From owner-sci-resources@net.bio.net Mon Sep 01 23:00:00 1997 Path: biosci!biosci!not-for-mail From: BIOSCI Administrator Newsgroups: bionet.sci-resources Subject: NIH GUIDE - PA-97-098 - V26(29) 08/29/97 Date: 2 Sep 1997 14:39:35 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 413 Sender: daemon@net.bio.net Approved: biosci-help@net.bio.net Distribution: world Message-ID: <5ui12n$kqu@net.bio.net> NNTP-Posting-Host: net.bio.net AUTOIMMUNITY: GENETICS, MECHANISMS, AND SIGNALING NIH Guide, Volume 26, Number 29, August 29, 1997 PA NUMBER: PA-97-098 P.T. National Institute of Allergy and Infectious Diseases National Institute of Diabetes and Digestive and Kidney Diseases National Institute of Arthritis, Musculoskeletal and Skin Diseases National Institute on Aging Office of Research on Women's Health, NIH PURPOSE The National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS), National Institute on Aging (NIA), and the Office of Research on Women's Health, National Institutes of Health (NIH) invite applications for new and innovative investigator-initiated basic and preclinical research into the immune responses underlying autoimmune disease and its regulation for preventive or therapeutic purposes. Three specific areas of emphasis are highlighted: 1) genetic susceptibility for autoimmune disease, including the MHC and other genetic loci; 2) role and regulation of co-stimulation of T cells in autoimmunity; and 3) signal transduction in the autoreactive response. 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, "AUTOIMMUNITY: GENETICS, MECHANISMS, AND SIGNALING" related to the priority area of Diabetes and Chronic Disabling Diseases. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0 or Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-512-1800). ELIGIBILITY Applications may be submitted by 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. Domestic and foreign institutions are eligible to apply for R01 grants. Foreign institutions are not eligible for FIRST awards (R29). Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as Principal Investigators. MECHANISMS OF SUPPORT Traditional research project grant (R01) AND FIRST award (R29) applications may be submitted in response to this announcement. Applications for R01 grants may request up to five (5) years of support; applications for R29 grants must request five years of support. Responsibility for the planning, direction, and execution of the proposed research for all applicable mechanisms of support will be solely that of the applicant. RESEARCH OBJECTIVES Background Autoimmune diseases result when the immune response is directed at the body's own tissues. Autoreactive immune responses may be initiated in response to either exogenous (from outside the body, such as a pathogen) or endogenous (from inside the body) antigens in the context of a genetic background susceptible to autoimmunity. Antigen is processed and presented to the T cell, whose response can be affected by the availability of co-stimulatory ligand-receptor interaction(s). The interaction of antigen with the T cell in the context of co-stimulatory signals results in activation of various signal transduction pathways (see below). In addition, the environment of this interaction, including cytokines present, amount and character of antigen present and co-stimulatory molecules, can affect the type of response and its intensity. Autoimmune diseases are more common in families. More than one gene is thought to underlie this genetic susceptibility with one of the important genetic loci being the Major Histocompatibility Complex locus. Marked progress in mapping areas of genetic susceptibility has been made for some diseases, including insulin dependent diabetes mellitus and systemic lupus erythematosus. For these two diseases, several of the susceptibility genes map to overlapping regions of the chromosome suggesting that the same or similar genes may be involved in the development of these different diseases. The fine mapping and identification of the genes should allow the evaluation of the functional consequences of their gene products. Evaluation of the interaction of multiple genes and the environment in the development of the autoimmune phenotype can follow. Further understanding of this process in the development of autoreactive responses could lead to novel approaches for the prevention or therapy of autoimmune diseases. Increasingly, basic research has emphasized the importance of more than one signal for the activation of T cells. The antigen-T cell receptor complex is primary, but equally, the presence or absence of other signals, called co-stimulation, can direct the interaction to the development of tolerance rather than activation. Blockade of the co-stimulatory signal has prevented the development of disease in animal models of multiple sclerosis, insulin dependent diabetes mellitus, and systemic lupus erythematosus. Recently, investigation of this path in ongoing autoimmune disease suggests that these molecules may be important in the perpetuation of the autoreactive response. The number of these co-stimulatory signals which have been identified is growing rapidly, initially including the B-7 family, and now expanded to include the CD40-CD40L family. With further understanding of the mechanisms, these molecules could be exploited to modulate the initiation or progression of autoimmune disease. Finally, much progress has been made in defining the intracellular and extracellular signaling pathways that mediate the consequences of the immune response after interaction of antigen and the immune system. These include the secretion of cytokines, production of cytotoxic T cells, activation of phosphoprotein signaling cascades, activation or repression of transcription factors, activation of cell death pathways, including apoptosis, and inflammatory cascades. The final common pathways of damage include release of proteases, nitric oxide and superoxide production, antigen-antibody complexes, and cytokines. Further understanding of these pathways in the development and regulation of the response to autoantigens and in mediating autoimmune disease may allow development of effective and innovative therapies for autoimmune disease. NIA has responsibility for supporting basic research and training in fundamental studies of immunology that relate to aging. Research Objectives and Scope The objective of this PA is to encourage the application of advances in basic immunology to understanding the pathogenesis and regulation of the immune response to self antigens, focusing specifically on genetic susceptibility, including the interaction of genes, role of co-stimulation of immune cells, mechanism of induction, perpetuation, and tissue injury in the autoreactive response. Further understanding of the pathogenic and regulatory processes of the autoreactive immune response should lead to new approaches for the prevention or treatment of autoimmune diseases. Examples of topics of research interest include, but are not limited to: o characterization of loci of genetic susceptibility to autoimmune disease, including overlapping loci for multiple diseases; characterization of the genes in these loci and their products, including the functional role of these genes; o mechanisms and interactions by which genes influence the susceptibility to development of autoimmune disease; o characterization of the role of co-stimulatory molecules in the response to self antigens; o identification of regulators (agonists and antagonists) of co- stimulatory molecules in the autoreactive response; o the role of apoptosis in the pathogenesis of autoimmunity and autoimmune disease; o the role of STAT proteins in the autoreactive immune response; potential for regulation of this response; and o characterization of cytokine expression and regulation in response to self antigens INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of the NIH that women and members of minority groups and their subpopulations must be included in all NIH supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification are provided that inclusion is inappropriate with respect to the health of the subjects of the purpose of the research. This policy results >From the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing research involving human subjects should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research", which have been published in the Federal Register of March 28, 1994 (FR 59 14508-14513) and the NIH Guide for Grants and Contracts, Vol. 23, No. 11, March 18, 1994. Investigators may obtain copies from these sources or from the program staff listed under INQUIRIES. Program staff may also provide additional relevant information concerning the policy. APPLICATION PROCEDURES Applications are to be submitted on the grant application for PHS 398 (rev. 5/95) and will be accepted on the standard application deadlines as indicated on the application kit. Application kits are available at most institutional offices of sponsored research and may be obtained from the Division of Extramural Outreach and Information Resources, National Institutes of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone (301) 435-0714, email: asknih@odrockm1.nih.gov. For purposes of identification and processing, item 2 on the face page of the application must be marked "YES". The PA number and the PA title must also be typed in section 2. The completed, signed original and five (5) legible, single-sided copies of the application must be sent or delivered to: DIVISION OF RESEARCH GRANTS NATIONAL INSTITUTES OF HEALTH 6701 ROCKLEDGE DRIVE, ROOM 1040, MSC 7710 BETHESDA, MD 20892-7710 BETHESDA, MD 20817-7710 (for express/courier service) R29 applications must include at least three sealed letters of reference attached to the face page of the original application. FIRST applications submitted without the required number of reference letters will be considered incomplete and will be returned without review. Applicants from institutions that have a General Clinical Research Centers (GCRC) funded by the NIH National Center for Research Resources may wish to identify the Center as a resource for conducting the proposed research. If so, a letter of agreement from the GCRC Program Director must be included in the application material. REVIEW CONSIDERATIONS Review Procedures Applications will be assigned on the basis of established PHS referral guidelines. Upon receipt, applications will be reviewed for completeness by the NIH Division of Research Grants. Incomplete applications will be returned to the applicant without further consideration. 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. As part of the initial merit review, all applications will receive a written critique and undergo a process in which only those applications deemed to have the highest scientific merit, generally the top half of the applications under review, will be discussed, assigned a priority score, and receive a second level review by the appropriate national advisory council. Review Criteria The five criteria to be used in the evaluation of grant applications are listed below. To put those criteria in context, the following information is contained in instructions to the peer reviewers. The goals of NIH-supported research are to advance our understanding of biological systems, improve the control of disease, and enhance health. The reviewers will comment on the following aspects of the application in their written critiques in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered by the reviewers in assigning the overall score weighting them as appropriate for each application. Note that the application does not need to be strong in all categories to be judged likely to have a major scientific impact and thus deserve a high priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to move a field forward. 1. Significance. Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge be advanced? What will be the effect of these studies on the concepts or methods that drive this field? 2. Approach. Are the conceptual framework, design, methods, and analyses adequately developed, well-integrated, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics? 3. Innovation. Does the project employ novel concepts, approaches or method? Are the aims original and innovative? Does the project challenge existing paradigms or develop new methodologies or technologies? 4. Investigator. Is the investigator appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers (if any)? 5. Environment. Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed experiments take advantage of unique features of the scientific environment or employ useful collaborative arrangements? Is there evidence of institutional support? The initial review group will also examine: the appropriateness of proposed project budget and duration; the adequacy of plans to include both genders and minorities and their subgroups as appropriate for the scientific goals of the research and plans for the recruitment and retention of subjects; the provisions for the protection of human and animal subjects; and the safety of the research environment. AWARD CRITERIA Applications will compete for available funds with all other favorably recommended applications. The following will be considered when making funding decisions: quality of the proposed project as determined by peer review, program balance, and availability of funds. INQUIRIES Written and telephone inquiries are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Inquiries regarding programmatic (research scope and eligibility) issues may be directed to: Elaine Collier, M.D. Division of Allergy, Immunology, and Infectious Diseases National Institute of Allergy and Infectious Diseases 6003 Executive Boulevard, Room 4A20 Bethesda, MD 20892-7640 Telephone: (301) 496-7104 FAX: (301) 402-2571 Email: ec5x@nih.gov Joan T. Harmon, Ph.D. Chief, Diabetes Research Section National Institute of Diabetes and Digestive and Kidney Diseases 45 Center Drive, MSC 6600 Bethesda, MD 20892-6600 Telephone: (301) 594-8808 FAX: (301) 480-3503 Email: JOAN_HARMON@NIH.GOV Susana Serrate-Sztein, M.D. Arthritis Branch National Institute of Arthritis, Musculoskeletal and Skin Diseases Natcher Bldg. Rm 5AS37G Telephone (301) 594-5032 FAX: (301) 480-4543 Internet: szteins@ep.niams.nih.gov Anna M. McCormick, Ph.D. Chief, Biology Branch Biology of Aging Program National Institute on Aging Gateway Building, Suite 2C231 Bethesda, MD 20892 Telephone: (301) 496-6402 FAX: (301) 402-0010 Internet: am38k@nih.gov Direct inquiries regarding fiscal matters to: Mrs. Pam Fleming Division of Extramural Activities National Institute of Allergy and Infectious Diseases 6003 Executive Boulevard, Room 4B30 Bethesda, MD 20892-7610 Telephone: (301) 496-7075 FAX: (301) 480-3780 Email: pf49e@nih.gov Linda Stecklein Division of Extramural Activities National Institute of Diabetes and Digestive and Kidney Diseases Natcher Building, Room 6As-49J Bethesda, MD 20892-6600 Telephone: (301) 594-8847 FAX: (301)480-3504 Email: steckleinl@ep.niddk.nih.gov Ms. Carol Fitzpatrick Grants Management Branch NIAMS, NIH Natcher Bldg. Rm 5AS43K Telephone: (301) 594-3506 FAX: (301) 480-4543 Internet: fitzpatric@ep.niams.nih.gov Mr. Joseph Ellis Grants Management Officer Grants and Contracts Management Office National Institute on Aging Gateway Building, Suite 2N212 Bethesda, MD 20892 Telephone: (301) 496-1472 FAX: (301) 402-3672 Internet: je14j@nih.gov AUTHORITY AND REGULATIONS This program is supported under authorization of the Public Health Service Act, Sec. 301(c), Public Law 78-410, as amended. The Catalogue of Federal Domestic Assistance Citations are No. 93.855 - Immunology, Allergy, and Transplantation Research, No. 93.847 - Diabetes, Endocrinology, and Metabolic Diseases, No. 93.846 - Arthritis, Musculoskeletal and Skin Diseases, and No. 93.366 - Aging Research. 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 review. The PHS strongly encourage all grant recipients to provide a smoke- free workplace and promote the non-use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or, in some cases, any portion of a facility) in which regular or routine education, library, day care, health care, or early childhood development services are provided to children. This is consistent with the EPA and PHS missions to protect and advance the physical and mental health of the American people. From owner-sci-resources@net.bio.net Mon Sep 01 23:00:00 1997 Path: biosci!biosci!not-for-mail From: BIOSCI Administrator Newsgroups: bionet.sci-resources Subject: NIH GUIDE - PAR-97-103 - V26(29) 08/29/97 Date: 2 Sep 1997 14:40:50 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 276 Sender: daemon@net.bio.net Approved: biosci-help@net.bio.net Distribution: world Message-ID: <5ui152$l2a@net.bio.net> NNTP-Posting-Host: net.bio.net PILOT CLINICAL TRIAL GRANT FOR NEUROLOGICAL DISEASE NIH Guide, Volume 26, Number 29, August 29, 1997 PA NUMBER: PAR-97-103 P.T. National Institute of Neurological Disorders and Stroke PURPOSE The NINDS is committed to identifying effective treatments for neurological disorders by supporting well-executed clinical trials. Before proceeding to a full-scale clinical trial, pilot clinical studies are often required. The NINDS announces its interest in supporting pilot studies required to obtain necessary information to clearly establish the clinical basis for proceeding to a full-scale trial. The purpose of NINDS Pilot Clinical Trial Grant For Neurological Disease is to obtain preliminary data and conduct studies to support the rationale for a subsequent full-scale clinical trial of an intervention to treat or prevent neurological disease. 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, NINDS PILOT CLINICAL TRIAL GRANT FOR NEUROLOGICAL DISEASE, is related to the priority area of chronic disabling conditions. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0 or Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202- 512-1800). ELIGIBILITY REQUIREMENTS Applications may be submitted by foreign and domestic, for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as principal investigators. MECHANISM OF SUPPORT The mechanism of support for the NINDS Pilot Clinical Trial Grant is the research project grant (R01). It is expected that most grants will not exceed $350,000 per year in direct costs for 3 years. RESEARCH OBJECTIVES The research project should directly address how the Pilot Grant will advance the design of a subsequent full-scale clinical trial. The application should also address the intrinsic scientific merit of the study conducted under the Pilot Grant, whether or not a full-scale trial is performed. The NINDS Pilot Clinical Trial Grant may include: -Studies to refine the intervention strategy (dosage, duration, delivery system) -Studies to define and refine the target population -Collection of preliminary data for establishing measures of efficacy and safety In preparing for the definitive clinical trial, a pilot study will address questions that are formulated to optimize the design of the eventual trial rather than address the clinical question with lower power. The objective of the NINDS Pilot Clinical Trial Grant is to increase the quality of clinical research to evaluate interventions for the treatment or prevention of neurological disease. To meet this objective the proposed pilot study must successfully incorporate creative and realistic solutions to difficult problems in clinical neurological research for the particular intervention being evaluated. INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of the NIH that women and members of minority groups and their subpopulations must be included in all NIH supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification is provided that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing research involving human subjects should read the "NIH Guidelines For Inclusion of Women and Minorities as Subjects in Clinical Research," which have been published in the Federal Register of March 20, 1994 (FR 59 14508-14513) and in the NIH Guide for Grants and Contracts, Vol. 23, No. 11, March 28, 1994. APPLICATION PROCEDURES Applications are to be submitted on the grant application form PHS 398 (rev. 5/95) and will be accepted at the standard application deadlines as indicated in the application kit. Applications kits are available at most institutional offices of sponsored research and may be obtained from the Division of Extramural Outreach and Information Resources, National Institutes of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone 301/435-0714, email: ASKNIH@odrockm1.od.nih.gov. The title and number of the program announcement must be typed in Section 2 on the face page of the application. As with most applications to NIH, the research plan is limited to 25 pages. All information for review of the NINDS Clinical Trial Planning Grant application must be included in the body of the application; appendices will not be considered during the review for this mechanism. The completed original application and four legible copies must be sent or delivered to: DIVISION OF RESEARCH GRANTS NATIONAL INSTITUTES OF HEALTH 6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710 BETHESDA, MD 20892 BETHESDA, MD 20817 (for express/courier service) In order to facilitate the review of applications assigned to the NINDS, the applicant should, at the same time, mail or deliver one copy of the application to: Dr. Lillian Pubols Chief, Scientific Review Branch NINDS, NIH Federal Building, Room 9C10 7550 Wisconsin Avenue Bethesda, Maryland 20892-9175 EMAIL: lp28e@nih.gov REVIEW CONSIDERATIONS Applications will be assigned on the basis of established PHS referral guidelines. Applications that are complete will be evaluated for scientific and technical merit by an appropriate peer review group convened in accordance with the standard NIH peer review procedures. For applications given primary assignment to the National Institute of Neurological Disorders and Stroke, the initial peer review group will be convened by the Institute. As part of the initial merit review, all applications will receive a written critique and undergo a process in which only those applications deemed to have the highest scientific merit, generally the top half of applications under review, will be discussed, assigned a priority score, and receive a second level review by the appropriate national advisory council or board. Review Criteria for research grant applications: The goals of NIH-supported research are to advance our understanding of biological systems, improve the control of disease, and enhance health. In the written review, comments on the following aspects of the application will be made in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in the assignment of the overall score. (1) Significance. Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge be advanced? What will be the effect of these studies on the concepts or methods that drive this field? In addition, the following must be addressed: - The state of equipoise in the medical and patient communities - The scientific basis for the proposed intervention including discussion of current practice and alternative interventions - Impact of the proposed intervention on health care and quality of life (2) Approach. Are the conceptual framework, design, methods, and analyses adequately developed, well-integrated, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics? The following should be addressed: (a) Study Design and Procedures. - Sequence of clinical studies, including the proposed pilot study, that will produce a definitive clinical trial - Translation of the clinical question into statistical hypotheses - Selection of outcome measure(s) - Inclusion and exclusion criteria - Secondary questions (including capacity for post hoc analyses) - Detailed protocol with standardized procedures that will be used for this pilot study - Ethical and safety issues, and quality control procedures - Necessity for randomization and masking (b)Data Analysis - Specific methods to be used for data analysis - The sample size for the pilot study may not be adequate to detect any but the largest treatment differences; however, the data from this study should provide a basis for providing sample size estimates for future trials. - Population and demographics of the clinical condition (3) Innovation. Does the project employ novel concepts, approaches or method? Are the aims original and innovative? Does the project challenge existing paradigms or develop new methodologies or technologies? (4) Investigator. Is the investigator appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers (if any)? The following should be addressed: - Training and expertise in the clinical problem and the proposed intervention - Training and expertise in clinical trials (5) Environment. Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed experiments take advantage of unique features of the scientific environment or employ useful collaborative arrangements? Is there evidence of institutional support? In addition, the adequacy of plans to include both genders and minorities and their subgroups as appropriate for the scientific goals of the research will be reviewed. Plans for the recruitment and retention of subjects will also be evaluated. The initial review group will also examine the provisions for the protection of human subjects, the safety of the research environment, and conformance with the NIH Guidelines for the Inclusion of Women and Minorities as Subjects in Clinical Research. AWARD CRITERIA Applications will compete for available funds with all other approved applications assigned to that IC. The following will be considered in making funding decisions: Quality of the proposed project as determined by peer review, availability of funds, and program priority. INQUIRIES Inquiries are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Joseph S. Drage, M.D. Training and Special Programs Officer, National Institute of Neurological Disorders and Stroke Telephone: (301) 496-4188 FAX: 301-402-0302 Email: jd66x@nih.gov Direct inquiries regarding fiscal matters to: Ms. Angeline Wilson Grants Management Branch National Institute of Neurological Disorders and Stroke Telephone: (301) 496-9231 FAX: 301-402-0219 Email: aw45j@nih.gov AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.853. 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. The PHS strongly encourages all grant and contract recipients to provide a smoke-free workplace and promote the non-use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people. From owner-sci-resources@net.bio.net Mon Sep 01 23:00:00 1997 Path: biosci!biosci!not-for-mail From: BIOSCI Administrator Newsgroups: bionet.sci-resources Subject: NIH GUIDE - PAR-97-102 - V26(29) 08/29/97 Date: 2 Sep 1997 14:40:37 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 248 Sender: daemon@net.bio.net Approved: biosci-help@net.bio.net Distribution: world Message-ID: <5ui14l$l1a@net.bio.net> NNTP-Posting-Host: net.bio.net NINDS CLINICAL TRIAL PLANNING GRANT NIH Guide, Volume 26, Number 29, August 29, 1997 PA NUMBER: PAR-97-102 P.T. National Institute of Neurological Disorders and Stroke PURPOSE The NINDS seeks to fund high quality clinical trials to evaluate treatments for neurological disorders. The NINDS Clinical Trial Planning Grant allows for early peer review of the rationale and design for clinical trials of treatments for neurological disorders and provides support for the development of a detailed clinical trial research plan, including a complete manual of operations and procedures. 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, THE NINDS CLINICAL TRIAL PLANNING GRANT, is related to the priority area of chronic disabling conditions. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0 or Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202- 512-1800). ELIGIBILITY REQUIREMENTS Applications may be submitted by foreign and domestic, for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as principal investigators. MECHANISM OF SUPPORT The mechanism of support will be the Developmental Planning Grant (R21), which will provide up to $150,000 in direct costs for a single year. The award cannot be renewed. RESEARCH OBJECTIVES The NINDS encourages clinical research to evaluate interventions to treat and prevent neurological disease. The NINDS has established the Clinical Trial Planning Grant because extensive efforts are required to develop a detailed study protocol and to organize an effective research group. After the basic design and rationale for a neurological treatment trial has been reviewed, the NINDS Clinical Trial Planning Grant supports the development of specific elements which will be essential to conducting a successful full-scale clinical trial, including adequate plans for recruitment of patients, experimental design and protocols, data management, analytical techniques, facilities, administrative procedures, and collaborative arrangements. Detailed information regarding the rationale of the clinical trial, based on adequate, preclinical science and preliminary clinical research, must be developed prior to submission and included in the application for a Clinical Trial Planning Grant. The purpose of the planning grant is not to obtain preliminary data or to conduct studies to support the rationale for the clinical trial. The expected product of the planning grant is a detailed clinical trial research plan including a complete manual of operations and procedures. INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of the NIH that women and members of minority groups and their subpopulations must be included in all NIH supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification is provided that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing research involving human subjects should read the "NIH Guidelines For Inclusion of Women and Minorities as Subjects in Clinical Research," which have been published in the Federal Register of March 20, 1994 (FR 59 14508-14513) and in the NIH Guide for Grants and Contracts, Vol. 23, No. 11, March 28, 1994. APPLICATION PROCEDURES Applications are to be submitted on the grant application form PHS 398 (rev. 5/95) and will be accepted at the standard application deadlines as indicated in the application kit. Applications kits are available at most institutional offices of sponsored research and may be obtained from the Division of Extramural Outreach and Information Resources, National Institutes of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone 301/435-0714, email: ASKNIH@odrockm1.od.nih.gov. The title and number of the program announcement must be typed in Section 2 on the face page of the application. As with most applications to NIH, the research plan is limited to 25 pages. All information for review of the NINDS Clinical Trial Planning Grant application must be included in the body of the application; appendices will not be considered during the review for this mechanism. The completed original application and four legible copies must be sent or delivered to: DIVISION OF RESEARCH GRANTS NATIONAL INSTITUTES OF HEALTH 6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710 BETHESDA, MD 20892 BETHESDA, MD 20817 (for express/courier service) In order to facilitate the review of applications assigned to the NINDS, the applicant should, at the same time, mail or deliver one copy of the application to: Dr. Lillian Pubols Chief, Scientific Review Branch NINDS, NIH Federal Building, Room 9C10 7550 Wisconsin Avenue Bethesda, Maryland 20892-9175 EMAIL: lp28e@nih.gov REVIEW CONSIDERATIONS Applications will be assigned on the basis of established Public Health Service guidelines. Applications that are complete will be evaluated for scientific and technical merit by an appropriate peer review group convened in accordance with the standard NIH peer review procedures. As part of the initial merit review, all applications will receive a written critique and undergo a process in which only those applications deemed to have the highest scientific merit, generally the top half of applications under review, will be discussed, assigned a priority score, and receive a second level review by the appropriate national advisory council or board. Review Criteria: All applications will be reviewed using the criteria below: (1) Rationale. The background and significance of the application must address the rationale for a future, full-scale, randomized clinical trial (RCT) including: - reasons for selection of intervention and mode of delivery including specific details such as dose or a particular procedure; - the biological mechanisms and clinical data that support conducting an RCT; - information adequate to determine the significance and need to perform an RCT; - compelling need to proceed with an RCT as soon as possible; impact on health care; - competitive therapies--advantages and disadvantages; - ethical issues surrounding an RCT and the disease under study; - a clear statement of the question that an RCT would address. (2) Experimental Design. The application for a planning grant will include a full description of the experimental design of the future RCT, including: - translation of the clinical question into a statistical hypothesis; - sample size and duration of the RCT; - endpoint(s) and data to be collected; - randomization, masking, and inclusion/exclusion criteria; - the strengths and weaknesses of the proposed methods, and possible alternatives; - ancillary therapies - capability to develop methods for standardization of procedures for data management and quality control. (3) Plans to Address Patient Recruitment/Retention. The application must address the following items: - plans for documenting the availability of the requisite eligible- patient pool; - plans for including women and minority individuals as trial participants - and plans for recruitment outreach, as appropriate; follow-up procedures to ensure collection of data at stated intervals. (4) Investigators. The application must include a clear statement of the leadership and proposed organization of the RCT, including: - identification of a principal investigator, and for multi-center trials, a core of potential center investigators; - professional training and experience of the RCT organizers in such areas as the clinical problem under study, administration of complex projects, and study design. - inclusion of statisticians, data managers and study coordinators; - plans to add or drop centers; essential committee structure, i.e., Planning, Steering, Executive. AWARD CRITERIA Applications will compete for available funds with all other approved applications assigned to that IC. The following will be considered in making funding decisions: Quality of the proposed project as determined by peer review, availability of funds, and program priority. INQUIRIES Inquiries are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Joseph S. Drage, M.D. Training and Special Programs Officer, National Institute of Neurological Disorders and Stroke Telephone: (301) 496-4188 FAX: 301-402-0302 Email: jd66x@nih.gov Direct inquiries regarding fiscal matters to: Ms. Angeline Wilson Grants Management Branch National Institute of Neurological Disorders and Stroke Telephone: (301) 496-9231 FAX: 301-402-0219 Email: aw45j@nih.gov AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.853. 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. The PHS strongly encourages all grant and contract recipients to provide a smoke-free workplace and promote the non-use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people. From owner-sci-resources@net.bio.net Mon Sep 01 23:00:00 1997 Path: biosci!biosci!not-for-mail From: BIOSCI Administrator Newsgroups: bionet.sci-resources Subject: NIH GUIDE - RFA ES-97-004 - V26(29) 08/29/97 Date: 2 Sep 1997 14:39:22 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 871 Sender: daemon@net.bio.net Approved: biosci-help@net.bio.net Distribution: world Message-ID: <5ui12a$kpm@net.bio.net> NNTP-Posting-Host: net.bio.net CENTERS FOR CHILDREN'S ENVIRONMENTAL HEALTH AND DISEASE PREVENTION RESEARCH NIH Guide, Volume 26, Number 29, August 29, 1997 RFA: ES-97-004 P.T. National Institute of Environmental Health Sciences U.S. Environmental Protection Agency, National Center for Environmental Research and Quality Assurance Letter of Intent Receipt Date: September 30, 1997 Application Receipt Date: January 21, 1998 PURPOSE The National Institute of Environmental Health Sciences (NIEHS), the Environmental Protection Agency (EPA) and the National Center for Environmental Health, Centers for Disease Control and Prevention (CDC), share the common objective of fostering research that will ultimately reduce the extent of adverse human health effects occurring as a consequence of exposure to hazardous environmental agents. The agencies recognize that these health impacts can be particularly detrimental for children due to pronounced differences in nature and extent of environmental exposure as well as in functional development when compared to adults. A Federal Executive Order of April 21, 1997, "Protection of Children from Environmental Health Risks and Safety Risks," charges agencies to consider special environmental risks to children in their activities. Accordingly, NIEHS and EPA invite grant applications for Centers that will develop multidisciplinary basic and applied research in combination with community-based prevention research projects to support studies on the causes and mechanisms of children's disorders having an environmental etiology, identify relevant environmental exposures, intervene to reduce hazardous exposures and their adverse health effects, and eventually decrease the prevalence, morbidity, and mortality of environmentally related childhood diseases. The purpose of awards in this program of Centers for Children's Environmental Health and Disease Prevention Research is to: Provide for multidisciplinary interactions among basic, clinical, and behavioral scientists interested in establishing outstanding, state- of-the-art research programs addressing environmental contributions to children's health and disease. Support a coordinated program of research/prevention Centers pursuing high quality research in environmental aspects of children's disease, with the ultimate goal of facilitating and accelerating translation of basic science knowledge into clinical applications or intervention strategies that can be used to reduce the incidence of environmentally related childhood disease. Develop fully coordinated programs that incorporate exposure assessment and health effects research with development and validation of risk management and health prevention strategies. Establish a national network that fosters communication, innovation, and research excellence with the ultimate goal of reducing the burden of morbidity among children as a result of exposure to harmful environmental agents. The long-range goal of this program is to promote translation of basic research findings into applied intervention and prevention methods, thereby enhancing awareness among children, their families, and health care practitioners regarding detection, treatment, and prevention of environmentally related diseases and health conditions. Each application is to be designed around a central scientific theme, specifically examining the role of environmental agents in one of the following research foci: (1) children's respiratory disease; (2) childhood learning; (3) growth and development (see Research Scope below). A minimum of two (2) basic biomedical research projects and one (1) community-based intervention research component must be proposed within each Center (see Description of a Center below). 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), "Centers for Children's Environmental Health and Disease Prevention Research," is related to the priority area of Environmental Health. 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 202-512-1800). THE EPA CHILDREN'S ENVIRONMENTAL HEALTH INITIATIVE The EPA recognizes that children's environmental health issues are a top priority and must become a central focus of the agency's efforts. This RFA is a component of the agency's overall initiative that, together with the efforts of partner agencies, will ensure that children receive the protection they need and deserve and help our nation fulfill its obligation to protect future generations. Potential applicants may obtain a copy of the EPA's national agenda to protect children's health from environmental threats (EPA 175- F-96-001) from the EPA program contact listed under INQUIRIES. ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic non-profit organizations, public and private, that meet the requirements stated in this RFA. Minority individuals, persons with disabilities, and women are encouraged to apply as Principal Investigators. The need for communication and interaction among awarded sites dictates that only domestic institutions in the United States will be eligible for these Center grant awards. MECHANISM OF SUPPORT The funding mechanisms to be used to assist the scientific community in participating in this grant program will be those of: 1) the National Institutes of Health (NIH) Specialized Center (P50); or 2) the Environmental Protection Agency's Office of Research and Development, administered in accordance with 40 CFR Part 30 and 40. Policies that govern grant award programs of each agency will prevail for respective sources of support. Support of grants pursuant to this RFA is contingent upon receipt of a sufficient number of applications of high scientific merit and of appropriated funds for this purpose. Because the nature and scope of the research proposed in response to this RFA may vary, it is anticipated that the size of the awards will also vary within the funding limits available (see Description of a Center). The maximum award will be $1 million in direct costs in the first and all subsequent years. Funding in subsequent years is contingent upon satisfactory progress during the preceding year and availability of funds. The total project period for an application submitted in response to this RFA may not exceed five years. The anticipated award date is August, 1998. FUNDS AVAILABLE Although this solicitation is included in fiscal plans of EPA and NIEHS for FY 1998, support for these Center grants is contingent upon availability of funds for this purpose. It is anticipated that an estimated total of $10 million, including direct and indirect costs, will be available for the first year of the program, which will support up to six Centers in FY 1998. It is expected that NIEHS and EPA may solicit additional new Specialized Center applications through subsequent issuance of a similar RFA addressing children's environmental health. RESEARCH OBJECTIVES Background Establishment by NIEHS and EPA of Centers for Children's Environmental Health and Disease Prevention Research recognizes the unique vulnerability of children to hazardous environmental exposures. The greater susceptibility of children to such exposures is likely related to changes in organ system growth as well as developmental and metabolic capacities that adjust during childhood. For example, lung surface area increases tenfold and gas exchange areas increases more than twenty-fold from birth to adulthood. Since many xenobiotics are absorbed through the alveolar epithelium, the lung represents a particularly sensitive organ. Moreover, the diets of children and their unique behavioral patterns such as crawling and hand-to-mouth activities augment the probability of certain exposures. In the past, standards regulating exposure to environmental health threats have been, in some cases, based on research and assessment of risks to adults. Often, the knowledge base to ensure that standards are protective of infants and children has not been adequate. Because children have very different metabolic, physiologic, and developmental processes, diets, and exposure patterns than adults, their health outcomes can differ drastically. There is a clear need for additional research that can more fully incorporate children's unique traits into risk assessment paradigms. Environmentally related childhood diseases represent an enormous public health problem. For example, asthma, the most common chronic childhood illness, afflicts nearly five million children and is the leading cause of children's emergency room use, hospital admission, and school absences. From 1982 to 1993, the prevalence, morbidity, and age-adjusted mortality rates for asthma increased significantly despite improvements in asthma diagnosis and management and improved understanding of the biology and immunology of the disease. The mortality rate attributed to asthma for children five to fourteen years of age has doubled since 1980 and is highest among African- American children, who are three times more likely than Caucasian children to die of this illness. Chronic asthma in children is highly associated with chronic respiratory disease in adulthood and has a huge health, societal, and economic impact. Approximately 20% of the 76.7 million children in the United States live in poverty. Children who live in these impoverished communities are exposed to multiple indoor and outdoor environmental pollutants at disproportionately high levels. Preambulatory and crawling children spend significant time indoors and are subjected to high levels of allergens found in carpeting, bedding, upholstered furniture, and house dust. Indoor pollution levels may also depend on heating sources, use of household chemicals, parental smoking habits, and the presence of nearby industrial or waste facilities, which may result in increased amounts of polycyclic aromatic hydrocarbons, volatile organic compounds, and particulates. In addition, it is estimated that 20-60% of children between one and five years of age are exposed to unsafe levels of organophosphate pesticides. Exposure to such agents may occur in both indoor living space and outdoor play areas. There is thus a particular need to address environmental health problems of children living in socioeconomically disadvantaged or medically underserved communities. The current initiative is intended to foster advancement in children's health through enhancing our understanding of basic disease mechanisms and promoting community-based prevention activities related to children's respiratory disorders, childhood learning, and growth and development. Collaborative, multidisciplinary research approaches are required to explore the dynamic interaction of children with their environment. This Center program therefore emphasizes integration of basic laboratory science with applied intervention strategies. Because the latter are also research projects, it is important to note that each intervention research project should include appropriate methodology for assessing its effectiveness (see 'Description of a Center' below). Centers are expected to have fully coordinated programs that incorporate exposure assessment and health effects research with development and validation of risk management and health prevention strategies. Moreover, involvement of the affected community in planning, implementing, and evaluating an intervention effort is essential. Community-based prevention/intervention research not only expands our understanding of the causes and remedies of environmentally related disorders, but also enhances the capacity of communities to participate in processes that shape research and intervention approaches. By bridging gaps between basic and applied researchers and between institutional researchers and community members, this program aims to improve our knowledge regarding detection, treatment, and prevention of environmentally related diseases in children. Research Scope and Objectives Centers for Children's Environmental Health and Disease Prevention Research are research-based Center grants designed to support interactive groups of research projects and core service facilities. Research activities included in these Center grants must comprise, by definition, a multidisciplinary approach to biomedical problems addressing one or more of the specific research topic areas announced in this RFA (see below). A Center should identify a central theme or focus of its research effort so that the subprojects involved are responsive to one or more of the specific research areas of children's environmental health supported by this grant program. Furthermore, the translational objective of this program requires that one of the subprojects consist of a community-based intervention. The following is the list of specific research topics that will be considered to be responsive, for purposes of the current RFA, to the research mission areas of EPA and NIEHS. These topics identify areas where research at the basic/applied interface is essential to potential development of new approaches that can be used for detection, prevention, treatment, and effective management of environmentally related childhood disorders. Respiratory Diseases Particulate and gaseous pollutants and volatile organic compounds, when inspired, can lead to inflammation of the airways and development of a spectrum of respiratory and systemic disturbances and diseases. This is especially true in the case of environmental agents, or their metabolic products, which have the capacity to access alveolar spaces and to diffuse or be transported into the blood stream. Such compounds may then exert adverse health effects at systemic target organs. The principal objective of research in this focus area is to understand the mechanisms of respiratory disease in children, including asthma, chronic obstructive pulmonary diseases, and allergy associated with chemical and biological environmental exposures. Additional research is needed to examine mechanisms of tissue damage, including that produced by reactive oxygen species generated as a result of exposure to environmental oxidants. These oxidants include ozone, nitrogen dioxide, and particulate matter. By virtue of their greater physical activity out-of-doors when pollution levels may be high, children may experience higher exposures to these hazards than adults. In response to such pollutant exposure, epithelial cells in the lung synthesize and release a variety of potent mediators that can contribute to a local inflammatory reaction and play a role in pathogenesis of respiratory disturbances. It is important to understand the basic mechanisms by which pollutants alter the inflammatory response in airways, resulting in airway hyperactivity, IgE antibody production, and asthma. It is equally important to address other mechanisms of lung dysfunction, including compromise of immunologic responsiveness and modulations of receptor signaling pathways. Childhood Learning Exposure to a number of common environmental contaminants, such as lead, polychlorinated biphenyls (PCBs), and mercury, may inhibit intellectual development in children and ultimately result in behavioral problems. For example, PCBs and their heat degradation products have long half-lives, cross the placenta, and are excreted in breast milk. Prenatal exposure to PCBs can cause significant developmental toxicities in animals. Children are more susceptible to PCB-induced toxic effects than adults, and these effects are more severe and influence more organ systems in children than in adults. These effects may persist throughout a child's lifespan, while in an adult only a portion of the lifespan may be affected. Continued research on toxic effects associated with low level developmental exposure to these contaminants is needed. Enhancing our understanding of the pathways by which these contaminants exert their toxic action may result in development of more effective interventions. Effects of intrauterine exposure to environmental hazards are of interest, including changes that occur in maternal biokinetics during pregnancy and determinants of placental transport and fetal accumulation of toxicants. Additional effort should also be focused on defining how such contaminants modify intellectual and behavioral development, especially in areas such as hyperactivity and learning disabilities. Alterations in cognitive and behavioral function due to exposure to such agents as metals, solvents, and pesticides have to date received little systematic attention. For the purposes of this RFA, research focusing exclusively on lead poisoning in children will be considered nonresponsive. Growth and Development In utero or postnatal exposure to a variety of environmental agents can have a profound influence on initial growth and development. One such area that merits research attention in both basic and applied science is sexual development. Endocrine-disrupting chemicals may affect a number of physiological processes, including onset of menses and puberty. Moreover, exposures during early windows of vulnerability may carry risks for later onset of adult diseases. For example, children susceptible to effects of air pollution have reduced lung development, leading to smaller lung capacity in adulthood; this difference may in turn have important ramifications for adult respiratory morbidity and mortality. It is also important to expand our understanding of the potential role of environmental factors in the etiology of birth defects. Parental exposure to organic solvents, agricultural chemicals, or heavy metals may increase the risk of having a child with a neural tube defect. For all of these research areas, attention should be given to mechanistic studies of toxicity. It is also desirable that exposure assessment research be included, where appropriate. Furthermore, it is important to evaluate the contribution of genetic heterogeneity to the disease process. Information on individual variability with respect to chemical sensitivity and metabolism of xenobiotic agents has a significant role in defining disease onset and progression. Asthma susceptibility, for example, is known to run in families. Identification of asthma susceptibility genes, which might interact with environmental factors to contribute to the rising incidence of this disease, would hold significant promise for designing new prevention and treatment approaches. Prospective applicants are strongly encouraged to discuss potential program relevancy issues as well as application preparation with the program staff contact cited under INQUIRIES in this RFA. Applicants should note that the research scope of this RFA does not include any long-term (longer than five years) studies. Description of a Center A Specialized Center provides the opportunity for investigators to engage in interdisciplinary and collaborative research directed toward a specific focus in children's environmental health. It is required that each Center include community-based intervention research as well as basic studies clearly related to a disease or dysfunction. The foundation of the intervention should be strongly linked to the basic science research. The basic science studies should be driven by the needs of the intervention project. Thus, a Center should have a central theme to which all research projects pertain. In addition, a Center may include core units to provide services to the various research projects and to support the organizational and administrative aspects of the program. Applications that include only basic or only intervention/ prevention research will not be responsive to this RFA. The minimal requirements for a Specialized Center of Research in Children's Environmental Health are as follows: Each Center will propose an overall research mission and plan that are responsive to the objectives of the Specialized Center Program set forth in the RFA (see Research Objectives above). Each Center will support at least two basic research projects that thematically address one or more research areas listed under Research Scope. Potential basic research projects should include mechanistic studies of environmental agents which contribute to adverse health outcomes in children. These may include: basic cellular and molecular mechanisms of toxicity; pathophysiology; epidemiology; and individual susceptibility. These basic research projects should be linked to the intervention research project described below. Interactions between investigators responsible for basic research and intervention research projects are expected to strengthen the research, enhance transfer of fundamental findings to an applied setting, and identify new research directions. [It is anticipated that a Center will devote 30-45% of its budget to basic research projects.] Each Center will support one project that develops, implements, and evaluates a community-based intervention/prevention program. Activities conducted under this RFA should be consistent with Federal Executive Order No. 12988 entitled, "Federal Actions to Address Environmental Justice in Minority Populations and Low-Income Populations." To the extent practicable and permitted by law, grantees shall make achieving environmental justice part of their project's mission by identifying and addressing, as appropriate, disproportionately high and adverse human health effects of environmental contaminants on minority, low-income, and medically underserved children, including African, Hispanic, Asian, and Native Americans. It is strongly encouraged that basic science projects be in a similar scientific area as the intervention research project in order to facilitate transfer of information from laboratory to the community. This project may take the form of a primary, secondary, or tertiary prevention. It is important to note that this project must specifically address all of the following parameters: (a) scientific basis of the proposed research and the hypothesis to be tested; (b) sample size needed, power considerations, procedures for sample selection, and recruitment and retention of a study population; (c) detailed description of a research design for the proposed intervention; (d) measurement instruments and their reliability and validity, considering both process and outcome evaluation; (e) data management and analysis methods; (f) identification and description of target community and known environmental health hazards; (g) means of establishing effective interaction and collaboration with community members. Because this project is intended to be community-based, the application must demonstrate a specific, existing linkage to a community-based organization and specific involvement of community members in development, conduct, and interpretation of the intervention. NIEHS, EPA, and CDC recognize that local health departments often play an important role in delivering public health services to the community. Therefore, applicants are also encouraged to consider including local, county, or state health departments in the proposed intervention research project. However, involvement of a local health department will not substitute for the required community- based organization. Applications lacking a demonstrable linkage to a community-based organization will be considered nonresponsive. [It is anticipated that a Center will devote 20-30% of its budget to one community-based intervention research project.] Each Center may support facility cores that provide a technique, service, or instrumentation that will enhance ongoing research efforts. Examples of such facilities are animal resources, cell/tissue culture, pathology, biostatistics, molecular biology, analytical chemistry, exposure assessment, etc. Budgeted Center projects as well as research projects external to the Center may have access to facility cores. The application should provide a total operational budget for each facility core together with the percentage of support requested from the Center grant. In addition, the Center must have in place and adequately described in the application management policies which ensure that budgeted Center projects are given highest priority in receiving services provided by the facility core. The application should explain the organization and proposed mode of operation of each core, including a plan for usage, priority setting, allocation of resources, and any applicable chargeback system. [It is anticipated that a Center will devote 10-20% of its budget to facility cores.] An administrative core unit which provides overall oversight, coordination, and integration of Center activities. An External Advisory Committee to the Center Director must be established. This group should consist of a group of three (3) to five (5) scientists, having expertise appropriate for the Center's research focus, plus one (1) representative from a community-based organization involved in community-based intervention research. Representation from a state or local health department is also encouraged. At least 67% of Committee members should be from outside the grantee institution. The membership of the advisory committee must be approved by the funding agency. The function of this Committee is to assist in evaluating the merit, value, and contribution of research projects; the relevance and importance of individual organizational elements to accomplishing the overall goals of the Center; and the effectiveness of the newly recruited Center scientist program. [It is anticipated that a Center will devote 10-15% of its budget to an administrative core.] To attract new investigators into children's environmental health research, each Center is encouraged to partially support up to two (2) newly recruited Center scientists. Up to $70,000 per year, direct cost, may be used for each newly recruited Center scientist to provide up to 75% salary support, technical support, equipment, and supplies. The duration of support as a newly recruited scientist is limited to two (2) years. Following termination of support as a newly recruited Center scientist, such an individual may, if appropriate, become or continue to be a part of a basic or community- based intervention research project and make use of Center facilities. Recruitment of women and underrepresented minority scientists is specifically encouraged. To the extent possible, the types of individuals sought and their expected roles should be described in the application if specific individuals have not been identified. [It is anticipated that a Center will devote no more than 14% of its budget to recruitment of new scientists.] SPECIAL REQUIREMENTS Annual meetings, to be held in Washington, DC or Research Triangle Park, NC, are planned for the exchange of information among investigators. Applicants must budget travel costs associated with these meetings in their applications. In addition, since these Centers include a community-based intervention, applicants are expected to maximize opportunities for information exchange between institutional researchers and community members. As part of this program, applicants must generate a report that describes community input, program implementation, and relevant findings. This report must be produced at least annually and distributed among community members in such a way that it can be easily comprehended by the public. Applicants must budget for production and dissemination of such reports. This requirement is intended to establish a minimal level of communication among project participants; additional, more frequent dissemination efforts may be appropriate. INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS The NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43) requires that women and members of minority groups and their subpopulations must be included in all NIH-supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification is provided that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This new policy supersedes and strengthens the previous policies (Concerning the Inclusion of Women in Study Populations, and Concerning the Inclusion of Minorities in Study Populations), which have been in effect since 1990. The new policy contains some provisions that are substantially different from the 1990 policies. Grantees, regardless of funding source, will be expected to adhere to this policy. All investigators proposing research involving human subjects should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research," which have been published in the Federal Register of March 28, 1994 (FR 59 14508-14513) and reprinted in the NIH Guide for Grants and Contracts, Volume 23, Number 11, March 18, 1994. Investigators also may obtain copies of the policy >From the program staff listed under INQUIRIES. Program staff may also provide further discussion concerning the policy. LETTER OF INTENT Prospective applicants are asked to submit, by September 30, 1997, a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, the identities of other key personnel and participating institutions, and the number and title of the RFA in response to which the application may be submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information that it contains allows EPA and NIEHS staff to estimate potential review workload and to avoid conflict of interest in the review. The letter of intent is to be sent to: Ethel Jackson, DDS, Chief, Scientific Review Branch Division of Extramural Research and Training National Institute of Environmental Health Sciences P.O. Box 12233, EC-24 Research Triangle Park, NC 27709 APPLICATION PROCEDURES Content of Applications A response to this RFA should consist of an application that includes a detailed description of a Specialized Center of Research in Children's Environmental Health consisting of at least two individual basic research projects, a community-based intervention research project, an administrative core, up to two newly recruited Center scientists, and, if applicable, one or more facility cores. The proposed research plan should present the applicant's perception of the Center's organization and component functions. This plan should demonstrate the applicant's knowledge, ingenuity, practicality, and commitment in organizing a multiproject research infrastructure for conducting basic and applied studies in children's environmental health sciences. The research plan for the Center and all component projects must address the "Research Scope" described earlier. The research grant application form PHS 398 (rev. 5/95) is to be used in applying for these awards. Application kits are available at most institutional offices of sponsored research or may be obtained from the Division of Extramural Outreach and Information Resources, National Institutes of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone 301/435-0714, email: ASKNIH@odrockm1.od.nih.gov. For individual projects or cores, page limits stated in the PHS 398 instructions must be followed. The overall Center application must also use the PHS 398 format to provide at the beginning of the application an overall summary of the Center's organization and cumulative aggregate budgeting for various research subprojects and cores. All information essential for evaluation of the application must appear in the body of the application rather than in an appendix. If IRB or IACUC review is unavoidably delayed beyond submission of the application, a follow-up IRB certification and/or IACUC verification from an official signing for the applicant organization must be sent to and received by the Scientific Review Administrator of the Special Emphasis Panel by March 2, 1998. If IRB certification and/or IACUC verification is not received by March 2, 1998, the application will be considered incomplete and returned to the applicant. The RFA label available in the PHS 398 (rev. 5/95) application form must be affixed to the bottom of the face page of the application. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title, Centers for Children's Environmental Health and Disease Prevention Research, and number, RFA ES-97-004, must be typed on line 2 of the face page of the application form and the YES box must be checked. To simplify administration of this joint NIEHS/EPA initiative, 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 6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710 BETHESDA, MD 20892-7710 BETHESDA, MD 20817 (for express/courier service) At the time of submission, two additional copies of the application must be sent to: Ethel Jackson, DDS Chief, Scientific Review Branch Division of Extramural Research and Training National Institute of Environmental Health Sciences P.O. Box 12233, EC-24 111 T.W. Alexander Drive, EC-24 Research Triangle Park, NC 27709 Research Triangle Park, NC 27709 (for express/courier service) Applications must be received by January 21, 1998. Schedule The following is the schedule planned for this initiative. It should be noted that this schedule may be changed without notification due to factors that were unanticipated at the time of announcement. Please contact the program official listed below regarding any changes in the schedule. Letter of Intent Receipt Date: September 30, 1997 Application Receipt Date: January 21, 1998 Initial Review Group Peer Review: March 1998 NAEHS Council/NCERQA Review: May 1998 Earliest Award Date: August 1, 1998 REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by DRG and for responsiveness to the RFA by NIEHS and EPA Staff. Incomplete applications will be returned to the applicant without further consideration. Any application that does not meet the minimum requirements as set forth in the 'Description of a Center' section of this RFA will be considered unresponsive to the RFA and returned to the applicant. This includes, but is not limited to, an evaluation by EPA and NIEHS Staff of the program relevancy of the proposed basic research and intervention research subprojects. Applications that are complete and responsive to the RFA will be evaluated for scientific and technical merit by an appropriate peer review group convened by the NIEHS and the EPA. This initial review group will function according to PHS policy, utilizing the review criteria stated below. As part of the initial merit review, a triage process may be used in which applications will be determined to be competitive or noncompetitive based on their scientific merit relative to other applications received in response to this RFA. Applications determined to be noncompetitive by the review committee will be withdrawn from further consideration, and the principal investigator will receive a summary statement reflecting the reviewers' evaluation. Applications judged to be competitive will be further discussed and assigned a priority score. Applications recommended for funding will then receive a second level review by both EPA's National Center for Environmental Research and Quality Assurance (NCERQA) and NIEHS's National Advisory Environmental Health Sciences Council (NAEHSC). Review Criteria Evaluation of applications will be based upon the following: 1. Research Plan Scientific and technical merit of each proposed basic research project, including originality, feasibility, innovation, and adequacy of experimental design. Scientific and technical merit of the proposed intervention research study, including the extent of community sanction, interaction, and participation. Extent to which the design demonstrates sensitivity to cultural and socioeconomic factors in the community. Demonstration of effective communication channels between institutional researchers and community members. Plans for useful and practical dissemination of findings within the affected community. Adequacy of statistical and analytical methods, data management, and process and outcome evaluation measures. Integration of basic and intervention research into a coherent enterprise with adequate plans for interaction and communication of information and concepts among investigators. Cohesiveness and multidisciplinary scope of the Center as a whole. Degree of interrelationships, collaboration, and synergism of research that might be expected to derive from Center support. Coordination and interdependence of individual projects and their capacity to result in a greater contribution to the overall goals of the Center than if each were pursued independently. Adequacy of plans to include both genders and minorities and their subgroups as appropriate for the scientific goals of the research. Plans for recruitment and retention of subjects will also be evaluated. (See INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS.) Appropriateness of policies to ensure the protection of human subjects and the humane care and use of laboratory animals. 2. Personnel Scientific, administrative, and leadership abilities of the Principal Investigator and other key participants, particularly, but not exclusively, in the area of the proposed research. The Principal Investigator should be an established research scientist with the ability to ensure quality control and the experience to administer effectively and integrate all components of the Center. A minimum time commitment of 25% is expected for this individual. Documented commitment of time by key personnel for the proposed studies. Procedures established for recruitment and evaluation of new Center scientists. Evidence of efforts to develop novel mechanisms for recruiting candidates among women and underrepresented minority investigators. Potential of new Center Scientists to become independent investigators in clinical, basic, or intervention research in children's environmental health. 3. Facilities and Management Adequacy of administrative and technical capabilities to conduct the research proposed. Scientific and organizational structure of the Center, including adequacy of arrangements for external review. Nature and quality of facility cores. Technical merit, justification, cost effectiveness, qualifications of staff, utility to investigators, and arrangements for internal quality control, allocation of resources, priority of usage, and day-to-day management. Adequacy of animal facilities and appropriateness of animal care management where animal work is proposed. Adequacy of clinical facilities and appropriateness of patient care management where clinical work is proposed. As appropriate, access to inpatient and outpatient children's health care units providing adequate numbers of patients for intervention research projects that require patient participation. [Applications from institutions that have a General Clinical Research Center (GCRC) funded by the NIH National Center for Research Resources may wish to identify the GCRC as a resource for conducting 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.] Institutional assurance to provide support to the Center in such areas as fiscal administration, personnel management, space allocation, procurement, planning, and budgeting. 4. Budgeting Appropriateness of the proposed budget and duration in relation to proposed research. AWARD CRITERIA The anticipated date of award is August, 1998. Approved applications will be considered for award based on scientific and technical merit; program balance; and availability of funds. Funding will be provided to each Center by a single award from either EPA or NIEHS or a combination of two separate awards. Administrative and budgetary policies of EPA and NIEHS will apply to these awards. In order to receive funding, an individual domestic institution's application for a Specialized Center grant must have three or more related, interactive, and high quality research subprojects that provide a multidisciplinary, yet thematic, approach to the problems to be investigated. At least one of the subprojects must be a community-based intervention. Awards will not be made for applications with research activities focused exclusively on intervention research or exclusively on basic research or for applications or components thereof proposing long-term epidemiological or large-scale clinical trial research. 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: Allen Dearry, Ph.D. Chemical Exposures and Molecular Biology Branch Division of Extramural Research and Training National Institute of Environmental Health Sciences P.O. Box 12233, EC-21 Research Triangle Park, NC 27709 Telephone: 919/541-4500 FAX: 919/541-2843 Email: dearry@niehs.nih.gov Christopher Saint, Ph.D. Assistant Center Director National Center for Environmental Research and Quality Assurance U.S. Environmental Protection Agency 401 M Street, SW (8723R) Washington, DC 20460 Telephone: 202/564-6909 FAX: 202/565-2448 Email: saint.chris@epamail.epa.gov Direct inquiries regarding fiscal matters to: Mr. David Mineo Chief, Grants Management Branch Division of Extramural Research and Training National Institute of Environmental Health Science P.O. Box 12233, EC-22 Research Triangle Park, NC 27709 Telephone: 919/541-1373 FAX: 919/541-2860 Email: mineo@niehs.nih.gov Mr. Jack Puzak Deputy Director National Center for Environmental Research and Quality Assurance U.S. Environmental Protection Agency 401 M Street, SW (8701R) Washington, DC 20460 Telephone: 202/564-6825 FAX: 202/565-2444 Email: puzak.jack@epamail.epa.gov AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance Number 66.500, 93.113, 93.114 and 93.115. Awards by NIEHS are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 100-607) and administered under PHS grant policies and Federal Regulations 42 CFR Part 52 and 45 CFR Part 74. EPA awards are made under the authority of 40 CFR Part 30 and 40. The program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. The PHS and EPA strongly encourage all grant recipients to provide a smoke-free workplace and promote the non-use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or, in some cases, any portion of a facility) in which regular or routine education, library, day care, health care, or early childhood development services are provided to children. This is consistent with the EPA and PHS missions to protect and advance the physical and mental health of the American people. From owner-sci-resources@net.bio.net Mon Sep 01 23:00:00 1997 Path: biosci!biosci!not-for-mail From: BIOSCI Administrator Newsgroups: bionet.sci-resources Subject: NIH GUIDE - RFA AI-97-003 - V26(29) 08/29/97 Date: 2 Sep 1997 14:39:06 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 833 Sender: daemon@net.bio.net Approved: biosci-help@net.bio.net Distribution: world Message-ID: <5ui11q$kkh@net.bio.net> NNTP-Posting-Host: net.bio.net ADOLESCENTS AND STD COOPERATIVE RESEARCH CENTER NIH Guide, Volume 26, Number 29, August 29, 1997 RFA: AI-97-003 P.T. National Institute of Allergy and Infectious Diseases Letter of Intent Receipt Date: October 15, 1997 Application Receipt Date: January 8, 1998 PURPOSE The purpose of this Request for Applications (RFA) is to stimulate multi-disciplinary, collaborative research to further understanding of sexually transmitted diseases (STDs) in adolescent populations and to develop and evaluate effective approaches to their prevention and control. The Sexually Transmitted Diseases Branch of the Division of Microbiology and Infectious Diseases (DMID) of the National Institute of Allergy and Infectious Diseases (NIAID) invites grant applications for an Adolescents and Sexually Transmitted Diseases Cooperative Research Center (STD CRC). The STD CRC will provide a multi- disciplinary approach to STD research by bridging biomedical, clinical, behavioral, and epidemiological research; will foster interaction among STD investigators; and will facilitate intervention-oriented research. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This RFA, Adolescents and Sexually Transmitted Diseases Cooperative Research Center (STD CRC), is related to the priority areas of STDs and AIDS. 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 202-512-1800). ELIGIBILITY REQUIREMENTS Applications will be limited to domestic institutions but may include an international component. Applications may be submitted by domestic for-profit and non-profit research institutions; public and private organizations, such as universities, colleges, hospitals, laboratories, units of State or local governments; and eligible agencies of the Federal government. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT The administrative and funding mechanism to be used to undertake this program will be the Cooperative Agreement (U19), an "assistance" mechanism, rather than an "acquisition" mechanism, in which substantial NIH scientific and/or programmatic involvement with the awardee is anticipated during performance of the activity. Under the cooperative agreement, the NIH purpose is to support and/or stimulate the recipient's activity by involvement in and otherwise working jointly with the award recipient in a partner role, but it is not to assume direction, prime responsibility, or a dominant role in the activity. Details of the responsibilities, relationships, and governance of the study funded under cooperative agreement(s) are discussed later in this document under the section Terms and Conditions of Award. The total requested project period for applications submitted in response to this RFA may not exceed 5 years. At this time, the NIAID has not determined whether and how this solicitation will be continued beyond the present RFA. The anticipated award date is August 1, 1998. FUNDS AVAILABLE The estimated total funds (direct and indirect costs) available for the first year of support for awards under this RFA will be $1.2 million. In Fiscal Year 1998, the NIAID plans to fund one Adolescents and STD CRC. The final number of awards to be made is dependent upon the availability of funds. The initial year's total costs, including direct and indirect costs, should not exceed $1.2 million for each award. The usual PHS policies governing grants administration and management will apply. This level of support is dependent on the receipt of a sufficient number of applications of high scientific merit. Although this program is provided for in the financial plans of the NIAID, awards pursuant to this RFA are contingent upon the availability of funds for this purpose. Funding beyond the first and subsequent years of the grant will be contingent upon satisfactory progress during the preceding years and availability of funds. RESEARCH OBJECTIVES Background In 1995, an estimated 14 million cases of STDs occurred in the United States. Approximately 65% occurred in people under 24 years of age; three million occurred in teenagers. Associated health care costs exceeded $ 8 billion. Because of infections acquired during adolescence, women and their infants bear a disproportionate share of disease burden and long term sequelae of STDs, including infertility, ectopic pregnancy, cervical cancer , fetal wastage, low birth weight, and congenital/perinatal infection. Additionally, STDs disproportionately impact the health of some minority populations. Both the incidence of STDs and their long-term and potentially fatal sequelae are consistently higher among African and Hispanic Americans than among white Americans. o Chlamydial infection is the most prevalent bacterial STD in the U.S. and a major cause of pelvic inflammatory disease (PID); over four million cases are diagnosed annually. In virtually all studies, adolescents appear to have greater risk for infection compared to older women. Cross-sectional studies and data collected from adolescent and family planning clinics have documented that adolescents 15-19 years have the highest rates of infection irrespective of socioeconomic status. Due to delays in diagnosis or inadequate therapy, 10 to 40 percent of these young women with chlamydial cervicitis develop PID. o Gonorrhea, the other major cause of PID, occurs at an annual rate of approximately 0.5 million new cases, 25 percent of which occur in teenagers. Although rates of infection have been steadily decreasing in the last decade, gonorrhea rates have declined slowly in adolescent populations compared to older age groups. o During the 1980s, the rate of syphilis increased in African- American adolescent males and females. Congenital syphilis rates were particularly high among pregnant adolescent women because perinatal care is less frequent in younger women. o Trichomoniasis affects over three million American women; in the US and throughout the world, it is not uncommon to find 25% of these infections in adolescents. o In the U.S., as many as 40 million people are believed to be infected with human papillomavirus (HPV). High-risk HPV types are causally associated with cervical cancer. Globally, cervical cancer is the most common cause of cancer-related death in women. In one study, the incidence rate for HPV infection in college-aged women during their first year of sexual activity with a single partner was 25%. Another study of female college students found a 50% prevalence of the young women had HPV infection. o Approximately 65 million Americans are afflicted with genital herpes, caused by herpes simplex viruses 1 & 2 (HSV). Genital herpes is a painful, recurrent, incurable disease with annual costs estimated to exceed $96 million. Serological evidence of genital herpes infection suggests that rates increase rapidly during adolescence. Estimated annual cases of genital herpes in teenagers and young adults in the U.S. increased from 15,000 yearly visits in 1966 to about 100,000 by 1995. o Both ulcerative and non-ulcerative STDs increase the risk of human immunodeficiency virus (HIV) transmission approximately 3-5 fold, independent of the effect of sexual behavior; and HIV infection, which decreases immune function, may alter the natural history and increase the prevalence of some STDs. One in five cases of AIDS is diagnosed in young people 20-29 years of age; given the length of the incubation period between HIV infection and onset of AIDS, virtually all of these people became infected as teenagers. Objectives and Scope In spite of decades of STD prevention and control programs and STD research, rates of infection continue to grow. The alarming dimensions of STDs and related health problems described above point to the need for more effective research that will lead to essential tools for preventing and controlling STDs, especially in adolescent populations. The 1996 report of the Institute of Medicine, "The Hidden Epidemic - Confronting Sexually Transmitted Diseases" identified adolescents as an underserved population that requires special emphasis in both STD research and STD service delivery. The report encourages efforts in prevention that are dependent upon the development of new biomedical tools (vaccines, topical microbicides and diagnostic tests), interventions and paradigms that are likely to be more effective for prevention and control of STDs in adolescent populations. The STD CRCs have been developed as multi-disciplinary research efforts that integrate clinical observations into basic biomedical research; apply the findings of basic research to the development of improved diagnostics, therapeutics, vaccines and topical microbicides; and integrate behavioral and epidemiological research needed to ensure the optimal utilization of these tools. The purpose of this RFA is to stimulate multi-disciplinary, collaborative research to further understanding of STDs in adolescent populations and to develop and evaluate effective approaches to STD prevention and control. The scientific complexity of the STD problems is such that coordinated, multi-disciplinary research is required to solve these problems. This will be accomplished through collaborations among scientists from various disciplines working in the scientific areas of biomedical, clinical, behavioral, and epidemiological research. In this RFA, the term scientific area refers to the four broad categories of investigation: (1) biomedical, (2) clinical, (3) behavioral, and (4) epidemiological research. The term discipline refers to investigators' specialized areas of expertise or training. Some examples of disciplines associated with the four scientific areas include but are not limited to (1) reproductive endocrinology, immunology, virology, and molecular biology; (2) gynecology, infectious diseases, and adolescent medicine; (3) psychology, sociology, and anthropology; (4) epidemiology, biostatistics, and computer modeling. Research on HIV infection is supported by the Division of Acquired Immunodeficiency Syndrome (DAIDS) and is not included in the scope of this RFA except in studies where it is directly linked to research on STDs as risk factors for HIV transmission or in alteration of the natural history of STDs. Applications must include: o at least three research projects: one should be in behavioral or epidemiological research in adolescent populations (of particular interest is research on social networks; and two or more projects that link disciplines within a single scientific area and at least one project that links disciplines in two different areas (disciplines and scientific areas are defined above); o research on two or more STD pathogens or syndromes selected from Diseases, Syndromes, and Areas of Interest listed below; o a strong clinical capability in adolescent medicine (described below) with accessible adolescent populations to participate in the clinical and behavioral/epidemiological research projects; and o provisions for the Principal Investigator of each CRC (also known as the CRC Director) to attend meetings with NIAID staff twice each year and for all CRC Project Leaders to attend CRC workshops twice during the program period. Diseases, Syndromes, and Areas of Interest Applicants are encouraged, but not limited, to consider research projects in the following areas: o Pathogens: Chlamydia trachomatis, Neisseria gonorrhoeae, Haemophilus ducreyi, Treponema pallidum, Trichomonas vaginalis, herpes simplex viruses 1 and 2, and human papillomavirus. In designing specific projects, use of human material to address basic research questions is highly recommended. o Adverse Outcomes of Pregnancy: Research is needed to define the epidemiology, pathogenesis, and immunology of STD-related adverse outcomes of pregnancy in adolescent populations. o Human Papillomavirus Infection: The NIAID's priorities in HPV include research on the epidemiology, natural history, pathogenesis, and immunology of infection , diagnosis and treatment in adolescent populations. o Pelvic Inflammatory Disease (PID): Additional research is needed in a number of areas, including diagnosis, epidemiology, pathogenesis, treatment, and long term sequelae. Of particular interest are age-related host factors that influence disease progression including tubal scarring. o Inter-Relatedness of Sexually Transmitted Infections: Because of the HIV epidemic, it is now recognized that infection with one sexually transmitted infection can alter susceptibility to and natural history of other STDs. Understanding the molecular bases of these interactions is needed, especially those that are age-related. For example, research is needed to examine the role of classical STDs in the acquisition and progression of HIV infection and on the role of HIV in alterations of the natural history, diagnosis, or response to treatment of STDs. One project on HIV infection may be included. o Reproductive Endocrinology: The role of reproductive hormonal changes, both endogenous (puberty) and exogenous, on the biology of susceptibility and resistance to infection is a high priority. o Immunology: Basic immunological research related to vaccine development for any of the pathogens or syndromes listed above is of interest. In order to make critical advances in this area vis a vis adolescent populations, functional collaborations between immunologists and microbiologists focused on the immune response in adolescent populations will be extremely important. Work on non- specific defense mechanisms including the role of defensins, normal flora (lactobacilli), mucus and pH is encouraged, especially in the context of changes associated with puberty and the use of hormonal contraceptives . o Behavioral/Epidemiological Research: Behavioral research is needed to decrease risk-associated behaviors and to increase health behaviors, specifically those related to seeking early diagnosis, treatment, and immunization. Also of interest is research on social networks; special attention should be paid to methods and evaluation outcomes that would be useful in characterizing social networks and in designing interventions for social networks. STD CRCs, because of their multi-disciplinary approach, are in a unique position to assess behavioral measures and evaluate interventions. o Topical Microbicides: Basic biomedical and clinical research leading to topical microbicide development to prevent sexually transmitted infections is needed. Topical microbicides are products for intravaginal use that are microbicidal (virucidal and/or bactericidal) but not necessarily spermicidal; they are used by women to prevent sexually transmitted infections (HIV and other STDs). Examples of such research include, but are not limited to, identifying early events in the infectious process, characterizing vaginal physiology and normal flora in adolescent populations, developing methods to measure and assess clinical significance of vaginal/cervical inflammation and comparing changes induced by microbicides in adolescent versus adult women. Clinical Capability As stated earlier, applications must have a strong clinical capability in adolescent medicine and access to adolescent populations to serve the clinical and behavioral and/or epidemiological research projects. In describing the clinical and laboratory facilities, the application should include specific information on the institution's present patient load, projections for patient involvement in future clinical investigations, history of recruitment of subjects, and disease prevalence as well as on the availability of appropriate biohazard facilities and safety procedures. Optional Developmental Component Applications may include a Developmental Fund Core to provide support for new investigators or pilot projects. Eligible investigators are individuals in the early or mid stages of their career who have NOT held an NIH grant including an R29, RO1, PO1, UO1, any research career or training grant (K or T awards), or any other type of grant or contract with annual direct costs in excess of $37,500 for research in STDs. Potential awardees and specific research projects to be pursued need not be identified in the CRC application. However, the application should include a one page description of the kind of project that might be funded under this mechanism and how it interdigitates with CRC research projects. Approval of the developmental funds portion of the application does not in any way commit the investigators to the execution of the sample project. In addition, the application must provide a description of review process and selection criteria for proposed projects. Budget Issues Budget requests within each project may include research-related costs for supplies, patient involvement and medical care, funds for limited investigator travel, and costs of publication. Proposals for studies that do not receive the majority of funding through the CRC will not be counted as a project. There must be concordance between the science proposed and the budget requested. Furthermore, if additional sources of funding have been identified for a project, then letters documenting a funding commitment must be included in the application. STD CRC award funds may be utilized to support the following research-related activities: o PI Level of Effort: The applicant Principal Investigator (STD CRC Director) must allot 15% of time to the administration of the CRC. If less effort is indicated, justification must be provided, including a written plan explaining how they will be able to successfully and fully meet the responsibilities demanded by these endeavors. Effort on scientific projects would be additional. o Shared Research Resources (Cores): The STD CRC may include funds for equipment, supplies, and services to expand and/or maintain clinical, laboratory, biostatistical, or behavioral facilities shared by research staff from at least two research projects. o Advisory group activities: The STD CRC funds may be used to support activities related to acquiring scientific advise from experts in the field. These advisory groups should be constituted after the grant award has been made and should not be named in the application. o Developmental Funds Core for New Investigators: This optional core sets aside and restricts funds solely to cover salaries and research costs for new investigator or pilot projects. There is no ceiling on the total dollar amount of the developmental funds pool, but once identified as developmental funds these monies constitute a restricted portion of the total CRC budget and will not be available for other CRC activities. The annual total amount for each developmental award may not exceed $40,000 and may be used for salary, technical support, laboratory supplies, and equipment. Supplies and equipment expenditures for each award may not exceed $20,000 annually. Projects and investigators funded under the developmental core may not receive subsequent awards from this pool. The duration of support is limited to three years. If the investigator achieves independent funding through a traditional research grant (R01) or a FIRST (R29) award prior to the end of the developmental award, the award must be terminated, and unexpended funds must be returned to the developmental funds pool. In general, the CRC should try to advance learning experiences in STD research and to make medical students, house staff and postdoctoral candidates more aware of STD research opportunities in the clinical, biomedical, and behavioral sciences. It is permissible for projects to include post-residency personnel who spend a maximum of one third of their time in clinical activities related to the research focus of the project. Formal training programs in clinical or basic sciences that include stipends for these students are supported by other funding mechanisms at the NIH, such as the National Research Service Awards (T-32s) and do not, therefore, fall within the purview of this request. Applicants from institutions that have a General Clinical Research Center (GCRC) funded by the NIH National Center for Research Resources may wish to identify the GCRC as a resource for conducting the proposed research. If so, a letter of agreement from either the GCRC program director or principal investigator should be included with the application. SPECIAL REQUIREMENTS Collaborative Organization The application should include a plan to maintain close collaboration and communication among members this STD CRC (and potentially among of the seven other STD CRCs) and an organizational chart showing the name, the organization and the scientific discipline of the Principal Investigator, the Project Leaders, and the key personnel for the projects and cores. The application must also include a signed letter of agreement from each collaborator and/or consultant to the program indicating willingness to participate in the program and a description of the exact nature of the participation. Terms and Condition of Award The following terms and conditions will be incorporated into the award statement and provided to the Principal Investigator as well as the institutional official at the time of award. These special Terms of Award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS Grant Administration Regulations at 45 CFR Parts 74 and 92, and other HHS, PHS, and NIH Grant Administration policy statements. The administrative and funding instrument used for this program is the cooperative agreement (U19), an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH scientific and/or programmatic involvement with the awardee is anticipated during the performance of the activity. Under the cooperative agreement, the NIH purpose is to support and/or stimulate the recipient's activity by involvement in and otherwise working jointly with the award recipient in a partner role, but it is not to assume direction, prime responsibility, or a dominant role in the activity. Awards will be made to an institution on behalf of a Principal Investigator who will be responsible for the coordination of STD CRC scientific and administrative activities. Support of all CRC activities will be coordinated through a Central Operations Office located within the applicant organization. 1. Awardee Rights and Responsibilities Awardees will have primary responsibility for defining the details for the project within the guidelines of the RFA and for performing the scientific activity, and agree to accept close coordination, cooperation, and participation of NIAID staff in those aspects of scientific and technical management of the project described in 2. below. Specifically, awardees have primary responsibilities as described below. Under the Cooperative Agreement, a partnership relationship exists between the recipient of the award and NIAID in which successful applicants are responsive to the guidelines and conditions set forth in the RFA. At the same time, investigators are expected to define research objectives and approaches in accord with their own interests and perceptions of novel and exploitable approaches to the research which ultimately is likely to result in improved prevention and control of STDs. It is the primary responsibility of the Principal Investigator to clearly state the objectives and approaches of the research, to plan and conduct the research stipulated in the proposal, and to ensure that the results obtained are analyzed and published in a timely manner. NIAID may periodically review and generate internal reports >From data and progress reports developed under this cooperative agreement. Awardees will retain custody of and have primary rights to the data developed under this award, subject to Government rights of access consistent with current HHS, PHS, and NIH policies. The multi-disciplinary and collaborative nature of the STD CRCs creates an extraordinary opportunity for information exchange and scientific advancement in STD research. Principal Investigators are expected to take advantage of this opportunity by participation in both formal events established expressly for this purpose and informal investigator-initiated dialogues. 2. NIAID Staff Responsibilities The NIAID will have substantial scientific/programmatic involvement during the conduct of this activity, through technical assistance, advice and coordination above and beyond normal program stewardship for grants, as described below. The NIAID will work closely with the Principal Investigators and shall be represented by a Scientific Coordinator (Program Officer). The Scientific Coordinator will be a program officer in the STD Branch of NIAID. During the award period, the NIAID Scientific Coordinator may provide appropriate assistance, advice, and guidance in: design of research activities; coordination and facilitation of information, technology, and reagent exchange between STD CRCs; data collection and analysis; assistance in review and selection of developmental fund applicants; and technical and administrative activities of CRCs. However, it is again emphasized that the role of NIAID will be to facilitate and not to direct the activities of the STD CRC. It is anticipated that decisions in all activities outlined within this RFA will be reached by consensus of the investigators and that the NIAID Scientific Coordinator will be given the opportunity to offer input to this process. 3. Collaborative Responsibilities The CRC Principal Investigator of the Adolescents and STDs CRC and the other seven STD CRCs and NIAID Scientific Coordinator will meet twice a year to review progress of the CRCs at the NIH in Bethesda, Maryland (or at a site designated by NIAID). The first such meeting will be a Post Award Meeting. In addition, two workshops for the Principal Investigators and CRC Project Leaders will be convened during the project period to share STD research advances, and to discuss STD research needs and opportunities, to develop collaborations. It is likely that workshops will be convened in Year 1 and Year 3 of the project period at the NIH in Bethesda, Maryland (or at a site designated by NIAID). Applicants should be aware that there are no additional travel monies available. Funds for travel to all meetings must be included in applicant's budget. A critical element of the STD CRCs' success is the degree of communication among its members. Therefore, additional informal meetings among participants from other STD CRCs as well as regular telephone and written communication will be encouraged. 4. Arbitration Any disagreement that may arise on scientific/programmatic matters (within the scope of the award) between award recipients and the NIAID may be brought to arbitration. An arbitration panel will be composed of three members -- one selected by the Principal Investigator, a second member selected by the NIAID, and the third member selected by the two prior members. This special arbitration procedure in no way affects the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations at 42 CFR part 50, subpart D, and HHS regulation at 45 CFR part 16. In the event that research supported by the Cooperative Agreement results in development of a therapeutic or other medical intervention, NIAID will retain the option to cross-file or independently file an application for investigational clinical trial (i.e., an Investigational New Drug Application [IND]) to the United States Food and Drug Administration. Reports of data generated by the CRC or any of its members which are required for inclusion in INDs and Clinical Brochures and for cross-filing purposes will be submitted by the Principal Investigator to the Scientific Coordinator upon request. Such reports will be in final draft form and include background information, methods, results, and conclusion. They will be subject to approval and revision by NIAID and may be augmented with test results from other Government sponsored projects prior to submission to the appropriate regulatory agency. STUDY POPULATIONS A strong emphasis is placed on studying STDs in adolescent populations that are disproportionately affected. These populations include women and minorities. Subjects may be recruited or specimens obtained from domestic sites or through collaborations with foreign institutions in developing countries if the collaboration is beneficial to the foreign country and offers the potential for collection of STD data that are pertinent to U.S. populations and could not be generated as effectively in the United States. INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of the NIH that women and members of minority groups and their subpopulations must be included in all NIH supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification are provided that inclusion is inappropriate with respect to the health of the subjects of the purpose of the research. This policy results >From the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing research involving human subjects should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research", which have been published in the Federal Register of March 28, 1994 (FR 59 14508-14513) and the NIH Guide for Grants and Contracts, Vol. 23, No. 11, March 18, 1994. Investigators may obtain copies from these sources or from the program staff listed under INQUIRIES. Program staff may also provide additional relevant information concerning the policy. LETTER OF INTENT Prospective applicants are asked to submit, by October 15, 1997, a letter of intent that includes a descriptive title of the overall proposed research; the name, address, and telephone number of the Principal Investigator; a list of the key investigators and their institution(s), and the number and title of the RFA in response to which the application may be submitted. Although the letter of intent is not required, is not binding, does not commit the sender to submit an application, and does not enter into the review of subsequent applications, the information that it contains allows NIAID staff to estimate the potential review workload and to avoid conflict of interest in the review. The letter of intent is to be sent to Dr. Madelon Halula at the address listed under INQUIRIES. APPLICATION PROCEDURES Before preparing an application, the applicant should carefully read the new information brochure accompanying the RFA, "NIAID Program Project Grants and Multiproject Cooperative Agreements". Instructions for formatting the application as outlined in the brochure should be followed carefully. Failure to follow the instructions may result in unnecessary delays in the review process. Applications are to be submitted on the standard research grant application form PHS 398 (rev. 5/95). Application forms are available at most institutional offices of sponsored research and >From the Division of Extramural Outreach Information Resources, National Institutes of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone (301) 435-0714, email: asknih@odrockm1.od.nih.gov. Applications from multi-component consortia must contain a single face page, an overall budget page, and separate budget pages for each institution involved. The RFA label available in the PHS 398 (rev. 5/95) application form must be affixed to the bottom of the face page of the application. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2 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 6701 ROCKLEDGE DRIVE - MSC 7710 BETHESDA, MD 20892-7710 BETHESDA, MD 20817 (for express/courier service) At the time of submission, two additional exact copies of the grant application and five sets of appendix material must also be sent to: Dr. Madelon Halula Division of Extramural Activities National Institute of Allergy and Infectious Diseases 6003 Executive Boulevard, Room 4C-16 Bethesda, MD 20892 Rockville, MD 20852 (for express/courier service) Applications must be received by the January 8, 1998. All components, subparts and sections of the application must be collated into the application, and the packages sent to the DRG and to the NIAID must each be complete in themselves. Applications that do not conform to the instructions contained in PHS 398 (rev. 5/95) application kit will be judged nonresponsive and will be returned to the applicant. Current NIH policy permits a component research project of a multiproject grant application to be concurrently submitted as a traditional individual research project (R01) application. If, following review, both the multiproject application and the R01 application are found to be in the fundable range, the investigator must relinquish the R0l and will not have the option to withdraw from the multiproject grant. This is an NIH policy intended to preserve the scientific integrity of a multiproject grant, which may be seriously compromised if a strong component project(s) is removed >From the program. Investigators wishing to participate in a multiproject grant must be aware of this policy before making a commitment to the Principal Investigator and awarding institution. REVIEW CONSIDERATIONS Review Method Upon receipt, applications will be reviewed for completeness by the Division of Research Grants (DRG) and for responsiveness by NIAID staff. Incomplete and non-responsive applications will be returned to the applicant without further consideration or review. As part of the initial merit review, a process may be used by the initial review group in which applications will be determined to be competitive or non-competitive based on their scientific merit relative to other applications received in response to the RFA. Applications judged to be competitive will be discussed and assigned a priority score. The NIAID will remove from competition those applications judged to be non-competitive for award and will notify the Principal Investigators and institutional business officials. For applications found non-competitive, summary reports will be very brief and will only highlight the major reason(s) for the non- competitive rating. Those applications judged by the reviewers to be competitive for award will be further reviewed for scientific and technical merit by a review committee convened by the Division of Extramural Activities, NIAID. The second level of review will be provided by the National Advisory Allergy and Infectious Diseases Council. Review Criteria The review criteria are stated in the NIAID Program Project Grants and Multiproject Cooperative Agreements brochure which accompanies the RFA. In addition, applicants are expected to address research priorities, objectives, and other requirements stated in this RFA as well as the following: o the scientific and technical significance, merit, and originality of the research projects and anticipated contributions to the prevention and control of STDs; o the scientific expertise and experience of the Principal Investigator, the Project Leaders and key project and core personnel; o documentation of a strong capability in adolescent medicine, adequate and appropriate patient populations, disease prevalence, and historical success of recruitment and retention of subjects; o inclusion of populations that are not currently represented in existing STD CRCs; o documentation of the sponsoring institution's commitment to the cooperative program and willingness to accept the participation and assistance of NIAID staff; o adequacy of proposed plan for coordination and communication within the applicant STD CRC and with NIAID and other STD CRCs; and o adequacy of review plan and selection criteria for new investigators making application to the optional Developmental Funds. In addition, applications from existing STD CRCs must include a comprehensive progress report (as stated above under Objectives and Scope) and demonstrate successful collaborative activities supported through their CRC. Applicants who have not had an STD CRC should explain how they will establish successful collaborative efforts. AWARD CRITERIA Funding decisions will be made on the basis of scientific and technical merit as determined by peer review, program priorities and balance, and availability of funds. Program balance takes into account pathogen(s) proposed for study, the potential impact on health of women, minorities and adolescents, as well as geographic distribution of the existing CRCs (of particular interest is access to populations that are currently not being studied in other STD CRCs). INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Dr. Penelope J. Hitchcock Division of Microbiology and Infectious Diseases National Institute of Allergy and Infectious Diseases 6003 Executive Boulevard, Room 3A-24 Bethesda, MD 20892 Bethesda, MD 20852 (for express/courier service Telephone: (301) 402-0443 Email: ph22k@nih.gov Direct inquiries regarding review issues, address the letter of intent to, and mail two copies of the application and all five sets of appendices to: Dr. Madelon Halula Division of Extramural Activities National Institute of Allergy and Infectious Diseases 6003 Executive Boulevard, Room 4C-16 Bethesda, MD 20892 Bethesda, MD 20852 (for express/courier service Telephone: (301) 402-2636 FAX: (301) 402-2638 Email: mh30x@nih.gov Direct inquiries regarding fiscal matters to: Ms. Sharie Bernard Division of Extramural Activities National Institute of Allergy and Infectious Diseases 6003 Executive Boulevard, Room 4B-33 Bethesda, MD 20892 Telephone: (301) 496-7075 Schedule Letter of Intent Receipt Date: October 15, 1997 Application Receipt date: January 8, 1998 Scientific Review Date: April 1998 Advisory Council Date: June 1998 Earliest Award Date: August 1998 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.855 Immunology, Allergic and Immunological Diseases Research and 93.856 Microbiology and Infectious Diseases Research. Grants are awarded 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 at 42 CFR Part 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of the Executive Order 12372 or Health Systems Agency review. The PHS and EPA strongly encourage all grant recipients to provide a smoke-free workplace and promote the non-use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or, in some cases, any portion of a facility) in which regular or routine education, library, day care, health care, or early childhood development services are provided to children. This is consistent with the EPA and PHS missions to protect and advance the physical and mental health of the American people. ADDENDUM STD CRCs can serve as important resources to increase awareness of the prevention, diagnosis, and treatment of STDs in the public health, the lay and the local medical communities. The NIAID has been involved with the Centers for Disease Control's (CDC) Accelerated Research Program in STDs. Several proposed projects for this CDC program involve collaborations between the existing STD CRCs and state and local health departments. Applicants with interest in this area should contact the Division of STDs/HIV, National Center for Prevention Services, CDC for information on support of outreach projects. From owner-sci-resources@net.bio.net Mon Sep 01 23:00:00 1997 Path: biosci!biosci!not-for-mail From: BIOSCI Administrator Newsgroups: bionet.sci-resources Subject: NIH GUIDE - PA-97-099 - V26(29) 08/29/97 Date: 2 Sep 1997 14:39:50 -0700 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 359 Sender: daemon@net.bio.net Approved: biosci-help@net.bio.net Distribution: world Message-ID: <5ui136$ks1@net.bio.net> NNTP-Posting-Host: net.bio.net GENES AND MECHANISMS UNDERLYING PRIMARY IMMUNODEFICIENCY NIH Guide, Volume 26, Number 29, August 29, 1997 PA NUMBER: PA-97-099 P.T. National Institute of Allergy and Infectious Diseases National Institute of Child Health and Human Development PURPOSE The National Institute of Allergy and Infectious Diseases (NIAID) and the National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), invite applications for research studies to: identify and characterize genes that cause primary immunodeficiency diseases; characterize the molecular mechanisms involved in primary immunodeficiency diseases which are not the result of a single defective gene; identify the immunologic role of defective gene products and their normal counterparts; and, based on this knowledge, develop more effective approaches for the diagnosis, treatment, and prevention of these 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. This Program Announcement, "GENES AND MECHANISMS UNDERLYING PRIMARY IMMUNODEFICIENCY", is related to the priority areas of Maternal and Infant Health and Diabetes and Chronic Disabling Diseases. 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 202-512-1800). ELIGIBILITY Applications may be submitted by 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. Domestic and foreign institutions are eligible to apply for R01 grants.