From owner-sci-resources@net.bio.net Fri Feb 04 22:00:00 1994 Path: biosci!biosci!not-for-mail From: Dave Kristofferson Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 23, no. 4, 28 January 1994 Date: 4 Feb 1994 21:09:56 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 726 Approved: biosci-moderator@net.bio.net Distribution: bionet Message-ID: <2iv9n4$cms@net.bio.net> NNTP-Posting-Host: net.bio.net $$XID NIHGUIDE 19940128 V23N04 P1O1 ************************************ No RFAs present NIH GUIDE - Vol. 23, No. 4 - January 28, 1994 $$INDEX BEGIN ******************************************************* NOTICES $$INDEX N1 ********************************************************** IMMUNE RESPONSES TO LYME DISEASE INFECTION AND VACCINATION (AI-94-008) National Institute of Allergy and Infectious Diseases National Institute of Arthritis and Musculoskeletal and Skin Diseases INDEX: ALLERGY, INFECTIOUS DISEASES; ARTHRITIS, MUSCULOSKELETAL, SKIN DISEASES NOTICES OF AVAILABILITY (RFPs AND RFAs) $$INDEX R1 ********************************************************** SYNTHESIS OF CONGENERS AND PRODRUGS (RFP NCI-CM-47012-20) National Cancer Institute INDEX: CANCER $$INDEX R2 ********************************************************** PHYSICAL ACTIVITY INTERVENTION IN HEALTH-CARE SETTINGS FOR HIGH-RISK SEDENTARY ADULTS - COORDINATING CENTER (RFP NHLBI-HC-94-07) National Heart, Lung, and Blood Institute INDEX: HEART, LUNG, BLOOD $$INDEX R3 ********************************************************** SURFACE MODIFICATION FOR BIOCOMPATIBILITY (RFP NIH-NINDS-94-04) National Institute of Neurological Disorders and Stroke INDEX: NEUROLOGICAL DISORDERS, STROKE ONGOING PROGRAM ANNOUNCEMENTS $$INDEX P1 ********************************************************** RESEARCH ON ORAL WOUND HEALING AND TISSUE REGENERATION (PA-94-031) National Institute of Dental Research INDEX: DENTAL RESEARCH This publication is available electronically to institutions via BITNET or INTERNET and is also on the NIH GOPHER. Alternative access is through the NIH Grant Line using a personal computer (data line 301/402-2221). Contact Dr. John James at 301/594-7270 for details. $$INDEX END ********************************************************* NOTICES $$N1 BEGIN ********************************************************** IMMUNE RESPONSES TO LYME DISEASE INFECTION AND VACCINATION NIH GUIDE, Volume 23, Number 4, January 28, 1994 RFA: AI-94-008 P.T. National Institute of Allergy and Infectious Diseases National Institute of Arthritis and Musculoskeletal and Skin Diseases Letter of Intent Receipt Date: February 7, 1994 Application Receipt Date: March 18, 1994 The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) will join with the National Institute of Allergy and Infectious Diseases (NIAID) to co-sponsor the Request for Application (RFA) AI-94-008 entitled "Immune Responses to Lyme Disease Infection and Vaccination," published in the NIH Guide for Grants and Contracts Vol. 23, No. 1, January 7, 1994. The NIAMS has a continuing interest in the support of research on Lyme disease, particular its chronic and arthritic manifestations. Applications received in response to this RFA that focus on issues relating to chronic Lyme disease, particularly arthritis, will be considered for funding by both the NIAID and NIAMS. INQUIRIES Interested investigators are encouraged to contact Program Staff to discuss potential applications and to obtain the full text of the amended RFA. Inquiries may be addressed to: Dr. Susana A. Serrate-Sztein Rheumatic Diseases Branch National Institute of Arthritis and Musculoskeletal and Skin Diseases Westwood Building, Room 405 Bethesda, MD 20892 Telephone: (301) 594-5593 FAX: (301) 480-7881 $$N1 END ************************************************************ NOTICES OF AVAILABILITY (RFPs AND RFAs) $$R1 BEGIN NCI-CM-47012-20 ****************************************** SYNTHESIS OF CONGENERS AND PRODRUGS NIH GUIDE, Volume 23, Number 4, January 28, 1994 RFP AVAILABLE: NCI-CM-47012-20 P.T. National Cancer Institute The Drug Synthesis and Chemistry Branch (DS&CB) of the Developmental Therapeutics Program (DTP), Division of Cancer Treatment (DCT), National Cancer Institute (NCI) is seeking contractors with expertise in chemical synthesis and drug design to synthesize a variety of compounds for evaluation as potential anti-AIDS or anti-cancer agents. The assigned objectives of this project are to design and synthesize the following: (a) congeners of lead compounds having confirmed activity to enhance activity or potency; (b) prodrugs with structural modifications that may provide altered pharmacokinetics, altered drug transport, improved bio-availability through increased water solubility, or increased chemical stability; (c) other altered structures that possess elements of both congeners and prodrugs; and (d) compounds related to natural products, e.g., alkaloids, heterocycles, nucleosides, and peptides. Each contractor should have available a fully operational facility, including all necessary equipment and instrumentation for all aspects of the contract. The nature of this project requires that the following restriction be applied: "The NCI signs legally binding agreements with certain suppliers (often pharmaceutical or chemical companies) that state that all information on compounds submitted by the supplier will be held confidential. The successful offeror will be expected to synthetically modify such commercially confidential (discreet) materials. Thus, pharmaceutical or chemical companies could obtain valuable data on new lead compounds. Therefore, in order to honor the confidentiality agreement with the original supplier, the NCI believes that the compounds cannot be sent to potential competitors of the supplier, and thus pharmaceutical and chemical companies must be excluded from the competition." For purposes of this restriction, a pharmaceutical or chemical company is defined as an organization that sells drugs and chemicals to the general public for profit. The Standard Industrial Classification (SIC) number is 8731. This is a recompetition of contracts currently held by the Georgia Tech Research Corporation (Georgia Institute of Technology), Purdue Research Foundation, and the University of Tennessee. It is anticipated that two cost-reimbursement contracts will be awarded for a period of two years beginning on or about September 30, 1994. INQUIRIES Request for Proposals (RFP) No. NCI-CM-47012-20 will be issued on or about January 31, 1994 and proposals will be due approximately 30 days thereafter. Copies of the RFP may be obtained by sending a written request to: Charles Lerner Research Contracts Branch, TCS National Cancer Institute Executive Plaza South, Room 603 Bethesda, MD 20892 Telephone: (301) 496-8603 $$R1 END ************************************************************ $$R2 BEGIN NHLBI-HC-94-07 ****************************************** PHYSICAL ACTIVITY INTERVENTION IN HEALTH-CARE SETTINGS FOR HIGH-RISK SEDENTARY ADULTS - COORDINATING CENTER NIH GUIDE, Volume 23, Number 4, January 28, 1994 RFP AVAILABLE: NHLBI-HC-94-07 P.T. National Heart, Lung, and Blood Institute The National Heart, Lung, and Blood Institute (NHLBI) is soliciting proposals for a Coordinating Center to participate in a multicenter clinical trial designed to develop and evaluate the effectiveness of various intervention approaches delivered in health-care settings in increasing and maintaining physical activity and cardiorespiratory fitness among sedentary men and women at elevated risk of coronary heart disease (CHD) by blood pressure (BP) or lipoprotein criteria. The study will also examine the cost-effectiveness of the various intervention approaches as well as the magnitude of effects on BP, lipoproteins, and weight and the long-term maintenance of those effects. In addition to one Coordinating Center to be awarded under RFP No. NHLBI-HC-94-07, an estimated total of three clinical center contracts will be awarded under a separate RFP. The Coordinating Center will have responsibility for the overall coordination, monitoring, and central management of all activities, including data entry and management, quality control, data analysis, and collaborative development of the study protocol, manual of operations, interventions, and data collection procedures. The Coordinating Center will also be charged with the responsibility of competitively selecting a Central Blood Laboratory to perform as a subcontract to the Coordinating Center after contract award. A planned total of 810 adult subjects will be randomized into three intervention groups and one comparison group. This will be a five year study with a projected award date of September 30, 1994. The primary study outcomes will be cardiorespiratory fitness (i.e., maximum oxygen uptake) and physical activity (frequency, intensity, duration, and estimated caloric expenditure). Because of the need for scientifically comparable data in a defined population and relevance to the U.S. health care system, offerors other than U.S. institutions will not be considered. This procurement will be a new award and is open to all offerors who meet the determination of responsibility as defined by FAR 9.104. INQUIRIES Request for Proposals (RFP) No. NHLBI-HC-94-07 is now available. Letters of Intent will be due two weeks after the release date of the RFP. Proposals will be due on March 21, 1994. All requests for this RFP must be submitted in writing, verbal requests will not be accepted. Written requests must reference RFP No. NHLBI-HC-94-07, include three self-addressed mailing labels, and be addressed to: John C. Taylor Contracting Office National Heart, Lung, and Blood Institute 7550 Wisconsin Avenue Federal Building, Room 200 Bethesda, MD 20892 Telephone: (301) 496-9655 $$R2 END ************************************************************ $$R3 BEGIN NIH-NINDS-94-04 ****************************************** SURFACE MODIFICATION FOR BIOCOMPATIBILITY NIH GUIDE, Volume 23, Number 4, January 28, 1994 RFP AVAILABLE: NIH-NINDS-94-04 P.T. National Institute of Neurological Disorders and Stroke The Neural Prosthesis Program of the National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health, is seeking a contract to create surfaces on implantable silicon microstructures for the purpose of controlling the interaction of neurons, glia, and related cells and their protein products with the microstructure. Biomaterials that penetrate into the central nervous system as the microscopic electrode shafts of the neural prostheses interact with neural and other tissues on a cellular and molecular level. In order to achieve tight coupling between these implanted microelectrodes and the target neural substrate, this interaction must be understood and controlled. This contract supported research will study these interactions with a long-term goal of rationally designing microelectrode surfaces to promote specific tissue interactions. The efficiency of these microelectrodes depends on the micro environment around stimulating sites. The surface of the microelectrodes and the proteins that adsorb to this surface have a major impact on the way in which different cell populations react to the implant. Neural growth cones are sent out from many neurons around a microelectrode following implantation. With appropriate surfaces it may be possible to get selected neurons to send processes directly to the microelectrodes. This study will investigate cellular and molecular responses to specific surface modifications of silicon microelectrodes. Personnel with established expertise in cell biology and surface science are needed. It is anticipated that one award will be made for a period of three years. Award is anticipated for September 1994. INQUIRIES This is not a Request for Proposals (RFP). RFP NIH-NINDS-94-04 will be issued on or about February 1, 1994 with proposals due on April 4, 1994. To receive a copy of the RFP, submit a written request along with two self-addressed mailing labels to: Laurie Leonard Contracts Management Branch National Institute of Neurological Disorders and Stroke Federal Building, Room 901 7550 Wisconsin Avenue Bethesda, MD 20892 ATTN: RFP NIH-NINDS-94-04 All responsible sources shall be considered by the agency. $$R3 END ************************************************************ ONGOING PROGRAM ANNOUNCEMENTS $$P1 BEGIN PA-94-031 ************************************************ RESEARCH ON ORAL WOUND HEALING AND TISSUE REGENERATION NIH GUIDE, Volume 23, Number 4, January 28, 1994 PA NUMBER: PA-94-031 P.T. National Institute of Dental Research PURPOSE The National Institute of Dental Research (NIDR) invites investigator-initiated grant applications to conduct multidisciplinary basic and clinical research on wound healing and tissue regeneration associated with the orofacial region. Applications that address the healing, regeneration and repair of oral tissues following periodontal diseases, trauma, and surgical treatment of birth defects such as cleft lip and palate and cancer are sought through this Program Announcement (PA). 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, Oral Wound Healing and Tissue Regeneration, is related to the priority area of oral health. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign, non-profit and for-profit, public and private organizations, such as dental or medical schools, universities and research institutions. Foreign institutions are not eligible for the First Independent Research Support and Transition (FIRST) Award (R29). Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT The mechanisms available for the support of research in response to this PA include the traditional research project grant (R01), FIRST (R29) Award, small grant (R03), and Interactive Research Project Grants. Responsibility for the planning, direction, and execution of the projects will be solely that of the applicants. RESEARCH OBJECTIVES Background Wound healing is a complex process in which a variety of cellular and matrix components act in concert to reestablish the integrity of injured tissue. The complexity of this process may be simplified into four broad categories of the healing response that coincide with the temporal sequence of normal healing: hemostasis; inflammation; cell proliferation (repair); and tissue remodelling. The problems of repair and regeneration of orally related tissues, however, have certain unique features. For example, materials used in osseous reconstruction of the jaw must withstand extreme physical stresses. Moreover, the presence of teeth in the wound area can expose the underlying tissues of the oral environment and thus complicate the healing process. In addition, microorganisms and the host response to microorganisms in the oral cavity can prevent or significantly prolong healing of damaged tissues. The purpose of this PA is to further both basic and clinical research relevant to wound healing and tissue regeneration following periodontal diseases as well as various types of orofacial trauma, such as surgical treatment of cleft lip and palate, ablation and reconstructive treatment for cancer of the orofacial area, and regeneration of functional salivary glands following chemotherapy and radiation. A brief description of the relevant portions of the three major NIDR program areas covered by this PA follows. Craniofacial Injuries and Disorders The craniofacial region is especially susceptible to injuries and wounds resulting from motor vehicle crashes, motorcycle and bicycle related accidents, injuries associated with sports and recreation, and interpersonal violence. Additional sources of trauma include surgical correction of congenital craniofacial deformities. Successful management of injuries and wounds of the craniofacial structures presents unique challenges. The diversity of tissues and structures in close proximity to each other and the variety of functions in which they participate, including speech, hearing, breathing, mastication and swallowing, compound the problem of treating orofacial trauma. Wound healing following reconstructive surgery must often accommodate tissue deficits, such as large bony defects, thus compounding problems of the wound healing process. Oral Cancer The management of cancer of the orofacial complex similarly presents a unique challenge to the health care profession. Cancer therapy may involve surgery, chemotherapy, radiation therapy, or any combination of the three. The variety of tissues that comprise the orofacial complex (e.g., glandular secretory tissues, connective and mucosal tissues) respond in select fashion to ablative and reconstructive treatment of tumors of the head and neck. Restoration of optimal function and normal appearance is a principal goal of the care and management of tumors of the head and neck. Because of the recurring nature of many types of cancers, therapy frequently must be repeated, often complicating the healing process. A serious side effect of therapy, especially that involving radiation or chemotherapy, is damage to the salivary glands and the immune system, which can in turn lead to a general impairment of healing, repair, and regeneration of the oral tissues. Periodontal Diseases Periodontal diseases comprise a group of related microbial- induced chronic inflammatory disorders that destroy the tissues supporting the teeth. These diseases can result in loss of substantial bone and soft tissue around the affected teeth, which challenges the clinician's efforts to restore full structure and supporting function to the periodontium. Periodontal healing is complicated by microbial recolonization of the subgingival sulcus, systemic diseases (e.g., diabetes), conditions in which there is direct bone contact with the root cementum (ankylosis), and the downward migration of epithelial cells, which prevents the reattachment of the fibrous periodontal ligaments to the cementum and alveolar bone. Major goals of periodontal therapy are, therefore, to inhibit microbial recolonization, prevent epithelial interference with proper integration of the soft and hard tissues, accelerate complete reformation of the lost alveolar bone without ankylosis or root resorption, reestablish a complete periodontal ligament network, and restore healthy gingival soft tissues. Major gaps exist in our understanding of the mechanisms by which healing of the periodontium can be accelerated and or enhanced by the clinician. Guided tissue regeneration of the periodontium, for example, while no longer considered experimental, remains an evolving technology requiring further research. Scope A selection of research topics appropriate for this PA is identified below. This list is illustrative and not exclusive, restrictive or in priority order. Investigators are encouraged to submit scientifically meritorious applications in any area of research responsive to the overall research objectives of this PA. Projects should be founded on a strong hypothesis as evidenced by preliminary data. Prior experience of the investigative team is an important element in demonstrating the likely success of the research proposed. o Molecular and Cellular Basis of Healthy Tissues Investigations that address the molecular and cellular characteristics of healthy oral tissues and their mechanisms for regeneration are central to understanding the goals of successful wound healing therapy. These studies include the role of cell adhesion molecules, isolation and characterization of tissue progenitor cells, normal gene expression in oral tissues, and molecular basis of homeostatic tissue cell replacement. In addition, studies of the influence of anatomical features, such as tooth root furcations, on proper healing of the oral tissues are needed. Investigations that identify cell lineages (e.g., cementoblasts) associated with periodontal wound healing are also appropriate. Also, studies that would advance an understanding of the molecular and cellular basis of periodontal guided tissue regeneration, as well as improve the methodology involved, are strongly encouraged. o Cytokines, Growth Factors, and Biological Response Modifiers Cytokines and polypeptide growth factors, including angiogenic growth factors and bone morphogenetic proteins, have been shown to regulate many of the processes involved in wound healing both in vitro and in animal models. The precise role of these factors in wound healing in the orofacial area requires further delineation. As some growth factors affect specific stages of healing and cell types in a temporal manner, it may be necessary to combine certain growth factors for complex wounds and to determine the optimal time for delivery of the factors. Furthermore, biological response modifiers that can control the activities of cytokines and growth factors need to be identified and characterized. The use of genetic therapies to deliver the genes for these proteins to the injured or defective sites represents an exciting contemporary approach for enhancing orofacial wound healing. o Biomaterials Development of new bone-derived, metallic, and synthetic materials for osseous reconstruction is central to the advancement of repair and regeneration of craniofacial and periodontal tissues. Moreover, the use of bone-inductive techniques with appropriate biodegradable and non-biodegradable scaffolding materials appears to offer new modalities for the treatment of congenital or acquired bone defects. Also, studies are needed to develop methods to evaluate the long-term performance of biomaterials, such as hydroxyapatite, ceramic, and coral implants, which are used in the repair of orofacial bone defects. Recent advances in the use of modified collagen matrices for the reconstruction of oral soft tissue, including the mucosal surfaces of the mouth, promise improved materials for soft tissue regeneration. Resorbable barrier materials, such as those used in guided tissue regeneration, are needed to prevent migration of tissues that interfere with structural and functional repair of the oral tissues. o Nutrition Wound healing is affected by a wide variety of metabolic and nutritional factors. Their effects on reparative and defense mechanisms are complex, additive and often synergistic. Studies are needed to determine the effects of nutritional factors on the regenerative process of oral tissues. Since metabolic and nutritional deficiencies can increase oral tissue susceptibility to injury and prolong the healing process, studies that will identify and establish effective treatment plans to prevent or correct the deficiencies are needed. o Aging, Systemic and Behavioral Conditions Studies are needed to clarify the mechanisms through which aging, systemic diseases (e.g., diabetes, Paget's disease), and behavioral practices (e.g., alcohol consumption, smoking) influence oral wound healing. Studies are also needed to develop improved means for promoting oral wound healing under such adverse conditions. o Radiation and Chemotherapy Radiation and chemotherapy have profound effects on the immune system, cell proliferation and tissue growth. These treatments appear to influence the healing process. Studies are therefore needed to define the effects of radiation and chemotherapy on, for example, production of cytokines and growth factors by oral tissues, the stability and integration of reconstructive biomaterials, and the molecular mechanisms involved in oral tissue damage. o Models of Oral Wounds The investigation of oral wound healing has been hampered by a lack of in vitro and suitable animal models. Furthermore, sensitive methods to quantify the histological, immunological, and biochemical events in the wound are needed. Models are needed in which it would be possible to study the effect of, for example, chronic inflammation, cytokines and growth factors, biomaterials, free radicals, aging, diabetes, or tobacco smoke on orofacial wound healing. The use of transgenic and gene knockout animals might provide important models for studying oral wound healing. o Technology Transfer and Clinical Application of Basic Science This PA encourages collaborative research efforts among clinicians, materials scientists, and basic scientists to transfer the knowledge gained in the laboratory to the clinical arena. Cooperative efforts between universities and for-profit as well as not-for-profit private organizations are encouraged in order to develop commercial applications that promote oral wound healing. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for clinical research grants and cooperative agreements are required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis should be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale must be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues should be addressed in developing a research design and sample site appropriate for the scientific objectives of the study. This information should be included in form PHS 398 (rev. 9/91) in items l-4 of the Research Plan and summarized in item 5, Human Subjects. Applicants are urged to carefully assess the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all such projects to include representation of the full array of United States racial, ethnic minority populations (i.e., Native Americans [including American Indians or Alaskan Natives], Asian/Pacific Islanders, Blacks, Hispanics). The rationale for studies on single minority population groups should be provided. For the purpose of this policy, clinical research is defined as human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including but not limited to clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded. However, every effort should be made to include human tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. For foreign awards, the policy on inclusion of women applies fully; since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. If the required information is not contained within the application, the application will be returned. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question(s) addressed or the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and will be reflected in assigning the priority score to the application. All applications for clinical research submitted to the NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. APPLICATION PROCEDURES Applications are to be submitted on grant application form PHS-398 (rev. 9/91), which may be obtained from the Office of Grants Information, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone 301-594-7248, and from the institution's office of sponsored research. To identify the application as a response to this PA, check "YES" on item 2a on the face page of the application and enter PA-94-031, "Wound Healing and Tissue Regeneration." Applications will be accepted at the standard application deadlines indicated in the application kits. Applications for the FIRST Award (R29) must include at least three sealed letters of reference attached to the face page of the original application. FIRST Award (R29) applications submitted without the required number of reference letters will be considered incomplete and will be returned without review. A signed, typewritten original of the application, and five signed photocopies, in one package must be submitted to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** REVIEW CONSIDERATIONS Applications will be assigned on the basis of established PHS referral guidelines. Applications will be reviewed for scientific and technical merit by initial review groups of the Division of Research Grants, NIH, or by the review group of the relevant Institute in accordance with the standard NIH peer review procedures. Following scientific-technical review, applications will receive a second level review by the appropriate national advisory council or board. AWARD CRITERIA Applications will compete for available funds with all other approved applications assigned to that institute, center or division. The following will be considered in making funding decisions: o Quality of the proposed project as determined by peer review o Availability of funds o Program balance among research areas of the announcement. INQUIRIES Written and telephone inquiries concerning this PA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Mohandas Bhat, M.D.S, Dr.P.H. Director, Craniofacial Development and Disorders Program Telephone: (301) 594-7648 Matthew A. Kinnard, Ph.D. Director, Oral Soft Tissue Diseases and AIDS Program Telephone: (301) 594-7641 Dennis F. Mangan, Ph.D. Director, Periodontal Diseases Program Telephone: (301) 594-7641 Extramural Program National Institute of Dental Research Westwood Building Room 509 Bethesda, MD 20892 Direct inquiries regarding fiscal matters to: Ms. Theresa Ringler Grants Management Office National Institute of Dental Research Westwood Building, Room 510 Bethesda, MD 20892 Telephone: (301) 594-7629 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.121. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158,(42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$P1 END ************************************************************ **THE MAILING ADDRESS GIVEN FOR SENDING APPLICATIONS TO THE DIVISION OF RESEARCH GRANTS OR CONTACTING PROGRAM STAFF IN THE WESTWOOD BUILDING IS THE CENTRAL MAILING ADDRESS FOR THE NATIONAL INSTITUTES OF HEALTH. APPLICANTS WHO USE EXPRESS MAIL OR A COURIER SERVICE ARE ADVISED TO FOLLOW THE CARRIER'S REQUIREMENTS FOR SHOWING A STREET ADDRESS. THE ADDRESS FOR THE WESTWOOD BUILDING IS: 5333 Westbard Avenue Bethesda, MD 20816 From owner-sci-resources@net.bio.net Mon Feb 07 22:00:00 1994 Path: biosci!biosci!not-for-mail From: Dave Kristofferson Newsgroups: bionet.sci-resources Subject: NSF - Summary of new documents on STIS - 30 January 1994 Date: 4 Feb 1994 21:03:29 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 104 Approved: biosci-moderator@net.bio.net Message-ID: <2iv9b1$c1u@net.bio.net> This message contains a summary of the documents added to the NSF STIS system in the previous week. Reference material concerning STIS follows the summary. ------------------------------------------------------------------------ ** NEW DOCUMENTS ON STIS ** Document Type: Bulletin Title: NSF Bulletin December 1993, Volume 21, No. 4 File size (bytes): 37798 STIS Filename: bul9312 Document Type: General Publication Title: N S F RELOCATION IS FINALIZED File size (bytes): 832 STIS Filename: ldasltr Document Type: Program Guideline Title: Management of Technological Innovation 1993 Focus on Management of Innovation for Environmentally Conscious Manufacturing File size (bytes): 17344 STIS Filename: nsf9363 Title: NSF 94-5 - Networking Infrastructure for Education Supplements, New Projects and Planning Grants File size (bytes): 24405 STIS Filename: nsf945 Title: NSF Institute for Science Education File size (bytes): 15655 STIS Filename: nsf946 Document Type: Recruit Title: Staff Associate for the Inter-American Institute for Global Change Research File size (bytes): 5984 STIS Filename: iaistaff Document Type: Report Title: NSF 93-173 - The Multinational Coordinated Arabidopsis thaliana Genome Research Project - Progress Report- Year Three File size (bytes): 201032 STIS Filename: nsf93173 ------------------------------------------------------------------------ ** UPDATES TO EXISTING STIS DOCUMENTS ** Document Type: Phone Book Title: NSF Alpha Telephone Directory File size (bytes): 114004 STIS Filename: phnalpha Document Type: SRS Data Brief Title: DB 93-324 Academic R&D Spending Increased in FY 1992 File size (bytes): 316 STIS Filename: db93324 Also available: db93324.ps ------------------------------------------------------------------------ ** FOR YOUR REFERENCE ** ------------------------------------------------------------------------ HOW TO OBTAIN DOCUMENTS The above files can be retrieved in electronic form using the STIS system. If you don't know how to use STIS, send an E-mail message to stisinfo@nsf.gov (Internet). You will receive a copy of the STIS flyer via E-mail. If you are already using STIS, you can use the information above to retrieve these files: Documents via E-mail: Send a message to stisserve@nsf.gov (Internet). Use the "STIS Filename" shown above in the "get" command. For example, to retrieve db93324, the text of your message should be as follows: get db93324 Anonymous FTP: FTP to stis.nsf.gov. Use the "STIS Filename" shown above to retrieve a file. For example, to retrieve db93324, you would enter: ftp> get db93324 WAIS or Gopher: Do a word search on the filename as shown in the summary. If you want a *printed* copy of a document: Send your name and postal mailing address, and the document title and number to "firstop@nsf.gov" (Internet). If you have problems with the above procedures: Send a message to "stis@nsf.gov" (Internet). From owner-sci-resources@net.bio.net Fri Feb 11 22:00:00 1994 Path: biosci!biosci!not-for-mail From: Dave Kristofferson Newsgroups: bionet.sci-resources Subject: NSF - Summary of new documents on STIS - 6 February 1994 Date: 11 Feb 1994 23:23:53 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 113 Approved: biosci-moderator@net.bio.net Distribution: bionet Message-ID: <2ji069$leh@net.bio.net> NNTP-Posting-Host: net.bio.net This message contains a summary of the documents added to the NSF STIS system in the previous week. Reference material concerning STIS follows the summary. ------------------------------------------------------------------------ ** NEW DOCUMENTS ON STIS ** Document Type: Bulletin Title: NSF February Bulletin Vol 21; No. 6 File size (bytes): 32051 STIS Filename: bul9402 Document Type: General Publication Title: NSF 94-10 Stis Users Guide File size (bytes): 58232 STIS Filename: nsf9410 Title: NSF 94-4 STIS Flyer File size (bytes): 4038 STIS Filename: nsf944 Also available: nsf944.ps Document Type: Letter Title: Current List of REU Sites File size (bytes): 49889 STIS Filename: reulist Document Type: Program Guideline Title: NSF 94-11-Cise Educational Infrastructure Program File size (bytes): 18172 STIS Filename: nsf9411 Title: NSF 94-9 - Graduate Research Traineeships, FY 1994 File size (bytes): 29004 STIS Filename: nsf949 Document Type: Recruit Title: Senior Executive Service Nationwide Vacancy Listing File size (bytes): 26789 STIS Filename: sesvac Title: Science Education Administrator (Associate Program Director) File size (bytes): 5232 STIS Filename: vex9410 Title: Program Assistant (Office Automation) File size (bytes): 5168 STIS Filename: vgs9433 Title: Senior Legislative Policy Analyst File size (bytes): 6383 STIS Filename: vgs9434 ------------------------------------------------------------------------ ** UPDATES TO EXISTING STIS DOCUMENTS ** Document Type: Committees Title: NSF Advisory Committee Meetings File size (bytes): 858 STIS Filename: cmpublic Document Type: Phone Book Title: NSF Alpha Telephone Directory File size (bytes): 113768 STIS Filename: phnalpha ------------------------------------------------------------------------ ** FOR YOUR REFERENCE ** ------------------------------------------------------------------------ HOW TO OBTAIN DOCUMENTS The above files can be retrieved in electronic form using the STIS system. If you don't know how to use STIS, send an E-mail message to stisinfo@nsf.gov (Internet). You will receive a copy of the STIS flyer via E-mail. If you are already using STIS, you can use the information above to retrieve these files: Documents via E-mail: Send a message to stisserve@nsf.gov (Internet). Use the "STIS Filename" shown above in the "get" command. For example, to retrieve phnalpha, the text of your message should be as follows: get phnalpha Anonymous FTP: FTP to stis.nsf.gov. Use the "STIS Filename" shown above to retrieve a file. For example, to retrieve phnalpha, you would enter: ftp> get phnalpha WAIS or Gopher: Do a word search on the filename as shown in the summary. If you want a *printed* copy of a document: Send your name and postal mailing address, and the document title and number to "firstop@nsf.gov" (Internet). If you have problems with the above procedures: Send a message to "stis@nsf.gov" (Internet). From owner-sci-resources@net.bio.net Fri Feb 11 22:00:00 1994 Path: biosci!biosci!not-for-mail From: Dave Kristofferson Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 23, no. 6, 11 Februrary 1994 Date: 11 Feb 1994 23:38:54 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 1764 Approved: biosci-moderator@net.bio.net Distribution: bionet Message-ID: <2ji12e$lt5@net.bio.net> NNTP-Posting-Host: net.bio.net $$XID NIHGUIDE 19940211 V23N06 P1O2 ************************************ X-comment: RFAs described: MH-94-007, DK-94-016, AI-94-012, AI-94-011 NIH GUIDE - Vol. 23, No. 6 - February 11, 1994 $$INDEX BEGIN ******************************************************* NOTICES $$INDEX N1 ********************************************************** FUNDING STRATEGIES FOR FY 94 National Institutes of Health INDEX: NATIONAL INSTITUTES OF HEALTH $$INDEX N2 ********************************************************** EARTHQUAKE DISASTER RELIEF National Institutes of Health INDEX: NATIONAL INSTITUTES OF HEALTH $$INDEX N3 ********************************************************** EXTRAMURAL ASSOCIATES DEVELOPMENT AWARD (RFA OD-94-002) National Institutes of Health INDEX: NATIONAL INSTITUTES OF HEALTH $$INDEX N4 ********************************************************** NATIONAL MULTIPURPOSE RESEARCH AND TRAINING CENTERS National Institute on Deafness and Other Communication Disorders INDEX: DEAFNESS, COMMUNICATIONS DISORDERS $$INDEX N5 ********************************************************** SUPPORT FOR MENTORED CAREER AWARDS (K20, K21) AND EXPEDITED REVIEW National Institute on Drug Abuse INDEX: DRUG ABUSE $$INDEX N6 ********************************************************** TIME-LABELED FETAL PRIMATE TISSUES AVAILABLE National Center for Research Resources INDEX: RESEARCH RESOURCES NOTICES OF AVAILABILITY (RFPs AND RFAs) $$INDEX R1 ********************************************************** CENTRAL LABORATORY FOR VIRAL ACTIVATION TRANSFUSION STUDY (RFP NHLBI- HB-94-11) National Heart, Lung, and Blood Institute INDEX: HEART, LUNG, BLOOD $$INDEX R2 ********************************************************** CLINICAL CENTERS FOR VIRAL ACTIVATION TRANSFUSION STUDY (RFP NHLBI-HB-94-12) National Heart, Lung, and Blood Institute INDEX: HEART, LUNG, BLOOD $$INDEX R3 05/06/94 ************************************************* RESEARCH TRANSITION GRANT PROGRAM IN CLINICAL MENTAL HEALTH SERVICES (RFA MH-94-007) National Institute of Mental Health INDEX: MENTAL HEALTH $$INDEX R4 05/20/94 ************************************************* RESEARCH USING THE UNITED STATES RENAL DATA SYSTEM (RFA DK-94-016) National Institute of Diabetes and Digestive and Kidney Diseases INDEX: DIABETES, DIGESTIVE, KIDNEY DISEASES $$INDEX R5 06/21/94 ************************************************* AFFECTING GRAFT SURVIVAL WITH DONOR IMMUNE TISSUE (RFA AI-94-012) National Institute of Allergy and Infectious Diseases INDEX: ALLERGY, INFECTIOUS DISEASES $$INDEX R6 07/13/94 ************************************************* BASIC BIOLOGY OF IMMUNE RESPONSES FOR VACCINE RESEARCH (RFA AI-94-011) National Institute of Allergy and Infectious Diseases National Institute on Aging INDEX: ALLERGY, INFECTIOUS DISEASES; AGING ERRATA $$INDEX E1 ********************************************************** MINORITY DISSERTATION RESEARCH GRANTS IN AGING (RFA AG-94-004) National Institute on Aging INDEX: AGING $$INDEX E2 ********************************************************** PREDOCTORAL FELLOWSHIP AWARDS FOR MINORITY STUDENTS (RFA GM-94-004) National Institute of General Medical Sciences INDEX: GENERAL MEDICAL SCIENCES $$INDEX E3 ********************************************************** APPLIED RESEARCH RELEVANT TO AN ELECTRONIC MEDICAL RECORD (RFA LM-94-002) National Library of Medicine Agency for Health Care Policy and Research INDEX: NATIONAL LIBRARY OF MEDICINE; HEALTH CARE POLICY $$INDEX E4 ********************************************************** OPERATION AND MAINTENANCE OF THE BIOLOGICAL DATA PROCESSING SYSTEM (RFP NCI-CM-57198-12) National Cancer Institute INDEX: CANCER This publication is available electronically to institutions via BITNET or INTERNET and is also on the NIH GOPHER. Alternative access is through the NIH Grant Line using a personal computer (data line 301/402-2221). Contact Dr. John James at 301/594-7270 for details. $$INDEX END ******************************************************** NOTICES $$N1 BEGIN ********************************************************** FUNDING STRATEGIES FOR FY 94 NIH GUIDE, Volume 23, Number 6, February 11, 1994 P.T. National Institutes of Health The information indicated below will guide the Institutes and Centers in their funding decisions on Research Project Grants (RPGs) in FY 94. Although these principles remain essentially the same as those for FY 1993, there are some changes. The changes include the fact that this year there is a distinction between principles and funding strategies. Section I, core principles, includes three statements that will be applicable for more than FY 94. On the other hand, funding strategies, which are detailed in Section II, may be changed from year to year depending on the appropriation level and associated Congressional directives. I. Core Principles 1. Grants will be awarded on the basis of reasonable and allowable costs, consonant with the principles of sound cost management and in consideration of Institute or Center (I/C) priorities, constraints on the growth of average grant costs, and the availability of funds. 2. The award of noncompeting research project grants at committed levels continues to be the cornerstone of the NIH Financial Management Plan and is the basis of the plan's credibility with the scientific community and Congress. 3. Determination of commitments for future years must take into consideration stability of support for investigators, optimum portfolio balance, and opportunities to address emerging problems. II. Fiscal Year 1994 Funding Strategies 1. For FY 1994 competing grants, the average increment for the subsequent noncompeting award may not exceed the direct cost level of the previous budget period by more than four percent. NIH staff may make exceptions for specifically justified programmatic requirements and one-time, non-recurring costs such as equipment. 2. Every effort will be made to accommodate shifts in the NIH fiscal situation. If conditions are such that funding at the committed levels is not possible, the I/Cs will consult with the Deputy Director for Extramural Research, NIH, to determine an appropriate resolution. 3. The average total cost of competing grants in the FY 1994 cohort will not increase by more than the Biomedical Research and Development Price Index (BRDPI) (4.19 percent) over the cohort of competing grants in FY 1993 (including special initiative small business grants - Small Business Innovative Research (SBIR)/Small Business Technology Transfer (STTR)). Given specific appropriation levels, some I/Cs may not be able to provide an increase consonant with the BRDPI. 4. When necessary, budgetary reductions from the requested level will be achieved through implementing a combination of initial review and Council/Board recommendations, staff review for cost allocability, allowability, and reasonableness, and programmatic adjustments to arrive at an appropriate funding level. 5. Based on adjustments to the project, I/C staff, in consultation with the principal investigator, will decide whether or not a new statement of specific aims is required. When reductions are 25 percent or more below the IRG recommended level, staff will obtain a revised statement of specific aims, a revised budget, and/or a revised timetable, as appropriate, for the project, which must be approved and countersigned by the institution and approved by program and grants management staff. To ensure initial review group understanding of the modified scope of a funded project, the approved statement of revised aims should be submitted by the investigator in competing continuation grant applications. 6. For competing continuation grants, one factor in arriving at the award amount will be the level of support in prior years and the extent to which the I/C can permit growth within the existing constraints on average costs. 7. The average length of research project grants will not exceed four years (excluding special initiative small business grants - SBIR/STTR). 8. In making funding decisions, I/Cs should factor in the total costs of a grant, especially at the margin of the funding plan. INQUIRIES For further information, contact the Grants Management Specialist or Health Scientist Administrator responsible for the grant. The names and telephone numbers are indicated on the Notice of Grant Award. $$N1 END ************************************************************ $$N2 BEGIN ********************************************************** EARTHQUAKE DISASTER RELIEF NIH GUIDE, Volume 23, Number 6, February 11, 1994 P.T. National Institutes of Health The National Institutes of Health wishes to inform grantees in the Los Angeles area who suffered recent earthquake damage or destruction of facilities, equipment, and/or supplies of the procedure to follow to seek public assistance to repair the damage. The Federal Emergency Management Agency (FEMA), Office of Emergency Services (OES) will accept such requests from public or private non-profit institutions and organizations. Requests must be submitted by institutional officials --- not by individual investigators --- following the instructions that will be provided by the OES. INQUIRIES Institutional Officials may contact: Mr. Charles Lilly Office of Emergency Services Federal Emergency Management Agency 150 East Colorado Boulevard Pasadena, CA 91101 Telephone: (818) 583-7747 Individuals who have already notified NIH staff of their damages are urged to make sure their institutional officials have initiated contact with the Federal Emergency Management Agency. For further clarification, contact: Dr. James F. O'Donnell Director, Office of Extramural Programs National Institutes of Health Building 31, Room 5B32 Bethesda, MD 20892 Telephone: (301) 402-0854 $$N2 END ************************************************************ $$N3 BEGIN ********************************************************** EXTRAMURAL ASSOCIATES DEVELOPMENT AWARD NIH GUIDE, Volume 23, Number 6, February 11, 1994 RFA: OD-94-002 P.T. National Institutes of Health Application Receipt Date: April 19, 1994 PURPOSE The Extramural Associates Program (EAP) is initiating a program to provide support to Extramural Associate (EA) Institutions with Extramural Associates who have participated in the NIH EA Program since 1991. The award will enable these institutions to establish or enhance an office of sponsored research and to provide for other research infrastructure needs. ELIGIBILITY Eligibility is limited to those domestic academic institutions that have a significant enrollment comprised of minorities (i.e., African Americans, Hispanics, Asians, Native Americans), or are women's colleges, and have a faculty member who participated in the NIH Extramural Associates Program since 1991. INQUIRIES Further information may be obtained from: Mr. Theodore W. Blakeney, Jr. Office of Extramural Programs National Institutes of Health Building 31, Room 5B38 Bethesda, MD 20892 Telephone: (301) 496-9728 $$N3 END ************************************************************ $$N4 BEGIN ********************************************************** NATIONAL MULTIPURPOSE RESEARCH AND TRAINING CENTERS NIH GUIDE, Volume 23, Number 6, February 11, 1994 P.T. National Institute on Deafness and Other Communication Disorders The National Institute on Deafness and Other Communication Disorders plans to issue a Request for Applications (RFA) for National Multipurpose Research and Training Centers (RTCs). These Centers are Congressionally mandated to include research, training, continuing education, and information dissemination in communication sciences and disorders. Both new and competing renewal applications are encouraged. The RFA will be issued within the next few months with a due date in October, 1994. INQUIRIES For further information, contact: Dr. Judith A. Cooper, Deputy Director National Institute on Deafness and Other Communication Disorders Executive Plaza South, Suite 400C Rockville, MD 20892 Telephone: (301) 496-5061 $$N4 END ************************************************************ $$N5 BEGIN ********************************************************** SUPPORT FOR MENTORED CAREER AWARDS (K20, K21) AND EXPEDITED REVIEW NIH GUIDE, Volume 23, Number 6, February 11, 1994 P.T. National Institute on Drug Abuse The National Institute on Drug Abuse (NIDA) is interested in expanding the number of qualified researchers, especially clinicians, engaged in biomedical and behavioral drug abuse and addiction research. To this end, NIDA has set aside an additional $1.7 million for mentored career awards (K20, K21) in Fiscal Year 1994. These programs give promising, new investigators the opportunity to work with established researchers for a period of up to five years. To enhance the number of applications that will be considered during this fiscal year, all non-AIDS K20 and K21 application received by the June 1, 1994 deadline and assigned to the NIDA will be reviewed through an expedited initial review process. AIDS K20 and K21 applications received by the May 1, 1994 deadline will be reviewed on their normal schedule. In order to facilitate the expedited initial review of these non-AIDS applications, in addition to the copies sent to the Division of Research Grants, a copy of each application must be sent directly to: Ms. Eleanor Friedenberg Office of External Program Review National Institute on Drug Abuse 5600 Fisher's Lane, Room 10-42 Rockville, MD 20857 Both AIDS and non-AIDS K20 and K21 applications will be reviewed in order to permit the selection of applications for funding by the National Advisory Council on Drug Abuse in September and funding of applications by September 30, 1994. INQUIRIES For further information, contact: Timothy P. Condon, Ph.D. Office of Science Policy, Education, and Legislation National Institute on Drug Abuse 5600 Fisher's Lane, Room 10A55 Rockville, MD 20857 Telephone: (301) 443-6071 $$N5 END ************************************************************ $$N6 BEGIN ********************************************************** TIME-LABELED FETAL PRIMATE TISSUES AVAILABLE NIH GUIDE, Volume 23, Number 6, February 11, 1994 P.T. National Center for Research Resources A series of nonhuman primate fetuses (logtailed macaque, Macaca fascicularis) will be made available in the coming year allowing interested investigators to track cohorts of cells labeled on specific days of gestation through the full course of fetal development. Fetuses labeled with tritiated thymidine on days 42, 55, 70, and 90 of gestation will be taken at four or five intervals ranging from one week to six months after labeling. Other fetal age cohorts may be available in the future. INQUIRIES Investigators interested in receiving specimens or more information may contact: Dr. Anita Hendrickson University of Washington SM-20 Seattle, WA 98195 FAX: (206) 543-1524 e-mail: anitah@u.washington.edu This project is partially supported by NCRR/NIH through the Regional Primate Research Center at the University of Washington. $$N6 END ************************************************************ NOTICES OF AVAILABILITY (RFPs AND RFAs) $$R1 BEGIN NHLBI-HB-94-11 ******************************************* CENTRAL LABORATORY FOR VIRAL ACTIVATION TRANSFUSION STUDY NIH GUIDE, Volume 23, Number 6, February 11, 1994 RFP AVAILABLE: NHLBI-HB-94-11 P.T. National Heart, Lung, and Blood Institute The National Heart, Lung, and Blood Institute issued Request for Proposals (RFP) NHLBI-HB-94-11, on January 28, 1994, and proposal will be due approximately eight weeks thereafter. It is anticipated that a three-year contract will be awarded on or about September 30, 1994. The contractor will serve as the Central Laboratory for a multicenter clinical trial designed to determine if viral activation in HIV-1 infected individuals is associated with blood transfusion. It is anticipated that approximately 330 patients will be tested and followed over a period of two years. The Principal Investigator must be on-site and have expertise in clinical pathology or transfusion medicine. Responsibilities of the central laboratory will include, but are not limited to, the following: (1) participate as a member of the Steering Committee in finalizing the details of the protocol and in completing the manual of operations; (2) develop procedures for the collection of blood samples and their processing, temporary storage and delivery to the Central Laboratory; (3) perform tests using the polymerase chain reaction (PCR) technology to quantitate the amount of CMV and HIV-1 present in peripheral blood mononuclear cells, quantitative culture of CMV and HIV-1 and other tests such as lymphocyte subsets and p24 relating to viral activation; (4) develop and implement collection procedures for the laboratory data; (5) utilize a computerized system to enter and edit the results from the blood tests and blind duplicates on a regular basis and transmit test results electronically to the Coordinating Center in an acceptable format; (6) assure standardization of all blood tests within the Central Laboratory and have an ongoing quality control program to assess and control within run and between run variability, accuracy, precision, and limits for each analyte; (7) store aliquots from each participating clinical center for the purpose of case-control or other special studies under conditions appropriate to prevent analyte degradation; and (8) contribute to the analysis and reporting of trial data. INQUIRIES Requests for copies of the RFP must include three self-addressed mailing labels and are to be directed to: Lynda A. Bindseil BDR Contracts Section National, Heart, Lung, and Blood Institute 7550 Wisconsin Avenue Federal Building, Room 610 Bethesda, MD 20892 $$R1 END ************************************************************ $$R2 BEGIN NHLBI-HB-94-12 ******************************************* CLINICAL CENTERS FOR VIRAL ACTIVATION TRANSFUSION STUDY NIH GUIDE, Volume 23, Number 6, February 11, 1994 RFP AVAILABLE: NHLBI-HB-94-12 P.T. National Heart, Lung, and Blood Institute This study will determine if viral activation occurs following blood transfusion and if leukocyte depletion or irradiation can prevent it. It also will evaluate the role of donor leukocytes producing this activation by examining the effects of removing leukocytes by filtration or abolishing their ability to proliferate by gamma irradiation. Finally, the study will examine the persistence of donor lymphocytes after transfusion. The project will require a total of at least 330 HIV-1 infected patients with CD4 counts below 250 cells/mm3 prior to their transfusion. Each clinical center will be expected to recruit and follow at least 33 patients in accordance with protocol requirements. Responsibilities will include, but are not limited to, the following: (1) participate as a member of the Steering Committee in finalizing details of the protocol and in completing the manual of operations; (2) coordinate with a blood bank, the preparation and transfusion of blood products for the patients; (3) collect clinical data on each patient and perform regular physical exams on the patients; (4) collect blood samples from patients for testing by a centralized laboratory; (5) transmit scientific data to a medical coordinating center; (6) participate in all committee and any subcommittee meetings; and (7) participate in developing and writing scientific presentations and manuscripts for publication. It is anticipated that several awards will be made from this solicitation and that awards will be made on or about September 30, 1994. It is anticipated that the awards will be multiple-year cost reimbursement completion contracts with a term of three years. INQUIRIES RFP No. NHLBI-HB-94-12 was released on January 26, 1994. Requests for copies of the RFP must include three self-addressed mailing labels and are to be directed to: Lynda A. Bindseil BDR Contracts Section National Heart, Lung, and Blood Institute 7550 Wisconsin Avenue Federal Building, Room 610 Bethesda, MD 20892 $$R2 END ************************************************************ $$R3 BEGIN MH-94-007 FULL-TEXT ************************************** RESEARCH TRANSITION GRANT PROGRAM IN CLINICAL MENTAL HEALTH SERVICES NIH GUIDE, Volume 23, Number 6, February 11, 1994 RFA AVAILABLE: MH-94-007 P.T. National Institute of Mental Health Application Receipt Date: May 6, 1994 THIS IS A NOTICE OF AVAILABILITY OF A REQUEST FOR APPLICATIONS (RFA); IT IS ONLY AN ABSTRACT OF THE RFA. POTENTIAL APPLICANTS MUST REQUEST THE COMPLETE RFA, WHICH CONTAINS ESSENTIAL INFORMATION FOR THE PREPARATION OF AN APPLICATION, FROM THE CONTACT LISTED IN "INQUIRIES," BELOW. FAILURE TO FOLLOW THE INSTRUCTIONS IN THE COMPLETE RFA MAY RESULT IN AN INCOMPLETE APPLICATION, WHICH WILL BE RETURNED TO THE APPLICANT WITHOUT REVIEW. PURPOSE The purpose of this RFA is to stimulate the development of programs of clinical mental health services research at institutions that currently have strong programs in mental health clinical research, but are not engaged in extensive clinical mental health services research. A second goal of this RFA is to bring the expertise of mental health clinical researchers and general health services researchers into the clinical mental health services research field and to promote their collaborations with each other and with clinical mental health services researchers. The development of programs focusing on the special mental health services issues of the following populations are strongly encouraged: minorities; persons who are homeless; persons who live in rural areas; or persons with AIDS, who are HIV positive, or at risk of contracting the AIDS virus. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This RFA, Research Transition Grant Program in Clinical Mental Health Services, is related to priority areas of alcohol and other drugs, mental health and mental disorders, and violent and abusive behaviors. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202/783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic public and private non- profit and for-profit organizations, including universities, colleges, hospitals, laboratories, units of State or local governments, and eligible agencies of the Federal government except for those institutions with extensive, ongoing collaborations between clinical mental health investigators and mental health services researchers. Women and minority investigators are encouraged to apply. MECHANISM OF SUPPORT This RFA will use the resource-related research project (R24). The R24 mechanism is used to support research projects that will enhance the capability of resources to serve biomedical research. The Research Transition Grant Program (RTGP) will be used by the National Institute of Mental Health (NIMH) to enhance research capability and clinical mental health services research program. Each award will be limited to five years of funding and is nonrenewable. This RFA is a one-time solicitation. FUNDS AVAILABLE It is anticipated that at least $2.5 million in total costs will be made available so that a minimum of five awards can be made. Each award will have a maximum yearly total cost amount of $500,000. RESEARCH OBJECTIVES Background. The RTGP in Clinical Mental Health Services is part of an integrated NIMH approach to institutional infrastructure development made up of several types of grants including: NIMH Developing Clinical Research Centers, Research Infrastructure Support Program (RISP) grants, Child and Adolescent Mental Health Services Research Centers, and Social Work Research Development Center grants. Together these provide a continuum of research infrastructure support for institutions with varying levels and types of mental health research activity. The RTGP grants are designed to enable institutions with current programs in clinical mental health research to develop into major clinical mental health services research settings, thus increasing the number of investigators obtaining extramural funding for work in the services research field. Expansion of the nation's clinical mental health services research infrastructure is a major priority for NIMH because it is essential for improving the care received by adults (including the elderly), adolescents, and children who suffer from mental and emotional disorders, particularly the most severe disorders. Mental Health Services Research. The field of mental health services research examines the impact of the organization, financing, management, and delivery of mental health services on the quality, cost, access to, and outcomes of care. There are two major components of services research: service systems research and clinical services research. Service systems research focuses on questions related to the organization, financing, and integration of mental health services. Clinical mental health services research focuses on the process and quality of care and the effectiveness in community settings of clinical interventions whose efficacy has been demonstrated in controlled clinical research environments. This RFA seeks to enhance the clinical mental health services component of services research. SPECIAL REQUIREMENTS A central philosophical principle underlying this program is that different institutions will require different types and amounts of development in clinical services research. Therefore, this RFA does not prescribe in any detail the nature of the activities to be applied for or supported. The following types of support may be requested under this program: o Partial salary support for clinical mental health services research faculty, particularly women and minorities o Training expenses in clinical mental health services research, such as tuition remission or course fees, for junior clinical faculty o Research patient recruitment, diagnosis, assessment, and follow-up o Consultation from clinical mental health services research investigators o Biostatistical and data-base management o Small equipment and research instruments o Research technicians and assistants o Developmental, feasibility, and/or pilot studies STUDY POPULATIONS SPECIAL INSTRUCTIONS FOR INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDIES For projects involving clinical research, NIH requires applicants to give special attention to the inclusion of women and minorities in study populations. If women or minorities are not included in the study populations for clinical studies, a specific justification for this exclusion must be provided. Applications without such documentation will not be accepted for review. APPLICATION PROCEDURES Applicants are to use the research grant application form PHS 398 (rev. 9/91). These forms are available at most institutional offices of sponsored research; from the Office of Grants Information Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone 301/594-7248; and from the Grants Management Branch, National Institute of Mental Health, 5600 Fishers Lane, Room 7C-05, Rockville, MD 20857, telephone 301/443-4414. The RFA number (MH-94-007) and the title, Research Transition Grant Program in Clinical Mental Health Services, must be typed in item 2a on the face page of the PHS 398 application form and the "YES" box must also be marked. Applicants must specify that the R24 mechanism is being used. Applicant institutions will need to demonstrate that they: (1) have a strong base of ongoing clinical mental health research activities; (2) need additional support to establish and maintain collaborative working relationships between clinical and services researchers; and (3) have the potential for building a mental health services research program that will equip them to compete effectively in future years for clinical mental health services research grants. The RFA label available in the PHS 398 application form must be affixed to the bottom of the face page of the application. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. All applications must be received by May 6, 1994 and will be reviewed in July. Applications received after the receipt date will be returned to the applicant without review. Submit, in one package, a signed original of the application, including the Checklist, and three signed copies to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** At the time of the submission, two additional copies of the application must also be sent to: Wright Williamson, M.S.W. Division of Extramural Activities National Institute of Mental Health 5600 Fishers Lane, Room 9C-14 Rockville, MD 20857 REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness and responsiveness. Incomplete or nonresponsive applications will be returned to the applicant without further consideration. Applications will be reviewed for scientific and technical merit by an initial review group (IRG) convened by the NIMH and composed primarily of non-Federal scientific experts. Final review is by the appropriate National Advisory Council; review by Council may be based on policy considerations as well as scientific merit. By law, only applications recommended for consideration for funding by the Council may be supported. Summaries of IRG recommendations are sent to applicants as soon as possible following IRG review. Criteria to be considered in evaluating applications for scientific/technical merit are listed in the RFA. AWARD CRITERIA Awards will be made on or before September 30, 1994. INQUIRIES Written and telephone requests for the RFA and the opportunity to clarify any issues or questions from potential applicants are welcome. Direct requests for the RFA and inquiries regarding programmatic issues to: Ann A. Hohmann, Ph.D., M.P.H. Services Research Branch National Institute of Mental Health 5600 Fishers Lane, Room 10C-06 Rockville, MD 20857 Telephone: (301) 443-3364 For further information on grants management issues, applicants may contact: Diana S. Trunnell Grants Management Branch National Institute of Mental Health 5600 Fishers Lane, Room 7C-15 Rockville, MD 20857 Telephone: (301) 443-3065 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance 93.242, Mental Health Research Grants. 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 RFA is not subject to the intergovernmental review requirements of Executive Order 12372, as implemented through DHHS regulations at 45 CFR Part 100. $$R3 END ************************************************************ $$R4 BEGIN DK-94-016 FULL-TEXT ************************************** RESEARCH USING THE UNITED STATES RENAL DATA SYSTEM NIH GUIDE, Volume 23, Number 6, February 11, 1994 RFA AVAILABLE: DK-94-016 P.T. National Institute of Diabetes and Digestive and Kidney Diseases Letter of Intent Receipt Date: April 20, 1994 Application Receipt Date: May 20, 1994 THIS IS A NOTICE OF AVAILABILITY OF A REQUEST FOR APPLICATIONS (RFA); IT IS ONLY AN ABSTRACT OF THE RFA. POTENTIAL APPLICANTS MUST REQUEST THE COMPLETE RFA, WHICH CONTAINS ESSENTIAL INFORMATION FOR THE PREPARATION OF AN APPLICATION, FROM THE CONTACT LISTED IN "INQUIRIES," BELOW. FAILURE TO FOLLOW THE INSTRUCTIONS IN THE COMPLETE RFA MAY RESULT IN AN INCOMPLETE APPLICATION, WHICH WILL BE RETURNED TO THE APPLICANT WITHOUT REVIEW. PURPOSE This initiative invites grant applications for biomedical and health services research, using the United States Renal Data System (USRDS) database. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This RFA, Research Using the United States Renal Data System, is related to the priority area of diabetes and chronic disabling conditions. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign organizations, both public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Minority individuals and women are encouraged to submit as Principal Investigators. MECHANISM OF SUPPORT Support of this program will be through the investigator initiated research project grant (R01) mechanism. Each grant award will be capped at $100,000 total cost (including direct and indirect cost) per year for a maximum of two years. The responsibility for planning, direction, and execution of the proposed project will be solely that of the applicant. Awards will be administered under PHS grants policy as stated in the PHS Grants Policy Statement. This RFA is a one-time solicitation. Generally, future unsolicited competing continuation applications will compete with all investigator-initiated applications and be reviewed according to the customary peer review procedures. The earliest possible award date will be April 1, 1995. FUNDS AVAILABLE For FY 1995, a total of $500,000 dollars has been committed to fund applications submitted in response to this RFA. Awarded funds will be used to obtain a data file from the USRDS Coordinating Center, and to support the independent analysis of the data file by the investigator. It is anticipated that approximately five awards will be made; however, this funding level is dependent upon the receipt of a sufficient number of applications of high scientific merit. Although this program is provided for in the financial plans of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the award of grants pursuant to this RFA is also contingent upon the availability of funds designated for this purpose. RESEARCH OBJECTIVES The USRDS database contains information on 462,000 Medicare patients who have been treated for end stage renal disease (ESRD) therapy since 1976. For each patient, the database includes information on basic demographics, the primary medical diagnosis which led to renal failure, dialysis records, hospital records, and transplantation information. Applications proposing to investigate issues which impact on the morbidity, mortality, well being, or cost of treatment for treated ESRD patients will be considered responsive to this RFA. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS FOR INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDIES For projects involving clinical research, NIH requires applicants to give special attention to the inclusion of women and minorities in study populations. If women or minorities are not included in the study populations for clinical studies a specific justification for this exclusion must be provided. Applications without such documentation will not be accepted for review. LETTER OF INTENT Prospective applicants are asked to submit, by April 20, 1994, a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, the identities of other key personnel and participating institutions, and the number and title of the RFA in response to which the application may be submitted. The letter of intent is to be sent to the Chief, Review Branch, Division of Extramural Activities at the address listed under INQUIRIES. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information that it contains is helpful in planning for the review of applications. It allows NIDDK staff to estimate the potential review workload and to avoid possible conflict of interest in the review. APPLICATION PROCEDURES Applications are to be submitted using form PHS 398 (rev. 9/91), available in the office of sponsored research at most academic or research institutions and from the Office of Grants Information, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone 301/594-7248. The RFA label available in the PHS 398 application form must be affixed to the bottom of the face page. Detailed instructions on submission procedures are described the RFA. REVIEW CONSIDERATIONS Applications that are complete and responsive to the RFA will be evaluated by an appropriate peer review group convened by the NIDDK in accordance with the usual NIH peer review procedures. Following review, the applications will be given a secondary review by the NIDDK Advisory Council unless not recommended for further consideration by the initial review group. Applications that are incomplete or unresponsive to the RFA will be returned to the applicant or held until the next regular receipt date and reviewed by the Division of Research Grants. INQUIRIES Written and telephone requests for the RFA and the opportunity to clarify any issues or questions from potential applicants are welcome. Direct requests for the RFA and inquiries regarding programmatic issues to: Camille A. Jones, M.D., M.P.H. Division of Kidney, Urologic, and Hematologic Diseases National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 3A-06 Bethesda, MD 20892 Telephone: (301) 594-7586 FAX: (301) 594-7501 Inquiries regarding fiscal matters may be directed to: Ms. Trude McCain Division of Extramural Activities National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 649 Bethesda, MD 20892 Telephone: (301) 594-7543 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.849. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$R4 END ************************************************************ $$R5 BEGIN AI-94-012 FULL-TEXT ************************************** AFFECTING GRAFT SURVIVAL WITH DONOR IMMUNE TISSUE NIH GUIDE, Volume 23, Number 6, February 11, 1994 RFA AVAILABLE: AI-94-012 P.T. National Institute of Allergy and Infectious Diseases Letter of Intent Receipt Date: April 15, 1994 Application Receipt Date: June 21, 1994 THIS IS A NOTICE OF AVAILABILITY OF A REQUEST FOR APPLICATIONS (RFA); IT IS ONLY AN ABSTRACT OF THE RFA. POTENTIAL APPLICANTS MUST REQUEST THE COMPLETE RFA, WHICH CONTAINS ESSENTIAL INFORMATION FOR THE PREPARATION OF AN APPLICATION, FROM THE CONTACT LISTED IN "INQUIRIES" BELOW. FAILURE TO FOLLOW THE INSTRUCTIONS IN THE COMPLETE RFA MAY RESULT IN AN INCOMPLETE APPLICATION, WHICH WILL BE RETURNED TO THE APPLICANT WITHOUT REVIEW. PURPOSE The Division of Allergy, Immunology and Transplantation (DAIT) of the National Institute of Allergy and Infectious Diseases (NIAID) invites applications for basic, preclinical and clinical studies to increase knowledge of the interaction between donor and recipient immunocompetent cells. These studies have the potential to help develop protocols for enhancing solid organ graft survival by infusion of donor cells prior to or after transplantation. Information from these studies could lead to the use of donor tissue to manipulate the recipient's immune system in a controlled and specific fashion, thereby increasing graft survival and improving the management of autoimmune diseases. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This RFA, Affecting Graft Survival With Donor Immune Tissue, is related to the priority areas of diabetes and chronic disabling diseases, and to immunization and infectious diseases. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-782-3238). ELIGIBILITY REQUIREMENTS Research grant applications may be submitted by domestic and foreign, for-profit and non-profit organizations, public and private institutions, such as universities, colleges, hospitals, laboratories, units of State or local governments, and eligible agencies of the Federal government. Foreign institutions are not eligible to apply for First Independent Research Support and Transition (FIRST) Awards. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT The mechanisms of support will be the individual research project grant (R01) and the FIRST Award (R29). Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. The total project period may not exceed five years; foreign awards may not exceed three years. FUNDS AVAILABLE The estimated funds available for the total (direct and indirect) first year costs of all awards made under this RFA will be $1,500,000. In Fiscal Year 1994, the NIAID plans to fund approximately seven R01s/R29s. Applications may not request more than four percent annual inflationary increases for future years. This level of support is dependent on the receipt of a sufficient number of applications of high scientific merit. Although this program is provided for in the financial plans of the NIAID, awards pursuant to this RFA are contingent upon the availability of funds for this purpose. Funding beyond the first and subsequent years of the grant will be contingent upon satisfactory progress during the preceding years and availability of funds. RESEARCH OBJECTIVES Background Successful transplantation relies on the ability to transplant a solid organ without rejection while maintaining a normal immune response to infectious agents. With the exception of transplants between identical twins, the only way to accomplish this is to induce a specific non-responsive (tolerant) state, whereby the grafted tissue is ultimately not recognized as foreign. Donor specific transplant tolerance has been achieved for solid organ transplantation in animal models via induction regimens using donor immunocompetent tissue, e.g., bone marrow and peripheral blood. The application of those induction regimens to humans would be served best by understanding fully the basic immunological mechanisms involved and the role of the donor immune tissue in inducing and maintaining this tolerant state. Research Objectives and Scope The objective of this RFA is to support innovative new research to characterize the immunocompetent cells responsible for and the mechanisms by which donor immune tissue or cells enhance graft survival. This RFA will support basic, preclinical, and clinical studies aimed at characterizing the interaction between donor and recipient immunocompetent cells. These studies have the potential to help develop protocols for enhancing graft survival by using an infusion of donor lymphoid or dendritic cells prior to or after solid organ transplantation, either alone or in combination with other agents, to make the recipient non-responsive to the donor. Information from these studies could lead to the use of donor tissue to manipulate the recipient's immune system in a controlled and specific fashion. Applications should focus on identifying the donor and recipient cells involved in and the mechanisms responsible for induction and maintenance of donor-specific non-responsiveness in the transplant setting. Areas of particular interest to the NIAID are listed in the RFA. Animal models must be used in a way that is applicable to human transplants. Therefore, although studies using just the infusion of donor immunocompetent cells may be proposed, this type of study must be focused on understanding the basic mechanisms of transplant tolerance induction and maintenance. Knowledge generated by this research project must be applicable to human transplantation where an underlying immunosuppressive regimen is used. Therefore, studies proposing to use a monotherapy must also show that currently accepted standard immunosuppressive regimen is or is not deleterious to the induction of the tolerant state. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS FOR INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDIES For projects involving clinical research, NIH requires applicants to give special attention to the inclusion of women and minorities in study populations. If women or minorities are not included in the study populations for clinical research, a specific justification for this exclusion must be provided. Applications without such documentation will not be accepted for review. LETTER OF INTENT Prospective applicants are asked to submit, by April 15, 1994, a letter of intent that includes a descriptive title of the overall proposed research, the name, address and telephone number of the Principal Investigator (Program Director), and the number and title of this RFA. Although the letter of intent is not required, is not binding, does not commit the sender to submit an application, and does not enter into the review of subsequent applications, the information that it contains allows NIAID staff to estimate the potential review workload and to avoid conflict of interest in the review. The letter of intent is to be sent to Dr. Olivia Preble at the address listed under INQUIRIES. APPLICATION PROCEDURES Applications are to be submitted on the standard research grant application form PHS 398 (rev. 9/91). These application forms may be obtained from the institution's office for sponsored research or its equivalent, or from the Office of Grants Information, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone (301) 594-7248. For purposes of identification and processing, item 2a on the face page of the application must be marked "YES" and the RFA number and the words "AFFECTING GRAFT SURVIVAL WITH DONOR IMMUNE TISSUE" must be typed in. Applications must be received by June 21, 1994. REVIEW CRITERIA The general criteria for applications are the review criteria used for traditional research project grant applications. AWARD CRITERIA Funding decisions will be made on the basis of scientific and technical merit as determined by peer review, program priorities, and the availability of funds. INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Requests for the RFA, as well as inquiries regarding programmatic issues, may be directed to: Stephen M. Rose, Ph.D. Division of Allergy, Immunology and Transplantation National Institute of Allergy and Infectious Diseases Solar Building, Room 4A14 Bethesda, MD 20892 Telephone: (301) 496-5598 FAX: (301) 402-2571 Direct inquiries regarding review issues, address the letter of intent to, and mail two copies of the application and the five sets of appendices to: Olivia Preble, Ph.D. Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4C19 Bethesda, MD 20892 Telephone: (301) 496-8208 FAX: (301) 402-2638 Direct inquiries regarding fiscal matters to: Ms. Barbara Huffman Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4C26 Bethesda, MD 20892 Telephone: (301) 496-7075 Schedule Letter of Intent Receipt Date: April 15, 1994 Application Receipt Date: June 21, 1994 Scientific Review Date: October 1994 Advisory Council Date: February 1995 Earliest Award Date: April 1995 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance, No. 93.855 - Immunology, Allergy and Transplantation Research. Awards will be made under the authority of the Public Health Service Act, Title III, Section 301 (Public Law 78-410, as amended; 42 USC 241) and administered under PHS grants policies and Federal Regulations 42 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$R5 END ************************************************************ $$R6 BEGIN AI-94-011 FULL-TEXT ************************************** BASIC BIOLOGY OF IMMUNE RESPONSES FOR VACCINE RESEARCH NIH GUIDE, Volume 23, Number 6, February 11, 1994 RFA AVAILABLE: AI-94-011 P.T. National Institute of Allergy and Infectious Diseases National Institute on Aging Letter of Intent Receipt Date: April 15, 1994 Application Receipt Date: July 13, 1994 THIS IS A NOTICE OF AVAILABILITY OF A REQUEST FOR APPLICATIONS (RFA); IT IS ONLY AN ABSTRACT OF THE RFA. POTENTIAL APPLICANTS MUST REQUEST THE COMPLETE RFA, WHICH CONTAINS ESSENTIAL INFORMATION FOR THE PREPARATION OF AN APPLICATION, FROM THE CONTACT LISTED IN "INQUIRES" BELOW. FAILURE TO FOLLOW THE INSTRUCTIONS IN THE COMPLETE RFA MAY RESULT IN AN INCOMPLETE APPLICATION, WHICH WILL BE RETURNED TO THE APPLICANT WITHOUT REVIEW. PURPOSE The Division of Allergy, Immunology and Transplantation (DAIT) of the National Institute of Allergy and Infectious Diseases (NIAID) and the Biology of Aging Program (BAP) of the National Institute on Aging (NIA) invite applications for basic studies designed to elucidate key processes underlying immune responsiveness that will facilitate new and improved approaches to vaccination for infectious diseases other than AIDS. There is increasing need to develop methods for achieving protective immunity that depend on manipulating elements of the immune system (e.g., the order, concentrations, and delivery of cytokines). There are numerous examples of potential vaccines that are ineffective because of weak immunogenicity that could become effective vaccines if properly presented to a prepared or modulated immune system. This RFA is intended to spur the acquisition of knowledge necessary to efficaciously and safely modulate elements of the immune system leading to protective immunization against infectious diseases. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This RFA, Basic Biology of Immune Responses for Vaccine Research, is related to the priority areas of diabetes and chronic disabling diseases, and to immunization and infectious diseases. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-782-3238). ELIGIBILITY REQUIREMENTS Research grant applications may be submitted by domestic, for-profit and non-profit organizations, public and private institutions, such as universities, colleges, hospitals, laboratories, units of State or local governments, and eligible agencies of the Federal government. Foreign organizations are not eligible to apply. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT The mechanism of support will be the Program Project (P01) grant. Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. The total project period may not exceed five years. FUNDS AVAILABLE The estimated total funds (direct and indirect costs) available for first year of support for all awards made under this RFA will be $3,000,000. In Fiscal Year 1995, the NIAID and the NIA plan to fund approximately four P01 awards. Applications may not request more than four percent annual inflationary increases for future years. Applications may not request budgets in excess of $750,000 total costs (direct and indirect) in the first year. An application with a first year requested amount in excess of the above will require written approval by senior NIAID and NIA officials via the program officers for acceptance of the application for processing. 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 and the NIA, awards pursuant to this RFA are contingent upon the availability of funds for this purpose. Funding beyond the first and subsequent years of the grant will be contingent upon satisfactory progress during the preceding years and availability of funds. RESEARCH OBJECTIVES Background The most effective procedure for managing human infectious diseases is preventive immunization (vaccination). Despite the remarkable successes of vaccination in eradicating smallpox and soon, poliomyelitis, and preventing illness and death of many millions of children, there remain many infectious diseases that have not yielded to vigorous attempts to develop vaccines. Furthermore, it is increasingly evident that successful vaccination of elderly humans is a special problem that needs to be addressed due to the declining competence of the immune system with age. The generation of protective immunity depends upon a responsive immune system. During the last 10 years, there has been a flood of new information in the field of immunology. Much has been learned about the mechanisms of defined, protein antigen processing and presentation of key epitopes in a manner that engenders effective immune responses. Yet, very little is known about the antigens of pathogenic microorganisms and how they could be presented to drive desired types of immune responses. Similarly, a great deal is known about subsets of T lymphocytes and the spectrum of cytokines each subset produces, as well as about B lymphocytes and their responses to cytokines. Yet, relatively little is known about the characteristics and generation of memory T and B cells, which are essential for long-lasting protective immunity. Moreover, the mechanisms responsible for the generation of cytotoxic T cells that are efficient in attacking and neutralizing cells in the body that are infected with viruses, bacteria and protozoa remain uncertain. Research Objectives and Scope The goal of this initiative is to further increase knowledge about the basic structures and functions of the immune system that lead to protective immunization against infectious diseases. HIV infection and its sequelae are not within the scope of this RFA. Examples of relevant research topics are provided below. However, the list of examples is neither complete nor restrictive: o Elucidation of the events and factors that lead to selective expression/expansion of morphologically and/or functionally distinguishable T cell subsets; o Studies on the phenotypic and functional stability of T cell subsets and control of the selective expression of cytokine genes by subsets of T cells; o The morphological and/or functional characteristics of memory B and T cells and clarification of mechanisms for generating specific memory cells; o Analysis of the roles played by different types and functional states of antigen processing/presenting cells and the cytokines they secrete in determining the major type of immune response, the effector mechanism expressed and/or isotypes of antibodies produced; and o Studies on the basic mechanisms that are affected by immunological adjuvants and examination of the immuno-enhancing properties of adjuvants All of the preceding examples represent central features of immune responses to antigens in general. However, they are particularly important, at present, in devising new approaches to vaccination against infectious, pathogenic organisms. Applications submitted in response to this RFA should focus on elucidating basic mechanisms that qualitatively and/or quantitatively enhance immune responses, both humoral and cell-mediated. Improved understanding of approaches to enhancing immune responses will be important not only to immunization of healthy, young adults but the elderly as well. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS FOR INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDIES For projects involving clinical research, NIH requires applicants to give special attention to the inclusion of women and minorities in study populations. If women or minorities are not included in the study populations for clinical research, a specific justification for this exclusion must be provided. Applications without such documentation will not be accepted for review. LETTER OF INTENT Prospective applicants are asked to submit, by April 15, 1994, a letter of intent that includes a descriptive title of the overall proposed research, the name, address and telephone number of the Program Director, the number and title of this RFA, and a list of the key investigators and their institution(s). Although the letter of intent is not required, is not binding, does not commit the sender to submit an application, and does not enter into the review of subsequent applications, the information that it contains allows NIAID staff to estimate the potential review workload and to avoid conflict of interest in the review. The letter of intent is to be sent to Dr. Mark Rohrbaugh at the address listed under INQUIRIES. APPLICATION PROCEDURES Applications are to be submitted on the standard research grant application form PHS 398 (rev. 09/91). These application forms may be obtained from the institution's office for sponsored research or its equivalent and from the Office of Grants Information, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone (301) 594-7248. For purposes of identification and processing, item 2a on the face page of the application must be marked "YES" and the RFA number and the words "Basic Biology of Immune Response for Vaccine Research" must be typed in. Applications must be received by July 13, 1994. REVIEW CRITERIA The general criteria for P01 applications are those review criteria used for traditional research project grant applications. For P01 grant applications, additional review criteria are used, which are outlined in the NIAID information brochure on Program Project Grants and Multiproject Cooperative Agreements. AWARD CRITERIA Funding decisions will be made on the basis of scientific and technical merit as determined by peer review, program needs and balance, and the availability of funds. INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct requests for the RFA and the information brochure, as well as inquires regarding programmatic issues to: M. Michele Hogan, Ph.D. Division of Allergy, Immunology and Transplantation National Institute of Allergy and Infectious Diseases Solar Building, Room 4A22 6003 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-7551 FAX: (301) 402-2571 Anna M. McCormick, Ph.D. Biology of Aging Program National Institute on Aging Gateway Building, Suite 2C231 Bethesda, MD 20892 Telephone: (301) 496-6402 FAX: (301) 402-0010 Direct inquiries regarding review issues, address the letter of intent to, and mail two copies of the application and the five sets of appendices to: Mark Rohrbaugh, Ph.D. Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4C22 6003 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-8424 FAX: (301) 402-2638 Direct inquiries regarding fiscal matters to: Mr. Jeffrey Carow Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4B29 6003 Executive Boulevard Bethesda, MD 20892 $$XID NIHGUIDE 19940211 V23N06 P2O2 ************************************ Telephone: (301) 496-7075 Schedule Letter of Intent Receipt Date: April 15, 1994 Application Receipt Date: July 13, 1994 Scientific Review Date: October 1994 Advisory Council Date: February 1995 Earliest Award Date: April 1995 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance, No. 93.855 - Immunology, Allergy and Transplantation Research and No. 93.866 - Aging Research. Awards will be made under the authority of the Public Health Service Act, Title III, Section 301 (Public Law 78-410, as amended; 42 USC 241) and administered under PHS grants policies and Federal Regulations 42 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$R6 END ************************************************************ ERRATA $$E1 BEGIN R3 19940114 APPEND RFA AG-94-004 BOTH *********************** MINORITY DISSERTATION RESEARCH GRANTS IN AGING NIH GUIDE, Volume 23, Number 6, February 11, 1994 RFA: AG-94-004 P.T. 34, FF; K.W. 0710010, 0710030 National Institute on Aging Application Receipt Date: March 18, 1994 The following correction is issued for RFA AG-94-004, which was published in the NIH Guide for Grants and Contracts, Vol. 23, No. 2, January 14, 1994. ELIGIBILITY The applicant investigator applying for a dissertation research grant must be a member of an ethnic or racial minority group enrolled in an accredited doctoral degree program in the biomedical, social, or behavioral sciences and must have approval of the dissertation topic by a named dissertation committee or other formal group for that purpose. The student must also be conducting or intending to conduct dissertation research on aging or problems related to aging. Research topics should fit within one or more of the areas described below for each individual program (see INQUIRIES). $$E1 END ************************************************************ $$E2 BEGIN R13 19940107 APPEND RFA GM-94-004 FULL ********************** PREDOCTORAL FELLOWSHIP AWARDS FOR MINORITY STUDENTS NIH GUIDE, Volume 23, Number 6, February 11, 1994 RFA: GM-94-004 P.T. 22, FF; K.W. 0720005 National Institute of General Medical Sciences Application Receipt Date: April 27, 1994 The January 7, 1994 issue of the NIH Guide for Grants and Contracts (Vol. 23, No. 1) published a Request for Applications for Predoctoral Fellowship Awards for Minority Students (RFA GM-94-004). Reference was made in that publication to a suggested format for institutional certification to be found at the end of the text. The following is that suggested format. SUGGESTED FORMAT FOR INSTITUTIONAL CERTIFICATION: PREDOCTORAL FELLOWSHIP AWARDS FOR MINORITY STUDENTS INSTITUTIONAL CERTIFICATION This is to certify that (FILL IN APPLICANT NAME) who submitted an application for an NIH Predoctoral Fellowship Award for Minority Students is: (1) currently enrolled in a Ph.D. or combined M.D./Ph.D. (or other combined professional doctorate/research Ph.D.) degree program in the biomedical sciences at this institution, or has been accepted by and agreed to enroll in such a program during the 1994-95 academic year; (2) an underrepresented minority student, i.e., belonging to a particular ethnic or racial group that has been determined by our institution to be underrepresented in biomedical or behavioral research in the U.S. OPTIONAL. This individual is a member of the (PLEASE CIRCLE ONE) Black, Hispanic, Native American, Pacific Islander, or other racial/ethnic group. (3) a U.S. citizen, non-citizen national, or permanent resident. Signature and Title of the Graduate Program Director. Signature and Title of the Authorized University Official. $$E2 END ************************************************************ $$E3 BEGIN R3 19940204 APPEND RFA LM-94-002 BOTH *********************** APPLIED RESEARCH RELEVANT TO AN ELECTRONIC MEDICAL RECORD NIH GUIDE, Volume 23, Number 6, February 11, 1994 RFA: LM-94-002 P.T. 34; K.W. 0710078, 0730045 National Library of Medicine Agency for Health Care Policy and Research Letter of Intent Receipt Date: March 28, 1994 Application Receipt Date: April 27, 1994 The Applied Research Relevant to an Electronic Medical Record RFA (LM-94-002), published in the NIH Guide for Grants and Contracts, Volume 23, Number 5, February 4, 1994, invited applications for cooperative agreements for applied research and development projects relevant to the development of an electronic medical record system (EMRS). The purpose of this amendment is to revise the Notice of Availability of the RFA and the RFA as follows: In the Notice of Availability, the following areas are revised: In the heading section at the top of the Notice, insert "Agency for Health Care Policy and Research" under the National Library of Medicine because AHCPR is a co-sponsor of the RFA. Under APPLICATION PROCEDURES, the first sentence of the sixth paragraph is revised to read: "Applications must be received by April 27, 1994." Under REVIEW CONSIDERATIONS, the third bullet in the third paragraph listing factors to be used in judging applications is revised to read: "compliance with the requirements noted in the SPECIAL REQUIREMENTS section of this RFA". In the RFA, the following areas are revised: In the heading section at the top of the Notice, insert "Agency for Health Care Policy and Research" under the National Library of Medicine because AHCPR is a co-sponsor of the RFA. Under RESEARCH OBJECTIVES, the third paragraph under Objectives and Scope on AHCPR areas of interest in applications is revised to read: "The AHCPR has particular interest in applications that address improvements in delivery of health services through the use of an EMRS. Such topics include, but are not limited to: o incorporation of guidelines, decision aids, expert systems, and reminder systems o use of EMRS data for multiple purposes including patient care, payment, research, utilization review, assessment of quality of care, outcome analysis, and planning o database development o security/confidentiality/privacy issues o behavioral, interface, and other issues related to user acceptance o accessing data and information sources o multi-media options o storage, transmission, and retrieval of images o cost/benefit evaluations o shareability and standards, including content, data-exchange, and vocabulary issues o transmission of EMRS data among institutions to improve patient care". Under APPLICATION PROCEDURES, the first sentence of the sixth paragraph is revised to read: "Applications must be received by April 27, 1994." Under REVIEW CONSIDERATIONS, the third bullet in the fourth paragraph listing factors to be used in judging applications is revised to read: "compliance with the requirements noted in the SPECIAL REQUIREMENTS section of this RFA". Under AWARD CRITERIA, the third paragraph is revised to read: "Applicants should be aware that in addition to scientific/technical merit, consideration will be given to program priorities, program balance, and total cost of the proposal when staff, the Board of Regents of NLM, and the National Advisory Council of AHCPR make their funding recommendations." INQUIRIES For further information regarding these revisions and for copies of the corrected RFA, direct inquiries to: Milton Corn, M.D. Division of Extramural Programs National Library of Medicine Building 38A, Room 5N505 Bethesda, MD 20894 Telephone: (301) 496-4621 FAX: (301) 402-0421 E-mail: corn@lhc.nlm.nih.gov James McAllister, M.P.H. Center for General Health Service Extramural Research Agency for Health Care Policy and Research 2101 E. Jefferson Street, Suite 501 Rockville, MD 20852 Telephone: (301) 594-1439 FAX: (301) 594-2155 E-mail: jmcallis@po3.ahcpr.gov $$E3 END ************************************************************ $$E4 BEGIN R3 19940121 APPEND RFA NCI-CM-57198-12 BOTH ***************** OPERATION AND MAINTENANCE OF THE BIOLOGICAL DATA PROCESSING SYSTEM NIH GUIDE, Volume 23, Number 6, February 11, 1994 RFP AVAILABLE: NCI-CM-57198-12 P.T. National Cancer Institute This is an amendment to the synopsis published in the daily CBD on January 5, 1994 and the NIH Guide for Grants and Contracts Vol. 23, No. 3, January 21, 1994. Offerors should note that this solicitation is a total small business set-aside under the Standard Industrial Classification (SIC) code 7379. The small business size standard is $14.5M. See Note (s):1. RFP No. NCI-CM-57198 will be issued on or about February 4, 1994 and proposals will be due approximately March 21, 1994. Copies of the RFP may be obtained by sending a written request to: Joyce A. Crooke Research Contracts Branch, TCS National Cancer Institute Executive Plaza South, Room 603 Bethesda, MD 20892 Telephone: (301) 496-8620 No collect calls will be accepted. $$E4 END ************************************************************ From owner-sci-resources@net.bio.net Fri Feb 11 22:00:00 1994 Path: biosci!biosci!not-for-mail From: Dave Kristofferson Newsgroups: bionet.sci-resources Subject: NIH GUIDE - RFA DK-94-016 - V23(06) 02/11/94 Date: 11 Feb 1994 23:39:00 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 427 Approved: biosci-moderator@net.bio.net Distribution: bionet Message-ID: <2ji12k$ltc@net.bio.net> NNTP-Posting-Host: net.bio.net $$XID RFA DK94016 DK-94-016 P1O1 *************************************** RESEARCH USING THE UNITED STATES RENAL DATA SYSTEM NIH GUIDE, Volume 23, Number 6, February 11, 1994 RFA: DK-94-016 P.T. National Institute of Diabetes and Digestive and Kidney Diseases Letter of Intent Receipt Date: April 20, 1994 Application Receipt Date: May 20, 1994 PURPOSE The purpose of this initiative is to invite grant applications for biomedical research questions that can be answered using the United States Renal Data System (USRDS) database. Awarded funds will be used to generate a tailored data file through the USRDS Coordinating Center, and to support the independent analysis of the data file by the investigator. 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), Research Using the United States Renal Data System, is related to the priority area of diabetes and chronic disabling conditions. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign organizations, both public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Minority individuals and women are encouraged to submit as Principal Investigators. MECHANISM OF SUPPORT Support of this program will be through the investigator initiated research project grant (R01) mechanism. Each grant award will be capped at $100,000 total cost (including direct and indirect cost) per year for a maximum of two years. Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. Awards will be administered under PHS grants policy as stated in the PHS Grants Policy Statement. This RFA is a one-time solicitation. Generally, future unsolicited competing continuation applications will compete with all investigator- initiated applications and be reviewed according to the customary peer review procedures. The earliest possible award date will be April 1, 1995. FUNDS AVAILABLE It is anticipated that approximately five awards will be made; however, this funding level is dependent upon the receipt of a sufficient number of applications of high scientific merit. Although this program is provided for in the financial plans of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the award of grants pursuant to this RFA is also contingent upon the availability of funds designated for this purpose. A total of $500,000 dollars have been set aside for this RFA in FY 1995. RESEARCH OBJECTIVES The number of patients being treated for End-stage renal disease (ESRD) in the United States has increased steadily since 1977. The total number of U.S. patients with treated ESRD was over 210,000 in 1990. End-stage renal disease treatment is costly. The 1990 estimated federal Medicare payments for ESRD patients averaged $36,600 per patient. The estimated total 1990 direct medical payments for ESRD by public and private payers was $7.26 billion. ESRD is a very serious condition, with high hospitalization rates and death rates. Thus, research to decrease the morbidity and mortality due to ESRD is urgently needed. The USRDS is a database with information on treated end stage renal disease patients and their treatment facilities in the United States. It is designed to serve as a resource to the academic and clinical medicine communities. The database contains information on approximately 462,000 Medicare patients who have had ESRD therapy at any time since 1976, including basic demographics, the primary medical diagnosis that led to renal failure, dialysis records, hospital records, and transplant information. For patients included in any of the USRDS special data collection studies, the specially collected information can be linked with their master file. In addition to patient-specific information, the database contains details on the 2,646 institutions that provide ESRD treatment services. Limited information is also available on non-Medicare funded ESRD patients who are being treated by the Department of Veterans Affairs. The USRDS database is supplemented by data from the U.S. Census Bureau. All release of data will be in compliance with the U.S. Privacy Act of 1974, and other relevant legislation. This information on patients may be supplied in encrypted form, so that identification of individuals is precluded. In addition, investigators seeking to use the data must supply written assurances that they will not use the data to attempt to identify individuals. Since 1989, the USRDS Coordinating Center has produced an annual data report which contains descriptive and analytic epidemiologic data on ESRD patients. The USRDS database has been very successful in providing data on several important issues in the biomedical research and clinical nephrology community. However, there are many other important questions that could be posed, and there is a multitude of data that can be analyzed. The purpose of this RFA is to solicit applications from investigators to pose and answer important biomedical and health research questions relevant to ESRD in the United States. Specific questions that would be considered responsive to this RFA include, but are not limited to, the following examples: o the relative incidence, prevalence, mortality, morbidity, and survival associated with various co-morbid conditions, causes of ESRD, modes of ESRD treatment, or subgroups of the treated ESRD population in the United States; o examination of the relative burden of disease in various minority groups; o ecologic analyses that relate prevalence of predisposing diseases to incidence and prevalence of treated and untreated ESRD in various subgroups of the population. o Analyses combining a biomedical research question and a health services research question. Creativity in using the data to develop descriptive, analytic, and hypothesis generating studies is encouraged. Applications proposing to investigate issues with a large impact on the health, well being, morbidity and mortality of treated ESRD patients will be considered responsive to this RFA. Investigators are urged to become familiar with the structure and data elements currently contained in the USRDS database, including data elements from relevant special studies. This information (including data dictionary, structure of the database, special studies data collection instruments) can be obtained from the Director, Epidemiology Program, Division of Kidney, Urologic and Hematologic Diseases, NIDDK, (301) 594-7586 (see INQUIRIES Section below). In addition, copies of the USRDS Annual Data Reports may be useful. The United States Renal Data System Annual Data Reports may usually be found in dialysis units, nephrology department libraries, and medical libraries; a copy of the 1993 Annual Data Report can be ordered through the National Technical Information Service (703) 487-4600, order number PB 93 202 786, for $77. The USRDS data release policy includes the following provisions: The sole purpose of providing the data is the conduct of legitimate biomedical and health services research by the Principal Investigator (PI). The investigator will not use the data to identify individual persons or institutions represented on the file. The investigator will not combine or link the data provided with any other collection or source of information that may contain information specific to individuals on the file, unless specific, written authorization has been obtained through the approval process. The investigator will not use the data for purposes that are not related to biomedical or health services research. The investigator will not publish or otherwise disclose the data in the file to any person unless the data have been aggregated (that is, combined into groupings of data such that the data are no longer specific to any individual within each grouping) and no cells (aggregates of data) contain information on fewer than 10 individuals. A copy of any aggregation of data intended for publication will be submitted to the USRDS Project Officer for review prior to publication; if the publication is not in conformity with the Privacy Act, it will not be published until revised to adhere to the Privacy Act provisions. Appropriate administrative, technical, procedural, and physical safeguards shall be established by the investigator to protect the confidentiality of the data and to prevent unauthorized access to it. The safeguards will provide a level of security outlined in OMB Circular No. A-130, Appendix III-- "Security of Federal Automated Information Systems," which sets forth guidelines for security plans for automated information systems in Federal agencies. The investigator is encouraged to contact Dr. Camille Jones (301-594-7586) or the USRDS Project Officer, Dr. Lawrence Agodoa (301-594-7553) to discuss the data request and to request a copy of the USRDS Data Release Policy and the USRDS Agreement for Data Release Form. Both may be reached via mail at the following address: KUH/NIDDK, Westwood Building, Room 3A-06, 5333 Westbard Avenue, Bethesda, MD 20892. The USRDS database Coordinating Center may also be contacted for information about the database (313-998-6610). The official request to the USRDS for USRDS data can be submitted at any time and must be done separately from submitting an application to the NIH in response to this RFA. If the only way that the investigator will be able to do the analysis is with funding from this RFA, the investigator should submit the request for USRDS data after the application has been approved. The USRDS process of reviewing a written request for data and generating and releasing the data takes approximately three months. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements are required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis must be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale must be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues must be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information must be included in the form PHS 398 (rev. 9/91) in Item 4 (Research Design and Methods) of the Research Plan AND summarized in Item 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations; i.e., Native Americans (including American Indians or Alaskan Natives), Asian/Pacific Islanders, Blacks, Hispanics. The rationale for studies on single minority population groups should be provided. For the purpose of this policy, clinical research is defined as human biomedical and behavioral studies of etiology, epidemiology, prevention and preventive strategies, diagnosis, or treatment of diseases, disorders or conditions, including but not limited to clinical trials. The usual NIH policies concerning research on human subjects also apply. For foreign awards, the policy on inclusion of women applies fully; since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. If the required information is not contained within the application, the application will be returned without review. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. LETTER OF INTENT Prospective applicants are asked to submit, by April 20, 1994, a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, the identities of other key personnel and participating institutions, and the number and title of the RFA in response to which the application may be submitted. The letter of intent is to be sent to the Chief, Review Branch, Division of Extramural Activities at the address listed under INQUIRIES. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information that it contains is helpful in planning for the review of applications. It allows NIDDK staff to estimate the potential review workload and to avoid possible conflict of interest in the review. APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 9/91) is to be used in applying for these grants. The form is available from most institutional offices of sponsored research and from the Office of Grants Information, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone 301/594-7248. The RFA label available in the PHS 398 application form must be affixed to the bottom of the face page. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2a of the face page of the application form and check the YES box. Submit a signed, typewritten original of the application, including the Checklist, and three signed, exact photocopies, in one package to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** At time of submission, two additional copies of the application must also be sent under separate cover to: Chief, Review Branch Division of Extramural Activities National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 605 Bethesda, MD 20892 Applications must be received by May 20, 1994. If an application is received after that date, it will be returned to the applicant. The Division of Research Grants (DRG) will not accept any application in response to this RFA that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. However, it is allowable to submit the same project as both an R01 and as a component project of a program project. The DRG will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of substantial revisions of applications previously reviewed. Such applications must not only include an introduction addressing the previous critique but also be responsive to this RFA. REVIEW CONSIDERATIONS Upon receipt, applications will be initially reviewed by the DRG for completeness. Incomplete applications will be returned to the applicant without further consideration. Evaluation for responsiveness to the program requirements and criteria stated in the RFA is an NIDDK staff function. If the application is not responsive to the RFA, NIDDK staff will return it to the applicant. Those applications that are complete and responsive will be evaluated in accordance with the criteria stated below for scientific/technical merit by an appropriate peer review group convened by the NIDDK. If the number of applications is large compared to the number of awards to be made, a preliminary scientific peer review may be conducted and applications withdrawn from further review if they are not competitive for the award. The NIDDK will notify the applicant and institutional official of this action. Those applications judged to be competitive will be further reviewed for scientific and technical merit in accordance with the usual NIH peer review procedures by an initial review group specifically convened for this RFA. Following this review, the applications may be given a second level review by the NIDDK Advisory Council unless not recommended for further consideration by the initial review group. Review criteria for this RFA are as follows: o Scientific/medical/public health significance of the proposed research. o Adequate justification and rationale for the project. Knowledge of literature with respect to the topic of interest. o Appropriateness and adequacy of the experimental approach and methodology proposed to carry out the research. o Realistic cost estimates for generating and analyzing the data. Appropriateness of the proposed budget and duration in relation to the proposed research. o Availability of resources necessary to perform the proposed research. o Qualifications and experience of the Principal Investigator and staff in epidemiologic research and clinical nephrology. o If the researcher is from a foreign country, the uniqueness of research such that it can only be performed outside of the United States must be demonstrated. AWARD CRITERIA The anticipated date of award is April 1, 1995. Applications will compete for available funds with all other applications recommended by the initial review group. The following will be considered in making funding decisions: o Quality of the proposed project as determined by peer review. o Availability of funds. o Programmatic balance among the studies recommended for funding. INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. Direct inquiries regarding programmatic issues to: Camille A. Jones, M.D., M.P.H. Division of Kidney, Urologic, and Hematologic Diseases National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 3A-06 Bethesda, MD 20892 Telephone: (301) 594-7586 FAX: (301) 594-7501 Inquiries regarding fiscal matters may be directed to: Ms. Trude McCain Division of Extramural Activities National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 649 Bethesda, MD 20892 Telephone: (301) 594-7543 Schedule Letter of Intent Receipt Date: April 20, 1994 Application Receipt Date: May 20, 1994 Initial Review: Fall 1994 Second Level Review: January 1995 Anticipated Date of Award: April 1, 1995 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.849. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. From owner-sci-resources@net.bio.net Fri Feb 11 22:00:00 1994 Path: biosci!biosci!not-for-mail From: Dave Kristofferson Newsgroups: bionet.sci-resources Subject: NIH GUIDE - RFA MH-94-007 - V23(06) 02/11/94 Date: 11 Feb 1994 23:39:17 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 478 Approved: biosci-moderator@net.bio.net Distribution: bionet Message-ID: <2ji135$lug@net.bio.net> NNTP-Posting-Host: net.bio.net $$XID RFA MH94007 MH-94-007 P1O1 *************************************** RESEARCH TRANSITION GRANT PROGRAM IN MENTAL HEALTH SERVICES NIH GUIDE, Volume 23, Number 6, February 11, 1994 RFA: MH-94-007 P.T. National Institute of Mental Health Application Receipt Date: May 6, 1994 PURPOSE Clinical mental health services research focuses on the process and quality of care and the effectiveness in "real world" settings of clinical interventions whose efficacy has been demonstrated in controlled clinical research environments. The purpose of this Request for Applications (RFA) is to stimulate the development of programs of clinical mental health services research at institutions that currently have strong programs in mental health clinical research, but are not engaged in extensive clinical mental health services research. A second goal of this RFA is to bring the expertise of mental health clinical researchers and general health services researchers into the clinical mental health services research field and to promote their collaborations with each other and with clinical mental health services researchers. Collaborations of this kind are greatly needed to bring new resources and talents to bear on the task of improving delivery of clinical mental health services in the nation. The development of programs focusing on the special mental health services issues of the following populations are strongly encouraged: minorities; persons who are homeless; persons who live in rural areas; or persons with AIDS, who are HIV positive, or are at risk of contracting the AIDS virus. Expansion of the nation's clinical mental health services research infrastructure is a major priority of the National Institute of Mental Health (NIMH) and is in response to recommendations made by the National Advisory Mental Health Council and by the Extramural Science Advisory Board. This RFA addresses recommendations set forth in the Clinical Services Research section of Caring for People with Severe Mental Disorders: A National Plan of Research to Improve Services and in the National Plan for Research on Child and Adolescent Mental Disorders. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This RFA, Research Transition Grant Program in Clinical Mental Health Services, is related to the priority areas of alcohol and other drugs, mental health, mental disorders, and violent adn abusive behaviors. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202/783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic public and private non- profit and for-profit organizations, including universities, colleges, hospitals, laboratories, units of State or local governments, and eligible agencies of the Federal government except for those institutions with extensive, ongoing collaborations between clinical mental health investigators and mental health services researchers. Women and minority investigators are encouraged to apply. MECHANISM OF SUPPORT This RFA will use the resource-related research project (R24). The R24 mechanism is used to support research projects that will enhance the capability of resources to serve biomedical research. The Research Transition Grant Program (RTGP) will be used by the National Institute of Mental Health (NIMH) to enhance research capability and clinical mental health services research program. Each award will be limited to five years of funding and is nonrenewable. This RFA is a one-time solicitation. FUNDS AVAILABLE It is anticipated that at least $2.5 million in total costs will be made available so that a minimum of five awards can be made. Each award will have a maximum yearly total cost amount of $500,000. RESEARCH OBJECTIVES Background. The Research Transition Grant Program (RTGP) in Clinical Mental Health Services is part of an integrated NIMH approach to institutional infrastructure development made up of several types of grants including: NIMH Developing Clinical Research Centers, Research Infrastructure Support Program (RISP) grants, Child and Adolescent Mental Health Services Research Centers, and Social Work Research Development Center grants. Together these provide a continuum of research infrastructure support for institutions with varying levels and types of mental health research activity. The RTGP grants are designed to enable institutions with current programs in clinical mental health research to develop into major clinical mental health services research settings, thus increasing the number of investigators obtaining extramural funding for work in the services research field. Expansion of the nation's clinical mental health services research infrastructure is a major priority for NIMH because it is essential for improving the care received by adults (including the elderly), adolescents, and children who suffer from mental and emotional disorders, particularly the most severe disorders. Mental Health Services Research. The field of mental health services research examines the impact of the organization, financing, management, and delivery of mental health services on the quality, cost, access to, and outcomes of care. There are two major components of services research: service systems research and clinical services research. Service systems research focuses on questions related to the organization, financing, and integration of mental health services. Clinical mental health services research focuses on the process and quality of care and the effectiveness in community settings of clinical interventions whose efficacy has been demonstrated in controlled clinical research environments. This RFA seeks to enhance the clinical mental health services component of services research. The four major areas of clinical mental health services research are assessment research, treatment research, rehabilitation research, and outcomes research. Examples of research topics in these four areas include, but are not limited, to: Assessment Research o Studies of the barriers to the accurate recognition and diagnosis of mental disorders, with special attention to (a) patient variables, such as culturally related beliefs or response patterns; and (b) provider variables, such as knowledge and attitudes about mental disorders o Research on the reliability, validity, and stability of symptom, quality-of-life, functioning, social status, and vocational status measures, particularly for individuals from different socioeconomic, ethnic, or cultural groups Treatment Research o Research on the applicability and effectiveness of clinically efficacious treatments in "real world" settings, such as community mental health centers, nursing homes, or primary care practices. o Studies of the relationship between the process of providing mental health services (e.g., therapeutic alliance) and outcomes of care (e.g., continuation in care and improved functioning) Rehabilitation Research o Studies to determine what types and combinations of rehabilitation services are most beneficial for severely mentally ill individuals with different clinical, social, and economic circumstances o Research on ways to maximize effective use of family expertise and client preferences in planning rehabilitation services Outcomes Research o Studies of the reliability and validity of instruments in multiple outcome domains (clinical, rehabilitative, humanitarian, and public welfare), particularly for understudied populations, e.g., persons who are homeless, migrants, minorities, rural residents o Research testing the performance over time of instruments measuring inherently unstable patient or client characteristics SPECIAL REQUIREMENTS Applicant institutions should describe a comprehensive and coherent plan of modification to the institution's current research environment that will expand the capacity of the clinical research program to carry out extramurally-funded, clinical services research. The plan must demonstrate the actual commitment of institutional resources, which may include hiring mental health services researchers, providing mental health training to institutional investigators experienced in health services research, and/or providing services research training to clinical investigators. However, a substantial commitment to a services research perspective is essential. A central philosophical principle underlying this program is that different institutions will require different types and amounts of development in clinical services research. Therefore, this RFA does not prescribe in any detail the nature of the activities to be applied for or supported. The following types of support may be requested under this program: o Partial salary support for clinical mental health services research faculty o Training expenses in clinical mental health services research, such as tuition remission or course fees, for junior clinical faculty o Research patient recruitment, diagnosis, assessment, and follow-up o Consultation from clinical mental health services research investigators o Biostatistical and data-base management o Small equipment and research instruments o Research technicians and assistants o Developmental, feasibility, and/or pilot studies The application should present a plan for the proposed RTGP. It should assess the current institutional and faculty capacity to conduct clinical mental health services research, identify unmet needs, and describe the activities to develop the institutional infrastructure and faculty capacity to conduct this research. The application should contain the following: o Statements of objectives, substantive clinical services research focus, and justification o Specification of the proposed research area and plan for development, including brief abstracts of ongoing and proposed clinical services research projects o Overview of the research development plan for the institution, including plans for recruitment and retention of faculty skilled in clinical services research o Assessment of institutional capacity, including interest and availability of senior faculty and experienced clinical mental health services investigators o Description of the institutional commitment to substantial financial support of a clinical mental health services research program o Description of equipment, space, and other facility resources that are available for clinical mental health services research and identification of needed enhancement o Assessment of junior faculty interest and capability to engage in clinical mental health services research and identification of training, mentoring, and consultation proposed to enhance the capacity to develop extramurally- fundable research o Description of procedures to be used to solicit, review for scientific merit, monitor, and evaluate the outcome of pilot or feasibility studies, including measures to assure the protection of human subjects o Abstracts of pilot projects approved for support pending the award of funding for the RTGP Applications are limited to 25 pages. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements will be required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis should be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale should be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues should be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information should be included in the form PHS 398 in Sections 1-4 of the Research Plan AND summarized in Section 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., Native Americans (including American Indians or Alaskan Natives), Asian/Pacific Islanders, Blacks, Hispanics). The rationale for studies on single minority population groups should be provided. For the purpose of this policy, clinical research includes human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including but not limited to clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded. However, every effort should be made to include human tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. For foreign awards, the policy on inclusion of women applies fully; since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. If the required information is not contained within the application, the application will be returned. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and will be reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. APPLICATION PROCEDURES Applicants are to use the research grant application form PHS 398 (rev. 9/91). These forms are available at most institutional offices of sponsored research; from the Office of Grants Information Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone 301/594-7248; and from the Grants Management Branch, National Institute of Mental Health, 5600 Fishers Lane, Room 7C-05, Rockville, MD 20857, telephone 301/443-4414. The RFA number MH-94-007 and the title, Research Transition Grant Program in Clinical Mental Health Services, must be typed in item number 2a on the face page of the PHS 398 application form; the YES box must also be marked. Applicants must specify that the R24 mechanism is being used. Applicant institutions will need to demonstrate that they: (1) have a strong base of ongoing clinical mental health research activities; (2) need additional support to establish and maintain collaborative working relationships between clinical and services researchers; and (3) have the potential for building a mental health services research program that will equip them to compete effectively in future years for clinical mental health services research grants. The RFA label available in the PHS 398 application form must be affixed to the bottom of the face page of the application. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. All applications must be received by May 6, 1994 and will be reviewed in July. Applications received after the receipt date will be returned to the applicant without review. Submit, in one package, a signed original of the application, including the Checklist, and three signed copies to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** At the time of the submission, two additional copies of the application must also be sent to: Wright Williamson, M.S.W. Division of Extramural Activities National Institute of Mental Health 5600 Fishers Lane, Room 9C-14 Rockville, MD 20857 REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness and responsiveness. Incomplete or nonresponsive applications will be returned to the applicant without further consideration. Applications will be reviewed for scientific and technical merit by an initial review group (IRG) convened by the NIMH composed primarily of non-Federal scientific experts. Final review is by the appropriate National Advisory Council; review by Council may be based on policy considerations as well as scientific merit. By law, only applications recommended for consideration for funding by the Council may be supported. Summaries of IRG recommendations are sent to applicants as soon as possible following IRG review. Criteria to be considered in evaluating applications for scientific/technical merit include: o Scientific and technical significance and originality of the focus of the proposed development plan and research o Appropriateness and adequacy of the proposed development plan and the potential for the plan to effect significant and lasting improvements in the institution's ability to conduct extramurally-funded clinical mental health services research o Nature, amount, and duration of non-Federal commitment to the project o Capability of the Principal Investigator and other senior staff to provide leadership in the effort to enhance the institution's clinical mental health services research capacity o Adequate representation of minorities and women o Appropriateness of the proposed budget o Adequacy of the proposed means for protecting against or minimizing adverse effects to human subjects AWARD CRITERIA Awards will be made on or before September 30, 1994. As part of the NIMH Public-Academic Liaison (PAL) initiative, special encouragement is given to applications that involve active collaborations between academic researchers and public sector agencies in planning, undertaking, analyzing, and publishing research pertaining to persons with severe mental disorders. The PAL initiative is based on the premise that important new advances in understanding and treatment of severe mental disorders can result from improved linkages between the Nation's scientific resources and the public sector agencies and programs in which many persons with severe mental disorders receive their care. The scope of the PAL initiative encompasses public sector agencies of all types that deal with children, adolescents, adults, and elderly persons with severe mental disorders. Factors considered in determining which applications will be funded include IRG and Council recommendations, PHS program needs and priorities, and availability of funds. INQUIRIES Potential applicants should contact NIMH staff as early as possible for information and assistance in initiating the application process. The NIMH program staff member listed below may be contacted for further information about mental health services research and for technical assistance in developing an application. Ann A. Hohmann, Ph.D., M.P.H. Services Research Branch National Institute of Mental Health 5600 Fishers Lane, Room 10C-06 Rockville, MD 20857 Telephone: (301) 443-3364 For further information on grants management issues, applicants may contact: Diana S. Trunnell Grants Management Branch National Institute of Mental Health 5600 Fishers Lane, Room 7C-15 Rockville, MD 20857 Telephone: (301) 443-3065 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance 93.242, Mental Health Research Grants. 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 RFA is not subject to the intergovernmental review requirements of Executive Order 12372, as implemented through DHHS regulations at 45 CFR Part 100. From owner-sci-resources@net.bio.net Fri Feb 11 22:00:00 1994 Path: biosci!biosci!not-for-mail From: Dave Kristofferson Newsgroups: bionet.sci-resources Subject: NIH GUIDE - RFA AI-94-012 - V23(06) 02/11/94 Date: 11 Feb 1994 23:39:11 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 487 Approved: biosci-moderator@net.bio.net Distribution: bionet Message-ID: <2ji12v$lu2@net.bio.net> NNTP-Posting-Host: net.bio.net $$XID RFA AI94012 AI-94-012 P1O1 *************************************** AFFECTING GRAFT SURVIVAL WITH DONOR IMMUNE TISSUE NIH GUIDE, Volume 23, Number 6, February 11, 1994 RFA: AI-94-012 P.T. National Institute of Allergy and Infectious Diseases Letter of Intent Receipt Date: April 15, 1994 Application Receipt Date: June 21, 1994 PURPOSE The Division of Allergy, Immunology and Transplantation (DAIT) of the National Institute of Allergy and Infectious Diseases (NIAID) invites applications for basic, preclinical and clinical studies to increase knowledge of the interaction between donor and recipient immunocompetent cells. These studies have the potential to help develop protocols for enhancing solid organ graft survival by infusion of donor cells prior to or after transplantation. Information from these studies could lead to the use of donor tissue to manipulate the recipient's immune system in a controlled and specific fashion, thereby increasing graft survival and improving the management of autoimmune diseases. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This Request for Applications (RFA), Affecting Graft Survival With Donor Immune Tissue, is related to the priority areas of diabetes and chronic disabling diseases, and immunization and infectious diseases. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-782-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign, for-profit and non-profit organizations, public and private institutions, such as universities, colleges, hospitals, laboratories, units of State or local governments, and eligible agencies of the Federal government. Foreign institutions are not eligible to apply for First Independent Research Support and Transition (FIRST) Awards. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT The mechanisms of support will be the individual research project grant (R01) and the FIRST (R29) award. Multidisciplinary approaches that involve collaborative efforts among investigators in the fields of basic immunology, molecular biology, cell biology, biochemistry, and clinical transplantation are strongly encouraged. The total project period for an application submitted in response to this RFA may not exceed five years; a foreign application may not request more than three years of support. This RFA is a one-time solicitation for new applications. Future competing renewal applications will compete with all investigator-initiated applications and will be reviewed according to customary referral and review procedures. FIRST awards are not renewable. FUNDS AVAILABLE The estimated funds available for the total (direct and indirect) first year costs of all awards made under this RFA will be $1,500,000. In Fiscal Year 1994, the NIAID plans to fund approximately seven R01s/R29s. Applications may not request more than four percent annual inflationary increases for future years. The usual PHS policies governing grants administration and management will apply. This level of support is dependent on the receipt of a sufficient number of applications of high scientific merit. Although this program is provided for in the financial plans of the NIAID, awards pursuant to this RFA are contingent upon the availability of funds for this purpose. Funding beyond the first and subsequent years of the grant will be contingent upon satisfactory progress during the preceding years and availability of funds. RESEARCH OBJECTIVES Background Successful transplantation relies on the ability to transplant a solid organ without rejection while maintaining a normal immune response to infectious agents. With the exception of transplants between identical twins, the only known way to accomplish this is to induce a specific non-responsive (tolerant) state, whereby the grafted tissue is ultimately not recognized as foreign. Donor specific transplant tolerance has been achieved for solid organ transplantation in animal models via induction regimens using donor immunocompetent tissue, e.g., bone marrow and peripheral blood. The application of those induction regimens to humans would be served best by understanding fully the basic immunological mechanisms involved and the role of the donor immune tissue in inducing and maintaining this tolerant state. Tolerance can be categorized into three types: (1) clonal deletion (central tolerance), (2) clonal anergy (peripheral tolerance), and (3) active cellular suppressive mechanisms. The most stable type of tolerance is clonal deletion, whereby specific reactive T cells (i.e., T cells bearing T-cell receptors that recognize the foreign tissue antigens) have been deleted from the repertoire entirely through negative selection in the thymus. The only way to develop an immune response to the antigen (i.e., "break" this type of tolerance) is to have selection and expansion of a T cell bearing a T-cell receptor that cross-reacts with the donor non-self antigens. The most reliable way to induce central tolerance is to engraft allogeneic stem cells. Donor specific lymphoid cells that develop in the presence of both host and donor antigens become tolerant to host antigens. Clonal anergy is defined as the functional inactivation of antigen-specific T cells. Normally, this type of immunological regulation is thought to be a "fail-safe" mechanism to inactivate self-reactive T cells that escape clonal deletion in the thymus. It has become increasingly obvious that specific inter-and intracellular signalling events are required to anergize a T cell versus activate it. While this mechanism of tolerance undoubtedly plays a major role in successful transplants in recipients who have long-term graft survival, anergy was established early in the life of the T cell and the T cell could still be activated by a non-specific mechanism. A breakdown of anergy would lead directly to rejection, e.g., when opportunistic infections such as CMV stimulate the immune system to produce IL-2 or by non-specific activation of the quiescent T cells that are capable of recognizing the graft. The third mechanism of donor-specific non-responsiveness, active cellular suppression, is probably the most important for transplantation. This active suppression relies on specific cells to down-regulate the immune response. For donor-specific non-responsiveness, the introduction of donor immunocompetent cells into the recipient appears to specifically turn off the recipient's immune response to the donor antigens. Recently, it has been shown that transfusions of donor blood, prior to transplantation, may enhance graft survival. Also, the administration of donor bone marrow cells, transfused pre- or peri-operatively under the cover of immunosuppressive agents, induces a donor-specific non-responsiveness that is transient in humans and has been long-lasting, if not permanent, in animal models. Additionally, organs that contain larger amounts of lymphoid tissue, such as the liver, appear to be well tolerated immunologically, and it has been suggested that this "tolerance" may result from the establishment of microchimerism in the recipient. This microchimerism has been studied and current hypotheses are that there is a subset of cells responsible for inducing and maintaining this tolerant condition. While progress has been made in phenotyping the tolerance-inducing donor cell, a number of important factors remain unclear: whether this cell is derived from the T-cell lineage; the in vivo mechanism operative in tolerance; what constraints for the route of administration exist; and timing of exposure of the recipient to this cell type in order to obtain transplant tolerance. Identification of the cells necessary for the induction and maintenance of donor-specific tolerance, the mechanisms involved, and timing of the regimen will greatly enhance human graft survival. Research Objectives and Scope The objective of this RFA is to support innovative new research to characterize the immunocompetent cells responsible for and the mechanisms by which donor immune tissue or cells enhance graft survival. This RFA will support basic, preclinical, and clinical studies aimed at characterizing the interaction between donor and recipient immunocompetent cells. These studies have the potential to help develop protocols for enhancing graft survival by using an infusion of donor lymphoid or dendritic cells prior to or after solid organ transplantation, either alone or in combination with other agents, to make the recipient non-responsive to the donor. Information from these studies could lead to the use of donor tissue to manipulate the recipient's immune system in a controlled and specific fashion. Applications should focus on identifying the donor and recipient cells involved in and the mechanisms responsible for induction and maintenance of donor-specific non-responsiveness in the transplant setting. Areas of particular interest to NIAID include, but are not limited to, the following: o identification of the donor cell(s) involved in the induction and maintenance of donor-specific non-responsiveness o determination of the optimal timing of administration of donor cells for inducing long lasting donor-specific non-responsiveness o determination of the optimal route of administration of the donor cells for induction of donor specific non-responsiveness o evaluation of the role of chimerism in the maintenance of tolerance (whether it be peripheral microchimerism or any other type and degree of chimerism) o identification of the mechanism(s) by which donor immunocompetent cells suppress the recipient immune response (1) what are the signals necessary to establish the tolerance? (2) where is the donor cell exerting its influence on the recipient immune response, i.e., in the periphery or centrally? (3) can donor cells be manipulated to enhance their tolerogenic capacity? Animal models must be used in a way that is applicable to human transplants. Therefore, although studies using just the infusion of donor immunocompetent cells may be proposed, this type of study must be focused on understanding the basic mechanisms of transplant tolerance induction and maintenance. Knowledge generated by this research project must be applicable to human transplantation where an underlying immunosuppressive regimen is used. Therefore, studies proposing to use a monotherapy must also show that currently accepted standard immunosuppressive regimen is or is not deleterious to the induction of the tolerant state. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements will be required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis should be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale should be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues should be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information should be included in the form PHS 398 in Sections 1-4 of the Research Plan AND summarized in Section 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., Native Americans (including American Indians or Alaskan Natives), Asian/Pacific Islanders, Blacks, Hispanics). The rationale for studies on single minority population groups should be provided. For the purpose of this policy, clinical research includes human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including but not limited to clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded. However, every effort should be made to include human tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. For foreign awards, the policy on inclusion of women applies fully; since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. If the required information is not contained within the application, the application will be returned. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and will be reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. NOTE: Peer review groups need adequate information about the composition of proposed study populations in all applications involving human subjects. To avoid delays in review of such applications, the NIAID therefore requires that, as a minimum, the application must contain demographic data about the clinic and/or in-patient population from which study subjects will be drawn: average hospital admissions per year; percentage distribution of black/hispanic/other minority/non-minority populations; gender; etc. Studies using non-hospital populations, such as community-based studies, should provide similar data about populations in the area or region from which the study subjects will be drawn. In the absence of current data, historical demographic information and/or previous recruitment data for similar studies from the proposed sites should be provided. LETTER OF INTENT Prospective applicants are asked to submit, by April 15, 1994, a letter of intent that includes a descriptive title of the overall proposed research, the name, address and telephone number of the Principal Investigator (Program Director), and the number and title of this RFA. Although the letter of intent is not required, is not binding, does not commit the sender to submit an application, and does not enter into the review of subsequent applications, the information that it contains allows NIAID staff to estimate the potential review workload and to avoid conflict of interest in the review. The letter of intent is to be sent to Dr. Olivia Preble at the address listed under INQUIRIES. APPLICATION PROCEDURES Applications are to be submitted on the standard research grant application form PHS 398 (rev. 09/91). These application forms may be obtained from the institution's office for sponsored research or its equivalent and from the Office of Grants Information, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone (301) 594-7248. For purposes of identification and processing, item 2a on the face page of the application must be marked "YES" and the RFA number and the words "AFFECTING GRAFT SURVIVAL WITH DONOR IMMUNE TISSUE" must be typed in. The RFA label available in the application form PHS 398 must be affixed to the bottom of the face page. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. FIRST 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. In preparing the application in response to this RFA, the applicant should bear in mind the research objectives of this RFA. Applications should be prepared according to the instructions in form PHS 398 (rev. 9/91). Failure to follow these instructions may result in delays in the review or in an incomplete application. It is highly recommended that the Chief of the Genetics and Transplantation Branch be contacted in the early stages of preparation of the application. (See program contact in INQUIRIES below.) Applications must be received by June 21, 1994. Applications that do not conform to the instructions contained in PHS 398 (rev. 9/91) application kit, will be judged non-responsive and will be returned to the applicant. Applications received after the receipt date will be returned without review. The Division of Research Grants (DRG) will not accept any application in response to this RFA that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. This does not exclude the submission of substantial revisions of an application already reviewed. These applications must, however, include an introduction addressing the previous critique. Submit a signed, typewritten original of the application, including the checklist, and three signed, exact, single-sided photocopies, in one package to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** At the time of submission, two additional exact copies of the grant application and all five sets of the appendix must also be sent to Dr. Olivia Preble at the address listed under INQUIRIES. Applicants from institutions that have a General Clinical Research Center (GCRC) funded by the NIH National Center for Research Resources may wish to identify the GCRC as a resource for conducting the proposed research. If so, a letter of agreement from either the GCRC program director or Principal Investigator could be included with the application. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by the NIH Division of Research Grants (DRG) and for responsiveness by NIAID staff; those judged to be incomplete will be returned to the applicant without review. Those considered to be non-responsive will be either returned without review or will be referred to the DRG as unsolicited applications, to be scheduled for initial review at the next DRG review cycle. Those applications that are complete and responsive may be triaged by an NIAID peer review group to determine their relative scientific merit. The NIAID will withdraw from competition those applications judged to be non-competitive for award and will notify the applicant and institutional business officials. Those applications judged by the reviewers to be competitive for award will be further reviewed for scientific and technical merit by a review committee convened by the Division of Extramural Activities, NIAID. Applicants may receive an abbreviated summary statement together with essentially unedited reviewers' comments. The second level of review will be provided by the National Advisory Allergy and Infectious Diseases Council. Review, Council and award dates are listed below under Schedule. The factors to be considered in the evaluation of scientific merit of each application will be those used in the review of traditional research project grant applications, including: the novelty, originality, and feasibility of the approach; the training, experience, and research competence of the investigator(s); the adequacy of the experimental design; and the adequacy and suitability of the facilities. While the following factors do not usually influence the priority score, they are nonetheless carefully considered by the initial review group: the appropriateness of the requested budget to the work proposed; the adequacy of protection of human subjects and/or animals in research; and the adherence to NIH guidelines concerning adequate representation of women and minorities in clinical research. Any documented concerns expressed by the initial review group about any of these factors on a given application may influence the recommendation of the Advisory Council concerning funding of that application. AWARD CRITERIA Funding decisions will be made on the basis of scientific and technical merit as determined by peer review, program priorities, and the availability of funds. INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Stephen M. Rose, Ph.D. Division of Allergy, Immunology and Transplantation National Institute of Allergy and Infectious Diseases Solar Building, Room 4A14 6003 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-5598 FAX: (301) 402-2571 Direct inquiries regarding review issues; address the letter of intent to; and mail two copies of the application and all five sets of appendices to: Olivia Preble, Ph.D. Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4C19 6003 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-8208 FAX: (301) 402-2638 Direct inquiries regarding fiscal matters to: Ms. Barbara Huffman Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4C26 6003 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-7075 Schedule Letter of Intent Receipt Date: April 15, 1994 Application Receipt Date: June 21, 1994 Scientific Review Date: October 1994 Advisory Council Date: February 1995 Earliest Award Date: April 1995 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance, No. 93.855 - Immunology, Allergy and Transplantation Research. Awards will be made under the authority of the Public Health Service Act, Title III, Section 301 (Public Law 78-410, as amended; 42 USC 241) and administered under PHS grants policies and Federal Regulations 42 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. From owner-sci-resources@net.bio.net Fri Feb 11 22:00:00 1994 Path: biosci!biosci!not-for-mail From: Dave Kristofferson Newsgroups: bionet.sci-resources Subject: NIH GUIDE - RFA AI-94-011 - V23(06) 02/11/94 Date: 11 Feb 1994 23:39:06 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 434 Approved: biosci-moderator@net.bio.net Distribution: bionet Message-ID: <2ji12q$ltp@net.bio.net> NNTP-Posting-Host: net.bio.net $$XID RFA AI94011 AI-94-011 P1O1 *************************************** BASIC BIOLOGY OF IMMUNE RESPONSES FOR VACCINE RESEARCH NIH GUIDE, Volume 23, Number 6, February 11, 1994 RFA: AI-94-011 P.T. National Institute of Allergy and Infectious Diseases National Institute on Aging Letter of Intent Receipt Date: April 15, 1994 Application Receipt Date: July 13, 1994 PURPOSE The Division of Allergy, Immunology and Transplantation (DAIT) of the National Institute of Allergy and Infectious Diseases (NIAID) and the Biology of Aging Program (BAP) of the National Institute on Aging (NIA) invite applications for basic studies designed to elucidate key processes underlying immune responsiveness that will facilitate new and improved approaches to vaccination for infectious diseases other than AIDS. There is increasing need to develop methods for achieving protective immunity that depend on manipulating elements of the immune system (e.g., the order, concentrations, and delivery of cytokines). There are numerous examples of potential vaccines that are ineffective because of weak immunogenicity that could become effective vaccines if properly presented to a prepared or modulated immune system. This Request for Applications (RFA) is intended to spur the acquisition of knowledge necessary to efficaciously and safely modulate elements of the immune system leading to protective immunization against infectious diseases. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This RFA, Basic Biology of Immune Responses for Vaccine Research, is related to the priority areas of diabetes and chronic disabling diseases, and to immunization and infectious diseases. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-782-3238). ELIGIBILITY REQUIREMENTS Research grant applications may be submitted by domestic, for-profit and non-profit organizations, public and private institutions, such as universities, colleges, hospitals, laboratories, units of State or local governments, and eligible agencies of the Federal government. Foreign organizations are not eligible to apply. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT The mechanism of support will be the Program Project (P01) grant. Research that involves collaborative efforts among investigators in the fields of basic immunology, molecular biology, cell biology, biochemistry, and infectious disease is strongly encouraged. The total project period for applications submitted in response to this RFA may not exceed five years. At this time, the NIAID and the NIA are administratively limiting the duration of P01 grants to four years; this administrative limitation may change in the future. If by the beginning of the last year of support, the NIAID and the NIA have not announced their intention to readvertise the RFA, P01 incumbents who wish to recompete are strongly encouraged to contact NIAID and NIA Program Staff concerning selection of an appropriate research grant mechanism before reapplying. FUNDS AVAILABLE The estimated total funds (direct and indirect costs) available for first year of support for all awards made under this RFA will be $3,000,000. In Fiscal Year 1995, the NIAID and the NIA plan to fund approximately four P01 awards. Applications may not request more than four percent annual inflationary increases for future years. Applications may not request budgets in excess of $750,000 total costs (direct and indirect) in the first year. An application with a first year requested amount in excess of the above will require written approval by senior NIAID and NIA officials via the program officers for acceptance of the application for processing. 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 and the NIA, awards pursuant to this RFA are contingent upon the availability of funds for this purpose. Funding beyond the first and subsequent years of the grant will be contingent upon satisfactory progress during the preceding years and availability of funds. RESEARCH OBJECTIVES Background The most effective procedure for managing human infectious diseases is preventive immunization (vaccination). Despite the remarkable successes of vaccination in eradicating smallpox and soon, poliomyelitis, and preventing illness and death of many millions of children, there remain many infectious diseases that have not yielded to vigorous attempts to develop vaccines. Furthermore, it is increasingly evident that successful vaccination of elderly humans is a special problem that needs to be addressed due to the declining competence of the immune system with age. The generation of protective immunity depends upon a responsive immune system. During the last 10 years, there has been a flood of new information in the field of immunology. Much has been learned about the mechanisms of defined, protein antigen processing and presentation of key epitopes in a manner that engenders effective immune responses. Yet, very little is known about the antigens of pathogenic microorganisms and how they could be presented to drive desired types of immune responses. Similarly, a great deal is known about subsets of T lymphocytes and the spectrum of cytokines each subset produces, as well as about B lymphocytes and their responses to cytokines. Yet, relatively little is known about the characteristics and generation of memory T and B cells which are essential for long-lasting protective immunity. Moreover, the mechanisms responsible for the generation of cytotoxic T cells that are efficient in attacking and neutralizing cells in the body that are infected with viruses, bacteria and protozoa remain uncertain. Research Objectives and Scope The goal of this initiative is to further increase knowledge about the basic structures and functions of the immune system that lead to protective immunization against infectious diseases. HIV infection and its sequelae are not within the scope of this RFA. Examples of relevant research topics are provided below. However, the list of examples is neither complete nor restrictive: o Elucidation of the events and factors that lead to selective expression/expansion of morphologically and/or functionally distinguishable T cell subsets; o Studies on the phenotypic and functional stability of T cell subsets and control of the selective expression of cytokine genes by subsets of T cells; o The morphological and/or functional characteristics of memory B and T cells and clarification of mechanisms for generating specific memory cells; o Analysis of the roles played by different types and functional states of antigen processing/presenting cells and the cytokines they secrete in determining the major type of immune response, the effector mechanism expressed and/or isotypes of antibodies produced; and o Studies on the basic mechanisms that are affected by immunological adjuvants and examination of the immuno-enhancing properties of adjuvants All of the preceding examples represent central features of immune responses to antigens in general. However, they are particularly important, at present, in devising new approaches to vaccination against infectious, pathogenic organisms. Applications submitted in response to this RFA should focus on elucidating basic mechanisms that qualitatively and/or quantitatively enhance immune responses, both humoral and cell-mediated. Improved understanding of approaches to enhancing immune responses will be important not only to immunization of healthy, young adults but the elderly as well. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements will be required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis should be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale should be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues should be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information should be included in the form PHS 398 in Sections 1-4 of the Research Plan AND summarized in Section 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., Native Americans (including American Indians or Alaskan Natives), Asian/Pacific Islanders, Blacks, Hispanics). The rationale for studies on single minority population groups should be provided. For the purpose of this policy, clinical research includes human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including but not limited to clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded. However, every effort should be made to include human tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. For foreign awards, the policy on inclusion of women applies fully; since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. If the required information is not contained within the application, the application will be returned. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and will be reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. LETTER OF INTENT Prospective applicants are asked to submit, by April 15, 1994, a letter of intent that includes a descriptive title of the overall proposed research, the name, address and telephone number of the Program Director, the number and title of this RFA, and a list of the key investigators and their institution(s). Although the letter of intent is not required, is not binding, does not commit the sender to submit an application, and does not enter into the review of subsequent applications, the information that it contains allows NIAID staff to estimate the potential review workload and to avoid conflict of interest in the review. The letter of intent is to be sent to Dr. Mark Rohrbaugh at the address listed under INQUIRIES. APPLICATION PROCEDURES Applications are to be submitted on the standard research grant application form PHS 398 (rev. 9/91). These application forms may be obtained from the institution's office for sponsored research or its equivalent and from the Office of Grants Information, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone (301) 594-7248. For purposes of identification and processing, item 2a on the face page of the application must be marked "YES" and the RFA number and the words "BASIC BIOLOGY OF IMMUNE RESPONSES FOR VACCINE RESEARCH" must be typed in. In preparing the application in response to this RFA, the applicant should bear in mind the research objectives of this RFA. P01 applications should be prepared using the guidance and instructions provided in the NIAID Information Brochure on Program Project Grants and Multiproject Cooperative Agreements, available from the program staff listed under INQUIRIES. Failure to follow these instructions may result in delays in the review or in an incomplete application. It is highly recommended that the program staff listed under INQUIRIES be contacted in the early stages of preparing the application. Applications must be received by July 13, 1994. Applications that do not conform to the instructions contained in PHS 398 (rev. 9/91) application kit, will be judged non-responsive and will be returned to the applicant. The RFA label available in PHS 398 must be affixed to the bottom of the face page. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. Applications received after the receipt date will be returned without review. If the application submitted in response to this RFA is substantially similar to a grant application already submitted to the NIH for review, but has not yet been reviewed, the applicant will be asked to withdraw either the pending application or the new one. Simultaneous submission of identical applications will not be allowed, nor will essentially identical applications be reviewed by different review committees. Therefore, an application cannot be submitted in response to this RFA that is essentially identical to one that has already been reviewed. This does not preclude the submission of substantial revisions of applications already reviewed, but such applications must include an introduction addressing the previous critique. Submit a signed, typewritten original of the application, including the checklist, and three signed, exact, single-sided photocopies, in one package to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892 At the time of submission, two additional exact copies of the grant application and all five sets of the appendix must also be sent to dr. Mark Rohrbaugh at the address listed under INQUIRIES. Applicants from institutions that have a General Clinical Research Center (GCRC) funded by the NIH National Center for Research Resources may wish to identify the GCRC as a resource for conducting the proposed research. If so, a letter of agreement from either the GCRC program director or Principal Investigator could be included with the application. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by the Division of Research Grants (DRG) and for responsiveness by NIAID staff; those judged to be incomplete will be returned to the applicant without review. Those considered to be non-responsive may be returned without review. Those applications that are complete and responsive may be subjected to a triage by an NIAID peer review group to determine their scientific merit relative to other applications received in response to this RFA. The NIAID and the NIA will withdraw from competition those applications judged to be non-competitive for award and will notify the applicant and institutional business officials. Those applications judged by the reviewers to be competitive for award will be 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 Advisory Councils of the NIAID and the NIA. The factors to be considered in the evaluation of scientific merit of each application will be those used in the review of traditional research project grant applications, including: the novelty, originality, and feasibility of the approach; the training, experience, and research competence of the investigators; the adequacy of the experimental design; and the adequacy and suitability of the facilities. For program project applications, additional review criteria are used, which are outlined in the NIAID Information Brochure on Program Project Grants and Multiproject Cooperative Agreements. While the following review factors do not usually influence the priority score, they are nonetheless carefully considered by the initial review group: the appropriateness of the requested budget to the work proposed; the adequacy of protection of human subjects and/or animals in research; and the adherence to NIH guidelines concerning adequate representation of women and minorities in clinical research. Any documented concerns expressed by the initial review group about any of these factors on a given application may influence the recommendation of the Advisory Council concerning funding of that application. AWARD CRITERIA Funding decisions will be made on the basis of scientific and technical merit as determined by peer review, program needs and balance, and the availability of funds. INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: M. Michele Hogan, Ph.D. Division of Allergy, Immunology and Transplantation National Institute of Allergy and Infectious Diseases Solar Building, Room 4A22 6003 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-7551 FAX: (301) 402-2571 Anna M. McCormick, Ph.D. Biology of Aging Program National Institute on Aging Gateway Building, Suite 2C231 Bethesda, MD 20892 Telephone: (301) 496-6402 FAX: (301) 402-0010 Direct inquiries regarding review issues, address the letter of intent to, and mail two copies of the application and the five sets of appendices to: Mark Rohrbaugh, Ph.D. Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4C22 6003 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-8424 FAX: (301) 402-2638 Direct inquiries regarding fiscal matters to: Mr. Jeffrey Carow Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4B29 6003 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-7075 Schedule Letter of Intent Receipt Date: April 15, 1994 Application Receipt Date: July 13, 1994 Scientific Review Date: October 1994 Advisory Council Date: February 1995 Earliest Award Date: April 1995 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance, No. 93.855 - Immunology, Allergy and Transplantation Research and No. 93.866 - Aging Research. Awards will be made under the authority of the Public Health Service Act, Title III, Section 301 (Public Law 78-410, as amended; 42 USC 241) and administered under PHS grants policies and Federal Regulations 42 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. From owner-sci-resources@net.bio.net Sun Feb 13 22:00:00 1994 Path: biosci!biosci!not-for-mail From: Dave Kristofferson Newsgroups: bionet.sci-resources Subject: NSF - Summary of new documents on STIS - 13 February 1993 Date: 14 Feb 1994 13:39:34 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 95 Approved: biosci-moderator@net.bio.net Distribution: bionet Message-ID: <2jor2m$ofb@net.bio.net> NNTP-Posting-Host: net.bio.net This message contains a summary of the documents added to the NSF STIS system in the previous week. Reference material concerning STIS follows the summary. ------------------------------------------------------------------------ ** NEW DOCUMENTS ON STIS ** Document Type: Recruit Title: Secretary (Office Automation) File size (bytes): 5057 STIS Filename: vgs9437 Title: Personnel Staffing and Classification Specialist File size (bytes): 5150 STIS Filename: vgs9438 Document Type: SRS Data Brief Title: DB 94 - 302 Median Salary of Employed Doctoral Scientists and Engineers Topped $60,000 in 1991 File size (bytes): 4205 STIS Filename: db94302 ------------------------------------------------------------------------ ** UPDATES TO EXISTING STIS DOCUMENTS ** Document Type: Committees Title: NSF Advisory Committee Meetings File size (bytes): 1119 STIS Filename: cmpublic Title: NSF Advisory Committee Meetings File size (bytes): 1119 STIS Filename: cmpublic Document Type: Letter Title: Current List of REU Sites File size (bytes): 40169 STIS Filename: reulist Document Type: Phone Book Title: NSF Alpha Telephone Directory File size (bytes): 111773 STIS Filename: phnalpha Document Type: SRS Data Brief Title: DB 93-324 Academic R&D Spending Increased in FY 1992 File size (bytes): 6034 STIS Filename: db93324 Also available: db93324.ps ------------------------------------------------------------------------ ** FOR YOUR REFERENCE ** ------------------------------------------------------------------------ HOW TO OBTAIN DOCUMENTS The above files can be retrieved in electronic form using the STIS system. If you don't know how to use STIS, send an E-mail message to stisinfo@nsf.gov (Internet). You will receive a copy of the STIS flyer via E-mail. If you are already using STIS, you can use the information above to retrieve these files: Documents via E-mail: Send a message to stisserve@nsf.gov (Internet). Use the "STIS Filename" shown above in the "get" command. For example, to retrieve db93324, the text of your message should be as follows: get db93324 Anonymous FTP: FTP to stis.nsf.gov. Use the "STIS Filename" shown above to retrieve a file. For example, to retrieve db93324, you would enter: ftp> get db93324 WAIS or Gopher: Do a word search on the filename as shown in the summary. If you want a *printed* copy of a document: Send your name and postal mailing address, and the document title and number to "firstop@nsf.gov" (Internet). If you have problems with the above procedures: Send a message to "stis@nsf.gov" (Internet). From owner-sci-resources@net.bio.net Wed Feb 16 22:00:00 1994 Path: biosci!biosci!not-for-mail From: Dave Kristofferson Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 23, no. 7, pt. 3, 18 February 1994 Date: 16 Feb 1994 16:23:22 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 1499 Approved: biosci-moderator@net.bio.net Distribution: bionet Message-ID: <2juddq$63k@net.bio.net> NNTP-Posting-Host: net.bio.net $$XID NIHGUIDE 19940218 V23N07 P3O4 ************************************ animal models for these disorders, and treatment of these disorders including enzyme replacement therapy, dietary therapy, drug therapy and gene therapy. The diseases of interest include disorders of cellular transport, lysosome metabolism, peroxisome metabolism, amino acid and organic acid metabolism, carbohydrate metabolism, purine and pyrimidine metabolism, metal metabolism, lipid metabolism, and mucopolysaccharide metabolism. Background The NIDDK has a continuing interest in supporting research in the area of genetic metabolic diseases. The Metabolic Diseases and Gene Therapy Research Program has a large portfolio of regular research and program project grants that study genetic metabolic diseases. For many of these diseases, the enzyme defects have been identified and the genes that are mutated have been cloned with grant support from this program. In addition, the NIDDK has recently funded three core centers for gene therapy of cystic fibrosis and other genetic diseases to accelerate progress in the development of this important technology. The diseases that historically have made up Garrod's inborn errors of metabolism are due to defects in particular enzymes that result in the use of alternative metabolic pathways, the production of abnormal metabolites and frequently the aberrant storage of undigested materials. In many cases, it is the build up of these aberrant metabolites that is toxic to several organ systems. With extension of the lifespan of patients with these diseases through therapy, it has become increasingly evident that most metabolic diseases affect several organ systems. One such example is Galactosemia. When this life-threatening liver disease is prevented by dietary restrictions, additional manifestations develop in other organs such as the ovarian failure, which is unmasked by treatment. Although treatment of primary manifestations is an important approach with tremendous therapeutic value, to adequately address the multisystemic nature of these disorders it is important to develop methods to correct the basic defect systemically. Scope Some examples of research topics that would be considered responsive to this solicitation include, but are not limited to, the following: o Identification of Basic Defects: This would include identifying the protein or enzyme that is defective, isolating the gene that is abnormal, identifying the mutations that cause the syndrome, and studying the structural and functional properties of both the normal and defective protein including X-ray crystallographic studies. Another important area is the development or improvement of diagnostic testing to enable earlier prenatal detection of metabolic diseases. o Cellular and Animal Models of the Metabolic Diseases: Cellular and animal models are particularly important for studying the underlying metabolic disturbance and for testing potential therapies. Cellular models would include the culture of appropriate cell types that manifest the defect for further study. Animal models can include identification and characterization of naturally occurring mutations, the creation of a knock out mutant or the introduction of a point mutation by homologous recombination, and the development of a chemically induced model that mimics features of the disease. o Identification of Toxic Metabolites and their Mechanism of Action: Enzyme deficiencies generate abnormal and/or excessive metabolites that may then be shunted though alternative pathways for degradation. In many cases, these metabolites are harmful to a variety of organ systems. For many metabolic diseases whose symptoms are attributed to the production of toxic metabolites, the actual toxic metabolites have not been identified nor has the mechanism of their detrimental effects been fully elucidated. For example, recent findings that sphingosine, a sphingolipid breakdown product, inhibits the activity of protein kinase C in vitro could help explain the mechanisms of toxicity in the pathogenesis of the sphingolipidoses. This mechanism may result in a progressive dysfunction of the signal transduction pathway vital for cell viability. Research that focuses on such elements in order to explain the pathophysiology of genetic metabolic diseases is needed. o Identification of Genetic Modifiers: As the genotypes of many metabolic disorders are studied for their ability to predict severity of disease, it is clear that genes other than those causing the primary defect can modify the phenotype. One classic example is that the persistence of fetal hemoglobin gene expression modifies the beta-thalassemia phenotype and, as a result, these patients have a milder clinical course. Identification of genes that modify the phenotype of other common genetic mutations is needed to explain the etiology of multiple phenotypes within a single genotype. o Development of Enzyme Replacement Therapy: Enzyme replacement therapy has been attempted for several metabolic diseases; however, in most cases the enzyme is degraded prior to reaching the target tissue. Recently, two different protein modifications have led to the development of enzyme replacement therapy for ADA deficiency and Gaucher Disease. Research is needed to develop methods for producing large quantities of biologically active enzymes; modifications directing targeting into organelles such as peroxisomes and into specific tissues, for example, by ligand-mediated internalization through cell surface receptors; and increasing protein half-life by protein modification or genetic engineering of amino acids important for signaling protein degradation. o Development of Dietary or Drug Therapy: Current treatment for most metabolic diseases consists of dietary restrictions, vitamin supplementation and/or drug therapy to prevent the build up of toxic metabolites. Research into new or improved dietary or drug therapy based on an understanding of the metabolic defect is needed. One area of research could be to develop drug therapy to prevent aggregation of mutant proteins and to promote proper folding and assembly of complex proteins. o Development of Gene Therapy: The area of gene therapy for metabolic diseases has evolved quickly. In order to further accelerate progress, many new directions must be evaluated for their feasibility as approaches for gene therapy. Studies of new viral vectors, chimeric vectors, improved techniques for homologous recombination and improvement in delivery vehicles such as liposomes and receptor-mediated endocytosis are examples of areas in need of further development. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements are required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis must be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale must be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues should be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information must be included in the form PHS 398 (rev. 9/91) in Item 4 (Research Design and Methods) of the Research Plan AND summarized in Item 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., Native Americans (including American Indians or Alaskan Natives), Asian/Pacific Islanders, African Americans, Hispanics). The rationale for studies on single minority population groups must be provided. For the purpose of this policy, clinical research is defined as human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including but not limited to clinical trials. The usual NIH policies concerning research on human subjects also apply. basic research or clinical studies in which human tissue cannot be identified or linked to individuals are excluded. However, every effort should be made to include human tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. For foreign awards, the policy on inclusion of women applies fully; since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. If the required information is not contained within the application, the review will be deferred until the information is provided. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and will be reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. APPLICATION PROCEDURES Applications are to be submitted on the grant application form PHS 398 (rev. 9/91) and will be accepted at the regular application deadlines as indicated in the application kit. The receipt dates for applications for AIDS-related research are found in the PHS 398 instructions. Application kits are available at most institutional offices of sponsored research and may be obtained from the Office of Grants Information, Division of Research Grants, National Institute of Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone 301/594-7248. The title and number of this program announcement must be typed in Section 2a on the face page of the application. 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. For investigators applying for support through the FIRST award (R29), three letters of references must be submitted with the application. An applicant submitting a revised application in response to this RFA must again submit reference letters. The completed original application and five legible copies must be sent or delivered to: Division of Research Grants National Institute of Health Westwood Building, Room 240 Bethesda, MD 20892** REVIEW PROCEDURES Several other Institutes at the National Institutes of Health also have an interest in supporting areas of research covered by this PA. Applications will be assigned on the basis of established Public Health Service referral guidelines and some applications may receive dual assignments. In the case of R01 and R29 applications, they 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 and criteria. Program project applications will be reviewed by initial review groups organized by the Institute to which the application is assigned. Following scientific-technical review, the applications will receive a second-level review by the Institute's national advisory council. AWARD CRITERIA Applications will compete for available funds with all other approved applications. The following will be considered in making funding decisions: quality of the proposed project as determined by peer review; availability of funds; and program balance among research areas of the announcement. INQUIRIES Written and telephone inquiries are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Requests for the NIDDK Program Project Guidelines and inquiries regarding programmatic issues may be directed to: Dr. Catherine McKeon Division of Diabetes, Endocrinology and Metabolic Diseases National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 621 Bethesda, MD 20892 Telephone: (301) 594-7582 FAX: (301) 594-9011 Direct inquiries regarding fiscal matters to: Ms. Donna Huggins Division of Extramural Activities National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 649 Bethesda, MD 20892 Telephone: (301) 594-7543 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.847 . Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99- 158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$P4 END ************************************************************ $$P5 BEGIN PA-94-037 ************************************************ GENETIC DISORDERS CAUSING MENTAL RETARDATION NIH GUIDE, Volume 23, Number 7, February 18, 1994 PA NUMBER: PA-94-037 P.T. National Institute of Child Health and Human Development PURPOSE The purpose of this Program Announcement (PA) is to encourage grant applications on genetic disorders that cause mental retardation. This includes research on molecular genetic mechanisms, biochemical and neuropathological processes in the brain, behavioral genetics, and other developmental processes that result in abnormal cognitive function. Research should be directed towards the screening, diagnosis, treatment, prevention, and/or amelioration of mental retardation and related developmental disabilities. 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, Genetic Disorders Causing Mental Retardation, is related to the priority area of chronic disabling conditions and maternal and infant health. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by foreign and domestic, for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Foreign institutions are not eligible for First Independent Research Support and Transition (FIRST) (R29) awards. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT Support of this program will be through the NIH research project grant (R01), FIRST (R29) award, and program project (P01) mechanisms. Investigators interested in submitting a program project are strongly encouraged to consult with NICHD program staff in the preparation of their applications. Applications of a multi-disciplinary nature may also be considered through the Interactive Research Project Grants (IRPG) program. RESEARCH OBJECTIVES Scope About one-third of all genetic disorders show some neurological involvement, and many of these represent neurodegenerative diseases of infancy. Genetic or genetically-influenced conditions rank among the leading causes of organically-based mental retardation. These problems can be addressed through studies of the location, organization, and regulation of genetic material. This may include research on molecular genetic mechanisms (genomic imprinting, triplet repeats, mitochondrial inheritance), gene mapping, enzymatic function, behavioral genetics, prenatal diagnosis, genetic counseling, epidemiologic studies, animal models, and gene therapy. Major areas of interest include: o Inborn errors of metabolism that specifically impact on brain function. This research focuses brain pathophysiology due to imbalances in amino acids, mucopolysaccharides, purines, lipids, and carbohydrates, or the dysfunction of cellular organelles (e.g., mitochondria, peroxisomes, lysosomes, or Golgi) that contributes to mental retardation and developmental disabilities. We are especially interested in the development of therapeutic strategies (genetic or pharmacological) that aid in the diagnosis and clinical management of these disorders. Specific examples of metabolic disorders with prominent MRDD include phenylketonuria, maternal phenylketonuria, Lesch-Nyhan, galactosemia, and adrenoleukodystrophy. o Down Syndrome is the leading genetic cause of mental retardation, occurring in about 1/800-1000 births. Research on Down Syndrome may focus on the behavioral heterogeneity, critical genes on chromosome 21, Alzheimer-like pathology, gene dosage compensation, chromosomal nondisjunction, cellular mosaicism, animal models, epidemiology, and prenatal screening issues. o Chromosomal abnormalities occur in three to four percent of live births. This may include aberrations associated with chromosome number, morphology, or structure. Partial deletions or duplications of chromosomal material are associated with contiguous gene syndromes (e.g., Charcot-Marie-Tooth, Smith-Magenis, Prader-Willi, Angelman, or WAGR), which often involve mental retardation. Chromosomal abnormalities may also affect placental development (confined placental mosaicism). Within the context of mental retardation, we are interested in molecular mechanisms that give rise to specific chromosomal abnormalities, genetic regulatory mechanisms (eg. genomic imprinting, uniparental disomy), epigenetic phenomena, and the identification of specific genes that affect brain function. o X-linked disorders may explain why males show a 25 to 35 percent higher incidence of mental retardation than females. We welcome research on genetic mechanisms specific to the X-chromosome (e.g., X-inactivation, gene regulation) that may be relevant to understanding some forms of X-linked mental retardation. o Fragile X syndrome is the leading cause of heritable mental retardation, affecting about 1/1400 males and 1/2500 females. The genetic defect is an unstable region of DNA on the X chromosome which becomes highly expanded when transmitted through the maternal lineage. Research on the expansion and transmission of triplet repeats, how they affect gene function, and the role of the FMR gene in brain function is encouraged. Support studies on the detection, behavioral assessment, and epidemiology of Fragile X syndrome in normal populations and in children with learning disabilities is also supported. o Rett syndrome is a neurological disorder that results in arrested development of motor and social skills at an early age, but it only appears in young girls (1/15,000 female births). The occurrence of this disorder suggests that it may involve spontaneous dominant mutations on the X chromosome, but more complex genetic models need to be considered. Research into the underlying defect in Rett Syndrome and how it affects brain development and behavior is especially encouraged. o Neural tube defects are among the most frequent and severe anomalies of central nervous system development, occurring in about 1/1000 live births. Although it appears that environmental as well as genetic factors play a role, the etiology and pathogenesis of these malformations are poorly understood. We support investigations in the genetic basis of neural tube defects, including the role of modifier genes that influence expression and penetrance, genetic networks (temporal and spatial) important for pattern formation in the developing brain and spinal cord, and animal models to elucidate mechanisms of normal neural tube development and to define the early developmental miscues that result in abnormal neural function. o Mitochondrial inheritance may explain some forms of mental retardation that cluster within families. Defects in oxidative phosphorylation and its by-products would be expected to impact most heavily on tissues like brain that have high energy demands and are sensitive to their metabolic environment. In order to understand the role of mitochondrial defects in mental retardation, we support research on mitochondrial genetics, regulation of mitochondrial function, replication, interaction of nuclear-encoded genes, and the development of model systems. o Development of animal models for specific brain disorders is rapidly advancing, thanks to advances in transgenic manipulation, stem cell culture, and embryology. We support the use of animal models for the study of pathophysiological mechanisms associated with brain dysfunction and the development of clinical strategies for the management of these disorders. We encourage research in behavioral genetics and comparative physiology in order to develop appropriate physiological and behavioral assessments. o Heterozygotes (carriers) often present phenotypic heterogeneity, which can complicate clinical management and counseling. In order to improve the assessment and treatment of mental retardation, we support research into the mechanisms of variable penetrance, allelic differences, genetic background, germ line mosaicism, X-inactivation, and/or environmental differences in the expression of genetic disorders. o Prenatal screening is central to the diagnosis and management of mental retardation and developmental disabilities. We support research in the development of safe and accurate methods for assessing the genetic status of the fetus, including amniocentesis, chorionic villus sampling, and analysis of fetal cells in the maternal circulation. We also support research in population genetics and the ethical, social, and legal consequences of these technologies. o Gene therapy is being developed for the treatment of specific genetic disorders that affect brain function. We encourage research in those disorders in which mental retardation is the primary clinical manifestation. This may include development of improved vectors for brain tissue, transcriptional and translational control of inserted genes, physiological studies on the expression and function of gene products within the brain, transplantation of genetically- modified cells or tissues, and relevant animal models. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements are required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis must be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear and compelling rationale must be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues should be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information must be included in the form PHS 398 (rev. 9/91) in Sections 1-4 of the Research Plan AND summarized in Section 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., Native Americans (including American Indians or Alaskan Natives), Asian/Pacific Islanders, Blacks, Hispanics). The rationale for studies on single minority population groups must be provided. For the purpose of this policy, clinical research is defined as human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including but not limited to clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded. However, every effort should be made to include human tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. For foreign awards, the policy on inclusion of women applies fully; since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. If the required information is not contained within the application, the review will be deferred until the information is provided. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and will be reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. APPLICATION PROCEDURES Applications are to be submitted on the grant application form PHS 398 (rev. 9/91) and will be accepted at the standard application deadlines as indicated in the application kit. The receipt dates for applications for AIDS-related research are found in the PHS 398 (rev. 9/91) instructions. Application kits are available at most institutional offices of sponsored research and may be obtained from the Office of Grants Information, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone 301/594-7249. The title and number of the announcement must be typed in Section 2a on the face page of the application. Applications for the FIRST Award (R29) must include at least three sealed letters of reference attached to the face page of the original application. FIRST Award (R29) applications submitted without the required number of reference letters will be considered incomplete and will be returned without review. The completed original application and five legible copies must be sent or delivered to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** REVIEW CONSIDERATIONS Several other Institutes at the National Institutes of Health also have an interest in supporting areas of research covered by this PA. Applications will be assigned on the basis of established Public Health Service referral guidelines and some applications may receive dual assignments. In the case of R01 and R29 applications, they 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 and criteria. Program project applications will be reviewed by initial review groups organized by the Institute to which the application is assigned. Following scientific-technical review, the applications will receive a second-level review by the Institute's national advisory council. AWARD CRITERIA Applications will compete for available funds with all other approved applications. The following will be considered in making funding decisions: o Quality of the proposed project as determined by peer review o Availability of funds o Program balance among research areas of the announcement INQUIRIES Written and telephone inquiries are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Dr. Ralph Nitkin Mental Retardation and Developmental Disabilities Branch National Institute of Child Health and Human Development 6100 Executive Boulevard, Room 4B09 Bethesda, MD 20892 Telephone: (301) 496-1383 FAX: (301) 402-2085 Direct inquiries regarding fiscal matters to: Mr. E. Douglas Shawver Office of Grants and Contracts National Institute of Child Health and Human Development 6100 Executive Boulevard, Room 8A-17 Bethesda, MD 20892 Telephone: (301) 496-1303 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.865, Research for Mothers and Children. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$P5 END ************************************************************ $$P6 BEGIN PAR-94-038 *********************************************** PREVENTIVE INTERVENTION RESEARCH CENTERS NIH GUIDE, Volume 23, Number 7, February 18, 1994 PAR NUMBER: PAR-94-038 P.T. 34; K.W. 0745027, 0715129 National Institute of Mental Health PURPOSE The National Institute of Mental Health (NIMH) invites applications for Preventive Intervention Research Centers (PIRCs) whose main goal is to bridge basic and clinical sciences, state-of-the-art methodologies, and public health research approaches, in order to address pressing prevention research problems that require multi-disciplinary, integrated research strategies. This program announcement is responsive to recommendations from the Institute of Medicine (Reducing Risks for Mental Disorders: Frontiers for Preventive Intervention Research) and the National Prevention Conference (The Prevention of Mental Disorders: A National Research Agenda). It also addresses recommendations outlined under "The National Plan for Research on Child and Adolescent Mental Disorders." HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. The PA, Preventive Intervention Research Centers, is related to the priority areas of suicide and mental disorders. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or" Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325, (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by public and private for-profit and non-profit domestic organizations such as universities, colleges, hospitals, laboratories, research institutions, units of State or local governments, and eligible agencies of the Federal government. Women and minority investigators are encouraged to apply. MECHANISMS OF SUPPORT Applications may be submitted using the developing center (P20) and mature center (P30) funding mechanisms. Support for a Developing PIRC (P20) may be requested for a single, non-renewable five-year period only, with a maximum request of $300,000 per year, plus negotiated institutional indirect costs. Support for a Mature Center (P30) can be requested for renewable five-year funding periods, with a maximum request of $1,000,000 per year, plus negotiated institutional indirect costs. Because the nature and scope of the research proposed in response to this PA may vary, it is anticipated that the size of an award will also vary. RESEARCH OBJECTIVES Background Since 1982, the NIMH has supported a number of Preventive Intervention Research Centers (PIRCs) with the aim of providing productive research environments where teams of investigators from a variety of disciplines would interact and develop focused programs of research on the prevention of mental and behavioral disorders and dysfunctions, and the promotion of mental health. To date, the PIRCs have included both infrastructure or core functions, as well as support for a set of interrelated research projects. Under the current announcement, PIRCs will move to a core function model; Center grants will cover cross cutting research functions such as data management, field coordination, and research planning and development activities around a substantive theme or set of themes. Costs for fully developed projects emerging from the Centers will be covered through regular research grant mechanisms. PIRC Characteristics and Functions Although the specific structure and organization of individual Centers will vary, all PIRCs are expected to help build the field of mental health prevention and promotion research by providing scientific leadership, an environment of research excellence, and models of community outreach and collaboration. To fulfill the mission outlined above, PIRCs are expected to perform a number of critical functions. These functions may be represented as individual core units of the Center, or they may be clustered together. In either case, all of the functions must be addressed in PIRC applications, although the relative emphasis of functions may vary from site to site. Functions include, but are not limited to: o Research agenda and theory development. PIRCs are expected to develop an organizing prevention/promotion research theme or set of themes and a research agenda that define the mission of the Center. For each theme, PIRC applications are expected to review the relevant empirical and theoretical literature, identify major unresolved issues, and present a plan for developing a rigorous, theory driven, multi-disciplinary research program to address these outstanding questions and clarify theory. o Methodology. PIRCs are expected to provide state-of-the-art, sophisticated methodological expertise to all Center related research projects. This function includes, but is not limited to, sample development, methods and instrument development, assessment and diagnosis, research design, statistics, and primary and secondary data analysis. PIRCs can also support relevant biological and behavioral research laboratories. PIRCs are strongly encouraged, where appropriate, to include a focus on methodological research aimed at solving design and statistical problems of critical importance to longitudinal field trials. o Data management. PIRCs are expected to provide state-of-the-art data management efforts in order to facilitate all aspects of data processing and analysis, and timely production of research publications. o Knowledge and technology transfer. PIRCs are expected to sponsor meetings and symposia in their thematic area, produce a variety of scientific publications and other outreach activities to disseminate findings and successful intervention technologies, and highlight ethical issues in preventive intervention research. o Mentoring. PIRCS are expected to provide prevention research scientist opportunities to new and established investigators. Special attention should be given to the recruitment of minority investigators. Centers are encouraged to apply for grants available to support developing scientists. The number of personnel awarded will depend upon the capacity of the Center's scientists, but will not exceed 15 percent of the awarded direct costs for the Center. o Opportunities for research collaboration. PIRCs are strongly encouraged to capitalize on opportunities for cross site and cross research project collaborations, where appropriate. Collaborative research planning activities, including piloting, can be included as PIRC sponsored activities. Fully developed collaborative projects will be funded through regular research grant mechanisms. o Community sanction/liaison. PIRCs are expected to develop and disseminate model processes for achieving community sanction and cultural competence for all aspects of prevention field experiments. Developing and Mature Centers There are two categories of grant applications under the PIRC program: applications for Developing Centers (P20) and applications for Mature Centers (P30). Although there is no absolute criterion to distinguish who should apply in which category, the following guidelines apply: o The category of Developing Centers (P20) is appropriate for institutions that are either (a) interested in developing a critical mass of research scholars necessary to conduct state-of-the-art prevention research, or (b) already have a critical mass of researchers from relevant disciplines, who are interested in re-focusing and integrating their research around a preventive intervention theme. Applicants in this category must have strong track records in research (although not necessarily in prevention research) and show promise of developing into fully functioning prevention research Centers. Developing Centers have research themes and existing collaborations, but need funds to recruit additional scientists, expand core functions, or fully develop a multi-disciplinary prevention research agenda. Each Developing PIRC will provide research experiences for at least two preceptees annually, to be selected from scientific disciplines related to the goals of the Center. Preceptorships are defined as supervised research experience. Each Center should relate functionally with relevant departments of professional and graduate schools, as are appropriate to the needs of the preceptees. o Mature Centers (P30) are fully developed entities that have the capacity to rapidly become mature, state-of-the-art research Centers by virtue of previous commitments of institutional resources, recruitment and/or development of an existing critical mass of prevention research scholars, the presence of substantial recent prevention publications in peer-reviewed research journals, active preventive intervention research grants, etc. In Mature PIRCs, funds can be requested to support research career development candidates at the same level of experience as would be appropriate for NIMH-supported scientist development and academic awards. Specific Research Topics In keeping with the public health mission of prevention research, PIRC research programs will generally focus on randomized controlled intervention trials, but may include studies that span the entire scientific continuum. For example, PIRCs can include generative risk factor and model building research to inform theory on the etiology and development of psychopathology (hypothesis development). The research program can also include methods development relevant to the design and testing of a new intervention model, or to the development of innovative design and analytical approaches for the field as a whole. Centers are also strongly encouraged to include cost-effectiveness and cost-benefit studies wherever appropriate in their research agenda. Intervention trials should be of two types: experimental tests of efficacy (controlled intervention trials of new intervention strategies) and of effectiveness (testing of efficacious interventions in controlled trials involving representative, defined populations.) Because of their logistical and methodological complexities, tests of effectiveness are particularly appropriate for inclusion in PIRC research programs. Similarly, PIRCs are encouraged, where appropriate, to include in their research programs plans for dissemination and/or services research once interventions have demonstrated effectiveness and are ready for adoption by service systems. Centers may direct their efforts to well defined single, multiple, or co-morbid conditions, and test intervention strategies aimed at individuals and/or families, schools, communities, service systems, or other relevant domains. The following are examples of areas within this framework that might serve as a focus for Centers. The list is neither exhaustive, nor exclusive: o Development of prevention trials aimed at changing risk factors and/or mediators associated with mental disorder and pre-clinical behavioral dysfunctions in children, adolescents, and their families. o Methodologic development and experimental testing of promotive interventions, with emphasis on identification and independent assessment of relevant mental health outcomes. o Establishment of prevention trials aimed at risk factors common to a number of disorders and/or maladaptive outcomes. o Generation of ecologically valid prevention trials with multiple intervention components that target risk and protective factors across a number of domains simultaneously. o Development of trials aimed at understanding optimal timing or scope of interventions, or subgroup differences in response to different intervention strategies. o Generation of prevention trials involving embedded universal, selected, and indicated intervention strategies. o Development of multi-component intervention strategies through systematic testing of individual modules which are later tested in combinations. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements will be required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis should be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale should be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues should be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information should be included in the form PHS 398 in Sections 1-4 of the Research Plan AND summarized in Section 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., Native Americans (including American Indians or Alaskan Natives), Asian/Pacific Islanders, Blacks, Hispanics). The rationale for studies on single minority population groups should be provided. For the purpose of this policy, clinical research includes human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including but not limited to clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded. However, every effort should be made to include human tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. For foreign awards, the policy on inclusion of women applies fully; since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. If the required information is not contained within the application, the application will be returned. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and will be reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. APPLICATION PROCEDURES It is strongly encouraged that potential applicants contact the Centers program staff very early in the planning process. NIMH staff will offer each potential applicant advice and information regarding program relevance and purpose so that applications will comply with administrative requirements, meet program standards, and contain sufficient information to permit an adequate Center program review. Applications are to be submitted on the grant application form PHS 398 (rev. 9/91) and will be accepted at the standard center application deadlines as indicated in the application kit. The number and title of this Program Announcement, Preventive Intervention Research Centers, PAR-94-038, must be typed in item number 2a on the face page of the PHS 398 application form. PHS regulations concerning application page-length apply to PIRC applications. In general, 25 pages of text are allowed for each core and research component of the Center. A submitted application will be reviewed within the category that it requests (i.e., Developmental or Mature); the IRG will not change categories as part of its review. Applicants should note that the metric system of measurement must be used if weights and measures are involved in the proposed research. Application kits containing the necessary forms and instructions are available at most institutional offices of sponsored research and may be obtained from the Office of Grants Information, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone 301/594-7248. The signed original and five legible copies of the completed application must be sent to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** REVIEW CONSIDERATIONS Applications will be assigned on the basis of established phs referral guidelines. Applications will be reviewed for scientific and technical merit by study sections of the National Institute of Mental Health, in accordance with the standard NIH peer review procedures. The following criteria will be considered when assessing the merit of a PIRC application: intrinsic merit of the proposed intellectual focus and research agenda, appropriateness of the Center approach, presence of high-quality research investigators from several fields, Center Director qualities, adequacy of research resources and environment, quality and appropriateness of the infrastructure and research career development components of the PIRC's activities, appropriateness of PIRC organization, quality of Center functions, adequacy of plans to achieve community sanction, feasibility and budget, inclusion of women and minorities, adequacy of protection of human and animal subjects. 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 work. If so, a letter of agreement from either the GCRC program director or principal investigator could be included with the application. All PIRC applications will be reviewed according to the procedures and criteria outline above. However, for the special case of applications for Developing PIRCs, the above criteria will be modified by the following: the nature and level of resource commitments from the home institution/department and from other participating institutions/departments are of necessity not of the level of the Mature PIRC; the quality of plans to recruit excellent new research faculty, or to further integrate the work of existing investigators around preventive intervention trials; the likelihood that the establishment of a Developing PIRC will facilitate existing research activities and serve as a mechanism to expand the proposed prevention research theme into a fully developed prevention research agenda. Following scientific-technical review, the application will receive a second-level review by the National Mental Health Advisory Council. AWARD CRITERIA Applications received in response to this announcement will compete with others submitted to NIMH for funding. In granting awards, the following criteria are considered: o Program relevance o Quality of application as documented by IRG and Council recommendations o Program balance o Availability of funding o Institute priorities Grants must be administered in accordance with the PHS Grants Policy Statement (rev. October 1, 1990). INQUIRIES Written and telephone inquiries are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Doreen Spilton Koretz, Ph.D. Prevention Research Branch Parklawn Building, Room 10-85 5600 Fishers Lane Rockville, MD 20857 Telephone: (301) 443-4283 For further information on grants management issues, applicants may contact: Diana Trunnell Grants Management Branch National Institute of Mental Health 5600 Fishers Lane, Room 7C-15 Rockville, MD 20857 Telephone: (301) 443-3065 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance 93.242, Mental Health Research Grants. 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 announcement is not subject to the intergovernmental review requirements of Executive Order 12372, as implemented through DHHS regulations at 45 CFR Part 100, or Health Systems Agency Review. $$P6 END ************************************************************ $$P7 BEGIN PA-94-039 ************************************************ ARTICULATION DISORDERS OF UNKNOWN ORIGIN IN CHILDREN NIH GUIDE, Volume 23, Number 7, February 18, 1994 PA NUMBER: PA-94-039 P.T. National Institute on Deafness and Other Communication Disorders PURPOSE The National Institute on Deafness and Other Communication Disorders (NIDCD) encourages research project applications to examine systematically the linguistic, phonologic, motoric, perceptual, cognitive, and other variables that have been posited to play a role in the genesis of articulation disorders of unknown origin in children. Research grant applications that address the nature of the disorder, subgroups within the disorder, and appropriate methods of prevention, diagnosis, and treatment of the disorder are encouraged. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This Program Announcement, Articulation Disorders of Unknown Origin in Children, is related to the priority area of clinical prevention services. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-11474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-11473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State or local governments, and eligible agencies of the Federal government. Foreign institutions are not eligible for First Independent Research Support and Transition (FIRST) (R29) awards. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT The support mechanisms for grants in this area will be the investigator-initiated research grant (R01) and the FIRST (R29) award. The NIH policies and submission dates that govern these mechanisms will prevail. RESEARCH OBJECTIVES Background One of the most common communication disorders in childhood is that of errors in speech sound production (articulation). It has been estimated that articulation disorders represent in excess of 75 percent of all speech disorders in children. A large number of these articulation disorders have no recognizable organic, neurogenic, or physical correlate. Children with articulation disorders of unknown cause constitute 99 percent of the caseloads of speech-language pathologists working in the schools. Importantly, these difficulties may have consequences throughout the lifespan of these children. Research on articulation disorders of unknown cause has focused on consideration of such variables as intelligence, motor skill, auditory discrimination, auditory memory, academic performance and socio-economic status, in an attempt to identify a causal link. The clinical observation that individual differences exist among these children and that effective intervention may depend on early identification and consideration of these relevant individual differences suggests that a number of complementary research perspectives be considered. Traditionally, these disorders have been viewed as a possible motor disorder: a difficulty in the motor control of articulation and the coordinated, connected production of speech sounds. More recently, this view has been extended to include the general processing, organization and cognitive representation of linguistic information. Within this viewpoint, children's speech productions are seen as manifestations of underlying forms and phonological processes. Because of their presumed importance in early phonetic learning, speech discrimination deficits have also been considered to be potentially important factors in the development and perpetuation of such articulation disorders. Models of adult neurogenic speech disorders have also been applied to this group of misarticulating children in an attempt to examine the role that a difficulty in programming the speech musculature for volitional production of phonemes might play in children with articulation disorders. The diagnostic label of developmental apraxia of speech derives from this model. This term has been used to describe the speech behavior of children with moderate to severe articulation disorders of nonorganic cause. Research Goals and Scope Although no causal relationships have yet been determined, possible causes have been proposed, and models that could explain the nature of the articulation disorder have subsequently been developed. As a result, several theoretical approaches to articulation disorders of unknown cause have emerged. Most propose that one strong causal factor may be accompanied by other less strong but still influential factors contributing to the disorder. Although a number of insights have been gained by considering these children from these different perspectives, many issues remain. Studies that may be proposed in applications submitted in response to this PA include, but are not limited to, the following: o Development of model systems of identification and evaluation of children with articulation disorders that consider the linguistic, phonologic, motoric, and cognitive aspects of normal development. o Identification of factors that place children at risk for developing articulation disorders and at risk for long-term problems of articulation. o Exploration of genetic factors associated with the development of articulation disorders of unknown cause. o Evaluation of acoustic-phonetic features of children's speech in order to identify predictors of subsequent articulatory disorders. o Delineation of subgroups of children with articulation disorders of unknown cause, using broad and interdisciplinary examinations of the linguistic, cognitive, motoric, perceptual, neurogenic, and genetic bases of the disorder. o Identification of appropriate techniques for the differential diagnosis and effective treatment of subgroups of this population. o Development, evaluation and standardization of improved phonological, motor and linguistic assessment and treatment procedures based on theoretical models. o Generation of incidence and prevalence data related to articulation disorders of unknown cause across age levels. o Determination of factors that enhance or diminish the efficacy of treatment for children with the disorder. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements are required to include minorities and females in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis must be placed on the need for inclusion of minorities and females in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale must be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues must be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information must be included in the form PHS 398 in Sections 1-4 of the Research Plan AND summarized in Section 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., Native Americans [including American Indians or Alaskan Natives], Asian/Pacific Islanders, African Americans, Hispanic Americans). The rationale for studies on single minority population groups should be provided. For the purpose of this policy, clinical research is defined as human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including but not limited to clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded. However, every effort should be made to include human tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. For foreign awards, the policy on inclusion of women applies fully; since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. If the required information is not contained within the application, the application will be returned. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific questions addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. APPLICATION PROCEDURES Applications are to be submitted on the grant application form PHS 398 (rev. 9/91) and will be accepted at the standard applications deadlines as indicated in the application kit. The receipt dates for applications for AIDS-related research are found in the PHS 398 instructions. Application kits are available at most institutional offices of sponsored research and may be obtained from the Office of Grants Information, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone 301-594-7248. The title and number of the announcement must be typed in Section 2a on the face page of the application. The completed original application and five legible copies must be sent or delivered to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** REVIEW CONSIDERATIONS Applications will be assigned on the basis of established PHS referral guidelines. Applications will be reviewed for scientific and technical merit by study sections of the Division of Research Grants, NIH, in accordance with the standard NIH peer review procedures. Following scientific-technical review, the applications will receive a second-level review by the appropriate national advisory council. AWARD CRITERIA Applications will compete for available funds with all other approved applications assigned to that ICD. The following will be considered in making funding decisions: o Quality of the proposed project as determined by peer review o Availability of funds o Program priorities among research areas of the announcement. INQUIRIES Written and telephone inquiries concerning this PA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Beth Ansel, Ph.D. Division of Communication Sciences and Disorders National Institute on Deafness and Other Communication Disorders Executive Plaza South, Suite 400-C Rockville, MD 20892 Telephone: (301) 402-3461 Direct inquiries regarding fiscal matters to: Ms. Sharon Hunt Grants Management Branch National Institute on Deafness and Other Communication Disorders Executive Plaza South, Suite 400-B Rockville, MD 20892 Telephone: (301) 402-0909 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.173. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$P7 END ************************************************************ $$P8 BEGIN PA-94-040 ************************************************ GENE THERAPY IN DUCHENNE MUSCULAR DYSTROPHY NIH GUIDE, Volume 23, Number 7, February 18, 1994 PA NUMBER: PA-94-040 P.T. 34; K.W. 0715140, 0745032 National Institute of Neurological Disorders and Stroke National Institute of Arthritis and Musculoskeletal and Skin Diseases PURPOSE The National Institute of Neurological Disorders and Stroke (NINDS) and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) encourage the submission of research grant applications to investigate the potential for gene therapy in Duchenne muscular dystrophy. Responses to this program announcement may include studies in appropriate animal models of gene replacement using viral vectors, myoblast transfer, or other means of dystrophin enhancement. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention goals of "Healthy People 2000," a PHS-led national activity for setting priorities. This program announcement, Gene Therapy in Duchenne Muscular Dystrophy, is related to the priority area chronic disabling conditions. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: No. 017-001-00474-0, or Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign, for-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State or local governments, and eligible agencies of the Federal government. Foreign institutions are eligible to apply for only regular research project grants (R01). Applications from minority individuals and women are encouraged. MECHANISMS OF SUPPORT The support mechanisms for grants in this area will be the investigator-initiated research project grant (R01), the First Independent Research Support and Transition (FIRST) award (R29), the program project grant (P01), and the center grant (P50). The Principal Investigator or program director, as well as any participating investigators, will plan, direct, and perform the research. Applicants for program project grants are requested to contact the NINDS representative listed below as early as possible in the planning stages. RESEARCH OBJECTIVES Duchenne muscular dystrophy (DMD) is the most common inherited neuromuscular disease, affecting approximately one in 3,500 male births. The disease is characterized by muscle necrosis and regeneration. Eventually, the regeneration cannot keep up with the necrosis, resulting in progressive muscle fiber loss. Affected boys are usually wheelchair-bound by age 12, with death occurring in the third decade. A milder variant, Becker muscular dystrophy, occurs once in 30,000 male births. Isolation of the X-linked DMD gene led to the discovery of dystrophin, the protein that is missing or defective in Duchenne muscular dystrophy and abnormal in Becker muscular dystrophy. Dystrophin is a 427-kd protein and an essential component of the inner surface of the sarcolemmal membrane. The full-length gene for dystrophin is huge, 2.4 megabases, and most mutations are frame-shift deletions (Duchenne) or internal in-frame deletions (Becker). The most frequently studied animal model of Duchenne muscular dystrophy is the mdx mouse, in which the homologous mutation also results in a lack of dystrophin. Like affected humans, the mdx mice have recurrent muscle fiber necrosis; regeneration, however, is very efficient, and the mice do not suffer generalized muscle fiber loss and weakness. A dog model with a similar mutation may be a superior model of DMD because its size and symptoms are much closer to humans. Unfortunately, the dog model has several disadvantages compared to the mouse, including slow breeding rate, scarcity, and expense. Among the potential genetic therapy approaches to dystrophin replacement that have been considered are direct injection of DNA, vector-mediated delivery, and myoblast transfer. These approaches all present major obstacles that must be overcome. The full-length dystrophin gene with its associated promoters and other regulatory elements may be too large to routinely introduce into muscle fibers directly or using a viral vector. Human cDNA, length about 14 kb, has been isolated, and a partial cDNA of only 6.3 kb has been cloned from a patient with only very mild symptoms, suggesting that such a smaller "minigene" could protect DMD muscles from necrosis. A gene of this size could be accommodated in an adenovirus or retrovirus vector. Myoblast transfer studies in mice have been reported, with the percentage dystrophin positive host muscle fibers varying widely. Several groups of investigators have also performed similar experiments in Duchenne muscular dystrophy boys. The procedure appears to be safe, but so far there is little evidence of increased strength or the production of dystrophin in the host muscle. This announcement solicits applications for any study whose ultimate goal is the successful genetic therapy of Duchenne muscular dystrophy. Examples are given below, but applications are not limited to these areas of research: o Improve methods to express dystrophin cDNAs in viral vectors, including adenovirus and retrovirus. o Develop techniques to increase the penetration of gene constructs into the muscle cells and their nuclei and to enhance the dispersion of injected gene constructs or myoblasts. o Develop strategies to enhance the efficiency of myoblast transfer therapy. o Investigate the feasibility of the 6.3 kb cDNA for genetic therapy. o Find alternative mechanisms to increase levels of existing dystrophin. o Assess the feasibility of injecting DNA directly into muscle From owner-sci-resources@net.bio.net Wed Feb 16 22:00:00 1994 Path: biosci!biosci!not-for-mail From: Dave Kristofferson Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 23, no. 7, pt. 2, 18 February 1994 Date: 16 Feb 1994 16:23:14 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 1499 Approved: biosci-moderator@net.bio.net Distribution: bionet Message-ID: <2juddi$61c@net.bio.net> NNTP-Posting-Host: net.bio.net $$XID NIHGUIDE 19940218 V23N07 P2O4 ************************************ The Secretary, Department of Health and Human Services (HHS) and the Secretary, Department of Energy (DOE) signed a Memorandum of Understanding (MOU) transferring the authority and resources to manage and conduct energy-related analytic epidemiologic research from DOE to HHS. This includes the authority, resources, and responsibility for the design, implementation, analysis, and scientific interpretation of analytic epidemiologic studies of the following populations: workers at DOE facilities; other workers potentially exposed to radiation; and workers exposed to potential hazards resulting from non-nuclear energy production and use. Scope The focus of grants should reflect: (1) retrospective occupational exposure assessment, (2) radiation measurement issues, (3) non-cancer morbidity and mortality outcomes, (4) meta-analysis and combined analysis methodologies, (5) uncertainty analysis, and (6) effects of measurement error on risk estimates. STUDY POPULATIONS Applicants are required to give added attention (where feasible and appropriate) to the inclusion of minorities and/or women study populations for research into the etiology of diseases, research in behavioral and social sciences, clinical studies of treatment and treatment outcomes, research on the dynamics of health care and its impact on disease, and appropriate interventions for disease prevention and health promotion. Exceptions would be studies of diseases that exclusively affect males or where involvement of pregnant women may expose the fetus to undue risks. If minorities and/or women are not included in a given study, a clear rationale for their exclusion must be provided. LETTER OF INTENT Prospective applicants are asked to submit, by April 1, 1994, a letter of intent that includes a descriptive title of the proposed effort, the name and address of the principal investigator, the names of other key personnel, and the participating institutions, and the number and title of this RFA. The letter of intent is requested in order to provide an indication of the number and scope of applications to be reviewed. This letter of intent does not commit the sender to submit an application, nor is it a requirement for submission of an application. The letter of intent is to be sent to Dr. Fleming at the address listed under INQUIRIES. APPLICATIONS PROCEDURES The research grant application form PHS 398 (rev. 9/91) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research; from the Office of Grants Information, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone 301/594-7248; and from NIOSH program administrator listed under INQUIRIES. The RFA label available in the PHS 398 (rev. 9/91) application form must be affixed to the bottom of the face page of the application. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number, Radiation Studies, OH-94-001, must be typed on line 2a of the face page of the application form and the YES box must be marked." Applications submitted in response to this RFA must be received on May 18, 1994. Submit a signed, typewritten original of the application, including the Checklist, and five photocopies of the PHS 398, in one package to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** The timetable for receiving applications and awarding grants in fiscal year 1994 is: Letter of Intent Receipt Date: April 1, 1994 Application Receipt Date: May 18, 1994 Initial Review: August 1994 Secondary Review: September 1994 Earliest Possible Start Date: September 30, 1994 Applications must be received on the above receipt date. To guard against problems caused by carrier delays, retain a legible proof-of-mailing receipt from the carrier, dated no later than one week prior to the receipt date. If the receipt date falls on a holiday, it will be extended to the following work day. REVIEW CONSIDERATIONS Applications will be reviewed by an initial review group convened by the NIOSH. The initial (peer) review is based on scientific merit and significance of the project, competence of the proposed staff in relation to the type of research involved, feasibility of the project, likelihood of its producing meaningful results, appropriateness of the proposed project period, adequacy of the applicant's resources available for the project, and appropriateness of the budget request. AWARD CRITERIA In the secondary (programmatic importance) review, the following factors will be considered: o The results of the initial review; o Magnitude of the problem in terms of numbers of workers affected; o Severity of the disease or injury in the worker population; and o Usefulness to applied technical knowledge in the identification, evaluation, and/or control of occupational safety and health hazards. Applicants will compete for available funds with all other approved applications. The following will be considered in making funding decisions: o Quality of the proposed project as determined by peer review o Availability of funds o Program balance among research areas of the announcement INQUIRIES Written and telephone requests for the RFA and the opportunity to clarify any issues or questions from potential applicants are welcome. Direct requests for the RFA, inquiries regarding programmatic issues, and address the letter of intent to: Roy M. Fleming, Sc.D. National Institute for Occupational Safety and Health Centers for Disease Control and Prevention 1600 Clifton Road, NE Building 1, Room 3053, Mail Stop D-30 Atlanta, GA 30333 Telephone: (404) 639-3343 Direct inquiries regarding fiscal matters to: Ms. Lisa Tamaroff Grants Management Branch, PGO Centers for Disease Control and Prevention 255 E. Paces Ferry Road, NE Room 300, Mail Stop E-13 Atlanta, GA 30305 Telephone: (404) 842-6796 AUTHORITY AND REGULATIONS This program is authorized under the Public Health Service Act, as amended, Section 301 (42 U.S.C. 241); the Occupational Safety and Health Act of 1970, Section 20 (a) (29 U.S.C. 669[a]); and the Federal Mine Safety and Health Amendments Act of 1977, as amended, Section 501 (30 U.S.C. 951). The applicable program regulations are in 42 CFR Part 52. The Catalog of Federal Domestic Assistance number is 93.262. This program is not subject to the Public Health System Reporting Requirements. Applications are not subject to review as governed by Executive Order 12372, Intergovernmental Review of Federal Programs. $$R7 END ************************************************************ $$R8 BEGIN HL-94-009 FULL-TEXT ************************************** CARDIOVASCULAR CONSEQUENCES OF SLEEP APNEA NIH GUIDE, Volume 23, Number 7, February 18, 1994 RFA AVAILABLE: HL-94-009 P.T. 34; K.W. 0715040, 0715187, 0785035 National Heart, Lung, and Blood Institute Letter of Intent Receipt Date: April 1, 1994 Application Receipt Date: May 23, 1994 THIS IS A NOTICE OF AVAILABILITY OF A REQUEST FOR APPLICATIONS (RFA); IT IS ONLY AN ABSTRACT OF THE RFA. POTENTIAL APPLICANTS MUST REQUEST THE COMPLETE RFA, WHICH CONTAINS ESSENTIAL INFORMATION FOR THE PREPARATION OF AN APPLICATION, FROM THE CONTACT LISTED IN "INQUIRIES," BELOW. FAILURE TO FOLLOW THE INSTRUCTIONS IN THE COMPLETE RFA MAY RESULT IN AN INCOMPLETE APPLICATION, WHICH WILL BE RETURNED TO THE APPLICANT WITHOUT REVIEW. PURPOSE The Division of Lung Diseases, Division of Epidemiology and Clinical Applications, and the National Center on Sleep Disorders Research are undertaking the development of a collaborative clinical study of cardiovascular consequences of sleep apnea, to be conducted in well characterized, existing population-based cohorts. Goals include determining the degree to which sleep apnea and milder degrees of sleep-related breathing disorders (SRBD) are independent or contributing risk factors for the development of cardiovascular and cerebrovascular disease, as well as examining possible associations with other cardiovascular risk factors. This RFA is both for clinical centers and the data coordinating center. It is estimated that the study will involve five to six clinical centers, each recruiting approximately 900 to 1,000 participants for in-depth studies of sleep apnea and SRBD from existing epidemiological cohorts. The solicitation is for five years. 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, Cardiovascular Consequences of Sleep Apnea, is related to the priority areas of heart disease and stroke, clinical prevention services, diabetes and chronic disabling diseases. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic, for-profit, and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of state and local governments, and eligible agencies of the Federal government. Foreign organizations are not eligible to apply and any international component of a domestic application must be minor in its magnitude and critical in what it would contribute. 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 a cooperative agreement (U01), an assistance mechanism. Under the cooperative agreement, the NIH assists, supports, and/or stimulates and is substantially involved with recipients in conducting a study by facilitating performance of the effort in a "partner" role. The anticipated award date is September 30, 1994. FUNDS AVAILABLE An estimated five to six awards for Clinical Centers and one award for a Data Coordinating Center will be made under this RFA. A maximum of about $16.3 million (including direct and indirect costs) over a five-year period will be awarded for the Clinical Centers and the Data Coordinating Center. Approximately $3.0 million will be available for the first year, $3.1 million for the second year, $3.3 million for the third year, $3.4 million the fourth year and $3.5 million for the last year. It is anticipated that the award for each Clinical Center will be about $400,000 total costs for the first year and the award for the Data Coordinating Center will be about $600,000 total costs for the first year. Because the nature and scope of the research proposed in response to this RFA may vary, it is anticipated that the size of an award will also vary in all years. At this time, the NHLBI anticipates that there may be a renewed competition after five years. However, the final decision will depend upon experience with the program during the first five years as well as financial considerations. RESEARCH OBJECTIVES Snoring, the most common symptom of sleep disordered breathing, has been implicated as a risk factor for the development of hypertension, ischemic heart disease, and cerebral infarction. Many of the adverse cardiovascular effects of snoring have been attributed to the substantial prevalence of obstructive sleep apnea among habitual snorers. The profound physiological derangements (hypoxemia, severe hypertension, tachycardia, fragmentation of sleep, arrhythmias) that often occur in association with sleep disordered breathing provide biologically plausible explanations for associations between sleep apnea and cardiovascular morbidity. However, it is not known whether sleep apnea is an independent vascular disease risk factor or a concomitant of established vascular or cerebral diseases or other risk factors (such as obesity or hypertension). Similarly, little is known regarding potential interactions between sleep apnea and other risk factors, or whether specific population subgroups may be particularly susceptible to adverse cardiovascular and cerebrovascular consequences associated with sleep apnea. Identification of factors that predispose to increased risk for SRBD is important for public health policy and for developing an improved understanding of disease pathogenesis that may include interactions among a number of risk factors in causing morbidity. This program seeks to accomplish this with an interactive, coordinated group of clinical centers working under a common protocol. This program is to be built upon established epidemiologic programs. It is anticipated that the sleep study would make use of data previously collected in existing cohort studies as well as any outcome information. For example, a number of studies supported by NHLBI, other components of NIH, National Center for Health Statistics, and other agencies have already collected much of the baseline information on hypertension, obesity, and other cardiovascular risk factors as well cardiovascular outcomes needed to examine relationships with sleep apnea and SRBD. Several epidemiology studies also include questionnaires on snoring that could be used to identify persons at high risk of sleep apnea. A total population of approximately 6,000 participants is anticipated. The sleep study population may include a wide range of samples from 40 years of age and above. It is not essential that all Clinical Centers have access to the full age range of subjects since certain established cohorts may be particularly suited to provide a unique aspect (age, gender, race, etc.) of their population for this program. The overall population to be studied should provide data that are broadly applicable to diverse minority groups as well as whites; thus, the composition of the study population in this RFA program must reflect this diversity. The timetable for this program may be roughly subdivided into three phases over a five year period. Phase I consists of planning and protocol development; phase II subject recruitment, protocol implementation, examinations and follow-up; phase III data analysis and prepare reports. STUDY POPULATIONS SPECIAL INSTRUCTIONS FOR INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDIES For projects involving clinical research, the NIH requires applicants to give special attention to the inclusion of women and minorities in study populations. If women or minorities are not included in the study populations for clinical studies, a specific justification for this exclusion must be provided. Applications without such documentation will not be accepted for review. LETTER OF INTENT Prospective applicants are asked to submit, by April 1, 1994, a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, the identities of other key personnel and participating institutions, and the number and title of the RFA in response to which the application may be submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information that it contains is helpful in planning for the review of applications. It allows NHLBI 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. C. James Scheirer at the address listed under INQUIRIES. APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 9/91) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research; or from the Office of Grants Information, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone (301) 594-7248; and from the NHLBI program staff listed under INQUIRIES. Applications must be received by May 23, 1994. If an application is received after this date it will be returned to the applicant without review. REVIEW CONSIDERATIONS Applicants are encouraged to submit and describe their own ideas on how best to meet the goals of the study, but they are expected to address issues identified under SPECIAL REQUIREMENTS of the RFA. Note that this document is not the RFA. Applications will be judged primarily on the scientific quality of the application, the appropriateness, facilities and access to subjects from existing, established epidemiology studies, adequacy of existing data, multidisciplinary nature of the study and group, approach to cost containment, the discussion of considerations relevant to this RFA, expertise of the investigators, their capability to perform the work proposed, and a demonstrated willingness to work as part of the collaborative group and with the NHLBI Project Scientist. The review group will assess (as further detailed in the RFA): Clinical Centers o Ability to utilize existing, established epidemiological cohorts to address the goals of this program; adequacy of the population and data set, and access to recruit the required numbers of subjects, including appropriate representation of minorities and women. o Scientific merit of the proposed sleep study protocol. o Qualifications, experience, and commitment of key personnel, including their previous experience conducting clinical or population based research. o Facilities, equipment and organizational structure to implement the protocol. o Rationale and cost-effectiveness of the research approach proposed. Data Coordinating Center o Scientific merit of the proposed research protocol. o Organizational, administrative, and supervisory ability and statistical expertise to serve as a Data Coordinating Center for multicenter, clinical or population based research. o Qualifications, experience, and commitment of key personnel. o Facilities, equipment and sub-contracts to function as a Data Coordinating Center. o Appropriateness of the budget for the work proposed. AWARD CRITERIA Applications recommended by the National Heart, Lung, and Blood Advisory Council will be considered for award based upon: (a) scientific and technical merit; (b) program balance, including in this instance, sufficient compatibility of features to make a successful collaborative program a reasonable likelihood; and (c) availability of funds. Letter of Intent Receipt Date: April 1, 1994 Application Receipt Date: May 23, 1994 Review by NHLBI Advisory Council: September 1-2, 1994 Anticipated Award Date: September 30, 1994 INQUIRIES Written and telephone inquiries are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Inquiries regarding this RFA and requests for the RFA may be directed to: James P. Kiley, Ph.D. Division of Lung Diseases National Heart, Lung, and Blood Institute Westwood Building, Room 6A15 Bethesda, MD 20892 Telephone: (301) 594-7443 FAX: (301) 594-7487 Direct inquiries regarding review and application procedures and address the letter of intent to: C. James Scheirer, Ph.D. Division of Extramural Affairs National Heart, Lung, and Blood Institute Westwood Building, Room 648 Bethesda, MD 20892 Telephone: (301) 594-7452 FAX: (301) 594-7407 Inquiries regarding fiscal and administrative matters may be directed to: Mr. Raymond L. Zimmerman Division of Extramural Affairs National Heart, Lung, and Blood Institute Westwood Building, Room 4A11C Bethesda, MD 20892 Telephone: (301) 594-7420 FAX: (301) 594-7492 AUTHORITY AND REGULATIONS This project is described in the Catalog of Federal Domestic Assistance No. 93.837. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR 74. This project is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$R8 END ************************************************************ ONGOING PROGRAM ANNOUNCEMENTS $$P1 BEGIN PAR-94-032 *********************************************** MARC FACULTY RESEARCH FELLOWSHIPS NIH GUIDE, Volume 23, Number 7, February 18, 1994 PAR NUMBER: PAR-94-032 P.T. National Institute of General Medical Sciences Application Receipt Dates: April 5 and December 5 THIS IS A RE-PUBLICATION OF THE PROGRAM ANNOUNCEMENT THAT APPEARED IN THE NIH GUIDE FOR GRANTS AND CONTRACTS ON FEBRUARY 4, 1994. PLEASE DISREGARD THE PREVIOUS VERSION. PURPOSE The Minority Access to Research Careers (MARC) Program of the National Institute of General Medical Sciences (NIGMS) provides research training opportunities for faculty and students at four-year colleges that have a substantial enrollment of students from underrepresented minority groups. As part of its ongoing commitment towards enhancing the research and research training environment at these colleges, NIGMS provides support for faculty at these institutions to enhance their research skills. This announcement describes the newly revised MARC Faculty Fellowship Programs. Faculty members who are recent recipients of the doctoral degree are encouraged to apply for the regular Postdoctoral Fellowship Award (F32) or to seek support at institutions with Institutional Postdoctoral Training Grants; there is no special MARC postdoctoral training program for these individuals. Information about F32 fellowships and training grants may be obtained from the relevant NIH Institute. MARC Faculty Predoctoral Fellowship The purpose of this program is to strengthen the research and research training opportunities of minority institutions by providing an opportunity for eligible faculty who lack the Ph.D. degree (or equivalent) to obtain the research doctorate. The expectation is that the candidate's training in a setting away from the home institution will expose the candidate to new ideas and will enhance the research and teaching environment of the home institution when the candidate returns. MARC Faculty Senior Fellowship The purpose of this program is to allow eligible faculty of minority institutions the opportunity to update their research skills and/or move into new areas of research through a year-long period of intensive research in a state- of-the-art research environment. The faculty member would have only minimal responsibilities at the home institution during the training period. The expectation is that these new skills will enhance the research and teaching environment of the home institution. ELIGIBILITY REQUIREMENTS MARC Faculty predoctoral and senior fellowships have the following common requirements. In addition, each mechanism has a few of its own specific requirements. To be eligible for either type of fellowship a candidate must: o be full-time, permanent faculty in biomedically-related science or mathematics at the home institution for at least three years at the time of submission of the application; (Note, permanent does not mean tenured or tenure-track but implies the expectation of continued employment in the normal course of events. Adjunct or part-time faculty are not eligible.) o intend to return to the home institution at the end of the training period; o demonstrate a commitment to research and teaching in a minority institution; o be seeking training in a science (including mathematics) related to biomedical or behavioral research; AND o be a citizen or a non-citizen national of the U.S., or have been lawfully admitted for permanent residence in the U.S., at the time of application. In addition, at the time of application for a MARC Faculty Predoctoral Fellowship, the candidate must be enrolled in OR have been accepted by and agreed to enroll in a Ph.D. or combined M.D./Ph.D. (or other combined professional doctorate/Ph.D.) training program in the biomedical or behavioral sciences. In addition, at the time of application for a MARC Faculty Senior Fellowship, at least seven years must have elapsed since the candidate received the Ph.D. degree or equivalent research or professional doctorate. The home institution is the college or university where the candidate is employed at the time of the application. The home institution must: o be a domestic private or public minority institution, that is, one with a significant enrollment of underrepresented minorities. For purposes of this announcement, underrepresented minorities are individuals belonging to racial/ethnic groups underrepresented in the biomedical or behavioral sciences. Nationally, these groups include African Americans, Hispanic Americans, Native Americans, and Pacific Islanders. Institutions must document eligibility by providing appropriate enrollment data; o offer at least the baccalaureate degree in the biomedical or behavioral sciences or mathematics; o support the candidate's plans for training; AND o guarantee and provide appropriate release time for faculty for research training. The training institution is the research university or research institution/center at which the training takes place. It may be a public or private, domestic or foreign institution. The training institution: o must offer a solid research environment as evidenced by a high-level of faculty involvement in biomedical research and a high-level of research support through competitive grants (or similar quality-based support, such as Howard Hughes Medical Institute support); o may NOT be the candidate's home institution; and o will be the sponsoring (applicant) institution. In addition, the sponsor, who will direct the candidate's research, must be a faculty member (or equivalent) at the training institution and have a distinguished record of achievement in research documented by high quality research publications and/or competitive research grant support. MECHANISM OF SUPPORT Awards under the MARC Faculty Predoctoral Fellowship will use the faculty fellowship (F34) award. Applicants may request up to five years of support. An applicant may request ONLY the following: a stipend equal to the actual annual salary, but not to exceed the stipend of a level 1 postdoctoral fellow (currently $20,700); tuition and fees as determined by the training institution; and an institutional allowance of $2000 per year to be used for costs directly related to the candidate's training. Funds will not be provided for purchasing equipment, although the institutional allowance may be used for this purpose PROVIDED that the equipment is DIRECTLY related to the candidate's training. No indirect costs will be paid. The candidate's stipend may be supplemented by either the home institution or the training institution using funds from non-Federal sources only. Awards under the MARC Faculty Senior Fellowship will use the senior fellowship (F33) award. Note that even though this mechanism is widely used throughout the NIH, applicants for the MARC Faculty Senior Fellowship should be aware of different eligibility requirements and review criteria. Applicants may request no less than one academic year (9 months) and no more than two years of support. A MARC Faculty Senior Fellowship applicant may request a stipend equal to the actual annual salary, but not to exceed the stipend of a level 7 postdoctoral fellow (currently $32,300); the actual amount of the stipend awarded will be prorated by the length of the award if the award is for less than 12 months. An applicant may also request an institutional allowance of $3000 per year to be used for expenses directly related to the candidate's training. No funds will be provided for purchasing equipment, travel, or housing. However, the institutional allowance may be used for equipment or travel to a scientific meeting provided that these are DIRECTLY related to the candidate's training. No indirect costs will be paid. The candidate's stipend may be supplemented by either the home institution or the training institution using non-Federal sources of funds only. MARC Faculty Senior Fellows will incur a payback obligation during the first 12 months of training, which can be satisfied on a month-by-month basis either by additional research training or by resuming a career in research or teaching. See the NIH Guide for Grants and Contracts, Vol. 22, No. 27, July 30, 1993, for more details. TRAINING OBJECTIVES The purpose of the MARC Faculty Fellowship Program is to enhance the research and research training capabilities of the home institution by offering faculty the opportunity to obtain training for the research doctorate OR, for those faculty with doctorates, to update or enhance their research skills through high quality research experiences. The expectation is that this training will enable the faculty to be better researchers, mentors, trainers, and role models in the home institution. APPLICATION PROCEDURES Applicants for MARC Faculty Predoctoral or MARC Faculty Senior Fellowships must use the Individual National Research Service Award form PHS 416-1 (rev. 10/91). These forms are available in most institutional offices of sponsored research; from the Office of Grants Information, Division of Research Grants, NIH, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone (301) 594-7248; and from the NIGMS MARC Program Office, at the address listed under INQUIRIES. If, at the time of application for a MARC Faculty Predoctoral Fellowship, the candidate has selected a research thesis advisor, that individual should serve as the sponsor. If a candidate has not yet selected a research thesis advisor, the head of the graduate program should nominate someone to serve as the candidate's sponsor. The application should indicate clearly that this is an interim arrangement and should describe procedures for selecting a permanent research thesis advisor. An application for either MARC Faculty Fellowship must contain a letter signed by appropriate officials of the HOME INSTITUTION, including the candidate's department head, (1) supporting the candidate's training plans; (2) guaranteeing the necessary release time for the candidate; (3) certifying the candidate's eligibility for the program; and (4) establishing the institution's eligibility as a minority institution through enrollment data. In addition, for MARC Faculty Predoctoral Fellowship candidates, this latter must describe the institution's commitment to the candidate. Submit a signed, typewritten original of the application, including the Checklist, at least three reference letters, the letter of support from the home institution, and two photocopies of the signed application in one package to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** Applications will be accepted for the April 5 and December 5 fellowship receipt dates ONLY. They will not be accepted for the August receipt date. In item 3, applicants must give the Program Announcement number, PAR- 94-032. In item 2, the name of the appropriate MARC Faculty Fellowship Program, Predoctoral or Senior, must be typed. REVIEW CONSIDERATIONS Applications will be evaluated for completeness by the Division of Research Grants and eligibility by staff in the NIGMS before review. Only those found to be complete and eligible will be reviewed for technical merit; others will be returned without review. Applications will be evaluated in accordance with the criteria stated below for scientific, technical, and training merit by appropriate peer review groups. NIGMS review committees will review the MARC Faculty Predoctoral Fellowship applications and committees from the Division of Research Grants will review the MARC Faculty Senior Fellowship applications. The second level of review for both types of fellowships will be provided by the senior staff in the NIGMS. It is critical that each application contain sufficient information about each element to enable the reviewers to make a reasoned evaluation. Review criteria o the applicant's qualifications and potential for a career as a researcher and teacher: for MARC Faculty Predoctoral Fellowship candidates, assessment will include academic record, honors, research experience, scientific publications and/or presentations, references, and training and career goals; for MARC Faculty Senior Fellowship candidates, assessment will include research and teaching experience, professional honors and awards, scientific publications and/or presentations, training and career goals, references, and plans for using research training to enhance research and teaching at the home institution; o quality and appropriateness of the proposed research training, including the specific research proposal; and o quality of the training environment, including, but not limited to, the qualifications and grant support of the sponsor. AWARD CRITERIA Awards will be made on the basis of the technical merit of the application. Among highly qualified candidates, preference may be given to those who demonstrate a strong commitment to research and teaching at a minority institution and who present evidence of strong support from the home and the training institutions, including the research sponsor. Review Schedule Application Receipt Dates: April 5 December 5 Initial Review: June February Secondary Review: August April Earliest Start: September May INQUIRIES Inquiries about the MARC Faculty Fellowship Programs are welcome. Questions concerning programmatic issues, including institutional eligibility, may be addressed to: Dr. Yvonne Maddox Minority Access to Research Careers Program National Institute of General Medical Sciences Westwood Building, Room 950 Bethesda, MD 20892 Telephone: (301) 594-7823 Questions concerning fiscal matters may be addressed to Ms. Toni Holland National Institute of General Medical Sciences Westwood Building, Room 935 Bethesda, MD 20892 Telephone: (301) 594-7819 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.880, Minority Access to Research Careers. Awards are authorized by sections 301 and 405 of the Public Health Service Act, as amended and administered under PHS grants policies and federal Regulations 45 CFR Part 74 and 45 CFR Part 92. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health systems Agency review. $$P1 END ************************************************************ $$P2 BEGIN PAR-94-034 *********************************************** MORE FACULTY DEVELOPMENT AWARD NIH GUIDE, Volume 23, Number 7, February 18, 1994 PAR NUMBER: PAR-94-034 P.T. National Institute of General Medical Sciences Application Receipt Dates: February 1, June 1, and October 1 PURPOSE The Minority Access to Research Careers (MARC) Program of the National Institute of General Medical Sciences (NIGMS) provides research training opportunities for faculty and students at four-year colleges that have a substantial enrollment of students from underrepresented minority groups. As part of its ongoing commitment towards enhancing the research and research training environment at these colleges, NIGMS provides support for faculty at these institutions to enhance their research skills. This announcement describes the new Faculty Development Award from the NIGMS Minority Opportunities for Research (MORE) Branch. This new program provides support for eligible faculty to spend the summer (or one academic term) every year for two to five years in full-time research in a research-intensive laboratory. ELIGIBILITY A candidate must: o be full-time, permanent faculty in biomedically-related science or mathematics at the home institution for at least three years at the time of submission of the application; (Note, permanent does not mean tenured or tenure-track but implies the expectation of continued employment in the normal course of events. Adjunct or part-time faculty are not eligible.); o have received the Ph.D. or equivalent at least seven years before the date of the application; o intend to return to the home institution at the end of the training period; o demonstrate a commitment to research and teaching in a minority institution; o plan to conduct research in a science (including mathematics) related to biomedical or behavioral research; AND o be a citizen or a non-citizen national of the U.S., or have been lawfully admitted for permanent residence in the U.S., at the time of application. The home institution is the college or university where the candidate is employed at the time of the application. The home institution must: o be a domestic private or public minority institution, that is, one with a significant enrollment of underrepresented minorities. For purposes of this announcement, underrepresented minorities are individuals belonging to racial/ethnic groups underrepresented in the biomedical or behavioral sciences. Nationally, these groups include African Americans, Hispanic Americans, Native Americans, and Pacific Islanders. Institutions must document eligibility by providing appropriate enrollment data; o offer at least the baccalaureate degree in the biomedical or behavioral sciences or mathematics; o support the candidate's plans; AND o guarantee and provide appropriate release time each year for the candidate for full-time research and to take courses at the research institution. The research institution is the university or other institution at which the candidate conducts his/her full- time summer research and takes courses. It may be a public or private, domestic or foreign institution. The research institution: o must offer a solid research environment as evidenced by a high-level of faculty involvement in biomedical research and a high-level of research support through competitive grants (or similar quality-based support, such as Howard Hughes Medical Institute support); AND o may NOT be the candidate's home institution. In addition, the sponsor, who will direct the candidate's research, must be a faculty member (or equivalent) at the research institution and should have a distinguished record of achievement in research documented by high quality research publications and/or competitive research grant support. MECHANISM OF SUPPORT Awards under this program will use the Minority School Faculty Development Award (K14). The applicant must request at least two years but not more than five consecutive years of support. The awards are renewable. RESEARCH OBJECTIVES The purpose of the MORE Faculty Research Award Program is to enhance the research and research training capabilities of the home institution by offering faculty the opportunity to update or enhance their research skills through high quality research experiences. The candidate will also have the opportunity to enroll in one course per academic term in fields directly related to the research in order to update his/her theoretical background. The expectation is that these new skills will enhance the research and teaching environment of the home institution. Ideally, the experience would lead to long-term collaborations between the candidate and the faculty of the research institution. Additional Information Candidates must engage in full-time research at the research institution for the summer (or other academic term) every year for at least two and not more than five consecutive years. Only ONE period of full-time research in a SINGLE academic OR calendar year will be supported. In addition, the candidate may enroll in one course per academic term at the research institution provided that the course is directly relevant to the candidate's research career development. All research and course work must be done at a single research institution unless an exception is granted by NIGMS in writing. The application must contain a letter signed by appropriate officials of the HOME INSTITUTION, including the candidate's department head, (1) supporting the candidate's plans; (2) guaranteeing the necessary release time for the candidate; (3) certifying the candidate's eligibility for the program; and (4) establishing the institution's eligibility as a minority institution through enrollment data. The application must also contain a statement, signed by the appropriate authorizing official, that the RESEARCH INSTITUTION agrees to the arrangements described in the application. If an award is made, the home institution and the research institution must establish the appropriate formal agreements. The PROPOSED RESEARCH SPONSOR is considered to be "key personnel" for this project and should be listed on page 2 of the application. The application MUST include a biographical sketch (form page FF) and description of grant support (form page GG) for the proposed research sponsor. In addition, the application should contain a letter of commitment from the sponsor describing his/her support for the applicant's research plan. Allowable Costs An applicant may request a salary equal to the candidate's actual annual salary and appropriate fringe benefits prorated for the period of time during which the candidate is engaged in full-time research at the research institution; salary support will not be provided for the time the candidate is enrolled in an academic course. The applicant may also request up to $3000 per year for supplies, equipment and other expenses, which may include travel to scientific meetings and/or the research site, provided that these costs are DIRECTLY related to the candidate's full-time research experiences. In addition, an applicant may request funds to pay tuition and fees for one course per academic term to be taken at the research institution. No funds will be provided for housing at the research site. Direct costs requested may not exceed $50,000 in any year. Indirect costs will be provided at eight percent of allowable direct costs. During the period of full-time research at the research institution, the candidate's salary may be supplemented by either the home institution or the research institution using non-Federal sources of funds only. APPLICATION PROCEDURES Applicants for the MORE Faculty Development Award (K14) are to use the regular research grant application form PHS 398 (rev. 9/91). These forms are available in many institutional offices of sponsored research; from the Office of Grants Information, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone (301) 594-7248; and from the NIGMS MARC Program Office at the address listed under INQUIRIES. In Item 2a, the candidate must give the PA number (PAR-94-034) and type the title "MORE FACULTY DEVELOPMENT AWARD." In item 2b, the candidate should type "K14." The HOME INSTITUTION will serve as the grantee institution. Submit a signed, typewritten original of the application, including the Checklist and other required supporting material, and five photocopies of the signed application and any appendices in one package to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** Applications will be accepted for the following research application receipt dates: February 1, June 1, and October 1. REVIEW CONSIDERATIONS Applications will be evaluated for completeness by the Division of Research Grants and eligibility by staff in NIGMS before review. Only those found to be complete and eligible will be reviewed for technical merit; others will be returned without review. Applications will be evaluated in accordance with the criteria stated below for scientific and technical merit by peer review groups in the Division of Research Grants. The second level of review will be provided by the senior staff in NIGMS. It is critical that the application contain sufficient information about each of these elements to enable the reviewers to make a reasoned evaluation. Review criteria o the applicant's qualifications and potential for a successful career as a researcher and teacher at a minority institution assessed in terms of research and teaching experience; professional honors and awards; scientific publications and/or presentations; references; training and career goals; and plans for using research experiences to enhance the research and teaching capability of the home institution. o quality and appropriateness of the proposed research and, if applicable, the associated course work; o quality of the research environment at the research institution, including, but not limited to, the qualifications and grant support of the sponsor; AWARD CRITERIA Awards will be made on the basis of the technical merit of the application. In addition, among highly qualified candidates, preference may be given to those who demonstrate a strong commitment to research and teaching at a minority institution and who present evidence of strong support from the home and the research institutions, including the research sponsor. Review Schedule Application Receipt Dates: March 1 July 1 November 1 Initial Review: June October February Secondary Review: August January May Earliest Start: September February June INQUIRIES Inquiries about the Faculty Development Award are welcome. Questions concerning programmatic issues, including institutional eligibility, may be addressed to: Dr. Yvonne Maddox Minority Access to Research Careers Program National Institute of General Medical Sciences Westwood Building, Room 950 Bethesda, MD 20892 Telephone: (301) 594-7823 Questions concerning fiscal matters may be addressed to Ms. Toni Holland Grants Management Specialist National Institute of General Medical Sciences Westwood Building, Room 935 Bethesda, MD 20892 Telephone: (301) 594-7819 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.880, Minority Access to Research Careers. Awards are authorized by sections 301 and 405 of the Public Health Service Act, as amended and administered under PHS grants policies and federal Regulations 45 CFR Part 74 and 45 CFR Part 92. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health systems Agency review. $$P2 END ************************************************************ $$P3 BEGIN PA-94-035 ************************************************ NEUROGENETIC DISORDERS OF INFANCY AND CHILDHOOD NIH GUIDE, Volume 23, Number 7, February 18, 1994 PA NUMBER: PA-94-035 P.T. 34; K.W. 1002019, 1002030 National Institute of Neurological Disorders and Stroke PURPOSE The National Institute of Neurological Disorders and Stroke (NINDS) announces the reissuance of a program announcement (originally published July 18, 1985) to notify the scientific community of continuing NINDS interest in the submission of research grant applications concerning neurogenetic disorders. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention goals of "Healthy People 2000," a PHS-led national activity for setting priorities. This program announcement, Neurogenetic Disorders of Infancy and Childhood, is related to the priority areas of chronic disabling conditions and maternal and infant health. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: No. 017-001-474-0, or Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by foreign and domestic, for-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State or local governments, and eligible agencies of the Federal government. Foreign institutions are not eligible for First Independent Research Support and Transition (FIRST) (R29) awards, program projects (P01), and center grants (P50). Applications from minority individuals and women are encouraged. MECHANISMS OF SUPPORT Applicants may use the research project grant (R01), program project (P01), center grants (P50), and FIRST (R29) award. Prospective applicants are encouraged to communicate with the NINDS program contact listed under INQUIRIES regarding the appropriate funding mechanism. RESEARCH OBJECTIVES Background It is estimated that of the 3,000 known genetic disorders, as many as one-third are primarily neurologic or have important neurologic involvement. Most of them have a low incidence, but collectively they represent an enormous burden on affected individuals, their families, and society. Many of these neurogenetic disorders manifest themselves early in life leading to either a premature death or to a lifelong disability with significant attendant psychological and economic hardships. Any attempt to group all the neurogenetic diseases of early life is somewhat arbitrary given that for many the underlying pathological mechanisms are incompletely understood. Examples of disorders of interest to the NINDS include: 1. Hereditary ataxias and related disorders such as Friedreich ataxia, ataxia telangiectasia, olivopontine cerebellar degeneration, Ramsay Hunt syndrome, abetalipoproteinemia, Machado-Joseph disease, and familial spastic paraparesis. 2. Movement disorders such as Juvenile Huntington disease, the dystonias including blepharospasm and spasmodic torticolis, tremor, myoclonus, and Hallervorden-Spatz disease. 3. Phakomatoses, or neurocutaneous syndromes such as neurofibromatosis, tuberous sclerosis, Sturge-Weber, and Von Hippel-Landau disease. 4. Mitochondrial encephalomyopathies such as the MELAS syndrome, Kearns-Sayre, and Leigh disease. 5. Hereditary disorders of nerve and muscle such as infantile spinal muscular atrophy, Charcot-Marie-Tooth disease, hereditary sensory and autonomic neuropathies, genetic myasthenic syndromes, metabolic myopathies, muscular dystrophies, and myotonias. In addition to diseases that have their major effects on the nervous system, many inborn errors of metabolism affect several systems, including the nervous system. The NINDS is interested in supporting research in the metabolic diseases where the research proposed is directed at the nervous system manifestations of the disorder. Examples of these metabolic diseases include, but are not limited to: 1. Disorders of lipid metabolism such as Gaucher disease, Niemann-Pick disease, the neuronal ceroid lipofuscinoses including Batten disease, the leukodystrophies, and the gangliosidoses including Tay-Sachs disease. 2. Disorders of carbohydrate metabolism such as galactosemia and hereditary fructose intolerance. 3. Glycogen storage diseases such as Von Gierke, Lafora disease, and Pompe disease. 4. Organic acidurias such as proprionic acidemia and methylmalonic acidemia. 5. Disorders of purine metabolism such as Lesch-Nyhan syndrome, and porphyria. 6. Disorders of amino acid metabolism and transport such as phenylketonuria, homocystinuria, maple syrup urine disease, urea cycle defects, Hartnup disease, and Lowe syndrome. 7. Disorders of mucopolysaccharide metabolism such as Hunter, Hurler, and Sanfilippo syndromes. 8. Disorders of metal metabolism such as Wilson disease and Menkes syndrome. There are numerous other neurological disorders that also result from genetic abnormalities such as the Laurence-Moon-Bardet-Biedl, Aicardi, Sjogren-Larsson, Prader-Willi and Angelman syndromes. In addition to those diseases that have a recognizable pattern of inheritance, there are many other neurological disorders that seem to have, in some cases, a familial basis. These may well represent neurogenetic disorders with multifactorial etiology. Such diseases can be as diverse as disorders of defective cellular migration (such as lissencephaly, heterotopias), neural tube defects, congenital hydrocephalus, myoclonic epilepsy, and narcolepsy. Research Goals and Scope Grant applications to study human neurogenetic disorders involving affected individuals and their family members are encouraged. Because the phenotypes of many neurogenetic disorders do not appear until childhood or early adolescence, the development of animal models is also important. Such models could make possible the detection of early biochemical changes, allow characterizations of the chemical pathology, and facilitate study of how genetic mutation disrupts the normal pathways of nervous system function. Areas of research interest include, but are not limited to, the following: A. Clinical Pathologic Correlations. Studies are needed to delineate the relationship of the clinical picture to pathological findings. Histopathological studies, including neurochemical studies of fresh tissue, which provide data for basic understanding of the relationship between pathophysiology and the evolution of clinical signs and symptoms, as well as the course of the disorder are encouraged. B. Genetics. Classical genetic studies have been used to establish the mode of inheritance for many of these disorders. This information will provide insight as to whether etiologic heterogeneity exists, and if sporadic cases are due to reduced penetrance or represent phenocopies. The most important contributions of genetic studies would be to establish the linkage relationships of the genes responsible for these disorders, and the identification of the defective gene and its normal biological role. State of the art methodologies for such studies should be used. C. Biochemistry. Studies should be directed at discovering the metabolic defect in each of these disorders and identifying its molecular basis. Successful biochemical studies will lead to an understanding of the pathogenic mechanisms and make possible the recognition of the heterozygote. Currently available advanced and sophisticated methodologies should be brought to bear on this important research. D. Neuroimaging. New neuroimaging technologies (PET, SPECT, MRI) can be applied to neurogenetic research problems and provide important clues about brain function under pathophysiological conditions and allow for correlation with the clinical disease state. E. Neuroepidemiology. There are some neurological diseases in which the genetic abnormality may not be the primary reason for the expression of the disorder. Epidemiological study of at risk families or clusters of cases might provide important clues of the interaction between genetic and non-genetic factors in producing the clinical symptomatology. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements will be required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder, or condition under study; special emphasis should be placed on the need for inclusion of minorities and women in studies of diseases, disorders, and conditions that disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale should be provided. The composition of the proposed study population must be described in terms of gender and racial or ethnic group. In addition, gender and racial or ethnic issues should be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information should be included in the form PHS 398 in Sections 1-4 of the Research Plan AND summarized in Section 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups; however, the NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of Unites States racial or ethnic minority populations: Native Americans (including American Indians or Alaska Natives), Asian or Pacific Islanders, Blacks, and Hispanics). The rationale for studies on single minority population groups should be provided. For the purpose of this policy, clinical research includes human biomedical and behavioral studies of etiology, epidemiology, prevention (and prevention strategies), diagnosis, or treatment of diseases, disorders, or conditions, including, but not limited to, clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded; however, every effort should be made to include human tissues from women and racial or ethnic minorities when it is important to apply the results of the study broadly. This directive should be addressed by applicants. For foreign awards, the policy on inclusion of women applies fully. Since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' population, including minorities. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and will be reflected in assigning the priority score to the application. All applications for clinical research submitted to the NIH are required to address these policies. If the required information is not contained within the application, the review will be deferred until the information is provided. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. APPLICATION PROCEDURES Applications are to be submitted on the grant application form PHS 398 (rev. 9/91) according to the instructions included in the application package. These application packages are available at the offices of sponsored research of most institutions eligible to receive Federal grants and from the Office of Grants Information, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone 301/594-7249. Applicants for program project grants should request a copy of the NINDS Guidelines: Program Project and Research Center Grants from the program staff listed under INQUIRIES. Receipt dates for new research project grant (R01) applications and FIRST (R29) awards and for program project (P01) and center grant (P50) applications are February 1, June 1, and October 1. FIRST 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. On page 1 of form PHS 398, check "YES" in Item 2a, enter the number of this Program Announcement in the space provided, and provide the name of this Program Announcement (Neurogenetic Disorders of Infancy and Childhood) in the blank space labeled "Title." Use the mailing label provided in the application package to mail the signed original and five exact copies of it to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** For program projects or center grants, submit the original and three copies to the Division of Research Grants. An additional two copies of the program project or center grant application must be sent to Dr. Judy Small at the address listed under INQUIRIES to expedite the processing of these applications for multidisciplinary efforts. REVIEW CONSIDERATIONS Several other Institutes at the National Institutes of Health also have an interest in supporting areas of research covered by this PA. Applications will be assigned on the basis of established Public Health Service referral guidelines and some applications may receive dual assignments. In the case of R01 and R29 applications, they 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 and criteria. Program project applications will be reviewed by initial review groups organized by the Institute to which the application is assigned. Following scientific-technical review, the applications will receive a second-level review by the Institute's national advisory council. AWARD CRITERIA The standard review criteria will be used to assess the scientific merit of applications. Applications will compete for available funds with all other applications. The following will be considered when making funding decisions: o quality of the proposed projects as determined by peer review, o availability of funds, and o program balance among research areas. INQUIRIES Written and telephone inquiries are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Questions concerning scientific aspects of this Program Announcement and application procedures may be addressed to: Dr. Judy A. Small Division of Convulsive, Developmental, and Neuromuscular Disorders National Institute of Neurological Disorders and Stroke Federal Building, Room 8C04 Bethesda, MD 20892 Telephone: (301) 496-5821 FAX: (301) 402-0887 Questions concerning fiscal aspects of this Program Announcement may be addressed to: Mr. King P. Bond, Jr. Grants Management Branch National Institute of Neurological Disorders and Stroke Federal Building, Room 1004 Bethesda, MD 20892 Telephone: (301) 496-9231 AUTHORITY AND REGULATIONS This program is described in the Catalogue of Federal Domestic Assistance, Number 93.853, Clinical Research Related to Neurological Disorders, and 93.854, Biological Basis Research in the Neurosciences. Grants will be awarded under the authority of the Public Health Service Act, Title IV, Section 301 (Public Law 78-410, as amended: 42 USC 241) and administered under PHS grants policies and Federal Regulations 42 CFR Part 52 and 45 CFR 74. This program is not subject to Health Services Agency review of the intergovernmental review requirements of Executive Order 12372. $$P3 END ************************************************************ $$P4 BEGIN PA-94-036 ************************************************ CHARACTERIZATION AND TREATMENT OF GENETIC METABOLIC DISEASES NIH GUIDE, Volume 23, Number 7, February 18, 1994 PA NUMBER: PA-94-036 P.T. 34; K.W. 0715135, 1002019, 0765035, 0745070 National Institute of Diabetes and Digestive and Kidney Diseases PURPOSE The purpose of this program announcement is to encourage research grant applications studying the mechanisms underlying the pathophysiology of genetic metabolic diseases. Research should be aimed at elucidating the genetic defects, examining their metabolic consequences, and devising and testing possible therapies for this group of devastating diseases. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This Program Announcement, Characterization and Treatment of Genetic Metabolic Diseases, is related to the priority area of chronic disabling conditions. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State or local governments, and eligible agencies of the Federal government. Foreign institutions are not eligible for First Independent Research Support and Transition (FIRST) (R29) awards and program projects (P01). Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT Support of this program will be through the NIH research project grant (R01), FIRST (R29) awards, and program projects (P01). All investigators interested in submitting a program project will need to discuss the application with NIDDK staff and obtain the NIDDK Program Project Guidelines prior to applying for support via this mechanism. The use of Interactive Research Project Grants (IRPG) is encouraged for multi-disciplinary approaches to this complex problem. Further information on the IRPG mechanism is available in the NIH Guide, Vol. 22, No. 16, April 23, 1993. RESEARCH OBJECTIVES The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) supports research on identifying and understanding the basic defects in causing genetic metabolic diseases, identifying alternative metabolic pathways, characterizing toxic metabolites and the mechanisms of their effects on multiple organs, development of From owner-sci-resources@net.bio.net Wed Feb 16 22:00:00 1994 Path: biosci!biosci!not-for-mail From: Dave Kristofferson Newsgroups: bionet.sci-resources Subject: NIH GUIDE - RFA HD-94-012 - V23(07) 02/18/94 Date: 16 Feb 1994 16:24:09 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 1277 Approved: biosci-moderator@net.bio.net Distribution: bionet Message-ID: <2judf9$673@net.bio.net> NNTP-Posting-Host: net.bio.net $$XID RFA HD94012 HD-94-012 P1O1 *************************************** ADOLESCENT MEDICINE HIV/AIDS RESEARCH NETWORK NIH GUIDE, Volume 23, Number 7, February 18, 1994 RFA: HD-94-012 P.T. National Institute of Child Health and Human Development National Institute of Allergy and Infectious Diseases Health Resources and Services Administration Letter of Intent Receipt Date: March 30, 1994 Application Receipt Date: May 13, 1994 PURPOSE The National Institute of Child Health and Human Development (NICHD) and the National Institute of Allergy and Infectious Diseases (NIAID), in responding to identified research needs in human immunodeficiency virus (HIV)-infected and at risk adolescents (U.S. Congress, Office of Technology Assessment, Adolescent Health- Volume I; Summary and Policy Options, OTA-H-468 (Washington DC: US Government Printing Office, April 1991)) and Public Law 103-43-- National Institutes of Health Revitalization Act of 1993, Title X, Subtitle D, Section 1031--Prospective Longitudinal Study on Adolescent Health, invite applications for cooperative agreements to participate in a clinical network to plan and conduct research on the medical, biobehavioral, and psychosocial aspects of HIV/AIDS, including access to care and its utilization in adolescents infected with HIV through sexual or drug-taking behaviors. The network will initially focus on adolescents between ages 15 and 19 years and, as funding becomes available, expand to include adolescents between the ages of 12 and 19 years. The Maternal and Child Health Bureau (MCHB), Division of Services for Children with Special Needs (DSCSN), Health Resources and Services Administration (HRSA) will provide the funds to support clinical sites to (1) develop the comprehensive health care infrastructure necessary to support clinical research where such infrastructure does not exist and (2) develop and disseminate treatment and policy guidelines specific to HIV-infected adolescents. Applicants for the Basic Science Group should have research experience pertinent to the objectives delineated in this RFA. Applicants for the Clinical Science Group must provide health care services to HIV-infected adolescents. Furthermore, they must demonstrate the proven capacity to reach sufficient numbers of adolescents with HIV infection and provide comprehensive adolescent HIV-related health care and support services (Track A) or submit a plan to provide comprehensive adolescent HIV-related health care and support services in support of clinical research (Track B). In addition, applicants for either Track A or Track B in the Clinical Science Group must be willing and able to participate in a cooperative program of research and evaluation with other successful applicants. Applicants are encouraged, where appropriate, to apply as a consortium in order to satisfy site, service, and recruitment requirements. Existing and operational consortia are preferred to those convened around grant requirements. Consortia may apply in Track A or Track B. Track A consortium applicants must demonstrate the capacity for comprehensive health care services at each participating site; Track B consortium applicants must submit a plan for using limited Track B funds to provide comprehensive health care services in support of clinical research at all participating sites where such service does not exist. The network will consist of a Basic Science Group and a Clinical Science Group; applicants may apply for funding in either group component or both. Applicants to the Clinical Science Group must indicate Track A or Track B consideration. NICHD, NIAID, and HRSA also invite applications for a cooperative agreement with a Data and Operations Center for the Network. This Data and Operations Center will manage data from surveys, studies, and interventions at the funded sites, consult on and perform the appropriate statistical analyses of the data, maintain the communications link for the network, and support the activities of research planning, protocol design, and information dissemination. This center will be functionally independent of all research sites, although it could be physically located at one of them. The assistance mechanism used to support this research is the cooperative agreement, which is similar to a traditional research grant, but one in which NIH and HRSA scientific and program staff participate with study investigators as partners in the research effort. 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), Adolescent Medicine HIV/AIDS Research Network, is related to the priority areas of health and well-being of special population groups and HIV infection. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of state and local governments, and eligible agencies of the Federal government. Minority investigators and women are encouraged to apply. It is expected that applicants for the Basic Science Group have research experience pertinent to the objectives of the network delineated in this RFA. MECHANISM OF SUPPORT The administrative and funding instrument to be used for this program will be a cooperative agreement (U01), an "assistance" mechanism (rather than an "acquisition" mechanism) in which substantial NIH and HRSA scientific and/or programmatic involvement with the awardee is anticipated during the performance of the activity. (PHS Grants Policy Statement, DHHS (OASH) 90-50,000 (rev. October 1, 1991). Under the cooperative agreement, the purpose of the NIH and HRSA 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. Specifically, members of the NICHD, NIAID, and HRSA scientific and program staff will cooperate with principal investigators as partners in the projects and serve as science collaborators or program managers. All parties will agree to accept the participatory and cooperative nature of the group process. Details of the responsibilities, relationship, and governance of the study to be funded under cooperative agreements are discussed later in this document under the section "Terms and Conditions of Award". The total project period for applications submitted in response to the present RFA may not exceed five years. The anticipated award date is September, 1994. At this time, NICHD, NIAID, and HRSA have not determined whether or how this solicitation will be continued beyond the present RFA. Awards and level of support depend on receipt of a sufficient number of applications of high scientific merit. Although this program is provided for in the financial plans of NICHD, NIAID, and HRSA awards pursuant to this RFA are contingent upon the availability of funds for this purpose. FUNDS AVAILABLE NIAID funds available for the support of this program are $300,000 (total costs). The estimated NICHD funds available for support of the entire program in Phase I (consisting of six months for planning and base protocol/management guidelines development) and Phase II (consisting of the subsequent six months for protocol implementation and subject recruitment) during the first year are $2,400,000 (total costs). These funds will support the direct cost of activities of the Basic Science Group, the clinical research activities of the Clinical Science Group, and the operations/support activities of the Data and Operations Center. Direct costs are approximated as follows: (1) For all non-laboratory components of the Basic Science Group - $235,000 (direct costs) for 8-10 awards. (2) For the clinical research activities of the Clinical Science Group - $875,000 (direct costs) for 8-10 awards. This amount includes subject encounter costs for two visits of the base protocol in year one for all awardees in the Clinical Science Group. (3) For the data operations and support services of the Data and Operations Center - $450,000 (direct costs). (4) For the support of the virology laboratory that is part of the Basic Science Group - $120,000 (direct costs). (5) For the support of the immunology laboratory that is part of the Basic Science Group - $120,000 (direct costs). In addition, the estimated HRSA funds available for support of the Track B clinical sites in Phase II and the resource capacity of the clinical sites are $250,000 (total costs). It is expected that supplemental NIH funds will be added in future years to cover costs of full year research staff at clinical sites and special studies to be undertaken in the assembled cohort enrolled in the base protocol. Track B awards include additional HRSA money to support the health care infrastructure in augmented service delivery in support of the clinical research agenda of the Network. It is anticipated that 8-10 Basic Science Group including one virology laboratory and one immunology laboratory, 8-10 Clinical Science Group including two-three Track B sites, and one Data/Operations Center awards will be made. This level of support is dependent on the receipt of a sufficient number of applications of high scientific and experiential merit. The number of awards and actual funds awarded depend on the overall scientific merit of the applications and the availability of funds. RESEARCH OBJECTIVES Background Through September 1993, 1,415 AIDS cases in adolescents (aged 13- 19 years) were reported to the National Centers for Disease Control and Prevention. Although adolescents comprise less than one percent of all reported AIDS cases, the impact of HIV infection during adolescence is far more profound. First, the long incubation period between initial HIV infection and the development of AIDS-defining conditions suggests that the majority of AIDS cases in persons between 20 and 29 years of age, which constitute nearly 20 percent of all reported AIDS cases, can be attributed to infection as teenagers. Secondly, HIV infection, and to some extent AIDS cases under the new case definition, are not accurately estimated through reporting mechanisms because adolescents lack easy access to medical care for diagnosis. Many may actually succumb to competing causes of mortality (e.g., violence). Recent blinded HIV serosurveys indicate a range of estimates: from prevalence rates of 0.34 per 1000 in 17-19 year applicants to the military, 1.7 per 1000 in the users of student health services on selected college campuses, 3.9 per 1000 in Job Corps applicants, to 88 per 1000 in an urban homeless youth center. Of the groups affected by HIV, the U.S. adolescent population is the one in which basic biologic issues are the most poorly understood and the one in which therapeutic and clinical management trials have not been effectively initiated. At the present time, it is not known how HIV infection affects continuing development in those adolescents who have been infected through sexual or injecting drug use practices. It is not clear how age at infection influences the course of maturation nor is it clear how maturation might proceed in HIV+ adolescents with repeated HIV sexual exposure, sexually transmitted disease co-morbidity, and/or pregnancy. The heterosexual transmission of HIV is attaining increasing importance as a mode of HIV spread to uninfected individuals. This mode of HIV transmission is particularly important in the adolescent population due to the high prevalence of high-risk behaviors. The factors which modulate the heterosexual transmission of HIV have not been determined. However, it is likely that the replication of HIV at genital mucosal surfaces plays a major role in the likelihood of the occurrence of viral transmission following heterosexual exposure. Previous studies have documented the presence of HIV and antibodies in cervical and seminal secretions. However, the prevalence of these markers and the relationship to other microbial pathogens in the adolescent population has not been defined. The determination of the prevalence of specific markers of HIV infection is an important first step in defining the relationship between these markers and heterosexual transmission. Little is known about the normal range of many routine laboratory values during the steroid-mediated phase of growth and development, particularly in immunologic parameters. This deficiency makes the choice of precise and accurate clinical disease indicators problematic for adolescent subjects in trials. Research Goals and Scope: This initiative calls for a descriptive examination of the full spectrum of HIV disease and its behavioral manifestations in adolescents who have become infected with HIV through sex and drug-taking behaviors in order to identify and pursue HIV/AIDS- specific research agenda in the adolescent population between the ages of 15 and 19 years of age. Adolescents between 12 and 15 years of age may be incorporated in future potential expansions of the network. The ultimate goal of this project is to achieve a better understanding of HIV disease progression and co-morbidity in adolescents and thus improve health care management; this goal will be addressed through the enrollment of approximately 200 HIV-infected adolescents into a standardized base protocol to characterize population-based spectrum of disease, disease progression, and the effect of comorbidity with other sexually- transmitted diseases and pregnancy in the adolescent population; and the standardization and evaluation of health care services. A secondary goal involves the resolution of remaining questions related to HIV infection in adolescents through the development of special studies to be undertaken in the assembled cohort enrolled in the base protocol. These unresolved questions include, but are not limited to, the susceptibility, infectivity, and transmissibility of HIV in adolescents, particularly related to developing genital mucosa; the characterization of the variation in adolescent immune function; the identification of useful adolescent-specific clinical markers of HIV disease progression; the effect of HIV on adolescent neuropsychologic function and development; and the influence and effect of specific adolescent behavioral patterns on risk-taking and health-seeking activities. The network will also produce and evaluate clinical management guidelines for adolescent HIV infection that recognize the unique biological and behavioral features of this group. The network will assist member units in establishing an interface with adolescent-eligible clinical drug and vaccine trials through a variety of mechanisms that are appropriate to the clinical research issues facing the group and take in account particular issues facing adolescents. Cooperative agreements are sought to establish a research network and permit the conduct of a wide-ranging, multi-stage series of investigations that address one or more of the clinical facets of HIV infection in adolescents. SPECIAL REQUIREMENTS The Adolescent Medicine HIV/AIDS Research Network will consist of two interactive groups, Basic Science and Clinical Science, managed by Steering and Executive Committees, supported by a Data and Operations Center, and advised by a Community Advisory Board. Organizational Components The Basic Science Group component will provide salary support to a group of scientists whose purpose is to set the scientific agenda for the Adolescent Medicine HIV/AIDS Research Network. The Basic Science Group will consist of one NICHD and one NIAID staff collaborator, 8-10 principal investigators who would include adolescent medicine specialist(s), immunologist(s), virologist(s), epidemiologist(s), endocrinologist(s), behavioralist(s), and other relevant disciplines with responsibility for setting the scientific agenda, refining the base study protocol, and developing substudy protocols to address the agenda and evaluation of the clinical management guidelines. Members of the Basic Science Group will participate in twice monthly conference calls during year 1 and attend two meetings per year: one specifically for the Basic Science Group and the other in conjunction with members of the Clinical Science Group and Community Advisory Board. Applications to become members of the Basic Science Group must include (1) documentation of clinical experience in adolescent health care or professional interest in adolescent issues; (2) record of published research relevant to adolescent health care issues; (3) submission of an original research module designed to further the adolescent HIV/AIDS research agenda. This research module may focus on any of the research areas listed in the Research Goals and Scope Section of this RFA or address unspecified research areas relevant to adolescent HIV infection that are consistent with the scope of this RFA. The Basic Science Group will hold its first meeting shortly after the grants are awarded. At that time, members will present briefly the research modules that formed the basis for their competitive awards. The purpose and scope of the cooperative agreement will be reviewed as will the current state of knowledge about the natural history of HIV infection in adolescents. The members of the Basic Science Group will prioritize the specific scientific goals and aims and construct a base study protocol that reflects these priorities and will address scientific questions concerning the natural history of HIV infection and disease in adolescents. Substudies that are also reflective of the research modules proposed by the Basic Science Group members and the overall goals of the cooperative agreement may be agreed upon at this time. Recognition that it will not be possible to implement all the research modules proposed for purposes of technical review is essential. Other limiting considerations will include: (1) studies that are feasible to undertake in the proposed research population; (2) the financial resources available to the Network; and (3) strategies that are likely to be most productive and cost-effective in addressing the research priorities of the Network. A format for pursuing special studies will be developed, implementation strategies will be discussed in preparation for interaction with the Clinical Science Group, and a timeline for submission to the Executive Committee will be drawn up. Laboratory support for the research network will consist of one AIDS Clinical Trials Group (ACTG)- certified immunology laboratory and one ACTG certified virology laboratory; both funded to support specific study components. Investigators from these two sites will be included in the Basic Science Group. ACTG certification provides an established quality control evaluation. Applicants for these two reserved positions will be required to submit only a research module as outlined above for other members of the Basic Science Group (item 3 above) as well as documentation of research experience specific to their discipline. The Clinical Science Group component will provide salary and program support to clinical sites providing health care services to adolescent populations. The Clinical Science Group will consist of 8-10 principal investigators who are adolescent medicine specialists at clinical sites that can enroll at least 20 HIV-positive adolescents and 10 HIV-negative but high-risk adolescents, between the ages of 15 and 19 years, into the base study while providing comprehensive health care services through other funding mechanisms. Track A sites are those with established comprehensive health care services for adolescents through HRSA-funded Ryan White Care Act Title IV/Pediatric Demonstration Projects or other funding mechanisms; Track B sites are those sites with a well-developed and operationally-supported plan for the provision of comprehensive health care services, but require funding for its implementation. This comprehensive care infrastructure is necessary to support the clinical research agenda of this network. The Clinical Science Group will interact with the Basic Science Group and be responsible for the generation of clinical management guidelines, enrolling adolescents into selected substudies, and potentially enrolling adolescents into clinical drug and vaccine trials (that are already supported through other mechanisms, e.g., ACTG, CPCRA, AVEG, AmFAR). Members of the Clinical Science Group will participate in twice monthly conference calls during Phase I and monthly thereafter and attend one annual meeting in conjunction with members of the Basic Science Group and one separate meeting focusing on clinical management and policy issues. Applications to participate in the Clinical Science Group should include information in three areas: staff, site, and patient population/geographic location. Applicants should document their ability to recruit a sufficient number of participants between the ages of 15 and 19 years, discuss their capacity to participate in the program and their ability to interact effectively with the Data and Operations Center, and state their willingness to follow the common protocol that will be produced by the Basic Science Group and to implement subsequent protocols targeting adolescent-specific research questions. The Data and Operations Center will manage two meetings of the entire Network including the Steering Committee during Phase I; one annual scientific meeting for Basic Science Group and one annual management/policy meeting for the Clinical Science Group during Phase II of Year 1; twice-monthly conference calls for the Basic Science Group during Year 1; twice monthly conference calls for the Clinical Science Group during Phase I and monthly conference calls thereafter; and ad hoc calls as necessary. The Center will support protocol development and distribution. It will also assume responsibility for site registration, any protocol-related training, monitoring of sites for accurate and complete data collection, regulatory compliance, and research subject safeguards. The Center will provide support to the Clinical Science Group for the development and dissemination of treatment and policy guidelines, as well as provide resources to the Community Advisory Board. The Center will be responsible for the integrity of the scientific databases by editing and entering data, as well as designing and maintaining the study database(s). In addition, this center will provide statistical consultation to both Science Groups as needed and analytic support. Applicants should document past experience with conducting other programs that required responsibilities similar to those outlined above. The applicant should submit a detailed plan of activities with time lines that would successfully implement the effort required to support the research network program. Separate applications must be made for the Clinical Science Group, the Basic Science Group, and the Data and Operations Center, even if a single organizational entity is applying for more than one activity. Regardless of whether the Data and Operations Center is located at one of the cooperating sites, it will maintain strict independence. Study Phases: Phase I It is expected that Phase I (six months) will be devoted to identification of the research agenda, the development of the base protocol, and the development of the clinical management guidelines. Work on these tasks will ensue at an organizational meeting of the entire Network at which group chairs and vice chairs are elected soon after awards. Work will continue by twice monthly conference calls, monitored by the Executive Committee, and culminate with an implementation meeting of the Steering Committee and the entire Network at month six. Study Phases: Phase II This Phase involves the training of clinical research staff, the recruitment of study subjects, the implementation of the base protocol for the Clinical Science Group sites, and the further protocol development of special studies for the Basic Science Group members. During this phase, Basic Science Group faculty, data/operations center staff, and NICHD and NIAID staff collaborators will meet annually for a scientific retreat. The Steering Committee members in conjunction with the entire Network will meet annually for scientific interactive sessions. Terms and Conditions of Award The following terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS Grants Administration Regulations at 45 CFR Part 74 and 92 and other HHS, PHS, and NIH grant administration policies. Business management aspects of these awards will be administered by the NICHD Grants Management Office in accordance with HHS, PHS, and NIH Grants Administration policies. It is envisioned at this time that all awarded funds will be administered by the NICHD Grants Management Office. The administrative and funding instrument to be used for this program will be a cooperative agreement (U01), an "assistance" mechanism (rather than an "acquisition" mechanism) in which substantial NIH and HRSA scientific and/or programmatic involvement with the awardee is anticipated during the performance of the activity. Under the cooperative agreement, the NIH purpose is to support and/or stimulate the recipient's activity by involvement in and otherwise working jointly with the award recipient in a partner role, but it is not to assume direction, prime responsibility, or a dominant role in the activity. Consistent with this concept, the dominant role and prime responsibility for the activity resides with the awardees for the project as a whole, although specific tasks and activities in carrying out the studies will be shared among awardees and the NICHD, NIAID, and HRSA staff collaborators. 1. The Primary Rights and Responsibilities of the Awardees are as follows: Basic Science Group: The Basic Science Group will consist of those awardees whose submissions were chosen on scientific merit. The Basic Science Group, with a chair and vice chair elected by its members, will o Retain the primary responsibility for defining and prioritizing the research agenda and submitting the agenda to the Steering Committee for approval o Specify research objectives for the base study to characterize population-based spectrum of disease and disease progression and secondary special studies, develop corresponding protocols, provide for monitoring the progress of various studies, and analyze and interpret study protocol results. It is expected that this responsibility will be undertaken with significant interaction with the members of the Clinical Science Group. o Consult and review Clinical Science Group plans for the evaluation of clinical management guidelines that address the unique biological, biobehavioral and psychosocial issues of adolescence including pharmacologic prophylaxis, the scope and frequency of medical monitoring, and organization of services, among others. o Basic Science Group awardees, as a group, will retain custody of and have primary rights to the protocol data developed under these awards, subject to government rights of access consistent with current HHS, PHS, and NIH policies. Protocol development for special studies shall be undertaken when two-thirds of the Basic Science Group members approve the research concept. o Laboratory Support awardees of the Basic Science Group will be expected to satisfy all responsibilities of Basic Science Group members as outlined above. In addition, these two members will provide expertise in areas of immunology or virology to the Basic Science Group and furnish laboratory services to the Network to support protocol-specified evaluations. Clinical Science Group: The Clinical Science Group will consist of those awardees whose submissions were chosen on clinical experience and capacity. The Clinical Science Group, with a chair and vice chair elected by its members, will o Participate in the production of the research agenda through review and evaluation at regularly scheduled interactive Network meetings and by submitting concepts for study (both primary or secondary analyses). Clinical Science Group members will be strongly encouraged to submit research concepts to the Basic Science Group and may participate in their subsequent protocol development. Decisions related to protocol development and protocol team formation are the responsibility of the Basic Science Group. o Retain primary responsibility for the implementation of the base protocol and secondary protocols where feasible and the recruitment and monitoring of study participants, associated data collection, and quality control. o Awardees will be required to accept and implement the common protocol developed by the Basic Science Group and all procedures approved by the Steering Committee. o Derive clinical management guidelines for the standardization of health care delivery across network sites that address the unique biological, biobehavioral, and psychosocial issues of adolescence including pharmacologic prophylaxis, the scope and frequency of medical monitoring, and service organization, overcoming barriers to care, among others; and submit a corresponding evaluation plan to the Basic Science Group for consultation and review. o Clinical Science awardees, as a group, will retain custody of and have primary rights to the data specific to guidelines evaluation developed under these awards, subject to government rights of access consistent with current HHS, PHS, and NIH policies. Study development for the secondary analyses of data generated through the clinical management guideline evaluation shall be undertaken when two-thirds of the Clinical Science Group members approve the research concept. o Clinical Science awardees, as a group, will convene consensus panels on the dissemination of clinical management guidelines and the definition of adolescent-specific HIV policy among other tasks consistent with functioning as a national resource body. o Clinical Science Group members will recruit two adolescent/family member community representatives from each clinical site, at least one of whom from each site must be an adolescent between 15 to 19 years to serve on the Community Advisory Board o Track B Awardees will be required to comply with the reporting requirements imposed on HRSA funded Title IV/ Pediatric- Adolescent Demonstration Projects. 2. Program Staff Involvement The research effort will be a cooperative venture with participation by all awardees as outlined above, the NICHD, the NIAID and HRSA. One NICHD, one NIAID, and one HRSA staff collaborator will: o Participate in the Steering Committee that oversees the establishment and maintenance of the Network and its progress in achieving program goals. o Assist Basic Science Group in the selection of research topics and the development of protocols for specific studies and interventions. o Assist Clinical Science Group in the development and evaluation of clinical management guidelines. o Arrange, when necessary, for the external peer review of the protocols for the base study, special studies, and clinical management guideline evaluation, clearing these studies for implementation. o Explore mechanisms to offer study subjects the opportunity to participate in clinical drug trials funded through mechanisms outside the network and provide this information and organizational support to clinical sites. o Assist the Executive Committee in monitoring the progress of ongoing studies, including field data collection, standardization of methods across study sites, and adherence to protocol and quality control measures. o Assist in data analyses, interpretation and publication of study results One NICHD, one NIAID, and one HRSA program manager, in addition to routine program management duties, will: o Assist in identifying the need to terminate or curtail the study (or an individual award) in the event of nonparticipation in the committee/group activities, substantial shortfall in participant recruitment, followup, data reporting, quality control, or other major breach of protocol, or substantive protocol changes without prior approval from the staff collaborators and Basic Science Group. 3. Collaborative Responsibilities: The Research Network The Research Network is composed of all principal investigators of the Basic Science Group, all principal investigators of the Clinical Science Group, all representatives of the Community Advisory Board, the principal investigator and project coordinator from the Data and Operations Center, and the NICHD, the NIAID, and HRSA staff collaborators and program managers. The entire Network will attend interactive annual meetings to inform and review the research agenda. The Steering Committee The Steering Committee is the main governing body of the Network. The Committee is composed of the Chair, Vice Chair, and two elected representatives from the Basic Science Group; the Chair, Vice Chair, and two elected representatives from the Clinical Science Group; the Chair and Vice Chair of the Community Advisory Board; the principal investigator and project coordinator from the Data and Operations Center; and the NICHD, NIAID, and HRSA staff collaborators. All members will have one vote each; NICHD, NIAID, and HRSA will have one vote each, and motions will carry with simple majority. The Chair and Vice Chair of the Steering Committee will be elected by the entire committee from among the principal investigators of the Basic Science Group and the Clinical Science Group; none of the NICHD, NIAID, or HRSA staff collaborators are eligible to serve as Chair or Vice Chair of the Steering Committee. The Steering Committee will o Maintain primary responsibility for the identification of adolescent HIV/AIDS research issues. o Approve the direction of the research effort, and facilitate the conduct and monitoring of the studies. o Approve the research agenda specific to its feasibility and clinical relevance and advise on the development of implementation strategies. o Approve the clinical management guidelines addressing the unique biological, biobehavioral, and psychosocial issues of adolescence including pharmacologic prophylaxis, the scope and frequency of medical monitoring, and service organization, among others; and the plans for their evaluation. The Executive Committee An Executive Committee, composed of the Steering Committee chair, the chair and vice-chair of the Basic Science Group, the chair and vice chair of the Clinical Science Group, the principal investigator and project coordinator of the Data and Operations Center, and the NICHD, NIAID, and HRSA staff collaborators will supervise the functioning of the network and will o Establish timelines for the completion of tasks and monitor progress o Coordinate the integration of data collection for base protocol and guidelines evaluation procedures o Oversee site participation and performance informing the appropriate program managers o Define rules regarding access to data and publication and direct the publication process. o The Steering Committee chair will chair the Executive Committee as well. 4. Arbitration Process The specific terms and conditions above and the details of arbitration procedures below pertaining to the scope and nature of the interaction among NICHD, NIAID, HRSA, and participating sites will be incorporated into the notice of grant award. These procedures will be in addition to the customary programmatic and financial negotiations that occur in the administration of grants. Arbitration procedures will be invoked only when agreement cannot be reached on programmatic issues that may arise between awardee(s) and the project coordinator(s) after the award has been made. In that event, an arbitration panel will be composed of three members-- one selected by the executive committee (with the NICHD, NIAID, and HRSA staff collaborators not voting) or by the individual awardee in the event of an individual disagreement, a second member selected by the program officers, and a third member selected by the two prior selected members. The decision of the arbitration panel by majority vote will be binding. This special arbitration procedure in no way affects the awardee's right to appeal an adverse action that is otherwise appealable in accordance with the PHS Regulations at 42 CFR Part 50, Subpart D and HHS Regulation at 45 CFR Part 16. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS It is NIH policy that applicants for NIH clinical research grants and cooperative agreements (i.e., research involving human subjects) are required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis must be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear and compelling rationale must be provided. The composition of the proposed study population at the clinical site must be described in terms of gender and racial/ethnic group. This information must be included in the form PHS 398 in Sections 1-4 of the Research Plan and summarized in Section 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., Native Americans [including American Indians or Alaskan Natives], Asian/Pacific Islanders, Blacks, Hispanics). It is envisioned that the cohort of adolescent study subjects assembled under the auspices of this cooperative agreement will exhibit appropriate and adequate ethnic, racial, and geographic representation of the affected population although individual sites may not each present the necessary balance. For the purpose of this policy, clinical research is defined as human biomedical and behavioral studies of etiology, epidemiology, prevention (and prevention strategies), diagnosis, or treatment of diseases, disorders or conditions, including, but not limited to, clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded. However, every effort should be made to include human tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by the applicants. For foreign awards, the policy on inclusion of women applies fully; since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. If the required information is not contained within the application, the application will be returned. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question addressed and the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and reflected in assigning the priority score to the application. All applications for clinical research submitted to the NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. LETTER OF INTENT Prospective applicants are asked to submit, by March 30, 1994, a letter of intent that includes a descriptive title of the proposed research, the name, address and telephone number of the Principal Investigator, the identities of other key personnel and participating institutions, and the number and title of the RFA in response to which the application may be submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information that it contains is helpful in planning for the review of applications. It allows ICD staff to estimate potential review workload and to avoid conflict of interest in the review. The letter of intent is to be sent to: Audrey Smith Rogers, Ph.D., M.P.H. Center for Research for Mothers and Children National Institute of Child Health and Human Development 6100 Executive Boulevard, Suite 4B11 Rockville, MD 20852 Telephone: (301) 496-7339 APPLICATION PROCEDURES Applications are to be submitted on form PHS 398 (rev. 9/91). This application form is available in the office of sponsored research at most academic and research institutions and from the Office of Grants Information, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda MD 20892, telephone (301) 594-7248 and from the NIH program administrator listed under INQUIRIES. Additional Materials to Include in the Application To permit evaluation of the merits of an application (peer review), information is needed on the following topics. Applicants to the Basic Science Group: While the objectives of the Network specifically relate to unresolved basic and clinical scientific questions about adolescent HIV/AIDS, the unique behavioral features of this age group must be recognized. Consequently, multidisciplinary representation will be sought in the membership of the Basic Science Group while its basic and clinical science focus is maintained. Applications to become members of the Basic Science Group must include: (1) documentation of clinical experience in adolescent health care or professional interest in adolescent issues; (2) record of published scientific research with relevance to adolescent medical, biological, biobehavioral, and/or behavioral issues; and (3) submission of an original research module written to demonstrate personal expertise in a specific area of interest consistent with the overall research objectives of this RFA. This research module will be used to judge the scientific and technical proficiency of the applicant. It is not required to be a fully-developed protocol and therefore should not include sections on study implementation, study timelines, or budgetary considerations. The research module must include a carefully defined statement of the problem consistent with the overall research objectives of this RFA, a comprehensive review of relevant literature, a detailed study strategy including design issues and proposed analyses, and a discussion of problems to be encountered in implementing the study which take in account particular issues facing adolescents. This module may address any research question consistent with the scope of this RFA. The research module may focus on the design of the base protocol examining the spectrum of HIV disease to be implemented in the first year of the study or on other areas requiring special studies to be undertaken in the assembled cohort enrolled in the base protocol in subsequent years. These include, but are not limited to: HIV interaction with adolescent pregnancy; co-morbidity with STDs; the susceptibility, infectivity and transmissibility of HIV in adolescents, particularly related to developing genital mucosa; the characterization of the variation in adolescent immune function; the identification of useful adolescent-specific clinical markers of HIV disease progression; the effect of HIV on adolescent neuropsychologic function and development; and the influence and effect of specific adolescent behavioral patterns on risk-taking and health-seeking activities. THIS LIST OF POTENTIAL SUBJECT AREAS IS NOT INCLUSIVE; RESEARCH MODULES IN RELEVANT AREAS CONSISTENT WITH THE FOCUS OF THIS RFA ARE VERY STRONGLY ENCOURAGED. If the applicant is successful, the proposed research module may or may not be chosen subsequently by the constituted Basic Science Group to be incorporated into the scientific agenda undertaken by the Adolescent Medicine HIV/AIDS Research Network. The proposed module should, nonetheless, be designed for implementation in the projected Network study population (see below), and be consistent with the research objectives of the RFA. This part of the application should not exceed the 25 page limit (including graphics) for the entire submission. In the event that the applicant is not chosen to participate in the Basic Science Group of the Research Network or, if chosen, learns that the applicant's submission will not be incorporated into the scientific agenda nor implemented in the network, the applicant retains all rights to the material and is free to pursue the funding and conduct of such a study through other mechanisms. The budget for Basic Science Group members should include salary support at 0.10 FTE, flat fee for office support services, and travel to three meetings (two days each) in the Washington DC area for year one only; for two meetings in Washington DC per year thereafter. Applicants for the Basic Science Group: Immunology and Virology Laboratory Two positions on the Basic Science Group are restricted for applicants who can provide currently established ACTG-certified immunology or virology laboratory support to Network research efforts. Applicants for these two reserved positions will be required to submit only a research proposal as outlined above in (3) using and completing the PHS 398 application kit. The budget for the immunology laboratory should include funding for the ACTG- defined lymphocyte panel for the entire study population for two visits in Phase II Year 1 and every six months thereafter as well as salary support for the Basic Science Group member at 0.10 FTE, flat fee for office support services, and travel to three meetings (two days each) in the Washington DC area for year one only; for two meetings in Washington DC per year thereafter. The budget for the virology laboratory in the first year of the grant should include funding for the storage of samples for the entire study population at baseline and every six months thereafter as well as salary support for the Basic Science Group member at 0.10 FTE, flat fee for office support services, and travel to three meetings (two days each) in the Washington DC area for year one only; for two meetings in Washington DC per year thereafter. Applicants for the Clinical Science Group Since the objectives of the Network specifically relate to unresolved basic and clinical scientific questions about adolescent HIV/AIDS, the proposed network must consist of established clinical sites delivering appropriate health care and support services to substantial adolescent populations. This RFA should not be construed as a funding opportunity to establish an adolescent health care delivery service. Furthermore, since adolescent participation in research should be an opportunity presented to those for whom health care is available and never as a means of health care or a substitute for it, clinical sites in the network must have developed strategies and mechanisms for providing for the health care and support needs of their adolescent populations (Track A) or submit a well-developed and operationally-supported plan to augment comprehensive health care and support services requiring funding for its implementation (Track B). HRSA funds for Track B will be available to a limited number of established sites to augment existing services so that clinical research may be conducted in a population of individuals receiving adequate comprehensive health care. Applications to participate in the Clinical Science Group should include information in three areas: staff, site, and patient population/geographic location. The description of these facilities and equipment should be provided on the Resources and Environment page of the PHS 398 application kit. All applicants must submit the following: (1) Documentation of three or more years clinical experience in adolescent health care for the physician Clinical Science Group member applicant and the research nurse or associate (if identified at the time of submission) to be supported by this grant. (2) A description of the site(s) (physical structure and administrative arrangement) in which health care and support services are provided or arranged for, including hours of operation, provision for off-hour coverage, and established patterns of referral. (3) The source of funding for the delivery of health care and support services to adolescents served by the clinic should be delineated, particularly the proportion of services rendered for which third party reimbursement is received. (4) Evidence of an interdisciplinary approach to the delivery of adolescent health care and support services is expected and the breadth of available services and qualifications of the corresponding providers should be listed and described. (5) Description of the adolescent population categorized by ages 10-14 years, 15-19 years, and 20-24 years served by the clinic as such: (a) adolescents in the catchment area of the clinic; (b) adolescents seen within the last year by the clinic; and (c) adolescents who regularly attend the clinic (each succeeding group should be a subset of the former). This information will be used in determining future expansions of the network. (6) Descriptors of these defined groups should include (if available) gender, race/ethnicity, socioeconomic strata, educational achievement, blinded serosurveys of HIV infection, AIDS case numbers (cumulative and annual), STD and pregnancy rates, substance abuse statistics, and other evidence of high risk behaviors. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear and compelling rationale must be provided. (7) Evidence of ability to enroll 20 HIV-infected adolescents and 10 HIV-negative but high risk adolescents between the ages of 15 and 19 years in the six month period of Phase II. (8) Documentation concerning adherence to clinic appointments and referrals or other measures should be included as evidence of the population's capacity and willingness to participate in clinical research. (9) The interaction between the clinic and the community it serves should be described. Of specific interest are community advisory or consultative groups that have substantial adolescent participation, efforts at parental or community education, the clinic policies for adolescent involvement in their own care and, where relevant, for parental involvement in adolescent care, and details of community existing or planned outreach and prevention programs to identify adolescents and bring them to care. (10) Budgets for the Clinical Science Group sites should include physician principal investigator salary support at 0.10 FTE, clinical associate/research nurse at 1.0 FTE for Phase II only, and two clinical visits for study subjects (examination and minimal laboratory) for the base study during Phase II. Travel for the principal investigator to three meetings (two days each) in the Washington DC area should be included. This includes one management policy/meeting. In addition, budgets should include travel costs for two adolescent/family representatives from each clinical site to the annual Steering Committee meeting. Track B sites should include a clearly-marked and separate budget sheet for augmented services in support of clinical research. Track A Applicants must submit the following: (1) Demonstration of availability of on-site gynecologic services and case management, on-site or established and functioning referral networks for mental health services, substance abuse treatment, and enabling services such as childcare and transportation. (2) Evidence of collaboration with other institutions, agencies, or community-based organizations for outreach, case identification, and access to clinical drug trials should be detailed. Every collaborative initiative cited should be accompanied by a letter of commitment specific to the activity of this RFA. Track B Applicants must submit the following: (1) Submission of a plan to provide any of the following services in support of clinical research: on-site gynecologic services and case management, to articulate with other institutions, agencies, or community-based organizations for outreach, case identification, mental health and substance abuse services, and access to clinical drug trials. The plan should be detailed and every collaborative initiative cited should be accompanied by a letter of commitment specific to the activity of this RFA. (2) Documentation of the availability or evidence of collaboration with other institutions, agencies, or community-based organizations to provide services not addressed in plan required in (1). Applicants for the Data Center should include the following information: (1) Expertise in the design of surveys, case control studies, cohort studies, and interventions. Applicants should provide a description of their experience designing these different types of projects with special emphasis on the required statistical expertise, as well as examples of past or current projects requiring this expertise. They should also identify individuals with this expertise on staff or available as consultants and provide their biographical sketches in PHS 398 application kit. (2) Documentation of understanding of the basic elements required for a data coordinating center. This should include an understanding of computer logistics, programming, coding, data processing, file building, and file maintenance. (3) Ability to finalize research protocols and questionnaires and to monitor quality control. This should include prior or current experience relative to the development of protocols, questionnaires, other research instruments, and interacting with multi-disciplinary teams. An indication of procedures used for training staff in the use of these protocols and questionnaires and quality control of data collection across several sites would be most useful. (4) Documentation that the personnel proposed for involvement in data management and data processing aspects of the project have experience in the management of large datasets, designing appropriate systems, computer programming, data coding, data entry, data editing, quality control, file building, file manipulation, and data analysis should be provided. (5) Description of facilities and equipment available, including computer hardware and software that are intended for use by this project, should be provided. (6) Documentation of understanding of the basic elements required for maintaining an operations center. This should include an understanding of establishing and maintaining the communications link for the Network and supporting the activities of research planning, protocol design, and development through team conference calls and information dissemination. (7) Description of resources available to support the development and effective national dissemination of treatment and policy guidelines specific to HIV positive adolescents. (8) The budget for the Data and Operations Center should include 0.5 FTE salary support for a principal investigator, service costs for data entry, management, and analysis; 0.25 FTE salary support for a project coordinator, 1.0 FTE salary support for research nurse/site monitor, site visit travel, conference calls, meetings, and resources for protocol development and committee/board support. The Center will also assume costs of Clinical Science Group treatment and policy guidelines development and dissemination. The RFA label available in the PHS 398 application form must be affixed to the bottom of the face page. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for evaluation. In addition, the RFA title and number ("Adolescent Medicine HIV/AIDS Research Network, HD-94-012") must be typed on line 2A of the face page of the application form and the "YES" box must be marked. In addition to RFA title and number, applicants must further designate on the face sheet that the application is submitted for (1) Basic Science Group; (2) Basic Science Group- Immunology Lab; (3) Basic Science Group- Virology Lab; (4) Clinical Science Group- Track A; (5) Clinical Science Group -Track B; or (6) Data Center. The signed, typewritten original of the application including the Checklist and three signed photocopies must be sent or delivered in one package to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** In addition, two copies of the application must be sent, under separate cover to: Susan Streufert, Ph.D. Division of Scientific Review National Institute of Child Health and Human Development 6100 Executive Boulevard, Room 5E01 Bethesda MD 20892 Applications must be received by close of business May 13, 1994. If an application is received after that date, it will be returned to the applicant without review. The Division of Research Grants (DRG) will not accept any application in response to this announcement that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. The DRG will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of a substantial revision of an application already reviewed, but such an application must follow the guidance in the form PHS 398 application instructions for the preparation of revised applications, including an introduction addressing the previous critique. REVIEW CONSIDERATIONS Pre-Review Assessment Upon receipt, applications will be examined by the Division of Research Grants for completeness. The NICHD will assess the applications for responsiveness. Incomplete applications will be returned to the applicant without further consideration. Applications not responsive to the RFA will also be returned. Applications to the Clinical Science Group will be assessed for responsiveness by NICHD and HRSA program staff to determine their suitability for consideration in Track A or Track B relative to other applications received in response to this RFA. Applicants to the Clinical Science Group, therefore, may be notified of their ability to compete in a Track other than the Track for which they originally sought funding. Review Considerations Complete and responsive applications will be evaluated in accordance with the criteria stated below for scientific/technical merit by a review group specifically convened by NICHD in consultation with NIAID and HRSA for this purpose. Further, applications to the Basic Science Group may be subjected to triage by an NICHD/NIAID peer review group to determine their scientific merit relative to other applications received in response to this RFA. The review criteria to be used are listed below. The NIH will withdraw from further competition those applications judged by triage to be noncompetitive for the award and notify the applicant PI and institutional official. Those applications, both to the Basic Science and the Clinical Science Groups, judged to be competitive will undergo further scientific merit review. The second level of review will be provided by the advisory councils of the participating awarding components. Review Criteria: o Scientific, technical, or medical significance and originality of the proposed research; o Appropriateness and adequacy of the experimental approach and methodology to carry out the research; o Qualifications and experience of the principal investigator and staff, particularly, but not exclusively, in the area of the proposed research; o Availability of the resources necessary to perform the research; o Appropriateness of the proposed budget and duration in relation to the proposed research; o Appropriateness of plans for the inclusion of women and minorities as subjects; o Appropriateness of methods and demonstrated willingness to work as a part of the cooperative study with the NICHD, NIAID, and HRSA scientists. In addition to these general criteria, additional review criteria will be used in evaluating several of the components as follows: Basic Science Group (Including Immunology and Virology Laboratories) o The degree to which the propose research promises to advance knowledge of adolescent HIV/AIDS and is concordant with current knowledge about this age group and disease. Clinical Science Group o Clinical training and experience specific to adolescent care o Evidence of interdisciplinary approach o Adequacy of site characteristics as detailed in the RFA Data and Operations Center o Expertise and experience in design and statistical analysis appropriate to this effort o Demonstrated ability or potential to serve as a center for multidisciplinary, multisite collaborative studies AWARD CRITERIA Applications recommended by the relevant National Advisory Councils will be considered for award based upon (a) scientific and technical merit as reflected in the priority score; (b) program balance including sufficient compatibility of features to make a successful collaborative program likely; (c) availability of funds; (d) geographic location of clinical sites; and (d) demographic and clinical characteristics of the population at the clinical site. Letter of Intent Receipt Date: March 30, 1994 Application Receipt Date: May 13, 1994 Review by NICHD Advisory Council: September 27, 1994 Anticipated Award Date: September 30, 1994 INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Two pre-submission conferences providing the same information will be held: March 9, 1994 from 11:00 AM-12:30 PM 6100 Building 5th Floor Conference Room 6100 Executive Boulevard Rockville, MD 20852 March 17, 1994 from 6:30-8:00 PM Century Plaza Hotel and Towers - Redwood Room 2025 Avenue of the Stars Los Angeles, CA 90067-4696 Direct inquiries regarding programmatic issues to: Audrey Smith Rogers, Ph.D., M.P.H. Center for Research for Mothers and Children National Institute of Child Health and Human Development 6100 Executive Boulevard, Suite 4B11 Rockville, MD 20852 Telephone: (301) 496-7339 Tina Johnson, M.A. Division of AIDS National Institute of Allergy and Infectious Diseases 6003 Executive Boulevard, Room 2A09 Rockville, MD 20852 Telephone: (301) 496-8214 Direct inquiries regarding administrative/fiscal matters to: Mr. E. Douglas Shawver Office of Grants and Contracts National Institute of Child Health and Human Development 6100 Executive Boulevard, Suite 8A17F Rockville, MD 20852 Telephone: (301) 496-1303 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.856. Awards are made under the authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74 and 92. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. From owner-sci-resources@net.bio.net Wed Feb 16 22:00:00 1994 Path: biosci!biosci!not-for-mail From: Dave Kristofferson Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 23, no. 7, pt. 4, 18 February 1994 Date: 16 Feb 1994 16:23:29 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 179 Approved: biosci-moderator@net.bio.net Distribution: bionet Message-ID: <2jude1$64v@net.bio.net> NNTP-Posting-Host: net.bio.net $$XID NIHGUIDE 19940218 V23N07 P4O4 ************************************ cells. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements will be required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis must be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale must be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues should be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information must be included in the form PHS 398 in Sections 1-4 of the research plan AND summarized in Section 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., Native Americans (including American Indians or Alaskan Natives), Asian/Pacific Islanders, Blacks, Hispanics). The rationale for studies on single minority population groups must be provided. For the purpose of this policy, clinical research is defined as human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including but not limited to clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded. However, every effort should be made to include human tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. For foreign awards, the policy on inclusion of women applies fully; since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. If the required information is not contained within the application, the review will be deferred until the information is provided. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question(s) addressed and the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and will be reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. APPLICATION PROCEDURES Applications are to be submitted on the grant application form PHS 398 (rev. 9/91) according to instructions contained in the application kit. Application kits are available from most institutional offices of sponsored research and may be obtained from the Office of Grants Information, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone 301-594-7248. Check "YES" in item 2a on the face sheet of the application and type "Gene Therapy in Duchenne Muscular Dystrophy." FIRST (R29) applications must include at least three sealed letters of reference attached to the face page of the original application. FIRST applications submitted without the required number of reference letters will be considered incomplete and will be returned without review. Applicants for the P01 or P50 should use the application format as described in the NINDS pamphlet, NINDS GUIDELINES: PROGRAM PROJECT AND RESEARCH CENTER GRANTS (rev. June 1992). Deadlines for the receipt of applications are February 1, June 1, and October 1. The completed original application and five exact copies must be sent or delivered to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** If the application is for a program project or center grant, submit the original and three copies to the Division of Research Grants. An additional two copies must be sent to Dr. Nichols at the address listed under INQUIRIES to expedite processing applications for multidisciplinary efforts. REVIEW CONSIDERATIONS Applications will be assigned on the basis of established PHS referral guidelines. Applications will be judged on scientific merit and program relevance in accordance with NIH policy and procedures involving peer review. An initial review will be made by an appropriate study section of the Division of Research Grants for regular research grants and FIRST awards, and by an appropriate institute committee for program projects and centers. A second level of review will be made by an appropriate national advisory council. AWARD CRITERIA Applications will compete for available funds with all other approved applications. The following will be used in making funding decisions: o Quality of the proposed project as determined by peer review o Availability of funds o Program balance among research areas of the announcement INQUIRIES Written and telephone inquiries are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Paul L. Nichols, Ph.D Developmental Neurology Branch National Institute of Neurological Disorders and Stroke Federal Building, Room 8C08 Bethesda, MD 20892 Telephone: (301) 496-5821 Richard W. Lymn, Ph.D. Muscle Biology Program National Institute of Arthritis and Musculoskeletal and Skin Diseases Westwood Building, Room 403 Bethesda, MD 20892 Telephone: (301) 594-9959 Bitnet: LYM@NIHCU Direct inquiries regarding fiscal matter to: Patricia P. Driscoll Grants Management Branch National Institute of Neurological Disorders and Stroke Federal Building, Room 10A14 Bethesda, MD 20892 Telephone: (301) 496-9231 Carol Clearfield Grants Management Branch National Institute of Arthritis and Musculoskeletal and Skin Diseases Westwood Building, Room 726 Bethesda, MD 20892 Telephone: (301) 594-9973 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.853 ("Clinical Research Related Neurological Disorders") and 93.854 ("Biological Basis Research in the Neurosciences"). Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-150, 42 USC 241 and 285) and administered under PHS grant 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. $$P8 END ************************************************************ From owner-sci-resources@net.bio.net Wed Feb 16 22:00:00 1994 Path: biosci!biosci!not-for-mail From: Dave Kristofferson Newsgroups: bionet.sci-resources Subject: NIH GUIDE - RFA HL-94-009 - V23(07) 02/18/94 Date: 16 Feb 1994 16:23:51 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 939 Approved: biosci-moderator@net.bio.net Distribution: bionet Message-ID: <2juden$663@net.bio.net> NNTP-Posting-Host: net.bio.net $$XID RFA HL94009 HL-94-009 P1O1 *************************************** CARDIOVASCULAR CONSEQUENCES OF SLEEP APNEA NIH GUIDE, Volume 23, Number 7, February 18, 1994 RFA: HL-94-009 P.T. 34; K.W. 0715040, 0715187, 0785035 National Heart, Lung, and Blood Institute Letter of Intent Receipt Date: April 1, 1994 Application Receipt Date: May 23, 1994 PURPOSE The Division of Lung Diseases, Division of Epidemiology and Clinical Applications, and the National Center on Sleep Disorders Research are undertaking the development of a collaborative clinical study of cardiovascular consequences of sleep apnea, to be conducted in well characterized, existing population-based cohorts. Goals include determining the degree to which sleep apnea and milder degrees of sleep-related breathing disorders (SRBD) are independent or contributing risk factors for the development of cardiovascular and cerebrovascular disease, as well as examining possible associations with other cardiovascular risk factors. This request for applications (RFA) is both for clinical centers and the data coordinating center. It is estimated that the study will involve five to six clinical centers, each recruiting approximately 900 to 1,000 participants for in-depth studies of sleep apnea and SRBD from existing epidemiological cohorts; there will be a single Data Coordinating Center. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This RFA, Cardiovascular Consequences of Sleep Apnea, is related to the priority areas of heart disease and stroke, clinical prevention services, diabetes and chronic disabling diseases. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic, for-profit, and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of state and local governments, and eligible agencies of the Federal government. Foreign organizations are not eligible to apply and any international component of a domestic application must be minor in its magnitude and critical in what it would contribute. Applications from minority individuals and women are encouraged. Awards for a Clinical Center and a Data Coordinating Center under this RFA will not be made to the same Principal Investigator (PI) to ensure that data analysis is done independently of data acquisition. The same institution may apply for both a Clinical Center and the Data Coordinating Center award, but the applications for each must be from different individuals. Data coordinating centers currently participating in epidemiology cohort studies are eligible. MECHANISM OF SUPPORT The administrative and funding instrument to be used for this program will be a cooperative agreement (U01), an assistance 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 to be funded under cooperative agreement(s) are discussed later in this document under the section Terms and Conditions of Award. The total project period for applications submitted in response to the present RFA may not exceed five years. The anticipated award date is September 30, 1994. Awards and level of support depend on receipt of a sufficient number of applications of high scientific merit. Although this program is provided for in the financial plans of the NHLBI, awards pursuant to this RFA are contingent upon the availability of funds for this purpose. Because the nature and scope of the research proposed in response to this RFA may vary, it is anticipated that the sizes of awards will also vary. At this time, the NHLBI anticipates that there may be a renewed competition after five years. However, the final decision will depend upon experience with the program during the first five years as well as financial considerations. FUNDS AVAILABLE An estimated five to six awards for Clinical Centers and one award for a Data Coordinating Center will be made under this RFA. A maximum of about $16.3 million (including direct and indirect costs) over a five-year period will be awarded for the Clinical Centers and the Data Coordinating Center. Approximately $3.0 million will be available for the first year, $3.1 million for the second year, $3.3 million for the third year, $3.4 million the fourth year and $3.5 million for the last year. It is anticipated that the award for each Clinical Center will be about $400,000 total costs for the first year and the award for the Data Coordinating Center will be about $600,000 total costs for the first year. RESEARCH OBJECTIVES Background Snoring, the most common symptom of sleep disordered breathing, has been implicated as a risk factor for the development of hypertension, ischemic heart disease and cerebral infarction. Many of these adverse cardiovascular effects of snoring have been attributed to the substantial prevalence of obstructive sleep apnea among habitual snorers. Obstructive sleep apnea is characterized by loud snoring and disrupted breathing during sleep. It is associated with a number of adverse clinical consequences, including daytime sleepiness, impaired performance, accidents and cardio/cerebrovascular morbidity and mortality. The relative risks of cerebrovascular accidents, ischemic heart disease, and myocardial infarctions range from 1.5 to 4 in snorers as compared to non-snorers. Hypertension is common in patients with sleep apnea, with studies suggesting that up to 40 percent of hypertensive patients may have significant sleep apnea. Improvement in hypertension control has been reported to occur in patients with both conditions following treatment of their apnea. Vascular mortality may be significantly higher among untreated or conservatively treated patients with sleep apnea compared to patients treated aggressively. In addition, patients with sleep apnea or heavy snoring may have up to a 50 percent decrease in brain blood flow during rapid eye movement (REM) sleep and as high as a 50 percent increase in the incidence of stroke. These findings raise the intriguing possibility of a potential etiologic relationship between sleep apnea and thrombotic stroke. Sleep apnea may be an independent vascular disease risk factor, a concomitant of established vascular or cerebral diseases or other risk factors (such as obesity or hypertension), but this remains to be determined. Similarly, little is known regarding potential interactions between sleep apnea and other risk factors, or whether specific population subgroups may be particularly susceptible to adverse cardiovascular and cerebrovascular consequences potentially associated with sleep apnea. Further elucidation of the relationship between sleep apnea and hypertension in African-Americans may be particularly important. Severe hypertension is more common and its consequences more severe in African-Americans than in whites, but the reasons for this are not clear. Risk factors for sleep apnea such as obesity and macroglossia are also common in African-Americans, and preliminary data suggest that, among young subjects, sleep apnea may be more prevalent among African-Americans than among whites. Sleep apnea could help elucidate the marked racial differences in hypertension and its consequences. Sleep apnea is also known to increase markedly in prevalence following menopause. Examining cardiovascular disease events and sleep apnea in post-menopausal women may provide insight into any possible changes in cardiovascular disease risk among women. Sleep apnea has been described in 30 percent or more of elderly subjects. The bases for strong relationships between aging and increased apneic activity are not understood, but may be related to changes in sleep quality, cerebral function, muscle tone, obesity, cardiac function and lung function with aging. Due to their reduced functional reserves and co-existing morbidity, elderly persons may be at greatest risk for exacerbation of underlying cardiovascular and cerebrovascular disease when exposed to the physiologic stresses associated with apnea and arousal from sleep. The profound physiological derangements (hypoxemia, severe hypertension, tachycardia, fragmentation of sleep, arrhythmias) that often occur in association with sleep disordered breathing provide biologically plausible explanations for associations between sleep apnea and cardiovascular morbidity. The increased risk of cardiovascular events shortly after awakening has been linked to sympathetic discharge associated with arousal, which can occur dozens of times each night in patients with sleep apnea. The use of cardiovascular medications may also be an important effect modifier on the relationship of CVD, its risk factors, and SRBD, since some of these agents have known side effects related to sleep and breathing. Identification of factors that predispose to increased risk for SRBD is important for public health policy, potentially enabling specific high risk populations to be targeted, as well as for developing an improved understanding of disease pathogenesis that may include interactions among a number of risk factors in causing morbidity. This program seeks to accomplish this with an interactive, coordinated group of clinical centers working under a common protocol in a multidisciplinary setting. A separate Data Coordinating Center will support protocol development, sample size calculations, common questionnaires, complete data analysis, data management, standardization of procedures, quality control and overall study coordination. Objectives and Scope The overall objective of this program (sleep study) is to utilize existing, well characterized, established population-based epidemiologic cohorts (parent studies) to determine the degree to which sleep apnea is an independent or contributing risk factor for the development of cardiovascular and cerebrovascular disease. It is also aimed at examining possible associations between sleep apnea, hypertension and stroke among different age, gender and ethnic groups. This program has five specific aims; however, other important areas may be appropriate for inclusion into this program and it is not restricted to only these five aims: o Determining the risk of CVD associated with sleep apnea and other sleep related breathing disorders independent of other cardiovascular disease risk factors; o Assessing potential interactions between sleep apnea, SRBD, and other vascular disease risk factors, particularly obesity and hypertension, in relation to CVD risk; o Examining the contribution of sleep apnea and SRBD to the development of other CVD risk factors, particularly hypertension; o Identifying population subgroups at greatest risk for adverse clinical outcomes from sleep apnea and SRBD, including those defined by age, gender and race; o Estimating the extent of medical care utilization, health care costs, and measures of quality of life associated with sleep apnea and SRBD. Although these five aims are identified, others may be appropriate. The design of the experimental protocol and identification of specific populations targeted for this program remain in the hands of the investigators. A number of possible components are listed for illustrative purposes. Study Population and Design This program is to be built upon established epidemiologic programs. It is anticipated that the sleep study would make use of data previously collected in existing cohort studies as well as any outcome information. For example, a number of studies supported by NHLBI, other components of NIH, National Center for Health Statistics and other agencies have already collected much of the baseline information on hypertension, obesity, and other cardiovascular risk factors needed to examine relationships with sleep apnea and SRBD. These studies together cover a wide age span, concentrated in single communities or distributed among multiple sites. Information on cardiovascular outcomes and development of risk factors such as obesity and hypertension is also being collected. Several epidemiology studies also include questionnaires on snoring and sleep-related breathing disorders, which could be used to identify persons at high risk of sleep apnea. Sleep Study Cohort A total population of approximately 6,000 participants (50 percent women and appropriate minority representation) is anticipated. The sleep study population may include a wide range of samples. For example, for ages 40 years and above: (a) subjects at increased risk for CVD because of other known risk factors (e.g., family history, hypertension, obesity, etc.); (b) subjects at risk for sleep apnea (but without severe apnea at entry); and/or (c) subjects with mild to moderate levels of apnea, but without known CVD. It is not essential that all Clinical Centers have access to the full age range of subjects since certain established cohorts may be particularly suited to provide a unique aspect (age, gender, race) of their population for this program. For data that are already collected or planned to be collected in the parent study, applicants should demonstrate availability, adequacy of the data set, standardization and reliability of data on the cohort to be included in the sleep study. Study Design It is envisioned that the sleep study will require approximately 900 to 1,000 well characterized participants recruited from established cohort studies or clinical trials in each of five to six clinical sites, which may themselves consist of more than one site. It is possible for one or more sites from a multicenter study to collaborate in recruiting a subset of their participants into the sleep study. It is expected that the sleep study design would include, as a minimum, baseline and repeated measures, as needed, of sleep-disordered breathing, sleep state, pulmonary and cardiac function, oxygen saturation, lipid and lipoprotein levels, endocrine function, blood pressure, obesity, and other cardiopulmonary risk factors. Given the cost of conducting laboratory polysomnography in the number of participants needed for this study and the difficulty with participants accepting additional measurements, applicants should probably utilize ambulatory measurements of sleep disordered breathing in non-laboratory settings. Polysomnography may be used to validate the ambulatory measurements in a subset of the population or in selected cases. Morbid outcomes may be defined with the use of several measures, such as evidence of left ventricular dysfunction, sustained hypertension, atherosclerosis, cognitive impairment, hospital admissions for treatment of ischemic heart disease, health care expenditures associated with CVD and cerebrovascular disease, measures of functional status, quality of life, and death. For any activities to be conducted through subcontracts, applicants should develop and describe such operational factors as access to subjects, organization of the facility, means of assuring quality control, data entry, plans for coordination, and a process for filing human subject assurances. Applicants should also provide all details of the experimental design, methods and procedures to be used in the proposed sleep studies. The proposed studies of successful applicants will be submitted to the Steering Committee for further consideration once the cooperative agreements have been awarded. It is anticipated that the final sleep protocol (including standardized data collection procedures) will be developed from among the highly meritorious studies proposed by the successful applicants. However, a decision to fund a particular Clinical Center will not commit the steering committee to conduct that Center's specific protocol. Timetable The timetable for the sleep study may be roughly subdivided into three phases over a five year period. There may be some overlap of functions within each of the phases, and the time estimates are only approximations. The purpose of the phases is to provide broad guidelines for the collaborative endeavor. Phase I: Planning and protocol months 0-12 development Phase II: Subject recruitment, protocol months 12-48 implementation, examinations, and follow-up. Phase III: Data analysis and report months 48-60 preparation The first twelve months of the study may be devoted to planning and protocol development, for example, to determine participant eligibility criteria; train staff in diagnostic procedures and sleep studies; help set up data acquisition and consent forms; define terms and outcome measures; develop a manual of operations, standardized protocol, questionnaires, forms, and procedures for quality control; and pretest data collection forms and procedures. The Data Coordinating Center will also play a key role in the planning and protocol development stage. Possible objectives in addition to assisting Clinical Centers in their planning and organization of the steering committee, are to help develop the study protocol and analytic plans; select a data acquisition, transfer, and management system; plan for any subcontracts for chemical analysis; establish a reading center for evaluating and interpreting sleep records collected or validated by ambulatory methods and polysomnography; develop procedures for quality control, training, standardization of procedures and certification; print the protocols and data forms; develop and produce a Manual of Operations, and take the lead for the orderly accumulation and transmission of data for the sleep study. In Phase II, the Clinical Centers will proceed with subject recruitment, protocol implementation, examinations and follow-up. The Data Coordinating Center will assist the Clinical Centers with respect to implementing the protocol, subject recruitment, data acquisition, and ongoing quality control. In Phase III, Clinical Centers and the Data Coordinating Center will conduct data analysis and prepare reports. SPECIAL REQUIREMENTS Characteristics of Existing Epidemiological Cohorts To promote and facilitate development of a collaborative program among the award recipients, and to permit assessment according to review criteria, a number of issues discussed below need to be addressed in each application for a Clinical Center. Applicants must have access to established, well characterized populations that include measures of CVD risk factors and outcomes. These may include studies supported by the National Institutes of Health or other federal, state, or private agencies. This program is primarily aimed at cohorts in ongoing epidemiological studies. However, those from recently completed studies may be proposed if they are in every way suitable for the study as specified in this RFA, including considerations of cost as discussed earlier under FUNDS AVAILABLE and subsequently under Budget and Related Issues, as well as under Review Criteria and Award Criteria. Applicants must describe plans for providing data from the parent study to the sleep study Data Coordinating Center and the concurrence of the parent study data source with these plans. Applicants should describe and document access to study participants and provide a brief, clear description of the characteristics, age distribution, other relevant baseline information of the potential population, and any unique features for use of their particular cohort in the sleep study. Applicants should also describe current procedures for collecting and classifying information on deaths, cardiovascular events, and other health outcomes. As described under study design, it is expected that the sleep study will require a number of cardiopulmonary and sleep measurements. Therefore, it is expected that the subjects of the established epidemiology cohort will have had measurements of certain minimum characteristics, such as blood lipids, glucose, insulin, cholesterol, hematocrit, blood pressure, ECG, body size and fatness, smoking status, medical/family history, as well as outcome measures such as left ventricular dysfunction, myocardial infarction, sustained hypertension, atherosclerosis, stroke, hospital admissions for treatment of ischemic heart disease, and cause specific mortality. The existing study should also have the means to re-contact and follow-up the identified cohort for CVD events. The parent study data that will be utilized in the sleep study should have been collected according to up-to-date and standard methods within five years of Phase II (on or about September 30, 1995) of the sleep study, as agreed to during protocol development. If such data are not available from the parent study or if certain minor baseline measurements are missing, investigators may propose methods for collecting these data as part of the sleep study. It is the responsibility of the principal investigators to provide documentation from appropriate parent study Steering Committees, Data and Safety Monitoring Boards and sponsoring agencies for use of their population for this program. Additional Material to Include in the Application It is envisioned that the Principal Investigator (PI) will be an established investigator in cardiovascular, pulmonary or sleep disorders research. Either the PI or a co- investigator should have demonstrated experience in sleep disorders research. For example, it would be desirable for the PI and Co-PI to have combined expertise in CVD risk factors, epidemiology and sleep disorders medicine. It is not essential that this investigative team be from the same institution. However, if applications involve investigators from different institutions there must be well documented plans for adequate communication, interactions and facilities to conduct the sleep aspects of the protocol. Clinical Center applicants must be able to interact effectively with the Data Coordinating Center to transmit and edit data and should discuss their capability to participate in a distributed data entry system if this approach is selected. Clinical Center applicants should also state their willingness, and that of the institutions involved, to participate in a cooperative and interactive manner with other Clinical Centers, the NHLBI and the Data Coordinating Center within the context of this collaborative research program. 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. Data Coordinating Center applicants should discuss various aspects of study design that would be important in developing the sleep study protocol, their familiarity with sleep disorders and cardiopulmonary risk factors and diseases, eligibility criteria, important considerations for making sample size and power calculations, baseline and outcome measures, methods and frequency of data collection and entry, monitoring accuracy of data collection, methods of data acquisition and transfer, quality control procedures including training and certification, chemical analysis of blood samples, centralized reading of sleep records, and plans for statistical analysis of results. Budget and Related Issues Applicants are expected to be able to complete the sleep study with the funding available through this RFA in conjunction with any already committed funding. A decision to award a sleep study application does not constitute a continued commitment to the parent study beyond its current project and budget period. Applications for the Clinical Centers and the Data Coordinating Center should present five budget periods of 12 months each. Applicants should provide adequate budget justification for each phase of the study and all applicable direct and indirect costs should be included. Estimates of staffing needs, including the Principal Investigator, Co-Investigator, other professional and support staff must be included. The suggested level of commitment for the Principal Investigator and Co-Investigator should be not less than 20 percent each. Other personnel such as clinic coordinator, sleep technician, research assistants and secretary should be carefully outlined and justified in the application. Travel costs for approximately three to four trips to Bethesda for two people should be included in the first year budget with reductions to two trips for two people in subsequent years. Any major equipment items should be well justified. If collaborations or subcontracts are involved which require transfer of funds from the grantee to other institutions, it is necessary to establish formal subcontract agreements with each collaborating institution. Budgets for subcontracts should be prepared using the same guidelines as for the main grant. Budgets can be escalated four percent for the remaining future years. Future year awards may be redistributed based on the final protocol, enrollment of subjects into the sleep protocol during a specified time frame and overall performance. The individual clinics are expected to project subject enrollment into the sleep protocol. Applicants for the Data Coordinating Center should prepare budgets that allow for roughly the standard coordinating center activities and responsibilities related in timing and scope to the above mentioned phases. Terms and Conditions of Award These special Terms of Award are in addition to and not in lieu of otherwise applicable OMB administrative guidelines, HHS Grant Administration Regulations at 45 CFR part 74, and other HHS, PHS, and NIH Grant Administration policy statements. [Part 92 applies when state and local governments are eligible to apply as a "domestic organization."] The administrative and funding instrument used for this program is a cooperative agreement (U01), an assistance mechanism (rather than an acquisition mechanism) in which substantial NIH scientific and/or programmatic involvement with the awardee is anticipated during performance of the activity. Under the cooperative agreement, the NIH purpose is to support and/or stimulate the recipient's activity by involvement in and otherwise working jointly with the award recipient in a partner role, but it is not to assume direction, prime responsibility or a dominant role in the activity. Consistent with this concept, the dominant role and prime responsibility for the activity resides with the awardee(s) for the project as a whole, although specific tasks and activities in carrying out the studies will be shared among the awardees and the NHLBI Project Scientist. Awardees will have the usual responsibilities of award recipients, including protocol development, participant recruitment and follow-up, data collection, quality control, interim data and safety monitoring, final data analysis and interpretation, and preparation of publications, as well as responsibilities for collaboration with other awardees, and collaboration with the NHLBI Project Scientist. The NHLBI Project Scientist (Branch Chief, Airways Diseases Branch, Division of Lung Diseases), in addition to the usual stewardship responsibilities, will have responsibilities in protocol development, quality control, interim data and safety monitoring, final data analysis and interpretation, preparation of publications, collaboration with awardees, and project coordination. Awardees will have lead responsibilities for the project as a whole and it is anticipated that the awardees will have lead responsibilities in all joint tasks and activities, except it is anticipated that the NHLBI Project Scientist will have lead responsibilities in quality control and catalyzing interim monitoring of data and safety and may, consistent with publication policy to be adopted by the Steering Committee, have lead responsibilities in the preparation of some publications. A Steering Committee, composed of the principal investigator(s) of each Clinical Center, the principal investigator(s) of the Coordinating Center, and the NHLBI Project Scientist will be the main governing body of the study and will have primary responsibility for developing common protocols, facilitating the conduct and monitoring of studies, and reporting study results. Each Field Site, the Coordinating Center and the NHLBI Project Scientist will have one vote. The Chairperson, who will be someone other than an NHLBI staff member, will be selected by the Steering Committee. Subcommittees will be established by the Steering Committee, as it deems appropriate; an NHLBI scientist (or where necessary, scientists) will serve on subcommittees as deemed appropriate by the NHLBI Project Scientist. The collaborative protocol will be developed by the Steering Committee. This protocol may be reviewed by an external committee convened by NHLBI. The protocol will be implemented only with the concurrence of the awardees and NHLBI. Data will be submitted centrally to the Coordinating Center. The protocol will define rules regarding access to data and publications. An independent Data and Safety Monitoring Board, to be appointed by NHLBI, will review progress at least annually and report to NHLBI. Awardees will retain custody of and have primary rights to their data developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies. The NHLBI reserves the right to terminate or curtail the study (or an individual award) in the event of (a) failure to develop or implement a mutually agreeable collaborative protocol, (b) substantial shortfall in participant recruitment, follow-up, data reporting, quality control, or other major breach of the protocol, (c) substantive changes in the agreed-upon protocol with which NHLBI cannot concur, (d) reaching a major study endpoint substantially before schedule with persuasive statistical significance, or (e) human subject ethical issues that may dictate a premature termination. Any disagreement that may arise in scientific/programmatic matters (within the scope of the award), between award recipients and the NHLBI may be brought to arbitration. An arbitration panel will be composed of three members--one selected by the Steering Committee (with the NHLBI member not voting) or by the individual awardee in the event of an individual disagreement, a second member selected by NHLBI, 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 the PHS regulations at 42 CFR part 50, Subpart D and HHS regulation at 45 CFR part 16. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements are required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of disease, disorder, or condition under study; special emphasis must be placed on the need for inclusion of minorities and women in studies of diseases, disorders, and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale must be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues must be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information must be included in the form PHS 398 (rev. 9/91) in Sections 1-4 of the Research Plan, and summarized in Section 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., Native Americans [including American Indians or Alaskan Natives], Asian/Pacific Islanders, Blacks, Hispanics). The rationale for studies on single minority population groups should be provided. For the purpose of this policy, clinical research includes human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including but not limited to clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are not subject to these policies. However, every effort should be made to include human tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. If the required information is not contained within the application, the application will be returned. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women in a study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and will be reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. LETTER OF INTENT Prospective applicants are asked to submit, by April 1, 1994, a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, the identities of other key personnel and participating institutions, and the number and title of the RFA in response to which the application may be submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information that it contains is helpful in planning for the review of applications. It allows NHLBI 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: C. James Scheirer, Ph.D. Division of Extramural Affairs National Heart, Lung, and Blood Institute Westwood Building, Room 648 Bethesda, MD 20892 Telephone: (301) 594-7452 FAX: (301) 594-7407 APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 9/91) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research; from the Office of Grants Information, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone (301) 594-7248; and from the NIH Project Scientist(s) listed under INQUIRIES. The RFA label available in the PHS 398 application form must be affixed to the bottom of the face page of the application. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed in line 2a of the face page of the application form and the YES box must be marked. Send or deliver the original, signed application and three legible complete photocopies to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** Send two additional copies of the application to: C. James Scheirer, Ph.D. Division of Extramural Affairs National Heart, Lung, and Blood Institute Westwood Building, Room 648 Bethesda, MD 20892 Telephone: (301) 594-7452 It is important to send these two copies at the same time as the original and three copies are sent to the division of research grants. Otherwise, the NHLBI cannot guarantee that the application will be reviewed in competition for this RFA. Applications must be received by May 23, 1994. If an application is received after this date it will be returned to the applicant without review. The Division of Research Grants (DRG) will not accept any application in response to this RFA that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. The DRG will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of substantial revisions of applications reviewed, but such applications must include an introduction addressing the previous critique. REVIEW CONSIDERATIONS General Considerations All applicants will be judged on the basis of the scientific merit of their proposed research project and their documented ability to conduct the essential study components as broadly outlined in the RESEARCH OBJECTIVES of this RFA. Review Method Upon receipt, applications will be reviewed by the DRG for completeness and by NHLBI staff for responsiveness to this RFA. Incomplete applications will be returned to the applicant without further consideration. If the application is judged unresponsive, the applicant will be contacted and given an opportunity to withdraw the application. If the application submitted in response to this RFA is substantially similar to a grant application already submitted to the NIH for review, but has not yet been reviewed, the applicant will be asked to withdraw either the pending application or the new one. Simultaneous submission of identical applications will not be allowed, nor will essentially identical applications be reviewed by different review committees. Therefore, an application cannot be submitted in response to this RFA that is essentially identical to one that has already been reviewed. This does not preclude the submission of substantial revisions of applications already reviewed, but such applications must include an introduction addressing the previous critique. Applications judged to be responsive by NHLBI staff will be reviewed for scientific and technical merit by an initial peer review group, which will be convened by the Division of Extramural Affairs, NHLBI, solely to review these applications. The initial review will include a preliminary evaluation to determine scientific merit relative to the other applications received in response to this RFA (triage); the NIH will remove from further consideration applications judged to be noncompetitive and promptly notify the Principal Investigator and the official signing for the applicant organization. Those applications judged to be competitive will be further evaluated for scientific/technical merit by the usual peer review procedures, including, if deemed appropriate, an applicant interview in or near Bethesda at the applicant's expense. Subsequently, they will be reviewed by the National Heart, Lung, and Blood Advisory Council. Review Criteria Applicants are encouraged to submit and describe their own ideas on how best to meet the goals of the RFA and their specific protocol, but they are expected to address issues identified under SPECIAL REQUIREMENTS of this Request for Applications. Applications will be judged primarily on the scientific quality of the application, the appropriateness, facilities and access to subjects from existing, established epidemiology studies, adequacy of existing data, multidisciplinary nature of the study and group, approach to cost containment, the discussion of considerations relevant to this RFA, expertise of the investigators, their capability to perform the work proposed, and a demonstrated willingness to work as part of the collaborative group and with the NHLBI Project Scientist. The review group will assess the scientific merit of the applications and related factors, including: Clinical Centers o Ability to utilize existing, established epidemiological cohorts to address the goals of this program; adequacy of the population, data set, and access to recruit the required numbers of subjects, including appropriate representation of minorities and women. o Importance and scientific merit of the proposed sleep study protocol, including adequacy of the methodology to carry out the proposed research plan. o Availability of adequate facilities and other resources including a plan for the administrative structure within the Clinical Center. o Rationale and cost-effectiveness of the research approach proposed and appropriateness of the budget. o Adequacy of data collection, preliminary analysis, reporting procedures, monitoring of study recruitment and subject follow-up, ability to process the volume of data expected within their Center and manage the individual study databases. Plans to ensure quality control of data. o Expertise, training, and experience of the investigators and staff, including the scientific and administrative abilities of the PI and co-investigators; their potential to accomplish the proposed research goals; the time they plan to devote to the program for the effective conduct of the study; their previous experience conducting clinical or population based research; their ability, experience and willingness to participate collaboratively with other Clinical Centers, the Data Coordinating Center, and the NHLBI in the manner summarized in the RFA. o Facilities, equipment, and organizational structure to effectively implement the proposed research. Data Coordinating Center o Understanding of the scientific, statistical, logistical, and technical issues underlying multicenter studies, including taking a leadership role in the area of study design, statistics, logistics, data acquisition and management, quality control, data analysis, and overall coordination. o Adequacy of the proposed plans for acquisition, transfer, management, and analysis of data; sleep reading center; quality control of data collection and monitoring, and overall coordination of Center activities. o The expertise, training, and experience of the investigators and staff, including the administrative abilities of the Principal Investigator and co-investigators, and the time they plan to devote to the program for effective coordination. o The administrative, supervisory, and collaborative arrangements for achieving the goals of the program, including willingness to cooperate with the participating Clinical Centers and the NHLBI. o Facilities, equipment, subcontracts, and organizational structure to effectively assist Clinical Centers in implementing the protocol and in data collection procedures and in overall coordination of study-wide activities. o Appropriateness of the budget for the work proposed. AWARD CRITERIA Applications recommended by the National Heart, Lung, and Blood Advisory Council will be considered for award based on (a) scientific and technical merit; (b) program balance, including in this instance, sufficient compatibility of features to make a successful collaborative program a reasonable likelihood; and (c) availability of funds. Letter of Intent Receipt Date: April 1, 1994 Application Receipt Date: May 23, 1994 Review by NHLBI Advisory Council: September 1-2, 1994 Anticipated Award Date: September 30, 1994 INQUIRIES Written and telephone inquiries are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Inquiries regarding programmatic issues may be directed to: James P. Kiley, Ph.D. Division of Lung Diseases National Heart, Lung, and Blood Institute Westwood Building, Room 6A15 Bethesda, MD 20892 Telephone: (301) 594-7443 FAX: (301) 594-7487 Inquiries regarding review and application procedures may be directed to: C. James Scheirer, Ph.D. Division of Extramural Affairs National Heart, Lung, and Blood Institute Westwood Building, Room 648 Bethesda, MD 20892 Telephone: (301) 594-7452 FAX: (301) 594-7407 Inquiries regarding fiscal and administrative matters may be directed to: Mr. Raymond Zimmerman Division of Extramural Affairs National Heart, Lung, and Blood Institute Westwood Building, Room 4A11C Bethesda, MD 20892 Telephone: (301) 594-7420 FAX: (301) 594-7492 AUTHORITY AND REGULATIONS This project is described in the Catalog of Federal Domestic Assistance No. 93.837. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR 74. This project is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. From owner-sci-resources@net.bio.net Wed Feb 16 22:00:00 1994 Path: biosci!biosci!not-for-mail From: Dave Kristofferson Newsgroups: bionet.sci-resources Subject: NIH GUIDE - RFA HS-94-006 - V23(07) 02/18/94 Date: 16 Feb 1994 16:23:44 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 804 Approved: biosci-moderator@net.bio.net Distribution: bionet Message-ID: <2judeg$65p@net.bio.net> NNTP-Posting-Host: net.bio.net $$XID RFA HS94006 HS-94-006 P1O1 *************************************** AHCPR RURAL CENTERS NIH GUIDE, Volume 23, Number 7, February 18, 1994 RFA: HS-94-006 P.T. Agency for Health Care Policy and Research Letter of Intent Receipt Date: April 15, 1994 Application Receipt Date: May 17, 1994 PURPOSE The Agency for Health Care Policy and Research (AHCPR) announces the availability of cooperative agreements to develop and manage AHCPR Rural Centers (Centers) to plan and carry out demonstrations of rural managed care systems in HHS Regions which do not currently have an AHCPR Rural Center: Regions I, III, VI, VII, and IX. This solicitation is part of AHCPR's Rural Health Initiative. (AHCPR now supports by contracts Rural Centers in Regions II, IV, V, VIII, and X). The Centers are encouraged to form consortia that include appropriate State health agencies and academic health science centers. Center staff should include appropriate multidisciplinary scientific and administrative experts. This Request for Applications (RFA) responds to a Fiscal Year (FY) 1994 directive from the Senate Appropriations Committee for AHCPR to make grants or cooperative agreements to rural States or health science centers to assist in the development and demonstration of managed care networks. The Committee is particularly concerned that changes in health care systems nationally that incorporate innovations in the organization, financing, and delivery of health care services will not be as accessible to rural populations as those in urban areas where market forces already effect changes. The Centers, with substantial input from staff and consultants at AHCPR, will conduct demonstrations of innovations in the delivery of health care services in rural areas of the Center's respective State or region. Priority will be given to demonstrations of organized networks of health services delivered to underserved populations such as populations living in a designated health professional shortage area, those living in isolated areas and/or impoverished areas, and uninsured and/or unemployed rural people. AHCPR will arrange for the conduct of independent evaluations of these demonstrations. 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), AHCPR Rural Centers, addresses several of those objectives. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0 or Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by: (1) domestic, non-profit organizations, public or private, including universities, clinics, units of State and local governments, non-profit firms, and non-profit foundations; or (2) consortia of organizations, if the application is submitted by a domestic, non-profit, public or private organization. For AHCPR Rural Centers demonstration projects, only non-profit organizations in HHS Regions I, III, VI, VII, and IX are eligible to apply. See discussion under "Objectives and Scope." Applications from minority and women investigators are encouraged. MECHANISM OF SUPPORT The administrative and funding instrument to be used for this program will be the cooperative agreement (U54), an assistance mechanism (rather than an acquisition mechanism), in which substantial AHCPR scientific and programmatic involvement with the awardee(s) is anticipated during the performance of the activity. These awards permit core funding in which the recipient organization may be reimbursed for administrative and staff support for: the planning, initiation, and monitoring of the demonstration(s); technical assistance in the implementation of statewide managed care plans; and dissemination mechanisms such as Center-sponsored newsletters. Any other support for these activities is available to grant-eligible institutions from AHCPR and other PHS agencies through their continuing programs of extramural investigator initiated research and not through this RFA. Demonstrations may be supported in their initial stages with core funds, although it is expected that most of the demonstrations will be sponsored with funds obtained from sources other than the core award. As noted below, review criteria include reference to the proposed Center's plans to attract and retain other funding sources in support of its demonstration(s). Details of the responsibilities, relationships, and governance of the projects to be funded under this cooperative agreement are listed under SPECIAL REQUIREMENTS. The total project period for applications submitted in response to this RFA may not exceed five years. The anticipated award date is September 1, 1994. Award of continuation funding beyond the initial budget period will depend upon availability of funds, satisfactory progress, and annual progress reviews according to customary AHCPR administrative procedures. This RFA is a one-time solicitation. FUNDS AVAILABLE The AHCPR expects to award a total of $10 million over five years under this RFA for up to five applicants. Up to $2 million will be available in FY 1994 and an average of $2 million for each of the next four fiscal years. RESEARCH OBJECTIVES Overview The Senate Committee Report on FY 1994 Appropriations (Report 103-143) directed AHCPR to "give grants or cooperative agreements to rural States or health sciences centers for planning (including an evaluation plan) and initiating a statewide or regional managed care system incorporating features of primary care, clinical preventive care services, and essential information networks to facilitate information transfer, including information on health care costs, quality measurement, and overall health care system performance." The Committee states that "because access to care is a major problem in rural States, the managed care network will be in a State" that has: 1. Limited public transportation infrastructure, 2. Geographic features that limit transportation, 3. Significant health status problems in the population, 4. Limited managed care penetration statewide, 5. Unemployment rates above the national average, 6. High percentage of the rural area designated as health professional shortage areas. The AHCPR supports and conducts health services research, including evaluations of health systems. This request for applications is for the planning and implementing of demonstration projects aimed at improving access to quality health care for rural residents, using managed care principles. These demonstration projects should be in States that reflect the six criteria specified in the Senate Committee report, as listed above. Through these activities the Centers, in collaboration with AHCPR and its consultants, will provide technical expertise to improve the effectiveness of health care services delivered to rural populations. Rural populations have been found to be in poorer health than most groups in urban and suburban communities. Some rural States with isolated populations have not provided for the inclusion of these citizens in managed care networks in spite of the anticipated role of such networks in health care reform. In many rural States provider networks, rural networks, and State managed care networks have not been formed, or, if formed, they may not be a part of a linked network of State and regional services. (A rural health network is a locally directed or governed organization that provides a set of defined health related and administrative services needed in the community served by the network.) These demonstrations are to be performed in the context of health care reform and on a statewide or regional basis. Because the involvement of many organizations, agencies, and individuals is essential to develop viable managed care systems, the participation of consortia is strongly encouraged. Consortia should include the appropriate public health authorities, health care providers, and analytic and technical expertise. The establishment of Centers will strengthen the effectiveness of consortia and facilitate collaborative arrangements among State health agencies, academic health science centers, and other groups necessary to design, implement, and monitor system changes in the delivery of health services in rural areas. Objectives and Scope The objective of this RFA for AHCPR Rural Centers is to provide support for planning, implementing, and monitoring health care system demonstrations. This solicitation is part of the Rural Health Initiative of AHCPR. Awards will be made for up to five Rural Centers (no more than one in each of the following HHS Regions: I (CT, MA, ME, NH, RI, and VT); III (DE, MD, PA, VA, and WV); VI (AR, LA, NM, OK, and TX); VII (IA, KS, MO, and NE); and IX (AZ, CA, HI, and NV). The Rural Centers will engage in the development and technical assistance required to implement the demonstrations, supported by substantial input from staff and consultants at AHCPR. As stated above, priority will be given to the demonstration of organized networks of health services delivered to underserved rural populations. AHCPR will arrange for the conduct of independent evaluations of these demonstrations. As an earlier step in its Rural Health Initiative, AHCPR contracted for five AHCPR Rural Centers in FY 1993, one each in Regions II (State University of New York at Buffalo), IV (University of North Carolina at Chapel Hill), V (University of Minnesota), VIII (Center for Health Policy Research, Denver), and X (University of Washington, Seattle). This solicitation is aimed at addressing needs in the remaining five Regions through cooperative agreements with rural States themselves, their academic health sciences centers, or other appropriate organizations. An application may be submitted jointly by State authorities with responsibility for rural health care and academic health centers engaged in rural health research activities. The awards will enable the designated AHCPR Rural Centers in those HHS Regions that do not presently have an AHCPR Rural Center to plan and initiate statewide or regional managed care system demonstration projects. As stated in the Senate Committee Report, the managed care systems shall incorporate features of primary care, clinical preventive services, and essential information networks. Most definitions of managed care characterize it as a system that integrates the financing and delivery of appropriate medical care by means of contracts with selected physicians and hospitals that: furnish a comprehensive set of health care services to enrolled members, usually for a predetermined monthly premium; utilize quality controls that providers agree to accept; incorporate financial incentives for patients to use the providers and facilities associated with the plan; and include an assumption of some financial risk by providers. These awards may be used to establish new centers and/or expand existing centers that address policy and health services research issues of special importance to rural populations (e.g., the effect on the rural population of the health care reform initiatives of the State). The Rural Centers demonstration projects should address, as appropriate, some of the following issues: o Arranging for primary care in rural areas, including such aspects as financing, recruitment, retention, and effective use of primary care providers and mid-level health care practitioners and the intended effect of these primary care arrangements on access to care. o Monitoring the appropriateness and effectiveness of rural health care services and procedures, including patient outcomes, and the effect of rural practice networks on quality of care. o Expanding existing networks or developing new managed care system models that provide access to high quality of care to the diverse rural populations within a State or region. o Linking appropriate rural health care delivery services and academic health science centers into consortia. o Linking providers in underserved areas with each other, and with responsible health care institutions and academic health centers, through information systems and telecommunications. o Developing internal and external information networks to facilitate information transfer, including information on health care costs, quality measurement, and overall health care system performance. o Developing community practice networks and community health plans that integrate health professionals and health care organizations supported through public funding with other providers. o Addressing the issues raised by border-crossing for rural managed care networks and antitrust concerns for newly forming health care networks and accountable health plans. Within the limits of these resources, the proposed Centers will plan, implement, and monitor the required demonstration projects and broadly disseminate project information and results. In addition to data collection and monitoring activities, including the associated assessment of processes and progress necessary for sound management of the projects, Centers must accommodate requirements of independent evaluations that may be arranged for by AHCPR. Centers will be expected to coordinate internal data collection and monitoring efforts with the independent evaluation to ensure the collection of data essential for both efforts. Work carried out by each Center will be multidisciplinary and must address important health services delivery issues (e.g., managed care systems; provider health networks; and State health care insurance reforms with special attention to their effects on access, cost, and quality for rural populations). It is expected that successful applicant organizations will include on their team appropriate multidisciplinary administrative and scientific personnel (e.g., experts in health services research and administration, medicine, dentistry, nursing, epidemiology, psychology, statistics, geography, economics, organizational behavior, law, and public health); and pertinent State official(s) responsible for health care reform and managed care in the State through cooperative relationships. Further priority consideration will be given to those applicants with a documented plan to coordinate with the overall State-level health system planning efforts. Successful applicant organizations must incorporate the scientific, technical, organizational, and physical resources necessary to carry out: (1) health services demonstrations; (2) technical assistance to health care providers and others; and (3) dissemination of project information and results. Many funding agencies in addition to AHCPR are providing resources for improving parts of the system for delivery of health care services to rural populations. These organizations include other parts of the Department of Health and Human Services (DHHS), including the Office of Rural Health Policy of the Health Resources and Services Administration (HRSA), the Health Care Financing Administration (HCFA), and the National Institutes of Health (NIH). They also include private philanthropic organizations such as the Robert Wood Johnson (RWJ) and Kellogg Foundations. This RFA encourages synergy of existing and developing resources in preparation for health care reform at the State or regional level. Appropriate and judicious use of these or other funding sources to complement each other where there are common goals is specifically endorsed and should be noted in the application under "Other Support," or sections 2 or 5 of the "Research Plan," as appropriate. Center Structure The Center Director must be a manager who can provide strong administrative leadership and be committed to this activity for at least 50 percent of his\her time. The Director will be responsible for the organization and operation of the Center and liaison with the research community and key State officials involved in the State's health care reform. The Center should be structured to facilitate appropriate cooperative arrangements among all members of the consortium such as State health departments; State or regional academic health centers; and outside entities including professional societies, subcontractors, rural provider networks and rural health alliances, and consumer groups. Personnel and institutional resources capable of developing and maintaining a substantial commitment to rural health services demonstrations must be available, and that availability should be documented by letters of commitment in the application under "Appendix." The Center may consist of core staff with significant time commitments to the demonstration and affiliate staff with lesser time commitments. Multidisciplinary collaboration within the Center is essential. In addition, the applicant must show a strong commitment to the Center and its development, including plans to support the organizational and management structure of the Center. Each Center is generally expected to share common resources with other components or departments of the applicant organization including: technical, clerical, and administrative personnel; instrumentation; computer resources; subject populations; and data bases. The Center may be a consortium of organizations operating within the State or Region. It is expected that members of a consortium will provide collateral or supplemental support to the applicant organization. It is expected that each funded Center will have an advisory committee that includes representation of those involved in preparing or implementing health care reforms for rural areas in the proposed demonstration State or region. Core funds may be used to support costs associated with an advisory committee, including the convening of periodic committee meetings to advise about management and programs. This advisory committee would typically be composed of: representatives from the Center's collaborating institutions; appropriate State officials; and senior national and regional representatives from outside of the consortium including health care policymakers, health services researchers, health care providers, and consumers. Budget and Related Issues A maximum of $400,000 first year total costs (direct plus indirect) may be requested for center support, and a maximum of $2,000,000 in total costs may be requested per application for the entire project period, which is not to exceed five years. In preparing budget requests, applicants are reminded that the reasonableness of proposed budgets is among the criteria to be used in the peer review of applications. Applicants should justify whether the scope of their applications calls for the full five years allowable duration and the maximum $2,000,000 (i.e., five years times $400,000) amount. If successful completion of the goals is anticipated within a shorter duration of time and/or at less cost, the application should reflect this. SPECIAL REQUIREMENTS The issuance of awards will be contingent on the availability of funds and on the quality of the applications. No awards will be made if, as result of the scientific and technical review, applications are not judged to be of high merit. The initial review committee may recommend support for less than the requested period or amount. Terms and Conditions of Award The administrative and funding instrument to be used for this program will be the cooperative agreement (U54), an assistance mechanism (rather than an acquisition mechanism), in which substantial AHCPR scientific and programmatic involvement with the awardee(s) is anticipated during the performance of the activity. Under the terms of these cooperative agreements, the awardee determines the organization and management of the Center as specified by this announcement and retains responsibility for all aspects of performance of the Center. The AHCPR, however, anticipates substantial programmatic involvement in the planning, implementation, and monitoring of demonstrations and in the provision of advice and technical assistance to the awardee. 1. Awardee Responsibilities The awardee(s) will have primary and lead responsibility for all activities and should describe in the application the plans to: o Establish and maintain appropriate collaborative arrangements with State agencies, academic health science centers, health care providers, and others appropriate to effect health care system changes; o Make available appropriate types of administrative, scientific, and analytical expertise to design proposed system changes for the demonstration(s); o Manage the process of implementing demonstration(s); o Participate in an independent evaluation arranged for by AHCPR in executing a rigorous evaluation plan; o Develop an information system that can generate the required data for measuring changes in health care delivery and health status; o Provide technical assistance in the planning and implementing of demonstrations, as appropriate, to collaborative groups and participants; o Disseminate project information and results based on system changes, especially in collaboration with AHCPR; and o Collaborate with AHCPR on data analysis, the preparation of background information, or other analytical activities relating to the appropriateness and effectiveness of health care for rural populations. The AHCPR is committed to disseminating the products of the Rural Centers as rapidly as possible. In this context, products include both written reports of project information and results, and the data themselves. The AHCPR will have access to the products of the Rural Centers upon request. All rights of access to the data will be consistent with AHCPR regulations 42 CFR 67, Subpart A, as well as with section 903(c) of the PHS Act. 2. AHCPR Staff Responsibilities The AHCPR Project Officer and other AHCPR staff will have substantial scientific and programmatic involvement during the conduct of this activity, through technical assistance, advice, and coordination beyond the normal program stewardship for grants. Collaboration on study design, protocol development, and design of an independent evaluation will occur after the award(s) is (are) made. Specifically, AHCPR's role during the project period will include providing technical assistance, advice, and support to the Principal Investigator in the areas of: o Facilitating program development and priority setting; o Planning and implementing of the demonstration(s); o Monitoring the Center's demonstrations; and o Disseminating the Center's project information and results through AHCPR's publication program and assisting in selecting additional mechanisms for effective dissemination. AHCPR may conduct or arrange for the conduct of a rigorous evaluation of each demonstration project, which could include specific before and after measurements for evaluating the effect(s) of system changes on the delivery and outcomes of rural health care. Each year's continuation award is subject to a progress review by AHCPR, in addition to the availability of funds. The progress review may involve a site visit to the Center by AHCPR staff and expert consultants to AHCPR. The progress review will address the Center's productivity, general compliance with the basic review criteria listed below, and adherence to the provisions of its approved application. If such a continuation review indicates that insufficient progress has been made, AHCPR may decide not to continue to fund the Center for the full project period. The substantial AHCPR involvement will apply in addition to and not in lieu of otherwise applicable PHS policies and Federal regulations. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS CONCERNING INCLUSION OF WOMEN AND MINORITIES IN RESEARCH STUDY POPULATIONS The AHCPR requires all applicants for research grants to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder, or condition under study. Special emphasis must be placed on including minorities and women in studies of diseases, disorders, and conditions which disproportionately affect them. This policy applies to males and females of all ages. If women or minorities are excluded or inadequately represented in research, a clear and compelling rationale should be provided. The AHCPR will not make awards for applications which do not comply. If the application does not contain the required information, it will be returned without review. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues should be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information should be included in the form PHS 398 in the Research Plan and summarized in the Section on Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, AHCPR recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., American Indians/Alaskan Natives, Asian/Pacific Islanders, African Americans, Hispanics). Where appropriate, the applicant must provide the rationale for studies on single minority population groups. Peer reviewers will address specifically whether the applicant's research plan conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific questions(s) addressed and the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and will be reflected in assigning the priority score to the application. LETTER OF INTENT Prospective applicants are asked to submit, by April 15, 1994, a letter of intent that includes the name, address, and telephone number of the Principal Investigator; states the number and title of the RFA in response to which the application may be submitted; and identifies all co-investigators and other key personnel and member institutions, community-based organizations, and any other participating organizations or institutions. Although a letter of intent is not required, is not binding, and does not enter into the consideration of any subsequent applications, the information allows AHCPR staff to estimate the potential review workload and avoid conflict of interest in the review. The Letter of Intent is to be sent to Dr. Norman W. Weissman at the address listed under INQUIRIES. APPLICATION PROCEDURES Applications are to be submitted on the grant application form PHS 398 (rev. 9/91). State and local government applicants may use form PHS 5161, Application for Federal Assistance. These forms are available at most institutional offices of sponsored research; the Office of Grants Information, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone (301) 594-7248; and from the Scientific Review Branch, Agency for Health Care Policy and Research, Suite 602, 2101 East Jefferson Street, Rockville, MD 20852, telephone (301) 594-1449. The RFA label available in the PHS 398 application form must be affixed to the bottom of the face page of the original copy of the application. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, type "RFA HS-94-006" and "AHCPR RURAL CENTERS" in Section 2a on the face page of the application form and the YES box must be marked. Complete information about the proposed Center must be submitted with the application. Consortium arrangements typically take the form of a formal agreement between the grantee and other organization(s). In the grant application, a separate budget must be included for each organization involved in the proposed consortium arrangement. The application must describe how the proposed Center will meet the awardee responsibilities described earlier under Terms and Conditions of Award. Follow the instructions for form PHS 398 where appropriate. However, the form PHS 398 was developed primarily for research project grants rather than Centers. Therefore, substitute the following headings for Sections 1 through 9 of Section C of the application and address the following issues (see Research Plan, pages 20- 24, of the instructions). (State and local governments using form PHS 5161 should address all of these following areas in the Program Narrative section of their application). For Sections 1 - 8 below, suggested page lengths are listed in parentheses. However, the cumulative length of these sections cannot exceed 25 pages. 1. Introduction and background; any special emphases of the proposed Center. (1 - 2 pages) 2. Currently available organizational resources. What resources such as staff and areas of expertise, ongoing rural research, organizational support and relationships, funds, and equipment, are available now to develop and implement the proposed Center? (2 - 3 pages) 3. Organizational changes that will be implemented to develop the proposed AHCPR Rural Center. What activities and organizational alignments will be undertaken to institute the proposed Center? (2 - 4 pages) 4. The nature of proposed and existing organizational relationships of the Center. Include, for example, the proposed Center's relationship with health care providers, State and local governments and other policy makers, the proposed advisory committee, and the research community. (2 - 4 pages) 5. The proposed Center's agenda in rural demonstrations, technical assistance, information system development, dissemination, and research projects. What activities and projects are currently in place with regard to rural health and/or health care reform? What problems in care delivery will be addressed by the demonstration project(s)? (8 - 12 pages) 6. The process of decisionmaking and lines of authority within the proposed Center. (1 - 2 pages) 7. The expected accomplishments of the proposed Center. (2 - 6 pages) 8. Human subjects. (the same as in '5' in the application instructions, page 22) 9. Consultants/collaborators. (the same as in '7' in the application instructions, page 23) 10. Consortium/contractual arrangements. (the same as in '8' in the application instructions, page 23) 11. Literature cited. (the same as in '9' in the application instructions, page 24) The completed original application, including the Checklist, and four legible copies (two copies when using the PHS 5161) must be sent or delivered to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** Applications submitted under this RFA must be received by the Division of Research Grants, NIH, by May 17, 1994. If an application is received after that date, it will be returned to the applicant. One copy, labeled "Advance Copy," must be submitted simultaneously to: Norman W. Weissman, Ph.D. Center for General Health Services Extramural Research Agency for Health Care Policy and Research 2101 East Jefferson Street, Room 502 Rockville, MD 20852-4908 Conference for Prospective Applicants The AHCPR plans to convene a conference for prospective applicants in Kansas City, Missouri on March 29, 1994, if there is sufficient interest from prospective applicants. At this proposed conference, AHCPR plans to discuss the programmatic and administrative details of the AHCPR Rural Centers and respond to questions concerning this RFA. Attendance is not a prerequisite to applying. Attendees must pay for their own travel and accommodation costs. Individuals with questions concerning this announcement, or unable to attend the conference, may contact Ms. Jean Carmody at telephone (301) 594-1357, extension 130, FAX (301) 594-2155. Those interested in attending the conference should mail or FAX their names, addresses, and telephone numbers to: Ms. Jean Carmody Center for General Health Services Extramural Research Agency for Health Care Policy and Research 2101 East Jefferson Street, Suite 502 Rockville, MD 20852-4908 REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed by the Referral Office, Division of Research Grants, NIH, for completeness, and by AHCPR staff for responsiveness to the RFA. Incomplete and/or non- responsive applications will be returned to the applicant without further consideration. The determination of any application as nonresponsive will be the sole responsibility of the AHCPR. All responsive applications will undergo peer review for scientific merit by a review committee of experts convened by AHCPR. When an application is reviewed, the peer review committee may recommend further consideration for funding or no further consideration. The committee also assigns priority scores to the applications for which further consideration was recommended. Recommendations of the peer review committee will be reviewed subsequently by AHCPR's National Advisory Council for Health Care Policy, Research, and Evaluation. The peer review process is rigorous, and only those applications judged to be of greatest merit will be recommended for further consideration. The general review criteria for AHCPR grant applications are: significance and originality from a scientific and technical viewpoint; adequacy of the proposed method(s); availability of data or proposed plan to collect data required for the project; adequacy of the plan for organizing and carrying out the project; qualifications and experience of the principal investigator and proposed staff; reasonableness of the proposed budget; and adequacy of the facilities and resources available to the applicant. Special Review Criteria In addition to the review criteria noted above, the review committee will independently evaluate each application in response to this RFA to assess: the quality of the proposed Center's program and general approach, including its proposed demonstration agenda, technical assistance, and dissemination plans; and the degree to which the Center's agenda reflects a realistic and well-conceived program in view of available skills, funding resources, and health care issues pertinent to the particular rural population(s) to be addressed. The following special scientific and technical review criteria will apply: o The extent to which the planned demonstration site(s) reflects the extreme challenges to rural health care delivery system reform as reflected by: 1. Limited public transportation infrastructure; 2. Geographic features that limit transportation; 3. Significant health status problems in the population; 4. Limited managed care penetration statewide; 5. Unemployment rates above the national average; and 6. A high percentage of the rural area designated as health professional shortage areas. o The quality of the organizational and institutional arrangements to operate the proposed Center, including plans for the use of an advisory committee by the Center; and links with State-level health planning efforts. Also, in the case of consortium applications, the degree of clarity in the differentiation of activities and a description of coordination efforts among organizational participants. Each component's role and responsibilities must be clearly described. This description must include the nature and extent of collateral or supplemental support provided to the applicant organization by other consortium members. o Evidence of the commitment of the applicant organization(s) to the provision of, and/or study of health care to rural populations, including plans to attract or retain other funding sources in support of its demonstration(s). o The actual and planned level of commitment of the applicant institution(s) to the proposed Center, including its specific plans to support its organizational and management structure. o The extent to which the proposed Center's plan reflects specificity in identifying problems to be addressed, and an awareness of significant methodological and data problems in designing, implementing, and monitoring rural health services demonstrations, such as availability of defined health status baseline information for the State or region, population based statistics on penetration of managed care, and available rural health care facility and related resource information. o The coordination of the proposed Center's planning and demonstration efforts, including the structure for sustaining ongoing monitoring of the processes for implementing the demonstration and progress towards its objectives, separate from AHCPR's independent and time- limited evaluation activity. o The degree to which the proposed Center's program includes representation from multiple appropriate scientific and administrative disciplines, including analytic and technical expertise, capable of planning and implementing demonstrations on rural issues and problems. o The qualifications, achievements, commitment, and number of senior personnel of the proposed Center, including the appropriateness of their specific time commitments. o The appropriateness of the proposed budget and the extent to which the fiscal plan provides assurance that effective use would be made of the funds awarded, including delineation of the service area(s) for which the proposed Center will be providing technical assistance in developing rural health demonstrations. AWARD CRITERIA Applications will compete for available funds with all other applications for this RFA. No awards will be made if, as result of the scientific and technical review, applications are not judged to be of high merit. The following will be considered in making funding decisions: quality of the proposed project as determined by peer review, program balance, and availability of funds. INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Norman W. Weissman, Ph.D. Center for General Health Services Extramural Research Agency for Health Care Policy and Research 2101 East Jefferson Street, Suite 502 Rockville, MD 20852-4908 Telephone: (301) 594-1357, ext. 130 Direct inquiries regarding fiscal matters to: Ralph L. Sloat Agency for Health Care Policy and Research 2101 East Jefferson Street, Suite 601 Rockville, MD 20852-4908 Telephone: (301) 594-1447 AUTHORITIES AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance number 93.226. Awards are made under authorization of the Public Health Service Act, Title IX, and administered under the PHS Grants Policy Statement and Federal Regulations 42 CFR 67, Subpart A. This program is not subject to the intergovernmental review requirements of Executive Order 12372. From owner-sci-resources@net.bio.net Wed Feb 16 22:00:00 1994 Path: biosci!biosci!not-for-mail From: Dave Kristofferson Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 23, no. 7, pt. 1, 18 February 1994 Date: 16 Feb 1994 16:23:06 -0800 Organization: BIOSCI International Newsgroups for Molecular Biology Lines: 1498 Approved: biosci-moderator@net.bio.net Distribution: bionet Message-ID: <2judda$5vu@net.bio.net> NNTP-Posting-Host: net.bio.net $$XID NIHGUIDE 19940218 V23N07 P1O4 ************************************ X-comment: RFAS described: DE-94-003, HD-94-012, HS-94-006, OH-94-001, HL-94- 009 NIH GUIDE - Vol. 23, No. 7 - February 18, 1994 $$INDEX BEGIN ******************************************************* NOTICES $$INDEX N1 ********************************************************** PURCHASE OF EQUIPMENT AND PRODUCTS UNDER NIH ASSISTANCE AWARDS - BUY AMERICAN PROVISIONS National Institutes of Health INDEX: NATIONAL INSTITUTES OF HEALTH $$INDEX N2 ********************************************************** DISCONTINUATION OF THE CNRS POSTDOCTORAL FELLOWSHIPS PROGRAM Fogarty International Center INDEX: FOGARTY INTERNATIONAL CENTER $$INDEX N3 ********************************************************** SALARY LIMITATION ON GRANTS AND CONTRACTS National Institutes of Health INDEX: NATIONAL INSTITUTES OF HEALTH NOTICES OF AVAILABILITY (RFPs AND RFAs) $$INDEX R1 ********************************************************** MAMMALIAN GENOTYPING SERVICE (RFP NIH-NHLBI-HV-94-14) National Heart, Lung, and Blood Institute INDEX: HEART, LUNG, BLOOD $$INDEX R2 ********************************************************** PHASE II CLINICAL TRIALS OF NEW CHEMOPREVENTIVE AGENTS (RFP NCI-CN- 45593-32) National Cancer Institute INDEX: CANCER $$INDEX R3 ********************************************************** PRECLINICAL EVALUATION OF INTERMEDIATE ENDPOINTS AND THEIR MODULATION BY CHEMOPREVENTIVE AGENTS (RFP NCI-CN-45594-32) National Cancer Institute INDEX: CANCER $$INDEX R4 05/06/94 ************************************************* ORAL MANIFESTATIONS OF HIV INFECTION (RFA DE-94-003) National Institute of Dental Research INDEX: DENTAL RESEARCH $$INDEX R5 05/13/94 ************************************************* ADOLESCENT MEDICINE HIV/AIDS RESEARCH NETWORK (RFA HD-94-012) National Institute of Child Health and Human Development National Institute of Allergy and Infectious Diseases Health Resources and Services Administration INDEX: CHILD HEALTH, HUMAN DEVELOPMENT; ALLERGY, INFECTIOUS DISEASES; HEALTH RESOURCES, SERVICES ADMINISTRATION $$INDEX R6 05/17/94 ************************************************* AHCPR RURAL CENTERS (RFA HS-94-006) Agency for Health Care Policy and Research INDEX: HEALTH CARE POLICY $$INDEX R7 05/18/94 ************************************************* OCCUPATIONAL RADIATION AND ENERGY-RELATED HEALTH RESEARCH (RFA OH-94-001) National Institute for Occupational Safety and Health INDEX: OCCUPATIONAL SAFETY; OCCUPATIONAL HEALTH $$INDEX R8 05/23/94 ************************************************* CARDIOVASCULAR CONSEQUENCES OF SLEEP APNEA (RFA HL-94-009) National Heart, Lung, and Blood Institute INDEX: HEART, LUNG, BLOOD ONGOING PROGRAM ANNOUNCEMENTS $$INDEX P1 ********************************************************** MARC FACULTY RESEARCH FELLOWSHIPS (PAR-94-032) National Institute of General Medical Sciences INDEX: GENERAL MEDICAL SCIENCES $$INDEX P2 ********************************************************** MORE FACULTY DEVELOPMENT AWARD (PAR-94-034) National Institute of General Medical Sciences INDEX: GENERAL MEDICAL SCIENCES $$INDEX P3 ********************************************************** NEUROGENETIC DISORDERS OF INFANCY AND CHILDHOOD (PA-94-035) National Institute of Neurological Disorders and Stroke INDEX: NEUROLOGICAL DISORDERS, STROKE $$INDEX P4 ********************************************************** CHARACTERIZATION AND TREATMENT OF GENETIC METABOLIC DISEASES (PA-94-036) National Institute of Diabetes and Digestive and Kidney Diseases INDEX: DIABETES, DIGESTIVE, KIDNEY DISEASES $$INDEX P5 ********************************************************** GENETIC DISORDERS CAUSING MENTAL RETARDATION (PA-94-037) National Institute of Child Health and Human Development INDEX: CHILD HEALTH, HUMAN DEVELOPMENT $$INDEX P6 ********************************************************** PREVENTIVE INTERVENTION RESEARCH CENTERS (PAR-94-038) National Institute of Mental Health INDEX: MENTAL HEALTH $$INDEX P7 ********************************************************** ARTICULATION DISORDERS OF UNKNOWN ORIGIN IN CHILDREN (PA-94-039) National Institute on Deafness and Other Communication Disorders INDEX: DEAFNESS, OTHER COMMUNICATIONS DISORDERS $$INDEX P8 ********************************************************** GENE THERAPY IN DUCHENNE MUSCULAR DYSTROPHY (PA-94-040) National Institute of Neurological Disorders and Stroke National Institute of Arthritis and Musculoskeletal and Skin Diseases INDEX: NEUROLOGICAL DISORDERS, STROKE; ARTHRITIS, MUSCULOSKELETAL, SKIN DISEASES This publication is available electronically to institutions via BITNET or INTERNET and is also on the NIH GOPHER. Alternative access is through the NIH Grant Line using a personal computer (data line 301/402-2221). Contact Dr. John James at 301/594-7270 for details. $$INDEX END ********************************************************* NOTICES $$N1 BEGIN ********************************************************** PURCHASE OF EQUIPMENT AND PRODUCTS UNDER NIH ASSISTANCE AWARDS - BUY AMERICAN PROVISIONS NIH GUIDE, Volume 23, Number 7, February 18, 1994 P.T. National Institutes of Health The National Institutes of Health (NIH) Revitalization Act (P.L. 103-43, June 10, 1993) places certain requirements on recipients of assistance with respect to the purchase of equipment and supplies. Specifically, section 2004 (Buy American Provisions) requires that if any equipment or product is authorized to be purchased with financial assistance provided pursuant to this Act for any of the fiscal years 1994 through 1996, entities receiving such assistance should, in expending the assistance, purchase only American-made equipment and products. Section 2004 further requires the Secretary of Health and Human Services, in providing financial assistance pursuant to this Act, to provide each recipient of the assistance a notice describing the above statement, made by the Congress. Thus, recipients of NIH assistance awards (including those subcontracts for substantive programmatic work under NIH assistance awards) are strongly encouraged, when purchasing equipment and products, to expend the assistance for American-made equipment and products, whenever possible. Beginning in fiscal year 1994, notices of grant and fellowship award will include a footnote containing the following language: "Pursuant to the NIH Revitalization Act (P.L. 103-43, June 10, 1993), section 2004, when purchasing equipment or products under this assistance award, the recipient should, whenever possible, purchase only American-made items." If you have any questions concerning this policy, contact the NIH grants management contact listed on the notice of grant or fellowship award. $$N1 END ************************************************************ $$N2 BEGIN ********************************************************** DISCONTINUATION OF THE CNRS POSTDOCTORAL FELLOWSHIPS PROGRAM NIH GUIDE, Volume 23, Number 7, February 18, 1994 P.T. 34; K.W. 1014006 Fogarty International Center The Fogarty International Center (FIC) announces that it is no longer accepting applications for the Centre National de la Recherche Scientifique/National Institutes of Health Postdoctoral Fellowships (CNRS/NIH - F07) program. Please note that this change is effective as of the date of this publication; therefore, applications for this program will not be accepted for the April 5, 1994 receipt date. INQUIRIES For further information, contact: CNRS/NIH Fellowship Program International Research and Awards Branch Fogarty International Center Building 31, Room B2C39 Bethesda, MD 20892 Telephone: (301) 496-1653 FAX: (301) 402-0779 $$N2 END ************************************************************ $$N3 BEGIN ********************************************************** SALARY LIMITATION ON GRANTS AND CONTRACTS NIH GUIDE, Volume 23, Number 7, February 18, 1994 P.T. National Institutes of Health The purpose of this notice is to provide updated information regarding the salary limitation as it relates to NIH grant and cooperative agreement awards (hereafter called 'grant'). This information also applies to extramural research and development contract awards. In addition, this notice describes a change in the way that NIH Institutes and Centers (I/Cs) are treating salaries in excess of the limit for any future years in competing grant awards. The last notice in the NIH Guide for Grants and Contracts regarding the salary limitation was in Vol. 20, No. 47, December 20, 1991. Fiscal Year (FY) 94 is the fifth consecutive year for which there is a legislatively mandated provision for the limitation of salary. Specifically, the Department of Health and Human Services (HHS) Appropriations Act for FY 94, Public Law 103-112, restricts the amount of direct salary an individual under a grant or applicable contract issued by the NIH to a RATE of $125,000 per year. Direct salary is exclusive of fringe benefits and indirect costs/general and administrative expenses. The salary limit of $125,000 has not increased from the FY 93 level. The NIH will continue to apply the limits to all grant and applicable contract awards and all funding amendments to existing awards made with FY 94 funds. Therefore, NIH grant and applicable contract awards for applications/proposals that request direct salaries of individuals in excess of a RATE of $125,000 per year will be adjusted in accordance with the legislative salary limitation, and will include a notification such as: According to the HHS Appropriations Act, "None of the funds appropriated in this title for the National Institutes of Health ... shall be used to pay the salary of an individual, through a grant or other extramural mechanism, at a rate in excess of $125,000 per year." The following are examples of the adjustments that NIH will make when salaries exceed the limit: EXAMPLE 1. INDIVIDUAL WITH FULL-TIME APPOINTMENT. Individual's institutional base* salary for a FULL-TIME (twelve month) appointment $150,000 Research effort requested in application/ proposal 50% Direct Salary requested $75,000 Fringe benefits requested (25% of salary) $18,750 Subtotal $93,750 Applicant organization's indirect costs at a rate of 45% of subtotal $42,188 Amount requested - salary plus fringe benefits plus associated indirect costs $135,938 If a grant/contract is to be funded, the amount included in the award for the above individual will be calculated as follows: Direct salary - restricted to a RATE of $125,000 multiplied by effort (50%) to be devoted to project $62,500 Fringe benefits (25% of allowable salary) $15,625 Subtotal $78,125 Associated indirect costs at 45% of subtotal $35,156 Total amount to be awarded due to salary limitation $113,281 Amount of reduction due to salary limitation ($135,938 requested minus $113,281 awarded) $22,657 * An individual's institutional base salary is the annual compensation that the applicant organization pays for an individual's appointment, whether that individual's time is spent on research, teaching, patient care, or other activities. Base salary excludes any income that an individual may be permitted to earn outside of duties to the applicant organization. EXAMPLE 2. INDIVIDUAL WITH HALF-TIME APPOINTMENT. Individual's institutional base salary for a HALF-TIME appointment (50% of a full-time twelve month appointment) $65,000 Research effort requested in application/ proposal 30% Direct Salary requested $19,500 Fringe benefits requested (25% of salary) $4,875 Subtotal $24,375 Applicant organization's indirect costs at a rate of 45% of subtotal $10,969 Amount requested - salary plus fringe benefits plus associated indirect costs $35,344 If a grant/contract is to be funded, the amount included in the award for the above individual will be calculated as follows: Direct salary - restricted to a RATE of $125,000 multiplied by 50% appointment by 30% effort to be devoted to project $18,750 Fringe benefits (25% of allowable salary) $4,688 Subtotal $23,438 Associated indirect costs at 45% of subtotal $10,547 Total amount to be awarded due to salary limitation $33,985 Amount of reduction due to salary limitation ($35,344 requested minus $33,985 awarded) $1,359 Other important points relating to both NIH grants and contracts are: o An individual's base salary, per se, is NOT constrained by the legislative provision for the limitation of salary. The rate limitation simply limits the amount that may be awarded and charged to NIH grant and applicable contract awards. An institution may supplement an individual's salary with non-federal funds. o The salary limitation does NOT apply to payments made to consultants under an NIH grant or contract although, as with all costs, such payments must meet the test of reasonableness. o The salary limitation provision DOES apply to those subawards/subcontracts for substantive work under an NIH grant or contract. In addition, the following three paragraphs apply to GRANT applications/awards only: o COMPETING grant applications submitted to the NIH may continue to request funding at the regular/actual rates of pay of all individuals for whom reimbursement is requested, even when these rates exceed the salary limitation. NIH staff will make necessary adjustments to requested salaries prior to award. o There is a change in the way that NIH I/Cs are treating salaries in excess of the limit for any FUTURE years beginning with COMPETING grant awards funded with FY 94 funds. Based upon experience and the expectation that the salary restriction will continue in future appropriations (although the amount of the limitation may change with future appropriations), NIH awards for COMPETING applications will reflect adjustments to all years of a project, including future years, so that no funds are awarded or committed for salaries over the limitation. o With regard to NON-COMPETING continuation grant applications submitted to NIH, these applications should request funds for salaries at rates of pay that DO NOT exceed the salary limitation. If the current committed level includes funds for salaries at a rate that exceeds the salary limitation, the excess may not be rebudgeted for any other purpose, and NIH staff will delete it from the award. For further information concerning policies relating to grants or contracts, contact any of the grants management offices and/or contracts management offices of the NIH funding components. $$N3 END ************************************************************ NOTICES OF AVAILABILITY (RFPs AND RFAs) $$R1 BEGIN NIH-NHLBI-HV-94-14 *************************************** MAMMALIAN GENOTYPING SERVICE NIH GUIDE, Volume 23, Number 7, February 18, 1994 RFP AVAILABLE: NIH-NHLBI-HV-94-14 P.T. National Heart, Lung, and Blood Institute The Hypertension and Kidney Diseases Branch, Division of Heart and Vascular Diseases, National Heart, Lung, and Blood Institute (NHLBI) has a requirement for the establishment of a large-scale genotyping service capable of genotyping large numbers of human and mammalian DNA samples as a cost-effective means to reliably and efficiently facilitate identification of genes responsible for cardiovascular, pulmonary and hematologic diseases. The genotyping service is to utilize polymerase chain reaction (PCR)-based techniques to provide highest quality genotypes and operate on a fee-for-service basis. Automated methods and robotics are required. The service will not isolate genomic DNA from tissues and cells, but must provide storage of the DNA, which will be provided by users of the service. Genotypic data will be provided to users of this service as hard-copies (e.g., graphs, photographs, autoradiographs) and on computer disc, where it must be compiled into simple software programs for use in more than one of the commonly used personal computing systems utilized by scientists. The service is to focus on production of samples and is expected in subsequent years to increase production capacity, while reducing the fee-for-service. Since other funding mechanisms are currently available to support the development of new technologies and methodologies to improve genotyping speed, quality, and cost, no funds will be available for this explicit purpose in the contract. However, the service is responsible for incorporating any applicable, newly developed technologies, methodologies, and their refinements, into the existing structure in subsequent years to improve genotyping quality, to decrease costs and to increase the production of genotypes. Genotyping projects will be submitted to the service, wherein a review panel of scientific experts, established and coordinated by the Contractor, will assess the scientific merit, feasibility, cost and, in conjunction with the NHLBI, programmatic relevance. In order to ensure that the service has sufficient work, projects outside of NHLBI programmatic relevance will be considered for genotyping. However, meritorious projects with NHLBI programmatic relevance will receive priority over projects supported through other sources. The purpose of this contract is to provide seed money for the establishment of the genotyping service. It will provide decreasing funds over a five-year period in order to allow for the service to become fully established, while maintaining itself by fee-for-service. Prospective offerors should have well-recognized expertise and experience in genomics, molecular genetics, informatics, robotics, and molecular biology. In particular, offerors should have experience in PCR-based methods to map genes. A single multi-year incrementally funded award is anticipated. RFP NIH-NHLBI-HV-94-14 will be released on or about February 18, 1994. INQUIRIES To receive a copy of the RFP, include three labels self-addressed with your mailing address and must cite RFP No. NIH-NHLBI-HV-94-14. Requests for copies of the RFP are to be sent to: Shari L. Spencer Contracts Operations Branch National Heart, Lung, and Blood Institute Federal Building, Room 4C04 Bethesda, MD 20892 $$R1 END ************************************************************ $$R2 BEGIN NCI-CN-45593-32 ****************************************** PHASE II CLINICAL TRIALS OF NEW CHEMOPREVENTIVE AGENTS NIH GUIDE, Volume 23, Number 7, February 18, 1994 RFP AVAILABLE: NCI-CN-45593-32 P.T. National Cancer Institute The National Cancer Institute (NCI) is seeking contractors qualified to perform Phase II Clinical Trials that are small short-term, efficient studies of potential chemopreventive agents. This work includes small,