed. A member of the NIAID staff will serve as Scientific Coordinator and will participate as a member of the research team. The Scientific Coordinator will be the Chief, Antiviral Research Branch, DMID. The Scientific Coordinator will interact closely with the Principal Investigator to assist with and facilitate the overall research planning and data analysis. During performance of the project the NIAID Scientific Coordinator may provide assistance by participating in the design of specific research group activities; advising in the selection of sources or resources, replacement of staff; coordinating or participating in collection and/or analysis of data; and, advising in management and technical performance. Involvement of the Scientific Coordinator comprises: a. Coordination between NIAID and Awardee. The establishment of channels of collaboration and communication is expected. Shortly after any award is made, key project personnel and NIAID staff will meet to discuss provision of NIAID technical assistance in accordance with the RFA guidelines. b. Collaborative Participation: Providing assistance in avoiding unwarranted duplication of effort; Retaining the option to suggest possible changes of direction in the research endeavors based on the acquisition, and provision to the awardee, of new information; The NIAID Scientific Coordinator may suggest studies within the scope of the award's objectives and research activities; may present to the investigators experimental findings from published sources or from contract projects in support of these suggestions; and may participate in the design of experiments, and Providing assistance, when appropriate, in designing protocols and in analysis and interpretation of research data. c. Provision of Important Information and Collaborations: Principal Investigators may not have immediate access to needed information. Therefore, NIAID will facilitate meeting these needs and ensure that the awardee(s) become active participants in the Antiviral Research Branch Preclinical Research Program. This Program consists of: (a) twelve U01 awards for research on potential molecular targets for novel antivirals and strategies for the design of new agents; (b) two N01 awards for the application of standard, well-characterized assay methodologies for the evaluation of the anti- herpesvirus and anti-respiratory virus potential of large numbers of compounds; (c) seven N01 awards for animal models of human viral infections (including papillomaviruses) that are used for evaluation of experimental therapies and research on pathogenesis; and (d) five U01 awards for studies of viral replication and pathogenesis that are targeted towards the eventual development of improved diagnostic methodologies. The interaction of the awardee(s) with other investigators in this program, as well as the consequent early receipt of data from those laboratories pursuing related research goals, will facilitate and expedite research progress. d. Provision of Needed Resources The NIAID may provide assistance by suggesting potential sources of agents for antiviral evaluation and/or facilitating the obtaining of these agents by the Principal Investigator. The specific agents to be tested will be decided upon by the Principal Investigator with assistance from the Scientific Coordinator. The application should include an estimate of how many compounds with therapeutic potential will be studied annually. e. Monitoring There shall be periodic on-site or reverse-site monitoring of the status of the Principal Investigator's research. Such visits may include discussions regarding scientific technique and methodology, review of data, review of data analysis, suggestions to improve the quality of the research, staff recruitment and training, and overall evaluation efforts. In addition, the NIAID Scientific Coordinator, as a part of the annual review process, will review the status of the research, using information obtained from site visits and the annual progress reports to justify continued funding. f. Annual Meeting The NIAID Scientific Coordinator will organize an annual symposium in Bethesda, Maryland at which the Principal Investigator(s) will discuss their progress. This symposium will include other NIAID Antiviral Research Branch-supported investigators engaged in preclinical antiviral research. This symposium will facilitate evaluation of the feasibility of the attempted antiviral approaches, and will promote productive interactions among Principal Investigators. Applicants should include funds for travel to this meeting for the Principal Investigator, and other key personnel if warranted, in their proposed budget. g. Ongoing Communication In addition to the annual symposium, the NIAID Scientific Coordinator will interact informally with each principal investigator through additional meetings, averaging once a year, at the Principal Investigator's institution or at professional scientific meetings as well as by teleconferences, regular telephone calls, and written communication. Arbitration Procedures The Terms and Conditions of Award, listed in this RFA, require that the NIAID Scientific Coordinator participate in the decision-making process concerning the continuation of an award based on successful performance of the Awardee during the planning, developmental, and implementation period of the U01. Disagreements (e.g., programmatic, technical, and evaluation) arising pursuant to these approvals will be arbitrated by an Arbitration Panel composed of one award recipient designee, one NIAID designee, and a third designee, with expertise in the relevant area, chosen by the other two. These special arbitration procedures in no way affect the Awardee's right to appeal an adverse action in accordance with PHS regulations at 42 CFR, Part 50, Subpart D and DHHS regulations at 45 CFR, Part 16. LETTER OF INTENT Prospective applicants are asked to submit, by November 6, 1992, a letter of intent that includes a descriptive title of the proposed research, and the names and affiliation(s) of proposed key investigators. The NIAID requests a letter of intent in order to provide an indication of the number and scope of applications to be received. The letter of intent does not commit the sender to submit an application, nor is it a requirement for submission of an application. The letter of intent will not enter into the review of any application subsequently submitted. It 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 Chief, Microbiology and Immunology Review Section Scientific Review Branch National Institute of Allergy and Infectious Diseases Solar Building, Room 4C20 6003 Executive Boulevard Rockville, MD 20892 APPLICATION PROCEDURES Applications are to be submitted on form PHS 398 (rev. 09/91). Application kits are available at most institutional business offices, and may be obtained from: Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Westwood Building, Room 449 Bethesda, MD 20892, telephone (301) 496-7441. The format and detail applicable to regular research grant applications must be followed. For purposes of identification and processing, mark "yes" in item 2a on the face page of the application. Also in item 2, under "number" list the RFA number, which is RFA AI-92-08, and under title type in "PAPILLOMAVIRUS IN VITRO CELL CULTURE SYSTEMS". In item 2b, "type of grant program", type in "COOPERATIVE AGREEMENT". In addition, the RFA label available in the application form PHS 398 must be affixed to the bottom of the face page and placed on top of the entire package. 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 research proposed should describe plans to accommodate the RFA research program requirements and NIAID staff involvement. The original and three copies are to be mailed or delivered to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** Two copies are to be mailed or delivered to: Dr. Olivia Preble Chief, Microbiology and Immunology Review Section Scientific Review Branch National Institute of Allergy and Infectious Diseases Solar Building, Room 4C20 6003 Executive Boulevard Rockville, MD 20892 Applicants using express mail or a courier service should change the zip code to 20852 for the Solar Building. Applications must be received by both DRG and Dr. Olivia Preble by December 10, 1992. Applications received after December 10, 1992 will be returned without review or will be sent to a DRG study section as an unsolicited R01 for that study section's next review cycle. If the application submitted in response to this RFA is substantially similar to a grant application already submitted to the NIH for review, but has not yet been reviewed, the applicant will be asked to withdraw either the pending application or the new one. Simultaneous submission of identical applications will not be allowed, nor will essentially identical applications be reviewed by different review committees. Therefore, an application cannot be submitted in response to this RFA that is essentially identical to one that has already been reviewed. This does not preclude the submission of substantial revisions of applications already reviewed, but such applications must include an introduction addressing the previous critique. REVIEW CONSIDERATIONS Applications will be received by the NIH Division of Research Grants (DRG) and will usually be assigned to NIAID. Should an application contain research plans that significantly overlap with programs of another institute, PHS Referral Guidelines will prevail in the assignment of that application. Review Procedures Applications will be reviewed by DRG for completeness and by NIAID staff to determine administrative and programmatic responsiveness to this RFA. Any application that is incomplete or does not meet the minimum requirements of this RFA will be returned to the applicant without scientific peer review. Applications considered complete and responsive to the RFA may be subjected to a triage review by an NIAID peer review group to determine their scientific merit relative to the other applications in response to the RFA. The NIAID will withdraw from competition those applications judged by the triage peer review group to be noncompetitive for award and will notify the applicant Principal Investigator and the institutional official. Those applications judged to be competitive for award will be reviewed by the standard NIH dual peer review system. The initial, or first level, review for scientific and technical merit will be conducted by the Scientific Review Branch of the Division of Extramural Activities, NIAID during February/March, 1993. The second level of review will be provided by the National Advisory Allergy and Infectious Diseases Council in June, 1993. REVIEW CRITERIA o Factors to be considered in scientific evaluation of the competitive applications include: o Originality and scientific merit of research approach, design, and methodology as well as the potential scientific, technical, or medical significance of the proposed research. There will be special interest in the advantages and limitations of proposed in vitro culture systems. o Research experience and competence of the Principal Investigator and staff to conduct the proposed studies. The experience of the Investigators with in vitro culture systems for papillomaviruses and expertise in papillomavirus molecular biology are important. o Adequacy of time/effort which the Principal Investigator and staff would devote to the proposed studies. o Adequacy of facilities and resources. o Reasonableness of proposed costs. AWARD CRITERIA While scientific merit is a prime consideration for selecting applications for award, programmatic relevance, reasonableness of proposed budget, and availability of funds also will be considered. INQUIRIES Direct inquiries relevant to the programmatic aspects of this RFA to: Dr. Catherine Laughlin Chief, Antiviral Research Branch Division of Microbiology and Infectious Diseases National Institute of Allergy and Infectious Diseases Solar Building, Room 3A-22 6003 Executive Boulevard Rockville, MD 20852 Telephone: (301) 496-8285 FAX: (301) 402-1456 Direct inquiries regarding review procedures and requirements to: Dr. Olivia Preble Chief, Microbiology and Immunology Review Section Scientific Review Branch National Institute of Allergy and Infectious Diseases Solar Building, Room 4C-20 6003 Executive Boulevard Rockville, MD 20852 Telephone: (301) 496-8208 FAX: (301) 402-2638 Direct inquiries regarding fiscal matters to: Mr. Todd Ball Grants Management Branch National Institute of Allergy and Infectious Diseases Solar Building, Room 4B-22 6003 Executive Boulevard Rockville, MD 20852 Telephone: (301) 496-7075 FAX: (301) 480-3780 Timetable Letter of Intent Receipt Date: November 6, 1992 Application Receipt Date: December 10, 1992 Review by Initial Review Group: February/March 1993 Review by NIAID Advisory Council: June 1993 Earliest Award Date: July 1, 1993 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.856, Microbiology and Infectious Diseases Research. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410; as amended. Awards will be administered under PHS grants policies and Federal Regulations 42 CFR Part 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. From owner-sci-resources@net.bio.net Wed Oct 07 23:00:00 1992 Path: biosci!NET.BIO.NET!kristoff From: kristoff@NET.BIO.NET (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 21, no. 36, pt. 2, 9 October 1992 Message-ID: Date: 8 Oct 92 23:55:34 GMT Sender: kristoff@net.bio.net Distribution: bionet Lines: 1313 $$XID NIHGUIDE 19921009 V21N36 P2O2 ************************************ unusual merit, need and promise, and in accordance with PHS policy governing such awards. Foreign institutions are not eligible for First Independent Research Support and Transition (FIRST) Awards (R29). MECHANISM OF SUPPORT This RFA solicits applications for the National Institutes of Health (NIH) individual research grant (R01) and FIRST (R29) awards 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 in September 1993. Administrative adjustments in project period and/or amount of support may be required at the time of the award. 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 Although the financial plans for fiscal year 1993 include $1.5 million for this program, award of grants pursuant to this RFA is contingent upon receipt of funds for this purpose. It is anticipated that about six 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. 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. If collaborative arrangements involve sub-contracts with other institutions, the NHLBI Grants Operations Branch (telephone 301-496-7257) may be consulted regarding procedures to be followed. RESEARCH OBJECTIVES The following are only examples and prospective applicants are urged to use their own ideas as to the area of research. Development of Cell Lines and Culture Systems The critical molecular events that lead to commitment of progenitor cells to the megakaryocytic lineage and to complete maturation of megakaryocytes to platelet production have not been identified. These studies require the development of cell lines that can enter and complete the normal maturation cycle. Immortalized cell lines could be generated that can be triggered to undergo differentiation under restricted conditions. Another approach would be to develop bone marrow culture systems that allow the transition of stem cells to megakaryocytes to be specifically monitored. This approach could employ precursor cells isolated from transgenic mice that possess megakaryocyte-specific promotors coupled to reporter molecules in conjunction with purified hematopoietic growth factors. The role of known oncogenes, growth factor receptors, and other signaling proteins could be investigated in the above systems with dominant negative suppressor techniques, antisense approaches, or injection of specific neutralizing antibodies. The function of previously unidentified components might be sought by somatic cell genetic techniques coupled to expression cloning methods. Nuclear and Cytoplasmic Development The biochemical steps that are responsible for the development and extent of polyploidy and for maturation of the cytoplasm and the formation of granule and membrane systems are not defined. The molecules that are specific to megakaryocytes and to different stages of development must be defined; new markers other than those currently used in studies of platelets should be sought. The cis acting regions and transacting factors of genes specifically expressed in megakaryocytes should be determined, and the effects of hematopoietic growth factors and cytokines on these events should be assessed. Specific areas of study that might elucidate nuclear development include the role of cyclins, kinases, phosphatases, and contractile proteins in endomitosis. Specific areas of study regarding cytoplasmic development include stage-specific events in granule formation and synthesis of membrane and cytoskeletal components, including targeting of proteins to specific structures. The mechanism by which the cytoplasm becomes organized into the mature platelets is unknown, and studies that could address this question would be useful. It would also be important to identify the specific growth factors that control nuclear and cytoplasmic development and platelet formation. Sensors and Signals Investigations are needed to clarify the sensors and molecular signals that modulate the plasma levels of the megakaryocyte specific growth factors and thereby regulate megakaryocytopoiesis. Platelet Production Newly available techniques might be used to clarify questions related to platelet production. For example, megakaryocytes that have been genetically labeled with short-lived reporter molecules might serve as in vivo markers for quantitating platelet production. The site of megakaryocyte fragmentation might be determined by injecting the labeled cells and measuring the formation of the circulating platelets. Genetic Defects in Megakaryocytopoiesis Chromosomal abnormalities have been associated with megakaryocytic leukemias, notably in Down syndrome and in adult leukemias in otherwise genetically normal individuals. Other congenital syndromes that include defects in megakaryocytopoiesis have been identified, such as TAR syndrome and Epstein's syndrome. In addition, a number of animal models of defective megakaryocytopoiesis have been described. Characterization of the genetic abnormalities in these various conditions could provide useful information on the factors regulating megakaryocytopoiesis. Special Requirements 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 must request additional travel funds for one meeting each year to be held in Bethesda, MD. Applicants must also include a statement in the applications indicating their willingness to participate in such meetings. 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 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 The NHLBI requests that prospective applicants submit a letter of intent that includes a descriptive title of the proposed research and identification of other participating institutions. 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 not acknowledged. A letter of intent is not binding, will not enter into the review of any application subsequently submitted, nor is it a necessary requirement for application. This letter of intent, which must be received by January 15, 1993, is to be sent to: Dr. Charles L. Turbyfill Division of Extramural Affairs, National Heart, Lung, and Blood Institute Westwood Building, Room 553 Bethesda, MD 20892 APPLICATION PROCEDURES Applications are to be submitted on the research grant application form PHS 398 (rev. 9/91). This form is available from most applicant institution's office of sponsored research or business office and from the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, 5333 Westbard Ave, Room 449, Bethesda, MD 20892. FIRST Award applications must include at least three sealed letters of reference attached to the face page of the original application. FIRST Award applications submitted without the required number of reference letters will be considered incomplete and will be returned without review. Application Receipt Date: March 15, 1993 REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by the DRG and for responsiveness to the objectives of the RFA 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 judged to be responsive will be reviewed for scientific and technical merit by an initial review group that will be convened by the Division of Extramural Affairs, NHLBI, solely to review these applications. This initial review will include a preliminary evaluation to determine scientific merit relative to the other applications received in response to the RFA (triage); the NHLBI will withdraw from further consideration applications judged to be noncompetitive and notify the Principal Investigator/program director and the applicant organization. Those applications judged to be competitive will be further evaluated for scientific/technical merit by the usual peer review procedures. The second level review will be by the National Heart, Lung, and Blood Advisory Council. INQUIRIES Inquiries regarding this program and requests for the RFA document to: Dr. Pankaj Ganguly Chief, Thrombosis and Hemostasis Branch Division of Blood Diseases and Resources National Heart, Lung, and Blood Institute Federal Building, Room 5C14 Bethesda, MD 20892 Telephone: (301) 402-2237 FAX: (301) 496-9940 Fiscal and administrative matters to: Ms. Jane R. Davis Chief, Blood Division Grants Management Section Division of Extramural Affairs National Heart, Lung, and Blood Institute Westwood Building, Room 4A15 Bethesda, MD 20892 Telephone: (301) 496-7257 FAX: (301) 402-1200 AUTHORITY AND REGULATIONS The programs of the Division of Blood Diseases and Resources, NHLBI, are described in the Catalog of Federal Domestic Assistance No. 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-93-004 ************************************************ SELECTIVE COGNITIVE DEFICITS IN NEURODEVELOPMENTAL DISORDERS NIH GUIDE, Volume 21, Number 36, October 9, 1992 PA: PA-93-004 P.T. 34; K.W. 0414005, 0715138, 1002030 National Institute of Neurological Disorders and Stroke PURPOSE The National Institute of Neurological Disorders and Stroke (NINDS) encourages the submission of research grant applications to pursue a promising new approach to cognitive neuroscience that will identify relations between cognitive function and neurostructure through the study of specific, atypical patterns of cognitive deficit associated with neurodevelopmental syndromes of known or suspected biological origin. Examples of three clinical entities that can be studied from this perspective are Williams syndrome, Turner syndrome and autism. An FY 91 NINDS workshop was devoted to the discussion and confirmation of the usefulness of in depth, systematic investigation of patterns or profiles of selective cognitive impairment in these unusual conditions. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention goals of "Healthy People 2000," a PHS-led national activity for setting priorities. This Program Announcement, Selective Cognitive Deficits in Neurodevelopmental Disorders, is related to the priority areas of infant health, chronic disabling conditions, and the related area of the neurological basis of cognition. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: No. 017-001-474-0, 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 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) Awards (R29), program project grants (P01), and center grants (P50). Applications from minority individuals and women are encouraged. MECHANISMS OF SUPPORT The support mechanisms for grants in this area will be the traditional investigator-initiated research project grant (R01), the FIRST award (R29), the program project grant (P01), and the center grant (P50). As consistent with the aforementioned mechanisms, the Principal Investigator or program director, as well as any participating investigators, will plan, direct, and perform the research. Applicants for program project grants should contact the NINDS representative listed below as early as possible in the planning stages. RESEARCH OBJECTIVES Most of the knowledge about the neurological bases of cognitive function in humans has been learned from studies of central nervous system trauma or disease in adults. Certain experiments of nature seen in neurodevelopmental syndromes affect the central nervous system in unique ways by producing specific as opposed to generalized cognitive deficit. Studies of these disorders, utilizing neurobiological and behavioral techniques, can be expected to yield new insights into the localization of cognitive function and the developmental course of the syndromic cognitive profiles. An example of this approach is an ongoing study of the biological basis of language and other cognitive functions in which behavioral, neuroanatomic, and neurophysiologic studies are being carried out in patients with Williams syndrome, a rare metabolic disorder. Children with this sporadically occurring condition have distinctive facial characteristics, low birth weight, digestive disorders in infancy, mental retardation, mild microcephaly, apparent sensitive hearing and supravalvular aortic stenosis. A unique behavioral profile has been identified in these patients in which there is a striking fractionation of higher cortical functions with linguistic abilities selectively preserved in the face of severe cognitive deficits. Studies of the development of language in Williams syndrome children are being conducted in conjunction with studies of brain structure and function to address specific questions about the neural substrate for this unusual neuropsychological profile. This research, and similar investigations, will contribute to our understanding of brain organization for language, and other cognitive functions, using a specific neurodevelopmental disorder as a model. Such an approach provides an unusual opportunity to investigate central issues of developmental cognitive neuroscience. In a parallel and possibly related investigation of autism, a developmental disorder characterized by a profound deficiency in social knowledge, affect, and communication, a new finding demonstrates severe impairment in ability to shift attention, a necessary developmental precursor to social communication. Evidence is presented that relates this deficit to neuroanatomic abnormalities found in the cerebellum of autistic patients in both autopsy and magnetic resonance imaging (MRI) studies and to findings of damage to the parietal lobe of the cerebrum as well. There is a clear contrast between autism and Williams syndrome in both behavioral deficits and neuroanatomic findings. Most autistic children have aberrant language development and marked deficits in social communication and patients with Williams syndrome have spared linguistic abilities, but general cognitive impairment, and show an intensity of affect, especially in social interaction. The basis for these behavioral distinctions may be the differences in neocerebellar structures for which the autistic and Williams syndrome subjects show divergent morphology. Turner syndrome is a genetic disorder associated with monosomy X that is characterized by a variety of somatic and cognitive deficiencies. The classical features of the syndrome include short stature, webbed neck, a broad chest, cubitus valgus, and failure of gonadal development. While females with Turner syndrome typically have normal verbal IQ scores, they consistently show selective impairments in tasks that are included in tests of performance IQ. The results of most studies present clear impairment in performance in spatial rotation and left-right discrimination tasks. Other studies report deficits in visual-spatial memory, visual-motor coordination, and motor learning. Slower motor responses have also been demonstrated in females with Turner syndrome. The etiology of these cognitive deficits is still unknown and there is considerable inter-individual variation in the neurocognitive phenotype of Turner syndrome. However, right hemisphere involvement is certainly indicated. Current studies are addressing the problems of variations in patterns of cognitive abilities with variations in karyotype in Turner syndrome, changes in patterns of cognitive abilities in response to hormone therapies, sources of deficits in social cognition, and neurophysiological indications (event-related potentials) of altered brain development in Turner syndrome. More extensive investigations of the etiologies and effects of these syndromes and carefully designed studies of other syndromes and conditions that result in atypical patterns of cognitive deficit are encouraged. Examples are various types of hydrocephaly and the fragile X syndrome. Because of the multi-leveled approach--behavioral, neurophysiological, and neuroanatomic--and the likelihood of small samples, multidisciplinary and collaborative studies will be most appropriate. 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 must be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale must be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues should be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information must be included in the form PHS 398 in Section 1-4 of the research plan AND summarized in Section 5, Human Subjects. Applicants/offerors are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., Native Americans (including American Indians or Alaskan Natives), Asian/Pacific Islanders, Blacks, Hispanics). The rationale for studies on single minority population groups must be provided. For the purpose of this policy, clinical research is defined as human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including but not limited to clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded. However, every effort should be made to include human tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. For foreign awards, the policy on inclusion of women applies fully; since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. If the required information is not contained within the application, the review will be deferred until the information is provided. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question(s) addressed and the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and will be reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. APPLICATION PROCEDURES Applications are to be submitted on the grant application form PHS 398 (rev. 9/91) according to instructions contained in the application kit. Application kits are available from most institutional offices of sponsored research and may be obtained from the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone 301-496-7441. Check "yes" in item 2a on the face sheet of the application and type "Selective Cognitive Deficits in Neurodevelopmental Disorders." FIRST Award applications must include at least three sealed letters of reference attached to the face page of the original application. FIRST Award applications submitted without the required number of reference letters will be considered incomplete and will be returned without review. Applicants for the P01 or P50 must use the application format described in the NINDS pamphlet, NINDS GUIDELINES: PROGRAM PROJECT AND RESEARCH CENTER GRANTS (Revised June 1992). Deadlines for the receipt of applications are February 1, June 1, and October 1. The completed original application and five exact copies must be sent or delivered to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** If the application is for a program project or center grant, please send the original and three copies to the Division of Research Grants. An additional two copies sent to the address below would be useful for expediting the processing of applications for multidisciplinary efforts. Applications will be assigned on the basis of established Public Health Service referral guidelines. Applications will be judged on scientific merit and program relevance in accordance with NIH policy and procedures involving peer review. An initial review will be made by an appropriate study section of the Division of Research Grants for research grants (R01) and FIRST awards (R29), and by an appropriate institute committee for program projects (P01) and centers (P50). A second level of review will be made by an appropriate national advisory council. AWARD CRITERIA Applications assigned to the NINDS will compete for available funds with all other approved applications assigned to the NINDS. The following will be used 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 For further information regarding this announcement, potential applicants may write or call: Sarah H. Broman, Ph.D. Developmental Neurology Branch National Institute of Neurological Disorders and Stroke Federal Building, Room 8C-06 Bethesda, MD 20892 Telephone: (301) 496-5821 For fiscal and administrative inquiries regarding this announcement, potential applicants may write or call: Dwight Mowery Grants Management Branch National Institute of Neurological Disorders and Stroke Federal Building, Room 1004 Bethesda, MD 20892 Telephone: (301) 496-9231 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance Nos. 93.853 and 93.854. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-150, 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. $$P1 END ************************************************************ $$P2 BEGIN PA-93-005 ************************************************ ARTHRITIS & SKIN DISEASES (MINORITY POPULATIONS) NIH GUIDE, Volume 21, Number 36, October 9, 1992 PA NUMBER: PA-93-005 P.T. 34, FF; K.W. 0715010, 0715185 National Institute of Arthritis and Musculoskeletal and Skin Diseases PURPOSE The National Institute of Arthritis and Musculoskeletal and Skin Diseases invites investigator-initiated grant applications and supplemental applications to carry out clinical and epidemiologic studies on the etiology, treatment, and prevention of arthritis, musculoskeletal, and skin diseases in minority populations and other populations at special risk. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This program announcement, Arthritis and Skin Diseases (Minority Populations), is related to the priority area of chronic disabling conditions and surveillance objectives. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Research grant applications may be submitted by domestic and foreign for profit and non-profit organizations, public and private, such as local governments, and eligible agencies of the Federal Government. Applications with minority individuals and women as Principal Investigators are encouraged. Foreign institutions are not eligible for First Independent Research Support and Transition (FIRST) Awards (R29). Applicants for the Clinical Investigator Awards (K08) and Individual National Research Service Awards (F32) must be U.S. citizens, non-citizen nationals, or non-citizens lawfully admitted for permanent residence. Applicants for the F32 Award must have received a doctorate degree as of the beginning date of the NRSA appointment. Applicants for the K08 Award must have an M.D. or equivalent degree. Applicants for the Fogarty International Research Collaboration Award (FIRCA) Award must be U.S. scientists who are Principal Investigators of NIH Research Project Grants (R, P, or U01 series) that are active and funded during the proposed FIRCA grant award period. Recipients of K awards are not eligible. For the FIRCA Award, the foreign collaborator's institution must be located in a country in the geographical regions commonly known as Central and Eastern Europe (including the former USSR), Latin America, and the non-US Caribbean. MECHANISMS OF SUPPORT Applications for the following mechanisms are considered appropriate responses to this announcement: the traditional research project grant (R01) and the FIRST Award (R29), the Clinical Investigator Award (K08), and the Individual National Research Service Award (F32). In addition, the FIRCA funding mechanism may be used by NIH grantees in the U.S. to collaborate with foreign investigators. Joint efforts between U.S. and foreign investigators are encouraged. Because the nature and scope of the research proposed in response to this RFA may vary, it is anticipated that the size of an award will vary also. SUMMARY o Background Major gaps in knowledge still exist about the incidence, prevalence, and natural history of most of the rheumatic, musculoskeletal, and skin diseases. The skin diseases in particular have lacked epidemiologic research. Although both cross-sectional and longitudinal studies are lacking for many diseases, the greatest need is for longitudinal investigations. Some population-based longitudinal data sources are available for studies of rheumatic diseases and osteoporosis, e.g., Framingham, Massachusetts; Rochester, Minnesota; NHANES I and Followup; and the Study of Osteoporotic Fractures (SOF). In the past decade, epidemiologic studies have made some progress in describing the frequency of osteoarthritis and some skin diseases, based upon nationally collected data by the National Center for Health Statistics. Epidemiologic studies from defined populations have contributed knowledge about cohorts at increased risk of disease, e.g., rheumatoid arthritis in Pima Indians and the higher incidence, prevalence, and mortality of systemic lupus erythematosus in Black females than in Caucasian and male populations. However, the key question, why some cohorts remain at increased risk of disease, is still unanswered. In general, less is known about the occurrence of arthritis, musculoskeletal, and skin diseases in American Blacks than in whites. Even less is known about other American minority groups. Data are also lacking on these diseases in children and the elderly. o Research Objectives and Scope The primary objective of this program announcement is to foster epidemiologic research in minority groups and other populations at special disease risk. Studies to be encouraged include: o The descriptive pattern of arthritis, musculoskeletal and skin diseases in populations o The etiology and modes of transmission of these diseases, including the relative contribution of both genetic and environmental factors influencing both the onset and course of the disease o Studies of disease burden, specifically on the frequency, cost, and personal and social sequelae of arthritis and musculoskeletal and skin diseases o New diagnostic technologies to update or develop criteria for the diagnosis and staging of many rheumatic and skin diseases and to define homogeneous clinical subsets for epidemiologic and basic science studies o Studies to generate and test etiologic hypotheses, especially for less studied rheumatic, musculoskeletal, and skin diseases o Family studies to evaluate the interplay of genetic and environmental contributions to the development and progression of rheumatic, musculoskeletal, and skin diseases o Longitudinal studies to describe the prognosis and outcomes among patients with rheumatic, musculoskeletal, and skin diseases, and to identify risk factors for disease onset, progression, and disability o Practical outcome assessment tools to define the impact of different medical, surgical, and rehabilitation management approaches for arthritis, musculoskeletal and skin diseases STUDY POPULATIONS Epidemiologic studies of the general population at risk for disease, as well as patient populations that have been diagnosed to have the diseases, will be accepted. Although new research projects are desired, applications based on on-going studies that were conceived for reasons other than the purposes of this program announcement are also encouraged. SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements are required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis must be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale must be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues should be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information must be included in the form PHS 398 (rev. 9/91) in Sections 1-4 of the Research Plan AND summarized in Section 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., Native Americans (including American Indians or Alaskan Natives), Asian/Pacific Islanders, Blacks, Hispanics). The rationale for studies on single minority population groups must be provided. For the purpose of this policy, clinical research is defined as human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including but not limited to clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded. However, every effort should be made to include human tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. For foreign awards, the policy on inclusion of women applies fully; since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. If the required information is not contained within the application, the review will be deferred until the information is provided. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and will be reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. APPLICATION PROCEDURES Applications for the R01, R29, K08, and FIRCA awards 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. FIRST (R29) Award applications must include at least three sealed letters of reference attached to the face page of the original application. First Award applications submitted without the required number of reference letters will be considered incomplete and will be returned to the applicant without review. The receipt dates for applications for AIDS-related research are also found in the PHS 398 (rev. 9/91) application kit. Supplemental application instructions for the K08 Award and the application dates are available in the publication "The K Awards" (rev. 10/91). Supplemental application instructions for the FIRCA award are available from the John E. Fogarty International Center. Applications for the FIRCA Award must include a letter of collaboration from the foreign investigator and the foreign investigator's biographical sketch, resources, and environment. Applications for the F32 Award are to be submitted on form PHS 416-1 and must include letters of reference and other supplemental material. Application kits and information booklets including relevant receipt dates are available at most institutional offices of sponsored research and may be obtained from the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone 301/496-7441. 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 the appropriate number of legible copies, as specified in the application kits, must be sent or delivered to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** REVIEW PROCEDURES Applications will be assigned on the basis of established Public Health Service referral guidelines. Applications will be reviewed for scientific and technical merit in accordance with the standard NIH peer review procedures. FIRCA Award applications will be reviewed by an initial review committee convened by the Fogarty International Center. Following scientific-technical review, the applications will receive a second- level review by an appropriate advisory council. AWARD CRITERIA Applications will compete for available funds with all other approved applications. The following will be considered in making funding decisions: o Quality of the proposed project as determined by peer review o Availability of funds o Program balance among research areas of the announcement Additional criteria for R29 and F32 applications include the potential for the applicant to carry out independent research, the quality of education, scientific training, research experience, and commitment to a research career, as well as the institutional commitment. Further criteria for F32 applications include the quality of the sponsor and training environment and the reference reports. 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: Ms. Reva C. Lawrence Epidemiology/Data Systems Program Officer National Institute of Arthritis and Musculoskeletal and Skin Diseases Building 31, Room 4C-13 Bethesda, MD 20892 Telephone: (301) 496-0434 Direct inquiries regarding fiscal matters to: Ms. Diane M. Watson Grants Management Officer National Institute of Arthritis and Musculoskeletal and Skin Diseases Westwood Building, Room 4A15C Bethesda, MD 20892 Telephone: (301) 496-7257 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.846, Arthritis, Musculoskeletal and Skin Diseases Research. Awards will be made under the authority of the Public Health Service Act, Title III, Section 301 (Public Law 410, 78th Congress, as amended, 42 USC 241) and administered under PHS grants policies and Federal regulations 42 CFR Part 52 and 45 CFR Part 74. This program is not subject to intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$P2 END ************************************************************ ERRATUM $$E1 BEGIN R2 19920925 APPEND RFA HL-92-11-P BOTH ********************** DIETARY PATTERNS AND BLOOD PRESSURE NIH GUIDE, Volume 21, Number 36, October 9, 1992 RFA: HL-92-11-P P.T. 34; K.W. 0710095, 0715115, 0755015 National Heart, Lung, and Blood Institute Letter of Intent Receipt Date: December 1, 1992 Application Receipt Date: January 15, 1993 This is to announce a change in the Letter of Intent Receipt Date and the Application Receipt Date that published in the NIH Guide for Grants and Contracts, Vol. 21, No. 34, September 25, 1992. The new Letter of Intent Receipt Date is December 1, 1992 (changed from November 1, 1992). The new Application Receipt Date is January 15, 1993 (changed from December 1, 1992). $$E1 END ************************************************************ $$XID RFA HD9401 HD-94-01 P1O1 ***************************************** SPECIALIZED RESEARCH CENTER PROGRAMS OR CENTER CORE GRANTS TO SUPPORT RESEARCH IN REPRODUCTION NIH GUIDE, Volume 21, Number 36, October 9, 1992 RFA: HD-94-01 P.T. 04; K.W. 0413002, 0710110, 0710115, 0710030 National Institute of Child Health and Human Development Letter of Intent Receipt Date: January 2, 1993 Application Receipt Date: May 18, 1993 PURPOSE The National Institute of Child Health and Human Development (NICHD) provides funding for a limited number of research centers in the reproductive sciences. These centers are broadly based investigative endeavors encompassing research of a biomedical nature. They are supported through either Center Core Grants (P30) or Specialized Research Center Grants (P50). These centers form a national network that fosters communication, innovation, and high quality research. Reproductive Sciences Research Centers provide a stimulating, multidisciplinary environment that attracts and nurtures both established and promising young investigators. Each Center works closely with the NICHD staff in participating in a Center Network and in carrying out its objectives in a manner consistent with the goals and mission of the NICHD. BACKGROUND The Reproductive Sciences Branch (RSB) of the Center for Population Research (CPR) of the NICHD supports basic and clinical research on reproduction that relies on a variety of approaches in biomedical sciences. Among the grant mechanisms used to provide research support, the RSB uses: (1) Specialized Research Center Grants (P50s) which support integrated groups of research projects and supporting core service facilities. The research activities included in such project grants must comprise, by definition, a multidisciplinary approach to biomedical problems in reproduction. These research programs may have more than one theme, focus, or emphasis but all of the projects involved must be responsive to one or more specific research areas of reproduction promulgated by the RSB. (2) Center Core Grants (P30s) which support Center Core facilities designed to enhance existing federally supported research projects within the purview of the RSB, CPR, NICHD. Such center awards require a critical mass of individual awards for which coordinated technical support would be cost-effective to the NIH. Core Grants provide no funds for the direct support of research projects other than for new program development; however, by making cost-effective resources and facilities available, they enhance the productivity of existing projects that are either integrated in a specialized research area or organized within a central theme of research. At present, the RSB supports a fixed number of centers with a commitment of five years of support that is competitively renewable for additional five-year periods. Committed support for one P50 Center and three P30 Centers ends in FY 1994, and it is anticipated that these Centers will submit renewal applications. While there are no additional Center positions available at this time, new groups of investigators, in addition to the current awardees, are invited to compete for the existing four positions in FY 1994. 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 RFA, Specialized Research Center Programs or Center Core Grants to Support Research in Reproduction, is related to the area of family planning. 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 Domestic institutions are eligible to apply for these centers. Applications prepared for this competition may not propose multi-institutional consortium arrangements. In order to receive funding, an individual domestic institution's application for a specialized reproductive research center (P50) must have three or more related, integrated, and high quality research projects that provide a multidisciplinary, yet thematic, approach to the problems to be investigated. These research projects may be accompanied by an appropriate number and type of core facilities, as described below, providing cost-effective technical support. The concurrent submission of an R01 or R29 research project application to do essentially the same research as that proposed in a subproject of a P50 Center application is permissible within the context of extant NIH policy. As a general policy, preference in selection for funding by NICHD will be given to the subprojects of the P50 Center in order to maintain the integrity of the program and the validity of its merit assessment. The coincident R01 or R29 application(s) will usually be expected to be withdrawn or relinquished. P50 projects must address one or more of the announced biomedical topics to be eligible for funding. A domestic institution's application for a reproductive sciences research Center Core facility (P30) must be predicated on the existence of a comprehensive research base in the reproductive sciences comprised of a substantial number of relevant, eligible, and funded research grants which will be active on April 1, 1994. Such grant projects must directly address one or more of the announced biomedical topics to be eligible for inclusion in the center. A majority of these grants must be supported by the NICHD. In addition, the eligibility for funding a core in a P30 Center is determined by the demonstrated need of a minimal number of three relevant NIH (or other federally reviewed and funded) research grants from the research base in the application. P30 Center grant funds support only active users of the core facilities and services from the research base (projects) proposed in the Center grant application and only serve programs of scientific research relevant to the mission of the RSB, CPR. Core facilities eligible for support under this announcement are organized activities directly providing reagents, assays, sophisticated technical services and technical expertise in areas required by multiple projects of a center. Such Core facilities neither directly conduct project type research nor serve as a funding source for non-Center technical services available elsewhere at the institution. It is expected that such Core facilities will be organized to provide training only for eligible users and only to the extent necessary to utilize the Core effectively. The general guideline request for information demonstrating research training program history and availability pertains to discussing the overall richness of the environment of the Center's setting and should not be confused with Core service needs per se. If a New Program Development (NPD) component is requested, it must be a single investigator's project description with a research plan formatted in the usual NIH research project style. Sufficient detail should be provided to allow a full peer-review evaluation of its merits. New Specialized Research Center Grant (P50) applications may not request more than $600,000 in direct costs for the first year. New Center Core Grant (P30) applications may not request more than $500,000 in direct costs for the first year. Renewal applications from existing P30 or P50 Centers may not request initial year direct costs exceeding 120 percent of the Council recommended direct costs for the final year of the preceding project period. Unless prior written approval of the NICHD has been obtained, applications with requests exceeding these guidelines will be administratively withdrawn by the NICHD and returned to the applicant. MECHANISM OF SUPPORT The support mechanisms for these programs are the P50 Specialized Reproductive Sciences Research Center Grant and the P30 Reproductive Sciences Research Center Core Grant. The applications should be prepared in a manner consistent with the policy and instructional details of this RFA and the general guidelines presented in the publications entitled either P50 SPECIALIZED RESEARCH CENTER GRANT GUIDELINES or P30 CENTER CORE GRANT GUIDELINES that are available from the NICHD offices listed below. The current policies and requirements that govern the research grant programs of NIH will prevail (Code of Federal Regulations, Title 42, Part 52 and Title 45, Part 75). The total project period for applications submitted to this RFA is five years. The anticipated award date will be April 1, 1994. FUNDS AVAILABLE Although this solicitation is included in the fiscal plans for FY 1994, support for these center grants is contingent upon the receipt of funds for these purposes. The number of grants to be awarded is also contingent upon a sufficient number of applications receiving high enough levels of merit to be considered for an award. It is expected that up to four awards will be made as a result of this announcement within the expected total costs limit of $3,600,000 available for the first year. RESEARCH OBJECTIVES The ultimate goals of biomedical research in the reproductive sciences are to develop new knowledge leading to clinical applications that will enable men and women to control their fertility with methods that are safe, effective, inexpensive, reversible, and acceptable to various population groups, and to overcome problems of infertility and reproductive disorders. Domestic U.S. Reproductive Sciences centers designated as "Specialized Reproductive Sciences Research Centers" (P50s) and as "Reproductive Sciences Research Centers" (P30s) are awarded funds for the support of comprehensive reproductive research programs of high quality that focus on topics deemed to be of high priority and significance because of their critically important relationship to the mission of the RSB, CPR. This Request for Applications (RFA) is specifically designed to stimulate the reproductive sciences research community to organize or to maintain reproductive sciences research centers of outstanding quality that, serving as national research resources, form a network that fosters communication, innovation, and high quality research. Applications are encouraged for the biomedical topics listed below: 1. Reproductive medicine: Fertility and infertility aspects 2. Mechanism(s) of follicular selection, atresia and ovulation 3. Neuroendocrinology of reproduction: Clarification of the regulatory mechanisms of the hypothalamo-pituitary-gonadal axis related to fertility 4. Regulatory mechanism(s) of gametogenesis 5. Mechanism of action of reproductive hormones, particularly at the cellular and genetic level; modification of action by growth factors 6. Mechanisms regulating gonadal or genital tract functions 7. Studies on fertilization, preimplantation embryo development, or blastocyst implantation 8. Immunological mechanisms regulating fertility SPECIAL REQUIREMENTS Applicants must request travel funds to attend an annual meeting of the directors of P50s and P30s. 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 (rev. 9/91) in Sections 1-4 of the Research Plan AND summarized in Section 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., Native Americans (including American Indians or Alaskan Natives), Asian/Pacific Islanders, Blacks, Hispanics). The rationale for studies on single minority population groups should be provided. For the purpose of this policy, clinical research includes human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including but not limited to clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded. However, every effort should be made to include human tissues from 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 Interested applicants should contact the RSB staff for an advisory consultation regarding reproductive sciences center grants (P50s and P30s). If an applicant intends to apply, it is strongly recommended, but not mandatory, that the applicant send a letter of intent to the RSB staff at the address listed below by January 2, 1994. This letter is to include a list of the titles of relevant research projects to be associated with the center, and the names of relevant key investigators. The letter of intent should be received by the RSB no later than January 2, 1993, but applicants are encouraged to send it as soon as they decide to apply for the grant so that the RSB staff can be of maximum assistance in the application process. The letter of intent is to be sent to the RSB staff contact listed at the end of this RFA. APPLICATION PROCEDURES The grant application form PHS 398 (rev. 09/91) is to be used to prepare these applications. The RFA number (HD-94-01) and the type of center grant request (P50 or P30) must be indicated on the face page of the application in item 2a. The RFA label available in the PHS form 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. The PHS 398 form is available from most business offices or grant/contract offices at most institutions and can also be obtained from NIH by calling 301/496-7441. It is especially important that applicants obtain and follow the supplemental NICHD guidelines for preparing the application. These guidelines address special organizational aspects that require certain tabulations in addition to the usual instructions. Applications must be submitted by May 18, 1993. Send or deliver the original, completed, signed application and three, signed complete copies to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** In addition to those applications mailed to the Division of Research Grants, two copies of the application must be sent under separate cover directly to: Laurance Johnston, Ph.D. Division of Scientific Review National Institute of Child Health and Human Development Building 6100, Room 5E01 Bethesda, MD 20892 Late applications will not be accepted and will be returned to the applicants. REVIEW CONSIDERATIONS An administrative review of the application will be performed by the Review, Program, and Grants Management staff for conformance to NIH policy and NICHD guidelines, as well as for relevance to the program purview of the RSB. Applications that fail to comply with NIH policy and/or NICHD guidelines will be formally returned to the applicant. Applications may be subjected to a triage by a peer review group to determine their potential competitiveness relative to other applications submitted. The Institute will withdraw from competition those applications judged by the triage procedure to be noncompetitive and notify the applicants and institutional business officials. Those applications judged to be competitive will be further evaluated by peer review for scientific/technical merit. The Scientific Review Administrator (SRA) of the Population Research Committee (PRC), NICHD, may forward the application to selected members of the PRC for their evaluation to determine if a site visit is needed. A site visit, however, is not a prerequisite for consideration of an application by the PRC. If a site visit is required, the SRA will communicate with the applicant for the visit arrangements as described in the guidelines. The initial review for scientific merit will be carried out by the PRC in November 1993. The second-level review will be made by the National Advisory Child Health and Human Development Council in January 1994. The earliest possible funding date is April 1, 1994. Review procedures and criteria are detailed in the P50 SPECIALIZED RESEARCH CENTER GRANT GUIDELINES and P30 CENTER CORE GRANT GUIDELINES (available from the NICHD offices listed below). AWARD CRITERIA The anticipated date of award is April 1, 1994. Funding decisions will be based on the IRG and NACHHD Council recommendations, program relevance, and the availability of funds. INQUIRIES For further information regarding programmatic issues, contact: Julia Lobotsky, M.S. Reproductive Sciences Branch Center for Population Research National Institute of Child Health and Human Development Building 6100, Room 8B01 Bethesda, MD 20892 Telephone: (301) 496-6515 For information on budget and fiscal matters, contact: Melinda Nelson Office of Grants and Contracts National Institute of Child Health and Human Development Building 6100, Room Bethesda, MD 20892 Telephone: (301) 496-5481 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.864, Population Research. Awards will be made under the authority of the Public Health Service Act 301 (42 USC 241) and 441 (USC 289d) and administered under PHS grants policies and Federal Regulations 42 CFR Part 52 and 45 CFR Part 74. This program is not subject to A-95 or Health Systems Agency review. From owner-sci-resources@net.bio.net Wed Oct 07 23:00:00 1992 Path: biosci!NET.BIO.NET!kristoff From: kristoff@NET.BIO.NET (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 21, no. 36, pt. 5, 9 October 1992 Message-ID: Date: 8 Oct 92 23:59:10 GMT Sender: kristoff@net.bio.net Distribution: bionet Lines: 981 $$XID RFA AI9213 AI-92-13 P1O1 ***************************************** WOMEN AND INFANTS TRANSMISSION STUDY (WITS II) NIH GUIDE, Volume 21, Number 36, October 9, 1992 RFA: AI-92-13 P.T. 34, AA, II; K.W. 0715008, 0715125, 0785055, 0745020 National Institute of Allergy and Infectious Diseases Letter of Intent Receipt Date: October 26, 1992 Application Receipt Date: January 14, 1993 PURPOSE The Vaccine Trials and Epidemiology Branch of the Division of AIDS (DAIDS) of the National Institute of Allergy and Infectious Diseases (NIAID) announces a Request for Applications (RFA) for funding the continuation of the Women and Infants Transmission Study (WITS). The purpose of this RFA is a competitive renewal of WITS I, a multi-site epidemiologic cohort study of HIV infected pregnant women and their offspring. New sites not participating in WITS I are encouraged to apply, as are current WITS I sites. Specific aims are: (1) to assess the effects of pregnancy on HIV disease progression, (2) determine maternal cofactors related to maternal-infant transmission and timing of transmission, (3) assess early diagnostic techniques to identify HIV-infected fetuses and infants, (4) evaluate the natural history of HIV infection among infants during an era of antiretroviral and other therapeutic modalities, and (5) assess the feasibility of future vaccine trials in this population. 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, Women and Infants Transmission Study (WITS II), 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. 017-001-10473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic non- profit, and for-profit research institutions; public and private organizations such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT Applicants funded under this RFA will be supported through National Institutes of Health (NIH) Cooperative Agreements (U01). Cooperative Agreements are awarded to institutions to encourage investigator-initiated research in areas of special importance to the NIH and if substantial programmatic involvement by NIH staff is anticipated. The interaction of NIAID staff with the investigators is expected to assist and facilitate the research. There is no intent, real or implied, for staff to direct a research site's activities or to limit the freedom of investigators. This RFA solicitation represents a onetime competition for a four year award with a specified deadline for receipt of applications. Program intents for extensions beyond the initial competitive segments are uncertain. If, by the end of the third year of award, NIAID has not announced an intention to reissue the RFA, awardees who plan to apply for continuing support should contact NIAID program officials for advice on how to recompete. FUNDS AVAILABLE Approximately $5,000,000 will be available for funding the total costs for the initial year of awards made pursuant to this RFA. NIAID anticipates making four to eight awards as a result of this RFA. The final number of awards to be made is dependent upon receipt of a sufficient number of applications of high scientific merit and availability of funds. Awards will be made for a 12-month budget period within a total project period of four years. Continuation of funds for each new budget period will be contingent on availability of funds and will be made on the basis of satisfactory performance in the areas of recruitment, retention, success in carrying out the WITS protocols, collaborative efforts with the other WITS sites, and scientific productivity. Annual progress reports will be required and should include a report on scientific, recruitment, and technical progress. Funding adjustments may be made related to both study performance and changing NIH research priorities. The earliest anticipated award dates will be July 1993. Under a separate and distinct initiative, the National Institute of Child Health and Human Development (NICHD) intends to independently support one or more clinical sites. Principal Investigators at those sites will collaborate with the NIAID sponsored sites in planning and carrying out the research agenda of WITS II. RESEARCH OBJECTIVES Background The growing magnitude of the HIV epidemic among women of child-bearing age and their infants is becoming apparent in many areas of the United States. The percentages of AIDS cases among women and children are increasing more rapidly than for any other risk groups. In the 1990s, the AIDS epidemic will continue to attack African American and Hispanic women and children in disproportionately high numbers. To date, more than 80 percent of pediatric AIDS cases have been caused by maternal-infant transmission. Moreover, virtually all new cases of pediatric HIV infection in infants and children will be due to maternal-infant transmission. In the face of this growing epidemic among women and their offspring, there are a number of critical and unanswered questions related to HIV infection during pregnancy and maternal-infant transmission. These include the impact of pregnancy on the health of HIV-infected women, mechanisms and timing of vertical HIV transmission, rates of maternal-infant transmission (overall and among different subpopulations of at-risk pregnant women), as well as understanding cofactors related to HIV transmission. In addition, major research issues appropriate therapeutic interventions include: (1) evaluating the impact of prenatal and intrapartum, (2) determining as early as possible which infants are HIV infected, (3) defining risk factors associated with rapid progression of disease among infants, and (4) understanding the natural history of pediatric HIV infection. The scientific and medical complexity of conducting valid epidemiologic studies of HIV-infected pregnant women and their offspring, in a way that addresses these research questions, is considerable. For example, to address research questions regarding maternal cofactors related to transmission, a cohort of approximately 1,000 pregnant HIV infected women and their offspring must be recruited. In addition, the laboratory techniques involved in HIV research are complex and rapidly evolving, requiring research efforts that can flexibly respond to expanding knowledge in this area. The Women and Infants Transmission Study II will continue and expand the Women and Infants Transmission Study (WITS I) that began in 1988. WITS I is co-sponsored by the NIAID and the NICHD. The current WITS study is conducted at five sites: a consortium of hospitals in the Boston, Worcester, Massachusetts area administered by Brigham and Women's Hospital in Boston, The Presbyterian Hospital in New York City, The State University of New York Health Sciences at Brooklyn, University of Illinois in Chicago, and University of Puerto Rico in San Juan. Anticipated final accrual for WITS I includes 500 HIV positive pregnant women, 400 infants born to these women, and 200 HIV positive nonpregnant women. WITS II will continue and expand this prospective natural history cohort study of HIV positive pregnant women and their offspring. It will rely heavily on the core protocols already in place for WITS I, but will also encourage new projects that may shed light on our understanding of maternal-infant HIV transmission and early diagnosis of fetal or infant HIV infection. New applicants should have a copy of the WITS I protocol summary and objectives of WITS I to aid them in preparing the RFA application. This information may be obtained from Dr. Mary Glenn Fowler, at the address listed under INQUIRIES. The research efforts of WITS II will complement a number of AIDS Clinical Trial Group (ACTG) perinatal and pediatric clinical trials currently underway or being planned. WITS II will also complement the Women's Interagency HIV Study funded by the NIAID and the Centers for Disease Control, which is evaluating the natural history of disease progression among HIV infected women. WITS II will have three major foci: o Continued evaluation of maternal cofactors related to maternal-infant HIV transmission including timing of transmission. o Assessment of promising early diagnostic techniques to rapidly identify HIV-infected infants. o Determination of the natural history of HIV infection among infants and children in an era of antiretroviral, prophylactic, and immunotherapy. Identification of infants at risk for rapid HIV disease progression will be an important element of this research. This component will be accomplished through follow up of infants currently enrolled in WITS I as well as infants born to pregnant HIV positive women enrolled in WITS II. Specific objective of WITS II are: o Determine maternal cofactors related to maternal-infant transmission, including assessment of mechanisms and timing of transmission. o Determine the impact of pregnancy on the natural history of HIV infection among women through the post partum period, including immunologic and virologic changes in pregnant HIV positive women. o Evaluate early diagnostic tests to determine infant HIV infection status as rapidly as possible. o Determine the natural history of HIV infection among congenitally exposed infants and children in light of antiretroviral, prophylactic, and immune-based therapy. o Assess the feasibility of future vaccine trials in a cohort of HIV infected pregnant women by evaluating their attitudes and potential willingness to take part in future clinical vaccine trials for themselves or their infants. To achieve the objectives of WITS II, the NIAID seeks applicants to help develop and carry out this continuing epidemiologic natural history study of pregnant HIV women and their children. New prospective sites as well as current WITS I sites are encouraged to apply. The template for this study will be the research protocols designed for WITS I, which includes a schedule of research visits with designated evaluations and data collection instruments (medical history questionnaires, physical exam forms, laboratory specimen collection procedures). In addition, specific new research studies are also encouraged that may provide critical information directed toward the primary research aims of WITS II. Applicants who are not current WITS sites may contact Dr. Mary Glenn Fowler (301/496-6177) to obtain a summary of the research protocol and objectives of WITS I. The applicants for this RFA should provide information that demonstrates scientific, technical, and operational capabilities to plan, implement, and participate effectively in a multi-site collaborative interdisciplinary research study. These capabilities will enable the applicant to respond to the urgent need to determine factors related to maternal-infant transmission; identify early diagnostic techniques to determine HIV status of infants; evaluate the natural history of HIV infection among infants and children; and assess feasibility of carrying out future vaccine trials. The application should demonstrate, at a minimum, the following capabilities: o Recruit and retain at least 30 and ideally over 50 HIV pregnant women and their children to fulfill the objectives of the WITS II study (See Specific Instructions, Section 1, Accrual and Retention Plan). Women should be recruited as early in pregnancy as possible. Demonstrated linkages with a Community Advisory Board will be required and linkages with other community based groups are strongly encouraged. (See Specific Instructions, Section 1, Linkages) o Carry out cohort studies of HIV infected pregnant women to evaluate factors related to maternal-infant transmission; determine mechanisms and timing of transmission; and assess early diagnostic studies to determine HIV status of infants born to HIV positive women. This effort will involve refinement and continuation of the current WITS I core protocols. o Implement follow up studies for the cohort of infants born to HIV positive women who are enrolled in WITS I and WITS II. Such studies would include assessment of survival, morbidity, growth and development, and quality of life for these children. Depending on the final selection of WITS II sites, successful new sites may subcontract with some current WITS I sites, if these sites do not recompete or secure a new award, to follow up infants currently enrolled in WITS I. Modification and refinement of existing WITS I protocols will be the template for this follow up. o Propose budgets, based on per patient capitation costs, to carry out the WITS protocols. o Carry out virologic, immunologic, and other laboratory studies relevant to the WITS protocols either on site or through linkages with an ACTU laboratory. Laboratory evaluations carried out on site must meet NIAID quality assurance requirements. o Coordinate and oversee specimen collection for the timely processing, storage, and retrieval of laboratory specimens as needed for WITS II studies. This would include the ability to transfer certain specimens to a central repository and transfer of other specimens to designated labs for early diagnostic and other specific laboratory studies. Structural Arrangements of the WITS II Cooperative Agreement WITS Steering Committee and Meetings The WITS II Steering Committee (WSC) will develop general WITS policies concerning subcommittee or working group structure and membership, publications, access to data, interim data monitoring, agendas for working group meetings, and developing and/or refining WITS protocols. Membership in the WSC will consist of one Principal Investigator from each WITS study site; the Principal Investigator of the Statistical and Clinical Coordinating Center (SACCC), which is responsible for central data management of the WITS study; and a program coordinator from the NIAID and the NICHD. The WSC will be chaired by an awardee Principal Investigator. The Chief of the Perinatal Transmission and Pediatric Section of the Vaccine Trials and Epidemiology Branch of the NIAID will serve as the NIAID program coordinator and the Special Assistant for Obstetrics in the Pediatric, Adolescent, and Maternal AIDS Branch, NICHD will serve as the NICHD program coordinator. The Program Coordinators together will have one vote on the WSC. The program coordinators and SACCC will assist in coordinating four WSC meetings per year in the Bethesda, Maryland area to discuss and define research activities with an agenda based on input from all WSC members. At the WSC meetings members will be responsible for suggesting and defining new inter-institutional studies as offered by the applicants consistent with Specific Instructions - Section 2 of the RFA, thus having been peer-reviewed and evaluated. The WSC will have a Publications Subcommittee and Working Groups set up as part of the infrastructure. Interim conference calls and/or meetings will be utilized by working groups and subcommittees. Data Access, and Publication In addition to the standard reporting requirements currently in existence for awardees of NIH research cooperative agreements, the following apply: It is the primary responsibility of the WITS Principal Investigators to clearly state the objectives and approaches of WITS II, to plan and conduct the research stipulated in WITS II, and to ensure that the results obtained are analyzed and published in a timely manner. The data obtained will be the property of the awardees. The NIAID and NICHD program coordinators will have access to the data generated under these cooperative agreements and may periodically review the progress by interim analyses. Information obtained from the data may be used by NIH program coordinators for the preparation of internal reports on WITS activities. WITS II publication policies will closely follow those established for WITS I, with the Principal Investigators taking the lead role in presentation and publication of scientific data generated by the WITS study. Specific publication policies will cover combined data from WITS I and WITS II, and will ensure that both WITS I and WITS II investigators contributions as well as those of the NIH program coordinators and the SACCC are appropriately acknowledged in terms of authorship and publications. All published (abstracts, peer reviewed manuscripts, reviews) and oral presentations of work supported in part or in total by the cooperative agreement must be acknowledged in the presentation and will include the mechanism, cooperative agreement number and Institute; for example, "This work was supported in part by the cooperative agreement number AI-92-13, NIAID." WITS awardee institutions will generate data that will be submitted to the SACCC. The total database for the WITS core protocols will include data from all funded sites. The use and publication of the data will be governed by policies established by the WITS investigators through the WSC. Final approval of publications will be by the WSC. Working groups and subcommittees such as a publication subcommittee, will be established by the WSC to coordinate efforts including, but not limited to, definition of research questions of interest, analysis of data, and publication of findings. The WSC will determine at the completion of WITS II whether or not to make the data from WITS II available to the public. These data could be made available through the National Technical Information Service. Data requestors would be asked to explicitly acknowledge the WITS research project and specific Principal Investigators or their designees in any publication or presentation involving the WITS data. Defined Working Relationship Within a Cooperative Agreement Assistance via a Cooperative Agreement differs from the traditional research grant in that in addition to the normal programmatic and administrative stewardship responsibilities, the component awarding the Cooperative Agreement anticipates substantial programmatic involvement during performance of the project. Within a cooperative agreement, a partnership relationship exists between the recipient of the award and NIAID. Each party to this partnership within WITS II will have rights and responsibilities as well as a defined working relationship. To be responsive to this cooperative agreement, an applicant must indicate willingness to work collaboratively with other WITS II investigators, with the assistance of the NIAID and NICHD program coordinators, in carrying out the WITS II research agenda. Awardee rights and responsibilities WITS II investigators will be responsible for overall conduct of the study including design of new studies, patient accrual and retention, production of high-quality data, and the analysis and publication of the research findings. WITS II investigators with the assistance of NIAID and NICHD program coordinators will establish and serve on the WSC and all working groups. NIH rights and responsibilities The NIAID and NICHD program coordinators, Chief of Vaccine Trials and Epidemiology Branch of NIAID and the Chief of the Pediatric, Adolescent and Medicine AIDS Branch, will assist the WITS II Principal Investigators. In addition, these coordinators, when appropriate, may designate other NIH staff to offer specific expertise on subjects determined by the WSC. It is again emphasized that the role of NIH will be to facilitate and not to direct the activity of the WITS II investigators. To ensure that the scientific research in WITS II is of the highest caliber and is directed appropriately to meet the objectives of WITS II, the NIH program coordinators may convene an external advisory scientific panel to review the WITS II protocol within the first year of the study. SPECIAL REQUIREMENTS Specific Instructions - Section 1 As part of items 1-4 of the research plan of PHS Form 398, applicants for the RFA awards should demonstrate the following minimum requirements Proficiency in conduct of epidemiologic research or clinical trials (5 page limit recommended) The applicant should describe the extent and scope of previous experience in carrying out epidemiologic or clinical trial studies; complications for women, infants and children and participation or capability to participate in multi-site clinical studies. The following should be done to permit an evaluation of performance: o Describe the epidemiologic research or clinical trials experience of key personnel in terms of kinds of studies and numbers and description of patients. o For current WITS sites, describe the total accruals to date, from the beginning of the study to the present, missed visits and retention data. In addition, applications from current WITS I sites should include information on data forms completion rates, data entry turn around time, and information on proportion of required repository specimen volumes that were actually collected, summarized across all patients by visit. For new sites, describe the anticipated potential accrual per year of pregnant HIV infected women. o Describe the level of scientific contribution in such studies (i.e., protocol design, cooperative efforts in carrying out the WITS protocols, oversight, handling of laboratory specimens, data management, publication contributions). o Describe the capability and willingness to administer a subcontract to follow up infants and children from the WITS I cohort who might be enrolled at a WITS I site that did not successfully recompete for WITS II. Assume semi-annual visits including physical and neuropsychological evaluations, and immunologic and virologic laboratory studies. Organizational Structure for Conduct of Epidemiologic or Clinical Trials (6-page limit recommended) The applicant should detail the essential features present at their site for the performance of multi-site clinical studies, including qualifications of key personnel and facilities. The narrative must specifically address the following: o Personnel - describe in detail, the qualifications of other staff (other than those key personnel already mentioned above in 1a), who would help conduct the study, as well as personnel for delivery of ancillary services. Culturally sensitive individuals reflective of local demographics should be represented among key staff as well as personnel for ancillary services. o Facilities - describe facilities and resources available for conducting the clinical studies and ancillary services (e.g., obstetrical, perinatal, and pediatric care facilities, outreach and social services, child care, transportation). Accrual and Retention Plan (6-page limit recommended, plus supporting letters) Applicants should document the capability to access a population of HIV pregnant women and their offspring. The applicant should document their potential ability to recruit a minimum of at least 30 and ideally 50 or more pregnant HIV infected women in the first year, a number that will help define the size of the first year budget. Especially useful is an assessment of local data derived from HIV prevalence newborn screening surveys. The application should describe: o The primary source(s) of WITS study subjects. o The demographic features of the HIV-positive pregnant women in the catchment area including HIV seroprevalence data, race/ethnicity, and risk transmission categories. o A plan for outreach to pregnant HIV women, including strategies for interaction with community health care providers or agencies that are likely to lead to referral of HIV-infected pregnant women into the WITS study. The number, background, and experience of staff who are culturally sensitive to the needs of these women should be described and provisions made for training to increase the sensitivity of WITS staff. o Policies and procedures for accessing referral patients, such as communication, provision of ancillary services, outreach and non-study related care, follow-up by research staff or primary care providers, and amount of primary care provided by the research study staff to the populations, should be mentioned. Letters of agreement to document, describe, and support interactions with specific referral sites must be provided. All applicants should present a plan to provide or refer WITS enrollees for comprehensive clinical care including substance abuse treatment when appropriate. Linkages (5-page limit recommended, plus supporting letters) The following support linkages are either REQUIRED as specified or strongly ENCOURAGED when not specified: o Community Advisory Board (REQUIRED). A Community Advisory Board (CAB) associated with each site should be established within two months of award. The purpose of the CAB is to foster interaction between the WITS personnel and HIV infected individuals in the community, community health providers, community leaders, and advocacy groups. (If an appropriate CAB is already in place, it is not necessary to establish a separated CAB for the WITS). Applicants may contact the WITS NIAID Program Coordinator, Dr. Mary Glenn Fowler, 301-496-6177, to clarify any questions regarding the CAB. o AIDS Clinical Trials Unit (ACTU): An establishment of linkage with a ACTU funded by the NIAID or the NICHD, if one is located within the same geographic area, is encouraged, and a letter of agreement describing the relationship should be included. (See Appendix 1 for listing). o Clinical Programs for Clinical Research on AIDS (CPCRA): An establishment of linkage with a CPCRA site if one is located within the same geographic area is encouraged, and a letter of agreement describing the relationship should be included. (See Appendix 2 for listing). o General Clinical Research Center (GCRC): Applicants from institutions that have a GCRC funded by the NIH National Center for Research Resources are encouraged to identify the GCRC as a resource for conducting the proposed research. A letter of agreement from either the GCRC Program Director or the Principal Investigator should be included with the application. (See Appendix 3 for listing). o Research Centers at Minority Institutions (RCMI): An establishment of linkage with an RCMI- funded or cofunded by the NIAID, if one is located within the same geographic area, is encouraged, and a letter of agreement describing the relationship should be included. (see Appendix 4 for listing) o Centers for AIDS Research (CFAR): An establishment of linkage with a CFAR funded by the NIAID, if one is located within the same geographic area, is encouraged and a letter of agreement describing the relationship should be included. (See Appendix 5 for listing) o National Institute on Drug Abuse (NIDA) Treatment and Research Centers: An establishment of linkage with a NIDA project, if one is located within the geographic area, is encouraged, and a letter of agreement describing the relationship should be included. (See Appendix 6 for listing) o American Foundation for AIDS Research Community-based Clinical Trials (CBCT) Network: An establishment of linkage with a CBCT, if one is located within the geographic region, is encouraged, and a letter of agreement describing the relationship should be included. (See Appendix 7 for listing) o AIDS Vaccine Evaluation Group (AVEG, NIAID): An establishment of linkage with an AVEG funded by NIAID, if one is located within the same geographic area, is encouraged and a letter of agreement describing the relationship should be included. (See Appendix 8 for listing) o Health Resources Services Administration (HRSA) AIDS Demonstration Project: An establishment of linkage with a HRSA AIDS Demonstration Project, if one is located within the same geographic area, is encouraged, and a letter of agreement describing the relationship should be included. (See Appendix 9 for listing) Applicants are encouraged to form other linkages, including, but not limited to, community-based organizations that serve populations at increased risk for HIV infection, designated State/County/Public Health AIDS Centers, and community-based AIDS clinics. A letter of agreement for each linkage should be included with the application. All letters of agreement should be explicit about the intended purpose and role of the collaborating site or organization, referencing prior successful collaborations. Laboratory Capabilities (5-page limit recommended) Applicants should demonstrate a capability to collect and process blood and cervical specimens for laboratory analyses including, but not limited to, immunology, virology assays and cultures, cervical cultures, serology, chemistry, and hematology studies. This capability could be either in the applicants' own laboratories, by a ACTG-certified laboratory, or other laboratories likely to be deemed suitable by peer reviewers and by NIAID staff. Funds will not be provided to support equipment, personnel, or facilities for the establishment of new laboratories, although funds may be requested for supplementary equipment at existing laboratories. Detailed justification is required. Awardee laboratories will be required to participate in a quality assurance (QA) program supported by the NIAID. A key part of the WITS protocols includes collection, transfer, and storage of designated laboratory specimens (urine and blood samples) at a central NIAID-supported specimen repository.The purpose is to permit future nested studies in which technologies, sample sizes, or hypotheses are not currently known or available. Applicants should indicate in their application (1) their agreement to transfer designated specimens; (2) describe their abilities to collect, store, and transfer required quantities of designated specimens to a central repository; and (3) their experience in similar activities. Data Coordination (5-page limit recommended) The WITS will be assisted by a Statistical and Clinical Coordinating Center (SACCC), contracted by the NIAID to provide extensive technical and logistical support for data analyses. This contract will: (1) provide statistical leadership; (2) establish and administer an effective and responsive data management system; (3) design and implement educational/training assistance to WITS investigators and quality assurance with respect to WITS data; and (4) facilitate communications, meetings, conference calls, publications, and study-related coordination between the clinical sites and the government. Applicants should present capabilities to do either (a) on-site data entry using SACCC-produced data entry modules or (b) photocopying and sending data collection instruments and sending them to the SACCC for data entry. If specific required hardware/software equipment for data entry is not available at an applicant site doing on-site data entry, it may be proposed in the budget. However, applicants are strongly encouraged to use existing facilities and data entry equipment already available to them at their site. For on-site data entry, computer tapes or diskettes that contain files of the site data will be sent to the SACCC. Inconsistencies found by the SACCC and reported to the sites will be the responsibility of the sites to resolve, irrespective of whether sites enter their own data or send hard copies to SACCC for data entry. The SACCC staff will support the WITS investigators in their analyses of the findings from WITS II. Each applicant will be sent a copy of the Request for Proposals for the SACCC so that the applicant can be aware of the full range of services to be provided by the SACCC. Specific Instructions - Section 2 - Development Research Component (Optional) The essential research for WITS II will be based on refinement of the WITS I protocols. However, WITS II also wishes to encourage a limited number of new research protocols to address the objectives of WITS II in light of the most current scientific knowledge available. Interested investigators may briefly describe (3-6 single spaced pages) specific research projects that they would propose to be added to WITS II that address specific research objectives of WITS II. Research areas of particular interest to the NIAID include evaluation of maternal-infant pairs with respect to genotypic sequencing, host effects related to transmission, placental and other studies which may shed light on timing and mechanisms of transmission, TB related studies, new diagnostic studies that might identify HIV infected infants in the newborn period or prenatally; and HIV vaccine feasibility studies. Applicants responding to this optional section should also complete a separate budget for this section using pages 3 and 4 of the budget section of PHS 398 application form (rev.9/91). Although the scientific merit of applications in this section will be peer reviewed and evaluated, this review will not be used in the overall scoring of the application. Specific Instructions for Preparing an Application Budget This section supplements the instructions for preparing a grant application form PHS 398 (rev. 9/91). Applicant budgets should follow the instructions contained in the PHS 398 (rev. 9/91) to complete the budget pages for Sections 1 and for Section 2 separately. In addition, for Section 1, applicants should include as additional budgetary attachments, worksheets showing the breakdown of separate budgets for the following components of the study: o A core budget that includes (1) personnel costs for the Principal Investigator and other key personnel (study coordinator, research assistant,); (2) travel for meetings to include four meetings of the study Principal Investigators to be held in the Bethesda, Maryland area, one national meeting, and one international meeting; (3) supplies--laboratory, data management, and other supplies needed to carry out the study; (4) community based efforts for recruitment of pregnant HIV infected women. Budgets should indicate funds allocated for support of community based personnel who would help with recruitment and retention, counselling and other logistic support. o Annual costs for recruitment and evaluation of pregnant women at a site, based on total estimated accrual per year, number of visits per year, clinical assessments, and laboratory costs per visit (See Appendix 10 for specific information regarding number of visits, costs anticipated for lab tests, and costs for shipping three urines and two pap smears per patient per year). Costs for ancillary services such as transportation, child care, and incentive costs related to patient visits should also be itemized in the budget worksheet. o Annual costs for evaluations of the offspring born to the HIV infected women enrolled in WITS II, based on total estimated accrual per year, number of visits per year, staff, clinical and neuropsychologic evaluations, and laboratory costs per visit. (See Appendix 11 for specifics on number of visits, and estimated costs for laboratory tests). Costs for ancillary services such as transportation, child care,and incentive costs related to patient visits should also be itemized in the budget worksheet. 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 both genders and all ages. Because this RFA addresses research on the effects of HIV infection among women and their infants, many of whom are from minority race/ethnicity groups, it is anticipated that women and minorities will be adequately represented in applications for this RFA. Because the research in this RFA is directed at the effects of HIV infection on women and their infants, the noninclusion of adult males in submitted proposals is justified. The composition of the proposed study population must be described in terms of racial/ethnic groups. In addition, 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 application Under SPECIAL INSTRUCTIONS, STUDY POPULATIONS. 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 U.S. racial/ethnic minority populations (i.e., Native American Indians or Native Alaskans, Asian/Pacific Islanders, African-American, Hispanics/Latinos). 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 PHS/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 may be exempted from these usual PHS/NIH policies. However, every effort would 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 as determined by NIAID program coordinator, the application will be returned. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of minorities in the proposed study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population(s) 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 agreement that do not comply with these policies. LETTER OF INTENT Prospective applicants are asked to submit, by October 26, 1992, a letter of intent that includes a descriptive title of the proposed research and 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 requested to provide an indication of the number and scope of applications to be reviewed. The letter of intent is not binding, does not commit the sender to submit an application, nor is it a requirement for submission of an application. The letter of intent is to be sent to: Mary Glenn Fowler, M.D., M.P.H. Vaccine Trials and Epidemiology Branch Division of AIDS National Institute of Allergy and Infectious Diseases 6003 Executive Boulevard, Room 2A24 Bethesda, MD 20892 (for express mail or courier, use Rockville, MD 20852) APPLICATION PROCEDURES The research grant application form PHS 398 (revised 9/91) is to be used in applying for these cooperative agreements. These forms are available from most institutional offices of sponsored research; the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone 301/496-7441; and from the NIH program coordinator named below. 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, "WOMEN AND INFANTS TRANSMISSION STUDY", RFA AI-92-13 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, 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 copies must also be sent directly to: Dr. Dianne Tingley AIDS Scientific Review Branch Division of Extramural Activities National Institute of Allergy and Infectious Diseases 6003 Executive Boulevard, Room 4C16 Bethesda, MD 20892 If sending the application by overnight mail or courier service use "Rockville, Maryland 20852". Applications must be received by both DRG and Dr. Tingley by January 14, 1993. Applications received after January 14, 1993 will be returned to the applicant without review. If the application submitted in response to this RFA is substantially similar to a grant application already submitted to the NIH for review, but has not yet been reviewed, the applicant will be asked to withdraw either the pending application or the new one. Simultaneous submission of identical applications will not be allowed, nor will essentially identical applications be reviewed by different review committees. Therefore, an application cannot be submitted in response to this RFA that is essentially identical to one that has already been reviewed. This does not preclude the submission of substantial revisions of applications already reviewed, but such applications must include an introduction addressing the previous critique. Applications that are not received as a single package from the Principal Investigator and that do not conform to the instructions contained in PHS 398 (rev. 9/91) and the specific instructions including the page guidelines to not exceed 32 pages for section 1 of this RFA will be judged non-responsive and will be returned to the applicant. Upon receipt, applications will be reviewed by DRG staff for completeness and NIAID staff for responsiveness. Incomplete applications will be returned to the applicant without further consideration. If the application is not responsive to the RFA, NIAID 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 a NIAID peer review group to determine their relative competitiveness. The NIAID will withdraw from further competition those applications judged to be non-competitive for award and will notify the Principal Investigator and institutional official. Those applications judged to be competitive will be evaluated in accordance with the criteria stated below for scientific/technical merit by an appropriate peer review group convened by the AIDS Review Section, DEA, NIAID. The second level of review will be provided by the National Advisory Allergy and Infectious Diseases Council in June 1993. The earliest possible award date is July 1993. Applications will be evaluated for scientific merit including the originality, feasibility, and technical excellence of the research projects. REVIEW CONSIDERATIONS This application must be directed at and address the research objectives identified in this RFA; that portion of the application corresponding to this research plan should follow in form the specific instructions given in this RFA. The primary factors that will be considered in the review of the application will be demonstrated ability or potential to recruit adequate numbers of HIV pregnant women into the study; capability to carry out the clinical and laboratory studies of WITS II including commitment to a multi-site research collaborative effort; and cost efficiency in carrying out the research protocols. The following specific factors will be considered in the review of the application: Section 1 o Prior success or demonstrated potential of the applicant to recruit adequate numbers of HIV pregnant women for the study. (To be competitive an applicant site should demonstrate the capability to recruit and retain at least 30 and ideally over 50 HIV pregnant women annually.) o Capability to carry out the clinical, and laboratory studies of WITS II, including adequacy of available physical facilities to accommodate conduct of physical examination, phlebotomy, interviewing, counselling, neurodevelopmental testing of infants and children, handling of laboratory specimens, and data management. o Potential for original research bearing on the research objectives of WITS II. o The professional qualifications and the scientific expertise of the Principal Investigator and key personnel in research areas emphasized by the study. This includes experience in multi-site collaborative efforts and adequacy of proposed staffing levels to meet the research objectives of the RFA. o The establishment and adequacy of community support linkages. o Evidence of institutional commitment to the study as demonstrated by administrative experience and capabilities and listing of resources that will be dedicated to the study. o Efficiency in terms of costing, and utilization of available resources. Section 2 Scientific merit of the proposed optional research study. AWARD CRITERIA Awards will be made on the basis of high scientific and technical merit, adequacy of funds and program relevance. However, after applications have been approved by the National Advisory Allergy and Infectious Diseases Council, NIAID staff reserve the right to give consideration to the following factors in the final selection of applications to be funded: WITS II sites reflect the racial/ethnicity and socioeconomic characteristics of the nation-wide HIV epidemic among women and infants and reflect the HIV-AIDS incidence/geographic distribution of the epidemic among U.S. women and their infants. 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 concerning programmatic issues to: Mary Glenn Fowler, M.D., M.P.H. Vaccine Trials and Epidemiology Branch Division of AIDS National Institute of Allergy and Infectious Diseases 6003 Executive Boulevard, Room 2A24 Bethesda, MD 20892 Telephone: (301) 496-6177 FAX: (301) 402-1506 or (301) 480-5703 Direct inquiries concerning fiscal and policy issues to: Jane Unsworth Chief, AIDS Grants Management Section Grants Management Branch Division of Extramural Activities National Institute of Allergy and Infectious Diseases 6003 Executive Boulevard, Room 4B25 Bethesda, MD 20892 Telephone: (301) 496-7075 FAX: (301) 480-3780 Direct inquiries concerning the review process and review requirements to: Dr. Dianne Tingley AIDS Scientific Review Branch National Institute of Allergy and Infectious Diseases 6003 Executive Boulevard, Room 4C16 Bethesda, MD 20892 Telephone: (301) 496-0818 FAX: (301) 402-2638 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance Nos. 93.856 and 93.855. 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 Public Health Service Act 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 Wed Oct 07 23:00:00 1992 Path: biosci!NET.BIO.NET!kristoff From: kristoff@NET.BIO.NET (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 21, no. 36, pt. 4, 9 October 1992 Message-ID: Date: 8 Oct 92 23:58:28 GMT Sender: kristoff@net.bio.net Distribution: bionet Lines: 1498 $$XID RFA CA9228 CA-92-28 P1O1 ***************************************** CLINICAL TRIALS OF CANCER THERAPY WITH BIOLOGICAL RESPONSE MODIFIERS NIH GUIDE, Volume 21, Number 36, October 9, 1992 RFA: CA-92-28 P.T. 34; K.W. 0755015, 0715035, 0740015 National Cancer Institute Letter of Intent Receipt Date: October 30, 1992 Application Receipt Date: December 22, 1992 PURPOSE The Division of Cancer Treatment (DCT), National Cancer Institute (NCI) invites applications to establish cooperative agreements for Clinical Trials of Cancer Therapy with Biological Response Modifiers (CATBRMs), for the development of novel approaches to such therapy. 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), Clinical Trials of Cancer Therapy With Biological Response Modifiers (CATBRMs), 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 Groups constituted according to the guidelines outlined in the RESEARCH OBJECTIVES, Section C are eligible to apply. Applying groups may include members from academic, non-profit and for-profit institutions. Involvement of intramural NIH personnel is limited as described under the RESEARCH OBJECTIVES, Section C, Composition of a CATBRM Group. Domestic and foreign organizations and institutions (non-profit or for-profit) are eligible. Governments and their agencies are also eligible. Applications from women and members of minority groups are encouraged. MECHANISM OF SUPPORT Support of this program will be through the Cooperative Agreement (U01), an assistance mechanism in which substantial NCI programmatic involvement with the recipient during performance of the planned activity is anticipated. The nature of NCI staff involvement is described in the section entitled SPECIAL REQUIREMENTS, A. Terms of Cooperation. Applicants will be responsible for the planning, direction, and execution of the proposed project. There is no intent, real or implied, for NCI staff to direct CATBRM activities or to limit the freedom of investigators. In addition to the requirements stated in this RFA, 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, revised October 1, 1990. This RFA is a reissuance of RFA CA-92-01. Applicants who did not apply to the first announcement, or who applied but did not receive an award, are encouraged to respond to this RFA. However, this reissued RFA is a one-time solicitation. Generally, future unsolicited competing renewal applications will compete as research project applications with all other investigator-initiated applications. However, should the NCI determine that there is sufficient continuing program need, the NCI will invite recipients of awards under this RFA to submit competitive continuation cooperative agreement applications for review. Each award will be made to the institution designated in the application as the applicant institution. All CATBRM study group activities will be coordinated through the Principal Investigator. Under the Cooperative Agreement, a relationship exists between the recipient of the award and the NCI, in which the CATBRM group is responsive to the requirements and conditions set forth in the RFA. Specifically, the Principal Investigator defines the details for the project within the guidelines of the RFA, retains primary responsibility for the performance of the activity, and agrees to accept close coordination, cooperation, and assistance of the NCI extramural staff (through the NCI Program Director) in all aspects of scientific and technical management of the project in accordance with the Terms of Cooperation. FUNDS AVAILABLE The NCI plans to make up to six awards for project periods up to four years, and has set aside $1.5 million total costs for the initial year's funding. The total funding level and number of awards to be made 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 National Cancer Institute, awards pursuant to this RFA are contingent upon continuing availability of funds. Applicants may request no more than four years of support. The earliest possible starting date for the initial annual period will be July 1, 1993. RESEARCH OBJECTIVES A. Background/Summary The clinical successes of biological response modifiers (BRMs) in cancer treatment are well known (e.g., single-agent `-interferon for hairy-cell leukemia; and the responses to IL-2 based therapy in renal cell carcinoma). These limited successes suggest a future role for BRMs in clinical oncology. Rapid developments in molecular biology, hybridoma technology, protein engineering, and other areas are providing new opportunities and challenges to investigators attempting to define this role. At an accelerating rate, new BRMs-- e.g., growth and differentiation factors; cytokines and colony-stimulating factors; murine, chimeric, and human monoclonal antibodies; and targeting agents such as immunotoxins, fusion proteins, and antibody fragments--have become available for clinical trials, and other agents now under preclinical study may be of interest as BRMs. New technologies, such as the use of gene-transfected cells and new methods of vaccine design, have led to novel approaches to such previously studied strategies as adoptive immunotherapy and active specific immunotherapy. Insights into possible combination regimens employing BRMs are also being made. At the same time, it is clear that much remains to be learned about the relationship between clinical and other biological effects of BRMs-- e.g., potential mechanisms of action, appropriate parameters for monitoring of patients, and development of endpoints which may predict clinical benefit. The NCI seeks, with this RFA, to foster innovative clinical trials of BRMs by peer-reviewed groups of highly experienced clinical and preclinical investigators who have the unique technical capabilities to study new agents in early clinical trials and to address hypothesis-driven issues of mechanisms of action. This initiative will establish Clinical Study Groups for Cancer Therapy with Biological Response Modifiers (CATBRMs), for the design and execution of novel clinical trials with BRMs. The Research Goals and Scope of this RFA will require a novel plan for clinical study of a given new agent or agents, adequately supported by prior preclinical, and if available, clinical, results. The application must describe how its objectives are in accord with the applicant's own interests and experience. The applicant must provide evidence of access to the agent(s) proposed for study. A detailed protocol for an initial clinical trial must also be included. The NCI will facilitate the institution of a peer-reviewed, investigator-initiated trial, participating as outlined in the section entitled SPECIAL REQUIREMENTS, A. Terms of Cooperation. Each CATBRM study group will be composed of: a Principal Investigator; one or more laboratory programs, each headed by a Program Leader, with the demonstrated expertise to design and carry out assays for the appropriate monitoring of patients on the study; one or more clinical programs, each headed by a Program Leader, with demonstrated expertise in conducting clinical trials of BRMs; and the NCI Program Director. The application may include investigators from one or more domestic or foreign academic, non-profit, and/or commercial institutions. Application under this RFA may also be a logical step to develop agents arising in National Cooperative Drug Discovery Groups (NCDDGs), P01s, or R01s. For this RFA, a BRM is defined as: "An agent or approach intended to modify the relationship between tumor and host by modifying a host's biological response to tumor cells, with resultant therapeutic benefit. This includes: agents or approaches which utilize or modify immunological mechanisms; naturally occurring or recombinantly produced regulatory molecules (e.g., cytokines, growth or differentiation factors); and monoclonal antibodies and their derivatives." (See B. Definitions, below) In responding to this RFA, applicants should propose clinical trials of BRM agents or strategies as so defined, where the focus of study is the testing of a biologic hypothesis. Generally, it is envisioned that this will be done in the context of small pilot clinical trials. Prospective applicants who plan to study agents which are not BRMs as defined, who plan large randomized clinical trials, or who plan trials solely to study issues of safety and efficacy apart from any other biologic hypothesis, will be referred to other NCI programs supporting clinical trials for cancer therapy. B. Definitions COOPERATIVE AGREEMENT--An assistance mechanism in which substantial NIH programmatic involvement with the recipient during performance of the planned activity is anticipated. STUDY GROUP FOR CLINICAL TRIALS OF CANCER THERAPY WITH BIOLOGICAL RESPONSE MODIFIERS (CATBRM STUDY GROUP)--A group consisting of a single Principal Investigator (who may also be a Program Leader); one or more laboratory programs, each headed by a Program Leader, with the demonstrated expertise to design and carry out assays for the appropriate monitoring of clinical trial subjects; one or more clinical programs, each headed by a Program Leader, with demonstrated expertise in conducting clinical trials of BRMs, and the NCI Program Director. Working under the guidance and direction of the Principal Investigator, the CATBRM study group (also referred to simply as a "study group" or a "group" in this RFA) pursues the common goal of the novel clinical development of new agents, regimens, or strategies for therapy of cancer with BRMs. Coordinated through the Principal Investigator, the CATBRM study group will employ a research plan and budget that clearly delineate the clinical and laboratory components of both the plan and the budget. CLINICAL PROGRAM--A research component of the overall group, with the expertise and experience to conduct clinical trials of BRMs based on the latest scientific developments. LABORATORY PROGRAM--A research component of the overall group, with the expertise and experience to carry out assays designed to investigate mechanisms of action of clinical BRM regimens. APPLICANT INSTITUTION--The institution, designated in the application, that assumes legal and fiscal accountability for the disposition of funds awarded. PARTICIPATING INSTITUTION--One or more investigators from a single institution who, together, participate in one of a group's clinical or laboratory programs. BIOLOGICAL RESPONSE MODIFIER--An agent or approach intended to modify the relationship between tumor and host by modifying a host's biological response to tumor cells, with resultant therapeutic benefit. This includes: agents or approaches which utilize or modify immunological mechanisms; naturally occurring or recombinantly produced regulatory molecules (e.g., cytokines, growth or differentiation factors); and monoclonal antibodies and their derivatives. PRINCIPAL INVESTIGATOR--By definition in Federal regulations, "a single individual designated by the grantee in the grant application and approved by the Secretary, who is responsible for the scientific and technical direction of the project" (42 CFR Part 52). The Principal Investigator is the person who assembles the CATBRM, submits the single application in response to this RFA, and is responsible for performance of the group as a whole and of each Program Leader. The Principal Investigator may be an M.D., D.O., or Ph.D., and may lead one of the Clinical or Laboratory Programs of the group. The Principal Investigator will also coordinate group activities. If the Principal Investigator is a Ph.D., a Clinical Investigations Leader who is an M.D. or D.O. will be designated on the initial group application. The Clinical Investigations Leader will, in such a case, lead the design and conduct of the clinical trial(s) conducted by the group. CLINICAL INVESTIGATIONS LEADER--An M.D. or D.O., designated on the initial grant application, who leads the design and conduct of the clinical trial(s) conducted by the group. The Principal Investigator, if an M.D. or D.O., may also be the Clinical Investigations Leader. PROGRAM LEADER--The director of one of the Clinical or Laboratory Programs of the group. NCI PROGRAM DIRECTOR--The extramural Program Director (cited in INQUIRIES) of the Biological Resources Branch, Biological Response Modifiers Program (BRMP), Division of Cancer Treatment (DCT), NCI, designated by the NCI, who provides guidance for the overall CATBRM program within the NCI, and who acts as NCI Coordinator for each CATBRM group, facilitating the role of the NCI in the group. PATENTABLE INVENTION--Any new and useful process, machine, manufacture or composition of matter, or any new and useful improvements thereof, as defined under the U.S. Patent Statute (35 USC 101). C. Composition of a CATBRM Group 1. The composition of a CATBRM group is envisioned as follows: a. A Principal Investigator, and if necessary as outlined above, a Clinical Investigations Leader; b. One or more Clinical Programs, each headed by a Program Leader, each experienced in clinical oncology, clinical immunology, and the conduct of clinical trials of BRMs for the treatment of human cancer; c. One or more Laboratory Programs, each headed by a Program Leader, each with demonstrated expertise in scientific disciplines necessary to design and conduct the laboratory assays for the appropriate monitoring of patients on the group's clinical trial; d. The NCI Program Director, who coordinates NCI involvement in the study group. 2. The Principal Investigator, in addition to providing scientific and administrative leadership, may also be a Program Leader. All Program Leaders will be directly responsible to the Principal Investigator. The formation of the group, the application in response to this RFA, the overall management of the group, and the allocation of funds to the various Clinical and Laboratory Programs based on performance and overall group needs at any given time will be the responsibility of the Principal Investigator and the applicant institution in accordance with PHS policies. 3. The specific makeup of the group's Clinical and Laboratory Programs, and the specific disciplines represented, should depend on the talents required to accomplish its scientific and technical objectives as perceived by the Principal Investigator and Program Leaders. The major consideration in structuring a CATBRM group should be the full mobilization of the expertise necessary to accomplish the group's research goals. While the specific makeup of different groups may vary, each group's Clinical and Laboratory Programs, when taken together, must include all necessary expertise for the achievement of its research goals. 4. An individual scientist or clinician may be proposed as a Principal Investigator or a Program Leader in more than one application. If so, the Principal Investigator must demonstrate in the application that there is no scientific or budgetary overlap or proprietary conflict with each individual's proposed activities. Likewise, individuals currently receiving funding via contracts, grants, or cooperative agreements may be funded under this RFA if there is no scientific or budgetary overlap or proprietary conflict in funded activities. An NIH intramural scientist may participate in a CATBRM group as a collaborator or consultant, but may not be a Program Leader or receive salary, equipment, supplies, or other remuneration from this program. The intramural scientist must provide a letter of commitment and a current curriculum vitae, and obtain appropriate NIH clearances prior to submission of the application. The Principal Investigator must incorporate into the application, in the usual grant format, a full description of the collaborative project, including technical details and methodology. The participation of an intramural scientist is independent of and unrelated to the role of the NCI Program Director as described in the SPECIAL REQUIREMENTS, A. Terms of Cooperation, 2.a. 5. A CATBRM group may include members from a single institution or a number of institutions, depending on the specific goals of the group. 6. Although a minimum of one Clinical and one Laboratory Program per group is necessary, no limit on the number of Programs per group is stipulated. In preparing applications, however, prospective Principal Investigators should keep in mind that effective, efficient cooperation can be difficult in groups with more than a few Clinical and Laboratory Programs. In addition, very large groups may require budgets large enough to be a limiting factor in funding decisions. 7. A CATBRM group may include one or more foreign members, or may consist entirely of investigators or programs located outside the United States. 8. Under the provisions of assistance through Cooperative Agreement, the NCI Program Director will participate as a member of the group in a manner specified in the Section SPECIAL REQUIREMENTS, A. Terms of Cooperation. The NCI Program Director will not conduct Clinical or Laboratory Programs. D. Research Goals and Scope 1. The goals of this RFA are: a. The development of novel approaches to the treatment of human cancer with BRMs, employing new agents, concepts, or treatment strategies. Applications must clearly seek new knowledge in this field. b. The clinical testing of such approaches by the conduct of one or more related, well-designed clinical trials with BRMs. A detailed clinical protocol must be submitted with the application (see APPLICATION PROCEDURES, below) and must describe the subsequent clinical trials envisioned by the applicant group. A central, common theme should be the focus of these protocols and the CATBRM group's efforts overall. c. Exploration of mechanisms of antitumor effect and resistance, and of the effects of modifications designed to alter these to clinical and biologic advantage. This includes concurrent laboratory studies which are designed to (a) elucidate observations or test hypotheses arising from the clinical trial(s), or (b) refine the clinical approaches used. Such studies may include in vitro or in vivo experiments, theoretical modelling, development of surrogate endpoints, or other studies as appropriate for the scientific goals of the application. d. Monitoring of specific immunomodulatory or other parameters, as appropriate for the scientific goals of the application. e. Observation of clinical effects (e.g., tumor responses, toxic side-effects) of the treatment regimen, and, if appropriate, correlation of these with other biologic endpoints. SPECIAL REQUIREMENTS A. Terms of Cooperation 1. Responsibilities of Awardees It is the responsibility of the CATBRM study group to develop the details of its research design; define its objectives and approaches; plan and conduct the research; analyze and interpret the data obtained; and publish the results. The NCI anticipates that decisions in all activities will be reached by group consensus under the leadership of the Principal Investigator, and that the NCI Program Director will have the opportunity to offer input to this process. a. Membership in the Group Group membership includes the Principal Investigator, the Clinical Investigations Leader, the Program Leaders, and the NCI Program Director. In no case will changes of Principal Investigator, Program Leaders, Clinical or Laboratory Programs, or participating institutions be made without prior approval from the NCI. Such approval may be sought either in the application for continuation grant (PHS 2590 (rev. 9/91)) or during the course of the budget period. In the latter case, the procedure for requesting prior approval is described in the "Methods for Grantees to Request Approvals," PHS Grants Policy Statement, page 8-5. b. Protocol Development As for all group activities, it is anticipated that decisions regarding protocol development will be reached by consensus of the group, under the leadership of the Principal Investigator. The Principal Investigator (or, if required, the Clinical Investigations Leader) shall designate a single Protocol Chairperson for each proposed clinical trial. The Principal Investigator will be responsible for communication with NCI, through the NCI Program Director. c. Protocol Submission The Principal Investigator will submit all group protocols to the NCI Program Director for review and approval. The NCI Program Director will coordinate any required NCI review (e.g., review by the Cancer Therapy Evaluation Program (CTEP) if the protocol is to be conducted under an NCI-held IND), and assure that the results of such review are communicated to the Principal Investigator. The Principal Investigator will be responsible for communicating the results of the protocol review to the group's Program Leaders and participating institutions. Disagreements arising from NCI protocol review that cannot be resolved by mutual discussion will be resolved by an arbitration panel. The panel will consist of one CATBRM group nominee, one NCI nominee, and a third member, chosen by the other two, with expertise in clinical trials of BRMs. The panel will review the NCI decision and recommend an appropriate course of action to the Director, DCT. These special arbitration procedures in no way affect the awardee's right to appeal an adverse determination in accordance with PHS regulations at 42 CFR Part 50, Subpart D, and HHS regulations at 45 CFR Part 16. The CATBRM group will not expend NCI funds to conduct any part of any NCI- disapproved CATBRM study unless the NCI disapproval has been modified by this arbitration process. d. Quality Control The awardee institution is responsible for ensuring that the group establishes mechanisms for quality control of therapeutic and diagnostic modalities employed in its trials. e. Study Monitoring The group will establish mechanisms for study monitoring. The awardee institution is responsible for assuring the group maintains accurate and timely knowledge of the progress of each study through: o Establishing procedures for assigning each new patient to a treatment group at the time of entry to the study; o Assuring that each Clinical and Laboratory Program is maintaining verifiable data, conducting studies in compliance with the approved clinical protocols, and complying with regulatory requirements for the protection of human subjects and investigational agent accountability; o Tracking and reporting of patient accrual and adherence to defined accrual goals; o Ongoing assessment of case eligibility and evaluability; o Timely medical review and assessment of patient data; o Rapid reporting of treatment-related morbidity (adverse drug reactions), in accordance with regulatory requirements, and measures to ensure communication of this information to all parties; and o Timely communication of results of studies. f. Data Management and Analysis The awardee institution is responsible for ensuring that the group develops procedures to ensure that data collection and management are: (1) adequate for quality control and analysis; (2) as simple as appropriate in order to encourage maximum participation of physicians entering patients and to avoid unnecessary expense; and (3) sufficiently uniform across the participating institutions. Data from protocols conducted under NCI-held INDs must also be available for external monitoring, in accordance with an agreement between the NCI and the FDA governing the NCIs responsibilities as a drug monitor. g. Compliance with Federally Mandated Regulatory Requirements The awardee institution retains the primary responsibility for establishing procedures for all participating institutions to comply with Food and Drug Administration (FDA) regulatory requirements for studies involving investigational agents, and Office of Protection from Research Risks (OPRR) requirements for the protection of human subjects. These procedures are: (1) Methods for assuring that each institution at which investigators are conducting group trials has a current, approved assurance on file with the OPRR. (2) Review and approval of each protocol by all responsible Institutional Review Boards (IRBs) prior to patient entry; review of each protocol at least annually by the IRB(s) so long as the protocol is active; review and approval of protocol amendments by the IRB(s). (3) Assurance that each patient (or each patient's legal representative) gives written informed consent prior to entry on study. (4) A system for assuring timely reporting of all serious and unexpected toxicities (adverse drug reactions, also referred to as ADRs) to the IRB and to the drug supplier in accordance with FDA requirements, and for informing the NCI Program Director of ADRs. For trials conducted under NCI-held INDs, this includes reporting of ADRs to the Investigational Drug Branch (IDB), CTEP, according to CTEP guidelines. (5) An on-site audit program for periodic data verification and review of regulatory responsibilities at each participating institution; for trials under NCI-held INDs, submission of reports of each such audit to NCI within six weeks of the audit. (6) For trials conducted under NCI-held INDs, a method of providing, upon request of the NCI, quarterly summaries of toxicity, efficacy, pharmacokinetics, and other laboratory data adequate to allow CTEP to fulfill its responsibility closely to monitor Phase I trials which it sponsors. (7) For trials conducted under NCI-held INDs, bi-weekly submission of comprehensive study data to CTEP's Clinical Trials Monitoring Service (CTMS), according to CTMS guidelines, if CTMS monitoring is deemed necessary by the NCI. This monitoring is necessary for the initial trial of a new agent in humans, and may be required for additional Phase I toxicity monitoring of trials, at the NCI's discretion. (8) For trials conducted under NCI-held INDs, implementation of the requirements for storage and accounting for investigational agents (described in the DCT Investigator's Handbook, which is available from the NCI Program Director upon request); registration of the protocol chairperson with CTEP's Drug Management Authorization Section for each such trial. The NCI will not approve a request for a group to add any institution that does not have an approved Assurance of Compliance for the Protection of Human Subjects on file with OPRR. The awardee institution will be responsible for assuring that no patients are accrued to a protocol at any participating institution until the protocol has been reviewed and approved by the IRB. Prompt, full compliance with all FDA-mandated requirements for investigational drug management will be required of all group investigators. These requirements may include suspension of protocol accrual, or changes in the conduct of a protocol (e.g., to insure patient safety). h. Progress Review The group will establish a mechanism for assessing performance of its members, with particular attention to accrual of adequate number of eligible patients onto CATBRM trials, timely submission of required data, conscientious observance of protocol requirements, preparation of manuscripts for publication, and participation in group leadership. Should the Progress Review process indicate poor performance by a participating institution, the awardee institution may request NCI approval to replace the institution according to the procedures outlined above in the SPECIAL REQUIREMENTS, A.1.a. of this RFA. i. Protocol Closure The NCI may request that a CATBRM protocol be closed to further patient accrual if: (a) the protocol's accrual goal has been met, (b) there has been an insufficient accrual rate, (c) there has been poor protocol performance, or (d) changes in drug availability make protocol completion unlikely. The NCI Program Director will submit any such request for protocol closure, with the reasons for the request, in writing to the Principal Investigator. If the group wishes to continue patient accrual, the Principal Investigator or the Clinical Investigations Leader must submit a written justification to the NCI Program Director for NCI review and approval. Without NCI approval, the group may not expend NCI funds for additional patient accrual to the protocol proposed for closure. Unresolved disagreements regarding the appropriateness of protocol closure for any of the above reasons will be submitted to arbitration by the process outlined above. Regulatory issues, such as those affecting patient safety, may require suspension of protocol accrual, or changes in the conduct of a protocol. As noted in the SPECIAL REQUIREMENTS, A.1.g. Terms of Cooperation, the group must comply fully with any suspension of accrual or other protocol modification mandated by federal regulatory officials. The awardee institution retains the primary responsibility for assuring group compliance with federally-mandated regulatory requirements. j. Attendance at Meetings The Principal Investigator, Program Leaders, and the NCI Program Director will meet periodically to review progress, plan and design research activities, and establish priorities. The Principal Investigator will determine the frequency of meetings, and will be responsible for scheduling the time and place of each meeting. No NCI staff member may chair group meetings. A critical determinant of group success will be the degree of communication among its members. Therefore, additional informal meetings among all participants as well as regular telephone and written communication is encouraged. k. Reporting Requirements Reporting requirements will be in agreement with FDA regulations and NCI procedures. Annual progress reports will be submitted to the NCI, and included in the non-competing research application. The report will include summary data on protocol performance by each participating institution, specific data on patient accrual, detailed reports of treatment associated morbidity, and other data deemed relevant by the Principal Investigator. In addition, quarterly data summaries will be provided as described above for trials of agents for which NCI holds the IND. l. Publication of Data Timely publication of major findings is encouraged. Publication or oral presentation of results obtained under this Cooperative Agreement will require appropriate acknowledgement of the NCI support. The Government, via the NCI Program Director, will have access to all data generated under this Cooperative Agreement and may periodically review the data. The awardee will retain custody of and primary rights to the data, consistent with current HHS, PHS, and NIH policies. 2. Nature of NCI Staff Participation As described throughout these Terms of Cooperation, the role of the NCI will be to assist and facilitate, not to direct, group activities. a. NCI Program Director The NCI shall designate a Program Director to guide the overall CATBRM program with the NCI. The NCI Program Director for the CATBRM program will be an extramural program director of the Biological Resources Branch, BRMP, DCT, NCI. The Program Director will also coordinate and facilitate NCIs role in each group. Decisions requiring NCI approval as outlined in these terms of cooperation will require the written approval of the NCI Program Director. The NCI Program Director will also insure that required approvals from other NCI components (for example, CTEP approval of protocols conducted under NCI-held INDs) are sought in a timely fashion and obtained. b. NCI as a Scientific Resource for CATBRM Group Activities The NCI Program Director will serve as a resource available to the group for specific scientific information with respect to treatment regimens and clinical trial design. c. NCI Assistance in Protocol Development While the CATBRM group's initial clinical protocol will have been developed as part of the application submitted to peer review, it is possible that the group will develop subsequent protocols within the objectives approved by peer review. The NCI Program Director will assist in developing such protocols by providing, as appropriate: (1) information about concurrent clinical trials in the group's area of research; (2) information about additional investigational agents relevant to the group's research goals; (3) assistance in applying additional government resources, as outlined below in section A.2.l. of these Terms of Cooperation; and (4) comments on the scientific rationale, design, statistical requirements, and implementation of the proposed protocol. All group protocols for which government funds from this cooperative agreement are expended will be subject to the terms of award, including these Terms of Cooperation. d. NCI Review of Proposed Protocols Awardees will conduct clinical protocols in accordance with the research objectives and methods approved by peer review. All protocols and protocol amendments must be submitted to the NCI Program Director for NCI review and approval. Awardees' initial protocols will have been scientifically approved by peer review. NCI will review subsequent protocols to insure they are within the scope of peer review. NCI will also review all protocols for safety considerations, as required by federal regulatory requirements. The NCI Program Director will coordinate and facilitate the review and approval process. The NCI will not provide investigational drugs or permit expenditure of NCI funds for a protocol that has not been approved according to the above procedures. The NCI Program Director will assist the group in developing any protocol revisions necessary to permit NCI approval of the protocol. Unresolved disagreements regarding NCI protocol review will be submitted to the same arbitration process outlined above. e. NCI Review of Quality Control and Study Monitoring For protocols involving NCI-held INDs, the NCI Program Director will coordinate any necessary NCI review and approval of quality control and study monitoring mechanisms to insure that FDA and OPRR-mandated regulatory requirements are met. The awardee institution will be responsible for insuring the group meets all federally-mandated regulatory requirements, as noted elsewhere in these Terms of Cooperation. f. NCI Review of Data Management and Analysis The NCI Program Director will review the group's mechanisms for data management and analysis (see above, A.l. Responsibilities of Awardees). Such mechanisms must be in place before NCI funds may be expended for any group clinical trial. Any disagreements between the NCI and the group relating to data management and analysis that cannot be resolved by bilateral discussions will be submitted to the same arbitration process previously outlined. g. Access to Data The Government, via the NCI Program Director, will have access to data generated under this Cooperative Agreement and may periodically review the data. However, the awardee will retain custody of and primary rights to the data, and timely publication of major findings by the group members is encouraged. Publications or oral presentation of work done under this agreement will require appropriate acknowledgement of the NCI support. Data from protocols conducted under NCI-held INDs must also be available for external monitoring, in accordance with an agreement between the NCI and the FDA governing the NCI's responsibilities as a drug monitor. h. NCI Involvement in Investigational Drug Management INDs for group trials may be held by the NCI, by a member of the group, or by an appropriate third party (such as the drug manufacturer, if not a member of the group). The proposed IND arrangements will be included in the initial application. The NCI must approve in advance any redistribution, outside the group, of biological and chemical materials received from the Government; and any dissemination of research findings resulting from the use of such materials so redistributed. The NCI Program Director will, in such instances, be responsible for assuring that any required approvals from other NCI officials are obtained. When the NCI is to file the initial IND or cross-file on an existing IND for an agent to be studied by a group, the NCI Program Director will coordinate NCI assistance (e.g., facilitating the completion of any necessary agreements between drug suppliers and NCI, or advising the Principal Investigator of FDA-mandated specific requirements and changes in requirements concerning investigational drug management). Investigators performing trials under Cooperative Agreements will be expected to comply with all FDA monitoring and reporting requirements for investigational agents. i. NCI Review of Mechanisms for Meeting Federally Mandated Regulatory Requirements The NCI Program Director will review the study group's mechanisms for meeting FDA regulatory requirements for investigational agents, and OPRR requirements for the protection of human subjects, and will determine whether review and approval by the NCI regulatory affairs officials is also required (specifically for studies under NCI-held INDs). If so, the NCI Program Director will facilitate that review and approval. j. NCI Review of Progress Performance of the group will be reviewed at least annually by the NCI Program Director on the basis of the group's annual reports and quarterly data summaries (described above under Responsibilities of Awardees). In addition, periodic accrual information may be requested from the group by the NCI Program Director for all active protocols when deemed appropriate. Insufficient patient accrual, progress, or noncompliance with the Terms of Award, including these Terms of Cooperation, may result in a reduction in budget, withholding of support, suspension, or termination of award. k. NCI Involvement in Protocol Closure The NCI may request that a CATBRM protocol be closed to further patient accrual if: (a) the protocol's accrual goal has been met; (b) there has been an insufficient accrual rate; (c) there has been poor protocol performance; or (d) changes in drug availability make protocol completion unlikely. The NCI Program Director will submit any such request for protocol closure, with the reasons for the request, in writing to the Principal Investigator. If the group wishes to continue patient accrual, the Principal Investigator or the Clinical Investigations Leader must submit a written justification to the NCI Program Director for NCI review and approval. Without NCI approval, the group may not expend NCI funds for additional patient accrual to the protocol proposed for closure. Unresolved disagreements regarding the appropriateness of protocol closure for any of the above reasons will be submitted to arbitration by the process outlined above. Regulatory issues, such as those affecting patient safety, may require suspension of protocol accrual, or changes in the conduct of a protocol. As noted in the SPECIAL REQUIREMENTS, A.1.g, the group must comply fully with any suspension of accrual or other protocol modification mandated by federal regulatory officials. The awardee institution retains the primary responsibility for assuring group compliance with federally-mandated regulatory requirements. l. Use of Other NCI Resources in Support of Group Activities Upon recommendation of the NCI Program Director, the NCI may make limited use of its contract based resources in support of group research activities. Use of such resources may be considered on an occasional basis, at the NCI's discretion, within its budgetary and programmatic constraints. m. NCI Review of Changes in Group Membership Post-award changes in a group's Principal Investigator, Program Leaders, Clinical or Laboratory Programs, or participating institutions will require NCI approval in accordance with the procedures described in the "SPECIAL REQUIREMENTS" section A.1.a. above. Failure of the awardee institution to propose an acceptable replacement for any of the above changes, or to demonstrate to the satisfaction of the NCI that the group's research can be completed in an appropriate and timely fashion, will result in withholding of support, suspension, or termination of this award. 3. The Terms of Cooperation described in this section are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS Grant Administration Regulations at 45 CFR Part 74, and other HHS, PHS, and NIH grant administration policy statements. B. Drug Information/IND's/Drug Supply 1. Patent status of agent(s) proposed for study. Since applicants are likely to propose studies with agents in early development, it is essential that each application address the patent status of the agent(s) proposed for study. If a patent already exists, or is pending, for an agent, the application should so state, and identify the patent holder. A letter, signed by the Principal Investigator and each Program Leader, recognizing the patent holder and status, must be included with the application prior to peer review. If patent coverage does not already exist for a proposed study agent, or if new patents (e.g., use patents) are to be filed, the application must include a detailed description of procedures for obtaining patent coverage for each such agent. This is essential to avoid patent disputes from delaying performance of awards by successful applicants. Procedures must also be described for resolution of legal problems within the group, should they arise. A formal agreement to these procedures, signed and dated by the organizational official authorized to enter into patent arrangements for each group member and member institution, must be on file at the Division of Extramural Activities, NCI prior to peer review. The specific patenting arrangements relevant to a group's application may vary widely depending upon the particular agent(s) proposed for study, the clinical trial(s) proposed, and the particular composition of a given group. Each applying group is encouraged to employ the arrangement most appropriate to its particular circumstances. Regardless of the arrangement used, however, its description MUST be included as part of the application. The description should be inserted following the overall Budget Section. Supporting documents (e.g., letters of agreement) should be included in the Appendix to the application. 2. IND status of agent(s) proposed for study. Each application must address the Investigational New Drug (IND) application status for each agent proposed for study. INDs for CATBRM clinical trials may be held by the applicant, or by the supplier of the agent. Alternatively, when desirable to facilitate the conduct of the clinical trial, the NCI may hold the IND or cross-reference an existing IND. Applicants are encouraged to propose the IND arrangement most appropriate to the goals of their application. If an IND already exists for an agent, the IND number and the identity of the IND holder should be included in the body of the application. For any agent for which an IND does not exist, the application must include enough information to demonstrate that an IND will be obtained in a timely fashion. This information should include: o a description of currently available preclinical data for the agent; o a list of additional preclinical studies which remain to be done in support of IND filing; o the anticipated date of IND filing; o In addition, the application should demonstrate that INDs for all agents to be used in the initial clinical trial will be available early enough to allow patient accrual to begin within three months of the date of award. o The application should also demonstrate that INDs for agents to be used in subsequent clinical trials are expected to be available early enough that continuous patient accrual to clinical protocols may be expected throughout the award period. o Applicants proposing to conduct a trial without an IND must demonstrate that all applicable FDA requirements will be met, consistent with the above guidelines. Discussions of IND issues should be inserted in the body of the application, following the overall Budget Section. Supporting documents (e.g., letters of agreement) should be included in the Appendix to the application. 3. Supply of agent(s) for clinical trials. Each application must describe the steps the applying group will take to insure adequate supplies of agents for the clinical trials proposed. Depending upon an applicant's particular circumstances, such information may include a discussion of mechanisms of procuring agents, timetables for production of agents, or evidence of industry collaboration. If possible, letters of support from pharmaceutical companies should be included. Discussions of drug supply issues should be inserted in the body of the application, following the overall Budget Section. Supporting documents (e.g, letters of agreement) should be included in the Appendix to the application. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements are required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis should be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale must be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues must be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information must be included in the form PHS 398 in 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 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 minorities differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. If the required information is not contained within the application, the application will be returned. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and will be reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. LETTER OF INTENT Prospective applicants are asked to submit, by October 30, 1992, a short 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 this RFA. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information that it contains is helpful in planning for the review of applications. It allows ICD staff to estimate the potential review workload and to avoid conflict of interest in the review. Letters of intent is to be sent directly to: Jon T. Holmlund, M.D. Biological Resources Branch Biological Response Modifiers Program National Cancer Institute-FCRDC Building 1052, Room 253 Frederick, MD 21702-1201 Telephone: (301) 846-1098 FAX: (301) 846-5429 APPLICATION PROCEDURES A. Minimal Requirements for Application Applications must meet the requirements listed below. Except for item 1, each of these must be briefly addressed in the INTRODUCTORY section of the application. The INTRODUCTORY section may reference a fuller discussion elsewhere in the application, provided that the location of that discussion is clearly given in the INTRODUCTORY section. 1. The research grant application form PHS 398 (rev. 9/91) is to be used. This form is available at most institutional business offices; from the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892 (telephone 301/496-7441); and from the NIH Program Administrator named below. 2. Name a single Principal Investigator, who is an M.D., Ph.D., or D.O., who will be responsible for the application, for group research activities, and for the dispersal of funds for the support of group activities. 3. If the Principal Investigator is a Ph.D., name a single Clinical Investigations Leader, who is an M.D. or a D.O., who will be responsible for the overall conduct of the group's clinical trials. 4. Identify the applicant institution that will assume legal and financial responsibility and accountability for the use and disposition of funds awarded on the basis of this RFA. 5. Provide, in the body of the application, a description of the patent status of the agent(s) to be studied, and of the group's plans to address patent issues, as discussed above in the SPECIAL REQUIREMENTS section B.1. of this RFA. Include supporting documents in an Appendix. 6. Provide, in the body of the application, a description of the IND status of the agent(s) proposed for study, including (in an Appendix) supporting information, as discussed above in the SPECIAL REQUIREMENTS section B.2. of this RFA. 7. State how the group plans to insure the availability of adequate drug supplies for the clinical trial. Include supporting material (e.g., letters of support from drug suppliers) in an Appendix. 8. Describe the group's overall goals and, in the context of these goals, describe how the group envisions the clinical development of the agent(s) and/or regimen(s) to be tested. 9. Include one detailed clinical protocol, for the first trial proposed. Include Notice of IRB Approval. Provide detailed evidence supporting the rationale for the protocol, including literature citations, and emphasizing the results of work done by the proposed group members. Describe any subsequent trials envisioned by the group during the award period; it is not necessary, however, to include additional detailed protocols. 10. Provide from the Principal Investigator and from each Program Leader a signed statement of acceptance of the provisions outlined under the SPECIAL REQUIREMENTS section A.1. Terms of Cooperation. 11. Provide a clear, concise plan that depicts the interrelationships among the members of the group and the contribution of each to fulfillment of group objectives. This plan may be in narrative and/or diagrammatic form; use the form which most clearly describes the group. The name, organization, and scientific discipline of the Principal Investigator, Program Leaders, and other key personnel should be included. 12. Provide a plan to assure the maintenance of close collaboration and effective communication among members of the group which will include letters of commitment to this plan by all Program Leaders. Include plans for scheduling group meetings, notifying group members (including the NCI), and documenting and disseminating group meeting proceedings. 13. Demonstrate that the Principal Investigator and the Program Leaders possess the necessary scientific skills and leadership qualities to conduct the proposed research successfully; include relevant research programs, experience, unique competencies, and pertinent publications. 14. Demonstrate the competence of the Principal Investigator to manage comprehensive research projects, and to coordinate and integrate research activities of diverse Clinical and Laboratory Programs. 15. Demonstrate that each component Clinical and Laboratory Program is required for the attainment of the group's objectives and that each has available the professional and technical personnel to permit efficient and successful conduct of the proposed research. Show that total personnel of the group are sufficient in quality and quantity to assure successful conduct of the proposed research. 16. Demonstrate for all key personnel the time available for this project and show for all key professional personnel: (1) title, identifying number, percentage of effort devoted to the project, direct costs, and project period of all awarded and pending grants, Cooperative Agreements, contracts, and industrial commitments regardless of source of funding; and (2) identify and explain areas of potential scientific and/or budgetary overlap with active and pending grants, contracts, and Cooperative Agreements and what support would be relinquished if this Cooperative Agreement award is made. Describe the steps that will be taken to insure successful completion of the group's research should a key member leave the group. 17. Demonstrate that each component Laboratory Program and the group as a whole have available the facilities required for conduct of the proposed research. Funds will not be provided for alteration or renovation of facilities under this Cooperative Agreement. 18. Demonstrate that the group may expect sufficient patient accrual to complete the clinical trial in a timely fashion. 19. Describe the quality control measures that will be used by the group, as required under the "SPECIAL REQUIREMENTS" section A.1., Terms of Cooperation. 20. Demonstrate the capability to conduct study monitoring, and data management and analysis, as required under the "SPECIAL REQUIREMENTS" section A.1., Terms of Cooperation. 21. Describe how the group will comply with federally mandated regulatory requirements, as outlined under the "SPECIAL REQUIREMENTS" section A.1., Terms of Cooperation, and demonstrate that each institution conducting group trials has a current, approved assurance on file with OPRR. 22. Describe how the group will comply with the NIH policies concerning inclusion of women and minorities in clinical research study populations ("STUDY POPULATIONS" section of this RFA). B. Method of Applying 1. Receipt Date The deadline for receipt of applications is December 22, 1992. Applications received after this date will be returned to the applicant without review. 2. General a. Submit a signed, typewritten original of the application, including a single 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 same time of submission, two additional exact, single-sided copies of the application must also be sent to: Referral Officer National Cancer Institute Westwood Building, Room 848 Bethesda, MD 20892 Telephone: (301) 496-3428 The NCI-FCRDC address under INQUIRIES is sufficient for express mail or courier service to that location. b. To expedite the review of your application, and to assure its identification with this RFA: (1) The application form must have "CLINICAL STUDY GROUPS FOR CANCER THERAPY WITH BIOLOGICAL RESPONSE MODIFIERS (CATBRMs) (RFA CA-92-28) on line 2a of the face page of the application form; personalized titles more fitting for your application should be listed on line 1 and not on line 2. The YES box on the face page must be marked. (2) The RFA label available in the application form PHS 398 (rev. 9/91) must be affixed to the bottom of the face page. Failure to use this label could result in delayed processing of your application such that it may not reach the review committee in time for review. (3) Applicants from institutions that have a General Clinical Research Center (GCRC) funded by the NIH National Center for Research Resources are requested to identify the GCRC as a resource for conducting the proposed research. 3. Organization of Application and Suggested Modifications of Form PHS 398 This RFA requires the submission of a single application for the proposed CATBRM study group. If the application submitted in response to this RFA is substantially similar to a research 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. Because of the possible multi-institutional nature of a group, and the special requirements in this RFA, additional suggestions regarding format and some modifications seem desirable to provide a comprehensive yet readily reviewable application. a. Each application should clearly identify the CLINICAL and LABORATORY programs proposed, the proposed costs attributable to each, and the relationship among the various programs. If it is not possible to do this using a single form PHS 398 (rev. 9/91), separate forms PHS 398 (rev. 9/91) may be used to describe the various programs. If this is done, the application must have one INTRODUCTION SECTION and consecutively numbered sections for each of the CLINICAL PROGRAMS and each of the LABORATORY PROGRAMS including the Clinical or Laboratory Program of the proposed Principal Investigator. Use form PHS 398 (rev. 9/91) for each CLINICAL PROGRAM and each LABORATORY PROGRAM, but omit the face page for the individual program. A single face page should apply to the entire application. Insert the INTRODUCTION after the Table of Contents. It is suggested that the title "Principal Investigator" for the section describing the Clinical or Laboratory Program of the Principal Investigator) be substituted for "Principal Investigator/Program Director" and that the Description" (grant application form, page 2) for each of the Clinical or Laboratory Program, in addition to describing the work proposed, provide a statement of relevance to the overall objectives of the proposed group. A single checklist should be provided for the overall application. Do not include a checklist for each Clinical or Laboratory Program. The 25-page limitation stipulated in the PHS-398 kit applies to each of the individual Clinical or Laboratory Programs. The overall Introductory Section should also be limited to 25 pages. All "Minimal Requirements for Application" must be discussed in the INTRODUCTORY section (or in the body of the application if only one Form PHS-398 (rev. 9/91) is used. As noted elsewhere in this RFA, include supporting documents in an Appendix. Sections pertaining to Clinical or Laboratory Programs should provide, for each program, a Detailed Budget for the First 12- Month Budget Period INCLUDING APPLICABLE INDIRECT COSTS FOR CONSORTIUM INSTITUTIONS and a Budget for the Entire Proposed Project Period. JUSTIFY BUDGET REQUESTS according to the guidelines in Form PHS-398. The formal clinical protocol submitted with the application should be in an APPENDIX to the application. Often the various research objectives necessary to reach the group's goals may need to be phased in, at least in part, in sequential fashion. In such cases, the budgets for the individual Clinical and Laboratory Programs should, logically, reflect an appropriate change in relative emphasis among objectives until an operational steady state situation is attained. Justification for phase-in budgets should also be provided. b. The application should begin with an INTRODUCTORY SECTION bearing the title CLINICAL STUDY GROUP FOR CANCER THERAPY WITH BIOLOGICAL RESPONSE MODIFIERS (CATBRM), and the phrase, "Prepared in Response to RFA No. CA-92-28." Form PHS 398 is to be used for this Introductory Section and must describe the proposed CATBRM group as a whole with respect to goals, objectives, and overall research plan. In this Introductory Section, list the Program Leaders as "Key Personnel Engaged on Project." Other key personnel must be listed in the proposed research plan for each individual Clinical or Laboratory Program. It is important to discuss any prior collaborative efforts among investigators in the group as well as advantages expected from the group effort, e.g., how the projects are mutually reinforcing, how collectively they will further the goals of the proposed research, etc. In the Introductory Section, a summary budget should reflect the consolidated TOTAL DIRECT COSTS of the entire proposed group. This should include the direct costs at the applicant institution and both direct and indirect costs at participating institutions. The Introductory Section should also provide, from the applicant institution, a Detailed Budget for the First 12-Month Period and a Budget for the Entire Proposed Project Period for Direct Costs for each of the following: (1) The Principal Investigator's Clinical or Laboratory Program; and (2) Management and coordination of group activities. Inasmuch as the Principal Investigator may also function as a Program Leader for his/her Laboratory Program, parts of form PHS 398 that duplicate information provided in the section describing the Principal Investigator's work need not be included in the Introductory Section. The Introductory Section should, however, contain any additional information about the proposed Principal Investigator or his/her institution as evidence of capability to carry out the scientific and administrative duties required in this RFA. c. The application will be reviewed as a whole as well as program by program. Therefore, prepare a detailed Table of Contents that will enable reviewers to find specific information readily and number all pages consecutively after the face page, which is page 1. Complete all items on the face page of the application (only one per application) as in a regular research grant proposal. Identify projects by number, title and Program Leader. Identify cores by letter, title and Program Leader. d. In order to facilitate project by project review, a complete PHS 398 form (rev. 9/91)--exclusive of face page and checklist--should be used for each program. This specifically includes project budgets and curriculum vitae. The C.V. of the Principal Investigator should be included in the INTRODUCTORY SECTION and in their individual Clinical or Laboratory Programs (if any); the C.V.s of all other personnel should appear only in the Clinical or Laboratory Programs or Cores with which they are affiliated; the INTRODUCTORY SECTION should use only brief textual descriptions of those personnel who appear elsewhere in the application. Such descriptions should be cross-referenced to the appropriate Program. REVIEW CONSIDERATIONS A. Review Procedure Upon receipt, applications will be reviewed by the DRG for completeness and responsiveness. Incomplete applications will be returned to the applicant without further consideration. Evaluation for responsiveness to this RFA is an NCI program staff function. Applications will be judged to determine whether or not they meet the goals and objectives of the program as described in the RFA. If an application is not responsive to the RFA, it will be returned to the applicant and the proposed Principal Investigator will be contacted to determine whether submission for review in competition with unsolicited applications at the next review cycle is desirable to the applicant. If an application is judged non-responsive to this RFA, any of its constituent Clinical or Laboratory Programs may be submitted as an investigator-initiated regular research grant (R01) at the next receipt date. Alternatively, the consortium of Clinical Programs, Laboratory Programs, or some combination of Clinical and Laboratory Programs could seek funding as a program project grant (P01). In either event, the application would require modification in accordance with either the R01 or P01 guidelines. Such new application would not be considered an application for a Cooperative Agreement, nor would it be considered a response to an RFA. Questions concerning the relevance of proposed research to the RFA may be directed to program staff listed under INQUIRIES. If the number of applications received is large compared to the number of awards to be made, the NCI may conduct a preliminary scientific peer review to eliminate those that are clearly not competitive for award. The NCI will remove from further competition those applications judged to be noncompetitive and notify the Principal Investigator and institution official. Those applications judged to be both competitive and responsive will be further evaluated, using the review criteria shown below, for scientific and technical merit by an appropriate peer review group convened by the Division of Extramural Activities, NCI. Following peer review, the applications will receive a second-level review by the National Cancer Advisory Board, which considers the special needs of the Institute and the priorities of the National Cancer Program. B. Peer Review Criteria 1. Extent of relevance of applicant's objectives to the clinical development of novel approaches to the treatment of cancer with BRM's. 2. Scientific merit and originality of proposed research. 3. Specific scientific and clinical merit of the proposed clinical trial. 4. Quality of data supporting the proposed clinical trial. 5. Scientific and technical merit of the proposed laboratory studies. 6. Evidence that the Principal Investigator and the Program Leaders possess the scientific skills and leadership qualities needed to conduct the proposed research successfully; experience, competence, commitment, and time availability of Principal Investigator, Program Leaders, and other key personnel. 7. Evidence that each component Clinical and Laboratory Program is required for the attainment of the group's objectives, and that each has available the professional and technical personnel to permit efficient and successful conduct of the proposed research. 8. Competence of Principal Investigator to develop, implement, and manage comprehensive research programs, and to coordinate and integrate research activities of diverse clinical and laboratory programs. 9. Adequacy of plans for effective intra-group communication and for assuring group cohesiveness. 10. Adequacy of existing physical facilities and resources of the Principal Investigator and Program Leaders. 11. Evidence that Clinical Programs are capable of completing the clinical trial in a timely fashion, including evidence of adequate patient accrual. 12. Evidence of approval and commitment of institutions represented by group members to group goals. 13. Commitment to accept provisions outlined under the "SPECIAL REQUIREMENTS" section A.1., Terms of Cooperation. 14. Evidence that appropriate steps have been taken to insure the protection of human subjects. 15. Evidence that the applicant is in compliance with NIH policies regarding the inclusion of women and minorities in clinical research study populations ("STUDY POPULATIONS" section of this RFA). The review group will critically examine the submitted budget and will recommend an appropriate budget and period of support for each approved application. AWARD CRITERIA The anticipated date of award is June 30, 1993. In addition to technical merit, availability of resources (including drug supplies for the proposed clinical trials) and overlap with existing studies sponsored by the Biological Response Modifiers Program will be considered in making awards. INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. The opportunity to clarify any issues and questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Jon Holmlund, M.D. Program Director, Biological Resources Branch Biological Response Modifiers Program National Cancer Institute-FCRDC Building 1052, Room 253 Frederick, MD 21701-1201 Telephone: (301) 846-1098 FAX: (301) 846-5429 Direct inquiries regarding fiscal matters to: Ms. Katharine Schulze Grants Management Specialist Grants Administration Branch National Cancer Institute Executive Plaza South, Room 242 6120 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-7800, Ext. 16 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 authorization of the Public Health Service Act, Title, 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 Wed Oct 07 23:00:00 1992 Path: biosci!NET.BIO.NET!kristoff From: kristoff@NET.BIO.NET (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 21, no. 36, pt. 1, 9 October 1992 Message-ID: Date: 8 Oct 92 23:53:56 GMT Sender: kristoff@net.bio.net Distribution: bionet Lines: 1506 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 19921009 V21N36 P1O2 ************************************ X-comment: RFAs described: AI-92-08, AI-92-13, CA-92-28, HD-94-01, HL-93-03-B NIH GUIDE - Vol. 21, No. 36 - October 9, 1992 $$INDEX BEGIN ******************************************************* NOTICES $$INDEX N1 ********************************************************** HUMAN SUBJECT PROTECTIONS WORKSHOPS National Institutes of Health Food and Drug Administration INDEX: NATIONAL INSTITUTES OF HEALTH; FOOD AND DRUG ADMINISTRATION $$INDEX N2 ********************************************************** REVISED PHS 416-9 APPLICATION FORM Division of Research Grants INDEX: DIVISION OF RESEARCH GRANTS NOTICES OF AVAILABILITY (RFPs AND RFAs) $$INDEX R1 ********************************************************** EVALUATION OF THE EFFECT OF A FAT MODIFIED DIET ON HORMONES DURING ADOLESCENCE (RFP NCI-CN-25502-51) National Cancer Institute INDEX: CANCER $$INDEX R2 ********************************************************** CULTURED NEURON PROBE (RFP NIH-NINDS-93-02) National Institute of Neurological Disorders and Stroke INDEX: NEUROLOGICAL DISORDERS, STROKE $$INDEX R3 ********************************************************** ANTIGENIC VARIATION OF HIV-1 AND RELATED LENTIVIRUSES (RFP NIH-NIAID- DAIDS-93-13) National Institute of Allergy and Infectious Diseases INDEX: ALLERGY, INFECTIOUS DISEASES $$INDEX R4 12/10/92 ************************************************* PAPILLOMAVIRUS IN VITRO CELL CULTURE SYSTEMS (RFA AI-92-08) National Institute of Allergy and Infectious Diseases INDEX: ALLERGY, INFECTIOUS DISEASES $$INDEX R5 01/14/93 ************************************************* WOMEN AND INFANTS TRANSMISSION STUDY (WITS II) (RFA AI-92-13) National Institute of Allergy and Infectious Diseases INDEX: ALLERGY, INFECTIOUS DISEASES $$INDEX R6 12/23/92 ************************************************* CLINICAL TRIALS OF CANCER THERAPY WITH BIOLOGICAL RESPONSE MODIFIERS (RFA CA-92-28) National Cancer Institute INDEX: CANCER $$INDEX R7 05/18/93 ************************************************* SPECIALIZED RESEARCH CENTER PROGRAMS AND CENTER CORE GRANTS TO SUPPORT RESEARCH IN REPRODUCTION (RFA HD-94-01) National Institute of Child Health and Human Development INDEX: CHILD HEALTH, HUMAN DEVELOPMENT $$INDEX R8 03/15/93 ************************************************* CELL AND MOLECULAR BIOLOGY OF MEGAKARYOCYTOPOIESIS (RFA HL-93-03-B) National Heart, Lung, and Blood Institute INDEX: HEART, LUNG, BLOOD ONGOING PROGRAM ANNOUNCEMENTS $$INDEX P1 ********************************************************** SELECTIVE COGNITIVE DEFICITS IN NEURODEVELOPMENTAL DISORDERS (PA-93- 004) National Institute of Neurological Disorders and Stroke INDEX: NEUROLOGICAL DISORDERS, STROKE $$INDEX P2 ********************************************************** ARTHRITIS & SKIN DISEASES (MINORITY POPULATIONS) (PA-93-005) National Institute of Arthritis and Musculoskeletal and Skin Diseases INDEX: ARTHRITIS, MUSCULOSKELETAL, SKIN DISEASES ERRATUM $$INDEX E1 ********************************************************** DIETARY PATTERNS AND BLOOD PRESSURE (RFA HL-92-11-P) National Heart, Lung, and Blood Institute INDEX: HEART, LUNG, BLOOD This publication is also available electronically to institutions via BITNET or INTERNET. Alternative access is through the NIH Grant Line using a personal computer. Contact Dr. John James at 301/496-7554 for details, or send an E-mail message to ZNS@NIHCU. $$INDEX END ********************************************************* NOTICES $$N1 BEGIN ********************************************************** HUMAN SUBJECT PROTECTIONS WORKSHOPS NIH GUIDE, Volume 21, Number 36, October 9, 1992 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 subjects. The meetings should be of special interest to those persons 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 the following: SOUTHWESTERN WORKSHOP DATES: November 16 & 17, 1992 LOCATION: Wyndham Warwick 5701 Main Street Houston, TX 77005 Telephone: (713) 526-1991 SPONSORS: University of Texas Health Science Center at Houston Prairie View A & M University REGISTRATION: Ms. Paula Knudson Executive Coordinator Office of Research Support Committee University of Texas Health Science Center at Houston P.O. Box 20036 Houston, TX 77225 Telephone: (713) 792-5048 TITLE: Geriatric Research as an Ethical Mandate: Politics, Policy, and Problems DESCRIPTION: Expanded life expectancies and expanding technologies are swelling the ranks of the frail and disabled elderly. Minimal research has been carried out to understand the problems this subject group and their families encounter in finding solutions to their health and social needs. The conference will identify key problems that need to be studied; isolate the risks and benefits associated with behavioral, clinical, or evaluation research designed to enroll this group as subjects; and pose solutions that will meet the needs of regulators, scientists, and the elderly. The program is designed to be of interest to physicians, nurses, pharmacists, scientific investigators, other health care professionals, clergy, lawyers, medical, nursing, social work students, psychologists and IRB members and administrators. Attention will be paid to Federal regulations with special emphasis on the assessment of risks---medical, legal, and psychosocial. Opportunities will be available through workshops, question periods, and informal discussions for participants to exchange ideas and interests with faculty and OPRR and FDA representatives. SOUTHEASTERN WORKSHOP DATES: January 14 & 15, 1993 LOCATION: Sheraton Sand Key Resort 1160 Gulf Boulevard Clearwater Beach, FL 33515 Telephone: (813) 595-1611 SPONSORS: University of South Florida Florida A & M University REGISTRATION: Ms. Eileen Highsmith Executive Secretary University of South Florida 4202 E. Fowler Avenue (MP.FAO-126) Tampa, FL 33620-7900 Telephone: (813) 974-2897 TITLE: Barriers to Informed Consent: Language, Age Factors, Trauma, and Women/Minority Issues DESCRIPTION: Today's researchers face numerous barriers to obtaining an informed consent. Such issues as age, language, mental capacity, and sobriety may affect the ability of subjects to give a truly informed consent. Many of these barriers oftentimes impact the pool of subjects which an investigator is willing (or able) to use in a research project. In addition, recent legislation from the Congress was designed to address the issue of inadequate numbers of women and minorities in research projects. This conference has been designed to address three main areas in which barriers to informed consent may exist: mental competence, ethnic and gender issues, and research with children and the elderly. The conference program is designed to be of value to physicians, nurses, pharmacists, scientific investigators, and other health care professionals. All IRB members, students in health care areas and administrators will also benefit from the conference. Attention will be given to Federal regulations governing research on human subjects, with special emphasis placed on the assessment of risks---medical, legal, and psychosocial. Ample opportunities will be provided to exchange ideas and interests, through question and answer sessions and informal discussions. SOUTHWESTERN WORKSHOP DATES: February 12 & 13, 1993 LOCATION: Sheraton Tempe Mission Palms Hotel 60 East 5th Street Tempe, AZ 85281 Telephone: (602) 894-1400 SPONSORS: Arizona State University Northern Arizona University REGISTRATION: Ms. Carol Jablonski IRB Coordinator Office of the Assistant Vice President for Research Arizona State University Tempe, AZ 85287-3403 Telephone: (602) 965-6788 TITLE: Contemporary Issues in Human Subject Research: Challenges for Today's IRBs DESCRIPTION: This program is designed to be a practical working session to explore contemporary issues in human subjects protection including regulations and assurances, categorization of research protocols, uses of special populations, experimental design and scientific merit, fetal tissue research, ethical/legal issues in human subjects research, and conflict of interest. As appropriate, topics will be discussed from the perspective of the clinical researcher and the behavioral/social science researcher. Issues will be discussed in a panel format with ample time for audience questions. An outstanding faculty has been assembled. This program should be of interest to researchers in clinical medicine and the behavioral and social sciences. Institutional Review Board members, university and hospital administrators, lawyers, ethicists, health care practitioners, students, and other persons with interests in human subject protection issues. For further information regarding these workshop or future NIH/FDA National Human Subject Protections Workshops, contact: Ms. Darlene Marie Ross Executive Assistant for Education Division of Human Subject Protections Office for Protection from Research Risks National Institutes of Health 9000 Rockville Pike Building 31, Room 5B59 Bethesda, MD 20892 Telephone: (301) 496-8101 $$N1 END ************************************************************ $$N2 BEGIN ********************************************************** REVISED PHS 416-9 APPLICATION FORM NIH GUIDE, Volume 21, Number 36, October 9, 1992 P.T. 34; K.W. 1014006 Division of Research Grants The Public Health Service (PHS) started mailing the revised Application for Public Health Service Individual National Research Service Continuation Award---PHS 416-9---to appropriate awardees in September 1992. This revision, dated 10/91, approved through 10/31/94, replaces the version that was revised 7/88 and approved through 4/30/91. The major changes in the revised continuation award application include: o an explanation of the required documentation regarding gender and minority representation in study populations, and o a new Checklist, form page 4, with an updated list of required assurances and certifications. The PHS mails the 416-9 application kits directly to individual awardees several weeks before the due date. Thus, sponsoring institutions need not stock the form. INQUIRIES Questions about the monthly mailings of applications kits may be directed to: Renewal Unit, Project Control Section Division of Research Grants Westwood Building, Room 253 Bethesda MD 20892 Telephone: (301) 496-7210 General questions regarding the use of the PHS 416-9 application may be directed to the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, telephone: (301) 496-7441 or the grants management specialist at the appropriate awarding institute or center of the PHS. $$N2 END ************************************************************ NOTICES OF AVAILABILITY (RFPs AND RFAs) $$R1 BEGIN RFP NCI-CN-25502-51 ************************************** EVALUATION OF THE EFFECT OF A FAT MODIFIED DIET ON HORMONES DURING ADOLESCENCE NIH GUIDE, Volume 21, Number 36, October 9, 1992 RFP AVAILABLE: NCI-CN-25502-51 P.T. 34, AA; K.W. 0710095, 0765025, 0760025 National Cancer Institute The National Cancer Institute (NCI), Prevention and Control Contracts Section (PCCS), intends to issue a Request for Proposal (RFP) NCI-CN-25502-51. The Division of Cancer Prevention and Control, NCI, is conducting a study to evaluate the effect of a fat-modified diet on hormones during childhood and adolescence. The study is being performed ancillary to the Diet Intervention Study in Children (DISC), a randomized clinical trial sponsored by the Division of Epidemiology and Clinical Applications, National Heart, Lung and Blood Institute (NHLBI). The objectives of DISC are to determine whether a fat-modified diet during childhood and adolescence will lower LDL-cholesterol and to assess the feasibility and safety of this diet. The objectives of the NCI ancillary study are to evaluate the effect of this fat-modified diet on sex hormones and to correlate characteristics of children and adolescents, such as age, Tanner stage, anthropometry, diet, and physical activity, with sex hormone levels. This solicitation seeks a contractor to store serum specimens collected for DISC, develop and issue an RFP for a laboratory to perform serum hormone assays, evaluate the offerors' proposals, award a subcontract to the best qualified laboratory offering the best buy for the Government, and monitor the laboratory to ensure high quality work and fulfillment of contractual obligations. This RFP will be available on or about October 2, 1992, with responses due approximately six weeks thereafter. No collect calls will be accepted. Copies of the RFP may be obtained by sending a written request to: Christine L. Ptak, Contract Specialist Research Contracts Branch, PCCS National Cancer Institute Executive Plaza South, Room 635 9000 Rockville Pike Bethesda, MD 20892 Telephone: (301) 496-8603 $$R1 END ************************************************************ $$R2 BEGIN RFP NIH-NINDS-93-02 ************************************** CULTURED NEURON PROBE NIH GUIDE, Volume 21, Number 36, October 9, 1992 RFP AVAILABLE: NIH-NINDS-93-02 P.T. 34; K.W. 0740050, 0710085, 0750005, 0706000 National Institute of Neurological Disorders and Stroke The Neural Prosthesis Program of the National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health, is seeking a contract to determine the feasibility of establishing connections with specific target neuronal populations in the mammalian central nervous system (CNS) by developing and evaluating a cultured neuron probe. If successful, the probes will be implanted into a mammalian CNS region and an attempt will be made to demonstrate two-way communication between the linking neurons and the target neurons. Personnel with established expertise in neurophysiology, biomaterials, and microfabrication are required. It is anticipated that one award will be made in May 1993, for a period of three years. This is not a Request for Proposals (RFP). To receive a copy of the RFP, please submit a written request to the following address, and supply this office with two self addressed mailing labels. All responsible sources will be considered by the agency. The RFP will be issued on or about October 8, 1992 with proposals due on December 7, 1992. Contracting Officer Contracts Management Branch, DEA National Institute of Neurological Disorders and Stroke Federal Building, Room 901 7550 Wisconsin Avenue Bethesda, MD 20892 Attention: RFP No. NIH-NINDS-93-02 $$R2 END ************************************************************ $$R3 BEGIN RFP NIH-NIAID-DAIDS-93-13 ******************************** ANTIGENIC VARIATION OF HIV-1 AND RELATED LENTIVIRUSES NIH GUIDE, Volume 21, Number 36, October 9, 1992 RFP AVAILABLE: NIH-NIAID-DAIDS-93-13 P.T. 34; K.W. 1002045, 0710070, 0755010, 0780005 National Institute of Allergy and Infectious Diseases The Vaccine Research and Development Branch, Basic Research and Development Program, Division of AIDS, National Institute of Allergy and Infectious Diseases (NIAID) has a requirement for a contractor to receive and process virus-infected, human-derived samples on a large scale basis and to isolate, expand and immunologically characterize HIV-1 and related lentiviruses from these samples. Specifically, the selected contractor will be responsible for: 1) performing virus isolation, expansion, and characterization from samples supplied to the Contractor; 2) performing specific immunological assays for HIV and related lentiviruses; 3) classifying all virus isolates received into antigenic subgroups based upon serological/immunological assays; 4) securing, receiving, cataloging, processing, and storing samples from both domestic and international sites, and distributing samples to other investigators; 5) providing inventory and a Database Management System; 6) providing facilities and resources; 7) reporting progress according to reporting requirements; 8) meeting with the Project Officer; 9) obtaining clearance for publication; and 10) implementing an orderly transition to a successor Contractor. This is an announcement for an anticipated Request for Proposals (RFP). RFP NIH-NIAID-DAIDS-93-13 will be issued on or about October 9, 1992 with a closing date tentatively set for December 22, 1992. One contract will be awarded as a result of this solicitation. It is expected that the contract will have a five-year period of performance. A level-of-effort cost-reimbursement contract is anticipated. Requests for the RFP shall be directed in writing to: Chief, Contract Management Branch, National Institute of Allergy and Infectious Diseases Solar Building, Room 3C07 Bethesda, MD 20892 FAX: (301) 402-0972 Please provide this office with three 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. That version includes only the statement of work and the Evaluation Criteria to be used for selection of the awardee. 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 the full-text version only. All proposals from responsible sources will be considered by the NIAID. This advertisement does not commit the Government to award a contract. $$R3 END ************************************************************ $$R4 BEGIN AI-92-08 FULL-TEXT *************************************** PAPILLOMAVIRUS IN VITRO CELL CULTURE SYSTEMS NIH GUIDE, Volume 21, Number 36, October 9, 1992 RFA AVAILABLE: AI-92-08 P.T. 34; K.W. 1002045, 0780015, 0740020 National Institute of Allergy and Infectious Diseases Letter of Intent Receipt Date: November 6, 1992 Application Receipt Date: December 10, 1992 THE REQUEST FOR APPLICATIONS (RFA) ANNOUNCED IN THIS NOTICE CONTAINS ESSENTIAL INFORMATION FOR THE PREPARATION OF AN APPLICATION. POTENTIAL APPLICANTS MAY OBTAIN THE RFA FROM THE CONTACT NAMED IN INQUIRIES, BELOW. PURPOSE The Antiviral Research Branch of the Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), invites Cooperative Agreement applications from organizational entities willing to participate, with the assistance of the NIAID, in furthering innovative in vitro approaches to the study of papillomavirus infections and their therapeutic control. The research goals of this solicitation are to stimulate the use of in vitro papillomavirus replication systems for research on (1) the events of papillomavirus replication and pathogenesis; and (2) the antiviral potential of experimental therapeutic agents. 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, Papillomavirus in Vitro Cell Culture Systems, is related to the priority area of sexually transmitted diseases. Potential applicants may obtain a copy of "Healthy People 222" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783- 3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign for-profit and non- profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT The funding mechanism to be used is the cooperative agreement (U01). The cooperative agreement differs from the traditional research grant in that there will be substantial programmatic involvement of NIAID staff above and beyond the levels required for traditional program management of grants. This RFA is a one-time solicitation. Future unsolicited competing continuation applications will compete with all investigator-initiated applications and be reviewed according to the customary NIH peer review procedures. FUNDS AVAILABLE It is expected that at least one application will be funded for a four-year period, contingent upon the receipt of a sufficient number of meritorious applications. It is expected that the total direct costs for the first year for successful applications will be around $175,000. However, individual awards may be higher or lower. RESEARCH OBJECTIVES Papillomavirus infection is a rapidly increasingly serious clinical problem in the United States and around the world. None of the currently available therapies has acceptable efficacy. The failure to develop a safe and effective therapy for these infections is due, in part, to the inability to replicate virus in vitro. In the past few years, several research groups have developed in vitro systems in which many of the events of papillomavirus replication have been reported to occur. The availability of these systems provides an unparalleled opportunity to investigate the mechanisms of papillomavirus replication and pathogenesis at a molecular level. This basic research may also result in the identification of viral genes which are promising targets for therapeutic intervention. In addition, these systems should provide a means to evaluate the potential anti-papillomavirus activity of experimental agents and provide a rational basis for selecting agents whose activity warrants further study in the animal models. The proposed systems may utilize either a human papillomavirus (HPV) or an animal papillomavirus as a model of HPV infection. Review Procedures A preliminary review will be done by NIAID staff upon receipt of the applications. Any application that is incomplete or judged to be unresponsive to this RFA will be returned to the applicant without technical review. Applications that are complete and responsive may be subjected to a triage procedure by peer review to determine competitiveness among the applications. Applications judged to be competitive for award will be reviewed in detail in accordance with established NIH peer review procedures, by a special review committee convened specifically for this purpose by the Division of Extramural Activities, NIAID. This will be followed by a second-level review by the National Advisory Allergy and Infectious Diseases Council in June 1993. LETTER OF INTENT Prospective applicants are asked to submit, by November 6, 1992, a letter of intent that includes a descriptive title of the proposed research, and the names and affiliation(s) of proposed key investigators. The NIAID requests a letter of intent in order to provide an indication of the number and scope of applications to be received. The letter of intent does not commit the sender to submit an application, nor is it a requirement for submission of an application. The letter of intent will not enter into the review of any application subsequently submitted. The letter of intent is to be sent to: Dr. Olivia Preble Chief, Microbiology and Immunology Review Section Scientific Review Branch National Institute of Allergy and Infectious Diseases Solar Building, Room 4C20 6003 Executive Boulevard Rockville, MD 20892 APPLICATION PROCEDURES Applications are to be submitted on form PHS 398 (rev. 9/91), that is available at most institutional business offices and from the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone (301) 496-7441. INQUIRIES Direct requests for the RFA and inquiries on programmatic issues to: Dr. Catherine Laughlin Chief, Antiviral Research Branch Division of Microbiology and Infectious Diseases National Institute of Allergy and Infectious Diseases Solar Building, Room 3A-22 6003 Executive Boulevard Rockville, MD 20852 Telephone: (301) 496-8285 Direct inquiries regarding review procedures to: Dr. Olivia Preble Chief, Microbiology and Immunology Review Section Scientific Review Branch National Institute of Allergy and Infectious Diseases Solar Building, Room 4C-20 6003 Executive Boulevard Rockville, MD 20852 Telephone: (301) 496-8208 FAX: (301) 402-2638 Direct inquiries regarding fiscal matters to: Mr. Todd Ball Grants Management Branch National Institute of Allergy and Infectious Diseases Solar Building, Room 4B-22 6003 Executive Boulevard Rockville, MD 20852 Telephone: (301) 496-7075 FAX: (301) 480-3780 AUTHORITY AND REGULATIONS This program is described in the Catalogue of Federal Domestic Assistance No. 93.856, Microbiology and Infectious Diseases Research. Awards are made under the authority of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR Part 52 and 45 CFR 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 AI-92-13 FULL-TEXT *************************************** WOMEN AND INFANTS TRANSMISSION STUDY (WITS II) NIH GUIDE, Volume 21, Number 36, October 9, 1992 RFA AVAILABLE: AI-92-13 P.T. 34, AA, II; K.W. 0715008, 0715125, 0785055, 0745020 National Institute of Allergy and Infectious Diseases Letter of Intent Receipt Date: October 26, 1992 Application Receipt Date: January 14, 1993 THE REQUEST FOR APPLICATIONS (RFA) ANNOUNCED IN THIS NOTICE CONTAINS ESSENTIAL INFORMATION FOR THE PREPARATION OF AN APPLICATION. POTENTIAL APPLICANTS MAY OBTAIN THE RFA FROM THE CONTACT NAMED IN INQUIRIES, BELOW. PURPOSE The Vaccine Trials and Epidemiology Branch of the Division of AIDS (DAIDS) of the National Institute of Allergy and Infectious Diseases (NIAID) announces the availability of an RFA for funding the continuation of the Women and Infants Transmission Study (WITS). The purpose of this RFA is a competitive renewal of WITS I, a multi-site epidemiologic cohort study of HIV infected pregnant women and their offspring. New sites not participating in WITS I are encouraged to apply, as are current WITS I sites. Specific aims are: (1) to assess the effects of pregnancy on HIV disease progression, (2) determine maternal cofactors related to maternal-infant transmission and timing of transmission, (3) assess early diagnostic techniques to identify HIV-infected fetuses and infants, (4) evaluate the natural history of HIV infection among infants during an era of antiretroviral and other therapeutic modalities, and (5) assess the feasibility of future vaccine trials in this population. 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, Women and Infants Transmission Study (WITS II), 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. 017-001-10473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic non-profit and for-profit research institutions; public and private organizations such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Applications from minority individuals and women are encouraged. MECHANISMS OF SUPPORT Applicants funded under this RFA will be supported through National Institutes of Health (NIH) Cooperative Agreements (U01). A Cooperative Agreement is a type of assistance through which an award is made to an institution to encourage investigator-initiated research in areas of special importance to the NIH and if substantial programmatic involvement by NIH staff is anticipated. This RFA solicitation represents a onetime competition for a four year award with a specified deadline for receipt of applications. Program intents for extensions beyond the initial competitive segment are uncertain. If, by the end of the third year of the award, NIAID has not announced an intention to reissue the RFA, awardees who plan to apply for continuing support should contact NIAID program officials for advice on how to recompete. FUNDS AVAILABLE Approximately $5,000,000 will be available for funding the total costs for the initial year of awards made pursuant to this RFA. The NIAID anticipates making four to eight awards as a result of this RFA. The final number of awards to be made is dependent upon receipt of a sufficient number of applications of high scientific merit and availability of funds. The earliest anticipated award date will be July 1993. RESEARCH OBJECTIVES Background The growing magnitude of the HIV epidemic among women of childbearing age and their infants is becoming apparent in many areas of the United States. The percentages of AIDS cases among women and children are increasing more rapidly than for any other risk groups. In the 1990s, the AIDs epidemic will continue to attack African American and Hispanic women and children in disproportionately high numbers. To date, more than 80 percent of pediatric AIDS cases have been caused by maternal-infant transmission. Moreover, virtually all new cases of pediatric HIV infection in infants and children will be due to maternal-infant transmission. In the face of this growing epidemic among women and their offspring, there are a number of critical and unanswered questions related to HIV infection during pregnancy and maternal-infant transmission. These include the impact of pregnancy on the health of HIV-infected women, mechanisms and timing of vertical HIV transmission, rates of maternal-infant transmission (overall and among different subpopulations of at-risk pregnant women), as well as understanding cofactors related to HIV transmission. The Women and Infants Transmission Study II will be a focused continuation of the current Women and Infants Transmission Study (WITS I), which began in 1988. WITS II will continue and expand this prospective natural history cohort study of HIV positive pregnant women and their offspring. It will rely heavily on the core protocols in place for WITS I, but will also encourage new projects that may shed light on our understanding of maternal-infant HIV transmission and early diagnosis of fetal or infant HIV infection. New applicants should mention to the NIAID contact person that they are new applicants, and they will receive a summary of the WITS I protocol, which is necessary in preparing a response to this RFA. Contact Dr. Mary Glenn Fowler, at the address listed under INQUIRIES. Specific objectives of WITS II are: o Determine maternal cofactors related to maternal-infant transmission including assessment of mechanisms and timing of transmission. o Determine the impact of pregnancy on the natural history of HIV infection among women through the post partum period including immunologic and virologic changes in pregnant HIV positive women. o Evaluate early diagnostic tests to determine infant HIV infection status as rapidly as possible. o Determine the natural history of HIV infection among congenitally exposed infants and children in light of antiretroviral, prophylactic, and immune- based therapy. o Assess the feasibility of future vaccine trials in a cohort of HIV infected pregnant women by evaluating their attitudes and potential willingness to take part in future clinical vaccine trials for themselves or their infants. To achieve the objectives of WITS II, the NIAID seeks respondents to help develop and carry out this continuing epidemiologic natural history study of pregnant HIV women and their children. New prospective sites as well as current WITS I sites are encouraged to apply. The template for this study will be the research protocols designed for WITS I. In addition, specific new research studies are also encouraged that may provide critical information directed toward the primary research aims of WITS II. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS For projects involving clinical research, NIH requires applicants to give special attention to the inclusion of women and minorities in study populations. 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. Because this RFA addresses research on the effects of HIV infection among women and their infants, many of whom are from minority race/ethnicity groups, it is anticipated that women and minorities will be adequately represented in applications for this RFA. LETTER OF INTENT Prospective applicants are asked to submit, by October 26, 1992, a letter of intent that includes a descriptive title of the proposed research and 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 binding, does not commit the sender to submit an application, nor is it a requirement for submission of an application. The letter of intent is to be sent to Dr. Mary Glenn Fowler, at the address listed under INQUIRIES. APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 9/91) is to be used in applying for these cooperative agreements. These forms are available at most institutional offices of sponsored research, the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, Maryland 20892, telephone 301/496-7441, and from the NIH Program Administrator named above. The RFA label available in the PHS 398 application form must be affixed to the bottom of the face page of the application. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA number, RFA AI-92-13 and the title, Women and Infants Transmission Study, 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, 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 copies must also be sent directly to: Dr. Dianne Tingley AIDS Scientific Review Branch Division of Extramural Activities National Institute of Allergy and Infectious Diseases 6003 Executive Boulevard, Room 4C16 Bethesda, MD 20892 If sending the application by overnight mail or courier service use Rockville, Maryland 20852. Applications must be received by both DRG and Dr. Tingley by January 14, 1993. Applications received after January 14, 1993 will be returned to the applicant without review. REVIEW CRITERIA This application must be directed at and address the research objectives identified in this RFA; that portion of the application corresponding to this research plan should follow in form the specific instructions available in the RFA. The primary factors that will be considered in the review of the application will be demonstrated ability or potential to recruit adequate numbers of HIV pregnant women into the study; capability to carry out the clinical and laboratory studies of WITS II including commitment to a multi-site research collaborative effort; and cost efficiency in carrying out the research protocols. AWARD CRITERIA Awards will be made on the basis of high scientific and technical merit, adequacy of funds, and program relevance. However, after an application have been approved by the National Advisory Allergy and Infectious Diseases Council, NIAID staff reserves the right to give consideration to the following factors in the final selection of applications to be funded: WITS II sites reflect the racial/ethnicity and socioeconomic characteristics of the nation-wide HIV epidemic among women and infants; and reflect the HIV-AIDS incidence/geographic distribution of the epidemic among U.S. women and their infants. INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. New applicants should request a copy of the WITS I protocol summary. Direct requests for a copy of the RFA and inquiries concerning programmatic issues to: Mary Glenn Fowler, M.D., M.P.H. Vaccine Trials and Epidemiology Branch Division of AIDS National Institute of Allergy and Infectious Diseases 6003 Executive Boulevard, Room 2A24 Bethesda, MD 20892 Telephone: (301) 496-6177 FAX: (301) 402-1506 or (301) 480-5703 Direct inquiries concerning fiscal and policy issues to: Jane Unsworth Chief, AIDS Grants Management Section Division of Extramural Activities National Institute of Allergy and Infectious Diseases 6003 Executive Boulevard, Room 4B25 Bethesda, MD 20892 Telephone: (301) 496-7075 FAX: (301) 480-3780 Direct inquiries concerning the review process and review requirements to: Dr. Dianne Tingley AIDS Scientific Review Branch Division of Extramural Activities National Institute of Allergy and Infectious Diseases 6003 Executive Boulevard, Room 4C16 Bethesda, MD 20892 Telephone: (301) 496-0818 FAX: (301) 402-2638 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance Nos. 93.856 and 93.855. 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 Public Health Service Act 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 CA-92-28 FULL-TEXT *************************************** CLINICAL TRIALS OF CANCER THERAPY WITH BIOLOGICAL RESPONSE MODIFIERS NIH GUIDE, Volume 21, Number 36, October 9, 1992 RFA AVAILABLE: CA-92-28 P.T. 34; K.W. 0755015, 0715035, 0740015 National Cancer Institute Letter of Intent Receipt Date: October 30, 1992 Application Receipt Date: December 22, 1992 THE REQUEST FOR APPLICATIONS (RFA) ANNOUNCED IN THIS NOTICE CONTAINS ESSENTIAL INFORMATION FOR THE PREPARATION OF AN APPLICATION. POTENTIAL APPLICANTS MAY OBTAIN THE RFA FROM THE CONTACT NAMED IN INQUIRIES, BELOW. PURPOSE The Biological Response Modifiers Program (BRMP), Division of Cancer Treatment (DCT), National Cancer Institute (NCI) invites applications to establish cooperative agreements for Clinical Trials of Cancer Therapy with Biological Response Modifiers (CATBRMs), for the development of novel approaches to such therapy. 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, Clinical Trials of Cancer Therapy With Biological Response Modifiers (CATBRMs), 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 Groups constituted according to the guidelines given in the RFA (briefly outlined under "RESEARCH OBJECTIVES" below) are eligible to apply. Applying groups may include members from academic, non-profit, and for-profit institutions. Involvement of intramural NIH personnel is limited as described in the RFA. Domestic and foreign organizations and institutions (non-profit or for-profit) are eligible. Governments and their agencies are also eligible. Applications from women and members of minority groups are encouraged. MECHANISM OF SUPPORT Awards will be made as cooperative agreements (U01). In cooperative agreements, unlike traditional research grants, substantial NCI programmatic involvement with the recipient during performance of the planned activity is anticipated. The nature of NCI staff involvement is described in the RFA. Applicants will be responsible for the planning, direction, and execution of the proposed project. Specifically, the CATBRM study group is responsive to the requirements and conditions set forth in the RFA. The Principal Investigator defines the details for the project in accordance with the Terms of Cooperation, retains primary responsibility for the performance of the activity, and agrees to accept close coordination, cooperation, and assistance of NCI extramural staff (through the NCI Program Director) in all aspects of scientific and technical management of the project. However, there is no intent, real or implied, for NCI staff to direct CATBRM activities or to limit the freedom of investigators. This RFA is a reissuance of RFA CA-92-01. Applicants who did not apply to the first announcement, or who applied but did not receive an award, are encouraged to respond to this RFA. However, this reissued RFA is a one-time solicitation. Generally, future unsolicited competing renewal applications will compete as research project applications with all other investigator-initiated applications. If the NCI determines that there is sufficient continuing program need, the NCI will invite recipients of awards under this RFA to submit competitive continuation cooperative agreement applications for review. FUNDS AVAILABLE NCI plans to make up to six awards for project periods up to four years, and has set aside $1.5 million total costs for the initial year's funding. The total funding level and number of awards to be made 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 National Cancer Institute, awards pursuant to this RFA are contingent upon continuing availability of funds. Applicants may request no more than four years of support. The earliest possible starting date for the initial annual period will be July 1, 1993. RESEARCH OBJECTIVES Cooperative Agreements will be established to support Clinical Study Groups for Cancer Therapy with Biological Response Modifiers (CATBRMs), for the design and execution of novel clinical trials with biological response modifiers (BRMs). CATBRM groups will be peer-reviewed groups of highly experienced clinical and preclinical investigators who have the unique technical capabilities to study new agents in early clinical trials and to address hypothesis-driven issues of mechanisms of action. The "Research Goals and Scope" of the RFA will require a novel plan for clinical study of a given new agent or agents, adequately supported by prior preclinical, and if available, clinical, results. The application must describe how its objectives are in accord with the applicant's own interests and experience. The applicant must provide evidence of access to the agent(s) proposed for study. A detailed protocol for an initial clinical trial must also be included. The NCI will facilitate the institution of a peer-reviewed, investigator-initiated trial, participating according to Terms of Cooperation outlined in the RFA. Each CATBRM study group will be composed of: a Principal Investigator; one or more laboratory programs, each headed by a Program Leader, with the demonstrated expertise to design and carry out assays for the appropriate monitoring of patients on the study; one or more clinical programs, each headed by a Program Leader, with demonstrated expertise in conducting clinical trials of BRMs; and the NCI Program Director. SPECIAL INSTRUCTIONS FOR INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDIES For projects involving clinical research, NIH requires applicants to give special attention to the inclusion of women and minorities in study populations. If women or minorities are not included in the study populations for clinical studies, a specific justification for this exclusion must be provided. Applications without such documentation will not be accepted for review. LETTER OF INTENT Prospective applicants are asked to submit, by October 30, 1992, a short 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 this RFA. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information that it contains is helpful in planning for the review of applications. It allows ICD staff to estimate the potential review workload and to avoid conflict of interest in the review. Letters of intent are to be sent to: Jon T. Holmlund, M.D. Biological Resources Branch Biological Response Modifiers Program National Cancer Institute NCI-FCRDC, Building 1052, Room 253 Frederick, MD 21702-1201 Telephone: (301) 846-1098 FAX: (301) 846-5429 APPLICATION PROCEDURES The deadline for receipt of applications is December 22, 1992. Applications received after this date will be returned without review to the applicant. The regular research grant application form PHS 398 (rev. 9/91) is to be used in applying. These forms are available at most institutional business offices; from the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, Westwood Building,Room 449, Bethesda, MD 20892, telephone 301/496-7741); and from the NIH Program Administrator named below. 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 your application such that it may not reach the review committee in time for review. Applicants from institutions that have a General Clinical Research Center (GCRC) funded by the NIH National Center for Research Resources are requested to identify the GCRC as a resource for conducting the proposed research. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed by the DRG for completeness and responsiveness. Incomplete applications will be returned to the applicant without further consideration. If an application is not responsive to the RFA, it will be returned to the applicant and the proposed Principal Investigator will be contacted to determine whether submission for review in competition with unsolicited applications (e.g., as an R01 or P01, after appropriate modification) at the next review cycle is desirable to the applicant. Questions concerning the relevance of proposed research to the RFA may be directed to the NIH Program Administrator listed under INQUIRIES. In cases where the number of applications is large compared to the number of awards to be made, the NCI may conduct a preliminary scientific peer review to eliminate those which are clearly not competitive for award. The NCI will remove from further competition those applications judged to be noncompetitive and notify the Principal Investigator and institution official. Those applications judged to be both competitive and responsive will be further evaluated, using review criteria described in the RFA, for scientific and technical merit by an appropriate peer review group convened by the Division of Extramural Activities, NCI. Following peer review, the applications will receive a second-level review by the National Cancer Advisory Board, which considers the special needs of the Institute and the priorities of the National Cancer Program. INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct requests for the RFA and inquiries regarding programmatic issues to: Jon Holmlund, M.D. Program Director, Biological Resources Branch Biological Response Modifiers Program National Cancer Institute-FCRDC Building 1052, Room 253 Frederick, MD 21701-1201 Telephone: (301) 846-1098 FAX: (301) 846-5429 Direct inquiries regarding fiscal matters to: Ms. Katharine Schulze Grants Management Specialist Grants Administration Branch Executive Plaza South, Room 242 6120 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-7800, Ext. 16 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 authorization of the Public Health Service Act, Title, 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. $$R6 END ************************************************************ $$R7 BEGIN HD-94-01 FULL-TEXT *************************************** SPECIALIZED RESEARCH CENTER PROGRAMS AND CENTER CORE GRANTS TO SUPPORT RESEARCH IN REPRODUCTION NIH GUIDE, Volume 21, Number 36, October 9, 1992 RFA AVAILABLE: HD-94-01 P.T. 04; K.W. 0413002, 0710110, 0710115, 0710030 National Institute of Child Health and Human Development Letter of Intent Receipt Date: January 2, 1993 Application Receipt Date: May 18, 1993 THE REQUEST FOR APPLICATIONS (RFA) ANNOUNCED IN THIS NOTICE CONTAINS ESSENTIAL INFORMATION FOR THE PREPARATION OF AN APPLICATION. POTENTIAL APPLICANTS MAY OBTAIN THE RFA FROM THE CONTACT NAMED IN INQUIRIES, BELOW. PURPOSE The Reproductive Sciences Branch (RSB), Center for Population Research (CPR), National Institute of Child Health and Human Development (NICHD), supports research on reproduction which relies on a variety of approaches in biomedical sciences. Among the grant mechanisms used to provide research support, the RSB uses: (1) Specialized Research Centers (P50s) which are integrated groups of research projects and supporting core service facilities. The research activities included in such project grants must comprise, by definition, a multidisciplinary approach to biomedical problems in reproduction. Although these research programs may have more than one theme, focus, or emphasis, all of the projects must be responsive to one or more of the specific areas of reproductive research which constitute the mission of the RSB, CPR, NICHD. (2) Center Core Grants (P30s) that support Center Core facilities designed to enhance a group of existing federally supported research projects within the purview of the RSB, CPR, NICHD. Such Center awards require a critical mass of individual, reproductive-oriented awards whose productivity and quality would be increased by support from central technical facilities. Institute policy requires recompetition for the P30/P50 Center Program in the Reproductive Sciences Branch. 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, Specialized Research Center Programs and Center Core Grants to Support Research in Reproduction, is related to the priority area of family planning. 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. Foreign organizations are not eligible. New Specialized Research Center Grant (P50) applications may not request more than $600,000 in direct costs for the first year. New Center Core Grant (P30) applications may not request more than $500,000 in direct costs for the first year. Renewal applications from existing P30 or P50 centers may not request initial year direct costs exceeding 120 percent of the Council recommended direct costs for the final year of the preceding project period. Unless prior written approval of the NICHD has been obtained, applications with requests exceeding these guidelines will be administratively withdrawn by the NICHD and returned to the applicant. Applications prepared for this competition may not propose multi-institutional consortiums. MECHANISM OF SUPPORT This RFA will use the Specialized Research Center Program (P50) and Center Core (P30) Grant mechanism to support research in reproduction. The total project period for applications submitted in response to this RFA is five years. The anticipated award date will be April 1, 1994. FUNDS AVAILABLE Although this solicitation is included in the fiscal plans for FY 1994, support for these center grants is contingent upon the receipt of funds for these purposes by the NICHD. The number of grants to be awarded is also contingent upon a sufficient number of applications receiving a high enough level of merit to be considered for an award. It is expected that up to four awards will be made as a result of this announcement within the expected total cost limit of $3,600,000 available for the first year. At present, the RSB supports a fixed number of centers with a commitment of five years of support that is competitively renewable for additional five-year periods. Support for one P50 Center and three P30 Centers ends in FY 1994 and it is anticipated that these Centers will submit renewal applications. Although there are no additional Center awards available at this time, new groups of investigators are invited to compete with the current awardees for the existing four awards. RESEARCH OBJECTIVES The ultimate goals of biomedical research in the reproductive sciences are to develop new knowledge leading to clinical applications that will enable men and women to control their fertility with methods that are safe, effective, inexpensive, reversible, and acceptable to various population groups, and to overcome problems of infertility and reproductive disorders. Domestic U.S. Reproductive Sciences centers designated as "Specialized Reproductive Sciences Research Center" (P50s) and as "Reproductive Sciences Research Centers" (P30s) are awarded for the support of comprehensive reproductive research programs of high quality that focus on topics deemed to be of high priority and significance because of their critically important relationship to the mission of the RSB, CPR. 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 It is strongly recommended, but not mandatory, that potential applicants send a letter of intent to the RSB staff at the address listed below by January 2, 1993. This letter is to include a list of the titles of the relevant research projects to be associated with the proposed center and provide the names of the relevant key investigators. The letter of intent is to be received by the RSB no later than January 2, 1993, but applicants are encouraged to send it as soon as they decide to apply for the grant so that the RSB staff can be of maximum assistance in the application process. 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 avoid conflict of interest in the review. The letter of intent is to be sent to the RSB staff contact listed under INQUIRIES. APPLICATION PROCEDURES Center grant applications must be structured in accordance with the specific policy and formatting guidelines presented in the RFA and the instructions found in the publications entitled either "P50 Specialized Research Center Grant Guidelines" or "P30 Center Core Grant Guidelines" that are available from the NICHD office listed below. Such guidelines require, for example, certain tabulations in addition to the usual instructions for the grant application form PHS 398 (rev. 09/91) used to prepare these applications. The current policies and requirements that govern the research grant programs of NIH will prevail (Code of Federal Regulations, Title 42, Part 52 and Title 45, Part 75). REVIEW CONSIDERATIONS An administrative review of the application will be performed by NIH staff for conformance to NIH policy and NICHD guidelines, as well as for relevance to the program purview of the RSB. Applications that fail to comply with NIH policy and/or NICHD guidelines will be formally returned to the applicant. Applications will be evaluated by the Population Research Committee, NICHD in November 1993. The second level review will be made by the National Advisory Child Health and Human Development Council in January 1994. Review procedures and criteria are detailed in the P50 SPECIALIZED RESEARCH CENTER GRANT GUIDELINES and P30 CENTER CORE GRANT GUIDELINES (available from NICHD offices listed below). AWARD CONSIDERATIONS The earliest possible funding date is April 1, 1994. Funding decisions will be based on the IRG review and NACHHD Council recommendations, program relevance, and the availability of funds. INQUIRIES For further information and a copy of the RFA, contact: Julia Lobotsky, M.S. Reproductive Sciences Branch Center for Population Research National Institute of Child Health and Human Development Building 6100, Room 8B01 Bethesda, MD 20892 Telephone: (301) 496-6515 To obtain copies of the NICHD Policy and Formatting Guidelines for P30 and P50 center grant applications, contact: Laurance Johnston, Ph.D. Division of Scientific Review National Institute of Child Health and Human Development Building 6100, Room 5E01 Bethesda, MD 20892 Telephone: (301) 496-1696 For information on budget and fiscal matters, contact: Melinda Nelson Office of Grants and Contracts National Institute of Child Health and Human Development Building 6100 Bethesda, MD 20892 Telephone: (301) 496-5481 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.864, Population Research. Awards will be made under the authority of the Public Health Service Act 301 (42 USC 241) and 441 (USC 289d) and administered under PHS grants policies and Federal Regulations 42 CFR Part 52 and 45 CFR Part 74. This program is not subject to A-95 or Health Systems Agency review. $$R7 END ************************************************************ $$R8 BEGIN HL-93-03-B FULL-TEXT ************************************* CELL AND MOLECULAR BIOLOGY OF MEGAKARYOCYTOPOIESIS NIH GUIDE, Volume 21, Number 36, October 9, 1992 RFA AVAILABLE: HL-93-03-B P.T. 34; K.W. 0780015, 0780020, 0760003, 0760020, 1002008, 1002019 National Heart, Lung, and Blood Institute Letter of Intent Receipt Date: January 15, 1993 Application Receipt Date: March 15, 1993 THE REQUEST FOR APPLICATIONS (RFA) ANNOUNCED IN THIS NOTICE CONTAINS ESSENTIAL INFORMATION FOR THE PREPARATION OF AN APPLICATION. POTENTIAL APPLICANTS MAY OBTAIN THE RFA FROM THE CONTACT NAMED IN INQUIRIES BELOW. PURPOSE The National Heart, Lung, and Blood Institute (NHLBI) announces the availability of an RFA on the above subject. The purpose of this initiative is to encourage research that may contribute to better understanding of regulation of the proliferation and maturation of megakaryocytes and the control of platelet production. It is hoped that the information generated will allow manipulation of megakaryocytopoiesis and platelet levels in pathological conditions. 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, Cell and Molecular Biology of Megakaryocytopoiesis, is related to the priority areas of platelet disorders and bone marrow transplantation. 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 202-782-3238). ELIGIBILITY REQUIREMENTS All domestic and foreign, public and private, for-profit and non-profit institutions and organizations are eligible to apply in response to this RFA. Awards in connection with this announcement will be made to foreign institutions only for research of very From owner-sci-resources@net.bio.net Thu Oct 08 23:00:00 1992 Path: biosci!NET.BIO.NET!kristoff From: kristoff@NET.BIO.NET (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 21, no. 35, pt. 1, 2 October 1992 Message-ID: Date: 9 Oct 92 01:57:28 GMT Sender: kristoff@net.bio.net Distribution: bionet Lines: 1506 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. ---------------------------------------------------------------------- $$XID NIHGUIDE 19921002 V21N35 P1O2 ************************************ X-comment: RFAs described: HD-93-08, DK-93-01, HS-93-01, HL-93-02-P NIH GUIDE - Vol. 21, No. 35 - October 2, 1992 $$INDEX BEGIN ******************************************************* NOTICES $$INDEX N1 ********************************************************** AVAILABILITY OF RESOURCE FOR DIETARY INTAKE AND NUTRITION RESEARCH National Heart, Lung, and Blood Institute INDEX: HEART, LUNG, BLOOD $$INDEX N2 ********************************************************** HUMAN SUBJECT PROTECTIONS WORKSHOPS National Institutes of Health Food and Drug Administration INDEX: NATIONAL INSTITUTES OF HEALTH; FOOD AND DRUG ADMINISTRATION NOTICES OF AVAILABILITY (RFPs AND RFAs) $$INDEX R1 ********************************************************** BREEDING AND EXPERIMENTAL FACILITY FOR WOODCHUCKS (MARMOTA MONAX) (RFP NIH-NIAID-DMID-93-10) National Institute of Allergy and Infectious Diseases INDEX: ALLERGY, INFECTIOUS DISEASES $$INDEX R2 12/18/92 ************************************************* FAMILY AND CHILD WELLBEING RESEARCH NETWORK (RFA HD-93-08) National Institute of Child Health and Human Development INDEX: CHILD HEALTH, HUMAN DEVELOPMENT $$INDEX R3 01/14/93 ************************************************* DIABETES ENDOCRINOLOGY RESEARCH CENTERS (RFA DK-93-01) National Institute of Diabetes and Digestive and Kidney Diseases INDEX: DIABETES, DIGESTIVE, KIDNEY DISEASES $$INDEX R4 01/22/93 ************************************************* GRANTS FOR HEALTH SERVICES DISSERTATION RESEARCH (RFA HS-93-01) Agency for Health Care Policy and Research INDEX: HEALTH CARE POLICY, RESEARCH $$INDEX R5 02/16/93 ************************************************* IMPROVING HYPERTENSIVE CARE FOR INNER CITY MINORITIES (RFA HL-93-02-P) National Heart, Lung, and Blood Institute INDEX: HEART, LUNG, BLOOD ONGOING PROGRAM ANNOUNCEMENTS $$INDEX P1 ********************************************************** CHEMORECEPTION AND NUTRITION (PA-93-001) National Institute on Deafness and Other Communication Disorders National Institute of Diabetes and Digestive and Kidney Diseases National Institute of Dental Research National Institute on Aging National Institute of Child Health and Human Development INDEX: DEAFNESS, OTHER COMMUNICATION DISORDERS; DIABETES, DIGESTIVE, KIDNEY DISEASES; DENTAL RESEARCH; AGING; CHILD HEALTH, HUMAN DEVELOPMENT $$INDEX P2 ********************************************************** PREVENTION OF END STAGE LIVER DISEASES BY MOLECULAR DIAGNOSIS (PA-93- 002) National Institute of Diabetes and Digestive and Kidney Diseases INDEX: DIABETES, DIGESTIVE, KIDNEY DISEASES $$INDEX P3 ********************************************************** RESEARCH INFRASTRUCTURE SUPPORT PROGRAM (PA-93-003) National Institute of Mental Health INDEX: MENTAL HEALTH This publication is also available electronically to institutions via BITNET or INTERNET. Alternative access is through the NIH Grant Line using a personal computer. Contact Dr. John James at 301/496-7554 for details, or send an E-mail message to ZNS@NIHCU. $$INDEX END ********************************************************* NOTICES $$N1 BEGIN ********************************************************** AVAILABILITY OF RESOURCE FOR DIETARY INTAKE AND NUTRITION RESEARCH NIH GUIDE, Volume 21, Number 35, October 2, 1992 P.T. 34; K.W. 0710095, 0780000 National Heart, Lung, and Blood Institute The Nutrition Coordinating Center (NCC) at the University of Minnesota is a unique national resource available for dietary data collection and nutrient calculation for epidemiological studies, clinical trials, and other medical research studies. The center provides standardized procedures for collecting food intake data and calculating nutrient intakes at the high level of specificity needed for investigations of the relationship between diet and disease. Investigators can use the services of the NCC in two ways. They can license use of the Minnesota Nutrition Data System (NDS). NDS is microcomputer-based software for interactive dietary data collection and nutrient calculation. NDS prompts the user to describe food intake at the level of detail required for dietary research and calculates the nutrient content of the intake. Then NDS presents the data on the screen, in printed reports, or in ASCII files that can be merged with other study data using statistical analysis software. The NDS database allows the user to describe over 150,000 foods and 6,000 brand name products. The database contains values for up to 93 nutrients, including soluble and insoluble fiber fractions, 23 individual fatty acids, and 18 amino acids. NDS can be used to guide 24-hour dietary recall interviews or to process food intake records. NDS can also be used to collect and analyze diet histories and to calculate the nutrient content of recipes or menus. A customized version of NDS is being used in the National Health and Nutrition Examination Survey (NHANES III) to collect dietary data from more than 30,000 Americans. Alternatively, investigators can send dietary intake records to NCC for processing. Data collection and processing procedures can be customized to meet the needs of specific studies. Investigators may reanalyze data collected in the past to take advantage of improved analytical data and new nutrients added to the database. Over the past 18 years, NCC has processed more than 300,000 records. NCC also provides a two-day training program for dietary interviewers. For investigators who send dietary intake records to NCC for processing, the training ensures the use of standardized data collection procedures tailored to the research protocol. Interviewers are certified following satisfactory completion of the training program and follow-up exercises. For investigators using the NDS directly, the training is designed to enhance use of the software to meet research protocol requirements. Over the past 18 years, NCC has trained and certified more than 700 dietary interviewers. NCC receives major support from the National Heart, Lung, and Blood Institute, the National Cancer Institute, and the National Center for Health Statistics. NCC services and software are used by investigators in academia, government, non-profit organizations, and industry. Users are required to pay a fee to cover part of the operational costs. For information and fee schedules, contact Marilyn Buzzard, Ph.D., Director, Nutrition Coordinating Center, 2221 University Avenue, SE, Suite 310, Minneapolis, MN 55414, telephone (612) 627-4869, FAX (612) 627-4191. INQUIRIES Abby Ershow, Sc.D. Lipid Metabolism - Atherogenesis Branch Division of Heart and Vascular Diseases National Heart, Lung, and Blood Institute Bethesda, MD 20892 Telephone: (301) 496-1681 FAX: (301) 496-9882 $$N1 END ************************************************************ $$N2 BEGIN ********************************************************** HUMAN SUBJECT PROTECTIONS WORKSHOPS NIH GUIDE, Volume 21, Number 35, October 2, 1992 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 subjects. The meetings should be of special interest to those persons 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 the following: SOUTHWESTERN WORKSHOP DATES: November 16 & 17, 1992 LOCATION: Wyndham Warwick 5701 Main Street Houston, TX 77005 Telephone: (713) 526-1991 SPONSORS: University of Texas Health Science Center at Houston Prairie View A & M University REGISTRATION: Ms. Paula Knudson Executive Coordinator Office of Research Support Committee University of Texas Health Science Center at Houston P.O. Box 20036 Houston, TX 77225 Telephone: (713) 792-5048 TITLE: Geriatric Research as an Ethical Mandate: Politics, Policy, and Problems DESCRIPTION: Expanded life expectancies and expanding technologies are swelling the ranks of the frail and disabled elderly. Minimal research has been carried out to understand the problems this subject group and their families encounter in finding solutions to their health and social needs. The conference will identify key problems that need to be studied; isolate the risks and benefits associated with behavioral, clinical, or evaluation research designed to enroll this group as subjects; and pose solutions that will meet the needs of regulators, scientists, and the elderly. The program is designed to be of interest to physicians, nurses, pharmacists, scientific investigators, other health care professionals, clergy, lawyers, medical, nursing, social work students, psychologists and IRB members and administrators. Attention will be paid to Federal regulations with special emphasis on the assessment of risks---medical, legal, and psychosocial. Opportunities will be available through workshops, question periods, and informal discussions for participants to exchange ideas and interests with faculty and OPRR and FDA representatives. SOUTHEASTERN WORKSHOP DATES: January 14 & 15, 1993 LOCATION: Sheraton Sand Key Resort 1160 Gulf Boulevard Clearwater Beach, FL 33515 Telephone: (813) 595-1611 SPONSORS: University of South Florida Florida A & M University REGISTRATION: Ms. Eileen Highsmith Executive Secretary University of South Florida 4202 E. Fowler Avenue (MP.FAO-126) Tampa, FL 33620-7900 Telephone: (813) 974-2897 TITLE: Barriers to Informed Consent: Language, Age Factors, Trauma, and Women/Minority Issues DESCRIPTION: Today's researchers face numerous barriers to obtaining an informed consent. Such issues as age, language, mental capacity, and sobriety may affect the ability of subjects to give a truly informed consent. Many of these barriers oftentimes impact the pool of subjects which an investigator is willing (or able) to use in a research project. In addition, recent legislation from the Congress was designed to address the issue of inadequate numbers of women and minorities in research projects. This conference has been designed to address three main areas in which barriers to informed consent may exist: mental competence, ethnic and gender issues, and research with children and the elderly. The conference program is designed to be of value to physicians, nurses, pharmacists, scientific investigators, and other health care professionals. All IRB members, students in health care areas and administrators will also benefit from the conference. Attention will be given to Federal regulations governing research on human subjects, with special emphasis placed on the assessment of risks---medical, legal, and psychosocial. Ample opportunities will be provided to exchange ideas and interests, through question and answer sessions and informal discussions. SOUTHWESTERN WORKSHOP DATES: February 12 & 13, 1993 LOCATION: Sheraton Tempe Mission Palms Hotel 60 East 5th Street Tempe, AZ 85281 Telephone: (602) 894-1400 SPONSORS: Arizona State University Northern Arizona University REGISTRATION: Ms. Carol Jablonski IRB Coordinator Office of the Assistant Vice President for Research Arizona State University Tempe, AZ 85287-3403 Telephone: (602) 965-6788 TITLE: Contemporary Issues in Human Subject Research: Challenges for Today's IRBs DESCRIPTION: This program is designed to be a practical working session to explore contemporary issues in human subjects protection including regulations and assurances, categorization of research protocols, uses of special populations, experimental design and scientific merit, fetal tissue research, ethical/legal issues in human subjects research, and conflict of interest. As appropriate, topics will be discussed from the perspective of the clinical researcher and the behavioral/social science researcher. Issues will be discussed in a panel format with ample time for audience questions. An outstanding faculty has been assembled. This program should be of interest to researchers in clinical medicine and the behavioral and social sciences. Institutional Review Board members, university and hospital administrators, lawyers, ethicists, health care practitioners, students, and other persons with interests in human subject protection issues. For further information regarding these workshop or future NIH/FDA National Human Subject Protections Workshops, contact: Ms. Darlene Marie Ross Executive Assistant for Education Division of Human Subject Protections Office for Protection from Research Risks National Institutes of Health 9000 Rockville Pike Building 31, Room 5B59 Bethesda, MD 20892 Telephone: (301) 496-8101 $$N2 END ************************************************************ NOTICES OF AVAILABILITY (RFPs AND RFAs) $$R1 BEGIN NIH-NIAID-DMID-93-10 ************************************* BREEDING AND EXPERIMENTAL FACILITY FOR WOODCHUCKS (MARMOTA MONAX) NIH GUIDE, Volume 21, Number 35, October 2, 1992 RFP: NIH-NIAID-DMID-93-10 P.T. 34; K.W. 1002002 National Institute of Allergy and Infectious Diseases The Enteric Diseases Branch of the Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, has a requirement for the continued development and use of sequelae such as chronic hepatitis and hepatoma. There is a requirement for colony born animals for planned experiments. The contractor will be responsible for the development and maintenance of a colony of breeding Marmota monax capable of yielding 100 weaned pups per year; for the performance of experimental protocols on woodchucks with viral agents, vaccines, and therapeutic agents; and for the maintenance of experimental animals. Request for Proposals (RFP) NIH-NIAID-DMID-93-10 is now available. Proposals will be due on November 13, 1992. It is anticipated that one cost-reimbursement, level-of-effort contract will be awarded for a period of five years. To receive a copy of this RFP, please supply this office with two self-addressed mailing labels. All inquiries must be in writing and addressed to the office below: Sara Southard Contract Specialist National Institute of Allergy and Infectious Diseases Solar Building, Room 3C07 6003 Executive Boulevard Bethesda, MD 20892 All responsible sources may submit a proposal that will be considered by the government. This advertisement does not commit the government to award a contract. $$R1 END ************************************************************ $$R2 BEGIN HD-93-08 FULL-TEXT *************************************** FAMILY AND CHILD WELLBEING RESEARCH NETWORK NIH GUIDE, Volume 21, Number 35, October 2, 1992 RFA AVAILABLE: HD-93-08 P.T. 34, AA; K.W. 0730010, 0730005 National Institute of Child Health and Human Development Application Receipt Date: December 18, 1992 THE REQUEST FOR APPLICATIONS (RFA) ANNOUNCED IN THIS NOTICE CONTAINS ESSENTIAL INFORMATION FOR PREPARATION OF AN APPLICATION. POTENTIAL APPLICANTS MAY OBTAIN THE RFA FROM THE CONTACT NAMED IN INQUIRIES, BELOW. PURPOSE The Demographic and Behavioral Sciences Branch of the Center for Population Research at the National Institute of Child Health and Human Development (NICHD) announces the availability of an RFA that invites applications for cooperative agreements (U01) to develop a research network to investigate the relationship of family factors to child welfare. The research network will conduct a systematic analysis of existing data to determine what can be learned by means of secondary data analysis about the relationship of family factors to child welfare. Each investigator in the network will be expected to have demonstrated expertise and access to at least one data set relevant to the topic. Also, applicants must demonstrate that they have both the substantive and statistical expertise to function as part of an interdisciplinary research network. Each investigator will be given support to pursue his or her individual research agenda, but a large part of the available resources will be held in reserve to address cooperative research questions agreed upon by the network. Each investigator will propose both an individual research plan and a cooperative research plan in which they identify areas of research that they would be willing to cooperate in implementing. 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, Family and Child Wellbeing Research Network, is related to the priority areas of family planning, educational and community-based programs, maternal and infant health, immunization and infectious diseases, and clinical preventive services. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "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 and local governments, and eligible agencies of the Federal government. Applications from minority individuals and women are encouraged. Institutions may submit applications on behalf of more than one Principal Investigator (PI), but each PI must submit a separate application. MECHANISM OF SUPPORT The funding mechanism to be used to support the research network will be the cooperative agreement (U01). Cooperative agreements are assistance mechanisms but differ from research project grants in that there will be substantial programmatic involvement of the NICHD Project Coordinator above and beyond the levels required for traditional program management of grants. Specifically, the Project Coordinator will assist the PI in the research network. All parties agree to accept the participatory and cooperative nature of the group process. This RFA is intended as a one time solicitation. The total project period for the research network is five years and applications submitted in response to the present RFA must not request support for more than five years. Should there be a sufficient continuing program need, the NICHD may reissue this RFA. The anticipated award date is July 1, 1993. FUNDS AVAILABLE It is anticipated that up to seven awards will be made. $1 million of direct cost support has been set aside to support the network for the first year of the award, and this amount will increase by an inflation factor in subsequent years of the network. Approximately one half of the resources allocated for the network will be devoted to support cooperative research. Resources available for cooperative research will be very small in the first year of the network, but will increase progressively in the subsequent years of the network. The percentage of funding for cooperative research will increase according to the following schedule: 20 percent in FY 93, 35 percent in FY 94, 50 percent in FY 95, 65 percent in FY 96 and 80 percent in FY 97. The level of support is dependent on the receipt of a sufficient number of applications of high scientific merit. Although this program will be provided for in the financial plan of the NICHD, the award of grants pursuant to this RFA is also contingent on the availability of funds for this purpose. RESEARCH OBJECTIVES There are a large number of social problems that impinge on the wellbeing of children. Among them, poverty and the emergence of an underclass population with a growing dependence on public transfer programs are highly visible areas of concern. Moreover, family factors such as marital instability, out-of-wedlock childbearing and changes in the demographic and economic structure of the family seem to be inextricably related to these and other problems affecting child wellbeing. It is important to describe fully these interconnections and to formulate and test models of the causes and consequences of these relationships. It is also important to elucidate the mechanisms of action by which family factors effect child wellbeing so that possible avenues of social intervention can be ascertained, and existing interventions, such as child support enforcement or child care subsidies, can be evaluated. The American family has undergone considerable change in modern times. These changes are associated with changes in the way children are raised and with changes in familial support structures that sustain and develop children into productive adults. It is the intent of this RFA to measure both family factors and child wellbeing very broadly to develop as comprehensive a picture as possible about the relationship between these considerations. It is important to understand how family factors and socio-economic conditions combine to nurture children and help them develop into productive adults from both an individual and societal perspective. It is important to understand how the intergenerational structure of the family marshals resources to care for dependent children and how intergenerational family processes relate to public intervention to sustain and develop children. The research network will confine its activity to secondary data analysis. The network will be assembled to achieve the broadest possible coverage in terms of research perspective, analytical technique and sources of data. The focus of the network is the United States, but the use of foreign data may be justified if it provides an important insight into the American condition. Investigators must demonstrate that they have a long term research agenda that is addressing important questions relevant to the research goals of this RFA. In addition they must describe the sources of data to which they have access and plan to use in their research plan. It is important to describe the extent to which the investigator has experience using these data. It is also important to outline the analytic plan of attack and to describe the statistical techniques that will be employed in each phase of the research plan. The investigator must propose a plan of action necessary to accomplish their personal research agenda in this area. Applicants must also present a research plan for work they suggest for collaborative undertaking. SPECIAL REQUIREMENTS The cooperative agreement assistance mechanism imposes special requirements on both the applicants and the NICHD. These requirements are detailed clearly in the full RFA. APPLICATION PROCEDURES The grant application form PHS 398 (rev. 9/91) is to be used in applying for this grant. The PHS 398 is available from most business offices or grants/contracts offices at most institutions and can also be obtained from the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone (301) 496-7441. Applications must be received at the Division of Research Grants by December 18, 1992. If an application is received after that date, it will be returned to the applicant without review. REVIEW CONSIDERATIONS Those applications that are complete, responsive, and competitive will be evaluated in accordance with the criteria stated in the RFA announcement for scientific/technical merit by a special Review Committee convened by the NICHD. The second level of review will be provided by the National Child Health and Human Development Advisory Council. AWARD CRITERIA The anticipated date of award is July 1, 1993. An attempt will be made to balance the network so that it will have a multi-disciplinary composition, a diversity of research issues, and broad coverage of extant data sources. Awards will be made on the basis of the scientific merit of each research application and the need to create a balanced network. INQUIRIES It is essential to obtain a full version of this RFA before writing an application. Inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. To obtain a full version of the RFA or make inquiries regarding programmatic issues contact: V. Jeffery Evans, Ph.D., J.D. Demographic and Behavioral Sciences Branch Center for Population Research National Institute of Child Health and Human Development 6100 Executive Boulevard, Room 8B13 Bethesda, MD 20892 Telephone: (301) 496-1174 FAX: (301) 496-0962 Direct inquiries regarding fiscal matters to: Ms. Melinda Nelson Office of Grants and Contracts National Institute of Child Health and Human Development Executive Plaza North Building, Room 505 Bethesda, MD 20892 Telephone: (301) 496-5481 FAX: (301) 402-0915 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.864. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations, 42 CFR Part 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372, or to Health Systems Agency review. $$R2 END ************************************************************ $$R3 BEGIN DK-93-01 FULL-TEXT *************************************** DIABETES ENDOCRINOLOGY RESEARCH CENTERS NIH GUIDE, Volume 21, Number 35, October 2, 1992 RFA AVAILABLE: DK-93-01 P.T. 04; K.W. 0715075, 0785050, 0765020, 0710030 National Institute of Diabetes and Digestive and Kidney Diseases Letter of Intent Receipt Date: December 14, 1992 Application Receipt Date: January 14, 1993 THE REQUEST FOR APPLICATIONS (RFA) ANNOUNCED IN THIS NOTICE CONTAINS ESSENTIAL INFORMATION FOR THE PREPARATION OF AN APPLICATION. POTENTIAL APPLICANTS MAY OBTAIN THE RFA FROM THE CONTACT NAMED IN INQUIRIES, BELOW. PURPOSE The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) invites applications for funding of one Diabetes Endocrinology Research Center (DERC) grant to be competitively awarded in Fiscal Year 1994. 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, Diabetes Endocrinology Research Centers, is related to the priority area of diabetes mellitus. 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 and local governments, and eligible agencies of the Federal government. Minority individuals and women are encouraged to submit as Principal Investigators. Foreign institutions are not eligible to apply. MECHANISM OF SUPPORT Support of this program will be through the National Institutes of Health (NIH) grant-in-aid core center (P30) award. Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. In addition to the requirements stated in the announcement, awards will be administered under PHS grants policy as stated in the PHS Grants Policy Statement. The anticipated award date will be December 1, 1993. FUNDS AVAILABLE The NIDDK anticipates awarding one DERC Grant in Fiscal Year 1994 on a competitive basis. The receipt of one competing continuation application is anticipated, which will be in competition with the other applications received in response to this announcement. The anticipated award will be for five years and will be contingent upon the availability of appropriated funds. Requests for support must be limited to no more than $750,000 indirect costs per year. Any application exceeding this amount will be returned to the applicant. RESEARCH OBJECTIVES The NIDDK-supported DERCs are part of an integrated program of diabetes-related research support provided by the NIDDK. These Centers have provided a focus for increasing collaboration and cost effectiveness among groups of successful investigators at institutions with established comprehensive diabetes research bases. The objectives of the DERCs are to bring together investigators from relevant disciplines in a manner that will enhance and extend the effectiveness of research related to diabetes and its complications. Applicants should consult with NIDDK staff concerning plans for the development of the Center. STUDY POPULATIONS SPECIAL INSTRUCTIONS FOR INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDIES It is NIH policy that women and minorities must be included in clinical study populations unless there is a good reason to exclude them. The study design must seek to identify any pertinent gender or minority differences. 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 not included in the study populations for clinical studies, a specific justification for this exclusion must be provided. Applications without such documentation will not be accepted for review. LETTER OF INTENT Prospective applicants are asked to submit a letter of intent by December 14, 1992. The letter of intent need only include a descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, the identities of other key personnel and participating institutions, and the number and title of the RFA in response to which the application may be submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information that it contains is helpful in planning for the review of applications. It allows NIDDK 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 the Chief, Review Branch, NIDDK at the address noted below. APPLICATION PROCEDURES Applications are to be submitted on the form PHS 398 (rev. 9/91), available at most institutional business offices and from the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone (301) 496-7441. On item 2a of the face page of the application, applicants must enter the RFA number and title. Applicants are strongly encouraged to request a copy of "Guidelines for Diabetes Endocrinology Research Centers." These guidelines contain important additional information about the format, content, and review criteria. Prospective applicants may obtain guidelines from and may address inquiries to Dr. Garfield at the address listed under INQUIRIES. Applications must be received by January 14, 1993. The original and three copies of the application must be sent or delivered to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** Two additional copies of the application must be sent under separate cover to: Review Branch National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 406 Bethesda, MD 20892 REVIEW CONSIDERATIONS Applications for a DERC grant will be evaluated by the NIH grant peer review process. Applications will be reviewed initially by an ad hoc review group convened by the NIDDK and subsequently by the National Diabetes and Digestive and Kidney Diseases Advisory Council. Schedule Letter of Intent Receipt Date: December 14, 1992 Application Receipt Date: January 14, 1993 Initial Review Dates: Jun/Jul 1993 Second Level Review Date: Sep/Oct 1993 Anticipated Award Date: December 1, 1993 INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. Direct inquiries regarding programmatic issues and requests to: Dr. Sanford A. Garfield Diabetes Centers Program Director Division of Diabetes, Endocrinology, and Metabolic Diseases National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 626 Bethesda, MD 20892 Telephone: (301) 496-7418 FAX: (301) 480-038 Direct inquiries regarding fiscal matters to: Ms. Linda Stecklein Team Leader and Grants Management Specialist Division of Extramural Activities National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 649 Bethesda, MD 20892 Telephone: (301) 496-7467 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.847. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$R3 END ************************************************************ $$R4 BEGIN HS-93-01 FULL-TEXT *************************************** GRANTS FOR HEALTH SERVICES DISSERTATION RESEARCH NIH GUIDE, Volume 21, Number 35, October 2, 1992 RFA AVAILABLE: HS-93-01 P.T. 34; K.W. 0730050, 0710030 Agency for Health Care Policy and Research Application Receipt Date: January 22, 1993 THE REQUEST FOR APPLICATIONS (RFA) ANNOUNCED IN THIS NOTICE CONTAINS ESSENTIAL INFORMATION FOR THE PREPARATION OF AN APPLICATION. POTENTIAL APPLICANTS MAY OBTAIN THE RFA FROM THE CONTACT NAMED IN INQUIRIES, BELOW. PURPOSE The Agency for Health Care Policy and Research (AHCPR) announces the availability of an RFA for grants for health services dissertation research. The AHCPR conducts research that will enhance the quality, appropriateness, and effectiveness of health care services, and access to such services. The provision of dissertation grant support is part of the effort of the AHCPR to stimulate the development of innovative and timely research on issues related to the delivery of health care services. Grant support is designed to aid the career development of new health services researchers and to encourage individuals from a variety of academic disciplines and programs to study complex issues with respect to health care services. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. The AHCPR urges applicants to submit grant applications with relevance to 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 REQUIREMENTS A student applying for a dissertation research grant must be enrolled in an accredited doctoral degree program in the social, management, medical, or health sciences. The student also must be conducting or intending to conduct dissertation research on issues related to the delivery of health care services as described below. The proposed Principal Investigator (PI) must be a registered doctoral candidate in resident or nonresident status. All requirements for the doctoral degree other than the dissertation must be completed by the time of the award. This information must be verified in a letter of certification from the thesis chairperson and submitted with the grant application (see APPLICATION PROCEDURES). The applicant may be either the institution that will administer the grant on behalf of the proposed PI or the proposed PI applying as an individual. Whenever feasible, the proposed PI is encouraged to have the application administered through an institution. A proposed PI for dissertation research grant support need not be a U.S. citizen. However, a PI who is not a U.S. citizen and does not have a permanent resident visa must apply through an institution. A PI who receives support for dissertation research under a grant from the AHCPR may not at the same time receive support under a predoctoral training grant or fellowship grant awarded by any other agency of the U.S. Department of Health and Human Services. MECHANISM OF SUPPORT This RFA will use the AHCPR small grant (R03). Responsibility for the planning, direction, and execution of the proposed project will be solely that of the proposed PI. In addition to the requirements stated in this RFA, awards will be administered under PHS grants policy as described in the PHS Grants Policy Statement. The budget of an application for a dissertation research grant must not exceed $20,000 in total direct costs for the entire project period. An application that exceeds this amount will be returned to the applicant. Investigators may request support only for the amount of time necessary to complete the dissertation. A dissertation research grant usually is awarded for a period of 12 months or less but may be awarded for up to 17 months. FUNDS AVAILABLE The AHCPR expects to fund about 15 to 20 dissertation research projects in 1993. The number of awards will depend on the availability of funds. RESEARCH OBJECTIVES Only applications that propose studies in the areas identified in section 902 of the Public Health Service Act are eligible for support. Section 902 authorizes research in the following areas: o Effectiveness, efficiency, and quality of health care services o Outcomes of health care services and procedures o Clinical practice, including primary care and practice-oriented research o Health care technologies, facilities, and equipment o Health care costs, productivity, and market forces o Health promotion and disease prevention o Health statistics and epidemiology o Medical liability o AIDS/HIV infection o Rural health services o Health of low-income, minority, elderly, and other underserved populations Applicants are encouraged to discuss the suitability of their research topics by letter or by phone with AHCPR staff members listed under INQUIRIES. SPECIAL INSTRUCTIONS TO APPLICANTS CONCERNING INCLUSION OF WOMEN AND MINORITIES IN RESEARCH STUDY POPULATIONS The AHCPR requires applicants for research grants to include minorities and women in study populations. If women or minorities are excluded or inadequately represented in research, a clear and compelling rationale should be provided. All applications for research submitted to the AHCPR are required to address this policy with respect to the inclusion of women and minorities. Applications without such documentation will not be accepted for review. APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 9/91) is to be used in applying for these grants, in accordance with the special instructions described here and in the application kit. Research grant application materials, special instructions for dissertation grant applications, and the RFA are available from: AHCPR Publications Clearinghouse P.O. Box 8549 Silver Spring, MD 20907 Telephone: 1-800-358-9295 Applications must be received by Friday, January 22, 1993, to Division of Research Grants, National Institutes of Health, Westwood Building, Room 240, Bethesda, MD 20892. A letter from the faculty committee or university official directly responsible for supervising the development and progress of the dissertation research must be submitted with the application. The letter must (1) fully identify the members of the committee and certify their approval of the dissertation proposal, (2) certify that all requirements for the doctoral degree except the dissertation are completed (or will be completed by the time for the grant award), and (3) note that the university official or faculty committee expects the doctoral candidate to proceed with the approved project proposal with or without AHCPR support. REVIEW CONSIDERATIONS Dissertation research grant applications will be reviewed under AHCPR review procedures by non-Federal experts, senior AHCPR staff members, and other experts in the Federal government. Reviewers will be selected on the basis of their health services research accomplishments and knowledge and their experience in research career development. Because reviews are rigorous, considerable methodological detail is important in the narrative of the application. All elements of the application will be considered in the review process. Primary emphasis will be given to the significance, scientific merit, and feasibility of the project. Applications may be subject to triage to determine their scientific merit relative to other applications received in response to this RFA. The AHCPR will withdraw from further consideration those applications judged by triage to be noncompetitive for award and notify the PI and institutional official. Those applications judged to be competitive will undergo further scientific merit review. Review results and funding decisions will be announced approximately five months after the submission date. Review criteria, award criteria, and continuation of support are described below. Review Criteria Applications are reviewed to determine their suitability to review criteria in four major areas: problem significance, research design, investigator's qualifications and support structure, and budgetary appropriateness. Detailed criteria for these areas, as they relate to dissertation research, are provided in the RFA. AWARD CRITERIA Reviewers will provide recommendations with regard to the scientific and technical merit of the application and whether it should receive further consideration. Funding decisions are based on the recommendations of the reviewers, the relevance of the project to program priorities, and the availability of appropriated funds. INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. Applicants are encouraged to discuss programmatic issues, such as the suitability of their research topics, by letter or telephone with: Julius Pellegrino, M.B.A., M.P.H. Program Coordinator, Dissertation Grants Center for General Health Services Extramural Research Executive Office Center, Suite 502 2101 E. Jefferson Street Rockville, MD 20852 Telephone: (301) 227-8357 Direct inquiries regarding instructions for completing the application to: Galen B. (Sandy) Warren, D.D.S., M.P.H. Office of Scientific Review Agency for Health Care Policy and Research Executive Office Center, Suite 602 2101 E. Jefferson Street Rockville, MD 20852 Telephone: (301) 227-8449 Direct inquiries regarding fiscal and administrative matters to: Ralph Sloat Chief, Grants Management Branch Agency for Health Care Policy and Research Executive Office Center, Suite 601 2101 E. Jefferson Street Rockville, MD 20852 Telephone: (301) 227-8447 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.226. Awards are made under authority of title IX of the Public Health Service Act, as amended (42 U.S.C. 299-299c-6), and administered under PHS grants policies and in accordance with regulations of Title 42 of the Code of Federal Regulations, Part 67, Subpart A. The requirements of Executive Order 12372, Intergovernmental Review of Federal Programs, are not applicable to AHCPR research grant programs. $$R4 END ************************************************************ $$R5 BEGIN HL-93-02-P FULL-TEXT ************************************* IMPROVING HYPERTENSIVE CARE FOR INNER CITY MINORITIES NIH GUIDE, Volume 21, Number 35, October 2, 1992 RFA AVAILABLE: HL-93-02-P P.T. 34; K.W. 0715115, 0414014, 0413001, 0403004, 0502017 National Heart, Lung, and Blood Institute Letter of Intent Receipt Date: November 30, 1992 Application Receipt Date: February 16, 1993 THE REQUEST FOR APPLICATIONS (RFA) ANNOUNCED IN THIS NOTICE CONTAINS ESSENTIAL INFORMATION FOR THE PREPARATION OF AN APPLICATION. POTENTIAL APPLICANTS MAY OBTAIN THE RFA FROM THE CONTACT NAMED IN INQUIRIES, BELOW. PURPOSE The Division of Epidemiology and Clinical Applications (DECA) invites applications for demonstration and education projects aimed at improvements in hypertensive care among inner city minority populations. The awards will be for a funding period of four years. The program will focus on community-based health education and/or other approaches for enhancing compliance and improving blood pressure control in urban minority populations. The intervention models should be widely applicable and economical. While hypertension is the focus of the program, a multiple risk factor approach may be used to assess changes in other cardiovascular risk factors. 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, Improving Hypertensive Care for Inner City Minorities, is related to the priority area of heart disease and stroke. 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, 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 organizations are not eligible to apply and domestic applications may not include international components. Applications from minority individuals, particularly African Americans and Hispanics, and women are encouraged. MECHANISM OF SUPPORT The support mechanism for this RFA will be the National Institutes of Health (NIH) demonstration and education (D&E) research grant (R18). Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. The total project period for applications submitted in response to the present RFA may not exceed four years. The anticipated award date is September 30, 1993. FUNDS AVAILABLE It is anticipated that three to five centers will be supported over the four year period of this program. An estimated total cost (direct and indirect) of $2,500,000 will be available for the first year of funding for the entire program, with an estimated four year total cost of $10,600,000. This level of support is dependent upon the receipt of a sufficient number of applications of high scientific merit. Although this program is provided for in the financial plans of the National Heart, Lung, and Blood Institute (NHLBI), awards pursuant to this RFA are contingent upon the availability of funds for this purpose. RESEARCH OBJECTIVES The primary objective of this four-year demonstration and education research program is to develop, and to evaluate for feasibility, acceptability, and effectiveness, methods to maintain therapy and control of hypertension, for both newly and previously diagnosed individuals, in inner city, primarily minority populations. The focus will be on community-based health education and other approaches for enhancing compliance and improving blood pressure control among inner city minority populations. The delivery of and adherence to the interventions is the main objective, rather than clinical algorithms used to treat hypertension. While the improvement of hypertensive care is the focus of this program, other cardiovascular disease risk factors may be included in the interventions, and changes in these factors should be assessed. The role of non-pharmacologic approaches to reducing blood pressure, including drug and alcohol avoidance, should be addressed. Primary outcome measures to assess the interventions may include: percentages aware of hypertension, screened for hypertension, treated for hypertension, responding to treatment, and controlled to normal levels of blood pressure; clinic attendance; and compliance with therapy. Secondary outcomes include the assessment of: effects on other CVD risk factors, e.g., cigarette smoking, overweight, lipid profile, and diabetes; health quality of life measures; and cost effectiveness of the interventions. The experimental design is not restricted by this RFA. Applicants should develop their own independent design, and provide justification for the proposed design. The designs should focus on an integrated approach including various management factors that have previously been shown to be effective. Health education and other approaches for enhancing compliance and improving blood pressure control should be adequately described. A randomized design, comparing special interventions against usual care would be one appropriate study design to test intervention models. If justified by the nature of the proposed intervention, i.e., delivery of an intervention to a social group (e.g., neighborhood or employee group), other designs will be considered responsive. Annual meetings, to be held in Bethesda, MD, are planned for the exchange of information among investigators. Applicants must budget the travel costs associated with these meetings in their applications. STUDY POPULATIONS Because of their excess burden of hypertension, African Americans should comprise a large proportion of the study population. Although there is no compelling evidence of excess burden from hypertension among Hispanics compared to the population at large, socioeconomic factors for inner-city members of this group may result in less than optimal hypertension detection and treatment. Therefore, the inclusion of Hispanics, which may be best accomplished by the inclusion of Hispanics as the majority of the sample at one of the study sites, may be proposed. Investigators should also consider other minority groups, as well as low socioeconomic whites, for inclusion. The inclusion of low socioeconomic-status (SES) whites may provide some means to separate the effects of SES and ethnicity. As the lowest hypertension control rates are seen in young African Americans, investigators should address the advantages and disadvantages of oversampling this younger segment of the population. SPECIAL INSTRUCTIONS TO 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 and minorities are not included in the study populations for clinical studies, 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 November 30, 1992, a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, the identities of other key personnel and participating institutions, and the number and title of the RFA in response to which the application may be submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information that it contains is helpful in planning for the review of applications. It allows NHLBI staff to estimate the potential workload and to avoid conflict of interest in the review. The letter of intent is to be sent to: C. James Scheirer, Ph.D. Review Branch, Division of Extramural Affairs National Heart, Lung, and Blood Institute Westwood Building, Room 548 Bethesda, MD 20892 Telephone: (301) 496-7363 FAX: (301) 402-1660 APPLICATION PROCEDURES The research grant application form 398 (rev. 9/91) is to be used in applying for this award. These forms are available at most institutional business offices; from the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone (301) 496-7441; and from the NHLBI Program Administrator named below. Applications must be received by February 16, 1993. If an application is received after that date, it will be returned to the applicant. The Division of Research Grants (DRG) will not accept any application in response to this announcement that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. The DRG will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of substantial revisions of applications already reviewed, but such applications must include an introduction addressing the previous critique. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed by NIH staff for completeness and responsiveness. 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 that are found to be responsive will be reviewed for scientific and technical merit by an initial review group, convened by the Division of Extramural Affairs, NHLBI solely to review these applications. The initial review will include an evaluation to determine scientific merit relative to other applications received in response to this RFA. The NIH will withdraw from further competition those applications judged non-competitive for award and notify the applicant Principal Investigator and institutional official. Those applications judged to be competitive will be further evaluated for scientific/technical merit by the usual peer review procedures, including, if deemed appropriate, a reverse site visit at the applicant's expense. Secondary review of applications will be conducted by the National Heart, Lung, and Blood Advisory Council. AWARD CRITERIA Applications recommended by the National Heart, Lung, and Blood Advisory Council will be considered for award based upon scientific and technical merit, overall program balance, and the availability of funds. The anticipated date of award is September 30, 1993. 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: P. Scott Allender, M.D. Prevention and Demonstration Research Branch Division of Epidemiology and Clinical Applications National Heart, Lung, and Blood Institute Federal Building, Room 604 7550 Wisconsin Avenue Bethesda, MD 20892 Telephone: (301) 496-2465 Direct inquiries regarding fiscal matters to: William W. Darby Section Chief, Grants Operations Branch Division of Extramural Affairs National Heart, Lung, and Blood Institute Westwood Building, Room 4A11 Bethesda, MD 20892 Telephone: (301) 496-7536 AUTHORITY AND REGULATIONS This project is described in the Catalog of Federal Domestic Assistance No. 93.837. 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 project is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$R5 END ************************************************************ ONGOING PROGRAM ANNOUNCEMENTS $$P1 BEGIN PA-93-001 ************************************************ CHEMORECEPTION AND NUTRITION NIH GUIDE, Volume 21, Number 35, October 2, 1992 PA NUMBER: PA-93-001 P.T. 34; K.W. 0710095, 1002004, 0705070 National Institute on Deafness and Other Communication Disorders National Institute of Diabetes and Digestive and Kidney Diseases National Institute of Dental Research National Institute on Aging National Institute of Child Health and Human Development PURPOSE The purpose of this Program Announcement (PA) is to foster basic and clinical research on the interactions between chemoreception and nutrition. This research may involve the effects of nutritional variables on taste, smell, and somatosensory chemoreception, or this research may involve the effects of chemosensory variables on nutrition and diet. 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, Chemoreception and Nutrition, is related to the priority area of nutrition. 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 and local governments, and eligible agencies of the Federal government. Applications from minority individuals and women are encouraged. Foreign institutions are not eligible for the First Independent Research Support and Transition (FIRST) Award (R29). MECHANISM OF SUPPORT The mechanisms available for the support of this program are research project grants (R01) and the FIRST Award (R29). 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. In such a case, a letter of agreement from either the GCRC program director or Principal Investigator must be included with the application. RESEARCH OBJECTIVES The support of nutrition research at the National Institutes of Health (NIH) includes studies designed to assess the consequences of food or nutrient intake and utilization in the intact organism, including humans, and the metabolic and behavioral mechanisms involved. These studies encompass investigation of nutrient variables at the cellular or subcellular level. These studies also include investigations of genetic/ environmental interactions in which a nutrient is a variable and dietary practices are expected to produce changes in health status, including the maintenance of health and the treatment of disease in humans. Current research in nutrition at the NIH is periodically reported in the Nutrition Coordinating Committee's publication entitled "Nutrition Research at the NIH," which includes examples of nutrition-related chemosensory research supported by the NIH. Potential applicants may obtain a copy of "Nutrition Research at the NIH" (NIH Publication No. 91-2611) through the Division of Research Coordination, Building 31, Room 4B63, Bethesda, MD 20892 (telephone 301-496-4982). The goal of this PA is to foster basic and clinical research that will lead to a better understanding of the interactions between chemoreception and nutrition and better preventive interventions for chemosensory and nutritional disorders. This research may involve the effects of nutritional variables on chemoreception, including taste, smell, and somatosensory responses related to oral and nasal chemoreception; this research may also be focused on the effects of chemosensory variables on nutrition and diet. A broad range of studies covering the molecular to the behavioral levels of research is encouraged. Interactions among investigators in various biomedical and behavioral fields and disciplines are encouraged, including nutrition, psychophysics, biochemistry, and molecular biology. Research topics might include those below. Investigators are encouraged to consider other topics relevant to this program. o Nutritional influences, including excessive nutrient intake, on the molecular structure and function of chemosensory epithelia and on secretory transport and other perireceptor events related to chemoreception, including mucosal defense mechanisms. o Alteration of chemosensory receptor membrane events, including the modification of sweet, bitter, sour, and salt taste sensation, by influencing receptor binding or second messenger activation. o Nutritional influences on the regeneration cycle of olfactory receptor neurons and taste bud cells under normal physiological conditions and after injury to the chemosensory systems. o Effects of dietary alterations in early life on the structure and function of chemosensory systems, including trigeminal chemoreception; effects of dietary alterations in early life on the development of sweet, bitter, sour, and salty taste and amiloride-sensitive sodium channels. o Mother-infant relationships involving odors and nutrition. o Relation of smell, taste, and somatosensory aspects of flavor perception to the amount of food consumed and the types of foods selected and rejected. o Genetic studies involving food preferences and individual differences in chemosensory abilities, for example, the ability to taste phenylthiourea and other bitter substances and to smell androstenone; studies of patients with Kallmann's disease or familial dysautonomia. o Associations between chemosensory disorders and altered food intake in age-related conditions and various chronic disease states, including oral and dental diseases (e.g., xerostomia, dental caries, and periodontal disease), obesity, diabetes, inborn errors of metabolism, and digestive, hepatic, and kidney diseases. o Effects of artificial sweeteners and salt substitutes on nutrition and chemoreception. o Nutritional and chemosensory status in special subpopulations, including minorities, nursing mothers, and postmenopausal women with burning mouth symptoms; individuals with pseudohypoparathyroidism associated with G protein deficiency and hyposmia; those receiving hormonal therapy. o Iatrogenic alterations of nutritional and chemosensory status resulting from interventions, such as oral and dental prosthesis, hemodialysis, irradiation, and chemotherapy. o Impact of the affective dimensions of chemoreception in health and disease on food choices and utilization; impact of depressive and eating disorders on chemosensory affect and sensitivity; impact of dysosmia and dysgeusia on food choices and intake. o Role of chemoreception in digestion and metabolism of nutrients. o Development of chemosensory test stimuli that mimic chemosensory properties of food and permit stimulus control. SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS. NIH and ADAMHA policy is that applicants for NIH/ADAMHA 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 From owner-sci-resources@net.bio.net Thu Oct 08 23:00:00 1992 Path: biosci!NET.BIO.NET!kristoff From: kristoff@NET.BIO.NET (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 21, no. 35, pt. 2, 2 October 1992 Message-ID: Date: 9 Oct 92 01:59:37 GMT Sender: kristoff@net.bio.net Distribution: bionet Lines: 1514 $$XID NIHGUIDE 19921002 V21N35 P2O2 ************************************ terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues must be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information must be included in the form PHS 398 in Sections 1-4 of the Research Plan AND summarized in Section 5, Human Subjects. Applicants/offerors are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, 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 reflected in assigning the priority score to the application. All applications for clinical research submitted to the NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. APPLICATION PROCEDURES Applications are to be submitted on the grant application form PHS 398 (rev. 9/91) and will be accepted at the standard application deadlines as indicated in the application kit. Application kits are available at most institutional offices of sponsored research and may be obtained from the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone 301/496-7441. 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 PROCEDURES Applications will be assigned on the basis of established PHS referral guidelines. Applications will be reviewed for scientific and technical merit by study sections of the Division of Research Grants, NIH, in accordance with the standard NIH peer review procedures. Following scientific-technical review, the applications will receive a second-level review by an appropriate National Advisory Council or Board. AWARD CRITERIA Applications will compete for available funds with all other approved applications. The following will be considered in making funding decisions: o Quality of the proposed project as determined by peer review o Program balance among research areas of the announcement o Availability of funds INQUIRIES Direct inquiries regarding the major areas of research interest in this nutrition program to: Chemoreception Rochelle Small, Ph.D. Division of Communication Sciences and Disorders National Institute on Deafness and Other Communication Disorders Executive Plaza South, Room 400-B 6120 Executive Boulevard Rockville, MD 20892 Telephone: (301) 402-3464 FAX: (301) 402-6251 Obesity and Nutrition Sciences Van S. Hubbard, M.D., Ph.D. Director, Obesity, Eating Disorders and Energy Regulation National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 3A18 Bethesda, MD 20892 Telephone: (301) 496-7823 FAX: (301) 402-1278 Oral Diseases and Conditions Joseph E. Ciardi, Ph.D. Director, Caries, Nutrition and Fluoride Program Extramural Programs National Institute of Dental Research Westwood Building, Room 509 Bethesda, MD 20892 Telephone: (301) 496-7784 FAX: (301) 496-4180 Aging Ann Sorenson, Ph.D. Biology of Aging Program National Institute on Aging Gateway Building, Room 2C231 7201 Wisconsin Avenue Bethesda, MD 20892 Telephone: (301) 496-6402 FAX: (301) 402-0010 Development Ephraim Y. Levin, M.D. Medical Officer, Endocrinology, Nutrition and Growth Branch Center for Research for Mothers and Children National Institute of Child Health and Human Development Executive Plaza North, Room 637 Bethesda, MD 20892 Telephone: (301) 496-5593 FAX: (301) 402-2085 Direct inquiries regarding fiscal matters to: Sharon Hunt Grants Management Branch Division of Extramural Activities National Institute on Deafness and Other Communication Disorders Executive Plaza South, Room 400-B Rockville, MD 20892 Telephone: (301) 402-0909 FAX: (301) 402-1758 Paulette Badman Grants Management Specialist Division of Extramural Programs National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 637 Bethesda, MD 20892 Telephone: (301) 496-7467 FAX: (301) 496-9721 Theresa Ringler Chief, Grants Management Section Program Operations Branch National Institute of Dental Research Westwood Building, Room 518 Bethesda, MD 20892 Telephone: (301) 496-7437 FAX: (301) 402-1260 Mary Daley Grants Management Branch National Institute on Aging Gateway Building, Room 2N212 7201 Wisconsin Avenue Bethesda, MD 20892 Telephone: (301) 496-1472 FAX: (301) 402-0066 Edgar Douglas Shawver Chief, Maternal and Child Research Grants Management Section Office of Grants and Contracts National Institute of Child Health and Human Development Executive Plaza North, Room 505 Rockville, MD 20892 Telephone: (301) 496-1303 FAX: (301) 402-0915 AUTHORITY AND REGULATIONS The programs of the National Institute on Deafness and Other Communication Disorders, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Dental Research, National Institute on Aging, and National Institute of Child Health and Human Development, are identified in the Catalog of Federal Domestic Assistance, Nos. 93.173, 93.848, 93.121, 93.866 and 93.865, respectively. 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. $$P1 END ************************************************************ $$P2 BEGIN PA-93-002 ************************************************ PREVENTION OF END STAGE LIVER DISEASES BY MOLECULAR DIAGNOSIS NIH GUIDE, Volume 21, Number 35, October 2, 1992 PA NUMBER: PA-93-002 P.T. 34; K.W. 0745020, 1002008, 1002019 National Institute of Diabetes and Digestive and Kidney Diseases PURPOSE The purpose of this Program Announcement (PA) is to encourage research on isolating the gene(s) or the full length cDNAs for the gene(s) of the many genetic liver diseases in which early diagnosis and treatment could avert progressive serious liver injury. Liver transplantation is often the only treatment for these diseases when they are not detected and treated early. Two of the liver diseases in which early diagnosis could be curative and in which much information exists about the gene and/or its location are Wilson's disease and hemochromatosis. 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, Prevention of End Stage Liver Diseases by Molecular diagnosis, is related to the priority area of diabetes and chronic disabling conditions. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic for-profit and non-profit United States organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Applications from minority individuals and women are encouraged. Foreign institutions are not eligible for First Independent Research Support and Transition (FIRST) Awards (R29). MECHANISM OF SUPPORT The Research Project Grant (R01), the FIRST Award (R29), and the Interactive Research Project Grant (interactive R01s) are all appropriate mechanisms. Program Project Grant (P01) or Center Grant (P30) applications will not be accepted. RESEARCH OBJECTIVES Hemochromatosis and Wilson's disease are two inherited diseases of trace metal metabolism that can cause end stage liver disease. If diagnosed early before the onset of significant liver damage, available treatments are usually effective. Unfortunately, both hemochromatosis and Wilson's disease are rarely diagnosed before the onset of symptoms in the liver or other organs. Both diseases result in liver cirrhosis for which liver transplantation is the only effective treatment. Currently, there is no easy means of early screening for either disease since the genetic defect has not been positively identified. Hemochromatosis, which affects approximately one in 300 persons, appears to be due to an excessive absorption of dietary iron that leads over years to excessive bodily iron stores that eventually cause cellular damage and organ injury in liver, heart, pancreas and gonads. If hemochromatosis is diagnosed, the organ injuries can be averted by phlebotomy to decrease the body iron stores to normal. The enzyme or transport protein responsible for the excessive absorption of iron has not been identified. It is not ferritin, transferrin, or the transferrin receptor. The new techniques of molecular biology promise to provide means of identifying the defect in hemochromatosis. The molecular techniques needed are probably not the conventional ones that proceed from the abnormal protein to the gene, but rather "reverse genetics" that first identifies the gene and from it the abnormal protein. Such techniques were successful in identifying the abnormality in cystic fibrosis and neurofibromatosis. Indeed, in hemochromatosis an advantage has been established already by the known linkage of this disorder with the HLA region on the short arm of chromosome 6. If the gene for hemochromatosis could be identified, genetic screening of newborns could be used to identify homozygotes and to initiate lifelong phlebotomy therapy before the onset of disease or organ damage. Wilson's disease, which affects approximately one in 10,000 persons, appears to be due to a genetic defect in the secretion of copper in bile that leads over time to a gradual accumulation of excessive copper stores in the liver, red blood cells, synovium, kidneys and brain. Untreated Wilson's disease leads to irreversible end stage liver disease and/or brain damage between the ages of 15 and 40 years. If Wilson's disease can be identified early, however, the copper accumulation can be prevented by chelation therapy (d-penicillamine) and the liver and brain disease completely averted. Unfortunately, Wilson's disease is rarely diagnosed early, and this is still an important cause of liver failure necessitating liver transplantation. Approaches that might be taken to identify the Wilson's disease gene also include those of reverse genetics by identifying genetic markers that co-segregate with this disease. Such studies require data collected from large families with Wilson's disease using multiple genetic markers. These studies have shown that this gene is located on chromosome 3. Further studies are needed to more closely locate the gene to a fragment of DNA that can be sequenced and characterized. Both of these examples of diseases that could benefit from appropriate early diagnosis through molecular biology techniques require the availability of large family cohorts to serve as subjects and controls. The availability of multi-generational families in which linkage analyses can be done will be very important to progress in these studies. Other liver diseases such as Alagille syndrome and Crigler-Najjar syndrome type I, in which early diagnosis may make available treatment(s) that can prevent serious liver malfunction, may also be submitted and be responsive to this PA. The emphasis in this announcement is on the diagnosis of the genetic defect and not on the treatment of the disease. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS It is NIH policy that women and minorities must be included in clinical study populations unless there is a good reason to exclude them, and the study design must seek to identify any pertinent gender or minority population differences. 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, 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 must be provided. For the purpose of this policy, clinical research is defined as human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including but not limited to clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded. However, every effort should be made to include human tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. For foreign awards, the policy on inclusion of women applies fully; since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. If the required information is not contained within the application, the review will be deferred until the information is provided. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and will be reflected in assigning the priority score to the application. All applications for clinical research submitted to the NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. APPLICATION PROCEDURES Applications are to be submitted on the grant application form PHS 398 (rev. 9/91) and will be accepted at the regular application deadlines as indicated in the application kit. FIRST (R29) Award applications must include at least three sealed letters of reference attached to the face page of the original application. FIRST Award applications submitted without the required number of reference letters will be considered incomplete and will be returned to the applicant without review. Application kits are available at most institutional business and grant/contract offices and may be obtained from the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone 301/496- 7447. The title and number of this 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 to initial review groups and to Institutes or Centers for possible funding on the basis of established PHS referral guidelines. Applications will be reviewed for scientific and technical merit by initial review groups of the Division of Research Grants in accordance with the standard NIH peer review procedures. Following scientific-technical review, the applications will receive a second-level review by an appropriate National Advisory Council. AWARD CRITERIA Applications will compete for available funds with all other approved applications. The following will be considered in making funding decisions: o Quality of the proposed project as determined by peer review o Availability of funds o Program balance among research areas of the announcement INQUIRIES Written and telephone inquiries are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Inquiries regarding programmatic issues may be directed to: Sarah C. Kalser, Ph.D. Liver and Biliary Diseases Program Director Division of Digestive Diseases and Nutrition National Institute of Diabetes and Digestive and Kidney Diseases 5333 Westbard Avenue, Room 3A-05 Bethesda, MD 20892 Telephone: (301) 496-7858 David G. Badman, Ph.D. Hematology Program Director Division of Kidney, Urologic, and Hematologic Diseases National Institute of Diabetes and Digestive and Kidney Diseases 5333 Westbard Avenue, Room 3A-05 Bethesda, MD 20892 Telephone: (301) 496-7458 Direct inquiries regarding fiscal matters to: Miss Aretina Perry Grants Management Branch National Institute of Diabetes and Digestive and Kidney Diseases Bethesda, MD 20892 Telephone: (301) 496-7467 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.848. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$P2 END ************************************************************ $$P3 BEGIN PA-93-003 ************************************************ RESEARCH INFRASTRUCTURE SUPPORT PROGRAM NIH GUIDE, Volume 21, Number 35, October 2, 1992 PA AVAILABLE: PA-93-003 P.T. 14; K.W. 0715129, 0785035, 0710030 National Institute of Mental Health THE PROGRAM ANNOUNCEMENT (PA) ANNOUNCED IN THIS NOTICE CONTAINS ESSENTIAL INFORMATION FOR THE PREPARATION OF AN APPLICATION. POTENTIAL APPLICANTS MAY OBTAIN THE PROGRAM ANNOUNCEMENT FROM THE CONTACT NAMED IN INQUIRIES, BELOW. PURPOSE The National Institute of Mental Health (NIMH) is committed to expanding the number of institutions capable of supporting state-of-the-art clinical and services research and thus increasing the number of investigators obtaining extramural funding for their research. Expansion of the clinical research infrastructure is a major priority of the NIMH; the Research Infrastructure Support Program (RISP) is a direct response of the NIMH to recommendations made by the National Advisory Mental Health Council and by the NIMH Extramural Science Advisory Board. The purpose of this PA is to stimulate the development of new resources at institutions capable of developing and maintaining programs of clinical and services research directed at the major mental disorders. 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 PA, Research Infrastructure Support Program, is related to the priority areas of mental health and mental disorders. 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 public and private, non-profit and for-profit organizations such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government, except for those institutions with NIMH research support exceeding $3,000,000 (in total costs) in fiscal year 1991. Women and minorities are encouraged to apply. MECHANISM OF SUPPORT Grants awarded in the RISP program will use the Resource-Related Research Project mechanism (R24) to contribute to the improvement of the capability of resources to serve biomedical research. RESEARCH OBJECTIVES Many institutions with access to large and varied populations of individuals with mental disorders are not able to launch research programs because of limited technical and scientific support available within their research environment. This program will assist in the development of these and other resources that will form part of the institution's clinical research infrastructure. Applicant institutions must describe a comprehensive and coherent plan of improvement to the institution's current research environment that will expand the capacity of investigators at the institution to carry out extramurally supported mental health research. The plan must have a focus on particular mental health clinical populations or diagnostic groups and must demonstrate accessibility of the population to institution-based investigators. The plan must also demonstrate the actual commitment of institutional resources which may include senior faculty release time, support staff, research bed costs, equipment costs assumed by the institution, and waiver of overhead costs. A central philosophical principle underlying this program is that different institutions will require different types of infrastructure development activities and initiatives. Therefore, this announcement does not prescribe in any detail the nature of the activities to be applied for or supported. The following types of support may be requested under this program: o Partial salary support for junior faculty, particularly women and minorities o Training expenses for junior faculty o Research patient recruitment, diagnosis, assessment, and follow-up o Clinical and scientific consultation, including expenses incurred by an external review and scientific advisory committee o Biostatistical and data-base management services o Small equipment and research instruments o Research technicians and assistants o Developmental, feasibility, or pilot studies STUDY POPULATIONS NIH POLICY CONCERNING INCLUSION OF MINORITIES AND WOMEN AS SUBJECTS IN RESEARCH Applications for grants and cooperative agreements and proposals for contracts that involve human subjects are required to include minorities and both genders 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 applies to all research involving human subjects and human materials, and applies to males and females of all ages. If one gender and/or minorities are excluded or are inadequately represented in this research, particularly in proposed population-based studies, a clear compelling rationale for exclusion or inadequate representation should 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. 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., American Indians or Alaskan Natives, Asians or Pacific Islanders, Blacks, Hispanics). Investigators must provide the rationale for studies on single minority population groups. 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. Applications for support of research involving human subjects must employ a study design with minority and/or gender representation (by age distribution, risk factors, incidence/prevalence, etc.) appropriate to the scientific objectives of the research. It is not an automatic requirement for the study design to provide statistical power to answer the questions posed for men and women and racial/ethnic groups separately; however, whenever there are scientific reasons to anticipate differences between men and women, and racial/ethnic groups, with regard to the hypothesis under investigation, applicants should include an evaluation of these gender and minority group differences in the proposed study. If adequate inclusion of one gender and/or minorities is impossible or inappropriate with respect to the purpose of the research, because of the health of the subjects, or other reasons, or if in the only study population available, there is a disproportionate representation of one gender or minority/majority group, the rationale for the study population must be well explained and justified. All applications for clinical research submitted to the NIH are required to address these policies. NIH funding components will not award grants that do not comply with these policies. APPLICATION PROCEDURES Applicants are to use the research grant application form PHS 398 (rev. 9/91) in applying for these grants. The number and title of this PA, Research Infrastructure Support Program, must be typed in item 2a on the face page of the PHS application form. Applications kits containing the necessary forms and instructions may be obtained from business offices and offices of sponsored research at most universities, colleges, medical schools, and other major research facilities. If such a source is not available, the necessary application materials may be obtained from the Grants Management Branch, National Institute of Mental Health, 5600 Fishers Lane, Room 7C-05, Rockville, MD 20857 (telephone 301/443-4414). The signed original and five legible copies of the completed application must be sent to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** REVIEW CONSIDERATIONS Applications will be reviewed for scientific and technical merit by an initial review group (IRG) composed of primarily non-Federal scientific experts. Final review is by the appropriate National Advisory Council, review by Council may be based on policy considerations as well as scientific merit. By law, only applications recommended by the Council may be considered for funding. Summary statements of IRG discussions are sent to applicants as soon as possible following IRG review. Review Criteria o Past research training record for both the program and the designated preceptors in terms of the rate at which former trainees establish independent and productive research careers o Past research training record in terms of the success of former trainees in obtaining individual awards such as fellowships, career awards, and research grants for further development o Objectives, design, and direction of the research training program o Caliber of preceptors as researchers including successful competetion for research support o Training environment including the institutional commitment, the quality of the facilities, and the availability of research support o Recruitment and selection plans for appointees and the availability of high quality candidates o The record of the research training program in retaining health- professional post-doctoral trainees for at least two years in research training or other research activities o When appropriate, the concomitant training of health-professional post-doctorates (e.g., individuals with the M.D., D.O., D.D.S.) with basic science post-doctorates (e.g., individuals with a Ph.D., Sc.D.) will receive special consideration Following scientific-technical review, the application will receive a second-level review by the appropriate National Advisory Council. AWARD CRITERIA Applications recommended for approval by the appropriate National Advisory Council will be considered for funding on the basis of overall scientific and technical merit of the research as determined by peer review, program needs and balance, and availability of funds. 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: Grayson S. Norquist, M.D., M.S.P.H. Deputy Director, Division of Epidemiology and Services Research National Institute of Mental Health Parklawn Building, Room 18C-26 5600 Fishers Lane Rockville, MD 20857 Telephone: (301) 443-3683 Direct inquiries regarding fiscal matters to: Stephen J. Hudak Chief, Grants Management Section National Institute of Mental Health Parklawn Building, Room 7C-23 5600 Fishers Lane Rockville, MD 20857 Telephone: (301) 443-4456 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.3. 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 regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$P3 END ************************************************************ $$XID RFA DK9301 DK-93-01 P1O1 ***************************************** DIABETES ENDOCRINOLOGY RESEARCH CENTERS NIH GUIDE, Volume 21, Number 35, October 2, 1992 RFA: DK-93-01 P.T. 04; K.W. 0715075, 0785050, 0765020, 0710030 National Institute of Diabetes and Digestive and Kidney Diseases Letter of Intent Receipt Date: December 14, 1992 Application Receipt Date: January 14, 1993 PURPOSE The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) invites applications for funding of one Diabetes Endocrinology Research Center (DERC) grant to be competitively awarded in Fiscal Year 1994. 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, Diabetes Endocrinology Research Centers, is related to the priority area of diabetes mellitus. 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 and local governments, and eligible agencies of the Federal government. Minority individuals and women are encouraged to submit as Principal Investigators. Foreign institutions are not eligible to apply. MECHANISM OF SUPPORT Support of this program will be through the National Institutes of Health (NIH) grant-in-aid core center (P30) award. Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. In addition to the requirements stated in this announcement, awards will be administered under PHS grants policy as stated in the PHS Grants Policy Statement. FUNDS AVAILABLE The NIDDK anticipates awarding one DERC Grant in Fiscal Year 1994 on a competitive basis. The receipt of one competing continuation application is anticipated, which will be in competition together with the other applications received in response to this announcement. The anticipated award will be for five years and will be contingent upon the availability of appropriated funds. Requests for support must be limited to no more than $750,000 in direct costs per year. Any application exceeding this amount will be returned to the applicant. RESEARCH OBJECTIVES The NIDDK-supported DERCs are part of an integrated program of diabetes-related research support provided by the NIDDK. These Centers have provided a focus for increasing collaboration and cost effectiveness among groups of successful investigators at institutions with established comprehensive diabetes research bases. The objectives of the DERCs are to bring together investigators from relevant disciplines in a manner that will enhance and extend the effectiveness of research related to diabetes and its complications. A Diabetes Center must be an identifiable unit within a single university medical center or a consortium of cooperating institutions, including an affiliated university. The overall goal of the DERC is to bring together, on a cooperative basis, clinical and basic science investigators in a manner that will enrich the effectiveness of diabetes research. An existing program of excellence in biomedical research in the area of diabetes and related metabolic and endocrine disorders is required. This research should be in the form of NIH-funded research projects, program projects, or other peer-reviewed research that is in existence at the time of submission of a Center application. Close cooperation, communication, and collaboration among all involved personnel of all professional disciplines are ultimate objectives. Applicants should consult with NIDDK staff concerning plans for the development of the Center. The DERCs are based on the core concept. Cores are defined as shared resources that enhance productivity or in other ways benefit a group of investigators working in diabetes or diabetes-related areas to accomplish the stated goals of the Center. Two other types of activities may also be supported with Center funding---a pilot and feasibility program and an enrichment program. The pilot and feasibility program provides modest support for new initiatives or feasibility research studies. This program is directed at new investigators or investigators established in other research disciplines, whose expertise may be applied to diabetes research. The center grant may also include limited funds for program enrichment such as seminars, visiting scientists, consultants, and workshops. 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. In such a case, a letter of agreement from either the GCRC program director or Principal Investigator should be included with the application. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS It is NIH policy that women and minorities must be included in clinical study populations unless there is a good reason to exclude them. The study design must seek to identify any pertinent gender or minority population differences. NIH and ADAMHA policy is that applicants for NIH/ADAMHA 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. This policy is applicable for every individual study or project proposed in the application. 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, 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. If the required information is not contained within the application, the application will be returned without review. LETTER OF INTENT Potential applicants are strongly encouraged to submit a letter of intent no later than December 14, 1992. The letter of intent need only include the names of the Principal Investigator/program director and principal collaborators, descriptive title of the potential application, identification of the organization(s) involved, and reference to the RFA number DK-93-01. The letter of intent is to be sent to the Chief, Review Branch, NIDDK at the address noted below. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information that it contains is helpful in planning the review of applications. It allows NIDDK staff to estimate the potential review workload and to avoid conflict of interest in the review. APPLICATION PROCEDURES Applicants are strongly encouraged to request a copy of "Guidelines for Diabetes Endocrinology Research Centers." These guidelines contain important additional information on the format, content, and review of applications and review criteria. Prospective applicants may obtain guidelines from and may address inquiries to: Dr. Sanford A. Garfield Diabetes Centers Program Director Division of Diabetes, Endocrinology, and Metabolic Diseases National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 626 Bethesda, MD 20892 Telephone: (301) 496-7418 FAX: (301) 480-0383 Applications are to be submitted on the form PHS 398 (rev. 9/91) available at most institutional business offices and from the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone (301) 496-7441. On item 2a of the face page of the application, applicants must enter the RFA title and number. 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 to the extent that it may not reach the review committee in time for review. Applications must be received by January 14, 1993. The original and three copies of the application must be sent or delivered to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** Two additional copies of the application must be sent under separate cover to: Review Branch National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 603 Bethesda, MD 20892 REVIEW CONSIDERATIONS Upon receipt, applications will be initially reviewed by the Division of Research Grants (DRG) for completeness. Incomplete applications will be returned to the applicant without further consideration. Evaluation of responsiveness to the program requirements and criteria stated in this RFA is an NIDDK staff function. Those applications that are complete and responsive will be evaluated in competition in accordance with the criteria stated below and in the DERC Guidelines for scientific/technical merit by an appropriate peer review group convened by the NIDDK. It is essential that the written application be in a form to be reviewed on its own merit, since no site-visit is anticipated. Following this review, the applications will be given a second level review by the National Diabetes and Digestive and Kidney Diseases Advisory Council. The initial review group will review each application using the criteria stated below: o Scientific excellence of the Center's research base that must have a broad and central focus in diabetes and may extend to related metabolism and endocrinology. The relevance of the separately funded research to the DERC and the likelihood for meaningful collaboration among Center investigators must be demonstrated. o Appropriateness and relevance of the cores and their modes of operation, facilities, and potential for contribution to ongoing research. Renewal applications must include the use, utility, quality control, cost effectiveness, and demonstrated progress of any developmental research in the shared resources. o For new applications, the pilot and feasibility program is judged on the basis of: (1) scientific merit of the studies as submitted and (2) the merit of the administrative process for selecting subsequent studies. In competitive renewal applications, emphasis is accorded to the program as a whole, including past track record and management of the program. o Efficiency and effectiveness of use and/or planned use of enrichment funds. o The scientific and administrative leadership abilities of the DERC Director and Associate Director and their commitment and ability to devote adequate time to the effective management of the DERC program. o The appropriateness of the DERC budgets for the proposed and approved work to be done in core facilities, for pilot and feasibility studies, and for enrichment in relation to the total Center program. o Institutional commitment to the program, including lines of accountability regarding management of the DERC grant and a commitment to establish new positions as necessary. o Enriched academic environment with resources to enable the activities to be conducted. o The institutional commitment to establishing new positions should be presented. o Appropriateness, suitability and integration of research training and other training programs into the overall Center. AWARD CRITERIA Applications will compete for available funds with all other applications submitted in response to this RFA and recommended by peer review. The following will be considered in making funding decisions: o Quality of the proposed Center as determined by peer review o Availability of funds o Overall balance in the DERC program Schedule Letter of Intent Receipt Date: December 14, 1992 Application Receipt Date: January 14, 1993 Initial Review Dates: Jun/Jul 1993 Second Level Review Dates: Sep/Oct 1993 Anticipated Award Date: December 1, 1993 INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. Direct inquiries regarding programmatic issues and requests to: Dr. Sanford A. Garfield Diabetes Centers Program Director Division of Diabetes, Endocrinology, and Metabolic Diseases National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 626 Bethesda, MD 20892 Telephone: (301) 496-7418 FAX: (301) 480-038 Direct inquiries regarding fiscal matters to: Ms. Linda Stecklein Team Leader and Grants Management Specialist Division of Extramural Activities National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 649 Bethesda, MD 20892 Telephone: (301) 496-7467 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.847. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$XID RFA HS9301 HS-93-01 P1O1 ***************************************** GRANTS FOR HEALTH SERVICES DISSERTATION RESEARCH NIH GUIDE, Volume 21, Number 35, October 2, 1992 RFA: HS-93-01 P.T. 34; K.W. 0730050, 0710030 Agency for Health Care Policy and Research Application Receipt Date: January 22, 1993 PURPOSE The Agency for Health Care Policy and Research (AHCPR) was established in December 1989 by P.L. 101-239 as the successor to the National Center for Health Services Research and Health Care Technology Assessment (NCHSR). The AHCPR conducts research that will enhance the quality, appropriateness and effectiveness of health care services, and access to such services. The AHCPR announces a Request for Applications (RFA) for grants for health services dissertation research. The provision of dissertation grant support is part of the effort of the AHCPR to stimulate the development of innovative and timely research on issues related to the delivery of health care services. Grant support is designed to aid the career development of new health services researchers and to encourage individuals from a variety of academic disciplines and programs to study complex issues with respect to health care services. HEALTHY PEOPLE 2000 The 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 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 REQUIREMENTS A student applying for a dissertation research grant must be enrolled in an accredited doctoral degree program in the social, management, medical, or health sciences. The student also must be conducting or intending to conduct dissertation research on issues related to the delivery of health care services as described below. The proposed Principal Investigator (PI) must be a registered doctoral candidate in resident or nonresident status. All requirements for the doctoral degree other than the dissertation must be completed by the time of the award. This information must be verified in a letter of certification from the thesis chairperson and submitted with the grant application (see APPLICATION PROCEDURES). The applicant may be either the institution that will administer the grant on behalf of the proposed PI or the proposed PI applying as an individual. Whenever feasible, the proposed PI is encouraged to have the application administered through an institution. This may be either the degree-granting institution or another nonprofit institution with which the proposed PI is professionally affiliated. In determining which institution is more appropriate, the student must consider the extent to which the resources of the designated institution are capable of supporting the proposed research effort. A proposed PI for dissertation research grant support need not be a citizen of the United States. However, a PI who is not a U.S. citizen and does not have a permanent resident visa must apply through an institution. Also, an application from a student enrolled in a foreign institution will be accepted provided that the application is in English and the PI applies through an institution. A PI who receives support for dissertation research under a grant from AHCPR may not at the same time receive support under a predoctoral training grant or fellowship grant awarded by any other agency of the U.S. Department of Health and Human Services. MECHANISM OF SUPPORT This RFA will use the AHCPR small grant (R03). Responsibility for the planning, direction, and execution of the proposed project will be solely that of the proposed PI. In addition to the requirements stated in this RFA, awards will be administered under PHS grants policy as described in the PHS Grants Policy Statement. The budget of an application for a dissertation research grant must not exceed $20,000 in direct costs for the entire project period. An application that exceeds this amount will be returned to the applicant. Investigators may request support only for the amount of time necessary to complete the dissertation. A dissertation research grant usually is awarded for a period of 12 months or less but may be awarded for up to 17 months. Investigators who need 18 months or more to complete the research project will be required to submit a continuation application for support beyond the first 12 months. Continuation support may be awarded if satisfactory progress is being made, but the direct costs of the entire project may not exceed $20,000. FUNDS AVAILABLE The AHCPR expects to fund about 15 to 20 dissertation research projects in 1993. The number of awards will depend on the availability of funds. RESEARCH OBJECTIVES Only applications that propose studies in the areas identified in section 902 of the Public Health Service Act are eligible for support. Section 902 authorizes research in the following areas: o Effectiveness, efficiency, and quality of health care services o Outcomes of health care services and procedures o Clinical practice, including primary care and practice-oriented research o Health care technologies, facilities, and equipment o Health care costs, productivity, and market forces o Health promotion and disease prevention o Health statistics and epidemiology o Medical liability o AIDS/HIV infection o Rural health services o Health of low-income, minority, elderly, and other underserved populations Applicants are encouraged to discuss the suitability of their research topics by letter or by phone with AHCPR staff members. (See INQUIRIES) Allowable Costs Expenses usually allowed under PHS research grants will be covered by AHCPR dissertation research grants. Allowable costs include the PIs salary; direct project expenses such as travel, data processing, and supplies; and for institutional applicants only, indirect costs. Fees for maintaining matriculation or other fees imposed on those preparing dissertations are allowable costs, provided the fees are required of all students of similar standing regardless of the source of funding. Applicants are expected to work full time on the project. Any level of effort that is less than full-time must be fully justified. For the purpose of calculating indirect costs, dissertation research grants are considered to be training grants. Therefore, in accordance with PHS policy, indirect costs are limited to eight percent of direct costs, payable only when the applicant is an institution. Other Conditions The following conditions apply to dissertation grants: A PI who discontinues or suspends a project during the grant period must inform the AHCPR immediately in writing. The AHCPR may suspend or terminate the grant as requested by the PI or on its own initiative. The dissertation constitutes the final report of the grant. The dissertation must be officially accepted by the faculty committee or university official responsible for the candidate's dissertation and must be signed by the responsible officials. Three copies of the dissertation must be submitted to the AHCPR. The dissertation and all financial status reports must be submitted in English. SPECIAL INSTRUCTIONS TO APPLICANTS CONCERNING INCLUSION OF WOMEN AND MINORITIES IN RESEARCH STUDY POPULATIONS The AHCPR requires 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 should be placed on the need to include 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 research, particularly in proposed population-based studies, a clear and compelling rationale should be provided. The composition of the proposed study population must be described in terms of gender and race/ethnicity. 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 on the form PHS 398 in Sections 1-4 of the Research Plan and summarized in Section 5, Human Subjects. State and local governments using form PHS 5161 should include this information in the Program Narrative section. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, the AHCPR recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., Native Americans, Asian/Pacific Islanders, Blacks, Hispanics). Where appropriate, the applicant should provide the rationale for studies on single minority population groups. All applications for research submitted to the AHCPR are required to address this policy. The AHCPR will not award grants for applications which do not comply. If the required information is not contained in the application, the application will be returned without review. Problem Significance o The project is focused on a significant problem in the delivery of health care. o The methodology or anticipated results of the project have national interest, provide a basis for generalized conclusions, or have important practical applicability. Research Design o The problem to be addressed by the research is clearly defined. o The application reflects an adequate knowledge of other research related to the problem. o Questions to be answered or hypotheses to be tested are well formulated and clearly stated. o Research methodology is fully described including, where applicable, explanation of sampling procedures, description of types and sources of data to be gathered, discussion of methodological problems expected to be encountered, and description of specific analyses to be undertaken. o The application adequately describes the plans for managing the project, including a tentative schedule for the main steps of the investigation within the project period requested. Investigator's Qualifications and Support Structure o The applicant shows promise as a health services research investigator. o The experience and training of the applicant are sufficient to carry out the research. o The available facilities and organizational arrangements are appropriate to the research. o Faculty advice, composition of dissertation committee, and support are suitable to the research being undertaken, as evidenced by the letter of support. Budgetary Appropriateness o The allocation of time and money reflects an understanding of the research tasks to be accomplished and of the problems likely to arise. o Where appropriate and feasible, the proposed approach uses data available or being collected through government and other sources. APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 9/91) is to be used in applying for these grants in accordance with the special instructions described here and in the application kit. Research grant application materials and special instructions for dissertation grant applications are available from: AHCPR Publications Clearinghouse P.O. Box 8549 Silver Spring, MD 20907 Telephone: 1-800-358-9295 The RFA label available in the PHS 398 application must be affixed to the bottom of the face page. Failure to use this label may result in delayed processing of an application such that it may not reach the review committee in time for review. In addition, the RFA title and number, HS-93-01, must be typed in the box marked Item 2a of the application face page. The original application and five copies must be sent directly to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** Applicants that are State and local governments may use form PHS 5161 and submit an original and two copies. Applications must be received by Friday, January 22, 1993. A letter from the faculty committee or university official directly responsible for supervising the development and progress of the dissertation research must be submitted with the application. The letter must: (1) fully identify the members of the committee and certify their approval of the dissertation proposal, (2) certify that all requirements for the doctoral degree except the dissertation are completed (or will be completed by the time of the grant award), and (3) note that the university official or faculty committee expects the doctoral candidate to proceed with the approved project proposal with or without AHCPR support. An attachment must identify all members of the applicant's faculty advisory committee, including for each the university departmental affiliation and rank, highest degree with name of degree granting institution, date conferred and major discipline. An application that does not conform to these instructions will be returned. Revised and resubmitted applications have seldom been funded, therefore, individuals are strongly encouraged to contact Dr. Pellegrino, at the address listed below, to discuss their intentions prior to submitting a revised application. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed by the Division of Research Grants for completeness and by AHCPR staff for responsiveness. Incomplete or unresponsive applications will be returned to the applicant. Dissertation research grant applications will be reviewed under AHCPR review procedures by non-Federal or Federal experts. Reviewers will be selected on the basis of their health services research accomplishments and knowledge and their experience in research career development. Because reviews are rigorous, considerable methodological detail is important in the narrative of the application. All elements of the application will be considered in the review process. Primary emphasis will be given to the significance, scientific merit, and feasibility of the project. Applications may be subject to triage to determine their scientific merit relative to other applications received in response to this RFA. The AHCPR will withdraw from further competition those applications judged by triage to be noncompetitive for award and notify the PI and institutional official. Those applications judged to be competitive will undergo further scientific merit review. Review results and funding decisions will be announced approximately five months after the submission date. Review criteria, award criteria, and continuation of support are described below. Review Criteria Applications are reviewed to determine their suitability to review criteria in four major areas: problem significance, research design, investigator's qualifications and support structure, and budgetary appropriateness. AWARD CRITERIA Reviewers will provide recommendations with regard to the scientific and technical merit of the application and whether it should receive further consideration. Funding decisions are made by the AHCPR based on the recommendations of the reviewers, the relevance of the project to program priorities, and the availability of appropriated funds. INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. Applicants are encouraged to discuss programmatic issues, such as the suitability of their research topics, by letter or telephone with: Julius Pellegrino, M.B.A., M.P.H. Program Coordinator, Dissertation Grants Center for General Health Services Extramural Research Executive Office Center, Suite 502 2101 E. Jefferson Street Rockville, MD 20852 Telephone: (301) 227-8357 Direct inquiries regarding instructions for completing the application to: Galen B. (Sandy) Warren, D.D.S., M.P.H. Office of Scientific Review Agency for Health Care Policy and Research Executive Office Center, Suite 602 2101 E. Jefferson Street Rockville, MD 20852 Telephone: (301) 227-8449 Direct inquiries regarding fiscal and administrative matters to: Ralph Sloat Chief, Grants Management Branch Agency for Health Care Policy and Research Executive Office Center, Suite 601 2101 E. Jefferson Street Rockville, MD 20852 Telephone: (301) 227-8447 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.226. Awards are made under authority of title IX of the Public Health Service Act, as amended (42 U.S.C. 299-299c-6), and administered under PHS grants policies and in accordance with regulations of Title 42 of the Code of Federal Regulations, Part 67, Subpart A. A copy of these regulations and the dissertation research grant application instructions will be among the materials sent to each applicant. The requirements of Executive Order 12372, Intergovernmental Review of Federal Programs, are not applicable to AHCPR research grant programs. From owner-sci-resources@net.bio.net Thu Oct 08 23:00:00 1992 Path: biosci!NET.BIO.NET!kristoff From: kristoff@NET.BIO.NET (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 21, no. 35, pt. 3, 2 October 1992 Message-ID: Date: 9 Oct 92 02:00:31 GMT Sender: kristoff@net.bio.net Distribution: bionet Lines: 962 $$XID RFA HD9308 HD-93-08 P1O1 ***************************************** FAMILY AND CHILD WELLBEING RESEARCH NETWORK NIH GUIDE, Volume 21, Number 35, October 2, 1992 RFA: HD-93-08 P.T. 34, AA; K.W. 0730010, 0730005 National Institute of Child Health and Human Development Application Receipt Date: December 18, 1992 PURPOSE The Demographic and Behavioral Sciences Branch of the Center for Population Research at the National Institute of Child Health and Human Development (NICHD) invites applications for cooperative agreements (U01) to develop a research network to investigate the relationship of family factors to child wellbeing. The research network will conduct a systematic analysis of existing data to determine what can be learned about the relationship of family factors to child wellbeing using extant data. The research network will also examine the public policy implications of its work and systematically pursue research leads that show promise for informing public policy. Each investigator in the network will be expected to have demonstrated expertise and access to at least one data set relevant to the topic. Also, applicants must demonstrate that they have both the substantive and statistical expertise to function as part of an interdisciplinary research network. Each investigator will be given support to pursue his or her individual research agenda, but a large part of the available resources will be held in reserve to address cooperative research questions agreed upon by the network. Each investigator will propose both an individual research plan and a cooperative research plan in which they identify areas of research that they would be willing to cooperate in implementing. 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, Family and Child Wellbeing Research Network, is related to the priority areas of family planning, educational and community-based programs, 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 202-783-3238). 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 and local governments, and eligible agencies of the Federal government. Applications from minority individuals and women are encouraged. Institutions may submit applications on behalf of more than one Principal Investigator (PI), but each PI must submit a separate application. MECHANISM OF SUPPORT The funding mechanism to be used to support the research network will be the cooperative agreement (U01). Cooperative agreements are assistance mechanisms but differ from research project grants in that there will be substantial programmatic involvement of the NICHD Project Coordinator above and beyond the levels required for traditional program management of grants. Specifically, the Project Coordinator will cooperate with the PI as a partner in the research network. All parties agree to accept the participatory and cooperative nature of the group process. This RFA is intended as a one time solicitation. The total project period for the research network is five years and applications submitted in response to the present RFA should not exceed five years. Should there be a sufficient continuing program need, the NICHD may reissue this RFA. The anticipated award date is July 1, 1993. FUNDS AVAILABLE It is anticipated that up to seven awards will be made. One million dollars of direct cost support have been set aside to support the network and this amount will increase by an inflation factor in subsequent years of the network. Approximately one half of the resources allocated for the network will be devoted to support cooperative research. Resources available for cooperative research will be very small in the first year of the network, but will increase progressively in the subsequent years of the network. The percentage of funding for cooperative research will increase according to the following schedule: 20 percent in FY 93, 35 percent in FY 94, 50 percent in FY 95, 65 percent in FY 96 and 80 percent in FY 97. The level of support is dependent on the receipt of a sufficient number of applications of high scientific merit. Although this program will be provided for in the financial plan of the NICHD, the award of grants pursuant to this RFA is also contingent on the availability of funds for this purpose. RESEARCH OBJECTIVES There is a heightened awareness in both public policy and research communities that the wellbeing of children is deteriorating and that family factors are important explanations of this phenomenon. Within public policy circles there is a growing frustration that basic information about family and child wellbeing is filled with gaps and is analyzed in an uneven manner. Within the research community there is a fundamental problem that family and child research is spread among a large number of disciplines, and these disciplines are so diverse in their research approaches that communication across fields is difficult. It is timely to create a systematic effort to both understand the relationship of family and child wellbeing from a multi-disciplinary point of view and address public policy concerns in a comprehensive and responsive manner. The NICHD wishes to assist the scientific community to mount a systematic attack using all sources of existing information. There are a large number of social problems that impinge on the wellbeing of children. Among them, poverty and the emergence of an underclass population with a growing dependence on public transfer programs are highly visible areas of concern. Moreover, family factors such as marital instability, out-of-wedlock childbearing, and changes in the demographic and economic structure of the family seem to be inextricably related to these and other problems affecting child wellbeing. It is important to describe fully these interconnections and to formulate and test models of the causes and consequences of these relationships. It is also important to elucidate the mechanisms of action by which family factors affect child wellbeing so that possible avenues of social intervention can be ascertained or existing interventions, such as child support enforcement or child care subsidies, can be evaluated. The American family has undergone considerable change in modern times. These changes are associated with changes in the way children are raised and with changes in familial support structures that sustain children and develop them into productive adults. It is the intent of this RFA to assist in measuring both family factors and child wellbeing very broadly to develop as comprehensive a picture as possible about the relationship between these considerations. It is also important to understand how family factors and socio-economic conditions combine to nurture children and help them develop into productive adults from both an individual and societal perspective. It is important to understand how the intergenerational structure of the family marshals resources to care for dependent children and how intergenerational family processes relate to public intervention to sustain and develop children. The research network is expected to confine its activity to secondary data analysis. This will enable the research community to exploit fully many of the sources of data that have been specially created for the research community by the NICHD and other agencies. These data sources include: The National Survey of Families and Households, The National Longitudinal Survey Youth Cohort and related Child Supplements, The June 1990 Marriage and Fertility Supplement of the Current Population Survey, The National Survey of Family Growth and others. In addition, there are many data resources of sub-national populations that should be fully analyzed. It is the intent of this RFA to utilize data containing a fair representation of women and minorities. In exceptional circumstances data confined to specialized populations may be used to enhance our understanding of selected dimensions of the research problem. The network will be assembled to achieve the broadest possible coverage in terms of research perspective, analytical technique, and sources of data. The focus of the network is the United States, but the use of foreign data may be justified if it provides an insight into the American condition. Investigators must demonstrate that they have a long-term research agenda that is addressing important questions relevant to the research goals of this RFA. In addition, they must describe the sources of data to which they have access and plan to use in their research plan. It is important to describe the extent to which the investigator has experience using these data. It is also important to outline the analytic plan of attack and to describe the statistical techniques that will be employed in each phase of the research plan. The PI must propose an individual research plan to accomplish his or her personal research agenda. The plan must have the same degree of specificity as an individual research grant (R01). A PI may request support for any type of research activity commonly available through research assistance mechanisms offered by the NICHD except the cost of collecting new data. It is anticipated that such support will be higher in the first year of the initial agreement than in subsequent years and will diminish progressively throughout the five years in which the network is in operation. The PI must also propose a cooperative research plan that will describe the proposed cooperative research effort that transcends his/her individual research programs. The cooperative research plan should propose questions of substantive and/or public policy significance that should be examined cooperatively and should indicate how their disciplinary and methodological perspectives could contribute to a cooperative research effort. Also, investigators should indicate which sources of data, with which they have familiarity and access, should be used in the cooperative research plan. SPECIAL REQUIREMENTS Terms and Conditions Awardee Responsibilities Each PI will have primary responsibility to define objectives and approaches and to plan, conduct, analyze, and publish results, interpretations, and conclusions of his/her studies. Awardees will retain custody of, and primary rights to, their data developed under these award, subject to Government rights of access, consistent with current HHS, PHS, and NIH policies. A budget supporting the individual research programs will be negotiated with the NICHD based on the corresponding budget presented in the application. Each investigator will have the right to publish based on the work of their individual research programs. Each PI will also propose a cooperative research plan in which they will identify research questions, protocols, and data sets that they propose to work on cooperatively. The Steering Committee will formulate a research plan for cooperative research that will distill the several individual cooperative research plans into a coherent plan and will involve allocating resources among the participating cooperative agreements to implement it. The cooperative research plan will be agreed upon by majority vote of the Steering Committee, but each PI will have the right of approval for any aspect of the cooperative research plan involving them. Due publication credit will be given to all work done cooperatively. Steering Committee Responsibilities Planning and implementation of the cooperative aspects of the study will be done by a Steering Committee consisting of the PI from each participating awardee institution and the NICHD Project Coordinator. If necessary, the Steering Committee may invite outside, non-voting expert consultants to their meetings for advice as common protocols are developed. o Plan the design and implementation of the cooperative research protocols o Participate in decision-making regarding allocation of funds for cooperative research protocols o Publish results, conclusions and interpretations of the cooperative protocols o Formulate publication policy and appoint a Publication Subcommittee, as judged necessary by the Steering Committee o Agree to accept the coordinating role of the committee and the cooperative nature of the group process NICHD Responsibilities The NICHD Project Coordinator will be the Family Demography Coordinator of the Demographic and Behavioral Sciences Branch, NICHD. He will: o Assist in all functions of the Steering Committee o Assist with the development of common protocols o Assist the steering committee in reviewing and commenting on each stage of the program before subsequent stages are started o Assist the steering committee in exercising the options of adding, modifying, or terminating aspects of the program o Assist in the analysis, interpretation and reporting of findings in the scientific literature and other media to the community at large o Have the option to withhold support to a participating institution, if technical performance requirements such as compliance with the protocol are not met o Continuous review of all activities to ensure objectives are being met The above responsibilities are in addition to, not in lieu of, the levels of involvement normally required for program stewardship of grants. Arbitration Procedures When agreement between an awardee and NICHD staff cannot be reached on programmatic and scientific-technical issues that may arise after the award, an arbitration panel will be formed. The panel will consist of one person selected by the PIs, one person selected by the NICHD staff, and a third person selected by these two members. The decision of the arbitration panel, by majority vote, will be binding. These special arbitration procedures in no way affect the awardee's right to appeal an adverse action in accordance with PHS regulations at 42 CFR Part 50, Subpart D, and HHS regulations at 45 CFR Part 16. Cooperative agreements are assistance mechanisms and are subject to the same administrative requirements as grants. The above Terms of Award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS grant administration regulation at 45 CFR Part 74, and other HHS, PHS, and NIH grant administration policies and procedures. Meetings Each investigator must budget for four meetings a year in the Washington, DC area. Each meeting will be approximately two days in length. During these meetings, the Steering Committee will decide upon the operating policies of the network, discuss ongoing research, formulate the collaborative research plan, and discuss the implications of their research with interested parties outside of the network who may be invited by the Steering Committee as the occasion warrants. If more meetings are necessary, as may be the case especially in the first year of the network, or if project personnel other than the PI are invited to the meetings, individual awards will be supplemented with appropriate funds. These meetings will be coordinated by the Project Coordinator. Communications There will be a much greater level of communication among network members than is normal for individual research project grants. Individual PIs must budget appropriately for greater telephone usage, more copies of research papers, and greater mailing costs than in a research grant (R01). The use of BITNET will also be encouraged. Expectation of Cooperation There will be high expectations of the members of the research network to interact with other members of the network, share research insights, cooperate in the design and implementation of a cooperative research plan, be responsive to needs of the cooperative work of the network, and be sensitive to the public policy significance of it all. Applicants must indicate their willingness to participate in these stated aspects of the network. The statement of willingness to cooperate should be included under Consortium/Collaborators, section C-8 of the Research Plan in the PHS 398 application. APPLICATION PROCEDURES The grant application form PHS 398 (rev. 9/91) is to be used in applying for this grant. 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 the 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. The PHS 398 is available from most business offices or grants/contracts offices at most institutions and can also be obtained from the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone (301) 496-7441. The research plan section of the application must conform to the guidelines of form PHS 398. The individual research plan should be presented first and should follow steps 1-4, i.e., Specific Aims, Background and Significance, Progress Report/Preliminary Studies, and Research Design and Methods, of the standard research plan section. The budget for the application must be predicated on the requirements of the individual research plan and on the cooperative research plan that the investigator is proposing to work on cooperatively. Since these applications will in fact be proposing two research plans, the individual and the collaborative, the standard 25-page limitation will not apply. However, applicants are encouraged not to exceed 40 pages. The budget instructions provided in the application form PHS 398 must be followed, and budget presentations must include budgets for the collaborative group efforts suggested in the application. Indirect costs will be provided. Budgets will be reviewed on the basis of appropriateness for the work proposed. Allowable costs and policies governing the research grant program of the NIH will prevail. In preparing the budget section of the application, each applicant must submit detailed budgets for his/her own research plans only. Applicants are encouraged to be mindful of the declining allocation of funds for individual protocols in future years. Budgets must be proposed accordingly. Submit a signed typewritten original of the application, including the Checklist, and three signed photocopies in one package to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** At the time of submission, two additional copies of the application must also be sent to: Laurance S. Johnston, Ph.D. Acting Deputy Director Division of Scientific Review National Institute of Child Health and Human Development Executive Plaza North, Room 520 Bethesda, MD 20892 Applications must be received at the Division of Research Grants by December 18, 1992. If an application is received after that date, it will be returned to the applicant. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed by DRG staff for completeness and NICHD staff for responsiveness. Incomplete applications will be returned to the applicant without further consideration. If the application is not responsive to the RFA, NICHD staff will return the application to the applicant. Applications may be triaged by an NICHD peer review group on the basis of relative competitiveness. The NICHD will withdraw from further competition those applications judged to be non-competitive for award and notify the applicant PI and institutional official. Those applications judged to be competitive will undergo further scientific merit review. Those applications that are complete, responsive, and competitive will be evaluated in accordance with the criteria stated below for scientific/technical merit by a special review committee convened by the NICHD. The second level of review will be provided by the National Child Health and Human Development Advisory Council. The review criteria for the individual research plans of the network are: o Scientific and technical significance and originality of proposed research; o Appropriateness and adequacy of the research approach and methodology proposed to carry out the research; o Qualifications and research experience of the PI and staff, particularly, but not exclusively, in the area of the proposed research; o Availability of resources necessary to perform the research; o Appropriateness of the proposed budget and duration in relation to the proposed research; o Access to and experience with sources of existing data suitable for the purposes of the research network. AWARD CRITERIA The anticipated date of award is July 1, 1993. An attempt will be made to balance the network so that it will have a multi-disciplinary composition, a diversity of research issues and broad coverage of extant data sources. Awards will be made on the basis of the scientific merit of the research application and the need to create a balanced network. 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: V. Jeffery Evans, Ph.D., J.D. Family Demography Coordinator Demographic and Behavioral Sciences Branch Center for Population Research National Institute of Child Health and Human Development 6100 Executive Boulevard, Room 8B13 Bethesda, MD 20892 Telephone: (301) 496-1174 FAX: (301) 496-0962 BITNET: EVANSJ@NIHHD01.BITNET Direct inquiries regarding fiscal matters to: Ms. Melinda Nelson Office of Grants and Contracts National Institute of Child Health and Human Development Executive Plaza North Building, Room 505 Bethesda, MD 20892 Telephone: (301) 496-5481 FAX: (301) 402-0915 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.864. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations, 42 CFR Part 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372, or to Health Systems Agency review. $$XID RFA HL9302P HL-93-02-P P1O1 ************************************** IMPROVING HYPERTENSIVE CARE FOR INNER CITY MINORITIES NIH GUIDE, Volume 21, Number 35, October 2, 1992 RFA: HL-93-02-P P.T. 34; K.W. 0715115, 0414014, 0413001, 0403004, 0502017 National Heart, Lung, and Blood Institute Letter of Intent Receipt Date: November 30, 1992 Application Receipt Date: February 16, 1993 PURPOSE The Division of Epidemiology and Clinical Applications (DECA) invites applications for demonstration and education projects aimed at improvements in hypertensive care among inner city minority populations. The awards will be for a funding period of four years. The program will focus on community-based health education and/or other approaches for enhancing compliance and improving blood pressure control in urban minority populations. The intervention models should be widely applicable and economical. While hypertension is the focus of the program, a multiple risk factor approach may be used to assess changes in other cardiovascular risk factors. 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, Improving Hypertensive Care for Inner City Minorities, is related to the priority area of heart disease and stroke. 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, 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 organizations are not eligible to apply and domestic applications may not include international components. Applications from minority individuals, particularly African Americans, Hispanics, and women are encouraged. MECHANISM OF SUPPORT The support mechanism for this RFA will be the National Institutes of Health (NIH) demonstration and education (D&E) research grant (R18). 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 four years. The anticipated award date is September 30, 1993. FUNDS AVAILABLE It is anticipated that three to five Centers will be supported over the four year period of this program. An estimated total cost (direct and indirect) of $2,500,000 will be available for the first year of funding for the entire program, with an estimated four year total cost of $10,600,000. This level of support is dependent upon the receipt of a sufficient number of applications of high scientific merit. Although this program is provided for in the financial plans of the National Heart, Lung, and Blood Institute (NHLBI), awards pursuant to this RFA are contingent upon the availability of funds for this purpose. RESEARCH OBJECTIVES Background Hypertension is a major independent risk factor for the development of cardiovascular disease, the leading cause of death in the U.S. Despite improvements in the treatment and control of hypertension in recent years, African Americans continue to experience higher morbidity and mortality from hypertension than the white population. Hypertension is more likely to appear earlier in life in African Americans. Adequate treatment is often hampered by socioeconomic factors. Complications of uncontrolled hypertension, including stroke and end-stage renal disease, occur earlier and more frequently in African Americans than in whites. In 1986, the age-adjusted stroke mortality rate was 83 percent higher in African Americans than in whites. While age-adjusted mortality rates for stroke are declining for both African Americans and whites, both for males and females, the rate of decline is lower for African Americans. The African American to white ratio of age-adjusted stroke mortality increased from 1.85 in 1980 to 1.93 in 1988 for males and from 1.75 to 1.83 over the same time for females (1,2). Although based on single blood pressure measurements, data regarding the prevalence, awareness, treatment, and control of hypertension in the U.S. are available from the 1976-80 National Health and Nutrition Examination Survey (NHANES II) (3). African Americans collectively have a higher prevalence of hypertension, based upon a 140/90 mm Hg cutpoint or taking antihypertensive medication, than whites (38 vs. 29 percent). Severe hypertension is four times as prevalent among African American males relative to white males. The following data on awareness, treatment, and control are for blood pressure cutpoints of 140/90 mm Hg; similar trends exist for the higher cutpoints of 160/95 mm Hg. Of those with hypertension, African Americans were shown to be slightly more aware of their hypertension (65.6 vs. 52.3 percent) than whites, and slightly more received pharmacologic therapy (38.5 vs. 32.6 percent). Nonpharmacologic therapy was not included in this analysis. While control rates for African Americans collectively were slightly better than for whites (13.3 vs. 10.9 percent), the hypertension of African American males was slightly less controlled than that of white males (5.8 vs. 6.1 percent). It is also noteworthy that these control rates were very low for all race-sex groups. An inverse relationship between socioeconomic status and health exists for a number of disease entities, findings that come primarily from studies of non-minority populations. Although data are somewhat limited for comparison between differing levels of socioeconomic status among African-Americans, a number of studies reveal that African Americans of lower socioeconomic status have a higher level of hypertension-related disease burden than more advantaged African Americans (6). The Hypertension Detection and Follow-Up Program (HDFP), which screened over 40,000 African Americans and entered over 4800 African Americans into the study, showed an inverse relationship between level of education, used as a measure for socioeconomic status, and severity of hypertension for both African Americans and whites. This inverse relationship between education and hypertension was more pronounced within the highest stratum of blood pressure. The gradient was essentially eliminated by stepped care antihypertensive drug therapy (7). Hispanics represent the second largest minority population in the U.S., and this group is rapidly growing. The Hispanic population is heterogenous. The Hispanic Health and Nutrition Examination Survey (HHANES) was conducted among three Hispanic subgroups (of Mexican, Cuban, and Puerto Rican origins) in the U.S. from 1982 to 1984 (8). Data from this survey reveal that Hispanics have lower prevalence of hypertension, higher awareness, higher treatment rates, and higher control rates compared to the rates for both whites and African Americans in NHANES II. It should be noted that the HHANES data are more recent than NHANES II. The San Antonio Heart Study provides additional data regarding hypertension among Mexican Americans. Data presented for four different definitions of hypertension (isolated and combined elevations using 160/95 and 140/90 mm Hg cutpoints) show a lower prevalence among Mexican Americans relative to non-Hispanic whites, although only two of the eight pairwise comparisons (four hypertensive definitions by gender) were statistically significant. After adjustment for age, body mass index, and non-insulin-dependent diabetes mellitus, Mexican Americans were shown to have a statistically significant lower prevalence of hypertension (9). Certainly these data indicate substantial room for improvement in the awareness, treatment, and control of hypertension for all Americans. African Americans, with both an increased burden of disease and problems with access to care, require special attention. While the data for Hispanics populations do not indicate excess disease burden, socioeconomic factors are likely to put many Hispanics at a disadvantage for optimal hypertension detection and management. Several investigators have shown improvement in the care for inner-city minority hypertensives. As an example, Levine and colleagues designed a long term program using a population-based intervention, administered under the direction of a task force of community leaders and organizations and the Johns Hopkins Medical Institutions. Five-year results demonstrate significant improvements in both behavioral objectives and blood pressure control. In summary, excess disease burden from hypertension in African Americans, combined with numerous socio-economic barriers to optimal care for many inner city individuals, provides a setting in which substantial improvements are both urgently needed and likely achievable. Objectives and Scope The primary objective of this four year demonstration and education research program is to develop, and to evaluate for feasibility, acceptability, and effectiveness, methods to maintain therapy and control of hypertension, for both newly and previously diagnosed individuals, in inner city, primarily minority populations. The focus will be on community-based health education and other approaches for enhancing compliance and improving blood pressure control among inner city minority populations. The delivery of and adherence to the interventions is the main objective, rather than clinical algorithms used to treat hypertension. While the improvement of hypertensive care is the focus of this program, other cardiovascular disease risk factors may be included in the interventions, and changes in these factors should be assessed. The role of non-pharmacologic approaches to reducing blood pressure, including drug and alcohol avoidance, should be addressed. Primary outcome measures to assess the interventions may include: percentages aware of hypertension, screened for hypertension, treated for hypertension, responding to treatment, and controlled to normal levels of blood pressure; clinic attendance; and compliance with therapy. Secondary outcomes include the assessment of: effects on other CVD risk factors, e.g., cigarette smoking, overweight, lipid profile, and diabetes; health quality of life measures; and cost effectiveness of the interventions. The experimental design is not restricted by this RFA. Applicants should develop their own independent design, and provide justification for the proposed design. The designs should focus on an integrated approach including various management factors that have previously been shown to be effective. Health education and other approaches for enhancing compliance and improving blood pressure control must be adequately described. A randomized design, comparing special interventions against usual care would be one appropriate study design to test intervention models. If justified by the nature of the proposed intervention, i.e., delivery of an intervention to a social group (e.g., neighborhood or employee group), other designs will be considered responsive. Annual meetings, to be held in Bethesda, MD, are planned for the exchange of information among investigators. Applicants must budget the travel costs associated with these meetings in their applications. STUDY POPULATIONS Because of their excess burden of hypertension, African Americans should comprise a large proportion of the study population. Although there is no compelling evidence of excess burden from hypertension among Hispanics compared to the population at large, socioeconomic factors for inner-city members of this group may result in less than optimal hypertension detection and treatment. Therefore the inclusion of Hispanics, which may be best accomplished by the inclusion of Hispanics as the majority of the sample at one of the study sites, may be proposed. Investigators should also consider other minority groups, as well as low socioeconomic whites, for inclusion. The inclusion of low socioeconomic status (SES) whites may provide some means to separate the effects of SES and ethnicity. As the lowest hypertension control rates are seen in young African Americans, investigators should address the advantages and disadvantages of oversampling this younger segment of the population. SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH and ADAMHA policy is that applicants for NIH/ADAMHA 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 approximate percentages by 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, 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 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 apply the results of the study broadly, and this should be addressed by applicants. If the required information is not contained in 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 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. LETTER OF INTENT Prospective applicants are asked to submit, by November 30, 1992, a letter of intent that includes a descriptive title of the proposed research; the name, address, and telephone number of the PI; the identities of other key personnel and participating institutions; and the number and title of the RFA in response to which the application may be submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information that it contains is helpful in planning for the review of applications. It allows NHLBI staff to estimate the potential workload and to avoid conflict of interest in the review. The letter of intent is to be sent to: C. James Scheirer, Ph.D. Review Branch, Division of Extramural Affairs National Heart, Lung, and Blood Institute Westwood Building, Room 548 Bethesda, MD 20892 Telephone: (301) 496-7363 FAX: (301) 402-1660 APPLICATION PROCEDURES The research grant application form 398 (rev. 9/91) is to be used in applying for this award. These forms are available at most institutional business offices; from the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone (301) 496-7441; and from the NHLBI Program Administrator named below. The RFA label available in the PHS 398 (rev. 9/91) application must be affixed to the bottom of the face page of the application. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2a of the face page of the application form and the YES box must be marked. Submit the 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 must also be sent to: C. James Scheirer, Ph.D. Review Branch, Division of Extramural Affairs National Heart, Lung, and Blood Institute Westwood Building, Room 548 Bethesda, MD 20892 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 16, 1993. If an application is received after that date, it will be returned to the applicant without review. The Division of Research Grants (DRG) will not accept any application in response to this announcement that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. The DRG will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of substantial revisions of applications already reviewed, but such applications must include an introduction addressing the previous critique. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by DRG and for 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 that are found to be responsive will be reviewed for scientific and technical merit by an initial review group, convened by the Division of Extramural Affairs, NHLBI solely to review these applications. The initial review will include an evaluation to determine scientific merit relative to other applications received in response to this RFA (triage). The NIH will withdraw from further competition those applications judged non-competitive for award and notify the applicant PI and the official signing for the applicant organization. Those applications judged to be competitive will be further evaluated for scientific/technical merit by the usual peer review procedures, including, if deemed appropriate, a reverse site visit at the applicant's expense. Secondary review of applications will be conducted by the National Heart, Lung, and Blood Advisory Council. Review Criteria The review group will assess the scientific merit of the study, including: o The documentation of the need for improving hypertensive care in this segment of the population, and the soundness of the rationale for the selection of the intervention methods. o Appropriateness and adequacy of the experimental approach and methodology proposed to carry out the research, including appropriate determination and discussion of the required sample size and adequate recruitment plans in accordance with sample size estimate. o Qualifications and research experience of the PI and staff, including: administrative abilities of the PI and co-PIs; experience of the key investigators in the area of the proposed research, including experience in adequate recruitment of participants into research projects; ability of investigators and other key personnel to devote adequate time for proper conduct of the study, over the duration of the study; representation of minority individuals among investigators and staff. o Appropriateness of the proposed budget and duration in relation to the proposed research. Applicants must describe in their application the potential for involvement with one or more community service organizations and the potential for the transfer of ownership of the interventional program to these organizations. It is hoped that longevity of the program beyond the funded period can be achieved in this manner. Although the actual transfer of ownership to these organizations is not a requirement of the study, the potential for transfer will be carefully addressed in the review of applications, and those applications without such a description will be considered to be non-responsive to this RFA. AWARD CRITERIA Applications recommended by the National Heart, Lung, and Blood Advisory Council will be considered for award based upon scientific and technical merit (priority scores), programmatic priorities, and the availability of funds. The anticipated date of award is September 30, 1993. 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: P. Scott Allender, M.D. Prevention and Demonstration Research Branch Division of Epidemiology and Clinical Applications National Heart, Lung, and Blood Institute Federal Building, Room 604 7550 Wisconsin Avenue Bethesda, MD 20892 Telephone: (301) 496-2465 Direct inquiries regarding fiscal matters to: William W. Darby Section Chief, Grants Operations Branch Division of Extramural Affairs National Heart, Lung, and Blood Institute Westwood Building, Room 4A11 Bethesda, MD 20892 Telephone: (301) 496-7536 AUTHORITY AND REGULATIONS This project is described in the Catalog of Federal Domestic Assistance No. 93.837. 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 project 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 Oct 11 23:00:00 1992 Path: biosci!NET.BIO.NET!kristoff From: kristoff@NET.BIO.NET (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NSF - Summary of new documents on STIS - 11 October 1992 Message-ID: Date: 12 Oct 92 18:57:53 GMT Sender: kristoff@net.bio.net Distribution: bionet Lines: 95 ** NEW DOCUMENTS ON STIS ** Document Type: General Publication Title: NSF 92-1 National Science Foundation Annual Report 1991 File size (bytes): 152480 STIS Filename: nsf921 Document Type: Press Release Title: NSF AWARDS VISITING PROFESSORSHIPS TO 22 WOMEN SCIENTISTS AND ENGINEERS File size (bytes): 5819 STIS Filename: pr9268 Title: SCRIPPS INSTITUTION OF OCEANOGRAPHY/UCSD OPENS NEW NSF-FUNDED STEPHEN BIRCH AQUARIUM-MUSEUM File size (bytes): 3865 STIS Filename: pr9270 Title: U.S. SCIENTISTS BEGIN 36TH CONSECUTIVE SEASON OF RESEARCH IN ANTARCTICA File size (bytes): 10201 STIS Filename: pr9271 Title: FUTURE NSF COMMISSIONERS NAMED File size (bytes): 5847 STIS Filename: pr9272 Title: NSF ANNOUNCES ITS FIRST AWARDS IN THE NEWLY INITIATED SUMMER SCIENCE CAMPS (SSC) PROGRAM File size (bytes): 9970 STIS Filename: pr9274 Title: NSF DIRECTOR TO RECOGNIZE TWO DECADES OF U.S. - HUNGARIAN SCIENTIFIC COOPERATION File size (bytes): 3568 STIS Filename: pr9275 Title: NEW PROCESS FOR MAKING DIAMOND COATINGS PATENTED File size (bytes): 4778 STIS Filename: pr9276 Title: NSF ANNOUNCES AWARDS TOTALING $16.4 MILLION FOR ACADEMIC RESEARCH FACILITIES UPGRADES File size (bytes): 5028 STIS Filename: pr9277 Title: ACADEMIC RESEARCH IN KANSAS RECEIVES EPSCoR File size (bytes): 3287 STIS Filename: pr9278 Document Type: Program Guideline Title: NSF 92-74 CISE Institutional Infrastructure - Research Infrastructure Program File size (bytes): 35330 STIS Filename: nsf9274 ------------------------------------------------------------------------ ** 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 nsf9274, the text of your message should be as follows: get nsf9274 Anonymous FTP: FTP to stis.nsf.gov. Use the "STIS Filename" shown above to retrieve a file. For example, to retrieve nsf9274, you would enter: ftp> get nsf9274 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 "pubs@nsf.gov" (Internet) or "pubs@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 Tue Oct 13 23:00:00 1992 Path: biosci!agate!spool.mu.edu!caen!batcomputer!cornell!rochester!cantaloupe.srv.cs.cmu.edu!das-news.harvard.edu!husc-news.harvard.edu!husc8.harvard.edu!mlevin From: mlevin@husc8.harvard.edu (Michael Levin) Newsgroups: sci.bio,bionet.sci-resources Subject: what do you use to look stuff up??? Message-ID: <1992Oct13.201140.16360@husc3.harvard.edu> Date: 14 Oct 92 00:11:39 GMT Distribution: usa Organization: Harvard University Science Center Lines: 13 Xref: biosci sci.bio:170 bionet.sci-resources:492 Nntp-Posting-Host: husc8.harvard.edu I'm a first year grad student in developmental bio, and I am wondering what people out there are using to look for papers on a given topic (computerized searches, I mean). We have a link to Medline here, but it seems that it is missing a lot of the non-medical (basic research stuff), although it certainly has a lot too (i.e., I can't figure out how they decide what to put in). Anyways, is there any database that one can search that covers all the normal biology journals? In addition, are there ones that specializes (or includes) physics and computer science journals also? Please reply to mlevin@husc8.harvard.edu. Mike Levin From owner-sci-resources@net.bio.net Wed Oct 14 23:00:00 1992 Path: biosci!bcm!cs.utexas.edu!sun-barr!ames!elroy.jpl.nasa.gov!sdd.hp.com!uakari.primate.wisc.edu!usenet.coe.montana.edu!news.u.washington.edu!ogicse!das-news.harvard.edu!husc-news.harvard.edu!husc8.harvard.edu!mlevin From: mlevin@husc8.harvard.edu (Michael Levin) Newsgroups: sci.bio,bionet.sci-resources Subject: where to find pre-doctoral sources of fellowships for non-minorities Message-ID: <1992Oct14.193500.16394@husc3.harvard.edu> Date: 14 Oct 92 23:34:59 GMT Distribution: usa Organization: Harvard University Science Center Lines: 6 Xref: biosci sci.bio:180 bionet.sci-resources:493 Nntp-Posting-Host: husc8.harvard.edu Is there anyplace I can look to find sources of pre-doctoral fellowships (like NSF, etc.) for non-minorities? Please reply to mlevin@husc8.harvard.edu. Mike Levin From owner-sci-resources@net.bio.net Thu Oct 15 23:00:00 1992 Path: biosci!NET.BIO.NET!kristoff From: kristoff@NET.BIO.NET (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 21, no. 37, pt.1, 16 October 1992 Message-ID: Date: 16 Oct 92 19:01:43 GMT Sender: kristoff@net.bio.net Distribution: bionet Lines: 1506 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. ---------------------------------------------------------------------- $$XID NIHGUIDE 19921016 V21N37 P1O2 ************************************ X-comment: RFAs described: DC-93-003, NR-93-01 NIH GUIDE - Vol. 21, No. 37 - October 16, 1992 $$INDEX BEGIN ******************************************************* NOTICES $$INDEX N1 ********************************************************** ADAMHA/NIH REORGANIZATION National Institutes of Health Alcohol Drug Abuse and Mental Health Administration INDEX: NATIONAL INSTITUTES OF HEALTH; ALCOHOL DRUG ABUSE AND MENTAL HEALTH ADMINISTRATION NOTICES OF AVAILABILITY (RFPs AND RFAs) $$INDEX R1 ********************************************************** CORE IMMUNOLOGY LABORATORY FOR ASSESSMENT OF AIDS VACCINES IN PRIMATES (RFP NIH-NIAID-DAIDS-93-15) National Institute of Allergy and Infectious Diseases INDEX: ALLERGY, INFECTIOUS DISEASES $$INDEX R2 12/22/92 ************************************************* NIDCD-NASA CENTER FOR VESTIBULAR RESEARCH (RFA DC-93-003) National Institute on Deafness and Other Communication Disorders INDEX: DEAFNESS, COMMUNICATION DISORDERS $$INDEX R3 01/26/93 ************************************************* RESEARCH ON CLINICAL CARE IN NURSING HOMES (RFA NR-93-01) National Center Nursing Research INDEX: NURSING RESEARCH ONGOING PROGRAM ANNOUNCEMENTS $$INDEX P1 ********************************************************** GENES DETERMINING STEM CELL SELF-RENEWAL AND COMMITMENT (PA-93-006) National Heart, Lung, and Blood Institute INDEX: HEART, LUNG, BLOOD $$INDEX P2 ********************************************************** INSTITUTIONAL TRAINING AWARDS IN NUTRITIONAL SCIENCES (PA-93-007) National Institute of Diabetes and Digestive and Kidney Diseases INDEX: DIABETES, DIGESTIVE, KIDNEY DISEASES $$INDEX P3 ********************************************************** ACADEMIC AWARD IN VASCULAR DISEASE (PAR-93-008) National Heart, Lung, and Blood Institute INDEX: HEART, LUNG, BLOOD $$INDEX P4 ********************************************************** NEURAL, ENDOCRINE, IMMUNE, AND VIRAL INTERACTIONS, BEHAVIOR, AND MENTAL HEALTH (PA-93-009) National Institute of Mental Health National Institute of Neurological Disorders and Stroke INDEX: MENTAL HEALTH; NEUROLOGICAL DISORDERS, STROKE This publication is also available electronically to institutions via BITNET or INTERNET. Alternative access is through the NIH Grant Line using a personal computer. Contact Dr. John James at 301/496-7554 for details, or send an E-mail message to ZNS@NIHCU. $$INDEX END ********************************************************* NOTICES $$N1 BEGIN ********************************************************** ADAMHA/NIH REORGANIZATION NIH GUIDE, Volume 21, Number 37, October 16, 1992 P.T. 34; K.W. 1014006 National Institutes of Health Alcohol Drug Abuse and Mental Health Administration On July 10, 1992, President Bush signed into law the ADAMHA Reorganization Act of 1992 (P.L. 102-321) merging the three research institutes of the Alcohol Drug Abuse and Mental Health Administration (ADAMHA) with the National Institutes of Health (NIH) and establishing a new agency, the Substance Abuse and Mental Health Services Administration. On October 1, 1992, the National Institute on Alcohol Abuse and Alcoholism (NIAAA), the National Institute on Drug Abuse (NIDA), and the National Institute of Mental Health (NIMH) merged with the NIH. The NIAAA, NIDA, and NIMH will continue to accept research grant and research training applications as they have in the past. No substantial changes in policy or procedure are anticipated. If changes or adjustments of policy or procedure are necessary, it will be announced in the NIH Guide. The ongoing policy previously announced jointly by the NIH/ADAMHA on the inclusion of women and minorities in clinical research study populations, will continue in force until revised or reissued. $$N1 END ************************************************************ NOTICES OF AVAILABILITY (RFPs AND RFAs) $$R1 BEGIN NIH-NIAID-DAIDS-93-15 ************************************ CORE IMMUNOLOGY LABORATORY FOR ASSESSMENT OF AIDS VACCINES IN PRIMATES NIH GUIDE, Volume 21, Number 37, October 16, 1992 RFP: NIH-NIAID-DAIDS-93-15 P.T. 34; K.W. 0715008, 0740075, 0710070, 0755010 National Institute of Allergy and Infectious Diseases The National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH) has a requirement to provide for the centralized performance of immunological assays to support preclinical AIDS vaccine trials in primates. The purpose of this contract is to support the NIAID in its mission to stimulate research towards discovery and testing of prototype vaccines for the acquired immunodeficiency syndrome (AIDS). The NIAID requires a Primate Core Immunology Laboratory to assay specimens from macaques, chimpanzees, or other primates for humoral and cellular immune responses induced by immunization with prototype Simian Immunodeficiency Virus (SIV) and Human Immunodeficiency Virus (HIV) vaccines. This effort will support the research of AIDS investigators, including three SIV Vaccine Evaluation Units (SIV VEU), a Chimpanzee Unit, the National Cooperative Vaccine Evaluation Group (NCVDG), the AIDS Vaccine Evaluation Group (AVEG), and other programs initiated by NIAID. Specifically, the selected contractor will be responsible for: (1) performing specific evaluations of cellular immune responses induced by vaccination; (2) performing specific evaluations of humoral immune responses induced by vaccination; (3) adapting, standardizing, providing quality assurance, and performing any newly developed immunological assays that may be identified during the period of the contract as offering potential for assessment of vaccine safety and immunogenicity; (4) receiving, cataloging, tracking, and maintaining an inventory of the specimens arriving for evaluation; and (5) maintaining test result database and transferring data to the AIDS Vaccine Clinical Trials Network (AVCTN) Data Coordinating and Analysis Center (DCAC). This is an announcement for an anticipated Request for Proposals (RFP). The issuance of RFP NIH-NIAID-DAIDS-93-15 will be on or about October 16, 1992, and proposals will be due by the close-of-business on January 5, 1993. It is anticipated that one contract will be awarded as a result of this solicitation and that the contract will have a five-year period of performance. A completion type cost-reimbursement contract is anticipated. Requests for the RFP must be directed in writing to: Kristi Hofacker, Contract Specialist Contract Management Branch National Institute of Allergy and Infectious Diseases Solar Building, Room 3C07 6003 Executive Boulevard Bethesda, MD 20892 Provide this office with three 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. That version includes only the Statement of Work and the Evaluation Criteria to be used for selection of the awardee. After examining this document, 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 (FAX: 301-402-0972). All proposals from responsible sources will be considered by the NIAID. This advertisement does not commit the Government to award a contract. $$R1 END ************************************************************ $$R2 BEGIN DC-93-003 FULL-TEXT ************************************** NIDCD-NASA CENTER FOR VESTIBULAR RESEARCH NIH GUIDE, Volume 21, Number 37, October 16, 1992 RFA AVAILABLE: DC-93-003 P.T. 34; K.W. 0785005, 1002061 National Institute on Deafness and Other Communication Disorders Letter of Intent Receipt Date: November 15, 1992 Application Receipt Date: December 22, 1992 THE REQUEST FOR APPLICATIONS (RFA) ANNOUNCED IN THIS NOTICE CONTAINS ESSENTIAL INFORMATION FOR THE PREPARATION OF AN APPLICATION. POTENTIAL APPLICANTS MAY OBTAIN THE RFA FROM THE CONTACT NAMED IN INQUIRIES, BELOW. PURPOSE The National Institute on Deafness and Other Communication Disorders (NIDCD) of the National Institutes of Health (NIH), in collaboration with the Life Sciences Division of the Office of Space Science and Applications, National Aeronautics and Space Administration (NASA), invite applications for the support of a ground-based research center to carry out research applicable to vestibular issues associated with space flight and fundamental knowledge about the vestibular system. In addition to research, the Center will include a research training component. The Center will conduct a number of research projects in humans and/or animals integrated into a program and centered around the vestibular control of balance and posture and the regulation of locomotion and other volitional movements. 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, NIDCD-NASA Center for Vestibular Research, is related to the priority areas of physical activity fitness, educational and community-based programs, 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 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. MECHANISMS OF SUPPORT This RFA will use the NIH Comprehensive Center (P60) grant mechanism. Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. The total project period for applications submitted in response to the present RFA must be five years. The anticipated award date will be July 1, 1993. This RFA is a one-time solicitation. At present, the NIDCD and NASA have made no commitment to continue support for the Center beyond five years. FUNDS AVAILABLE One Center will be supported jointly by NIDCD and NASA at a level of up to $1 million total (direct plus indirect) costs per annum for a project period of five years. Although this Center is provided for in the financial plans of the NIDCD and NASA, awards pursuant to this RFA are contingent upon the availability of funds for this purpose. RESEARCH OBJECTIVES The major research objective of this RFA is to characterize the relative roles of the semicircular canal, otolithic organ and canal-otolithic organ interactive inputs to the vestibulo-spinal reflexes and the balance motor control systems. A requisite component of this research effort includes the development of a computational model of the sensory-to-motor transformation relating the vestibular balance control system to its neural substrates. This model should be driven and validated by experimental data generated by this project. The Center is intended to support a team of investigators pursuing basic and applied studies at the systems and neuronal substrate levels to conduct an integrated, multidisciplinary inquiry into the vestibular bases of balance control. The purpose of the research training component of the Center is to develop opportunities for training individuals to conduct research in the vestibular sciences. The research training program will provide multidisciplinary training for physicians, predoctoral trainees and postdoctoral trainees in the areas of vestibular science that are encompassed by the application. The research training component of the Center must provide opportunities for individuals with varying levels of research experience. SPECIAL REQUIREMENTS The program director and one additional investigator of the Center will meet annually in the Washington, DC area with the scientific program staffs of the Division of Communication Sciences and Disorders, NIDCD, and the Life Sciences Division, NASA, to review the progress of the Center in the areas of research and research training. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS For projects involving clinical research, NIH requires applicants to give special attention to the inclusion of women and minorities in study populations. 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 November 15, 1992, a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the Center director, the identities of other key personnel and participating institutions, and the number and title of the RFA in response to which the application may be submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information that it contains is helpful in planning for the review of applications. It allows NIDCD 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: Earleen Elkins, Ph.D. Chief, Scientific Review Branch National Institute on Deafness and Other Communication Disorders Room 400-B, Executive Plaza South 6120 Executive Boulevard Rockville, MD 20892 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 business offices; from the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, Maryland 20892, telephone 301/496-7441; and from the NIH program administrator named below. Applications must be received by December 15, 1992. REVIEW CONSIDERATIONS Incoming applications determined by NIH staff to be complete and responsive will undergo scientific merit review and a site visit or applicant interview in the Washington, DC area. These applications will be evaluated in accordance with the criteria stated in the RFA for scientific/technical merit by an appropriate peer review group convened by the Institute and NASA. The second level of review will be provided by the National Deafness and Other Communication Disorders Advisory Council and the NASA Life Sciences Division. If the number of applications received is large, the NIDCD may conduct a preliminary scientific peer review to eliminate those applications that are clearly not competitive. AWARD CRITERIA The anticipated date of award is July 1993. Selection will be made jointly by the NIDCD and NASA on the basis of assessment of the applications by peer review, considerations of programmatic balance, and the appropriation of allocated funds for this RFA. INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. The opportunity to clarify any issues and 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-B 6120 Executive Boulevard Rockville, MD 20892 Telephone: (301) 402-3461 FAX: (301) 402-6251 Direct inquiries regarding fiscal matters to: Sharon Hunt Grants Management Branch 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. $$R2 END ********************************************************** $$R3 BEGIN NR-93-01 FULL-TEXT *************************************** RESEARCH ON CLINICAL CARE IN NURSING HOMES NIH GUIDE, Volume 21, Number 37, October 16, 1992 RFA AVAILABLE: NR-93-01 P.T. 34; K.W. 0785130, 0730050 National Center for Nursing Research Letter of Intent Receipt Date: November 24, 1992 Application Receipt Date: January 26, 1993 THE REQUEST FOR APPLICATIONS (RFA) ANNOUNCED IN THIS NOTICE CONTAINS ESSENTIAL INFORMATION FOR THE PREPARATION OF AN APPLICATION. POTENTIAL APPLICANTS MAY OBTAIN THE RFA FROM THE CONTACT NAMED IN INQUIRIES, BELOW. PURPOSE The goal of this RFA is to enhance quality of care and quality of life of nursing home residents by increasing understanding of the influences of contextual factors and by determining clinical strategies that increase independence and self management among residents, maintain family participation in care, and encourage discharge to home whenever possible. 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, Research on Clinical Care in Nursing Homes, is related to the priority areas of older persons as a targeted group and to chronically disabling conditions. Potential applicants may obtain a copy of the "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 and local governments, and eligible agencies of the Federal Government. Applications from minority individuals and women are encouraged. Applicants must demonstrate access to nursing homes appropriate to the study proposed. MECHANISM OF SUPPORT This RFA will use the National Institutes of Health (NIH) individual research grant (R01). Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. This RFA is a one time solicitation. The total project period proposed may not exceed four years. The anticipated average direct cost of an award is $150,000. The anticipated award date will be July 1, 1993. FUNDS AVAILABLE It is estimated that up to $1.0 million will be available to fund the first-year total costs of applications submitted in response to this RFA. It is anticipated that four to five applications will be funded. RESEARCH OBJECTIVES 1. Determine the influence of structural and organizational factors on the effectiveness of clinical interventions. 2. Examine the effectiveness of specific clinical interventions for older persons in nursing homes in terms of clinical quality (e.g., related to changes in functional status and quality of life) and related fiscal (e.g., related to changes in costs) outcomes. 3. Identify linkages among clinical assessments conducted in nursing homes, clinical interventions, and anticipated clinical and fiscal outcomes. Applications must address objective one and either two or three. BACKGROUND With the increasing longevity of our population, the number of the older persons is increasing, including those over 85 years who are frequent users of nursing homes. Many issues have been raised about the quality and appropriateness of clinical care provided in these settings. This RFA is designed to address these issues. There are several areas that could be addressed. How best to assess and plan clinical interventions to meet individual requirements of nursing home residents needs to be addressed. The relationship of assessment strategies to clinical interventions and outcomes requires further investigation. Examinations are needed of potential differences among those with varying lengths of stay. Also, examinations are needed of clinical intervention strategies for residents who have the potential for discharge home, improvement in their health status, as well as those who are not expected to survive. It is important that the natural clinical setting be examined for influences on the effectiveness of intervention strategies, such as through exploration of clinical management strategies to achieve staff adherence to plans of care. In addition, clinical interventions that take the resident milieu into consideration continue to require study. 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 inclusion must be provided. Applications without such documentation will not be accepted for review. LETTER OF INTENT Prospective applicants are asked to submit, by November 24, 1992, a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, the names of other key personnel and consultants, the participating institution(s), and the number and title of the RFA in response to which an application may be submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information that it contains is extremely helpful in planning for the review of applications. It allows NCNR 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: Ethel Jackson, D.D.S. Chief, Office of Review National Center for Nursing Research Building 31, Room 5B25 9000 Rockville Pike Bethesda, MD 20892 APPLICATION PROCEDURES Applications must be received by January 26, 1993. If an application is received after that date, it will be returned to the applicant without review. The research grant application form PHS 398 (rev. 9/91) is to be used to apply for these grants. These forms are available at most institutional business offices and from the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892 telephone 301-496-7441. REVIEW CONSIDERATIONS Applications will be evaluated according to the review criteria stated in the RFA for scientific and technical merit by an appropriate peer review group convened by the Office of Review, National Center for Nursing Research. Applications may be subjected to triage by the peer review group to determine their scientific merit relative to other applications received in response to this RFA. Criteria for triage will be the same as those noted above. The second level of review will be provided by the National Advisory Council for Nursing Research. AWARD CRITERIA The anticipated date of award is July 1, 1993. Decisions to make awards are based on the scientific merit of the application reflected in the priority score, availability of funds with NCNR for this purpose, and NCNR research program priorities. INQUIRIES Written and telephone inquiries concerning this RFA are encouraged and may be directed to either of the following individuals. The program staff welcome the opportunity to clarify any issues or questions from potential applicants. Patricia Moritz, Ph.D., R.N. Nursing Systems Branch National Center for Nursing Research Westwood Building, Room 754 Bethesda, MD 20892 Telephone: (301) 496-0523 (for copies of the RFA) Telephone: (303) 844-6163 (for scientific matters) Direct inquiries regarding fiscal matters to: Sally Nichols Grants Management Officer National Center for Nursing Research Westwood Building, Room 748 Bethesda, MD 20892 Telephone: (301) 496-0237 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.331, Nursing 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-93-006 ************************************************ GENES DETERMINING STEM CELL SELF-RENEWAL AND COMMITMENT NIH GUIDE, Volume 21, Number 37, October 16, 1992 PA NUMBER: PA-93-006 P.T. 34; K.W. 1002058, 0785070 National Heart, Lung, and Blood Institute PURPOSE The National Heart, Lung, and Blood Institute (NHLBI) announces the availability of a Program Announcement (PA) on the above subject. The purpose of this initiative is to encourage research aimed at providing an understanding of the genetic and molecular mechanisms responsible for controlling hematopoietic stem and progenitor cell self-renewal, commitment, 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, Genes Determining Stem Cell Self-Renewal and Commitment, is related to the priority areas of hematologic disorders and bone marrow transplantation. 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 foreign and domestic, for-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. Awards in connection with this announcement 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. Foreign institutions are not eligible for First Independent Research Support and Transition (FIRST) Awards (R29). MECHANISM OF SUPPORT This PA will use the National Institutes of Health (NIH) individual research grant (R01) and FIRST (R29) awards. 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. Because the nature and scope of the research proposed in response to this PA may vary, it is anticipated that the size of an award will also vary. Applications for R29 awards may request no more than $350,000 direct costs. Administrative adjustments in project period and/or amount of support may be required at the time of the award. All current policies and requirements that govern the research grant programs of the NIH will apply to grants awarded in connection with this PA. RESEARCH OBJECTIVES The purpose of this initiative is to encourage research aimed at providing an understanding of the genetic and molecular mechanisms responsible for controlling hematopoietic stem and progenitor cell self-renewal, commitment, and differentiation. The production of blood cells, a process called hematopoiesis, takes place in the bone marrow. Hematopoiesis begins with the most primitive, pluripotent hematopoietic stem cell which is believed to be present as only one of every 1,000 to 100,000 nucleated bone marrow cells. The stem cell can either self-renew or differentiate into myeloid or lymphoid stem cells, which in turn can further differentiate and mature, ultimately giving rise to all the circulating blood cells. Each of these complex hematopoietic pathways is under the influence of one or more hematopoietic growth factors (colony stimulating factors) or cytokines that enhance cellular proliferation and maturation and other substances that exert negative or inhibitory effects on the process. The past decade has witnessed the cloning and characterization of several hematopoietic growth factors. Many of these have already assumed a role in medical treatment. However, since these factors typically have more than one action, some of these actions may be undesirable in a given case. For example, some cytokines used to ameliorate chemotherapy-induced neutropenia may have the undesirable effect of stimulating the growth of tumor cells or of activating mature neutrophils. Hence, growth factors alone provide insufficiently precise control of the hematopoietic system. Growth factors are only a part of a complex system regulating hematopoiesis. For each growth factor there is a receptor, signal transducers, and responsive genetic elements. Many of these receptors have been characterized; some can be the target of therapeutic attack through molecules designed to compete with their natural ligands. Much current work focuses on signal transduction. Intervention via signal transducers may be complicated by the fact that some signal transducers are common to several pathways serving different functions. Studies in several animal and cell culture systems support the idea that tyrosine kinase receptors, Ras and protein kinase C are part of a common signaling pathway. Thus, identification of responsive genetic elements for growth factors may be the best approach to obtain the specificity required for therapeutic intervention. The hematopoietic stem cell and blood cell progenitors face a succession of "decisions," i.e., choices among alternative pathways. For example, between the quiescent stem cell and the mature neutrophil lie perhaps five such decisions: (a) whether to remain quiescent or to divide; (b) if to divide, whether to remain multipotential (self-renew) or to restrict potentiality; (c) if to restrict potentiality, whether to become a lymphoid or a myeloid stem cell; (d) if to become a myeloid stem cell, whether to become an erythroid, megakaryocytic, or granulocytic progenitor; and (e) if to become granulocytic, whether to become a neutrophilic, eosinophilic, or basophilic progenitor. What these decisions represent at the molecular level, which result in commitment of multipotent progenitors to differentiate along a given lineage, remains elusive. The hypothesis behind this initiative is that each such decision represents activation of a set of genes via a "master" gene. The purpose of this initiative is to identify the genes responsible for the particular alternative pathways selected. The concept of master genes in hematopoiesis has been advanced by studies using approaches in normal and transformed cell culture systems, isolation of multipotent cell lines derived from mouse bone marrow, and the use of hematopoietic cells transformed in vitro by oncogene-containing acute leukemia viruses. Alterations in gene expression can have profound effects on the growth and differentiation of hematopoietic cells. Thus, it is important to understand the mechanisms by which