From owner-sci-resources@net.bio.net Thu Sep 02 23:00:00 1993 Path: biosci!net.bio.net From: kristoff@net.bio.net (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 22, no. 32, pt. 1, 3 September 1993 Message-ID: Date: 3 Sep 93 01:41:43 GMT Sender: kristoff@net.bio.net Lines: 1505 Approved: biosci-moderator@net.bio.net NOTE: The NIH Guide may be split into more than one mail message to avoid truncation during e-mail distribution. The first message always begins with the RFP/RFA summary sections followed by the appended texts of the full RFP/RFAs. ---------------------------------------------------------------------- $$XID NIHGUIDE 19930903 V22N32 P1O2 ************************************ X-comment: RFAs described: AG-94-002, CA-93-038, AI-93-019 NIH GUIDE - Vol. 22, No. 32 - September 3, 1993 $$INDEX BEGIN ******************************************************* NOTICES $$INDEX N1 ********************************************************** PUBLICATION DATES FOR THE NIH GUIDE $$INDEX N2 ********************************************************** SMALL BUSINESS TECHNOLOGY TRANSFER PROGRAM National Institutes of Health INDEX: NATIONAL INSTITUTES OF HEALTH $$INDEX N3 ********************************************************** WITHDRAWAL OF INTERIM NIH GUIDELINES FOR THE SUPPORT AND CONDUCT OF THERAPEUTIC HUMAN FETAL TISSUE TRANSPLANTATION RESEARCH IN LIGHT OF SUPERSEDING PROVISIONS OF PUBLIC LAW 103-43, THE NATIONAL INSTITUTES OF HEALTH REVITALIZATION ACT OF 1993 National Institutes of Health INDEX: NATIONAL INSTITUTES OF HEALTH $$INDEX N4 ********************************************************** HHS HUMAN RESEARCH SUBJECT PROTECTION REGULATIONS PERTAINING TO IN VITRO FERTILIZATION (IVF) OF HUMAN OVA MODIFIED BY THE NIH REVITALIZATION ACT National Institutes of Health INDEX: NATIONAL INSTITUTES OF HEALTH $$INDEX N5 ********************************************************** CHANGES IN APPLICATION PROCEDURES FOR FELLOWSHIPS SUPPORTED BY THE MINORITY ACCESS TO RESEARCH PROGRAM National Institute of General Medical Sciences INDEX: GENERAL MEDICAL SCIENCES NOTICES OF AVAILABILITY (RFPs AND RFAs) $$INDEX R1 ********************************************************** APPLICATIONS DEVELOPMENT PROGRAM (RFP NHLBI-HO-94-01) National Heart, Lung, and Blood Institute INDEX: HEART, LUNG, BLOOD $$INDEX R2 ********************************************************** CANCER PREVENTION AND CONTROL SURVEILLANCE MASTER AGREEMENT (MAA NCI-CN-35551-05) National Cancer Institute INDEX: CANCER $$INDEX R3 11/29/93 ************************************************* MENOPAUSE AND HEALTH IN AGING WOMEN (RFA AG-94-002) National Institute on Aging National Institute of Nursing Research Office of Research on Women's Health INDEX: AGING; NURSING RESEARCH, WOMEN'S HEALTH $$INDEX R4 12/07/93 ************************************************* IDENTIFICATION AND EVALUATION OF TISSUE MARKERS FOR PATHOLOGICAL CLASSIFICATION OF HUMAN GLIOMAS (RFA CA-93-038) National Cancer Institute INDEX: CANCER $$INDEX R5 01/21/94 ************************************************* NATIONAL COOPERATIVE DRUG DISCOVERY GROUPS FOR THE TREATMENT OF OPPORTUNISTIC INFECTIONS ASSOCIATED WITH ACQUIRED IMMUNODEFICIENCY SYNDROME (NCDDG-OI): TUBERCULOSIS (RFA AI-93-019) National Institute of Allergy and Infectious Diseases INDEX: ALLERGY, INFECTIOUS DISEASES ONGOING PROGRAM ANNOUNCEMENTS $$INDEX P1 ********************************************************** DRUG ABUSE TREATMENT FOR WOMEN OF CHILDBEARING AGE AND THEIR CHILDREN (PA 93-106) National Institute on Drug Abuse INDEX: DRUG ABUSE $$INDEX P2 ********************************************************** MEDICAL IMAGING DATABASES (PA-93-107) National Cancer Institute National Institute of Neurological Disorders and Stroke National Library of Medicine INDEX: CANCER; NEUROLOGICAL DISORDERS, STROKE; NATIONAL LIBRARY OF MEDICINE $$INDEX P3 ********************************************************** BEHAVIORAL RESEARCH IN SEXUALLY TRANSMITTED DISEASES (PA-93-108) National Institute of Allergy and Infectious Diseases National Institute of Child Health and Human Development National Institute on Aging INDEX: ALLERGY, INFECTIOUS DISEASES; CHILD HEALTH, HUMAN DEVELOPMENT; AGING ERRATA $$INDEX E1 11/24/93 ************************************************* MULTICOMPONENT VACCINE DEVELOPMENT (RFA AI-93-017) National Institute of Allergy and Infectious Diseases INDEX: ALLERGY, INFECTIOUS DISEASES This publication is available electronically to institutions via BITNET or INTERNET and is also on the NIH GOPHER. Alternative access is through the NIH Grant Line using a personal computer (data line 301/402-2221). Contact Dr. John James at 301/594-7270 for details. $$INDEX END ********************************************************* NOTICES $$N1 BEGIN ********************************************************** THE NIH GUIDE FOR GRANTS AND CONTRACTS WILL NOT BE PUBLISHED ON SEPTEMBER 10, 1993. THE NEXT ISSUE WILL BE SEPTEMBER 17, 1993. $$N1 END ************************************************************ $$N2 BEGIN ********************************************************** SMALL BUSINESS TECHNOLOGY TRANSFER PROGRAM NIH GUIDE, Volume 22, Number 32, September 3, 1993 P.T. 34; K.W. 1016004 National Institutes of Health Application Receipt Date: December 1, 1993 The purpose of this announcement is to inform the public of a new set- aside funding opportunity that requires collaboration of small businesses with research institutions. Public Law 102-564, signed October 28, 1992, requires the National Institutes of Health (NIH), Public Health Service, Department of Health and Human Services, and certain other Federal agencies to reserve a specified amount of their extramural research or research and development (R&D) budgets for a Small Business Technology Transfer (STTR) program. The legislation is intended to: o stimulate and foster scientific, technical, and technological innovation through cooperative R&D carried out between small businesses and research institutions; o foster technology transfer between small businesses and research institutions; o increase private sector commercialization of innovations derived from Federal R&D; and o foster and encourage participation of socially and economically disadvantaged small businesses and women-owned small businesses in technological innovation. The STTR program is a three-year pilot program the begins in fiscal year (FY) 1994 and consists of the following three phases: PHASE I: The objective of this phase is to determine the scientific, technical, and commercial merit and feasibility of the proposed cooperative effort and the quality of performance of the small business concern, prior to providing further Federal support in Phase II. PHASE II: The objective of this phase is to continue the research or R&D efforts initiated in Phase I. Funding shall be based on the results of Phase I and the scientific and technical merit and commercial potential of the Phase II application. PHASE III: The objective of this phase, where appropriate, is for the small business concern to pursue with non-federal funds the commercialization of the results of the research or R&D funded in Phases I and II. The amount and period of support for STTR awards are as follows: PHASE I: Awards may not exceed $100,000 for direct costs, indirect costs, and negotiated fixed fee for a period normally not to exceed one year. PHASE II: Awards may not exceed $500,000 for direct costs, indirect costs, and negotiated fixed fee for a period normally not to exceed two years. A Phase I award must have been issued in order to apply for a Phase II award. (ONLY Phase I awards will be issued in FY 1994.) It is anticipated that approximately 40 STTR grants will be awarded by the NIH in FY 1994 from funds set aside for this purpose. The applicant organization must be the small business. As required by the legislation, at least 40 percent of the project is to be performed by the small business and at least 30 percent of the project is to be performed by the research institution. INQUIRIES Eligibility requirements, definitions, application procedures, review considerations, application forms and instructions, and other pertinent information are contained in the "Omnibus Solicitation of the National Institutes of Health for Small Business Technology Transfer (STTR) Grant Applications," available from: Massachusetts Technological Laboratory, Inc. 13687 Baltimore Avenue Laurel, MD 20707 Telephone: (301) 206-9385 FAX: (301) 206-9722 The OMNIBUS SOLICITATION is for the single application receipt date of December 1, 1993, for grant awards to be made in FY 1994. Contact points for inquiries regarding each NIH awarding component's program interests concerning the STTR program are contained in the OMNIBUS SOLICITATION. $$N2 END ************************************************************ $$N3 BEGIN ********************************************************** WITHDRAWAL OF INTERIM NIH GUIDELINES FOR THE SUPPORT AND CONDUCT OF THERAPEUTIC HUMAN FETAL TISSUE TRANSPLANTATION RESEARCH IN LIGHT OF SUPERSEDING PROVISIONS OF PUBLIC LAW 103-43, THE NATIONAL INSTITUTES OF HEALTH REVITALIZATION ACT OF 1993 NIH GUIDE, Volume 22, Number 32, September 3, 1993 P.T. 34; K.W. 0783005, 0755055, 0780005 National Institutes of Health SUMMARY: The National Institutes of Health (NIH) is announcing the withdrawal of its interim guidelines for the support and conduct of therapeutic human fetal tissue transplantation research because of the superseding provisions of P.L. 103-43, the National Institutes of Health Revitalization Act of 1993. A summary of pertinent provisions of the Act is provided below. Background On January 22, 1993, President Clinton issued a directive to the Secretary of Health and Human Services ending a five-year moratorium on Federal funding of therapeutic transplantation research that uses human fetal tissue derived from induced abortions. Secretary of Health and Human Services Donna E. Shalala notified the National Institutes of Health (NIH) of the President's action, and then formally revoked the moratorium on February 1, 1993. At the same time, the Secretary, through the Acting Assistant Secretary for Health, directed the NIH to develop interim guidelines based on the recommendations of the 1988 Human Fetal Tissue Transplantation Research Panel to ensure that Federal funding of human fetal tissue transplantation research does not encourage the choice of abortion. Accordingly, the NIH prepared, and transmitted to the Acting Assistant Secretary for Health, interim policy guidelines based on the recommendations of the 1988 Human Fetal Tissue Transplantation Research Panel and the Advisory Committee to the Director, NIH. Those interim guidelines were published in the NIH Guide for Grants and Contracts on March 19, 1993 (Vol. 22, No. 11). Action The NIH Interim Guidelines for the Support and Conduct of Therapeutic Human Fetal Tissue Transplantation Research are hereby withdrawn in light of the comprehensive and superseding provisions of P.L. 103-43, enacted June 10, 1993. Final guidelines will not be issued. Additional Information Attention is directed to section 498A of the Public Health Service Act (42 U.S.C. 289g-1) added by P.L. 103-43, the NIH Revitalization Act of 1993. The provisions of that section pertinent to research on transplantation of fetal tissue are summarized as follows: o Human fetal tissue means tissue or cells obtained from a dead human embryo or fetus after a spontaneous or induced abortion, or after a stillbirth. o Human fetal tissue may be used regardless of whether the tissue is obtained pursuant to a spontaneous or induced abortion or pursuant to a stillbirth. o The Secretary of Health and Human Services may conduct or support research on the transplantation of human fetal tissue for therapeutic purposes. o The woman donating the human fetal tissue must sign a statement declaring that the tissue is being donated for therapeutic transplantation research, the donation is being made without any restriction regarding the identity of individuals who may be the recipients of transplantations of the tissue, and the donation is being made without her (the donor) having been informed of the identity of those individuals who may be the recipients. o The attending physician must sign a statement declaring that the tissue has been obtained in accord with the donor's signed statement and that full disclosure has been made to the donating woman of (1) the attending physician's interest, if any, in the research to be conducted with the tissue, and (2) any known medical risks to the donor or risks to her privacy that might be associated with the donation of the tissue and are in addition to the risks associated with the woman's medical care. In the case of tissue obtained pursuant to an induced abortion, the attending physician's statement must also declare that the consent of the woman for the abortion was obtained prior to requesting or obtaining consent for donation, the abortion was conducted in accord with applicable State Law, and no alteration of the timing, method, or procedures used to terminate the pregnancy was made solely for the purposes of obtaining the tissue. o The individual with the principal responsibility for conducting the research must sign a statement declaring that the individual is aware that the tissue is human fetal tissue donated for research purposes and may have been obtained pursuant to a spontaneous or induced abortion or pursuant to a stillbirth; that the principally responsible researcher has provided such information to other individuals with responsibilities regarding the research; that the principally responsible researcher will require, prior to obtaining the consent of a person to be a recipient of a transplantation of the tissue, written acknowledgment of receipt of the foregoing information by such recipient; and that the principally responsible researcher has had no part in any decisions as to the timing, method, or procedures used to terminate the pregnancy made solely for the purposes of the research. o Human fetal tissue may be used only if the head of the agency or other entity conducting the research involved certifies to the Secretary of Health and Human Services that the statements required herein will be available for audit by the Secretary [HHS]. o Research involving the transplantation of human fetal tissue for therapeutic purposes must be conducted in accord with applicable State law and the Secretary may not provide support for such research unless the applicant for assistance agrees to so conduct the research. The conduct of such research by the Secretary must be in accord with applicable State and local law. The provisions of section 498B of the Public Health Service Act (42 U.S.C 289g-2), added by P.L. 103-43, the NIH Revitalization Act of 1993, are summarized as follows: o It shall be unlawful for any person to knowingly acquire, receive, or otherwise transfer any human fetal tissue for valuable consideration if the transfer affects interstate commerce. (Valuable consideration does not include reasonable payments associated with the transportation, implantation, processing, preservation, quality control, or storage of human fetal tissue.) o It shall be unlawful for any person to solicit or knowingly acquire, receive, or accept a donation of human fetal tissue for the purpose of transplantation of such tissue into another person if the donation affects interstate commerce, the tissue will be or is obtained pursuant to an induced abortion, and (1) the donation will be or is made pursuant to a promise to the donating individual that the donated tissue will be transplanted into a recipient specified by such individual; (2) the donated tissue will be transplanted into a relative of the donating individual; or (3) the person who solicits or knowingly acquires, receives, or accepts the donation has provided valuable consideration for the costs associated with such abortion. (Valuable consideration does not include reasonable payments associated with the transportation, implantation, processing, preservation, quality control, or storage of human fetal tissue.) o Any person who violates these provisions shall be (1) fined in accordance with Title 18 United States Code, except that the fine shall be not less than twice the amount of any valuable consideration received, (2) imprisoned for not more than 10 years, or (3) penalized as described in both (1) and (2). INQUIRIES Written comments may be mailed or delivered (between 9 a.m. and 5 p.m. weekdays). Comments received may be inspected at the same location during these hours. F. William Dommel, Jr., J.D. Senior Policy Advisor Office for Protection from Research Risks Building 31, Room 5B63 Bethesda, MD 20892 Telephone: (301) 496-7005 $$N3 END ************************************************************ $$N4 BEGIN ********************************************************** HHS HUMAN RESEARCH SUBJECT PROTECTION REGULATIONS PERTAINING TO IN VITRO FERTILIZATION (IVF) OF HUMAN OVA MODIFIED BY THE NIH REVITALIZATION ACT NIH GUIDE, Volume 22, Number 32, September 3, 1993 P.T. 34; K.W. 0783005, 0755055, 0780005 National Institutes of Health The National Institutes of Health Revitalization Act of 1993 (P.L. 103- 43) nullified the provisions of section 204(d) of part 46 of title 45 of the Code of Federal Regulations (45 CFR 46.204(d)). The provisions- -which are now void--read: "No application or proposal involving human in vitro fertilization may be funded by the Department until the application or proposal has been reviewed by the Ethical Advisory Board and the Board has rendered advice as to its acceptability from an ethical standpoint." The practical effect of this nullification is that research applications and proposals involving in vitro fertilization (IVF) of human ova may be conducted or funded by HHS and its components without the prior review and advice of a national advisory body. IRB (Institutional Review Board) review and approval continues to be required in accord with 45 CFR 46.205. It is anticipated that applications and proposals involving certain types of human IVF research will still be subject to special review on a case-by-case basis, at the discretion of the Department and its components. INQUIRIES For further information, contact F. William Dommel, Jr., J.D. Senior Policy Advisor Office for Protection from Research Risks Building 31, Room 5B63 Bethesda, MD 20892 Telephone: (301) 496-7005 $$N4 END ************************************************************ $$N5 BEGIN ********************************************************** CHANGES IN APPLICATION PROCEDURES FOR FELLOWSHIPS SUPPORTED BY THE MINORITY ACCESS TO RESEARCH PROGRAM NIH GUIDE, Volume 22, Number 32, September 3, 1993 P.T. 34; K.W. 1014006 National Institute of General Medical Sciences The National Institute of General Medical Sciences (NIGMS) announces two changes in application procedures for fellowships supported by the Minority Access to Research Careers (MARC) Program. The NIGMS MARC Program provides MARC Predoctoral Fellowships, which support predoctoral research training for graduates of MARC Honors Undergraduate Research Training programs, and MARC Faculty Fellowships, which support research training at the pre- or postdoctoral level for faculty of institutions having a substantial enrollment of students from underrepresented ethnic minority groups. The first policy applies to applications for both types of MARC Fellowships, that is, both the Predoctoral and Faculty Fellowship programs. Applications for MARC fellowships will be accepted for the April 5 and December 5 receipt dates ONLY; the NIGMS will no longer accept MARC fellowship applications for the August 5 receipt date. The second policy applies to applications for PREDOCTORAL training support, including MARC Predoctoral Fellowships and those MARC Faculty Fellowships that seek support for PREDOCTORAL training; it DOES NOT apply to applicants seeking postdoctoral support in the MARC Faculty Fellowship Program. Beginning with the December 5, 1993 receipt date, all applicants for MARC predoctoral support must indicate that EITHER they are already enrolled in a Ph.D. or combined M.D./Ph.D. training program OR they have been accepted by and agreed to enroll in a Ph.D. or combined M.D./Ph.D. training program. The training program must be described in the application. Applications that lack this information at the time of the initial review will be deferred until this information is received. INQUIRIES Further information or clarification may be obtained from: NIGMS MARC Program Office National Institute of General Medical Sciences Westwood Building, Room 950 Bethesda, MD 20892 Telephone: (301) 594-7823 $$N5 END ************************************************************ NOTICES OF AVAILABILITY (RFPs AND RFAs) $$R1 BEGIN NHLBI-HO-94-01 ******************************************* APPLICATIONS DEVELOPMENT PROGRAM NIH GUIDE, Volume 22, Number 32, September 3, 1993 RFP AVAILABLE: NHLBI-HO-94-01 P.T. 34; K.W. 1004000, 1004017 National Heart, Lung, and Blood Institute The overall objective of this contract is to analyze, evaluate, design, program, test, implement, document, maintain, and enhance National Heart, Lung, and Blood Institute (NHLBI) mainframe and microcomputer applications and systems. Offerors will be required to present plans detailing the technical approaches, procedures, and time schedules for accomplishing these objectives. Nine new mainframe and microcomputer applications and systems will be developed. In order to develop these nine systems, the following five stages will be completed by the Contractor: (1) Analysis; (2) Evaluation; (3) Design/Specification, (4) Programming, and (5) Testing/Implementation. Fifteen mainframe and microcomputer applications and systems will be maintained and enhanced. Maintenance and enhancements will include, but are not limited to, the following: (1) enhancement of current utilities to meet new information requirements of users as well as those of the NHLBI; (2) assurance that the database is valid and accurate and is utilized as the official NHLBI database; (3) review and update of the system, sub-systems, reports, and user documentation as required; (4) addition of new sub-systems and utilities as requirements demand; and (5) maintenance and enhancement will be performed to accommodate changes made by the Division of Research Grants and the Division of Computer Research Technology, NHLBI reorganizations, end of fiscal year changes, interfaces to and with new internal and external systems, requests for new data elements or information based on user needs, new reporting and monitoring requirements, support of new scientific initiatives, and integration of new data sources and technology. It is anticipated that 14 full-time equivalents will be required for the successful completion of the study. This announcement is not a request for proposals (RFP). It is anticipated that RFP No. NHLBI-HO-94-01 will be available on or about September 20, 1993, with proposals due on November 10, 1993. INQUIRIES To receive a copy of the RFP, submit a written request along with three self-addressed mailing labels to: Joanne C. Deshler Division of Lung Diseases, Contracts Operations Branch National Heart, Lung, and Blood Institute Westwood Building, Room 654 Bethesda, Md 20892 This proposed program is a 100% set-aside for small business competition. Only responsible small business firms as defined in Part 19 of the Federal Acquisition Regulation are asked to respond to this synopsis. The Standard Industrial Classification (SIC) Code is 7379. $$R1 END ************************************************************ $$R2 BEGIN NCI-CN-35551-05 ****************************************** CANCER PREVENTION AND CONTROL SURVEILLANCE MASTER AGREEMENT NIH GUIDE, Volume 22, Number 32, September 3, 1993 MAA AVAILABLE: NCI-CN-35551-05 P.T. 34; K.W. 0715035, 0745027, 0795003 National Cancer Institute The National Cancer Institute, Division of Cancer Prevention and Control is soliciting proposals to provide information required for cancer control surveillance. The primary purpose is to conduct surveys and similar evaluation processes. The term "survey" is used to connote a full range of studies, including probability sample surveys and specialty studies requiring data abstraction. The Master Agreement Announcement (MAA) is tentatively scheduled for release on or about October 5, 1993. It is anticipated that multiple master agreements will be awarded pursuant to the MAA, each having a five year period of performance. Since MAs are unfunded, the obligation of funds will be accomplished solely through the award of master agreement orders (MAOs), issued under the terms of this MA. The MAOs will be issued on either a cost or fixed price basis. The Standard Industrial Code applicable to this procurement is 7379. The MA holder, upon award of a MAO, will coordinate and implement the requested survey(s), including data collection, processing and reporting for surveillance activities to be designed and developed by NCI alone or in collaboration with other organizations. INQUIRIES Copies of the MAA may be obtained by sending a written request, citing the MAA number to: No collect calls will be accepted. Mr. Gary Topper Research Contracts Branch, PCCS National Cancer Institute Executive Plaza South, Room 635 Bethesda, MD 20892 Telephone: (301) 496-8603 $$R2 END ************************************************************ $$R3 BEGIN AG-94-002 FULL-TEXT ************************************** MENOPAUSE AND HEALTH IN AGING WOMEN NIH GUIDE, Volume 22, Number 32, September 3, 1993 RFA AVAILABLE: AG-94-002 P.T. 34, II; K.W. 0710010, 0413002, 1002061 National Institute on Aging National Institute of Nursing Research Office of Research on Women's Health Letter of Intent Receipt Date: October 15, 1993 Application Receipt Date: November 29, 1993 THIS IS A NOTICE OF AVAILABILITY OF A REQUEST FOR APPLICATIONS (RFA); IT IS ONLY AN ABSTRACT OF THE RFA. POTENTIAL APPLICANTS MUST REQUEST THE COMPLETE RFA, WHICH CONTAINS ESSENTIAL INFORMATION FOR THE PREPARATION OF AN APPLICATION, FROM THE CONTACT LISTED IN "INQUIRIES," BELOW. FAILURE TO FOLLOW THE INSTRUCTIONS IN THE COMPLETE RFA MAY RESULT IN AN INCOMPLETE APPLICATION, WHICH WILL BE RETURNED TO THE APPLICANT WITHOUT REVIEW. PURPOSE The National Institute on Aging (NIA), the National Institute of Nursing Research (NINR), and the Office of Research on Women's Health (ORWH) invite cooperative agreement applications for Clinical Sites to conduct prospective longitudinal studies of the natural history of menopause and the decline in ovarian function in women. The primary objective of this initiative is to characterize the chronology of the biological and psychosocial antecedents and sequelae of the menopausal transition and the effect of this transition on subsequent health and risk factors for age-related disease. Applications are also requested for a Central Laboratory to conduct standardized assays and for a Coordinating Center to coordinate the collection, management, and analysis of a common data set. 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, Menopause and Health in Aging Women, is related to the priority area of older adults and preventive services. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Due to the need for close coordination and monitoring, no foreign or international components will be considered in this RFA. Applications from minorities and women are encouraged. 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 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. Applicants will be responsible for the planning, direction, and execution of their individual proposed project and for planning and participating in collaborative activities with other award recipients under this RFA. The total project period for applications submitted in response to this RFA may not exceed five years. The anticipated award date is July 1, 1994. FUNDS AVAILABLE It is expected that up to $2.3 million (total cost) for first year expenses will be available in Fiscal Year 1994 to fund five Clinical Sites plus a Coordinating Center and a Central Laboratory. Separate applications must be submitted if an institution seeks selection as both a Clinical Site, Coordinating Center and/or Central Laboratory. The requested total funding (direct plus indirect costs) for the first-year may not exceed $350,000 for Clinical Site applications, $250,000 for Coordinating Center applications and $300,000 for Central Laboratory applications. For the entire five years of the project, total (direct plus indirect) costs requested per application may not exceed $1.75 million for the individual research projects, $1.25 million for the Coordinating Center and $1.5 million for the Central Laboratory. Although this program will be provided for in the financial plans of the NIA and co-sponsors of this RFA, the award of grants pursuant to this RFA is contingent upon receipt of applications of high scientific merit and upon the availability of funds. RESEARCH OBJECTIVES The goal of this RFA is to stimulate comprehensive multidisciplinary research into the natural history of menopause and the role of the perimenopausal transition on woman's aging and subsequent susceptibility to disease. Because this initiative aims to generate epidemiologic studies in premenopausal women of the chronology and characteristics of the perimenopausal transition per se, and not to launch clinical intervention trials of hormone or other therapies, applications focused on testing treatment strategies will be considered not responsive to this RFA. Awardees are expected to recruit a cohort of premenopausal women to characterize the causes and consequences of the pre- to postmenopausal transition. Planned research should: o identify and utilize appropriate markers of ovarian aging (e.g., FSH, LH, or, preferably, other state-of-the art measures) and relate these markers to alterations in menstrual cycle characteristics as women approach and traverse menopause o elucidate factors that differentiate (1) symptomatic from asymptomatic women and (2) women most susceptible to long-term pathophysiological consequences of ovarian hormone deficiency from those who are protected; o collect and analyze data on demographics, health and social characteristics, race/ethnicity, reproductive history, pre-existing illness, physical activity and health practices. After addressing these general requirements, proposed studies should focus on a specific system or function(s) affected by, or of relevance to, menopause. Examples of topic areas of interest are in the RFA that must be requested from the program contacts listed under INQUIRIES. STUDY POPULATIONS SPECIAL INSTRUCTIONS FOR INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDIES NIH policy is that applicants for NIH clinical research grants and cooperative agreements are required to give special attention to the inclusion of minorities and women in study populations. For the purpose of this RFA, investigations are limited to studies of menopause, an event which occurs only in women. If minorities are not included in the study populations, 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 strongly encouraged to submit, by October 15, 1993, a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, the identities of other key personnel and participating institutions, and the number and title of the RFA in response to which the application may be submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information allows NIH 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. Sherry Sherman at the address listed under INQUIRIES. APPLICATION PROCEDURES Applications are to be submitted on the PHS 398 (rev. 9/91) application form. 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 program administrators named below. The RFA label contained in the application kit must be affixed at the bottom of the face page of the application. Failure to use this label could delay processing of the application. In addition, the RFA title, number and type of application: "Clinical Site," "Coordinating Center," or "Central Laboratory" must be typed on line 2a of the face page of the application form and the YES box must be checked. Submit a signed, typewritten original of the application, including the Checklist, and three signed, exact photocopies, in one package to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** Two copies of the application with appendices must also be sent to: Chief, Scientific Review Office National Institute on Aging Gateway Building, Suite 2C212 Bethesda, MD 20892 The deadline for receipt of applications is November 29, 1993. Materials will not be accepted after this date. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed by NIH staff for completeness and responsiveness. Incomplete and nonresponsive applications will be returned to the applicant without further consideration. Those applications that are complete and responsive will be evaluated for scientific/technical merit by an appropriate peer review group convened by the NIA. INQUIRIES The letter of intent and requests for the RFA may be addressed to: Dr. Sherry Sherman Geriatrics Program National Institute on Aging Gateway Building, Room 3E327 Bethesda, MD 20892 Telephone: (301) 496-1033 Programmatic inquiries related to social and behavioral research on menopause or of relevance to the National Institute of Nursing Research should be directed to: Dr. Marcia Ory Behavioral and Social Research Program National Institute on Aging Gateway Building, Room 2C234 Bethesda, MD 20892 Telephone: (301) 496-3136 Dr. Sharlene Weiss National Institute of Nursing Research Westwood Building, Room 757 Bethesda, MD 20894 Telephone: (301) 594-7496 Direct inquiries regarding fiscal matters to: Ms. Joanne Colbert Grants and Contracts Management Office National Institute on Aging Gateway Building, Room 2N212 Bethesda, MD 20892 Telephone: (301) 496-1472 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.866 (Aging Research). Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations, 42 CFR Part 52 and 45 CFR Parts 74 and 92. This program is not subject to the intergovernmental review requirements of Executive Order 12372, or to the Health Systems Agency review. $$R3 END ************************************************************ $$R4 BEGIN CA-93-038 FULL-TEXT ************************************** IDENTIFICATION AND EVALUATION OF TISSUE MARKERS FOR PATHOLOGICAL CLASSIFICATION OF HUMAN GLIOMAS NIH GUIDE, Volume 22, Number 32, September 3, 1993 RFA AVAILABLE: CA-93-038 P.T. 34; K.W. 0760003, 0715035 National Cancer Institute Letter of Intent Receipt Date: October 6, 1993 Application Receipt Date: December 7, 1993 THIS IS A NOTICE OF AVAILABILITY OF A REQUEST FOR APPLICATIONS (RFA); IT IS ONLY AN ABSTRACT OF THE RFA. POTENTIAL APPLICANTS MUST REQUEST THE COMPLETE RFA, WHICH CONTAINS ESSENTIAL INFORMATION FOR THE PREPARATION OF AN APPLICATION, FROM THE CONTACT LISTED IN "INQUIRIES," BELOW. FAILURE TO FOLLOW THE INSTRUCTIONS IN THE COMPLETE RFA MAY RESULT IN AN INCOMPLETE APPLICATION, WHICH WILL BE RETURNED TO THE APPLICANT WITHOUT REVIEW. PURPOSE The Cancer Diagnosis Branch of the Division of Cancer Biology, Diagnosis and Centers, National Cancer Institute (NCI) invites applications for cooperative agreements from institutions to identify and evaluate tissue markers for improving the pathological classification of human gliomas. Precise pathologic diagnosis and/or classification of gliomas is often difficult. Since the incidence and mortality of brain tumors are increasing, and gliomas constitute the most common class of these important tumors, improved classification would be beneficial to clinicians making decisions about patient management. For the purposes of this RFA, gliomas are meant to include astrocytomas, mixed astrocytomas/oligodendrogliomas, and oligodendrogliomas. The purpose of the proposed awards is to extend and expand the ongoing inter-institutional studies the Glioma Marker Network to increase the availability of patient resources and enhance the technical capabilities of the Network to efficiently test clinical correlative hypotheses. The Network will carry out collaborative studies designed to continue the evaluation of a variety of glioma markers, identify additional promising markers, and correlate the markers with clinical parameters. The cooperative studies funded by this RFA will optimize the use of rare tissue resources. This RFA will also provide funding for coordinated management and statistical analyses of data collected by Network investigators. These studies will take advantage of the synergy resulting from collaborations among neuropathologists, clinicians, cancer biologists, and statisticians. 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, Identification and Evaluation of Tissue Markers for Pathological Classification of Human Gliomas, is related to the priority area of cancer. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202/783-3238). ELIGIBILITY REQUIREMENTS Applicant organizations must be located in the United States, Canada, or Mexico. Non-profit organizations and institutions, and government agencies are eligible to apply. For-profit organizations are also eligible. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT The administrative and funding mechanism to be used to support the Glioma Network is the cooperative agreement (U01), an assistance mechanism in which substantial NCI program staff involvement with the recipient during performance of the planned activities is anticipated. Under the cooperative agreement, the NCI purpose is to support and/or stimulate the recipient's activities by collaborating and otherwise working jointly with the award recipient in a partner role. The awardees retain full responsibility for the planning and direction of the projects within the guidelines of the RFA and for performance of the proposed studies. There is no intent, real or implied, for NCI staff to direct awardee activities or limit the freedom of the funded investigators. The anticipated average amount of direct costs will be $125,000. This RFA is a one-time solicitation. However, if it is determined that there is sufficient continuing program need, the NCI will invite recipients of awards under this RFA to submit competitive continuation cooperative agreement applications for review according to the procedures described in REVIEW CONSIDERATIONS. FUNDS AVAILABLE The NCI anticipates making four to six new and/or competing awards for project periods up to four years and anticipates a total of $1,200,000 will be set aside for the initial year's funding. Because of the nature and scope of the research proposed in response to this RFA may vary, it is anticipated that the sizes of awards will vary also. Funding in response to this RFA is dependent on the receipt of a sufficient number of applications of high scientific merit. Although the program is provided for in the financial plans of the NCI, the award of cooperative agreements pursuant to this RFA is contingent on the availability of funds appropriated for fiscal year 1994. RESEARCH OBJECTIVES The objective of this RFA is to invite applications for cooperative agreements to extend and expand the Glioma Marker Network currently carrying out studies to identify and evaluate molecular markers for improving the pathological classification of human gliomas. Applicants should propose studies with hypotheses designed to evaluate tumor markers and to correlate markers with clinical parameters. Applications should discuss application of molecular genetic, cytogenetic, immunohistological, and/or biochemical techniques to studies of glial tumor markers that will be useful in tumor classification. Collaborations among neuropathologists, clinicians, cancer biologists, and statisticians are critical to these types of studies and are specifically encouraged. Applicants should address approaches to establishing correlations between tumor markers and clinical parameters. The hypotheses to be tested by the proposed studies should be clearly stated and the rationale for the study design and experimental techniques selected thoroughly discussed. Sufficient preliminary data should be provided to support the feasibility of the proposed studies. Applications should include a discussion of the statistical issues related to study design and data analysis. A goal of the RFA is to promote collaborative studies to optimize the use of rare tissue resources. The cooperative agreement mechanism was chosen to facilitate the coordinated management of tissue resources with associated clinical data and the statistical analyses of data generated in collaborative studies. Applicants should discuss their anticipated contribution to collaborative studies carried out by the Network. 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 and minorities are not included in the study populations for clinical studies, a specific justification for this exclusion must be provided. Applications without such documentation will not be accepted for review. LETTER OF INTENT Prospective applicants are ask to submit, by October 6, 1993, a letter of intent that includes a descriptive title of the proposed project, the name, address, and telephone number of the Principal Investigator, the names of key personnel, any collaborating institutions, and the number and title of the RFA in response to which the application may be submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, it is requested in order to provide an indication of the number and scope of the applications to be reviewed. This information allows NCI staff to estimate potential workload and to avoid conflict of interest in the review. The letter of intent is to be sent to Dr. James W. Jacobson at the address listed under INQUIRIES. APPLICATION PROCEDURES The grant application form PHS 398 (rev. 9/91) is to be used for the cooperative agreement application. These forms are available from most offices of sponsored research; from the Office of Grants Information, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892-4500, telephone 301/584-7248; and from the NCI Program Director named below. The RFA label available in the application form PHS 398 (rev. 9/91) must be affixed to the bottom of the face page. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time to be reviewed. The RFA number and title must be typed on line 2a of the face page of the application form as well. Applications must be received by December 7, 1993. Applications received after this date will be returned. REVIEW CONSIDERATIONS Review Procedures Upon receipt, applications will be reviewed (initially) by the Division of Research Grants for completeness. Incomplete applications will be returned to the applicant without further consideration. Evaluation for responsiveness to the RFA is an NCI program staff function. An application judged non-responsive will be returned by the NCI, but may be resubmitted as an investigator-initiated regular research grant (R01) at the next receipt date. The application would require modification in accordance with the R01 guidelines. The new application would not be considered an application for a cooperative agreement, nor would it be considered a response to this RFA. If the number of applications is large compared to the number of awards to be made, the NCI may conduct a preliminary scientific peer review (triage) to determine their relative competitiveness by an NCI peer review group. The NIH will remove from further competition those applications that are judged to be noncompetitive and notify the applicant Principal Investigator and institutional official. Those applications judged to be competitive and responsive will be evaluated for technical merit, according to the review criteria stated in the RFA, by an appropriate peer review group convened by the Division of Extramural Activities, NCI. The second level of review will be by the National Cancer Advisory Board. AWARD CRITERIA The anticipated date of award is September 1, 1994. Awards will be based on the peer reviewed priority score and programmatic priorities. INQUIRIES Written and telephone inquiries concerning the objectives and scope of this RFA, inquiries about whether or not specific activities would be responsive, and requests for the RFA are encouraged and may be directed to: James W. Jacobson, Ph.D. Division of Cancer Biology, Diagnosis, and Centers National Cancer Institute Executive Plaza North, Room 513 6130 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-1591 FAX: (301) 402-1037 Direct inquires regarding fiscal and administrative matters to: Robert E. Hawkins, Jr. Grants Administration Branch National Cancer Institute Executive Plaza South, Room 243 6120 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-7800 Ext. 13 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.394, Cancer Detection and Diagnostic Research. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is no subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$R4 END ************************************************************ $$R5 BEGIN AI-93-019 FULL-TEXT ************************************** NATIONAL COOPERATIVE DRUG DISCOVERY GROUPS FOR THE TREATMENT OF OPPORTUNISTIC INFECTIONS ASSOCIATED WITH ACQUIRED IMMUNODEFICIENCY SYNDROME (NCDDG-OI): TUBERCULOSIS NIH GUIDE, Volume 22, Number 32, September 3, 1993 RFA AVAILABLE: AI-93-019 P.T. 34; K.W. 0715165, 0755060, 0715008 National Institute of Allergy and Infectious Diseases Letter of Intent Receipt Date: November 15, 1993 Application Receipt Date: January 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 It is the purpose of this RFA to invite Cooperative Agreement applications aimed at the discovery of new, more effective, selective, and diverse therapeutic agents to treat and prevent infection caused by Mycobacterium tuberculosis. Applications that include research projects or participation from the private sector (e.g., pharmaceutical, chemical, or biotechnological companies) are encouraged. Research in the following areas is needed to provide the foundation for improvements in therapeutics for tuberculosis, particularly in the setting of HIV infection: unique metabolic activities for drug targeting; biochemistry and molecular mechanisms of M. tuberculosis-host interactions; inhibitors of enzymatic and regulatory functions, and of biochemical pathways; mechanisms of overcoming drug resistance; and discovery and biochemical characterization of promising natural products or synthetic chemical compounds. These activities should be directed toward selective drug or strategy targeting that inhibits M. tuberculosis with minimal toxicity for the host. It is anticipated that multidisciplinary approaches by scientists from a combination of academic, non-profit research, and commercial organizations, with the assistance of NIAID, will be necessary to effectively accelerate the drug discovery process for treatment of tuberculosis. 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, National Cooperative Drug Discovery Groups for the Treatment of Opportunistic Infections Associated with Acquired Immunodeficiency Syndrome (NCDDG-OI) Including Tuberculosis, is related to the priority area of HIV infection. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325, (telephone (202) 783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic for-profit and non-profit organizations, public and private organizations, such as universities, colleges, hospitals, laboratories, units of State or local governments, and eligible agencies of the Federal government. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT Awards will be made as Cooperative Agreements (U01s). The Cooperative Agreement funding mechanism differs from the traditional research grant in that the Government component (NIAID) awarding the Cooperative Agreement anticipates substantial programmatic involvement during performance. The nature of NIAID staff participation is described in the RFA. However, it is the Principal Investigator who defines his/her objectives in accord with his/her interests and perceptions of approaches to the treatment of AIDS-associated opportunistic infections. The applicant institution and the Principal Investigator will be responsible for the Group's application. Awards will be made to the applicant institution on behalf of the group as a whole and not to individual research projects within the Group. Respondents to this RFA may include new applications for a maximum period of four years support and competitive supplements to currently funded NCDDG-OI Groups for research focused on M. tuberculosis. This RFA is a one-time solicitation. Plans for continued support in this area are indefinite at this time. If by the end of the third year of the award, the NIAID has not announced its intent to re-issue the RFA, incumbents should contact NIAID program staff and consider submitting investigator-initiated (R01) applications which will compete with all investigator-initiated applications and be reviewed according to the customary NIH peer review procedures. FUNDS AVAILABLE It is estimated that no more than one or possibly two new Groups will be funded for drug discovery against M. tuberculosis as a result of this RFA. A maximum of $3.4 million (including direct and indirect costs) will be available over the four year period, including approximately $0.8 million (direct and indirect costs) during the first year. Awards and level of support are dependent on the receipt of a sufficient number of applications of high scientific merit. Because the nature and scope of the research proposed in response to this RFA may vary, it is anticipated that the size of awards will vary also. Applications with budgets in excess of $800,000 total (direct and indirect) costs for the first year will be returned without review. Budget requests must be adequately justified and commensurate with the complexity of the project. Although this program is provided for in the financial plans of the NIAID, awards pursuant to this RFA are contingent upon the availability of funds for this purpose. RESEARCH OBJECTIVES It is the intention of this RFA to encourage investigators to collaborate in new, multidisciplinary approaches to drug discovery against human tuberculosis. It is recognized that the ultimate objective of selective therapy against microbial infection requires a solid knowledge base of the biology, composition, physiology, molecular biology, and host interactions of infectious agents. The objective of this RFA is to stimulate original and innovative research of sound scientific rationale, requiring comprehensive team effort, that is likely to result in the discovery of agents effective against M. tuberculosis. Examples of research projects considered responsive to this RFA may include, but are not necessarily restricted to, the following: o Identification and development of drug evaluation assays for molecular targets, with selectivity for M. tuberculosis, such as recombination repair mechanisms, elongation factors, cell wall assembly, and others with potential for mycobactericidal consequences. o Identification of bacterial virulence determinants and development of drug evaluation assays for essential mycobacterial gene products, particularly biochemical activities expressed in vivo and associated with pathogenicity. o In vitro and in vivo testing of new chemical entities with potential for mycobactericidal activity within a framework of logical plans that examine structure-activity relationships and potential toxicities. o Development, validation, and implementation of drug evaluation systems capable of predicting cidal and sterilizing activity of new agents, or combinations of agents, against M. tuberculosis. o Studies on the effects of drugs on slow-growing M. tuberculosis, such as those found in granulomatous tubercular lesions, identification of drugs with extended lengths of biological activity, and development of methods to assess post-antibiotic effect on M. tuberculosis. o Development, validation, and implementation of improved models for in vivo drug evaluations, such as immunosuppressed animals, or mice with disrupted interferon-gamma genes or other immune effector genes. o Development and evaluation of biological entities, such as recombinant mycobacteriophage as drug or suicide gene delivery vehicles, and evaluation of these for efficacy and safety. o Identification and development of systems to predict emergence of resistance to established and newly identified antibiotics, and to evaluate new therapies for their ability to prevent or overcome resistance. SPECIAL REQUIREMENTS The applicant institution will provide a Central Operations Office for the Group, will be responsible for the performance of the entire Group, and will be accountable for the funds awarded. The participation of the Government through the NIAID extramural staff is intended to facilitate a concerted effort by all members of the Group by providing appropriate scientific input, by accessing appropriate databases, and by providing ancillary testing available under other mechanisms. The interaction of academic and non-profit research institutions with commercial organizations and the Government is strongly encouraged and is expected to favor expeditious discovery and development of agents active against human tuberculosis. An NCDDG-OI must be composed of two independent laboratory research projects and may consist of scientists from a combination of academic, non-profit research, and commercial organizations. For the purpose of this RFA, two projects within a single company or academic department will not be considered independent. This limitation on the number of independent projects from the same academic department or private sector company is intended to increase the diversity and multi-disciplinary expertise available to the Group. Each NCDDG-OI will be assembled by the Principal Investigator to form a multidisciplinary consortium that acts as a unit and represents the various skills needed to successfully design, synthesize, and evaluate, at the preclinical level, potential therapeutic agents useful in the treatment of opportunistic infections in AIDS patients. While it is anticipated that complete drug discovery and development of new therapies will not occur within the project period for all Groups, a rationale for the most likely utility of discoveries made within the NCDDG-OI must be included. Specifically excluded from the Group's activities are studies related to clinical evaluations. Projects or cores with proposed animal model development must be essential to targeted drug discovery and required to attain the objectives of the Group. Random or large scale screening of compounds will not be supported under this RFA. Each applicant Group must provide a detailed description of the approach to be used for obtaining patent coverage for discoveries and for licensing where appropriate, in particular where the invention may involve investigators from more than one institution. In addition, each Group must provide a detailed description of the procedures to be followed for the resolution of legal problems which may develop. The NIAID will not be a partner in any patents or royalties ensuing from this research. STUDY POPULATIONS SPECIAL INSTRUCTIONS FOR INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDIES For projects involving clinical research, NIH requires applicants to give special attention to the inclusion of minorities and women in study populations. If women and minorities are not included in the study populations for clinical studies, a specific justification for this exclusion must be provided. Applications without such documentation will not be accepted for review. LETTER OF INTENT Prospective applicants are asked to submit, by November 15, 1993, a letter of intent that includes a descriptive title of the proposed research, brief description of the proposed research, the name, address (including institution), and telephone number of the Principal Investigator, the identity of project leaders and titles of their projects, other key personnel and their institutions, and the number and title of this RFA. Although a letter of intent is not required, is not binding, and does not enter into the review of the application, the information that it contains allows NIAID to estimate the potential workload for reviewers and to avoid possible conflict of interest in the review progress. The letter of intent is to be sent to Dr. Dianne Tingley at the address listed under INQUIRIES. APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 9/91) is to be used in applying for these grants. This form is available at most institutional offices of sponsored research and from the Office of Grants Information, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone 301-594-7248. Additional instructions for preparation of applications are provided in the RFA. Applications not received by January 21, 1994, will be considered non-responsive and returned to the applicant without review. REVIEW CONSIDERATIONS Applications will be reviewed by the Division of Research Grants (DRG) for completeness and by NIAID staff to determine responsiveness to this RFA. Incomplete and non- responsive applications will be returned to the applicant without further consideration or review. Those applications that are complete and responsive may be subjected to triage by an NIAID peer review group to determine their scientific merit relative to the other applications received in response to this RFA. The NIAID will remove from further competition those applications judged by a triage peer review group to be noncompetitive for award and will notify the applicant and the institutional business official. Those applications judged to be competitive for award will be further reviewed for scientific and technical merit by an appropriate NIAID review committee. Detailed review criteria are provided in the RFA. A second level of review will be provided by the NIAID Council. AWARD CRITERIA One or two awards are anticipated under this RFA. The primary criterion for award is the scientific and technical merit of the application as judged by peer reviewers and reflected in the priority score. Additional award criteria are the availability of funds, receipt of a sufficient number of scientifically meritorious applications that are responsive to this RFA, and overall programmatic relevance and priority. INQUIRIES Written and telephone requests for the RFA and the opportunity to clarify issues or questions from potential applicants are welcome. Requests for the RFA and inquiries regarding programmatic or scientific issues may be directed to: Barbara Laughon, Ph.D. Division of AIDS National Institute of Allergy and Infectious Diseases Solar Building, Room 2C35 6003 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 402-2304 FAX: (301) 402-3211 Inquiries pertaining to review of applications may be directed to: Dianne Tingley, Ph.D. Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4C16 6003 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-0818 FAX: (301) 402-2638 Inquiries regarding fiscal matters may be directed to: Ms. Jane Unsworth Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4B22 6003 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-7075 FAX: (301) 480-3780 Schedule Letter of Intent Receipt Date: November 15, 1993 Application Receipt Date: January 21, 1994 Scientific Review Date: March 1994 Advisory Council Date: June 1994 Anticipated Award Date: July/August 1994 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance, 93.856 - Microbiology and Infectious Diseases Research and 93.855 - Immunology, Allergic and Immunological Diseases Research. Grants are awarded under the authority of the Public Health Service Act, Section 301 (42 USC 241) and administered under the PHS grants policies and Federal Regulations, most specifically at 42 CFR Part 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of the Executive Order 12372 or Health Systems Agency Review. $$R5 END ************************************************************ ONGOING PROGRAM ANNOUNCEMENTS $$P1 BEGIN PA-93-106 ************************************************ DRUG ABUSE TREATMENT FOR WOMEN OF CHILDBEARING AGE AND THEIR CHILDREN NIH GUIDE, Volume 22, Number 32, September 3, 1993 PA NUMBER: PA-93-106 P.T. 34; K.W. 0404009 National Institute on Drug Abuse PURPOSE The purpose of this program announcement is to stimulate research to improve the effectiveness of drug abuse treatment for women of childbearing age and their offspring. 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, Drug Abuse Treatment for Women of Childbearing Age and Their Children, is related to the priority area of health promotion/alcohol and other drugs. A copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0 or Summary Report: Stock No. 017-001-00473-1) may be obtained through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign for-profit and non-profit, public and private organizations such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal Government. Women and minority investigators are encouraged to apply. MECHANISM OF SUPPORT This program announcement will use the National Institutes of Health (NIH) individual research grant (R01). Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. Support will be provided for a period of up to five years (renewable for subsequent periods) subject to From owner-sci-resources@net.bio.net Thu Sep 02 23:00:00 1993 Path: biosci!net.bio.net From: kristoff@net.bio.net (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 22, no. 32, pt. 2, 3 September 1993 Message-ID: Date: 3 Sep 93 01:42:17 GMT Sender: kristoff@net.bio.net Lines: 1158 Approved: biosci-moderator@net.bio.net $$XID NIHGUIDE 19930903 V22N32 P2O2 ************************************ continued availability of funds and progress achieved. In fiscal year 1994, it is anticipated that $5 million will be available from the National Institute on Drug Abuse (NIDA) to fund approximately eight to nine grants under this announcement. Research projects requiring substantial programmatic support, such as the establishment of new comprehensive services or the addition of a substantial component to an existing program, are encouraged under this announcement. If required in support of research objectives, funds may be expended on drug abuse treatment costs, rental and operation of facilities, approved renovation and modification of facilities (subject to limits and conditions specified in the PHS grants policy), and other costs normally allowable under existing PHS grants policy. Funds may not be used for new construction or to replace existing treatment funding. RESEARCH OBJECTIVES Summary Research studies are sought to investigate effective and cost-effective drug abuse treatment for women and their children. Research is sought to: (1) improve outcomes of drug abuse treatment for women of childbearing age and their young children; (2) improve treatment recruitment, retention, and compliance; (3) improve interventions for women with co-existing mental disorders and to reduce family and social dysfunction; (4) improve the drug abuse treatment environment, delivery of services, and service linkages in order to facilitate recovery from drug abuse; and (5) understand and remove barriers to drug abuse treatment for women, particularly for pregnant women and women with children. Background This announcement builds on a NIDA program of research established with Requests for Applications 89-03 (Research Demonstration Grants on Drug Treatment ... For Pregnant Women) and 90-12 (Research Demonstration Applications on Drug Abuse Treatment for Women of Child-Bearing Age and their Offspring). Both new applicants and those investigators previously funded under the above-cited programs are eligible. The treatment needs of women often differ from those of men. Women who abuse drugs face a variety of barriers to treatment entry, engagement in treatment, and long-term recovery. Barriers to entry include a lack of economic resources, referral networks, women-oriented services, and conflicting child-related responsibilities. Engagement in treatment and consequent long-term recovery are hampered by the primarily male orientation of traditional models of drug treatment and aftercare; by women-specific problems such as low self-esteem, low employability, and a lack of appropriate services to treat social, psychiatric, and medical disorders. Women who are addicted are also more likely to engage in high-risk sexual behavior, such as sex in exchange for crack, that increases the risk of becoming pregnant as well as the risk of contracting infectious diseases such as HIV. Maternal drug abuse may complicate delivery of offspring and compromise the newborn child's chance of normal mental and physical development. Research on improved therapeutic programs and supportive services is needed to address drug abuse treatment and medical treatment needs of the mother and child before and after delivery. Research presently underway suggests a number of areas in which further investigation is needed. Applications focused on culturally appropriate treatment strategies and program models for women and children of special populations (i.e., programs designed to serve unique needs of specific racial/ethnic minorities), women in high-risk groups (e.g., engaged in prostitution), or under criminal justice supervision are of particular interest. Additional study is needed on methodological issues such as research design and the measurement of behavior change. Research may focus on outreach strategies to improve entry of women into drug abuse treatment, on removing barriers to treatment, and on making such treatment more attractive (e.g., by providing a range of health services, by adding child care to programs and/or allowing mothers to have their children live with them in residential treatment). Studies suggest that women may benefit from services such as assertiveness training, counseling to build self-esteem, social skills enhancements, social network interventions, treatment for depression, and counseling in family planning and birth control. Case management approaches to coordinate services and maintain the integrity of treatment plans can improve treatment outcomes. Other useful components include psychoeducational strategies and relapse prevention. Program Description Research is sought to improve the outcomes of treatment for women of childbearing age, including treatment for mothers and their young children; improve recruitment, retention, and compliance with treatment; investigate strategies to deal with comorbidity and family/social dysfunction; improve the drug abuse treatment program environment and the delivery of treatment services in order to facilitate recovery from drug abuse, and to investigate the impact of barriers to entry and engagement in drug abuse treatment that exist for women, particularly pregnant women and women with young children. Applicants are advised to review existing information relevant to the treatment of drug abusing women and their children, including pregnant and postpartum women. The NIDA will support studies to investigate the short- and long-term effectiveness of comprehensive drug abuse treatment for women and their young children based in a variety of settings (e.g., hospitals, outpatient clinics, residential facilities, home-based care). Areas of research interest include research to: o Improve treatment recruitment, retention, compliance, and outcomes for women, with and without children, and their children. o Evaluate the effectiveness of psychosocial interventions developed for women, or gender-specific modifications of existing therapeutic approaches. o Investigate the effectiveness and cost-effectiveness of drug abuse treatment, aftercare, and ancillary services for women, including pregnant women and women with young children, designed to address medical, mental health, social, vocational, educational, family, and related problem areas. o Improve linkages and reduce overlap between service providers and to enhance ancillary service support structures. o Investigate the roles of comorbidity, family/social dysfunction, marital discord, criminal behavior, low employability, homelessness, and other factors that predict relapse to illicit drug use, and identification of effective treatment strategies for dealing with these. o Improve treatment program environments for women, including overcoming barriers to implementation of effective treatment programs and improving treatment service delivery to help engagement in treatment and long-term recovery. o Reduce the impact of barriers to drug abuse treatment that exist for women, particularly for pregnant women or women with young children. The importance of a sound research plan and qualified research staff cannot be over-emphasized. It is recommended that investigators use the most rigorous methodology consistent with the purposes of the research. All applications should address issues of project feasibility and collaborative arrangements, study design, sampling procedures, implementation of the intervention, instrumentation and measurement, data collection, quality control, tracking of clients, followup, and data analysis, as appropriate. Investigators are encouraged to offer HIV testing and counseling in accordance with current guidelines to subjects identified during the course of the research as being at risk for HIV acquisition or transmission. In high-risk populations, investigators are encouraged to assess the effects of new interventions on the acquisition and transmission of infectious diseases, including HIV. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS Applications for clinical research grants and cooperative agreements that involve human subjects are required to include minorities and both genders in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder, or condition under study; special emphasis should be placed on the need for inclusion of minorities in studies of diseases, disorders, and conditions which disproportionately affect them. This policy applies to all research involving human subjects and human materials, and applies to males and females of all ages. If minorities are excluded or are inadequately represented in this research, particularly in proposed population-based studies, a clear compelling rationale for exclusion or inadequate representation should be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group, together with a rationale for its choice. In addition, racial/ethnic issues should be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., American Indians or Alaskan Natives, Asians or Pacific Islanders, Blacks, Hispanics). Investigators must provide the rationale for studies on single minority population groups. Applications for support of research involving human subjects must employ a study design with minority and/or gender representation (by age distribution, risk factors, incidence/prevalence, etc.) appropriate to the scientific objectives of the research. It is not an automatic requirement for the study design to provide statistical power to answer the questions posed for men and women and racial/ethnic groups separately; however, whenever there are scientific reasons to anticipate differences between men and women, and racial/ethnic groups, with regard to the hypothesis under investigation, applicants should include an evaluation of these gender and minority group differences in the proposed study. If adequate inclusion of one gender and/or minorities is impossible or inappropriate with respect to the purpose of the only study population available, there is a disproportionate representation of one gender or minority/majority group, the rationale for the study population must be well explained and justified. The NIH funding components will not make awards of grants, cooperative agreements or contracts that do not comply with this policy. For research awards which are covered by this policy, awardees will report annually on enrollment of women and men, and on the race and ethnicity of subjects. 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. Applicants who are currently supported under NIDA research demonstration program (R18) will be considered competing continuations (type 2) R01s and may submit their applications for the competing continuation receipt dates of November 1, March 1, or July 1. 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 Grant Information, Division of Research Grants, National Institutes of Health, Westwood Building, Room 240, Bethesda, MD 20892, telephone 301/594-7248. The title and number of the announcement must be typed in Item 2a on the face page of the application. The completed original and five permanent, legible copies of the PHS 398 form must be delivered to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** REVIEW PROCEDURES The Division of Research Grants, NIH, serves as a central point for receipt of applications for most discretionary DHHS grant programs. Applications received under this announcement will be assigned to an initial review group (IRG) in accordance with established PHS referral guidelines. The IRGs, consisting primarily of non-Federal scientific and technical experts, will review the applications for scientific and technical merit in accordance with the standard NIH peer review procedures. Notification of the review recommendations will be sent to the applicant after the initial review. Applications will receive a second-level review by an appropriate Advisory Council, whose review may be based on policy considerations as well as scientific merit. Only applications recommended for further consideration by the Council may be considered for funding. AWARD CRITERIA Applications recommended for further consideration by an appropriate Advisory Council will be considered for funding on the basis of overall scientific, clinical and technical merit of the proposal as determined by peer review, appropriateness of budget estimates, program needs and balance, policy considerations, adequacy of provisions for the protection of human subjects, and availability of funds. INQUIRIES Written and telephone inquiries are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Frank Tims, Ph.D. or Jack Blaine, M.D. Division of Clinical Research National Institute on Drug Abuse 5600 Fishers Lane, Room 10A-30 Rockville, MD 20857 Telephone: (301) 443-4060 Direct inquiries regarding fiscal matters to: Chief, Grants Management Branch National Institute on Drug Abuse 5600 Fishers Lane, Room 8A-54 Rockville, MD 20857 Telephone: (301) 443-6710 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.279. Awards are made under authorization of the Public Health Service Act, Section 301, and administered under PHS policies and Federal Regulations at Title 42 CFR 52 "Grants for Research Projects", Title 45 CFR Part 74 & 92, "Administration of Grants" and 45 CFR Part 46, "Protection of Human Subjects". Title 42 CFR Part 2, "Confidentiality of Alcohol and Drug Abuse Patient Records" may also be applicable to these awards. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$P1 END ************************************************************ $$P2 BEGIN PA-93-107 ************************************************ MEDICAL IMAGING DATABASES NIH GUIDE, Volume 22, Number 32, September 3, 1993 PA NUMBER: PA-93-107 P.T. 34; K.W. 0735015, 1004008, 0706030 National Cancer Institute National Institute of Neurological Disorders and Stroke National Library of Medicine PURPOSE The National Cancer Institute (NCI) through the Diagnostic Imaging Research Branch (DIRB) of the Radiation Research Program, the National Library of Medicine (NLM), and the Division of Stroke and Trauma, National Institute of Neurological Disorders and Stroke (NINDS) are seeking grant applications that will address new medical imaging database designs that focus on non-textual paradigms. The goal of medical imaging databases is to provide a means for organizing a large mass of heterogeneous, changing, pictorial, and symbolic data into a structured environment that can be synthesized, classified, and presented in an organized efficient manner to facilitate optimal decision making in a health care environment. A properly organized imaging database can compensate for human memory limitations and provide an environment for improved patient care, research, and education. Development of an effective and useful medical imaging database must take place in an interdisciplinary environment, using the medical knowledge from radiologists, radiation and medical oncologists, neurologists and other specialties in collaboration with the database research community and the imaging expertise of the computer and Picture Archiving and Communications System (PACS) sciences. 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, Medical Imaging Databases, is related to the priority area of cancer. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by foreign and domestic, for-profit and non-profit, public and private organizations, such as universities, colleges, hospitals, laboratories, units of State and local governments and eligible agencies of the Federal government. Applications from minority individuals and women are encouraged. Foreign institutions are not eligible for First Independent Research Support and Transition Awards (R29). MECHANISM OF SUPPORT Applications considered appropriate responses to this announcement are the traditional research project grants (R01) and the First Independent Research Support and Transition (FIRST) award (R29). Although no funds are specifically set aside for funding grants submitted in response to this program announcement, the Radiation Research Program regards research in this area as high priority. Awards will be administered in accordance with PHS grants policy as described in the PHS Grants Policy Statement, DHHS, Publication No. (OASH) 90-50,000 revised October 1, 1990. Because of the nature and scope of the research proposed in response to this Program Announcement may vary, it is anticipated that the size of an award will vary also. RESEARCH OBJECTIVES Background Today, medical imaging database management and searches are largely performed by skilled human investigators. Although considerable progress has been achieved in recent years in the development of new strategies for rapid and efficient textual retrievals from text databases, very little effort has gone into the development of techniques for non-textual searches. Similarly, since medical images are poorly incorporated into the overall collection of data on cancer patients, there is very little attempt to cohesively gather information from images of different patients for correlation with other critical parameters of their disease. The wealth of information that is potentially accessible, but not available through any currently available technology, would contribute to new clinical knowledge about disease progression, prognostic indicators for outcome assessment in patients scheduled for treatment, and the ability to assess outcome in patients who have undergone treatment. Research Goals and Scope Although much research has already been done in the development of "next generation databases," more research is needed to address the complex issues of developing the tools for medical imaging databases in a clinical environment. The research goals of this Program Announcement include the following: 1. Development of a descriptive language for medical images that describes image features that define the oncologic content of images and develops a standardized vocabulary for the geometric description of the images; 2. Development and implementation of advanced query languages that use pictorial and symbolic-based object-oriented data modeling to support complex non-textual queries; 3. Development of new database models that incorporate the following features: a. index an imaging database using image features; b. support spatial relations for queries that can detect change, such as by shape and size, but are robust enough to adjust for deformations; c. develop object-oriented solutions that can handle levels of uncertainty in identifying objects with fuzzy boundaries; d. support temporal relations that reflect both the history of the patient, as is currently best known, as well as what was in the database at any given point in time; e. allow for the development of ad hoc and customized schema that evolve as the user gathers new data and knowledge by navigating through or perusing the database; f. solve integrity problems, such as resolving a situation when two databases contain contradictory information; g. carry out search and analysis processes that are both accurate and timely and allow for the interaction of a human investigator. 5. Development of tools that allow for the cohesive unification of data and information from hospital information systems, radiological information systems, image archives and imaging machines into one system for incorporation into the electronic medical record for incorporation into the electronic medical record. Research and implementations of database systems must proceed in interdisciplinary environments that successfully combine the expertise and knowledge from the medical community with that of the database and computer science disciplines. APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 9/91) is to be used in applying for this program announcement and will be accepted at the standard application deadlines as indicated in the application kit. These forms are available at most institutional offices of sponsored research and from the Office of Grants Information, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, 5333 Westbard Avenue, Bethesda, MD 20892, telephone (301-594-7248). The PA number and title must be typed on line 2a of the face page of the application form. The completed original application and five legible copies must be sent to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** All PHS and NIH grants policies will apply to applications received in response to this announcement. FIRST (R29) award applications must include at least three sealed letters of reference attached to the face page of the original application. FIRST (R29) award applications submitted without the required number of reference letters will be considered incomplete and will be returned without review. 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, 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. 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 the research areas of this announcement INQUIRIES Written and telephone inquiries concerning the objectives and scope of this PA and inquiries about whether or not specific proposed research would be responsive are encouraged and may be directed to: Dr. Sandra Zink Radiation Research Program National Cancer Institute Executive Plaza North, Suite 800 Bethesda, MD 20892 Telephone: (301) 496-9360 Dr. George N. Eaves Division of Stroke and Trauma National Institute of Neurological Disorders and Stroke Federal Building, Room 8A-13 Bethesda MD 20892-9905 Telephone: (301) 496-4226 Dr. Roger Dahlen Extramural Programs National Library of Medicine Building 38, Room 5S522 Bethesda, MD 20892 Telephone: (301) 496-4221 Direct inquiries regarding fiscal matters to: Barbara A. Fisher Grants Management Specialist National Cancer Institute Executive Plaza South, Room 242 Bethesda, MD 20892 Telephone: (301) 496-7800, ext. 66 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance Number 93.395, Cancer Treatment Research and Number 93.854, Biological Basis Research in the Neurosciences. 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 Part 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$P2 END ************************************************************ $$P3 BEGIN PA-93-108 ************************************************ BEHAVIORAL RESEARCH IN SEXUALLY TRANSMITTED DISEASES NIH GUIDE, Volume 22, Number 32, September 3, 1993 PA NUMBER: PA-93-108 P.T. 34; K.W. 0404000, 0715182, 0745027 National Institute of Allergy and Infectious Diseases National Institute of Child Health and Human Development National Institute on Aging PURPOSE The National Institute of Allergy and Infectious Diseases (NIAID), the National Institute of Child Health and Human Development (NICHD), and the National Institute on Aging (NIA) invite applications for intervention-oriented behavioral research on sexually transmitted diseases (STDs). The prevention and control of STDs relies on several strategies: blocking transmission, seeking early diagnosis and treatment, utilizing available vaccines, and altering risk-associated behaviors over the life course. Each strategy has a behavioral component that is critical to the success of STD prevention and control. Behavioral research to reduce the incidence, prevalence, and severity of STDs should include multidisciplinary efforts that incorporate the measurement of microbiologic and/or disease outcomes as well as behavioral outcomes. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This program announcement, Behavioral Research in Sexually Transmitted Diseases, is related to the priority area of sexually transmitted diseases. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-10473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign, non-profit and for-profit research institutions; public and private organizations such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Applications from minority and female investigators are encouraged. Foreign institutions are not eligible for the First Independent Research Support and Transition (FIRST) award (R29). MECHANISM OF SUPPORT This program announcement will use the National Institutes of Health (NIH) investigator-initiated 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 maximum duration of support for a given project period is five years. Investigators interested in collaborative and interactive research efforts around the central theme of behavioral research for the prevention and control of STDs may consider submission of interactive research project grants (IRPGs). Such investigators should first contact NIH program staff listed under INQUIRIES for advice on this mechanism and the method of application. RESEARCH OBJECTIVES Background In November 1989 and April 1990, the NIAID convened two interdisciplinary conferences on integrated behavioral research for the prevention and control of STDs to develop an intervention-oriented behavioral research agenda. The reports of these conferences are found in Appendix 1 of Research Issues in Human Behavior and Sexually Transmitted Diseases in the AIDS Era, Washington, DC: American Society for Microbiology, 1991, available from the publisher. The research objectives of this program announcement are based on the recommendations of those conferences. Magnitude and Impact of STDs Despite control efforts to prevent the spread of STDs, including human immunodeficiency virus (HIV) infection, both bacterial and viral STDs remain epidemic in many areas of the United States. Current estimates predict that there will be 10 to 13 million new cases of STDs this year, not including HIV infection. Associated costs are likely to exceed $5 billion. Complications of STDs include infertility, ectopic pregnancy, anogenital cancer, fetal wastage, low birth weight, and congenital/perinatal infection. Furthermore, recent studies indicate that ulcerative diseases as well as the more prevalent non-ulcerative STDs increase the risk of HIV transmission at least three- to five-fold. The long-term sequelae of STDs cause significant morbidity and mortality, and women and their infected infants bear much of the associated disease burden. Additionally, STDs disproportionately affect the health of several minority populations and a significant proportion of adolescents in the United States. Both the incidence of STDs and their long-term, potentially fatal sequelae are consistently higher among black and Hispanic Americans than among white Americans. Over 60 percent of all STD cases occur in people less than 25 years of age, and 3 million teenagers are infected with an STD each year. Transmission Dynamics The persistence, spread, and progression of STDs are related not only to biological factors but also to behavioral and social factors. According to May and Anderson's model on transmission dynamics, the reproductive rate of infection or the average number of sexually transmitted infections generated by an infected person is a function of (1) transmission probability, (2 contact rates, and (3) duration of infectiousness. In addition to biological factors, transmission probability is affected by the type and frequency of sexual behavior and the extent to which each behavior facilitates transmission. Contact rates are a function of the absolute number of partners as well as the characteristics of sexual partners encountered over a specified period of time. Duration of infectiousness, or the period of time during which an individual remains infectious, is determined by recognition of symptoms or risk and health-seeking behaviors, which lead to diagnosis and treatment. Behavioral interventions to prevent the acquisition, spread, and progression of STDs are associated with all three elements of May and Anderson's model. Decreasing transmission probability requires changing individuals' behaviors, including decreasing or eliminating sexual behaviors known to facilitate STD transmission and increasing condom use behavior. Decreasing contact rates calls for reduction in the number of sexual partners. Decreasing the period of infectiousness can be accomplished through symptom recognition, risk awareness, and increased health-seeking behavior as well as use of effective vaccines. STD Prevention and Control Strategies The ultimate outcome of behavioral research activities will be the design, implementation, and evaluation of interventions to decrease behaviors associated with STD risk and to increase health-seeking behaviors. The sequential research steps needed to build effective interventions are: 1. basic research to define antecedents associated with specific behaviors (including beliefs, perceptions, and motivations); 2. development of hypotheses derived from basic research concerning new approaches to STD prevention, treatment, and control; 3. pilot tests of intervention components on small, well defined samples; 4. experimental or quasi-experimental tests of complete interventions (formed from several components evaluated in pilot tests) to detect behavioral and microbiological effects. It should be noted that some of the behavioral research that has been conducted for HIV/AIDS prevention may augment or accelerate basic research or hypothesis development related to other STDs. For example, frequency of unprotected intercourse, number of sexual partners, and asymptomatic infection similarly affect the transmission dynamics of all STDs, including HIV infection. However, antecedents of preventive action may differ for STDs that are fatal (e.g., HIV infection), compared to those that incur long term consequences (e.g., pelvic inflammatory disease or genital herpes), or those that present only as an acute disease without long term sequelae (e.g., treatable bacterial STDs). Moreover, the factors that affect duration of infectiousness are different for HIV and many STDs. Infectiousness may be limited by curative therapy for bacterial STDs, and there is an available vaccine for one viral STD (hepatitis B). While the scientific areas covered in the following research objectives are very broad, it is not expected that any single application will cover the range of scientific areas described below. Applicants are encouraged to focus their investigations. A. Decrease Transmission Probability and Contact Rates The goal of research to decrease transmission probability and contact rates is to reduce risk of exposure to and acquisition of STDs through: (1) postponing coital debut; (2) reducing frequency of sexual practices associated with higher rates of transmission; (3) reducing numbers of sexual partners; and (4) increasing use of barrier contraceptives (e.g., condoms). While other NIH programs support research on these behaviors for HIV prevention (see addendum section), research targeted by this program announcement focuses on the reduction of the incidence, prevalence, and severity of STDs other than HIV and should include microbiologic and/or disease outcomes as well as behavioral outcomes. 1. Individual Factors: To change behaviors that put people at risk for STDs or their sequelae, individuals must recognize that there is a problem in their environment that is both serious and personally relevant; be motivated to act; and have the relevant knowledge, skills, and tools to undertake recommended action. Specific areas for research include, but are not limited to: o identification of antecedents and determinants of behaviors relevant to STD risk reduction in different populations (i.e., does the threat of PID and its sequelae motivate women to take preventive action against STDs); o ascertainment of optimal content, format, and venues for delivering information about acquisition and transmission of STDs and the serious consequences associated with these infections (i.e., what misperceptions about STDs are related to sexual risk taking, how is information concerning STDs conveyed through formal and informal networks of communication, and how can these networks be used to deliver programs that will result in a decrease in incident disease); o identification of skills needed to prevent STD transmission and optimal mechanisms to impart those skills (i.e., what is the best way to increase consistent condom use among individuals with genital herpes who may be asymptomatic but shedding virus). 2. Environmental Factors: In addition, impediments in the social environment must be identified and removed or diminished if individual behavioral change to reduce risk of STDs is to be initiated and sustained. Thus, research may focus on the individual as the target of the intervention or larger social structures. Specific areas of STD-related research on environmental factors may include: o determination of key norms that govern behaviors associated with STD transmission and development of strategies to modify them (i.e., what are the norms governing sexual intercourse during treatment for a bacterial STD, how do they vary by subpopulation, and what intervention strategies would be effective to modify them); o increase the adoption and diffusion of new and existing technologies to prevent STDs, such as barrier methods, that are compatible with human skills, dispositions, and perceptions related to STDs, including those technologies that can be controlled exclusively by women (i.e., what characteristics of vaginal suppositories enhance or discourage use among women, and which should be considered in the development of new topical microbicides to prevent STDs). On the basis of the findings of this research, STD interventions that target either individuals, groups, or the social environment will then be designed, implemented, and evaluated. B. Decrease the Duration of Infectiousness The goal of research in this area is to decrease the infectious period through increasing health-seeking behaviors leading to early diagnosis and treatment of STDs. 1. Diagnosis and Treatment: Behavioral research is needed to increase appropriate use of diagnostic tests. Given the high prevalence of asymptomatic disease, effective strategies should encourage individuals to seek STD screening on the basis of recognition of risk-related behavior rather than symptoms, which may not be present or recognized. For treatment to be effective, the patient must comply with the prescribed regimen. Optimal treatment for STDs includes taking medication, abstaining from sex during treatment (i.e., until the infection is no longer transmissible), referring partners for screening, and returning for follow-up screening or care after treatment, as necessary. Examples of research areas of interest include, but are not limited to, the following, and all should include both behavioral and microbiologic outcomes: o identification of antecedents and determinants of health-seeking behaviors that lead to STD diagnostic screening and medication compliance; o determination of level of current knowledge about benefits associated with screening, early treatment and medication compliance, and identification of misperceptions and other barriers to use; determination of optimal content, format, and venues for information delivery about screening and treatment; o development of behavioral instruments accompanied by microbiologic or disease measures that can (1) identify women at risk for repeat infection, (2) distinguish women with infection limited to the lower genital tract from those at risk for progression to upper genital tract infection, and (3) distinguish women with upper tract infection from those at risk for chronic sequelae; o determination of characteristics of health care provider-patient interaction that support and sustain diagnostic screening and compliance with treatment; o identification of barriers (from the perspective of both the patient and the health care provider) to appropriate use of screening and treatment; and o ascertainment of the impact of product characteristics (e.g., programmed timers to prompt pill taking) on medication compliance. 2. Vaccination: It is likely that vaccines for several STDs will be available by the end of this decade. To make full use of these powerful tools there is a critical need to dissect and understand the behavioral aspect of vaccine acceptance and compliance. Poor acceptance of the hepatitis B vaccine underscores this need. Immunization for hepatitis B has been available since 1982, yet the overall impact on incidence has been negligible. Rates of infection remain high even among high risk groups (i.e., homosexual men). Lack of use and poor compliance with the hepatitis B vaccine regimen underscore the need for research on the complex processes by which an individual arrives at a decision to either accept or decline immunization. This information will be essential in the development of clinical trial protocols and will be critical in increasing the likelihood of use of approved STD vaccines. Examples of research areas of interest include, but are not limited to: o identification of antecedents, determinants, and motivators of vaccine acceptance and compliance; o measurement of current knowledge about benefits associated with STD vaccine acceptance and identification of misperceptions and other barriers to use; o determination of optimal content, format, and venues for information delivery about vaccine availability; and o determination of characteristics of patient-provider interaction that support and sustain vaccine acceptance and compliance. Research to decrease the duration of infectiousness should produce detailed and specific information concerning increased use of diagnosis as well as acceptance of and compliance with treatment and vaccination. These findings will point to elements of interventions that are appropriate for pilot testing. Promising elements can then be folded into more complete interventions, which will be implemented and evaluated in experimental trials. Study Design Considerations In requiring investigators to measure both behavioral and disease or microbiologic outcomes, investigators will need to establish linkages to clinical settings where diagnostic capabilities are present. Treatment becomes an issue (1) if signs or symptoms make disease apparent, or (2) if infection is detected upon screening. In either case, consideration must be given to providing treatment. In addition, intervention research that results in significant benefit to cases should make provisions to provide a similar program to subjects who served as controls. However, other appropriate research designs may go beyond the clinical setting. For example, investigators may wish to consider epidemiologic research or add a component to an ongoing epidemiologic study (i.e., piggybacking an STD component on an existing survey that includes the collection of biologic samples). Epidemiologic research that expands beyond traditional demographic factors to include STD-related behaviors and infection status is integral and complementary to intervention-oriented research. Traditionally, epidemiologic surveys have focused on demographic and ecologic risk factors, such as age, race, sex, and population density. While these may be important indices of risk, they are not amenable to change. It is equally important that epidemiologic research monitor behaviors that may have a demonstrated relationship to STDs and are theoretically changeable. In this way, epidemiologic findings will identify which behaviors are important to consider in constructing pilot programs. Additional areas for research include, but are not limited to: o epidemiologic studies focused on factors associated with transmission probability and contact rates such as age of coital debut, number of partners, as well as factors influencing selection of partners from high risk populations; and o epidemiologic studies to identify sexual and other behaviors that increase risk of transmission or disease progression (e.g., douching or dry sex). Within the context of the research objectives of this program announcement, submission of applications that focus on methodologic research to improve data collected on sexual behaviors, creating valid and reliable indices of important outcome variables, and to probe factors that affect the quality of these data are encouraged. Clinical Assessment and Study Population As stated earlier, applicants are required to assess change in relevant behaviors and status of infection. Therefore, proposed projects must have ties to clinical facilities to characterize subjects with respect to sexually transmitted pathogens including, but not limited to, Chlamydia trachomatis, Neisseria gonorrhoeae, Treponema pallidum, human papillomavirus (HPV), herpes simplex virus type 2 (HSV-2), and human immunodeficiency virus (HIV). Although populations at risk for STDs are also at risk for HIV, studies that focus exclusively on HIV are not included under this program announcement. Certain populations continue to be at greater risk of STD acquisition, transmission, and progression, and they share a disproportionate burden of related disease; applicants are encouraged to investigate research questions in ethnic, racial, gender, and age groups as well as social environments in which risk is greatest. Special emphasis is placed on inner-city minorities, women, and adolescents. 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 under Research Plan items 1-4 and 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 and 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 applicants 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 that do not comply with these policies. APPLICATION PROCEDURES Applications are to be submitted on the grant application form PHS 398 (rev. 9/91) and will be accepted on the standard application deadlines for investigator-initiated applications: February 1, June 1, and October 1. Application kits are available at most institutional offices of sponsored research and may be obtained from the Office of Grants Information, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449 Bethesda, MD 20892, telephone 301-594-7248. The title and number of the announcement must be typed in Item 2a on the face page of the application and the "YES" box marked. Applications for the FIRST Award (R29) must include at least three sealed letters of reference attached to the face page of the original application. FIRST Award (R29) applications submitted without the required number of reference letters will be considered incomplete and will be returned without review. The completed original application and five legible copies must be sent to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** REVIEW CRITERIA Applications will be assigned on the basis of established PHS referral guidelines. Applications will be reviewed for scientific and technical merit by relevant study sections of the Division of Research Grants, NIH in accordance with standard NIH peer review procedures. Following scientific-technical review, the applications will receive a second-level review by the appropriate national advisory council or board. INQUIRIES The opportunity to clarify issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Heather Miller, Ph.D. Sexually Transmitted Diseases Branch National Institute of Allergy and Infectious Diseases Solar Building, Room 3A-26 Bethesda, MD 20892 Telephone: (301) 402-0443 FAX: (301) 402-1456 Arthur A. Campbell Center for Population Research National Institute of Child Health and Human Development 6100 Executive Boulevard, Room 8B07 Bethesda, MD 20892 Telephone: (301) 496-1101 FAX: (301) 496-0962 Marcia Ory, Ph.D., M.P.H. Behavioral and Social Research Program National Institute on Aging Gateway Building, Room 2C234 7201 Wisconsin Avenue Bethesda, MD 20892 Telephone: (301) 496-3136 FAX: (301) 402-0051 Direct inquiries regarding fiscal matters to: Mr. Todd Ball Grants Management Branch National Institute of Allergy and Infectious Diseases Solar Building, Room 4B-22 Bethesda, MD 20892 Telephone: (301) 496-7075 Ms. Melinda B. Nelson Office of Grants and Contracts National Institute of Child Health and Human Development 6100 Executive Boulevard, Room 8A17 Bethesda, MD 20892 Telephone: (301) 496-5481 Ms. Vicki Maurer Grants and Contracts Management Office National Institute on Aging Gateway Building, Room 2N212 Bethesda, MD 20892 Telephone: (301) 496-1472 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 13.856 "Microbiology and Infectious Disease Research". Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. ADDENDUM The National Institute of Mental Health (NIMH) Office of AIDS Programs supports research to better understand, assess, and treat the neuropsychiatric, behavioral, and psychosocial aspects of HIV infection and AIDS. Preventing or changing high risk behaviors and maintaining low risk behaviors are the only available strategies to prevent the further spread of HIV infection. The NIMH supports both preintervention and intervention studies in its behavioral and psychosocial program which includes identification of determinants of high-risk sexual and drug-using behaviors; determinants of maintaining low-risk behaviors, especially for hard-to-reach and special populations; the social contexts in which risk-taking behaviors occur; the impact of affective states (e.g., depression, anxiety, social isolation) on risk behavior; the affects of cognitive impairment on adherence to risk-reduction guidelines; the design, testing, and evaluation of theory-driven behavioral interventions designed to prevent and reduce high-risk behaviors for HIV infection and maintain low-risk behaviors in children, adolescents, and adults; research on interventions targeted to populations for which current research data are not available; the promotion of help-seeking behaviors such as counseling, social support, and early intervention services; adherence to medical treatment for HIV infection among different populations; and the psychological and psychosocial impact of HIV and AIDS upon individuals, families, and communities. For more information, contact: Ellen Stover, Ph.D., Director, Office of AIDS Programs, National Institute of Mental Health, Parklawn Building, Room 10-75, 5600 Fishers Lane, Rockville, MD 20857, telephone (301) 443-7281. $$P3 END ************************************************************ ERRATUM $$E1 BEGIN R3 19930806 APPEND RFA AI-93-017 BOTH *********************** MULTICOMPONENT VACCINE DEVELOPMENT NIH GUIDE, Volume 22, Number 32, September 3, 1993 RFA: AI-93-017 P.T. 34; K.W. 0740075, 1002045, 0710070 National Institute of Allergy and Infectious Diseases Letter of Intent Receipt Date: October 1, 1993 Application Receipt Date: November 24, 1993 The following change is made to RFA AI-93-017, published in the NIH Guide for Grants and Contracts, Vol. 22, No. 28, August 6, 1993: INQUIRIES The FAX number for Dr. David L. Klein should be: (301) 496-8030. $$E1 END ************************************************************ From owner-sci-resources@net.bio.net Thu Sep 02 23:00:00 1993 Path: biosci!net.bio.net From: kristoff@net.bio.net (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 22, no. 32, pt. 3, 3 September 1993 Message-ID: Date: 3 Sep 93 01:43:01 GMT Sender: kristoff@net.bio.net Lines: 1420 Approved: biosci-moderator@net.bio.net $$XID RFA AI93019 AI-93-019 P1O1 *************************************** NATIONAL COOPERATIVE DRUG DISCOVERY GROUPS FOR THE TREATMENT OF OPPORTUNISTIC INFECTIONS ASSOCIATED WITH ACQUIRED IMMUNODEFICIENCY SYNDROME (NCDDG-OI): TUBERCULOSIS NIH GUIDE, Volume 22, Number 32, September 3, 1993 RFA: AI-93-019 P.T. 34; K.W. 0715165, 0755060, 0715008 National Institute of Allergy and Infectious Diseases Letter of Intent Receipt Date: November 15, 1993 Application Receipt Date: January 21, 1994 PURPOSE The National Institute of Allergy and Infectious Diseases (NIAID) invites applications for the establishment of National Cooperative Drug Discovery Groups for the Treatment of Opportunistic Infections Associated with Acquired Immunodeficiency Syndrome (NCDDG-OI) focusing on tuberculosis. It is the purpose of this Request for Applications (RFA) to invite applications focused on the discovery of new, more effective, selective, and diverse therapeutic agents to treat and prevent infection caused by Mycobacterium tuberculosis. Research in the following areas is needed to provide the foundation for improvements in therapeutics for tuberculosis (TB), particularly in the setting of HIV infection: unique metabolic activities for drug targeting; biochemistry and molecular mechanisms of M. tuberculosis-host interactions; inhibitors of enzymatic and regulatory functions and biochemical pathways; mechanisms of overcoming drug resistance; and identification of natural products or synthetic chemical compounds with promise for development as TB therapies. Research activities should be directed toward discovery of selective drugs or molecular strategies that are lethal for M. tuberculosis with minimal toxicity for the host. It is anticipated that multidisciplinary approaches by scientists from a combination of academic, non-profit research, and commercial organizations, with the assistance of the NIAID, will be necessary to effectively accelerate discovery of new therapeutics. Applications that include research projects or core components from the private sector (e.g., pharmaceutical, chemical, or biotechnological companies) are encouraged. M. tuberculosis is the single opportunistic infection targeted in this RFA because of the compelling public health emergency and the need for additional therapies to overcome multi-drug resistant infections. Investigators pursuing similar drug discovery for other AIDS-associated opportunistic infections (OIs) are strongly encouraged to apply through other research support mechanisms. 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, National Cooperative Drug Discovery Groups for the Treatment of Opportunistic Infections Associated with Acquired Immunodeficiency Syndrome (NCDDG-OI), is related to the priority area of HIV infection. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic for-profit and non-profit organizations, public and private organizations, such as universities, colleges, hospitals, laboratories, units of State or local governments, and eligible agencies of the Federal government. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT Awards will be made as Cooperative Agreements (U01s). The Cooperative Agreement is an assistance mechanism, rather than an acquisition mechanism, in which substantial NIAID programmatic involvement is anticipated. The NIAID will support and/or stimulate research activity by collaborating and otherwise working jointly with the award recipient in a partner role, but is not to assume direction, prime responsibility, or a dominant role in the activity. Details of the responsibilities, relationships, and governance of studies funded under a cooperative agreement are discussed later under SPECIAL REQUIREMENTS. In applying for a cooperative agreement, the Principal Investigator defines his/her objectives in accord with his/her interests and perceptions of approaches to the discovery of new treatments against tuberculosis. The applicant institution and the Principal Investigator will be responsible for the Group's application. Awards will be made to the Principal Investigator's institution on behalf of the Group as a whole and not to individual research projects within the Group. Respondents to this RFA may include new applications for a maximum period of four years support and competitive supplements to currently funded NCDDG-OI Groups for research focused on M. tuberculosis. Because the varied talents and commitment required for effective drug discovery will be from diverse disciplines and may be located at geographically disparate locations, it is anticipated that Project Leaders within a Group may be associated with different institutions. Each application must include two projects from independent laboratories. For the purpose of encouraging new collaborations under this RFA, projects within a single private company will not be considered independent. Similarly, two projects within the same academic department will not be considered independent. The Group will be led by a Principal Investigator who will also lead a scientific project. The applicant institution of the Principal Investigator will provide a Central Operations Office for the Group (usually as part of the Principal Investigator's research project), will be responsible for the performance of the entire Group, and will be accountable for the funds awarded. This RFA is a one-time solicitation. Plans for continued support in this area are indefinite at this time. If by the end of the third year of the award, the NIAID has not announced its intent to re-issue the RFA, incumbents should contact NIAID program staff and consider submitting investigator-initiated (R01) applications that will compete with all investigator-initiated applications and be reviewed according to the customary peer review procedures. Under the Cooperative Agreement, a negotiated partner relationship exists between the recipient of the award and the NIAID in which the Group is responsive to the requirements and conditions set forth in this RFA. The interaction of academic and non-profit research institutions with commercial organizations and the Government is encouraged and is expected to favor expeditious discovery and preclinical development of agents active against tuberculosis and to facilitate their subsequent development for clinical trials. All policies and requirements that govern the grant program of the U.S. Public Health Service and the National Institutes of Health (NIH) apply. FUNDS AVAILABLE At the present time, it is estimated that no more than one to two new Groups will be funded for drug discovery against M. tuberculosis as a result of this RFA. Approximately $3.4 million (including direct and indirect costs) will be available over the four year period, including approximately $0.8 million (direct and indirect) during the first year. Any application received with a budget in excess of $0.8 million total costs (direct and indirect) for the first year will be returned without review. Awards and level of support are dependent on the receipt of a sufficient number of applications of high scientific merit. Because the nature and scope of the research proposed in response to this RFA may vary, it is anticipated that the size of awards will vary also. Budget requests must be adequately justified and commensurate with the complexity of the project. Although this program is provided for in the financial plans of the NIAID, awards pursuant to this RFA are contingent upon the availability of funds for this purpose. RESEARCH OBJECTIVES Background Acquired Immunodeficiency Syndrome (AIDS) is a disease that destroys host immunological defenses against a variety of infections. As of December 31, 1992, 253,448 cases of AIDS had been reported to the Centers for Disease Control and Prevention (CDC) and more than 171,890 (67.8%) of these patients have died. Recent projections indicate that between 800,000 to 1,200,000 persons in the United States may be infected with human immunodeficiency virus (HIV), the infectious virus associated with AIDS. Opportunistic infections (OIs) are the most frequent causes of morbidity and mortality in people with AIDS and are the principal reasons for hospitalization. Individuals infected with HIV are susceptible to a range of protozoal, fungal, viral, and bacterial infections. Pneumocystis carinii pneumonia (PCP) remains the most common opportunistic infection reported to the CDC for new cases of AIDS (approximately 50% of cases in 1990). Because of a strong epidemiological association between HIV infection and the development of TB, the CDC has recently included pulmonary TB in the 1993 expanded surveillance case definition for AIDS. Persons co-infected with HIV and TB have an increased risk of developing active and rapidly fatal pulmonary TB compared with persons without HIV infection. In addition, there is an association between lowered CD4+ T-lymphocyte counts in HIV-infected individuals and localized extrapulmonary TB or disseminated or miliary TB. Available drugs to treat opportunistic infections including TB lack the potency to completely eradicate infecting microorganisms without assistance from immune mechanisms. Prolonged HIV-mediated immunosuppression requires prolonged treatment schedules, and prophylaxis regimens against recurrences must often be maintained throughout the remaining lifetime of people with AIDS. Combined infection with HIV and M. tuberculosis has contributed to a public health crisis in many areas of the United States, particularly where health care delivery systems are inadequate. Recent outbreaks of multidrug-resistant tuberculosis and the emergence of certain strains resistant to all approved anti-tuberculous therapies poignantly illustrate the critical requirement to identify more effective therapeutic approaches. The need exists for more potent and selective therapeutic agents with activity against the OIs, and particularly multi-drug resistant forms of M. tuberculosis. The NCDDG-OI program was launched in 1990 for the purpose of stimulating discovery research in order to lay the foundation for development and commercialization of therapeutic agents targeted against the AIDS-associated OIs. Within the currently funded NCDDG-OI program, the following approaches are presently being pursued for OIs other than TB, and therefore serve as examples of research approaches: molecular modelling of chemical structures to inhibit vital metabolic enzymes; macrolide transport and activity; immunotherapy; gene cloning, expression, and structure-activity relationships of candidate drugs; inhibitors of protein N-myristoylation, cell wall biosynthesis, topoisomerases; synthesis and assay of drug analogs, unique chemical classes, heterocyclics; development of improved animal models for in vivo drug evaluations. M. tuberculosis is included as an opportunistic pathogen associated with AIDS by the CDC and within the NCDDG-OI program. Previous RFA issuances have focused on: Pneumocystis carinii, Toxoplasma gondii, Cryptosporidium parvum, Mycobacterium avium, Cryptococcus neoformans, Candida albicans, and cytomegalovirus. Similarities that exist between drug targets in M. avium and M. tuberculosis will provide a framework for information exchange between investigators supported as a result of this RFA and those already funded as Groups within the NCDDG-OI program. As part of the cooperative nature of this program, compounds identified as active against any of the OIs may be shared and evaluated by all Groups. Because of the compelling public health need for new, more effective therapies to overcome the threat of multi-drug resistant TB, only research focused on M. tuberculosis will be supported under this re-issuance of the NCDDG-OI program RFA. Research Goals and Objectives of the NCDDG-OI Program The goals of the NCDDG-OI program relative to this RFA are: to foster innovative, multi-disciplinary research, conceptualization and targeted discovery of drugs and strategies to treat and prevent tuberculosis (TB); to support efficacy and pharmacological evaluations leading to selection of candidate therapies through collaboration among investigators and with the NIAID; and to assist in the preclinical development of therapies for evaluation in clinical trials supported by other mechanisms. Scientific Scope, Restrictions, and Exclusions Applications for this NCDDG-OI RFA should stress creative approaches to the discovery of effective therapies to treat TB through a comprehensive team effort. It is recognized that the ultimate objective of selective therapy against microbial infection requires a solid knowledge base of the biology, composition, physiology, molecular biology, and host defense mechanisms against infectious agents. Applications should emphasize the following: specific scientific objectives focusing on targeted drug discovery; integration and coordination of research aims from different scientific disciplines; and research rationales, plans, and approaches designed to identify candidate therapeutics within the support period requested. The Group's objectives and goals must be relevant and compatible with the NCDDG-OI program's missions and directions as stated in this RFA. It is not a requirement of this RFA that a complete development plan for new drugs or biological agents be proposed, although applications which include research projects or core components from the private sector (e.g., pharmaceutical, chemical, or biotechnological companies) are encouraged. Projects focusing on the early phases of new target identification and drug development are appropriate. However, each application must clearly state in an introductory section how information from the proposed projects will directly accelerate new drug discovery and what therapeutic approaches are likely to ultimately derive from these studies. Priority will be given to proposed therapies with potential for combatting multi-drug resistant tuberculosis, improving prophylaxis approaches, practicality of administration to HIV-infected people, and low toxicity. Examples of research projects considered responsive to this RFA include, but are not necessarily restricted to, the following: o Identification and development of drug evaluation assays for molecular targets with selectivity for M. tuberculosis, such as recombination repair mechanisms, elongation factors, cell wall assembly, and others with potential for mycobactericidal consequences of inhibition. o Development of drug evaluation assays for essential mycobacterial gene products, particularly biochemical activities expressed in vivo and associated with pathogenicity. o In vitro and in vivo evaluation of new chemical entities with potential for mycobactericidal activity within a framework of logical plans that examine structure-activity relationships and potential toxicities. o Development, validation, and implementation of drug evaluation systems capable of predicting bactericidal and sterilizing activity of new agents, or combinations of agents against M. tuberculosis. o Studies on the effects of drugs on slow-growing M. tuberculosis, such as those found in granulomatous tubercular lesions, identification of drugs with extended lengths of biological activity, and development of methods to assess post-antibiotic effect on M. tuberculosis. o Development, validation, and implementation of improved models for in vivo drug evaluations, such as immunosuppressed animals, or animals with disrupted interferon-gamma or other immune effector genes. o Development and evaluation of biological entities, such as recombinant mycobacteriophage as drug or suicide gene delivery vehicles, and evaluation of these for efficacy and safety. o Identification and development of systems to predict emergence of resistance to established and newly identified antibiotics, and to evaluate new therapies for their ability to prevent or overcome resistance. Discovery and evaluation of new potential therapeutics is the major goal of this initiative. It is anticipated that no more than one or two Groups will be supported to pursue drug discovery research against M. tuberculosis as a result of this RFA. Projects or cores that include proposed animal model development must be integrated within the major goal of targeted drug discovery and required to attain the Group's objectives. Funds for evaluation of new agents in animal models may be withheld until compounds generated by the Group are available for animal efficacy studies. It is strongly encouraged that discovery of new mycobactericidal targets and associated therapies with selectivity for these targets be the focus of all applications. Exclusions: Random or large scale screening of compounds will not be supported. Organisms other than M. tuberculosis causing infections associated with AIDS have been excluded from this RFA. Scientists studying opportunistic infections whose research does not lie within the areas defined as responsive to this RFA are strongly encouraged to apply for investigator-initiated grants through the R01, R29, R43 (Small Business Innovative Research Program), Interactive Research Project Grants, or other existing funding mechanisms. No clinical trials will be supported under this RFA. Although studies required for the clinical development of identified potential treatments are beyond the scope of this RFA, development through private venture capital is encouraged. Alternatively, an NCDDG may request that the NIAID assist in certain developmental tasks supported by other mechanisms (NIAID Staff Responsibilities: Nature of NIAID Participation). DEFINITIONS ADMINISTRATIVE SUPPORT - Administrative efforts that provide support for the overall management of the cooperative agreement and services shared by the Group as a whole. Administrative support for the Group's activities should be included in that of the Principal Investigator's project, and be administered by the Principal Investigator's organization. ARBITRATION PANEL - A panel that may be formed to review any scientific or programmatic activity that is impeding progress within a Group. It will be composed of one Group designee, one NIAID designee, and a third designee with expertise in the relevant area and chosen by the other two. The interaction of this panel is detailed in "Terms of Award". AWARDEE INSTITUTION - The awardee institution establishes and operates the Central Operations Office that funds Group members and is legally and fiscally accountable for the disposition of funds awarded in accordance with PHS policies. COOPERATIVE AGREEMENT - An assistance mechanism in which substantial NIAID programmatic involvement with the recipient organization during the performance of the planned activity is anticipated. DISCOVERY - The term "discovery" is used explicitly to limit activities of the NCDDG-OI to preclinical identification, design and development of new therapeutic entities. DRUG - In the context of the NCDDG-OI program, the term "drug" is used broadly to encompass new synthetic agents, natural and biological products or novel therapeutic strategies designed to effectively treat tuberculosis. INVENTION - A new drug or innovative treatment that is or may be patentable under Title 35 of the United States Code. NATIONAL COOPERATIVE DRUG DISCOVERY GROUP for the Treatment of Opportunistic Infections (NCDDG-OI) - In this RFA the terms NATIONAL COOPERATIVE DRUG DISCOVERY GROUP, NCDDG-OI, and "Group" are synonymous. Two laboratory research projects representing diverse scientific disciplines and organizations which join together under a single Principal Investigator and which function as a unit with a common goal: the conceptualization, invention, and evaluation of new entities and strategies for the treatment of tuberculosis. All applications must consist of two independent Projects conducted by at least two independent laboratories. For the purpose of this RFA, two projects within a single company or within a single academic department will not be considered independent. This limitation on the number of independent projects from the same academic department or private sector company is intended to increase the diversity and multi-disciplinary expertise available to the Group. An NCDDG-OI Group consists of the following: (1) a Principal Investigator, (2) two research projects, (3) a Scientific Advisors Panel, and (4) an NIAID Scientific Coordinator (see below). NIAID NCDDG-OI PROGRAM DIRECTOR - A Senior Scientist of the NIAID extramural staff who coordinates NIAID's participation in the NCDDG-OI program. NIAID SCIENTIFIC COORDINATOR - A Senior or Associate Scientist of the NIAID extramural staff who functions as a peer with the Principal Investigator and Project Leaders and facilitates the partnership relationship between NIAID and the Group. The Scientific Coordinator will be assigned to each Group by the NCDDG-OI program director. PRINCIPAL INVESTIGATOR - The person who assembles the NCDDG-OI, who is responsible for the performance of the Group as a whole and who submits the single application in response to this RFA. The Principal Investigator will coordinate Group activities scientifically and administratively and should be project leader of one of the Research Projects of the Group. PROJECT LEADER - The leader of one of the scientific research projects of the NCDDG-OI who is directly responsible to the Principal Investigator. Project Leaders will not be supported by more than one Cooperative Agreement awarded under this RFA unless the research is clearly and separately delineated in each application. Individuals currently supported under an existing NCDDG-OI or other programs may be funded under this RFA provided there is no scientific or budgetary overlap in funded activities. RESEARCH PROJECT - A discrete, specified project with a separate budget that relates to the overall theme and objectives of the NCDDG-OI. A maximum of two research projects per Group is stipulated. SCIENTIFIC ADVISORS PANEL - A panel, comprised of two to three peers from the scientific community, whose mission is to provide the Principal Investigator with comprehensive review of the Group's activities and progress, consult on future goals and strategies, and recommend alternative directions, as appropriate. Selection and appointment of the Panel is the responsibility of the Principal Investigator. Members of the Panel will not be affiliated with any of the institutions comprising the Group. A Scientific Advisors Panel is required of all Groups. The composition of the designated Panel will be provided to the NIAID within the first year of funding. The Panel will provide the Principal Investigator and the NIAID Scientific Coordinator with a comprehensive written review of the Group's activity during the second and third years of funding. Reviews will encompass timeliness of progress in individual projects relative to original projections; progress relative to the Group's objectives and needs; continued relevance of a given project to the Group's function; continued coordination of the Group's objectives with the objectives of the NCDDG-OI program; and recommendations for new directions, as appropriate. The Principal Investigator will invite the Scientific Coordinator to all meetings of the Panel, which may be combined with Group meetings. SCIENTIFIC SUPPORT CORE COMPONENT - Facilities for equipment and services which are shared by two projects of the NCDDG-OI may be provided for within a Research Project. Examples of Scientific Support Core components are: biochemical assays, in vitro or animal model testing, production of monoclonal antibodies, scale-up synthesis of drugs. The core can be defined as a component with established techniques and assays which perform a service function resulting in an economy of effort and savings in the overall costs of the NCDDG-OI. The core unit is to be described in the research plan of the projects and in adequate detail to enable the evaluation of its scientific and technical merit. A CORE COMPONENT cannot be considered toward fulfilling the required two research projects per Group. (See details for preparation of the budgets under XI. APPLICATION PROCEDURES). SPECIAL REQUIREMENTS Terms and Conditions of Award NOTE: Failure to abide by any of the Terms of Award pertaining to awardee responsibilities stipulated in this Section may result in the withholding of funds by the NIAID until compliance with the Terms is restored. A. Working Relationships Within a Cooperative Agreement Under the Cooperative Agreement, a negotiated partner relationship exists between the recipient of the award and NIAID in which the Group is responsive to the requirements and conditions set forth in this RFA. The participation of the Government through the NIAID extramural staff is intended to facilitate a concerted effort by all members of the network of Groups by providing appropriate scientific input, by coordinating efforts among Groups, by making available to Groups biological materials for testing, by accessing appropriate data bases, and by providing ancillary testing and other resources, such as reagents, samples or experimental animals, available under existing Government contracts. The interaction of academic and non-profit research institutions with commercial organizations and Government is strongly encouraged and is expected to favor expeditious preclinical discovery and development of new drugs for the treatment of tuberculosis. B. Patent coverage Since the discovery of agents active against tuberculosis is the objective of this effort, and since active involvement by industrial laboratories is facilitated by the existence of adequate patent coverage, it is essential that applicants provide plans to assure such coverage. With the potential for involvement of multiple institutions, the patent situation could be complicated. Each applicant Group must, therefore, provide a detailed description of the approach to be used for obtaining patent coverage and for licensing where appropriate, in particular where the invention may involve investigators from more than one institution. In addition each Group must provide a detailed description of the procedures to be followed for the resolution of legal problems that may develop. Attention is drawn to the reporting requirements of 35 U.S.C. Parts 200-212 and 37 CFR Part 401 or FAR 55.227-11. Instructions were also published in the NIH GUIDE FOR GRANTS AND CONTRACTS, Vol. 19, No. 23, June 22, 1990. Note that non-profit organizations (including universities) and small business firms retain the rights to any patent resulting from Government contracts, grants or Cooperative Agreements. Also, a Presidential memorandum of February 18, 1983 extended to all business concerns, regardless of size, the first option to the ownership of rights to inventions as provided in P.L. 96-517. As a result of this memorandum, the relationships among industrial organizations and other participants are simplified, since all Group members can now be full partners in the research and in any inventions resulting therefrom. The specific patenting arrangements among the institutions may vary, and could include joint patent ownership, exclusive licensing arrangements, etc. Applicants are encouraged to develop an arrangement that is most suitable for their own particular circumstances. Federal regulation clause 37CFR401 and HHS Inventions regulations at 45 CFR Parts 6 and 8 require that NIH be informed of inventions and licensing occurring under NIH funded research. Invention and licensing reports must be submitted to Extramural Invention Reports Office, Office of Extramural Research, Building 31, Room 5B41, NIH. C. Awardee Rights and Responsibilities and Nature of NIAID Participation It is the primary responsibility of the Principal Investigator to clearly define the objectives and approaches of the Group, to plan and conduct the research stipulated in the proposal, and to ensure that the results obtained are analyzed and published in a timely manner. The data obtained will be the property of the awardee. Meetings a. Two mandatory Group meetings are required per year. The Principal Investigator and Project and Core Leaders will meet to review progress, plan and design research activities, and establish priorities within the Group. The Principal Investigator will be responsible for scheduling the time and place (generally at one of the performance sites), for notifying the Scientific Coordinator at least thirty days prior to the meeting date, and for preparing concise (2-3 pages) minutes or summaries of the Group meetings which will be delivered to the members of the Group including the Scientific Coordinator within thirty days following the meeting. NIAID Scientific Coordinator will participate but not chair Group meetings. b. One mandatory meeting of the entire NCDDG-OI program will be held each year at a site designated by NIAID (Bethesda, Maryland is anticipated) during which all Principal Investigators and Project Leaders will present significant findings in symposium format. Data presented at this meeting are selected by the individual presenters in consultation with their Principal Investigator thus affording appropriate protection of proprietary or commercially sensitive information. c. Group communications. A critical determinant of Group success will be the degree of communication among members. Therefore, in addition to the three meetings listed above, additional meetings for coordination of Group activities may be necessary. Regular telephone and written communication will be important and are encouraged. d. Groups will designate a Scientific Advisors Panel within the first year of funding. The Principal Investigator will convene a meeting, or meetings, of the Group with the Panel during the second and third years which may be in conjunction with the required Group meetings (see item 1, above). The Panel will meet with the Group, and advise the Principal Investigator on the Group's progress, future goals, strategies and new directions, as appropriate. The Panel will provide the Principal Investigator with a comprehensive written review (2 to 3 pages) of the Group's activity each year. Members of the Panel will not be affiliated with any of the institutions comprising the Group. Publications The Principal Investigator will be responsible for the timely submission to the Scientific Coordinator of all abstracts, manuscripts, and reviews (co)authored by members of the Group and supported in part or in total under this Agreement. The Principal Investigator and Project Leader are requested to submit manuscripts to the Scientific Coordinator within three weeks of acceptance for publication so that an up-to-date summary of program accomplishments can be maintained. Publications or oral presentations of work done under this Agreement are the responsibility of the Principal Investigator and appropriate Project Leader. All publications (abstracts, peer reviewed manuscripts, reviews) and oral presentations of work supported in part or in total by the NCDDG-OI cooperative agreement must be acknowledged as part of the presentation and will include the mechanism, cooperative agreement number and Institute; for example, "This work was supported in whole (or in part) by the NCDDG-OI program, cooperative agreement number U01-AI-12345, NIAID." Progress Reports An annual Progress Report will be submitted with the Application for Continuation Grant which must include significant experimental data obtained and a complete and cumulative list of all publications (abstracts, manuscripts, reviews) (co)authored by Group members and supported in part or in total under this Agreement. Each Progress Report should also include a brief section outlining intra-Group interactions which have augmented activities, citing specific occurrences (e.g., compound X was synthesized under Project 1 and transferred to Project 2 for bioassays). Inter-Group collaboration with other NCDDG-OIs should be specified, where applicable. Interaction with the Scientific Coordinator and the NIAID during the reporting period should be described. The Progress Report must also include basic information as instructed with PHS 2590 Noncompeting Continuation Application forms. Rights to Data Although the NIAID Scientific Coordinator has a right of access to the data (see NIAID staff responsibilities below), the applicant will retain custody of and rights to the data. Information obtained from the data may be used by the Scientific Coordinator for the preparation of internal reports on the Group's activities. Timely publication of major findings is strongly encouraged. The NIAID Scientific Coordinator may assist the Groups by providing them with compounds for voluntary initial and confirmatory testing. In testing compounds supplied by the NIAID, the Groups agree to abide by any confidentiality agreement between the NIAID and a third party who may have supplied the compounds for testing through NIAID. The applicant institution and the Principal Investigator will be responsible for the Group's application. The award will be made to the applicant institution on behalf of the Group as a whole and not to individual research projects within the Group. The applicant institution will provide a Central Operations Office for the Group, will be responsible for the performance of the entire Group, and will be accountable for the funds awarded. D. NIAID Staff Responsibilities: Nature of NIAID Participation Assistance via a Cooperative Agreement differs from the traditional research grant in that, in addition to the normal programmatic and administrative stewardship responsibilities, the awarding component (NIAID) anticipates substantial programmatic involvement during performance of the research program. NIAID shall participate as a member of the Group and shall be represented by a Scientific Coordinator or the NCDDG-OI program director. The Coordinator shall be selected from the Developmental Therapeutics Branch of the Division of Acquired Immunodeficiency Syndrome, or from the Division of Microbiology and Infectious Diseases, which are extramural programs of the NIAID. During performance of the award, the NIAID Scientific Coordinator, may provide appropriate assistance, advice, and guidance by: participating in the design of Group activities; advising in the selection of sources or resources; coordinating or participating in collection and/or analysis of data; advising in management and technical performance; or participating in the preparation of publications. However, the role of NIAID will be to facilitate and not to direct the activities. It is anticipated that decisions in all activities will be reached by consensus of the Group and that NIAID staff will be given the opportunity to offer input to this process. The manner of reaching this consensus and the final decision-making authority will rest with the Principal Investigator. o NIAID Participation in Design of Group Activities, Development of Research Protocols and Evaluation of Results a. The NIAID Scientific Coordinator, like other Group members, may suggest studies within the scope of the Group's objectives and research activities; may present to the Group experimental findings from published sources or from contract projects in support of these suggestions; may participate in the design, but not in the execution, of experiments agreed to by the Group; and may participate in the analysis of results. b. The NIAID Scientific Coordinator may assist the Group or other individual members in research planning, particularly by: o providing needed resources and information that may not be otherwise be available to the Group; o providing data from testing conducted in resource contract laboratories; o providing information concerning work being conducted in other NIAID-supported extramural projects, in order to reduce or prevent duplication of efforts. c. The Scientific Coordinator may serve as a resource for information, laboratory testing, and biological supplies, when such resources are not a normal requirement of the Group's day-to-day research activities but may be required on an occasional basis. The NIAID has a contract program for the preclinical development of compounds for the treatment of AIDS-associated opportunistic infections, including animal models. These resources are intended for initial studies and may not be available on a continual basis. Examples of potential assistance include: reference compounds for standardization of test systems, facilitation of confirmatory testing at research sites including other NCDDG-OI Groups, limited testing in appropriate animal model(s), focused searches of NIAID's computer files of chemical structures and biological activity, chemical re-synthesis, analysis, formulation, and toxicology testing through existing pre-clinical development contracts (contingent upon NIAID's recommendation and prioritization), and networking with other NIH staff, NCDDGs, other collaborators and other Government and non-Government researchers who may provide guidance, expertise or resources to facilitate development of therapies identified by the Group. In addition, the NIAID supports Phase I, Phase II and Phase III clinical trials through a variety of mechanisms. These clinical development resources are available to study promising therapies brought forward from sources such as the NCDDG-OI program. It is understood that the Government provides its consulting and testing services in the interest of promoting experimental anti-infective agents through preclinical and clinical testing and development in the most expeditious fashion, and that newly marketed agents that have utilized this service will be offered to the public at a reasonable cost. NIAID Participation in Collection and Analysis of Data, Procedures for Submission of Results to NIAID, and Preparation of Group Findings for Presentation and Publication In addition to the special reports and stipulations described below, reporting requirements will be identical to those currently in existence for awardees of traditional NIH research project grants. a. The principal end product of NCDDG-OI activities will be the discovery of new entities and strategies for development to clinical trials for AIDS-associated OIs including tuberculosis. Subsequent developmental work through private resources is encouraged. Alternatively, the Group may recommend that development be sponsored by NIAID (see below). In the latter case, it will be necessary for the Principal Investigator, appropriate Project Leaders and NIAID Scientific Coordinator to collaborate in the analysis, summarization, preparation, and presentation of data to the appropriate NIAID staff and its advisory committees. b. NIAID will retain the option to cross-file or independently file an application for investigational clinical trial; e.g., an Investigational New Drug (IND) application to the United States Food and Drug Administration of any invention resulting from these NIAID supported Cooperative Agreements. Reports of data generated by the Group or any of its members required for inclusion in INDs and Clinical Brochures and for cross-filing purposes will be submitted by the Principal Investigator to the Scientific Coordinator upon request. Such reports will be in final draft form and include background information, methods, results, and conclusions. They will be subject to approval and revision by NIAID and may be augmented with test results from other Government sponsored projects prior to submission to the appropriate regulatory agency. E. Arbitration Process Inasmuch as certain activities under VIII. Special Requirements: Terms and Conditions of Award require approval by NIAID staff during performance of this Cooperative Agreement, specifically, reports intended for inclusion in INDs and Clinical Brochures, change in Principal Investigator or Project Leader, redistribution of biological materials received through the Scientific Coordinator and dissemination of research findings resulting from the use of these materials, NIAID will establish an arbitration process to resolve any differences of opinion with regard to scientific-programmatic matters. An arbitration panel, composed of one Group designee, one NIAID designee, and a third designee with expertise in the relevant area and chosen by the other two, will be formed to review any disagreements regarding scientific-programmatic issues that are restricting progress. This arbitration process in no way affects the right of an award recipient to appeal selected post award administrative decisions in accordance with HHS, PHS, and NIH regulations. These special arbitration procedures for scientific-programmatic matters in no way affect the awardee's right to appeal an adverse action in accordance with PHS regulations at 42 CFR Part 50, Subpart D, and HHS regulations at 45 CFR Part 16. These special Terms and Conditions 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. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements are required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis should be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale 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 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 Section 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 populations 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 studies. 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 the study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and will be reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. Applicants from institutions that have a General Clinical Research Center (GCRC) funded by the NIH National Center for Research Resources may wish to identify the GCRC as a resource for conducting the proposed research. If so, a letter of agreement from either the GCRC program director or Principal Investigator could be included with the application. LETTER OF INTENT Prospective applicants are asked to submit, by November 15, 1993, a letter of intent that includes a descriptive title of the overall proposed research, the name, address, telephone number, and institution of the Principal Investigator, descriptive title, name of prospective project leaders and other key investigators, and the institution for each component research project, and the number and title of this 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 applications, the information that it contains is helpful in planning for the review of applications. It allows NIAID staff to estimate the potential workload of the reviewers and to avoid possible conflict of interest in the review. The letter of intent is to be sent to Dr. Dianne Tingley at the address listed under INQUIRIES. APPLICATION PROCEDURES Special Instructions for Preparing Applications These instructions for preparing the NCDDG-OI application supplement the instructions found in form PHS 398 (rev. 9/91), which is available as an application kit at most grantee institutions and from the Division of Research Grants, Office of Grants Information, National Institutes of Health 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone 301-594-7248. Additional instructions are required because the form PHS 398 is designed primarily for individual research grant (R01) applications, whereas the Group application consists of research projects interrelated by a common theme. Items that require modification for U01 applications, in addition to other information not requested in form PHS 398, are detailed below: A. Introductory Section Face Page of Form PHS 398 Complete items 1 through 18 as instructed. Please note that this should be Page 1 of the entire application; all succeeding pages should be numbered consecutively. To ensure the identification of your application with this RFA, the application form must have "National Cooperative Drug Discovery Group for Treatment of Opportunistic Infections (NCDDG-OI) RFA AI-93-019" typed on item 2a of the face page of the application form and the YES box must be marked. o Overall Description. Use Page 2 of Form PHS 398 Provide a succinct but accurate description of the OVERALL goals of the NCDDG-OI, addressing the major, common theme of the Group. Do not exceed space provided. Under "Key Personnel Engaged on Project," list the Principal Investigator of the overall NCDDG-OI, followed by the Project Leaders of the component research projects and cores and then the other key personnel. o Table of Contents. Use Page 3 of Form PHS 398 The NCDDG-OI application should be assembled and paginated as one complete application. Bearing in mind that the application will be scientifically reviewed project by project, prepare a detailed table of contents that will enable reviewers to readily locate specific information pertinent to the overall U01 application as well as to each component research project and core. A page reference should be included for each summary budget (overall) as well as the budget for each project. Further, each project should be identified by number, title and responsible Project Leader. Page locations of summary tables following suggested formats shown in Tables I-IV of this document (APPENDIX) should be indicated in the Table of Contents. o Composite Budget To aid in peer review, applicants are requested to prepare a Composite Budget for the first twelve month budget period using a format such as that shown in Table I of this RFA. Do not use page 4 of form PHS 398 for this purpose. Detailed justification for budget elements should not be presented here, but in the individual budget of the projects and cores. Summary budgets should be prepared for the total Group application. The maximum dollar request permitted under this RFA is $0.8 million total costs (direct and indirect) during the first year, and $3.4 million over the four year period. o Summary Budget by Category. Use page 5 from the Form PHS 398 Prepare a Summary Budget by category for ALL YEARS of the requested support. o Personnel Listing and Distribution of Effort for "Other Support" Applicants are requested to list all professional and non-professional participants in the Group, including those with no salary requested, for the first year of requested support using a format such as that shown in Table II. Using a format such as Table III, a similiar distribution of professional effort (%) for other support would be helpful for peer review. o Research Plan a. Program Introduction - Statement of Group Objectives The NCDDG-OI should be viewed as a program of interrelated research projects -- each capable of standing on its own scientific merit, but complementary to one another. It is very important to establish the programmatic theme in the first few sentences describing the collaboration. The introduction is an important section, for it provides the investigator an opportunity to give conceptual wholeness to the overall program by giving a statement of the general problem area and by laying out a broad strategy for attacking the problems. The introductory section should briefly state the rationale of the research proposed in each project describing how it relates to drug discovery and the anticipated approach to achieve the work proposed. It is essential to demonstrate that each component research project contributes to the attainment of the Group's objectives and that each has available the professional and technical personnel to permit efficient and successful conduct of the proposed research; i.e., it is important to show that the total personnel of the Group are sufficient in quality, number, and committed time and effort to assure successful conduct of the proposed research. Therefore, the first section of the NCDDG-OI application should contain: o A clear, concise plan in narrative and diagrammatic form that depicts the interrelationships among the members of the NCDDG-OI and the contribution of each to fulfillment of Group objectives. o An organizational chart of the NCDDG-OI showing the name, organization, and scientific discipline of the investigators comprising the Group. o A plan to ensure maintenance of close collaboration and effective communication among members of the Group in accord with Section VIII, Special Requirements. The application should include plans for scheduling Group meetings, notifying Group members, including the NIAID Scientific Coordinator, and documenting and disseminating Group meeting proceedings. o Letters of commitment to the overall plan and acceptance of the participation of the NIAID Scientific Coordinator. o A rationale for the drug discovery approach(es) proposed and discussion of the therapeutic approaches which may derive from the research projects. o The anticipated unique advantages to be expected from the Group operating within the proposed collaborative efforts; how the projects are mutually reinforcing; and how collectively they will further the stated goals of the proposed research. b. Organizational and Administrative Structure of the NCDDG-OI Describe in detail and by diagram the chain of responsibility for decision-making and administration beginning at the level of Principal Investigator and including the different research Project Leaders and other investigators. Indicate where in the chain of responsibility advisory groups will be used. Describe their role in establishing quality control of the research efforts. c. Consortium Arrangements An application that includes research activity involving institutions other than the sponsoring organization is considered a consortium effort. It is imperative that care be taken in preparing any consortium application so that the programmatic, fiscal, and administrative considerations are fully explained. The policy governing consortia is described in the NIH GUIDE FOR GRANTS AND CONTRACTS (Vol. 14, No. 7, June 21, 1985), which should be available at the sponsoring institution's business office, or in the Office of Grants Inquiries' publication entitled, "Guidelines for Establishing and Operating Consortium Grants," January 1989, which may be obtained by calling 301-594-7248. These guidelines should be read carefully before an application is developed. If clarification of the guidelines is needed, the applicant is encouraged to contact grants management staff, Ms. Jane Unsworth, at 301-496-7075. d. Patent Coverage Provide a description of the Group's plan for assuring adequate patent coverage of new inventions that may issue as a result of Government funding of this U01. NOTE: A formal statement of Patent Agreement among all Group members and their institutions as well as a detailed description of procedures to be followed for the resolution of legal problems which may develop, signed and dated by the organizational official authorized to enter into patent arrangements for each Group member and member institution, is to be submitted to Dr. Barbara Laughon in advance of the application receipt date (for Dr. Laughon's complete address see INQUIRIES, below.) Should the Group wish to place all inventions and discoveries resulting from these studies within the public domain, a letter to that effect must be submitted to Dr. Laughon in lieu of the patent agreement prior to submission of the application. The letter must be co-signed by the Principal Investigator, Project Leaders, and each of the business officials representing the respective institutions. B. Individual Research Projects The strength of the application will be judged mainly on the basis of the quality of each research project. Therefore, the reviewers will expect each project to be described in the same detail as for a regular research grant application, to enable them to judge the scientific merit solely on the basis of the written applications. The portion of the application for each component research project should be prepared in the same manner as an R01 application, following carefully the instructions found in the grant application kit form PHS 398 (rev. 9/91). A few modifications are pointed out below for selected items, to address the interactive, collaborative contributions of the individual project. Face Page of Form PHS 398. Complete a Face Page of form PHS 398 for each project. Page 2 of form PHS 398. Provide an abstract of the research proposed in the project. Prepare the abstract according to the instructions provided on page 2 of form PHS 398. In addition, the abstract should contain a brief description of how the research project will contribute towards attainment of the Group's objectives. Under "Personnel Engaged on Project", follow instructions on page 2 of PHS 398, listing all individuals participating in the project, beginning with the Project Leader. Page 3 of Form PHS 398. Prepare a Table of Contents for the research project using page 3 of form PHS 398. Pages 4 and 5 of Form PHS 398. Detailed first year budget and budget for entire project period: follow instructions on pages 16-19 of the form PHS 398 instructions. The budget pages should have the project number and the project leader's name in the upper left hand of each budget page. Funds for attending the Group meetings and the annual NCDDG-OI program meeting (section VIII.C.1) should be included in the budget. Funds to cover operating costs of the NCDDG-OI program annual meeting may be contributed by one or more Groups. NIAID will provide administrative supplements for this purpose, as needed. Funds to cover expenses incurred by the Scientific Advisors Panel should be included in the Principal Investigator's component of the application. Pages 6 - 7 of Form PHS 398. Provide the biographical sketches and information on "Other Support" of all participating investigators in the Project. FOLLOW INSTRUCTIONS CAREFULLY. If a similar R01 or R29 is submitted concurrently or is pending, it should be so stated in this section. Incomplete, inaccurate or ambiguous information about OTHER SUPPORT, whether active or pending, may lead to delays in the review of the application. Research Plan: Follow the instructions indicated in IV. C., pages 19 through 22 of the form PHS 398 Instructions, completing items 1 through 4 in detail. In addition, attention should be given to integration of the component project into the overall Group project. As with a regular research grant application, the overall research plan for each project should not exceed 25 pages (from Specific Aims through Research Design and Methods). The following points should be addressed in the appropriate sections. Item 1 - Specific Aims: In addition to listing the specific objectives for the total period of requested support for the component, state the overall objective or long-term goal of the research and its relationship to the goals of the NCDDG-OI and how it relates to other projects or cores in the Group. Item 2 - Significance: In addition to the overall biological significance of the proposed research, this section should indicate the relevance of the project to the drug discovery efforts of the Group. Item 7 - Collaborative Arrangements: This item should include a brief statement of the collaborative contribution that this project will make towards the achievement of the Group's objectives, and with which component projects it will actively interact. Collaborative arrangements anticipated, either internal or external to the Group should be described and documents with letters from collaborating investigators. C. Scientific Core Support Scientific core support units, if required, must be included as subprojects within the budgets of one of the Projects. Core support may be provided as consortia if performed at institutions different from that of the Principal Investigator (see Consortium Arrangements, above.) Describe the role and importance of the core as a resource to the NCDDG-OI as a whole. Indicate the specific service(s) such core support will provide and the projects it will serve, e.g., production of monoclonal antibodies and distribution to research projects 1 and 2. This section should present a clear description of the facilities, techniques, and professional skills that the core will provide. The role of the core leader and each of the key participants should be described. The portion of the application describing each scientific core should be prepared with the same level of detail as an R01 application in order for the technical merit and appropriateness of each core to be evaluated. A summary table following the format suggested in Table IV (Appendix) should be submitted listing any cores and showing the apportionment of core resources between the research projects. In the event that any core support subproject is located at an institution other than that of the project it supports, the following form PHS 398 pages should be used and the instructions for preparing a consortium budget should be followed: Face Page Form PHS 398. Complete the form and enter a descriptive name of the requested core (e.g., Administrative Core, Monoclonal Antibody Production Core) in item 1, Title of Project. Pages 4 and 5 of Form PHS 398: Complete the budget pages providing justifications with the same detail as in research projects. The budget for core units should be presented according to the instructions indicated on pages 16-19 of the form PHS 398 Instructions. A detailed budget is required for the first year (form PHS 398, page 4) and a budget summary for all additional years (form PHS 398, page 5). Explicit detailed budget justifications for all years should be included. Pages 6 - 8 of form PHS 398. Provide the biographical sketches and information on "Other Support" of all participating investigators in the Core. FOLLOW INSTRUCTIONS CAREFULLY. Incomplete, inaccurate or ambiguous information about OTHER SUPPORT, whether active or pending, may lead to delays in the review of the application. Include information required to describe Resources and Environment available to the Core as well as appropriate sections pertaining to vertebrate animals. D. General Instructions The research grant application form PHS 398 (rev. 9/91) is to be used in applying for cooperative agreements. These forms are available at most institutional offices of sponsored research, and from the Office of Grants Information, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone (301) 594-7248. The RFA label available in form PHS 398 (rev. 9/91) must be affixed to the bottom of the face page of the original signed application. Failure to use this label could result in delayed processing of the application such that it may not reach the committee in time for review. Applications that are not received as a single package from the Principal Investigator and that do not conform to the instructions contained in PHS 398 (rev. 9/91) applications kit will be judged non-responsive and will be returned to the applicant. The applicant may include additional detailed information in an appendix, but this should be limited only to information essential to the application. Item D of form PHS 398: "Specific Instructions, Appendix" should be carefully followed in preparing appendix material. Applicants are advised to place data or information crucial to the research plan within the application itself and not in the appendix; failure to abide by this requirement may result in an inadequate review. All appended material must be clearly labelled and cross-referenced to indicate the specific project to which it applies. Prepare five sets of the appendix, including only relevant reprints, making sure that the reprints are cross-referenced to specific projects as well. Submit a signed, original of the application, including the Checklist, and three signed, single-sided photocopies, in one package to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** At the same time as the submission to DRG, send two additional exact copies of the application with the five sets of appendices, in a separate package, directly to: Dianne Tingley, Ph.D. Division of AIDS National Institute of Allergy and Infectious Diseases Solar Building, Room 4C16 6003 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-0818 Applications must be received by January 21, 1994. Applications received after that date will be returned without review. The Division of Research Grants (DRG) will not accept an application in response to this RFA which is essentially the same as one pending initial review, unless the applicant withdraws the pending application. DRG will not accept an application which is essentially the same as one already reviewed. Simultaneous submission of identical applications will not be allowed, nor will essentially identical applications to be reviewed by different review committees. This restriction is superseded by an NIH policy permitting concurrent submission of a duplicate R01 and a component of a multi-project application. The NIH policy however, further stipulates that should both the R01 and the multi-project application be considered for funding, the R01 will be relinquished in favor of the multi-project application. REVIEW CONSIDERATIONS Applications will be reviewed by the Division of Research Grants for completeness and by NIAID staff to determine administrative and programmatic responsiveness to this RFA; those judged to be non-responsive will be returned to the applicant without review. Applications with budgets in excess of $800,000 total (direct and indirect) first year costs will be returned without review. Those applications that are complete and responsive may be subjected to triage by an NIAID peer review group before or during the scientific review, to determine their scientific merit relative to the other applications received in response to this RFA. The NIAID will remove from further competition those applications judged to be noncompetitive for award and will notify the applicant (Principal Investigator) and responsible institutional official. Those applications that are complete and responsive will be evaluated in accordance with the criteria stated below for scientific/technical merit by an appropriate review committee convened by the NIAID. In the event of multiple, highly qualified applications, final funding recommendations will be based on highest Program priorities. The second level of review will be provided by the National Advisory Allergy and Infectious Diseases Council. Review Criteria The application must be directed towards the attainment of the stated programmatic goals (see Research Objectives). The following factors are the criteria used by peer review groups in the scientific and technical review of applications for drug discovery: o The scientific and technical merit of the program as a whole, as well as that of each individual research project and core components, for realization of drug discovery objectives; the scientific and technical significance of the overall program goals; the development of a well-defined central research focus; and originality and uniqueness of proposed research. Each project must be supportable on its own merit. o Relevance of the Group's objectives to the discovery of new entities and strategies for the treatment of tuberculosis and the likelihood that new potential therapies will be identified during the course of the proposed study. Priority will be given to proposed therapies with potential for combatting multidrug resistant tuberculosis, improving prophylaxis approaches, practicality of administration to HIV-infected people, and low toxicity. o Specific competencies of the Principal Investigator and Project Leaders to conduct the proposed work: documented research experience, commitment, and time availability of Principal Investigator, Project Leaders, and other key personnel. While there is no mandatory percent effort set, it is anticipated that, due to the complexity and time required to maintain a well-coordinated and productive research effort, a minimum 20 percent effort by the Principal Investigator and each Project Leader may be important to the success of the Group. o Documented research experience and accomplishments of investigators in the research areas outlined in the RFA; accomplishments of the Group to date (for competitive supplement applications). o Technical merit of proposed methods for producing and evaluating test materials, and technical sufficiency of methods for evaluation of new discoveries, test systems, models, etc. o Administrative experience and competence of Principal Investigator in the development, implementation, and management of comprehensive research programs; and plans for effective intra-Group communication and for assuring Group cohesiveness within each project and within the Group as a whole. o Adequacy of existing physical facilities and resources of the Principal Investigator and Project Leaders, including biohazard containment facilities. o Documented commitment of institutions represented by Group members; documented capability of Principal Investigator's institution to serve as Central Operations Office for the Group. The initial review group may make recommendations regarding appropriateness of applicants' specific aims to programmatic goals, deletion of projects or cores not essential to drug discovery, administrative oversight by program staff, and disaggregation of outstanding projects for consideration as individual research grants. The initial review group will review each project and core within the application individually, followed by scoring of the application as a whole. AWARD CRITERIA The primary criterion for award is the scientific and technical merit of the application as judged by peer reviewers and reflected in the priority score. Additional award criteria are the availability of funds, receipt of a sufficient number of scientifically meritorious applications that are responsive to this RFA, and overall programmatic relevance and priority. INQUIRIES The opportunity to clarify issues or questions about the RFA from potential applicants is welcome. Direct inquiries regarding the RFA and programmatic issues should be sent to: Barbara Laughon, Ph.D. Division of AIDS National Institute of Allergy and Infectious Diseases Solar Building, Room 2C35 6003 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 402-2304 FAX: (301) 402-3211 Inquiries pertaining to review of applications may be directed to: Dianne Tingley, Ph.D. Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4C16 6003 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-0818 FAX: (301) 402-2638 Inquiries regarding fiscal matters may be directed to: Ms. Jane Unsworth Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4B22 6003 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-7075 FAX: (301) 480-3780 Schedule Letter of Intent Receipt Date: November 15, 1993 Application Receipt Date: January 21, 1994 Scientific Review Date: March 1994 Advisory Council Date: June 1994 Award Date: July/August 1994 AUTHORITY AND REGULATIONS This program is described in the catalog of Federal Domestic Assistance, 93.856 - Microbiology and Infectious Diseases Research and 93.855 - Immunology, Allergic and Immunologic Diseases Research. Awards are made under the authority of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grant policies and Federal Regulations 42 CFR Part 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency Review. From owner-sci-resources@net.bio.net Thu Sep 02 23:00:00 1993 Path: biosci!net.bio.net From: kristoff@net.bio.net (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 22, no. 32, pt. 4, 3 September 1993 Message-ID: Date: 3 Sep 93 01:43:44 GMT Sender: kristoff@net.bio.net Lines: 1378 Approved: biosci-moderator@net.bio.net $$XID RFA CA93038 CA-93-038 P1O1 *************************************** IDENTIFICATION AND EVALUATION OF TISSUE MARKERS FOR PATHOLOGICAL CLASSIFICATION OF HUMAN GLIOMAS NIH GUIDE, Volume 22, Number 32, September 3, 1993 RFA: CA-93-038 P.T. 34; K.W. 0760003, 0715035 National Cancer Institute Letter of Intent Receipt Date: October 6, 1993 Application Receipt Date: December 7, 1993 PURPOSE The Cancer Diagnosis Branch of the Division of Cancer Biology, Diagnosis and Centers, National Cancer Institute (NCI) invites applications for cooperative agreements from institutions to identify and evaluate tissue markers for improving the pathological classification of human gliomas. Precise pathologic diagnosis and/or classification of gliomas is often difficult. Since the incidence and mortality of brain tumors are increasing, and gliomas constitute the most common class of these important tumors, improved classification would be beneficial to clinicians making decisions about patient management. For the purposes of this RFA, gliomas are meant to include astrocytomas, mixed astrocytomas/oligodendrogliomas, and oligodendrogliomas. The purpose of the proposed awards is to extend and expand the ongoing inter-institutional studies of the Glioma Marker Network to increase the availability of patient resources and enhance the technical capabilities of the Network to efficiently test clinical correlative hypotheses. The Network will carry out collaborative studies designed to continue the evaluation of a variety of glioma markers, identify additional promising markers, and correlate the markers with clinical parameters. The cooperative studies funded by this RFA will optimize the use of rare tissue resources. This RFA will also provide funding for coordinated management and statistical analyses of data collected by Network investigators. These studies will take advantage of the synergy resulting from collaborations among neuropathologists, clinicians, cancer biologists, and statisticians. 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), Identification and Evaluation of Tissue Markers for Pathological Classification of Human Gliomas, is related to the priority area of cancer. Potential applicants may obtain a copy of "Healthy people 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202/783-3238). ELIGIBILITY REQUIREMENTS Applicant organizations must be located in the United States, Canada, or Mexico. Non-profit organizations and institutions, and government agencies are eligible to apply. For-profit organizations are also eligible. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT The administrative and funding mechanism to be used to support the Glioma Network is the cooperative agreement (U01), an assistance mechanism in which substantial NCI program staff involvement with the recipient during performance of the planned activities is anticipated. Under the cooperative agreement, the NCI purpose is to support and/or stimulate the recipient's activities by collaborating and otherwise working jointly with the award recipient in a partner role. Details of the responsibilities, relationships, 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 awardees retain full responsibility for planning and direction of the projects within the guidelines of the RFA and for performance of the proposed studies. There is no intent, real or implied, for NCI staff to direct awardee activities or limit the freedom of the funded investigators. Awards will be administered under PHS grants policy as stated in the Public Health Service Grants Policy statement, DHHS Publication No. (OASH) 90-50,000, revised October 1, 1990. This RFA is a one-time solicitation. However, if it is determined that there is sufficient continuing program need, the NCI will invite recipients of awards under this RFA to submit competitive continuation cooperative agreement applications for review according to the procedures described in REVIEW CONSIDERATIONS. FUNDS AVAILABLE The NCI anticipates making four to six awards for project periods up to four years and anticipates a total of $1,200,000 will be set aside for the initial year's funding. Because of the nature and scope of the research proposed in response to this RFA may vary, it is anticipated that the sizes of awards will vary also. Funding in response to this RFA is dependent on the receipt of a sufficient number of applications of high scientific merit. The earliest feasible start date for the initial awards will be September 1, 1994. Although the program is provided for in the financial plans of the NCI, the award of cooperative agreements pursuant to this RFA is contingent on the availability of funds appropriated for fiscal year 1994. RESEARCH OBJECTIVES Background Gliomas, the most common CNS tumors in adults, are divided into three major classes that are characterized by differences in clinical behavior. The highly malignant glioblastoma multiform are uniformly fatal with no effective therapy available. Well differentiated astrocytomas and oligodendrogliomas are least malignant and are generally amenable to surgery and radiation therapy. Overall oligodendrogliomas have a better prognosis than comparable astrocytomas. Anaplastic astrocytomas, a diverse group of tumors with intermediate malignancy, have a variable clinical outcome. Approximately half the patients with anaplastic astrocytomas respond well to a combination of radiotherapy and chemotherapy. The histological classifications currently in use do not identify the subset of patients who will have a better clinical outcome or who will respond to specific therapy. The identification of these patients would enable clinicians to design more effective treatment regimens. The inability of classification schemes to predict outcome and response to therapy suggests that there are biologically distinct subsets of tumors that cannot be distinguished morphologically. Significant variation in tumor classification can result from using different histological classification schemes. In addition, classification of anaplastic astrocytomas using any single classification scheme fails because the clinical behavior of these tumors is highly variable. Neuropathologists from the current Glioma Marker Network have focused on identifying histological features that contribute to differences in classification. Mixed astrocytomas/oligodendrogliomas, which appear to have a favorable prognosis, have been identified as being particularly difficult to classify using the current classification schemes. The application of molecular genetic, cytogenetic, and immunohistological techniques to the study of CNS tumor markers is being reported more frequently in the literature. Common chromosomal alterations, mutations in tumor suppressor genes and gene overexpression or amplification have been reported in gliomas. Correlation of chromosomal alterations and molecular markers with tumor initiation and progression and with clinical parameters may aid in the classification of the tumors and the identification of a subset of gliomas with high malignant potential and poor clinical outcome. Promising prognostic markers need to be evaluated in larger scale clinical trials before they can be used by clinicians for patient management. Research Goals and Scope The objective of this RFA is to invite applications for cooperative agreements to extend and expand the Glioma Marker Network currently carrying out studies to identify and evaluate molecular markers for improving the pathological classification of human gliomas. Applicants should propose studies with hypotheses designed to evaluate tumor markers and to correlate markers with clinical parameters. Applications should discuss the use of molecular genetic, cytogenetic, immunohistological, and/or biochemical techniques in studies of glial tumor markers that will be useful in tumor classification. Collaborations among neuropathologists, clinicians, cancer biologists, and statisticians are critical to these types of studies and are specifically encouraged. Applicants should address approaches to establishing correlations between tumor markers and clinical parameters. The hypotheses to be tested by the proposed studies should be clearly stated and the rationale for the study design and experimental techniques selected thoroughly discussed. Sufficient preliminary data should be provided to support the feasibility of the proposed studies. Applications should include a discussion of the statistical issues related to study design and data analysis. A goal of the RFA is to promote collaborative studies to optimize the use of rare tissue resources. The cooperative agreement mechanism was chosen to facilitate the coordinated management of tissue resources with associated clinical data and the statistical analyses of data generated in collaborative studies. Applicants should discuss their anticipated contribution to collaborative studies carried out by the Network. SPECIAL REQUIREMENTS The Cooperative Agreements (U01) will require cooperation between an NCI representative (Program Administrator) and the Principal Investigators (PIs) of the individual funded projects in order to facilitate effective interactions among the cooperating institutions. The Program Administrator will assist in coordinating the activities of the research groups and in the exchange of information. The following terms and conditions will be incorporated into the award statement and provided to the Principal Investigator(s) and the institutional officials at the time of award. Awardee Rights and Responsibilities Awardees are responsible for proposing research projects to advance the goals set forth in the RFA and for participating in the development and conduct of Network studies. All studies approved by the Coordinating Committee will be conducted by the members of the Network with responsibilities for specific aspects of the study determined by the Committee at the time the study is developed. The PI and one other member of each cooperating institution are required to attend meetings of the Coordinating Committee to help formulate policies and protocols for the Network, to facilitate implementation of these policies and to participate in the analysis of data submitted by the participating research groups. Awardees will retain custody and primary rights to their data developed under these awards, subject to Government rights of access consistent with current DHHS, PHS and NIH policies. NCI Staff Responsibilities The Program Administrator (identified under INQUIRIES) has two areas of responsibility, administration of the program and collaboration with funded investigators. The Program Administrator will coordinate and facilitate the programs supported by these Cooperative Agreements, but will not direct activities of the Research Network. As a voting member of the Coordinating Committee, the Program Administrator will attend and participate in all meetings and assist in developing operating policies, quality control procedures and consistent polices for dealing with recurring situations that require coordinated action. The Program Administrator will communicate NCI policies and priorities to the Coordinating Committee. The Program Administrator will monitor research progress and may review the activities of individual laboratories for compliance with the protocols, quality control procedures and policies established by the Coordinating Committee. The Program Administrator can recommend withholding of support, suspension or termination of an award for failure to comply with Network or NCI policies. Collaborative Responsibilities The NCI Program Administrator and the awardees are responsible for establishing a Coordinating Committee as defined below. The Coordinating Committee will develop operating policies and research protocols which will be submitted to the Program Administrator for review of concurrence to NCI policies prior to implementation. The Program Administrator will facilitate the review of the policies and protocols and discuss the results of the review with the Coordinating Committee. An arbitration system, as detailed below, will be available to resolve differences between the Program Administrator and the members of the Coordinating Committee. The Coordinating Committee will review the plans for Network studies and operating procedures proposed by the individual research groups to insure overall compatibility with the goals of the RFA. Members of the Coordinating Committee will be responsible for redefining research goals and for defining strategies for Network studies in order to optimize progress and the efficient use of tissue resources. The Coordinating Committee will also be responsible for coordinating Network activities such as the design and implementation of a central data base for tissue samples and associated clinical data, design of required forms, distribution of reagents and tissue samples, pathological review of tissue samples, monitoring research progress, data collection, statistical design for data analysis and maintaining quality assurance. The Coordinating Committee will consist of the NCI Program Administrator and two members from each cooperating institution, preferably a clinician or neuropathologist and a basic scientist or statistician. One of the two members must be the Principal Investigator. The Coordinating Committee will be responsible for electing a chairperson, who will not be the Program Administrator. This may be a rotating position. The Chairperson of the Coordinating Committee will be responsible for coordinating the Committee activities, for preparing agendas for meetings and conference calls, for scheduling and chairing meetings. The Program Administrator will attend and participate in all meetings of the Coordinating Committee and should be kept informed of interactions between research groups. The Coordinating Committee will prepare an annual report of Network activities which will include reports from each participating research group. Each Principal Investigator is responsible for the timely preparation of a report of individual group activities. The Coordinating Committee will meet three times the first year; first, shortly after the cooperative agreements are awarded to plan basic operating procedures and to initiate integration of the participating programs and twice more to monitor Network progress, and will meet twice yearly thereafter. The meetings may be held at any of the participating institutions or at any other convenient location with concurrence of the NCI. The meetings will be used to plan research activities, coordinate tissue utilization, establish priorities, monitor progress, and address administrative issues. Arbitration Procedures An arbitration panel of external consultants will be created to resolve any irreconcilable differences of opinion related to scientific/programmatic matters between the Program Administrator and the members of the Coordinating Committee with respect to implementation of a proposed operating policy. The panel will include one member selected by the Coordinating Committee without participation of the Program Administrator, one member selected by the NCI and a third member selected by the other two members of the arbitration panel. The NCI arbitration process for the Cooperative Agreement in no way affects the rights of awardees to appeal selected postaward administrative decisions in accordance with PHS regulation at 42 CFR part 50, subpart D and HHS regulations 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 applications 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 or 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 populations-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 American [including American Indians or Alaskan Natives], Asian/Pacific Islanders, Blacks, Hispanics). The rationale for studies on single minority population groups should be provided. For the purpose of this policy, clinical research is defined as human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including, but not limited to, clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded. However, every effort should be made to include human tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. For foreign awards, the policy on inclusion of women applies fully; since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. If the required information is not contained within the application, the application will be returned. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question(s) addressed and the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and will be reflected in assigning the priority score to the application. All applications for clinical research submitted to 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 ask to submit, by October 6, 1993, a letter of intent that includes a descriptive title of the proposed project, the name, address, and telephone number of the Principal Investigator, the names of key personnel, any collaborating institutions, and the number and title of the RFA in response to which the application may be submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, it is requested in order to provide an indication of the number and scope of the applications to be reviewed. This information allows NCI staff to estimate potential workload and to avoid conflict of interest in the review. The letter of intent is to be sent to Dr. James W. Jacobson at the address listed under INQUIRES below. APPLICATION PROCEDURES The grant application form PHS 398 (rev. 9/91) is to be used for the cooperative agreement application. These forms are available from most offices of sponsored research; from the Office of Grants Information, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892-4500, telephone 301/584-7248; and from Dr. James W. Jacobson at the address and telephone number listed under INQUIRIES below. The RFA label available in the application form PHS 398 (rev. 9/91) must be affixed to the bottom of the face page. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time to be reviewed. The RFA number and title must be typed on line 2a of the face page of the application form as well. Submit a signed typewritten original of the application, including a checklist, and three signed, exact, clear, and single-sided photocopies in one package to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892-4500** At the time of submission, send two additional copies of the application to: Ms. Toby Friedberg, Referral Officer Division of Extramural Activities National Cancer Institute Executive Plaza North, Room 636 6130 Executive Boulevard Bethesda, MD 20892 Applications must be received by December 7, 1993. Applications received after this date will be returned. The Division of Research Grants (DRG) will not accept any application in response to this announcement that is the same as one currently pending initial review, unless the applicant withdraws the pending application. The DRG will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of substantial revisions of applications already reviewed, but such application must include an introduction addressing the previous critique. Special Instructions for Preparation of Cooperative Agreement Applications Applicants must propose feasible scientific studies that address the goals of the RFA with specific reference to the issues discussed in the REVIEW CRITERIA section. It is critical that each applicant address issues relating to participation in a cooperative agreement research network. Each applicant should include specific plans for responding to the "Terms and Conditions of Award" discussed above. Applicants should indicate their willingness to interact with the other awardees and provide a clear description of the nature of proposed interactions. They should also describe how they will comply with the involvement of the NCI representative. Each applicant should anticipate the participation of the Principal Investigator and one other member of the research group on the Coordinating Committee that meets three times in the first year and twice yearly in each subsequent year. Travel funds for attending the Coordinating Committee meeting should be included as a budget line item. For planning purposes either three trips to Washington DC or one trip each to the East Coast, West Coast, and Central U.S. may be proposed for the first year. REVIEW CONSIDERATIONS Review Procedures Upon receipt, applications will be reviewed (initially) by the DRG for completeness. Incomplete applications will be returned to the applicant without further consideration. Evaluation for responsiveness to the RFA is an NCI program staff function. An application judged non-responsive will be returned by the NCI, but may be resubmitted as an investigator-initiated regular research grant (R01) at the next receipt date. The application would require modification in accordance with the R01 guidelines. The new application would not be considered an application for a cooperative agreement, nor would it be considered a response to this RFA. If the number of applications is large compared to the number of awards to be made, the NCI may conduct a preliminary scientific peer review (triage) by an NCI peer review group to determine their relative competitiveness. The NIH will remove from further competition those applications that are judged to be noncompetitive and notify the applicant Principal Investigator and institutional official. Those applications judged to be competitive and responsive will be evaluated for technical merit according to the review criteria stated below by an appropriate peer review group convened by the Division of Extramural Activities, NCI. The second level of review by the National Cancer Advisory Board considers the special needs of the Institute and the priorities of the National Cancer Program. Review Criteria Reviewers will be asked to review the grant applications by considering the following criteria: 1. Scientific merit and feasibility of the proposed research and its relevance to the goals and objectives of the RFA. 2. The appropriateness of the proposed techniques and methodologies to be used. 3. Qualifications, experience and proposed responsibilities of the Principal Investigator and other key personnel. 4. Demonstration of access to appropriate patient populations or access to frozen and/or fixed tumor tissue samples, with associated clinical data. 5. Adequacy of discussion of statistical issues related to study design and data analysis. 6. Adequacy of proposed collaboration between basic scientists and clinicians. 7. Plans for effective cooperation and coordination among participating awardees and the NCI. 8. Availability and quality of facilities and resources for the proposed research. 9. Adequacy of provisions for the protection of human subjects. The review group will critically examine the submitted budget and will recommend an appropriate budget and period of support for each favorably recommended application. AWARD CRITERIA The anticipated date of award is September 1, 1994. Awards will be based on the peer reviewed priority score and programmatic priorities. INQUIRIES Written and telephone inquiries concerning the objectives and scope of this RFA are encouraged. The Program Director welcomes the opportunity to clarify any issues or questions from potential applicants. Direct inquiries regarding programmatic issues to: James W. Jacobson, Ph.D. Division of Cancer Biology, Diagnosis and Centers National Cancer Institute Executive Plaza North, Room 513 6130 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-1591 FAX: (301) 402-1037 Direct inquires regarding fiscal and administrative matters to: Robert E. Hawkins, Jr. Grants Administration Branch National Cancer Institute Executive Plaza South, Room 243 6120 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-7800 Ext. 13 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.394, Cancer Detection and Diagnostic Research. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is no subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$XID RFA AG94002 AG-94-002 P1O1 *************************************** MENOPAUSE AND HEALTH IN AGING WOMEN NIH GUIDE, Volume 22, Number 32, September 3, 1993 RFA: AG-94-002 P.T. 34, II; K.W. 0710010, 0413002, 1002061 National Institute on Aging National Institute of Nursing Research Office of Research on Women's Health Letter of Intent Receipt Date: October 15, 1993 Application Receipt Date: November 29, 1993 PURPOSE The National Institute on Aging (NIA), the National Institute of Nursing Research (NINR), and the Office of Research on Women's Health (ORWH) invite cooperative agreement applications for Clinical Sites to conduct prospective longitudinal studies of the natural history of menopause and the decline in ovarian function in women. The primary objective of this initiative is to characterize the chronology of the biological and psychosocial antecedents and sequelae of the menopausal transition and the effect of this transition on subsequent health and risk factors for age-related disease. To promote essential collaborative aspects of this initiative, applications are also requested for a Central Laboratory to conduct standardized assays of markers of ovarian aging or aging of the ovarian-hypothalamo-pituitary axis and for a Coordinating Center to coordinate the collection, management, and analysis of a common data set. (The Clinical Sites, the Central Laboratory, and the Coordinating Center are referred to hereinafter as "Organizational Components or Components.") Because the menopausal experience in minority women has been particularly neglected, special emphasis in minority populations on the unique biological and socio-cultural factors that may differentially influence the menopausal transition and its consequences is an integral part of this initiative. Applications that propose studies in populations that are predominantly or totally of minority composition are strongly 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 Request for Applications (RFA), Menopause and Health in Aging Women, is related to the priority area of older adults and preventive services. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Due to the need for close coordination and monitoring, no foreign or international components will be considered in this RFA. Applications from minorities and women are encouraged. 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 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 under the section Terms and Conditions of Award. Applicants will be responsible for the planning, direction, and execution of their individual proposed project and for planning and participating in collaborative activities with other award recipients under this RFA. All parties agree to accept the participatory and cooperative nature of the group process. Awards will be administered under PHS grants policy as stated in the PHS Grants Policy Statement, DHHS Publication NO. (OASH) 90-50,000, revised October 1, 1990. The total project period for applications submitted in response to this RFA may not exceed five years in duration. Proposed research should pose hypotheses or questions that can be successfully addressed in this period. The anticipated award date is July 1, 1994. It is anticipated that there will be a renewed competition after five years because extended longitudinal follow-up beyond the initial project period is strongly desired. If the program of cooperative agreements are not continued, the awardees may submit grant applications through the usual investigator-initiated grants program. FUNDS AVAILABLE It is expected that up to $2.3 million (total cost) for first year expenses will be available in Fiscal Year 1994 to fund five Clinical Sites plus a Coordinating Center and a Central Laboratory from applications submitted in response to this RFA. If an institution seeks to be selected for more than one type of Organizational Component, separate applications must be filed for each Component, with distinct budgets that are independent of each other and do not overlap in either objectives or budget items. The requested total funding (direct plus indirect costs) for the first year may not exceed $350,000 for Clinical Site applications, $250,000 for Coordinating Center applications and $300,000 for Central Laboratory applications. For the entire five-year project period, total (direct plus indirect) costs requested per application may not exceed $1.75 million for each Clinical Site, $1.25 million for the Coordinating Center and $1.5 million for the Central Laboratory. Within these limits, escalations after the first year for recurring costs are limited to 4 percent per year. Applications failing to meet these requirements will not be reviewed. This level of support is dependent on the receipt of a sufficient number of applications of high scientific merit. Although this program will be provided for in the financial plans of the NIA and co-sponsors of this RFA, the award of grants pursuant to this RFA are contingent upon the availability of funds for this purpose. RESEARCH OBJECTIVES Background Menopause is a universal phenomenon in female aging. Although the decline in ovarian function is increasingly believed to play a significant role in the etiology of short- and long-term disorders and diseases, relatively little research has focussed on menopause and scientific information is limited on the physiological and behavioral changes preceding and following the cessation of menses. Striking hormonal aberrations have been observed in the perimenopause and profound metabolic alterations are known to occur in very different biological systems, such as the musculoskeletal system (accelerated loss of bone and muscle), the urogenital system (atrophy) and the central nervous system (hot flashes, mood and memory alterations and sleep disturbances). Reduced ovarian hormone levels may play a key role in osteoporosis, and are associated with an increase risk of cardiovascular disease (CVD) and other disorders, such as urinary incontinence. There is considerable individual variation among women in the manifestation of perimenopausal signs and symptoms. The peri- and postmenopausal experience encompasses a complex interaction of socio-cultural, psychological, and environmental factors as well as biological changes relating strictly to altered ovarian hormone status or deficiency. In the U.S., the perimenopausal experience is usually perceived largely in negative terms -- as a transitional phase dominated by disturbing physical and mental symptoms. It has been suggested that highly negative characterizations of menopause may be due to an over-sampling of clinical populations of perimenopausal women, who, seeking treatment for symptoms, were more readily available for study and whose experiences represented the extremes of a difficult transition. Importantly, our knowledge base on menopause is extremely narrow in that it applies almost exclusively to white women (of Northwest European ancestry) -- very little is known about the range of perimenopausal experiences in women of other racial/ethnic (i.e., African, Asian, Native American, Hispanic) background(s). The socio-cultural and behavioral antecedents and consequences of menopause have also not been well addressed and major gaps exist in our understanding of factors that may profoundly influence the perception of, and response to, perimenopausal symptoms and sequelae. Because of a general lack of accurate information, there has also been considerable confusion with respect to the potential risks and benefits to be realized by long-term postmenopausal hormone therapy. The NIH Women's Health Initiative (WHI) will explore a variety of important issues and interventions relevant to postmenopausal health, such as the effects of dietary fat, specific dietary factors, and hormone replacement therapy on endpoints that include cardiovascular disease, osteoporosis; and breast, colon, and endometrial cancer. However, an assessment of pre- and perimenopausal women, and hence an understanding of the natural history of menopause, is not among its objectives. This RFA will complement the WHI by providing information on the period preceding the cessation of menstruation, which may be crucial in clarifying why certain segments of postmenopausal women may benefit more from hormone therapy than others. Objectives and Scope The goal of this RFA is to stimulate comprehensive multidisciplinary research into the natural history of the menopause and the effect of the perimenopausal transition on woman's aging and subsequent susceptibility to disease. Thus this RFA is relevant to the implementation of Public Law 103-43, National Institutes of Health Revitalization Act of 1993, Title VIII, Section 801, which directs the NIA, in cooperation with other Institutes, Centers and Divisions (ICDs), to support research on the aging processes of women, with special emphasis on the changes associated with the transition from pre- to postmenopause, and the effect of this transition on disorders and complications related to aging and reduced ovarian hormone levels. Because this initiative aims to generate epidemiologic studies in premenopausal women of the chronology and characteristics of the perimenopausal transition per se, and not to launch clinical intervention trials of hormone or other therapies, applications focused on testing treatment strategies will be considered not responsive to this RFA. However, it is recognized that as premenopausal women approach and traverse the menopause, there will be subgroups who have symptoms and/or other indications that are of sufficient concern to warrant consideration of treatment with estrogen or other agents. Hence, proposed research should address potential symptoms and problems that may arise and require management and formulate approaches with respect to providing information and/or referral. Proposed studies should also include methods for statistical handling of women who start and stop estrogen therapy and of women whose menopausal experience may be confounded by medications and procedures such as hysterectomy/oophorectomy, radiation therapy which may induce an apparent or artificial menopause, etc. A number of research areas have been identified in a background paper titled "The Menopause, Hormone Therapy, and Women's Health" [U.S. Congress, Office of Technology Assessment, OTA-BP-BA-88, Washington DC:U.S. Government Printing Office, May 1992] and in "Report of the National Institutes of Health: Opportunities for Research on Women's Health [S/N 017-040-00522-9 obtainable from the Superintendent of Documents, Government Printing Office, P.O. Box 371954, Pittsburgh, PA 15230-7954; FAX 202-512-2250]. Additional research opportunities were identified at the March 1993 NIH Workshop on Menopause: Current Knowledge and Recommendations for Research. The research objectives or aims of this initiative reflect a consolidation of major recurring themes from these sources. Because of the multidisciplinary nature of this RFA, applicants, either individually or in collaboration with others, should demonstrate interdisciplinary skills and expertise in a variety of areas such as gynecology, reproductive endocrinology, internal medicine, geriatrics, nursing, cardiology, neurology, bone metabolism, muscle and renal physiology, nutrition, psychology, sociology, epidemiology, and biostatistics. Awardees at Clinical Sites are expected to recruit a cohort of premenopausal women to characterize the chronology and physiological concomitants and consequences of the pre- to postmenopausal transition. Planned research by all Clinical Sites and, where appropriate, by the Coordinating Center and the Central Laboratory, should: o identify and utilize appropriate markers of ovarian aging or aging of the ovarian-hypothalamo-pituitary axis (e.g., FSH, LH, or, preferably, other state-of-the art measures) and relate these markers to alterations in menstrual cycle characteristics as women approach and traverse menopause o elucidate factors that differentiate (1) symptomatic from asymptomatic women and (2) women most susceptible to long-term pathophysiological consequences of ovarian hormone deficiency from those who are protected; o insure adequate statistical power to evaluate the transition from pre- to postmenopause in women undergoing natural menopause o collect and analyze data on demographics, health and social characteristics, race/ethnicity, reproductive history, pre-existing illness, physical activity, health practices After addressing these general requirements, studies proposed by Clinical Sites should focus on a specific system or function(s) affected by, or of relevance to, menopause. Examples of topic areas of interest include, but are not limited to: o determinants of the age of menopause; age and menopause-related changes in the female genitourinary tract; changes in circadian and ultradian biorhythms o effects of menopause on alterations in body composition and biological function (i.e., changes in muscle mass, adiposity and fat patterning, skeletal mass, gastrointestinal function, cardiovascular and renal function, immune function, cognitive function, etc); o the effect of the pre- to postmenopausal transition on bone mass, bone quality, the recruitment and activity of bone cells (or their precursors), markers of bone metabolism, the response of bone and bone cells to mechanical stress o transmenopausal changes in cardiovascular risk factors and characteristics such as cardiac or arterial responsiveness, calcification or atherosclerosis progression o menopause-related changes in nutrition and metabolism o psychosocial interactions of menopausal symptoms and sequelae with women's health-related behaviors, sexuality, social functioning and use of health care o psychosocial, cultural and behavioral determinants of perceptions of, and responses to, menopausal symptoms; factors affecting treatment choices and management strategies for menopausal symptoms SPECIAL REQUIREMENTS The broad outline of areas of interest presented above is offered only as a point of departure. Studies proposed for Clinical Sites should include discussion of design (including parameters and outcomes), eligibility criteria, protocol issues, content of baseline and follow-up examinations and related statistical and data management issues. Research planned for Clinical Sites and for the Central Laboratory should indicate which measurements should be made in common and include the rationale for selecting those measurements and their proposed frequency. All prospective awardees should describe strategies for the establishment of collaborative arrangements with other awardees. The initial meetings of awardees of all Components (Clinical Sites, Coordinating Center and Central Laboratory) and NIH program staff will serve to coordinate the individual research projects by developing operational definitions for the perimenopause, determining the feasibility of adopting common age-ranges and eligibility criteria and establishing a common data set for baseline and follow-up examinations. It is anticipated that approximately six months will be required for the development of a protocol and the drafting of a manual of procedures for the generation of the common data set. A Steering Committee will have overall responsibility for the development and finalization of the collaborative protocol. The principal investigators of the Clinical Sites, the Coordinating Center, the Central Laboratory and the NIA program administrator will comprise the voting members of the Steering Committee. The protocol will be subject to review by an outside expert group. The study will proceed into its second (or implementation) phase only with the concurrence of both the awardees and the NIH. Designated NIH staff will meet in Bethesda with Principal Investigators and key staff up to four times in the first year and at least every six months thereafter to discuss new developments, review research progress and difficulties, coordinate ongoing research and plan future research activities. Applicants should include a statement about their willingness to participate in such activities. Travel funds for key staff (two to three people) to attend these meetings should be included as a budget line item in each application. Organizational Components 1. Clinical Sites A Clinical Site is the institution that receives an award for recruiting a cohort of premenopausal women and for conducting the investigation(s) under this RFA. The Principal Investigator (PI) is encouraged (as appropriate) to form a multidisciplinary team to focus on biomedical and psychosocial aspects of the menopausal transition. Applications for individual sites should provide evidence of ability to recruit an adequate number of subjects in order to yield statistically sound results in the proposed area of concentration. There should be evidence of strong institutional support for the site and a stated willingness to follow shared aspects of design, measures and analysis as approved by the Steering Committee. An organizational structure for the site should be set forth in the application, designating lines of authority and responsibility. 2. Coordinating Center The Coordinating Center (CC) will interface with the Clinical Sites, the Central Laboratory, an Advisory Panel, and the NIA program administrator on a variety of topics ranging from seeking and compiling information to providing technical assistance. The CC will have the primary responsibility of standardizing data collection and management and analysis of the common data set. It will work with projects to maximize the potential for cross-site comparability of data; and, ensure that protocols and definitions are consistent across projects through training sessions. It will provide key assistance in designing the data collection system for the shared data and will also be responsible for developing and monitoring quality control. Its staff will collect, edit, store, and analyze shared data generated by the Clinical Sites and participate with other awardees as co-authors in preparing manuscripts that report results from the common data set. In addition, the CC will perform a variety of functions, such as, developing a cross-project Manual of Procedures; maintaining a directory of investigators and co-investigators; arranging all meetings, e.g., for the Steering Committee and ad-hoc meetings of project directors; and facilitating information exchange among the Clinical Sites and NIH. The latter role will include compiling specific reports and developing and implementing common formats across Clinical Sites for all reports, protocols and descriptions (e.g., progress reports, instrument protocols, manuals of operation). The CC will also devise plans for the dissemination of information from new research developments to women, their health care providers, the research community, and policy makers. 3. Central Laboratory The Central Laboratory will have primary responsibility for conducting laboratory determinations in biological samples collected from study subjects for the purposes of establishing the common data set. Prospective awardees should identify the measurements to be made in common and include the rationale for selecting those measurements and the proposed frequency. The final selection of assays will be determined by the Steering Committee during the development of the protocol for establishing the common data set. 4. Steering Committee The Steering Committee will serve as the main decision-making body for the shared aspects of the study. The Steering Committee will have overall responsibility for the study and will develop modifications in the site-specific protocols to facilitate establishment of a common data set using the information provided in this RFA as a guide. The Committee will consist of the Principal Investigator from each Clinical Site, the Coordinating Center, the Central Laboratory, and the NIA Program Administrator. At its first two meetings, the Steering Committee will be convened by the NIA Program Administrator. A chairperson (not from NIH) will be elected subsequently. The Steering Committee will meet every three to six months as needed. 5. Advisory Panel An Advisory Panel (AP) will be selected by the Steering Committee to serve in an advisory capacity to the study and to all of its Organizational Components. The functions of the AP include reviewing project-specific and common core protocols and making suggestions to the awardee(s) and the NIA Program Administrator; monitoring individual project performance, using materials provided by the Coordinating Center; monitoring protocols and information supplied through the Coordinating Center for possible adverse effects associated with the studies; reviewing and advising the awardee(s) and the NIA Program Administrator regarding design and/or protocol changes requested by individual investigators; and reviewing and advising the awardee(s) and the NIA Program Administrator regarding analyses and publications involving multi-project use of common core data. The Panel will consist of experts in relevant medical, behavioral, statistical, and bioethical fields and will convene once per year. Candidates should not be recruited to serve on the Panel or be named prior to the review of the applications by NIA. However, applicants are encouraged to enumerate areas of expertise appropriate for representation on the Panel. The experts must be independent of all Components participating in the cooperative agreement (i.e., not scientifically or fiscally involved). A chair will be elected by members of the Advisory Panel with input from the NIA Program Administrator. The chairperson of the Steering Committee, the Principal Investigator from the Coordinating Center, and the NIA Program Administrator will all participate as non-voting members during each Panel meeting. Per NIH regulations, Panel members will be reimbursed for necessary travel, but will not receive consultant fees for input to individual projects. Travel funds for members of the AP are to be included as a line item in the budget of Coordinating Center applications. Terms and Conditions of Award The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS Grant Administration Regulations at 45 CFR Parts 74 and 92 and other HHS, PHS, and NIH Grant Administration policy statements. The administrative and funding instrument used for this program is 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 working jointly with the award recipient in a partner role, but it is not to assume direction, prime responsibility or a dominant role in this 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 collaborative aspects will be shared among the awardees and the NIA Program Administrator. 1. Awardee Responsibilities Awardees will have primary authorities and responsibilities to define objectives and approaches, and for participant recruitment and follow-up, quality control, data analysis and interpretation, and for preparation of publications from their site-specific protocols. Awardees at the Clinical Sites shall retain custody of, and primary rights to the site-specific data developed under their award, subject to Government rights of access consistent with current HHS, PHS, and NIH policies. In addition, awardees of all Organizational Components (Clinical Sites, Coordinating Center and Central Laboratory) will engage in collaborative activities through participation in Steering Committee meetings and conference calls in the development and implementation of a common protocol establishing a shared data set. Data for the shared data set will be submitted to the Coordinating Center where it will be archived. Protocols developed by the Steering Committee will define rules regarding access to data and publication of findings from analysis of the shared data set. 2. Staff Responsibilities The NIA Program Administrator will have substantial scientific/programmatic involvement during conduct of this activity, through technical assistance, advice and coordination above and beyond normal program stewardship for grants. The awardee agrees to accept assistance from the NIA Program Administrator, as described below: o Participation in the development of the protocol for common measures o Monitoring of performance issues relating to steering committee assignments necessary for the development of the common protocol, recruitment, follow-up, quality control, adherence to protocol and attainment of study objectives. o Providing technical assistance in the formulation or consideration of refinements and adjustments of study objectives, designs and protocols. o Assistance in analysis and reporting of intervention study results The NIA Program Administrator may provide advice on staffing, statistical requirements, and will cooperate with awardees in considering protocol adjustments. In instances where there has been significant involvement in study design and analysis by the NIA Program Administrator, and in accordance with Publication Guidelines developed by the Steering Committee and with NIH policies regarding staff co-authorship of publications resulting from extramural awards, he/she may cooperate with awardees as co-authors in preparing manuscripts that report results from these studies. 3. Collaborative Responsibilities A Steering Committee, composed of the Principal Investigators of each Clinical Site, the Principal Investigator of the Coordinating Center, the Principal Investigator of the Central Laboratory, and the NIA Program Administrator will be the main governing board of the study and will have primary responsibility for developing a protocol for the shared aspects of the study. The Steering Committee will develop modifications in the site-specific protocols to facilitate establishment of a common data set using the information provided in this RFA as a guide. The Steering Committee will also establish subcommittees to oversee major operational components of the study. One vote will be given to each Principal Investigator and to the NIH. The Steering Committee will meet every three to six months as needed. 4. Arbitration Any disagreement that may arise on scientific/programmatic matters (within the scope of the award), between award recipients and the NIH may be brought to arbitration. An arbitration panel will be composed of three members -- one selected by the Steering Committee (with the NIH member not voting) or by the individual awardee in the event of an individual disagreement, a second member selected by the NIH, and the third member selected by the two prior selected members. This special arbitration procedure in no way affects the awardee's right to appeal an adverse action that is other wise appealable in accordance with the PHS regulations at 42 CFR part 50, subpart D and HHS Regulation at 45 CFR part 16. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements are required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis 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. For the purpose of this RFA, investigations are limited to studies of menopause, an event which occurs only in women. If 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 race/ethnic group. In addition, racial/ethnic issues should be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information must be included in the form PHS 398 (rev. 9/91), Parts 1-4 of the Research Plan and summarized in Part 5, Human Subjects under the heading "Study Populations." Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., Native Americans (including American Indians or Alaskan Natives), Asian/Pacific Islanders, Blacks, Hispanics). The rationale for studies on single minority population groups should be provided. For the purpose of this policy, clinical research includes human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including but not limited to clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded. However, every effort should be made to include human tissues from racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. If the required information is not contained within the application, the application will be returned. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of minorities in a study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and will be reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. LETTER OF INTENT Prospective applicants are strongly encouraged to submit, by October 15, 1993, a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the PI, the identities of other key personnel and participating institutions, and the number and title of the RFA in response to which the application may be submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information allows NIA 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. Sherry Sherman at the address listed under INQUIRIES. APPLICATION PROCEDURES Applications are to be submitted on the PHS 398 (rev. 9/91) application form. This form is 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 program administrators listed under INQUIRIES. Essential information on budgets and direct and indirect cost limits is discussed under FUNDS AVAILABLE, budget information on travel for steering committee meetings is discussed under SPECIAL REQUIREMENTS, and budget information about travel to advisory committee meetings is under the description of the advisory committee. 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 must be included with the application. The RFA label available in the application kit must be affixed at the bottom of the face page of the application. Failure to use this label could delay processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title, number, and type of application: "Clinical Site," "Coordinating Center," or "Central Laboratory" must be typed on line 2a of the face page of the application form and the YES box must be checked. Submit a signed, typewritten original of the application, including the Checklist, and three signed, exact photocopies, in one package to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** Two copies of the application with appendices must also be sent to: Chief, Scientific Review Office National Institute on Aging Gateway Building, Suite 2C212 Bethesda, MD 20892 The deadline for receipt of applications is November 29, 1993. Materials will not be accepted after this date. If an application is received after that date, it will be returned to the applicant. The Division of Research Grants (DRG) will not accept any application in response to this announcement that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. Nor will the DRG accept any application that is essentially the same as one already reviewed. This does not preclude the submission of substantial revisions of applications already reviewed, but such applications must include an introduction addressing the previous critique. Applicants must obtain Institutional Review Board (IRB), and if applicable, Institutional Animal Care and Use Committee approval of their application prior to submission. Applications not having these approvals will be returned without review. If approval is not obtained prior to submitting the application, appropriate certifications must be received by the Scientific Review Administrator (SRA) responsible for the review within 60 days after the receipt date, unless requested earlier by the SRA. It is the applicant's responsibility to respond to this requirement. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed by NIH staff for completeness and responsiveness. Incomplete and nonresponsive applications will be returned to the applicant without further consideration. 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 NIA. Applications may be subjected to triage by an NIA 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 identified below. The NIH will withdraw from further competition those applications judged by triage to be noncompetitive for award and notify the applicant Principal Investigator and institutional official. Those applications judged to be competitive will undergo further scientific merit review. The second level of review will be provided by the National Advisory Council on Aging and other relevant Advisory Councils. The major review criteria to be used in the evaluation of applications for all Organizational Components (Clinical Sites, Coordinating Center and Central Laboratory) of this RFA include: significance of the proposed activities to the goals of the RFA; qualifications, experience and commitment of the investigators and their ability to devote the required time and effort to the project; appropriateness and adequacy of the experimental approach and methodology proposed to carry out the research; an understanding of the scientific objectives of the program, as evidenced by discussion of issues relating to the design and implementation of the collaborative aspects of the program; the willingness to work collaboratively with other awardees and with the NIA program administrator in the manner summarized in the RFA; institutional commitment to the requirements of the project and appropriateness of the total budget and budgetary requests. Preference will be given to those applicants who have experience in and commitment to women's health research. Additional review criteria for the Clinical Sites include: scientific merit of the research proposed, justification for proposed sample sizes, assurance that projected sample sizes can be obtained, estimates of subject attrition, adequacy of inclusion of minorities, and appropriateness of suggested measures to be performed in the collaborative protocol. Additional review criteria for the Coordinating Center include: prior experience in functioning as a Coordinating Center in a multi-site study; experience of the Principal Investigator and other key personnel in statistical, data management, quality control, study coordination and administrative aspects of multi-center clinical studies; and proposed data collection and monitoring system. Additional review criteria for the Central Laboratory include: expertise and experience in serving as a Central Laboratory; appropriateness of suggested measures to be performed in the collaborative protocol; laboratory expertise with the procedures, assay methods to be used; adequacy of plans for ensuring maintenance and coordination of quality control standards; adequacy of facilities and supportive environment, including space and equipment for the work proposed; ability to accommodate samples for all sites; and suggested protocol for shipping, handling, and storage of samples as well as for management and transmission of data resulting from the laboratory determinations. AWARD CRITERIA Applications recommended by the National Advisory Council on Aging and other relevant council(s) 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: October 15, 1993 Application Receipt Date: November 29, 1993 Review by National Advisory Council on Aging: June 1994 Anticipated Award Date: July 1994 INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues related to physiologic research on menopause and address the letter of intent to: Dr. Sherry Sherman Geriatrics Program National Institute on Aging Gateway Building, Room 3E327 Bethesda, MD 20892 Telephone: (301) 496-1033 For programmatic issues related to social and behavioral research on menopause, inquiries may be directed to: Dr. Marcia Ory Behavioral and Social Research Program National Institute on Aging Gateway Building, Room 2C234 Bethesda, MD 20892 Telephone: (301) 496-3136 For programmatic issues of relevance to the National Institute of Nursing Research, inquiries may be directed to: Dr. Sharlene Weiss, Ph.D., R.N. National Institute of Nursing Research Westwood Building, Room 757 Bethesda, MD 20894 Telephone: (301) 594-7496 Direct inquiries regarding fiscal matters to: Ms. Joanne Colbert Grants and Contracts Management Office National Institute on Aging Gateway Building, Room 2N212 Bethesda, MD 20892 Telephone: (301) 496-1472 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.866 (Aging Research). Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations, 42 CFR Part 52 and 45 CFR Parts 74 and 92. This program is not subject to the intergovernmental review requirements of Executive Order 12372, or to the Health Systems Agency review. From owner-sci-resources@net.bio.net Thu Sep 09 23:00:00 1993 Path: biosci!NET.BIO.NET!kristoff From: kristoff@NET.BIO.NET (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: No NIH Guide This Week Message-ID: Date: 10 Sep 93 07:06:41 GMT Sender: kristoff@net.bio.net Distribution: bionet Lines: 5 Approved: sci-resources-moderator@net.bio.net $$MAIL BEGIN *********************************************************** There will be no E-Guide distributed this week, the next issue will be for 9/17/93. $$MAIL END************************************************************** From owner-sci-resources@net.bio.net Thu Sep 09 23:00:00 1993 Path: biosci!NET.BIO.NET!kristoff From: kristoff@NET.BIO.NET (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NSF - Summary of new documents on STIS - 5 September 1993 Message-ID: Date: 10 Sep 93 07:24:09 GMT Sender: kristoff@net.bio.net Distribution: bionet Lines: 115 Approved: sci-resources-moderator@net.bio.net ** NEW DOCUMENTS ON STIS ** Document Type: Bulletin Title: BUL 92-21-1 NSF September 1993 Bulletin Volume 21; No.1 File size (bytes): 45859 STIS Filename: bul9321 Document Type: News Title: TIP30820 RESEARCH COLLECTIONS IN SYSTEMATICS AND ECOLOGY File size (bytes): 5596 STIS Filename: tip30820 Document Type: Press Release Title: PR 93-66 NEBRASKA RECEIVES THREE-YEAR EPSCoR AWARD TO STRENGTHEN RESEARCH EFFORTS File size (bytes): 3224 STIS Filename: pr9366 Document Type: Program Guideline Title: NSF 93-115 DOE/NSF/USDA Joint Program on Collaborative Research in Plant Biology File size (bytes): 56021 STIS Filename: nsf93115 Title: NSF 93-116 RESEARCH COLLECTIONS IN SYSTEMATICS AND ECOLOGY File size (bytes): 25593 STIS Filename: nsf93116 Title: NSF 93-129 NSF NATO Postdoctoral Fellowship in Science & Engineering 1993-1994 File size (bytes): 19428 STIS Filename: nsf93129 Title: NSF 93-132 - Advanced Technological Education File size (bytes): 78296 STIS Filename: nsf93132 Document Type: Recruit Title: Supervisory Criminal Investigator (Special Agent-in-Charge) File size (bytes): 5456 STIS Filename: vgm9386 ------------------------------------------------------------------------ ** UPDATES TO EXISTING STIS DOCUMENTS ** Document Type: General Publication Title: NSF 91-10 STIS Brochure File size (bytes): 4456 STIS Filename: nsf9110 Document Type: Phone Book Title: NSF Alphabetical Listing File size (bytes): 91935 STIS Filename: phnalpha Title: NSF Organizational Directory File size (bytes): 99554 STIS Filename: phnorg Document Type: Press Release Title: PR 93-66 NEBRASKA RECEIVES THREE-YEAR EPSCoR AWARD TO STRENGTHEN RESEARCH EFFORTS File size (bytes): 3224 STIS Filename: pr9366 ------------------------------------------------------------------------ ** FOR YOUR REFERENCE ** ------------------------------------------------------------------------ HOW TO OBTAIN DOCUMENTS The above files can be retrieved in electronic form using the STIS system. If you don't know how to use STIS, send an E-mail message to stisinfo@nsf.gov (Internet) or stisinfo@NSF (BITNET). You will receive a copy of the STIS flyer via E-mail. If you are already using STIS, you can use the information above to retrieve these files: Documents via E-mail: Send a message to stisserv@nsf.gov (Internet) or stisserv@NSF (BITNET). Use the "STIS Filename" shown above in the "get" command. For example, to retrieve pr9366, the text of your message should be as follows: get pr9366 Anonymous FTP: FTP to stis.nsf.gov. Use the "STIS Filename" shown above to retrieve a file. For example, to retrieve pr9366, you would enter: ftp> get pr9366 WAIS or Gopher: Do a word search on the filename as shown in the summary. If you want a *printed* copy of a document: Send your name and postal mailing address, and the document title and number to "firstop@nsf.gov" (Internet) or "firstop@nsf" (BITNET). If you have problems with the above procedures: Send a message to "stis@nsf.gov" (Internet) or "stis@NSF" (BITNET). From owner-sci-resources@net.bio.net Mon Sep 13 23:00:00 1993 Path: biosci!NET.BIO.NET!kristoff From: kristoff@NET.BIO.NET (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NSF - Summary of new documents on STIS - 12 September 1993 Message-ID: Date: 14 Sep 93 00:51:36 GMT Sender: kristoff@net.bio.net Distribution: bionet Lines: 58 Approved: sci-resources-moderator@net.bio.net ** NEW DOCUMENTS ON STIS ** Document Type: Program Guideline Title: NSF 93-124 - Summer Institute in Japan For U.S. Graduate Students in Science and Engineering, including Biomedical Science and Engineering File size (bytes): 44405 STIS Filename: nsf9312 Document Type: SRS Data Brief Title: DB 93-316 Asian Science and Engineering Degrees Top 700,000 File size (bytes): 4115 STIS Filename: db93316 ------------------------------------------------------------------------ ** FOR YOUR REFERENCE ** ------------------------------------------------------------------------ HOW TO OBTAIN DOCUMENTS The above files can be retrieved in electronic form using the STIS system. If you don't know how to use STIS, send an E-mail message to stisinfo@nsf.gov (Internet) or stisinfo@NSF (BITNET). You will receive a copy of the STIS flyer via E-mail. If you are already using STIS, you can use the information above to retrieve these files: Documents via E-mail: Send a message to stisserv@nsf.gov (Internet) or stisserv@NSF (BITNET). Use the "STIS Filename" shown above in the "get" command. For example, to retrieve db93316, the text of your message should be as follows: get db93316 Anonymous FTP: FTP to stis.nsf.gov. Use the "STIS Filename" shown above to retrieve a file. For example, to retrieve db93316, you would enter: ftp> get db93316 WAIS or Gopher: Do a word search on the filename as shown in the summary. If you want a *printed* copy of a document: Send your name and postal mailing address, and the document title and number to "firstop@nsf.gov" (Internet) or "firstop@nsf" (BITNET). If you have problems with the above procedures: Send a message to "stis@nsf.gov" (Internet) or "stis@NSF" (BITNET). From owner-sci-resources@net.bio.net Thu Sep 16 23:00:00 1993 Path: biosci!net.bio.net From: kristoff@net.bio.net (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 22, no. 33, pt. 3, 17 September 1993 Message-ID: Date: 17 Sep 93 02:00:06 GMT Sender: kristoff@net.bio.net Lines: 930 Approved: biosci-moderator@net.bio.net $$XID RFA CA93032 CA-93-032 P1O1 *************************************** DEVELOPMENT AND EVALUATION OF MINIMAL ACCESS SURGERY IN CANCER TREATMENT NIH GUIDE, Volume 22, Number 33, September 17, 1993 RFA: CA-93-032 P.T. 34; K.W. 0785210, 0715035, 0755015 National Cancer Institute Letter of Intent Receipt Date: October 20, 1993 Application Receipt Date: December 22, 1993 PURPOSE The Cancer Therapy Evaluation Program (CTEP), Division of Cancer Treatment (DCT), National Cancer Institute (NCI) invites applications for cooperative agreements from institutions or consortia, including the DCT Clinical Trials Cooperative Groups, capable of and interested in performing phase II and phase III evaluations of minimal access surgery. Minimal access surgery, which is synonymous with minimally invasive surgery, has become increasingly prominent in the diagnosis and treatment of benign conditions. Case reports and small series have been published documenting the use of minimal access surgery in the care of patients with cancer. The NCI is interested in a timely evaluation of minimal access techniques that have the potential for significantly decreasing the morbidity, cost, and inconvenience of cancer treatment. Determination of the effectiveness of minimal access surgery in the treatment of cancer is critical, before minimal access techniques become the standard of care for cancer therapy in the community. Phase III studies should be designed to evaluate minimal access surgery versus standard surgery. Phase II studies should evaluate the practicality and safety of minimal access surgery for specific tumor sites. It is essential for institutions or consortia to have surgeons with experience in minimal access surgery and evidence of patient accrual to complete a phase II or III study or studies in a timely manner. Solid tumors that are relevant to this Request for Applications (RFA) include cancers of the brain, lung, stomach, pancreas, colon, ovary, endometrium, and cervix. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This RFA, Development and Evaluation of Minimal Access Surgery In Cancer Treatment, is related to the priority area of cancer. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Applications from minority individuals and women, as well as new and experienced investigators, are encouraged. An applicant institution may consist of a single institution or a consortium of institutions functioning as an integrated unit under the guidance and direction of a single Principal Investigator for the purpose of accessing a sufficient patient population. Foreign institutions are ineligible to apply or be a collaborating institution within an application from a domestic organization. All accrued patients must be treated in the United States. It is essential for institutions/consortia to have surgeons with experience in minimal access surgery and evidence of patient accrual to complete a phase II or III study or studies in a timely manner. 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 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. Awards and level of support depend on receipt of a sufficient number of applications of high scientific merit. Because the nature and scope of the research proposed (phase II versus phase III studies) in response to this RFA may vary, it is anticipated that the size of awards will vary also. The total project period for applications submitted in response to the present RFA may not exceed three years. The anticipated award date is July 1, 1994. Although this program is provided for in the financial plans of the NCI, awards pursuant to this RFA are contingent upon the availability of funds for this purpose. This RFA is a one-time solicitation. At this time the NCI has not determined whether or how this solicitation will be continued beyond the present RFA. If the NCI does not continue the program, awardees may submit grant applications through the usual investigator-initiated grants program. FUNDS AVAILABLE Approximately $750,000 in total costs per year for three years will be committed to fund applications submitted in response to this RFA. It is anticipated that the funds will be able to support two phase III awards, four phase II awards, or some combination thereof. RESEARCH OBJECTIVE Background Minimal access surgery has been proposed to decrease the trauma of surgical access without limiting exposure of the operative field. Approaches used include laparoscopic, thoracoscopic, endoluminal, and perivisceral. Advantages to minimal access surgery include accelerated recovery and convalescence, with a corresponding decrease in length of hospital stay and hospital expenses, as well as a quicker return to normal activity. Wound complications, including infections, are also decreased. Potential benefits include a decreased incidence of post-operative pneumonia, deep vein thrombosis, and adhesion formation. In oncology, minimal access surgery may be useful to obtain adequate tissue for accurate diagnosis of malignancy, to ascertain the degree of spread, to stage the disease, and to assess operability. Definitive cancer surgery may be performed using minimal access techniques. Recent reports have documented the use of minimal access surgery in cancers of the brain, lung, stomach, liver, pancreas, gallbladder, kidney, colon, ovary, endometrium, and cervix. For certain benign conditions, minimal access surgery has become the standard of care. Laparoscopic cholecystectomy was first reported in 1989. In 1992, it is estimated that more than 20 percent of all cholecystectomies were performed using minimal access techniques. Both patient preference and physician enthusiasm have engendered this change, although there has not been a phase III evaluation of the two techniques to ascertain differences in morbidity, mortality, convalescence, and cost. In gynecology, interval tubal ligations, resections of ectopic (tubal) pregnancies, fulguration of endometriosis, and ovarian cystectomies are done routinely via laparoscope. There is concern among the surgical community that minimal access techniques may become the standard of care for patients with cancer without direct evaluation against traditional, open surgical techniques. Objectives and Scope Solid tumors potentially relevant to this RFA account for significant cancer incidence, morbidity, mortality, and expense. This RFA is intended to promote phase II and III evaluation of minimal access surgery in the management of patients with solid tumors. This RFA is not intended to duplicate or supplement support for any phase II or phase III trials supported by any other mechanism. Phase III studies will evaluate minimal access surgery versus standard surgical technique, including cancers of the brain, lung, stomach, pancreas, colon, ovary, endometrium, and cervix. Developmental phase II studies will be aimed at broadening the applicability of minimal access surgery for specific tumor sites by evaluating the practicality and safety of this approach. Each application is expected to focus on a specific type of solid tumor. An applicant institution may submit more than one application. In addition, an individual scientist, individual institution, or consortium of institutions may be included on more than one application (or tumor site). All institutions accruing patients must be able to document adequate surgical experience with minimal access surgery as well as adequate patient accrual to complete a phase II or III trial in a timely manner. For phase III trials, outcomes of interest include morbidity (acute and chronic), mortality, efficacy of treatment, length of hospital stay, time to return to normal activities, quality of life, and cost. Applications should include an analysis of what outcomes are expected to vary importantly between minimal access surgery and conventional surgery. It is recommended that costs be measured in terms of health-related resource utilization, such as hospital days, operating room time, office visits, and days until resumption of normal activities. Applications should include documentation of a cost-related data source that is comprehensive and available to the researcher. Applications must include a statistical section describing plans for analysis of data designed to test the hypotheses, as well as a power/sample size analysis for cost and clinical endpoints. It is possible that collection of data on cost from a subset of patients may be adequate. For phase III trials, or phase II trials focusing on rare tumors, investigators are encouraged to work with multi-center organizations or form a consortium of institutions in order to access sufficient number of patients to test the proposed hypotheses. DEFINITIONS AWARDEE - The organization to which a cooperative agreement is awarded and that is responsible and accountable to the NCI for the use of funds provided and for performance of the cooperative agreement-supported project. PRINCIPAL INVESTIGATOR (PI) - The single individual designated by the awardee in the cooperative agreement who is responsible for the scientific and technical direction of the project. STATISTICAL CENTER - Applicant institutions proposing phase III trials must have a Statistical Center for collection and analysis of patient data. Responsibilities will include participating in the planning and coordination of study design methodologies, data management, analysis, data monitoring, and reporting of data. The Statistical Center need not be at the PI's institution. NCI PROGRAM DIRECTOR - The CTEP Surgical Oncology Grants Program Director, who will be coordinating DCT's interactions and providing overall guidance within the NCI (see INQUIRIES below). He/she is available for consultation during preparation of applications as well as the duration of research conducted through this cooperative agreement. He/she serves in a back-up role for the NCI Coordinator. NCI COORDINATOR - The Head, Surgery Section, Clinical Investigations Branch, CTEP, DCT, who interacts scientifically with the institutions (see INQUIRIES below). STEERING COMMITTEE - A committee composed of the PI, an investigator from each institution collaborating with the Awardee Institution, and the NCI Coordinator that will serve as the governing board of each study (see Terms and Conditions of Award below). COORDINATING COMMITTEE - This committee will be established to coordinate the activities among several Awardee Institutions performing studies in a single tumor site. This committee composed of the members of the Steering Committee from each Awardee Institution will serve as the governing board of the studies for that tumor site (see Terms and Conditions of Award below). SPECIAL REQUIREMENTS Because the Terms and Conditions of Award discussed below will be included in all awards issued as a result of this RFA, it is critical that each applicant include specific plans for responding to these terms. Plans must describe how the applicant will comply with staff involvement. The following terms and conditions will be incorporated into the award statement and provided to the Principal Investigator(s) as well as institutional official at the time of the award. Terms and Conditions of the Award These special Terms of Award are in addition to and not in lieu of otherwise applicable OMB administrative guidelines, HHS Grant Administration Regulations at 45 CFR part 74 and 92, and other HHS, PHS, and NIH Grant Administration policy statements. The administrative and funding instrument to be used for this program will be 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 the specific tasks and activities in carrying out the studies will be shared among the awardees and the NCI Coordinator. The cooperative agreements will require cooperation between the CTEP staff (through the NCI Coordinator) and the Principal Investigator of each of the Awardee Institutions. The NCI Coordinator will assist in coordinating the activities of the Awardee Institutions as defined below and in facilitating exchange of information. 1. Awardee Rights and Responsibilities The Awardee is responsible for the proposed research project to advance the goals of the RFA. Awardee has primary authority and responsibility to define objectives and approaches and to plan, conduct, analyze, and publish results, interpretations, and conclusions of their studies. Awardee is responsible for accessing sufficient numbers of cancer patients to meet accrual goals and for providing expertise in minimal access surgery and experience in clinical trials. a. Protocol Development The PI, with NCI Coordinator's assistance, is responsible for coordinating protocol development, protocol submission, study conduct, quality control and study monitoring, data management and analysis, protocol amendments/status changes, adherence to federally mandated regulations, and protocol and performance reporting. The PI will be responsible for communicating with the appropriate CTEP staff through the NCI Coordinator. b. Protocol submission Prior to activation of the protocol(s), the PI will submit them to the NCI Coordinator to solicit for comments and suggestions. The PI will communicate the NCI Coordinator's comments and suggestions to the collaborating institutions. c. Quality Control The Awardee will establish mechanisms for quality control of therapeutic and diagnostic modalities employed in its trials. Quality control at a minimum must consist of: 1. Pathology: Verification of pathologic diagnosis in cases where known variability in the accuracy of histologic diagnosis is a potentially serious problem and where pathology data may provide important prognostic information. 2. Radiation Therapy: Review (either concurrent or retrospective) of port films and compliance with protocol-specified doses for individuals patients, where relevant. Determination of adequacy of radiation delivery with the assistance of the Radiological Physics Center (RPC), whose functions usually include equipment dosimetry, periodic institutional visits, and other aspects of physics review. 3. Chemotherapy: Review of flow sheets with determination of protocol compliance in dose administration and dosage modification. 4. Surgery: assessment of adequacy of protocol-specified surgical procedures through review of operative notes, study-specific surgical forms, and, where appropriate, video tapes. d. Study Conduct and Monitoring The Awardee will establish mechanisms for study monitoring including an independent Data and Safety Board (see Collaborative Responsibilities below). The Awardee is responsible for ensuring accurate and timely knowledge of the process of each study through: 1. registration, tracking and reporting of patient accrual and adherence to defined accrual goals; 2. ongoing assessment of case eligibility and availability; 3. timely medical review and assessment of patient data; 4. rapid reporting of treatment-related morbidity and measures to ensure communication of this information to all parties; 5. interim evaluation and consideration of measures of outcome, as consistent with patient safety and good clinical trials practice; 6. timely communication of results of studies. e. Data Management and Analysis The Awardee will develop procedures to ensure that data collection and management are (a) appropriate for quality control and analysis; (b) as simple as appropriate in order to encourage maximum participation of physicians entering patients and to avoid unnecessary expense; and (c) sufficiently uniform across the consortia institutions. For phase III trials, the Awardee must have a Statistical Center for collection and analysis of patient data. Responsibilities of the Statistical Center will include participation in the planning and coordination of study design methodologies, data management, and analysis, data monitoring, and reporting of data. A Statistical Center is not required for phase II trials but some formal structure is required for data management and analysis. f. Compliance with Federally Mandated Regulatory Requirements. The Awardee is responsible for establishing procedures for all participating institutions to comply with Office for Protection from Research Risks (OPRR) requirements for the protection of human subjects. These procedures are methods for assuring that the Awardee Institution and each institution participating in the research conducted under this cooperative agreement has a current, approved assurance with the OPRR; that each protocol is reviewed and approved by the responsible Institutional Review Board (IRB) prior to patient entry; that each protocol is reviewed at least annually by the IRB so long as the protocol is active; that amendments are approved by the IRB; and that each patient (or legal representative) gives written informed consent prior to entry on study. g. Progress review For multi-institution trials, the PI will establish a mechanism for assessing performance of its consortia participants, with particular attention to accrual of adequate numbers of eligible patients onto consortium trials, timely submission of required data and conscientious observance of protocol requirements. This mechanism will include a procedure to recommend an adjustment of institutional funds within the consortium as appropriate for the level of participation in consortium activities, including but not limited to accrual. If the progress review indicates poor performance by a participating institution, the Awardee may replace the institution. Any changes in the participation must be noted in the application for continuation support (PHS 2590, rev. 9/91). If in the course of the budget period the Awardee chooses to change consortium institutions, the new consortium institutions must have an approved Assurance of Compliance for the Protection of Human Subjects on file with OPRR. The Awardee will be responsible for assuring that no patients are accrued to a protocol at a participating institution until the protocol has been reviewed and approved by the IRB. If a change in consortium institutions involves a change in key personnel or a change of scope or research objectives, the Awardee must request the prior approval of the NCI. The procedure for requesting prior approval is described in the "Methods for Grantees to Request Approvals", PHS Grants Policy Statement, p.8-6 (rev. 9/1/91). h. Attendance at meetings The PIs of the awardee institutions and the NCI Coordinator will meet initially to discuss research plans and establish priorities. Subsequent periodic meetings will be scheduled to review progress and coordinate research activities. Each Awardee should anticipate the need to participate in one meeting per year to coordinate activities. i. Publication of Data Timely publication of major findings by the awardees is encouraged. Publication or oral presentation of work done under this agreement will require appropriate acknowledgment of NCI support. The NCI will have access to data generated under this cooperative agreement and may periodically review the data. However, the awardee institutions will retain custody and primary rights to the data developed under these awards consistent with current HHS, PHS, and NIH policies. 2. NCI Staff Responsibilities a. NCI Program Director, CTEP The role of the NCI Program Director, CTEP, as described throughout these terms of cooperation, is to assist and facilitate but not to direct research activities. He/she will serve in an administrative capacity, will be involved in coordinating DCT's interactions, will provide overall guidance within the NCI and will monitor progress. He/she will serve in a back-up role for the NCI Coordinator. b. NCI Coordinator, CTEP The NCI Coordinator will interact scientifically with the Awardees. During the period of the award, the Awardees will have the primary authority to determine research priorities and statistical needs. The NCI Coordinator may provide appropriate assistance by participating in the design of research activities, review of protocols, establishment of priorities, and review of progress. The NCI Coordinator may seek advice from other appropriate CTEP staff regarding the proposed protocol(s), including safety, quality control, statistical design and tumor specific issues. Although the Awardee(s) are responsible for statistical analysis of data, NCI staff may provide computer processing and statistical evaluations if requested by the Awardee. In addition, the NCI Coordinator also may relay guidance on studies of cost analysis from the Applied Research Branch, SP, DCPC, NCI, and the Agency for Health Care Policy and Research, DHHS. The NCI Coordinator will monitor protocol progress. The NCI Coordinator may request that a protocol be closed to accrual for reasons including: (a) insufficient accrual rate; (b) accrual goal met; (c) poor protocol performance; (d) patient safety and regulatory concerns; (e) study results are already conclusive; (f) emergence of new information that diminishes the scientific importance of the study question; and (g) failure to collect data in a timely manner. NCI will not permit the expenditure of funds for a study after requesting closure (except for patients already on study). If disagreements develop over NCI-recommended study closure for reasons other than patient safety or regulatory concerns, the arbitration process described in "Arbitration" below will be established. Progress will be reviewed at least annually by the NCI Coordinator as well as the NCI Program Director on the basis of information provided at the annual meetings with the PIs and the progress report(s) submitted in the non-competing application(s). In addition, periodic accrual information may be requested from the PI by the NCI Coordinator or the NCI Program Director for all active studies when deemed appropriate. The NCI reserves the right to reduce the budget, withhold support, and to suspend, terminate or curtail a study or an award in the event of insufficient patient accrual or progress, or noncompliance with the terms of award, including these Terms and Conditions of Award. 3. Collaborative Responsibilities a. Steering Committee It is anticipated that decisions in all research activities conducted under this cooperative agreement will be reached by consensus of the collaborators participating in the project under the leadership of the PI and that the NCI Coordinator will have the opportunity to offer input to this process. For multi-institutional trials, a Steering Committee composed of the PI, one investigator from each collaborating institution, and the NCI Coordinator will be the main governing board of the study and will have primary responsibility for research design and protocol development, participant recruitment and follow-up, data collection, quality control, interim data and safety monitoring, final data analysis, and preparation of publications. All members of the Steering Committee will have one vote. For phase III trials, the Steering Committee will also include a representative of the Statistical Center, who will have one vote. The chair of the Steering Committee, who will be someone other than the NCI Coordinator, will be selected by the its members. Subcommittees will be established by the Steering Committee, as it deems appropriate; the NCI Coordinator will serve on subcommittees as he/she deems appropriate. For phase III trials, the Steering Committee will appoint an independent Data and Safety Monitoring Board (DSMB). The DSMB will review the studies at least annually and report to the NCI Coordinator. The composition and operating procedures and policies of this Board will be determined by the Steering Committee after the issuance of the award. The members of this Board will be selected based on the members' technical and clinical experience, absence of conflict of interest and knowledge of good clinical trial methodology. The size of the DSMB should be limited and should not exceed seven voting non-government individuals. The NCI Coordinator, the NCI Program Director and the PI will participate as non-voting members and will not chair the DSMB. The Awardee agrees to abide by the decisions of the DSMB. b. Coordinating Committee If there is more than one Awardee for a tumor site, the Coordinating Committee will serve as the governing board for all studies for that tumor site. In this situation, the NCI Coordinator will work with the Coordinating Committee to develop a common collaborative protocol for the Awardees, if necessary. Awardees will be required to accept and implement the common collaborative protocol and procedures approved by the Coordinating Committee. The Coordinating Committee is composed of the members of the Steering Committee from each Awardee. All members of the Coordinating Committee will have one vote. For collaborative phase III trials, the Coordinating Committee will also include one representative from each Statistical Center, who will have one vote per representative. The chair of the Coordinating Committee, who will be someone other than the NCI Coordinator, will be selected by the its members. Subcommittees will be established by the Coordinating Committee, as it deems appropriate; the NCI Coordinator will serve on subcommittees as he/she deems appropriate. For collaborative phase III trials, the Coordinating Committee will appoint an independent Data and Safety Monitoring Board (DSMB). The DSMB will review the studies at least annually and report to the NCI Coordinator. The composition and operating procedures and policies of this Board will be determined by the Coordinating Committee after the issuance of the award. The members of this Board will be selected based on the members' technical and clinical experience, absence of conflict of interest and knowledge of good clinical trial methodology. The size of the DSMB should be limited and should not exceed seven voting non-government individuals. The NCI Coordinator, the NCI Program Director and the PI will participate as non-voting members and will not chair the DSMB. The Awardees agree to abide by the decisions of the DSMB. 4. Arbitration Any disagreement that may arise on scientific/programmatic matters between award recipients and the NCI may be brought to arbitration. An arbitration panel will be composed of three members -- one selected by the Steering Committee or Coordinating Committee (with the NCI member non-voting) or by the individual Awardee in the event of an individual disagreement, a second member selected by the NCI, and the third member selected by the two prior selected 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 FEMALES 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 that disproportionately affect them. This policy is intended to apply to males and females of all ages. If females or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale must be produced. 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 included 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 disease, disorders, or conditions, including but nor 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 make to include human tissues from females 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 females and 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 applications. 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: In addition to the requested information about the composition of proposed study populations involving human subjects, peer review groups need similar information about the clinical or regional populations from which the samples are drawn in order to evaluate the extent of participation by women and minorities. To avoid delays in review of such applications, the NCI advises that, as a minimum, the application should provide gender/minority information on hospital admissions, accruals to trials, and patient catchment areas. Studies involving non-hospital populations, such as community-based studies should provide similar data abut populations in the area or region from which the study subjects will be drawn. In the absence of current data, historical demographic information and/or previous recruitment data for similar studies from the proposed study sites should be provided. Further, any specific plans for increasing gender/minority representation in studies should also be included in the application to facilitate review. LETTER OF INTENT Prospective applicants are asked to submit, by October 20, 1993, a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, the names of 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, it is requested in order to provide an indication of the number and scope of applications to be reviewed. The letter of intent is to be sent directly to: Dr. Roy S. Wu Division of Cancer Treatment National Cancer Institute Executive Plaza North, Room 734 6130 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-8866 FAX: (301) 480-4663 APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 9/91) is to be used to apply for cooperative agreements. 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 the NCI Program Director listed under INQUIRIES. All costs required for the proposed studies must be included in the application and fully justified. These costs include the additional costs of clinical research, including patient accrual, quality assurance, data management and data analysis, travel, an on-site audit program, and an independent Data and Safety Monitoring Board. If capitation costs are requested for reimbursement for patient accruals, the cost per patient must be broken down and justified, e.g.: a. estimate of physician time spent on research (e.g., to obtain informed consent, to fill out data form, and others) and the resultant cost. b. estimate of data manager or nurse time to meet research requirements (e.g., compiling and mailing data, specimens) and the resultant cost. c. cost of mailing or handling research-related patient specimens, forms, materials (e.g., slides, X-ray) d. other consultant costs (e.g., pathology, radiology) Travel funds for one meeting per year for the PI to coordinate activities should be included in the budget. Applicants must state in their applications if they or any of their collaborating investigators will/have submitted another application or are participating as a collaborator in more than one application in response to this RFA. If the applicant or the collaborating investigator is contributing the same population of patients to two different studies in separate applications the applicant must choose which study will get these patients if both studies are judged meritorious by the reviewers. Applicants must describe plans to accommodate stated program requests, criteria, and staff involvement. The RFA label available in the research grant application form PHS 398 (rev. 9/91) must be affixed to the bottom of the face page. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA number and title must be typed on line 2a of the face page of the application form. Submit a signed, typewritten original of the application, including the Checklist, and three signed, exact, clear and single-sided photocopies, in one package to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892-9912** At the time of submission, send two additional copies of the application to: Ms. Toby Friedberg Referral Officer Division of Extramural Activities National Cancer Institute Executive Plaza North, Room 636 6130 Executive Boulevard Bethesda, MD 20892 Applications must be received by December 22, 1993. If an application is received after that date, it will be returned to the applicant without review. If the application submitted in response to this RFA is substantially similar to a research grant application already submitted to the NIH for review, but has not yet been reviewed, the applicant will be asked to withdraw either the pending application or the new one. Simultaneous submission of identical applications will not be allowed, nor will essentially identical applications be reviewed by different review committees. Therefore, an application cannot be submitted in response to this RFA that is essentially identical to one that has already been reviewed. This does not preclude the submission of substantial revisions of applications already reviewed, but such applications must include an introduction addressing the previous critique. REVIEW CONSIDERATIONS All applications will be judged on the basis of the scientific merit of the proposed project and the documented ability of the investigators to meet the RESEARCH OBJECTIVES of the RFA. Although scientific and technical merit of the proposed protocol is important, it will not be the sole criterion for evaluation of a study. Other considerations, such as the importance and timeliness of the clinical trial, access to patients, and multidisciplinary nature of the studies, will be part of the evaluation criteria. Review Method Upon receipt, applications will be reviewed by the Division of Research Grants (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 NCI program staff function. Applications that are judged non-responsive will be returned to the applicant by the NCI. An application judged to be non-responsive to the RFA may be submitted as an investigator-initiated research grant (R01) or program project grant (P01). The applications would require modification in accordance with either the R01 or P01 guidelines. The revised application would not be considered an application for a cooperative agreement nor would it be considered a response to an RFA. Questions concerning the responsiveness of proposed research to the RFA are to be directed to program staff listed under INQUIRIES. If the number of applications submitted is large compared to the number of awards to be made, the NCI may conduct a preliminary scientific peer review (triage) to eliminate those that are clearly not competitive. The NCI will remove from competition those applications judged to be noncompetitive for award and notify the applicant and the institutional business official. Those applications judged to be both responsive and competitive will be further evaluated according to the review criteria stated below for scientific and technical merit by an appropriate peer review group convened by the Division of Extramural Activities, NCI. The second level of review will be by the National Cancer Advisory Board. Review Criteria The factors considered in evaluating the scientific merit of each application will be: o extent to which the application addresses the goals and objectives of the RFA; o adequacy of applicant's plans for addressing the special scientific and technical program requirements presented in the RFA; o demonstrated expertise both in minimal access surgery and conduct of clinical trials; o appropriateness and adequacy of the experimental approach and methodology proposed to carry out the research; o demonstration of availability of and access to appropriate patients for phase II/III trials; o adequacy of planned research to evaluate potential differences between minimal access surgery and standard surgical techniques in terms of effectiveness, morbidity (acute and chronic), mortality, time of convalescence, cost, and quality of life; o adequacy of power/sample size analysis for clinical endpoints and cost; o adequacy of the available facilities and data management resources; o documentation of a cost-related data source that is comprehensive and available to the researcher; o evidence of competence with regard to the mechanisms for quality control, study monitoring, data management and reporting, and data analysis. o plans for effective interaction and coordination among cooperating institutions within an application and with the NCI; o adequacy of provisions for the protection of human subjects; o adequacy for plans for the inclusion of female and minorities. The reviewers will critically examine the submitted budget and will recommend an appropriate budget and period of support for each meritorious application. AWARD CRITERIA Applications recommended by the National Cancer Advisory Board will be considered for award based on (a) scientific and technical merit of the application as reflected in the priority score, (b) availability of resources and study population, and (c) availability of funds. Furthermore, the applicant organization must indicate a commitment to accept provisions outlined under the SPECIAL REQUIREMENTS section, Terms and Conditions of Award. The anticipated date of award is July 1, 1994. Letter of Intent Receipt Date: October 20, 1993 Application Receipt Date: December 22, 1993 Review by the National Cancer Advisory Board: May 30, 1994 Anticipated Award Date: July 1, 1994 INQUIRIES Written and telephone inquiries concerning the objectives and scope of this RFA and inquires about whether specific proposed research would be response are encouraged. Program staff welcome the opportunity to clarity any issues or questions from potential applicants. Direct inquiries regarding scientific issues to: Edward L. Trimble, M.D., M.P.H. Division of Cancer Treatment National Cancer Institute Executive Plaza North, Suite 741 Bethesda, MD 20892 Telephone: (301) 496-2522 FAX: (301) 402-0557 Direct inquiries regarding programmatic issues and address the letter of intent to: Roy S. Wu, Ph.D. Grants Program Director Division of Cancer Treatment National Cancer Institute Executive Plaza North, Room 734 Bethesda, MD 20892 Telephone: (301) 496-8866 FAX: (301) 480-4663 Direct inquiries regarding fiscal matters to: Ms Carolyn Mason Grants Administration Branch National Cancer Institute Executive Plaza South, Room 242 6120 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-7800, ext. 59 FAX: (301) 496-8601 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.395, Cancer Treatment Research. Awards are made under the authorization of the Public Health Service Act, Title IV Sections 301, 410, and 411, Part A (Public Law 78-410, 42 USC 241 as amended, Public Law 99-158, 42 USC 285a) and administered under PHS grants policies and Federal Regulations at 42 CFR Part 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems agency review. From owner-sci-resources@net.bio.net Thu Sep 16 23:00:00 1993 Path: biosci!net.bio.net From: kristoff@net.bio.net (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 22, no. 33, pt. 2, 17 September 1993 Message-ID: Date: 17 Sep 93 01:59:35 GMT Sender: kristoff@net.bio.net Lines: 1026 Approved: biosci-moderator@net.bio.net $$XID NIHGUIDE 19930917 V22N33 P2O2 ************************************ needles (works) to other IVDUs while 46 percent of HIV-negative IVDUs are injecting with used needles. It is unknown whether or not any disclosure of HIV seropositivity is occurring among the needle-sharing individuals. Since it is apparent that these individuals are engaging in high-risk behavior, it is important to study barriers to disclosure. It is estimated that there are a significant number of drug users who have not been reached through standard AIDS education program efforts or the drug treatment system to receive risk-reduction counseling and education, particularly those who are the male or female sexual partners of drug users, who may have been exposed to HIV infection, but who may be unaware of their risk. Additionally, partner notification activities directed toward women may help in preventing the perinatal transmission of HIV. Out-of-treatment drug users recruited in NIDA's ongoing community-based efforts often have no previous drug treatment experience (40 percent) and many report no prior history of having been tested for HIV (35 percent). These data emphasize the need to study diverse populations of individuals, particularly the hard-to-reach out-of-treatment injection drug-using populations. Since the implementation of partner notification in 1936 as part of a national syphilis prevention program in the United States, sexually transmitted disease (STD) control centers have identified and informed a number of otherwise unsuspecting individuals of their potential exposure to an STD, thus, allowing them to receive rapid and effective intervention. Traditionally, two complementary processes have been used to notify the partners: (1) patient referral where the infected partner assumes the responsibility to inform their own sexual partners and refer them for counseling and testing; (2) contract patient referral which differs from patient referral in that while index clients are encouraged to inform their own sex and needle-sharing partners, locator information will be collected on partners that are voluntarily identified by the index client and if the index client is unable to notify the partner(s) in three working days, a disease intervention specialist (DIS) outreach worker will initiate the provider referral. Whereas some combination of these strategies continues to be the mainstay of STD control programs, there have been no community-based evaluations for effectiveness in preventing disease transmission or lowering rates of disease in injection drug users at STD programs. Most recently, partner notification has been applied for the prevention of HIV infection. In the AIDS Surveillance and Prevention Cooperative Agreements supported by the CDC, States are required to design and implement procedures for the confidential notification of sex and needle-sharing partners of AIDS patients and HIV-positive individuals. Whereas this is currently being implemented in all publicly funded clinics, little data exist on the role of partner notification in preventing HIV transmission. Wykoff et al. (1988, 1989) documented the outcome of provider referrals in a rural area in South Carolina with low HIV seroprevalence. Of 316 sex and needle-sharing partners of HIV-positive individuals who were named in a single health district over a two-year period, 66 percent were contacted and agreed to be tested. Of these, 18 percent were found to be infected with HIV. Subsequent follow-up indicated that risk behaviors significantly decreased for both infected and uninfected partners following notification and counseling. The Centers for Disease Control and Prevention (Division of STD/HIV Prevention) conducted an evaluation of partner notification activities based in STD clinics for HIV and syphilis prevention. This multi-site evaluation focused on the randomized assignment of index patients to existing partner notification strategies to assess the ability of the strategies to identify individuals at risk for infection by measuring which methods of partner notification result in the largest number of partners presenting for testing. A behavioral follow-up portion of the evaluation has not been implemented at this time. In addition, a limited amount of information was gathered on the needle-sharing partners of those HIV-positive injecting drug users. It should, therefore, be emphasized that significant gaps in research remain. For example, would the same results be achieved via other contacts? Is education without notification equally effective? While there remains a strong need for disclosure regarding infection status, there are substantial barriers and problems regarding disclosure, particularly for individuals with few resources. Since knowledge of serostatus appears to have a positive moderating effect on risk behavior, there is a clear and critical need to identify the presence of HIV at the earliest opportunity through a confidential HIV testing and counseling program. In addition to HIV counseling and testing of a drug user at time of entry into treatment or at community clinics, one aspect of comprehensive client services can involve partner notification efforts to provide counseling and testing services to this otherwise potentially hidden at-risk population. If the sex and/or needle-sharing partners are found to be infected, they, too, can receive early intervention for HIV disease, and transmission of disease could be interrupted. Additionally, studying networks of users and following the chain in the referral process from HIV infected individuals to other individuals in their drug-using networks can provide critical information about the future prospects of the epidemic. As noted in this section, NIDA and CDC have collaborated, and will continue to collaborate, in the development and implementation of this program announcement. Program Description Applicants are advised to review existing information relevant to partner notification and to commit to providing additional basic knowledge to a field that is currently lacking in such. Following analysis of information obtained via informal disclosure and/or observation studies, applicants will develop methodologies and design controlled studies to determine the impact of new/existing methodologies (patient and third-party partner notification) for HIV-positive partner notification on prevention/treatment efforts and the degree of effectiveness in altering at-risk behaviors in the HIV-positive person and those that he or she informs. Issues of general concern include understanding who selects which model, the level of compliance, where applicable, with the model and the subsequent behavioral and psychological impact as a function of adoption and compliance for all individuals. It is also of primary interest to evaluate how barriers to informal disclosure differ from those encountered in formal programs as well as to understand whether or not the barriers are different for men and women and what effects this may have. Additionally, this project should document issues and impediments affecting public health, medical and social support, community services, and strategies that can be used to overcome these difficulties. The importance of a sound research plan and qualified research staff cannot be over-emphasized. It is recommended that investigators use the most rigorous methodology (qualitative and quantitative) consistent with the purposes of the research. Where controlled trials are not feasible, other types of controls may be used, including case control, equivalent comparison groups, or other designs. While many treatment and/or community agencies do not have a research department, applicants may wish to enter into collaboration with well-qualified researchers. Applicants are strongly urged to address issues of project feasibility and collaborative arrangements, study design, sampling procedures, implementation of client assignment to the interventions, instrumentation and measurement, data collection, quality control, tracking of clients, follow-up, and data analyses, as appropriate. It is essential that the applicant discuss the potential barriers to implementing this type of study and discuss strategies to deal with these issues. Particularly critical to discuss are issues related to collaboration, confidentiality, number of subjects, anticipated staff and further types of substudies. It is critical that power analyses to support cell size and overall number of study participants be included to insure adequate numbers to test different hypotheses. It is also expected that applicants will demonstrate a clear understanding of the social, legal, political, and ethical arguments and ramifications involved with research related to partner notification and strategies to effectively increase disclosure of HIV status. Investigators are required to offer HIV testing and counseling in accordance with current guidelines to subjects identified as being at risk for HIV acquisition or transmission. In high-risk populations, investigators are encouraged to assess the effects of new interventions on the acquisition and transmission of infectious diseases, including HIV. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements will be required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis should be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale should be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues should be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information should be included in the form PHS 398 in Sections 1-4 of the Research Plan AND summarized in Section 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., Native Americans (including American Indians or Alaskan Natives), Asian/Pacific Islanders, Blacks, Hispanics). The rationale for studies on single minority population groups should be provided. For the purpose of this policy, clinical research includes human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including but not limited to clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded. However, every effort should be made to include human tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. For foreign awards, the policy on inclusion of women applies fully; since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. If the required information is not contained within the application, the application will be returned. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and will be reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. APPLICATION PROCEDURES Applications are to be submitted on the grant application PHS 398 form (rev. 9/91) and will be accepted at the standard AIDS-related application deadlines as indicated in the application kit. Application kits are available at most institutional offices of sponsored research and may be obtained from the Office of Grant Information, Division of Research Grants, National Institutes of Health, Westwood Building, Room 240, Bethesda, MD 20892, telephone 301-594-7248. The title and number of the announcement must be typed in Item 2a on the face page of the application. The completed original and five permanent, legible copies of the PHS 398 form must be submitted to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** REVIEW CONSIDERATIONS The Division of Research Grants, NIH, serves as a central point for receipt of applications for most discretionary DHHS grant programs. Applications received under this announcement will be assigned to an initial review group (IRG) in accordance with established PHS referral guidelines. The IRGs, consisting primarily of non-Federal scientific and technical experts, will review the applications for scientific and technical merit in accordance with the standard NIH peer review procedures. Notification of the review recommendations will be sent to the applicant after the initial review. Applications will receive a second-level review by an appropriate Advisory Council, whose review may be based on policy considerations as well as scientific merit. Only applications recommended for further consideration by the Council may be considered for funding. AWARD CRITERIA Applications recommended for further consideration by an appropriate Advisory Council will be considered for funding on the basis of overall scientific, clinical and technical merit of the application as determined by peer review, appropriateness of budget estimates, program needs and balance, policy considerations, adequacy of provisions for the protection of human subjects, and availability of funds. INQUIRIES Written and telephone inquiries are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Richard Needle, Ph.D., M.P.H. National Institute on Drug Abuse 5600 Fishers Lane, Room 9-A-30 Rockville, MD 20857 Telephone: (301) 443-6720 Direct inquiries regarding fiscal matters to: Chief, Grants Management Branch National Institute on Drug Abuse 5600 Fishers Lane, Room 8-A-54 Rockville, MD 20857 Telephone: (301) 443-6710 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.279. Awards are made under authorization of the Public Health Service Act, Section 301 and administered under PHS policies and Federal Regulations of Title 42 CFR 52 "Grants for Research Projects", Title 45 CFR Part 74 and 92, "Administration of Grants" and 45 CFR Part 46, "Protection of Human Subjects". Title 42 CFR Part 2, "Confidentiality of Alcohol and Drug Abuse Patient Records" may be applicable to these awards. Title 42 Part 241(d) "Certificates of Confidentiality and Communicable Disease Reporting" will also apply. This program is not subject to the intergovernmental review requirements of Executive Order 12372.BREAST CANCER: ETIOLOGY AND PREVENTION $$P3 END ************************************************************ $$P4 BEGIN PA-93-112 ************************************************ NIH GUIDE, Volume 22, Number 33, September 17, 1993 PA NUMBER: PA-93-112 P.T. 34; K.W. 0715035, 0745027, 0755030 National Cancer Institute PURPOSE The Chemical and Physical Carcinogenesis Branch, Division of Cancer Etiology (DCE), National Cancer Institute (NCI), invites investigator-initiated grant applications for multidisciplinary research on the etiology and prevention of breast cancer. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This Program Announcement (PA), Breast Cancer: Etiology and Prevention, is related to the priority area of cancer. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0 or Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325, telephone 202-783-3238. ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic and foreign, for-profit and non-profit, public and private organizations, such as universities, colleges, hospitals, laboratories, units of state or local governments, and eligible agencies of the Federal government. Applications from women and minority investigators are encouraged. Foreign institutions are not eligible for First Independent Research Support and Transition (FIRST) (R29) awards. MECHANISM OF SUPPORT Support of this program will be through the National Institutes of Health (NIH) traditional research project grant (R01) or the FIRST award (R29). Applicants will be responsible for the planning, direction, and execution of the proposed project. Because the nature and scope of the research proposed in response to this PA may vary, the size of an award may vary also. For FIRST awards, the total direct costs of the five-year funding period may not exceed $350,000; the direct costs in any one year may not exceed $100,000. Except as otherwise stated in this PA, awards will be administered under PHS grants policy as stated in the Public Health Service Grants Policy Statement, DHHS Publication No. (OASH) 90-50,000, revised October 1, 1990. RESEARCH OBJECTIVES Background Breast cancer affects more women per year than any other cancer and continues to be a leading cause of death in the United States. It has been estimated that about 18 percent of all female cancer deaths in the U.S. will be due to breast malignancies and that approximately 46,000 women in the U.S. will die of breast cancer in 1993. The average mortality rate for breast cancer in the U.S. is 27.5 per one hundred thousand. Further, recent data point to an unexplained increase in breast cancer incidence and mortality rates. Since breast cancer incidence increases with age, this finding is of particular concern because the "baby boom" generation is entering middle age and medical advances continue to increase average U.S. life expectancy. The NCI has made breast cancer one of its highest priorities and it is expected to be a continuing priority of the NCI and the U.S. Congress for the foreseeable future. The following research questions are relevant to this initiative: (1) What is the target cell in the breast that ultimately becomes the cancer cell and what are the characteristics that could make it identifiable? (2) What molecular events initiate breast cancer and what factors (diet, hormones, etc.) stimulate proliferation of the initiated cell? (3) What is the natural history of breast cancer and what new markers, among the probes now available or under investigation, might be most promising for characterizing normal breast tissue at its various stages of development, distinguishing normal from abnormal, following the natural history longitudinally, and assessing the efficacy of chemopreventive agents? (4) What is the mechanism that conveys a protective effect of first birth on breast cancer risk in humans? (5) What are the critical hormonal interactions with genetic constituents that can lead to breast cancer and how can chemopreventive agents modulate the outcome? Research Goals and Scope The objectives of this PA are designed to encourage investigator-initiated multidisciplinary research to address research questions in the etiology and prevention of breast cancer. A discussion of specific topic areas that are encouraged by this PA follows. Endocrinology (Hormones/Growth Factors) - The role of hormones in etiology and chemoprevention that may affect neoplastic processes, either by acting alone or in conjunction with non-hormonal chemical carcinogens and inhibitors, should be studied in vitro and in vivo. Endocrine imbalance, namely in estrogens and progesterone, is considered highly pertinent in the etiology of breast cancer. The most characteristic property of these hormones is their elicitation of cell proliferation and differentiation in breast tissue. In addition, hormonal interactions with genetic constituents and their receptors, and the modulating effects of chemopreventive agents, should be investigated. Recently, estrogen/progesterone-driven cell proliferation has been proposed as the critical element leading to breast cancer in women. Also of interest is the role in mammary anticarcinogenesis of members of the steroid-thyroid hormone superfamily of nuclear receptors and their ligands (such as retinoids, retinoic acid receptors, and retinoid X receptors). Further, studies on the efficacy and mechanisms of combination chemoprevention of breast cancer, including the use of cytokines, are encouraged. Anticarcinogenesis/Chemoprevention - Chemoprevention studies are encouraged on the inhibition/suppression of breast cancer in vivo and in vitro, including the use of appropriate sources of human tissue/cell lines. Also of interest are markers of intermediate endpoints as they relate to determining the efficacy of chemopreventive agents. These endpoints may include hormone determinations (estrogen, progesterone, prolactin and other peptides, growth factors and their receptors, estrone metabolites), oncogenes and tumor suppressor genes and their products, and susceptibility genes. A growing number of promising chemopreventive agents for mammary carcinogenesis have been identified in experimental animal model systems, for which the mechanisms of action require detailed investigations (e.g., N-acetylcysteine, anethole trithione, carbenoxolone, curcumin, fumaric acid, glycyrrhetinic acid, oltipraz). Further, studies are needed on the mechanisms of action of chemoprotective/chemopreventive agents that emphasize the effects on phase I and phase II enzyme systems in breast cancer prevention and that are directed at elucidation of the proximate and ultimate chemical structures responsible for chemoprotection/chemoprevention. Investigations on the role of free radical inhibition in the prevention of breast cancer are also needed. Discovery and chemical identification of naturally-occurring inhibitors of mammary carcinogenesis, as well as chemical synthesis and modulation of the structure of compounds, are needed in order to understand structure-activity relationships as a basis for chemoprevention of breast cancer. Molecular Genetics - There is evidence in animal model and human studies that mutations and chromosomal changes are involved in the neoplastic process in breast cancer. It is also evident from studies in colon cancer and other models that multiple changes ("hits") are necessary for the initiation and progression of normal breast cells to evolve to the final neoplastic and metastatic state. Additional studies are needed to define the molecular events involved in the etiology of breast cancer, to identify molecular markers for each stage in the initiation and progression of the disease, and to identify specific genes and gene products involved in the process. For these studies on the genetics of breast cancer, additional relevant animal and cell culture models may be needed. Transgenic technologies may be especially powerful. Cell Biology - Studies of the organization, proliferation and differentiation of breast tissue, principally primary human luminal mammary epithelial (HLME) cells, during normal development and progression to malignancy are needed, including studies of the interaction between normal and malignant epithelial cells and the surrounding stroma. Research on the regulation of cell proliferation of normal or tumor cells is needed, both in primary culture and in primary transplants in immunodeficient animal hosts. The differentiating effects of hormones and growth factors on normal mammary epithelial cells from premenopausal women at various physiological states needs to be studied. Guanine nucleotide binding proteins (G proteins), which are associated with mammary cell growth and differentiation, need to be understood for their role in endocrine tumors of the breast. Studies are needed to obtain efficient transformation of breast tissue, particularly primary HLME cells, to pre-malignant and malignant cells in vitro and in vivo, emphasizing current concepts of molecular and hormonal carcinogenesis. The specific objectives of such studies are to (1) define conditions, both in primary cultures and in immunodeficient animals with xenografts, that allow transformation of primary HLME cells using chemical and/or physical agents as well as hormones and growth factors, and (2) delineate markers (e.g., biochemical, cytological, histopathological, molecular) that identify specific stages of in vitro and in vivo mammary epithelial transformation and distinguish particular preneoplastic states in the multi-step process. The hormone-mediated growth advantage of early preneoplastic breast lesions, compared to normal breast epithelial tissue at different stages of differentiation, needs to be characterized and the consequences elucidated. Since the development of these preneoplastic breast lesions is likely to be hormonally driven, early estrogen response genes, as well as growth factors and protooncogenes, should be examined. Following hormonal exposure, primary animal and human breast cells in culture should be studied and correlated with in vivo data. Aberrant gene expression should be studied initially at the chromosomal level and then at the level of the gene. Gene amplification and suppression, as well as chromosomal abnormalities due to hormonal exposure, should provide important clues to progressive breast cell alterations leading to neoplastic development. Metabolism - Many polycyclic aromatic hydrocarbons (PAHs) have been established in animals as breast carcinogens. Metabolic activation of PAHs in various tissues is known to proceed by two major mechanisms, one- and two- electron oxidation. The interaction of reactive metabolites with potential target molecules (DNA, RNA, protein) and the relative contribution of the two oxidation pathways in mammary tissue is unknown. Studies also need to be undertaken on which breast tissue P450 isozymes are involved in metabolic activation/detoxification and on the nature of enzyme induction itself. Breast tissue from at-risk populations and animal models can be used for the detection and quantitation of DNA adducts of these mammary carcinogens in target tissue. Since many of these adducts are not widely available as reference standards, synthesis of adducts is also an area of emphasis that needs to be coordinated with efforts to identify and study markers of exposure and to determine carcinogen dosimetry. The metabolism of xenobiotics in breast tissue may lead to the generation of free radical or oxygen radical intermediates. The reaction of these radicals with lipids can lead to lipid peroxidation, with subsequent cellular and molecular changes. Additional studies on the role of different types of dietary fat in the process of lipid peroxidation, and its effects on the carcinogenic process in breast tissue, are needed. Several demonstrated rodent mammary carcinogens are present in tobacco smoke including heterocyclic amines (PHIP), nitropyrenes (1- and 4-), dinitropyrenes (1,3- and 1,8-), and PAHs [benzo(a)pyrene, benzo(c)phenanthrene, dibenzo(a,l)pyrene]. The metabolism of these compounds needs to be examined in human breast tissue/cell lines and compared with other organs; standards for these compounds and most of their metabolites are available in the NCI Chemical Carcinogen Reference Standards Repository. Epidemiologic Correlates/Interspecies Comparisons - Epidemiologic investigations have revealed that women who have a full-term pregnancy early in their childbearing years have a reduced risk of breast cancer. The biologic basis for this protection is not understood yet the observation suggests that prevention opportunities exist. Basic research is needed on the protective effect of early full-term pregnancy on the incidence of breast cancer, specifically the effects of the length of the period between menarche and first full-term pregnancy which might be critical for the initiation of breast carcinogenesis. The hormonal levels and bioavailability of estrogen and other mammogenic hormones in premenopausal women (parous compared to nulliparous) should be studied. Animal models of this protective effect could be of significant value. Retroviruses - The demonstrated etiologic role of retroviruses in mouse mammary carcinoma and the possible analogy to human mammary carcinoma make it important to determine if retroviruses play a role in the etiology of human breast cancer. New findings report the identification of several messenger RNA (mRNA) species, including a full length mRNA of the human endogenous retrovirus (HERV) sequence and its probable association with retroviral particles observed in a human teratocarcinoma cell line. These observations and the new technology used provide a basis for additional studies to examine this and other endogenous retroviruses for possible etiologic significance in human breast cancer. Accordingly, applications are encouraged to address the possible role of endogenous and also exogenous retroviruses in the etiology of human breast cancer. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS The NIH has formulated policies concerning inclusion of women and minorities in clinical research study populations. It is policy 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. 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. This PA does not seek applications for clinical research. Basic research in which human tissues cannot be identified or linked to individuals are excluded from the policy on women and minorities. 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. APPLICATION PROCEDURES Applications are to be submitted on the research grant application form PHS 398 (rev. 9/91) and will be accepted on the standard receipt dates as indicated in the application package. The application package is 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 the NCI Program Director named below. 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 title and number of the PA must be typed in Section 2a on the face page of the application. The signed, typewritten original of the application and five signed, exact, clear, and single-sided 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** REVIEW CONSIDERATIONS Applications will be assigned on the basis of established PHS referral guidelines. Upon receipt, applications will be reviewed for completeness by NCI program staff. Incomplete applications will be returned to the applicant without further consideration. Applications will be reviewed for scientific and technical merit by study sections of the DRG, NIH, in accordance with standard NIH peer review procedures. A second level of review will be by an appropriate national advisory council or board. AWARD CRITERIA Applications will compete for available funds with all other approved applications. Awards will be made primarily on the basis of scientific merit but responsiveness to the PA, overall program balance, and the availability of resources are important considerations that will be taken into account. INQUIRIES Written and telephone inquiries concerning the objectives and scope of this PA, or inquiries about whether or not specific proposed research would be responsive, are encouraged and may be directed to: Dr. David G. Longfellow Division of Cancer Etiology National Cancer Institute Executive Plaza North, Suite 700 Bethesda, MD 20892 Telephone: (301) 496-5471 FAX: (301) 496-1040 Written and telephone inquiries of a budgetary, administrative, and/or policy nature may be directed to: Ms. Joseph H. FitzGerald Grants Administration Branch National Cancer Institute Executive Plaza South, Suite 243 Bethesda, MD 20892 Telephone: (301) 496-7800, Ext. 15 FAX: (301) 496-8601 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.393, Cancer Cause and Prevention Research. Awards are made under the authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74 or 45 CFR Part 92. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. It should be noted that the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) has an interest in basic research to elucidate the nature, function, and action of hormones, growth factors, and their receptors in general, but not in the specific emphasis of this PA, which is the role of hormones as co-factors or initiators/promoters of carcinogenesis in the breast. Applications that do not address this specific theme will be given an institute assignment based on the "Referral Guidelines for Funding Components of PHS 1992." $$P4 END ************************************************************ $$P5 BEGIN PAR-93-113 *********************************************** GERIATRIC ACADEMIC PROGRAM NIH GUIDE, Volume 22, Number 33, September 17, 1993 PAR NUMBER: PAR-93-113 P.T. 34; K.W. 0710010, 0710030, 0785035 National Institute on Aging PURPOSE The National Institute on Aging (NIA) solicits applications for the support of academic career development programs for junior faculty in geriatrics. This is a modification of an ongoing program. New "alternative track" eligibility criteria for junior faculty are added. 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, Geriatric Academic Program, is related to the priority area preserving independence in people aged 65 and older. 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 Applicant institutions must have a geriatric fellowship program and a strong base of research and clinical activities in geriatrics. Programs may be conducted at two or more institutions. Eligibility criteria for junior faculty are described under RESEARCH OBJECTIVES. MECHANISM OF SUPPORT The mechanism of support will be the institutional research career award (K12). RESEARCH OBJECTIVES There is increased recognition of the growing need for trained personnel in geriatrics. A committee sponsored by the National Academy of Sciences (J. Am. Geriatrics Soc. 35:773-91 (1987)) emphasized that filling this need will require enough academic leaders in geriatrics to train the needed number of geriatricians. The committee emphasized that high-quality training in research, teaching, and clinical practice were all necessary for the development of such leaders, and that this could best be done in an environment where there were enough geriatric researchers, teachers, and practitioners to provide thorough experience for future academic leaders. Developing academic leadership requires a continuum of support from the fellowship to the senior faculty level. Support for geriatric fellowships is available through several programs, including NIA Geriatric Research Institutional Training (GRIT) award, the Health Resources and Services Administration's Faculty Training Projects in Geriatric Medicine and Dentistry, Veterans Administration fellowships, and other sources. However, stable career development support at the junior faculty level is also extremely important in establishing academic careers. Career development support for individual junior faculty in geriatrics is provided by NIA's Academic Award (NIH Guide for Grants and Contracts, Vol. 10, No. 5, March 27, 1981), and by its Clinical Investigator Award (NIH Guide for Grants and Contracts, Vol. 13, No. 8, June 29, 1984). The NIA continues to encourage applications for these awards for suitable candidates and institutions. This announcement describes an institutional form of the Academic Award, the Geriatric Academic Program (GAP) Award. This award is appropriate for institutions having sufficient faculty with a stable base of ongoing research in geriatrics and related disciplines to serve as mentors for several junior faculty over an extended period. Since strengthening the science base of geriatrics and gerontology is a goal of this award, collaboration among clinical, basic, epidemiologic, behavioral, and social researchers in support of career development activities is particularly encouraged. Collaboration with basic science researchers in gerontology is particularly desirable. Junior Faculty Eligibility Junior faculty to be supported by the program must have a health professional degree in the clinical sciences (M.D., D.O., or D.D.S, or equivalent) and must have either completed at least one year of fellowship training in geriatrics or geropsychiatry or obtained certification of Added Qualifications in Geriatric Medicine from the American Board of Internal Medicine/American Board of Family Practice. It is not necessary for the fellowship training to have been at the applicant institution. ALTERNATIVE TRACK: Exceptional candidates who have received at least two years of fellowship training and Board Certification or Eligibility in a medical subspecialty with major relevance to aging disorders or geropsychiatry, and who propose to embark on a training program to enter the field of geriatrics/gerontology, may qualify by an alternative track. Criteria for alternative track qualification include: (1) a clear relevance of the trainee's interests and proposed training program to the field of geriatrics/gerontology; (2) evidence of the trainee's long-term commitment to geriatrics/gerontology; (3) a firm agreement by both the candidate and the institution that prior to the completion of the trainee's program, he/she will have obtained sufficient clinical training in geriatric medicine to qualify him/her for American Board of Internal Medicine/American Board of Family Practice Certificate of Added Qualifications in Geriatric Medicine; and (4) a firm commitment that the trainee will take the examination for Added Qualifications in Geriatric Medicine no later than five years after embarking on his/her training program. The junior faculty will be selected for sponsorship by the program locally, which must develop a plan for recruitment and selection of junior faculty. The program must include a plan for providing research, teaching, and clinical activities for developing academic leaders in geriatrics, including formal didactic training, if appropriate. It is expected that the plan will be carried out mainly at the sponsoring institution, although short periods of training elsewhere may be included. Although no exact division of time among clinical, teaching, and research activities is required, at least 75 percent of time spent on program activities must be spent in research. The total program should be well-balanced and no one type of activity should be followed to the exclusion of others. The program director should possess the scientific expertise, leadership, and administrative abilities to coordinate and supervise a development program of this scope. Faculty sponsors should be established researchers with a stable base of current research support. The program must also include a plan for external review of the selection and progress of sponsored individuals and the overall conduct of the program. This review should be conducted once yearly, and written reports are to be submitted to the NIA with the awardee's annual progress reports. Allowable costs The award will support a program providing up to five years of salary support and a limited amount for research expenses for junior faculty, under the leadership of a program director, who will oversee the program, and faculty sponsors who will serve as mentors for individual junior faculty to oversee their academic development and to arrange appropriate activities needed for further development. For each junior faculty member so sponsored, the award will also provide up to ten percent of each sponsor's salary and fringe benefits for the first three years of sponsorship. The award will also support a limited amount of core resources needed for sponsored individuals' career development (e.g., key clinical research center personnel or animal facilities) if central administration improves their effectiveness. Up to five years of renewable support may be requested by the grantee institution. Individual junior faculty sponsored by the program may be supported for three to five years. No more than three persons at an awardee institution may begin their sponsored activities in any yearly budget period of this award, and one may begin sponsored activities in the fourth and fifth years. The total number of sponsored individuals may increase to eight in the third year of the award and remain constant or diminish thereafter. Salary -- Compensation for sponsored individuals based on the institution's salary scale for faculty at an equivalent experience level, but not to exceed $50,000 per year per individual, plus commensurate fringe benefits for essentially full-time (75-100%) effort. NIH policy encourages supplementation from non-government sources. Support for up to ten percent of the program director's time may be requested for administrative and other activities relating to the award. If the program director is a sponsor, he/she may receive an additional ten percent of salary. Sponsor's Support -- For each sponsored junior faculty, up to ten percent of each sponsor's salary or $10,000, whichever is less, and commensurate fringe benefits. Research and Development Support -- Applicants may request a maximum of $10,000 per year during the first two years of support for each sponsored junior faculty for research project requirements and related support, e.g., technical personnel costs, supplies, equipment, travel, tuition for necessary courses, and medical insurance premiums. Each awardee institution's Continuation Application for the third year of support, and for each subsequent year, should include a request for funds to cover the cost of an expanded research program for any sponsored individuals who will begin their third year of support during that budget period. This request should be written by the sponsored individuals who will begin their third year of support during that budget period. This request should be written by the sponsored individuals and include a budget for their remaining period of support. An amount up to $20,000 per year for research support may be requested for this period. The request should contain evidence of progress during the first two years, plans for an expanded research program, and a detailed budget with justification for use of the increased funding. Funds will be awarded contingent upon their availability and favorable program review. Consultant costs -- Funds for travel and other expenses associated with annual external review of the program (see above) should be requested. Indirect costs -- Reimbursement of actual indirect costs at a rate of up to but not exceeding eight percent of total direct costs of each award, exclusive of tuition, fees, and expenditures for equipment. APPLICATION PROCEDURES Applications are to be prepared on form PHS 398 (rev. 9/91). Applicants must follow the supplemental instructions for applications for this award, available from the Geriatrics Program, NIA. The PHS 398 application form is available at most institutional offices of sponsored research and from the Office of Grants Information, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone 301/496-7248. On item 2a enter: NIA Geriatric Academic Program Award. A letter of intent is not a prerequisite for applying; however, prospective applicants are encouraged to send a letter briefly describing scientific goals, and resources of the proposed project. This letter is to be sent to the NIA contact listed under INQUIRIES, at least three months before the submission deadline. A completed original application and three copies must be sent to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** The NIA contact office listed under INQUIRIES also must receive two copies of the application at the time of submission. The application should identify: A program director who will assume overall responsibility for management of the program. The application should describe plans for recruitment and selection of junior faculty to be sponsored, quality control of the program, and maximizing commitment of sponsored individuals to aging research after the completion of support. Faculty sponsors. The sponsors' past and present research, clinical and teaching activities should be described, as well as their previous experience in training fellows and junior faculty, and the current status of all fellows and other individuals whom they have previously trained. The faculty and institution's plans for providing research, clinical and teaching experience for sponsored individuals, including examples of the types of research projects to be undertaken, provision of experience in other laboratories to learn pertinent techniques, needed didactic training in gerontology, other basic sciences, research methodology, statistics, and clinical and teach responsibilities. Plans for efforts to recruit minority trainees where applicable, consistent with NIH's policy of encouraging such recruitment. Such plans are a required component of applications for NIH research training programs. Additional information on NIH's minority recruitment policy may be found in the NIH Guide for Grants and Contracts, Vol. 15, No. 4, March 28, 1986. REVIEW CONSIDERATIONS Applications will be received by the NIH Division of Research Grants and will be assigned to the NIA. Responsive applications will be assigned to an appropriate review group convened by the NIA. Following initial review group review, the applications will be evaluated by the National Advisory Council on Aging. REVIEW CRITERIA Applications will be judged on: o The research capabilities of faculty sponsors in areas related to geriatrics. o The abilities and record of faculty sponsors in developing junior faculty in geriatrics. o The institution's plans and commitment to the development of junior faculty's abilities in geriatrics. Renewal applications will also be judged on the career development of individuals sponsored by the program date. Funded GAP projects will be periodically reviewed to evaluate progress, as a basis for decisions on continued funding or phase-out. INQUIRIES Written and telephone inquiries are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: James K. Cooper, M.D. Geriatric Research and Training Program National Institute on Aging Gateway Building, Room 3E327 7201 Wisconsin Avenue Bethesda, MD 20892 Telephone: (301) 496-6761 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.866. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$P5 END ************************************************************ From owner-sci-resources@net.bio.net Thu Sep 16 23:00:00 1993 Path: biosci!net.bio.net From: kristoff@net.bio.net (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 22, no. 33, pt. 1, 17 September 1993 Message-ID: Date: 17 Sep 93 01:58:12 GMT Sender: kristoff@net.bio.net Lines: 1505 Approved: biosci-moderator@net.bio.net NOTE: The NIH Guide may be split into more than one mail message to avoid truncation during e-mail distribution. The first message always begins with the RFP/RFA summary sections followed by the appended texts of the full RFP/RFAs. ---------------------------------------------------------------------- $$XID NIHGUIDE 19930917 V22N33 P1O2 ************************************ X-comment: RFAs described: CA-93-032, CA-93-040 NIH GUIDE - Vol. 22, No. 33 - September 17, 1993 $$INDEX BEGIN ******************************************************* NOTICES OF AVAILABILITY (RFPs AND RFAs) $$INDEX R1 ********************************************************** CLINICAL CENTERS AND COORDINATING CENTER FOR A SAFETY FOLLOW-UP STUDY TO THE POSTMENOPAUSAL ESTROGEN/PROGESTIN INTERVENTIONS TRIAL (RFP NHLBI-HR-94-02 & NHLBI-HR-94-03) National Heart, Lung, and Blood Institute INDEX: HEART, LUNG, BLOOD $$INDEX R2 ********************************************************** TUBERCULOSIS DRUG SCREENING (RFP NIAID-DAIDS-94-24) National Institute of Allergy and Infectious Diseases INDEX: ALLERGY, INFECTIOUS DISEASES $$INDEX R3 ********************************************************** ANIMAL MODEL TESTING OF TUBERCULOSIS DRUGS (RFP NIAID-DAIDS-94-25) National Institute of Allergy and Infectious Diseases INDEX: ALLERGY, INFECTIOUS DISEASES $$INDEX R4 12/22/93 ************************************************* DEVELOPMENT AND EVALUATION OF MINIMAL ACCESS SURGERY IN CANCER TREATMENT (RFA CA-93-032) National Cancer Institute INDEX: CANCER $$INDEX R5 01/07/94 ************************************************* IMMUNOBIOLOGY OF AIDS LYMPHOMA (RFA CA-93-040) National Cancer Institute INDEX: CANCER ONGOING PROGRAM ANNOUNCEMENTS $$INDEX P1 ********************************************************** DEVELOPMENT OF HIGH CONNECTIVITY NONMAMMALIAN MODELS (PA-93-109) National Center for Research Resources INDEX: RESEARCH RESOURCES $$INDEX P2 ********************************************************** HEALTH CARE SERVICES FOR PERSONS WITH HIV INFECTION (PA-93-110) Agency for Health Care Policy and Research National Institute on Alcohol Abuse and Alcoholism National Institute on Drug Abuse National Institute of Mental Health INDEX: HEALTH CARE POLICY, RESEARCH; ALCOHOL ABUSE, ALCOHOLISM; DRUG ABUSE; MENTAL HEALTH $$INDEX P3 ********************************************************** PARTNER NOTIFICATION TO HIV-INFECTED DRUG USERS (PA-93-111) National Institute on Drug Abuse INDEX: DRUG ABUSE $$INDEX P4 ********************************************************** BREAST CANCER: ETIOLOGY AND PREVENTION (PA-93-112) National Cancer Institute INDEX: CANCER $$INDEX P5 ********************************************************** GERIATRIC ACADEMIC PROGRAM (PAR-93-113) National Institute on Aging INDEX: AGING This publication is available electronically to institutions via BITNET or INTERNET and is also on the NIH GOPHER. Alternative access is through the NIH Grant Line using a personal computer (data line 301/402-2221). Contact Dr. John James at 301/594-7270 for details. $$INDEX END ********************************************************* NOTICES OF AVAILABILITY (RFPs AND RFAs) $$R1 BEGIN NHLBI-HR-94-02/NHLBI-HR-94-03 **************************** CLINICAL CENTERS AND COORDINATING CENTER FOR A SAFETY FOLLOW-UP STUDY TO THE POSTMENOPAUSAL ESTROGEN/PROGESTIN INTERVENTIONS TRIAL NIH GUIDE, Volume 22, Number 33, September 17, 1993 RFP AVAILABLE: NHLBI-HR-94-02 NHLBI-HR-94-03 P.T. 34; K.W. 0755015, 0760025 National Heart, Lung, and Blood Institute The National Heart, Lung, and Blood Institute (NHLBI) intends to negotiate with: (1) George Washington University, (2) Johns Hopkins University, (3) Stanford University, (4) University of California, Los Angeles, (5) University of California, San Diego, (6) University of Iowa, (7) University of Texas, San Antonio, and (8) Bowman Gray School of Medicine for conduct of safety follow-up of women recruited into the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. The active phase of the three-year PEPI Trial required these institutions to collect data to evaluate the effects of five study treatment regimens on cardiovascular disease risk factors. The duration of the PEPI Trial represents the longest duration to date of a clinical trial assessing the effects of hormone replacement therapies. However, the long-term risks and benefits of hormonal therapies in postmenopausal women remains controversial. The proposed three and one-half year study provides for minimal safety follow-up of the existing PEPI cohort. The primary focus of the safety follow-up will be three annual endometrial biopsies and mammograms, in the cohort of 875 women, beginning in February 1994. Six months will be allowed for analysis of the data collected during the three-year safety follow-up. Inherent duplication of cost to the Government and unacceptable delays in completing the project make competition unfeasible for this phase of the study, which provides for safety follow-up of the subjects and analysis of collected data. $$R1 END ************************************************************ $$R2 BEGIN NIAID-DAIDS-94-24 **************************************** TUBERCULOSIS DRUG SCREENING NIH GUIDE, Volume 22, Number 33, September 17, 1993 RFP AVAILABLE: NIAID-DAIDS-94-24 P.T. National Institute of Allergy and Infectious Diseases The Developmental Therapeutics Branch, Basic Research and Development Program, Division of AIDS, National Institute of Allergy and Infectious Diseases (NIAID), has a requirement for the directed acquisition and evaluation of potential tuberculosis antimicrobials. The Request for Proposals (RFP) will contain two parts, with separate work statements for each part. Part A is the directed acquisition, distribution, and database component of this effort and Part B is the evaluation component. In Part A, the contractor will acquire compounds for screening against M. tuberculosis, maintain a computerized inventory for tracking of compounds, and coordinate and distribute compounds for evaluation (to the Contractor for Part B). Part B will require the evaluation and screening of compounds with potential as anti-tuberculosis agents. In Part B, the contractor will evaluate and screen compounds for antimicrobial activity against M. tuberculosis, evaluate the potential of selected compounds to inhibit the replication of intracellular M. tuberculosis, and develop and utilize new assays. Offerors may respond to more than one Part, but must submit separate Technical and Business proposals for each (under separate cover) to be considered. In order to avoid any potential conflict of interest by the acquisition contractor (Part A), a mandatory qualification criterion will be included to exclude pharmaceutical or chemical companies from participating as offerors. A pharmaceutical or chemical company is defined as an organization that sells drugs and/or chemicals to the general public for profit. An organization with any such commercial activity shall be excluded from competition. Also, approaches to Part B using a "virulent" form of M. tuberculosis must have a Bio-Safety Level 3 Facility at time of award to qualify. This announcement is a new solicitation and it is anticipated that there will be one award for each Part. The issuance of the RFA will be on or about September 17, 1993, and proposals will be due by COB on or about December 17, 1993. One cost-reimbursement, five-year contract is anticipated for each Part. INQUIRIES A short-form version of the RFA will be available, for informational purposes, which includes only the background information, the full Statement of Work, and Evaluation Criteria. There is sufficient information in this document to enable prospective offerors to determine if they have the expertise/capability to meet the Government's requirements. A full-text version will also be available, which includes all the necessary information, business forms, etc., in order to submit a proposal. There are a limited number of full-text versions available. Therefore, request the short form RFP first, then the full-text version only if you are going to submit a proposal. All requests must be in writing. Specify whether you are requesting the short-version or the full-text version of the RFP. FAX requests are acceptable, but it is preferred that requests be made in writing and two self-addressed mailing labels be provided. Requests for the RFA may be directed to: Mr. Ross Kelley Contract Management Branch National Institute of Allergy and Infectious Diseases Solar Building, Room 3C07 6003 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-2509 FAX: (301) 402-0972 $$R2 END ************************************************************ $$R3 BEGIN NIAID-DAIDS-94-25 **************************************** ANIMAL MODEL TESTING OF TUBERCULOSIS DRUGS NIH GUIDE, Volume 22, Number 33, September 17, 1993 RFP AVAILABLE: NIAID-DAIDS-94-25 P.T. National Institute of Allergy and Infectious Diseases The Developmental Therapeutics Branch, Basic Research and Development Program, Division of AIDS, National Institute of Allergy and Infectious Diseases (NIAID), has a requirement for animal model testing of potential therapies against Tuberculosis (TB). The Contractor will be required to: test potential therapeutic agents for efficacy in a mouse model and provide relevant strains of TB to do so; demonstrate the ability to modify or improve the proposed model and design alternative protocols; perform additional studies such as efficacy in models or acute infection measuring mortality as the endpoint, comparison of different strains of TB in efficacy evaluations, determinations of optimal dosages, routes, and schedules of administration. Offerors must have a Bio-Safety Level 3 animal facility at time of award to be considered. Therapeutic agents to be evaluated will be supplied by the Government, through a contract to be awarded for the acquisition of compounds for TB research. This announcement is for a new solicitation and it anticipated that there will be one award made. The issuance of the Request for Proposals (RFP) will be on or about September 17, 1993, with proposals due by COB on or about December 17, 1993. A five-year, cost-reimbursement contract is anticipated. INQUIRIES Requests for the RFA may be directed to: Mr. Bruce E. Anderson Contract Management Branch National Institute of Allergy and Infectious Diseases Solar Building, Room 3C07 6003 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-8371 FAX: (301) 402-0972 A short-form version of the RFA will be available, for informational purposes, which includes only the background information, the full Statement of Work, and Evaluation Criteria. There is sufficient information in this document to enable prospective offerors to determine if they have the expertise/capability to meet the Government's requirements. A full-text version will also be available, which includes all the necessary information, business forms, etc., in order to submit a proposal. There are a limited number of full-text versions available. Therefore, request the short-form RFP first, then the full-text version only if you are going to submit a proposal. All request must be in writing. Specify whether you are requesting the short version or full-text version of the RFP. FAX requests are acceptable, but it is preferred that requests be made in writing and two self-addressed mailing labels be provided. $$R3 END ************************************************************ $$R4 BEGIN CA-93-032 FULL-TEXT ************************************** DEVELOPMENT AND EVALUATION OF MINIMAL ACCESS SURGERY IN CANCER TREATMENT NIH GUIDE, Volume 22, Number 33, September 17, 1993 RFA AVAILABLE: CA-93-032 P.T. 34; K.W. 0785210, 0715035, 0755015 National Cancer Institute Letter of Intent Receipt Date: October 20, 1993 Application Receipt Date: December 22, 1993 THIS IS A NOTICE OF AVAILABILITY OF A REQUEST FOR APPLICATIONS (RFA); IT IS ONLY AN ABSTRACT OF THE RFA. POTENTIAL APPLICANTS MUST REQUEST THE COMPLETE RFA, WHICH CONTAINS ESSENTIAL INFORMATION FOR THE PREPARATION OF AN APPLICATION, FROM THE CONTACT LISTED IN "INQUIRIES," BELOW. FAILURE TO FOLLOW THE INSTRUCTIONS IN THE COMPLETE RFA MAY RESULT IN AN INCOMPLETE APPLICATION, WHICH WILL BE RETURNED TO THE APPLICANT WITHOUT REVIEW. PURPOSE The Cancer Therapy Evaluation Program (CTEP), Division of Cancer Treatment (DCT), National Cancer Institute (NCI) invites applications for cooperative agreements from institutions or consortia, including the DCT Clinical Trials Cooperative Groups, capable of and interested in performing phase II and phase III evaluations of minimal access surgery. Minimal access surgery, which is synonymous with minimally invasive surgery, has become increasingly prominent in the diagnosis and treatment of benign conditions. Case reports and small series have been published documenting the use of minimal access surgery in the care of patients with cancer. The NCI is interested in a timely evaluation of minimal access techniques that have the potential for significantly decreasing the morbidity, cost, and inconvenience of cancer treatment. Determination of the effectiveness of minimal access surgery in the treatment of cancer is critical, before minimal access techniques become the standard of care for cancer therapy in the community. Phase III studies should be designed to evaluate minimal access surgery versus standard surgery. Phase II studies should evaluate the practicality and safety of minimal access surgery for specific tumor sites. It is essential for institutions or consortia to have surgeons with experience in minimal access surgery and evidence of patient accrual to complete a phase II or III study or studies in a timely manner. Solid tumors that are relevant to this RFA include cancers of the brain, lung, stomach, pancreas, colon, ovary, endometrium, and cervix. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This RFA, Development and Evaluation of Minimal Access Surgery In Cancer Treatment, is related to the priority area of cancer. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Applications from minority individuals and women, as well as new and experienced investigators, are encouraged. An applicant institution may consist of a single institution or a consortium of institutions functioning as an integrated unit under the guidance and direction of a single Principal Investigator for the purpose of accessing a sufficient patient population. Foreign institutions are ineligible to apply or be a collaborating institution within an applicant institution. All accrued patients must be treated in the United States. It is essential for institutions/consortia to have surgeons with experience in minimal access surgery and evidence of patient accrual to complete a phase II or III study or studies in a timely manner. 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 in the RFA under the section Terms and Conditions of Award. Awards and level of support depend on receipt of a sufficient number of applications of high scientific merit. Because the nature and scope of the research proposed (phase II versus phase III studies) in response to this RFA may vary, it is anticipated that the size of awards will vary also. The total project period for applications submitted in response to the present RFA may not exceed three years. The anticipated award date is July 1, 1994. Although this program is provided for in the financial plans of the National Cancer Institute, awards pursuant to this RFA are contingent upon the availability of funds for this purpose. This RFA is a one-time solicitation. At this time the NCI has not determined whether or how this solicitation will be continued beyond the present RFA. If the NCI does not continue the program, awardees may submit grant applications through the usual investigator-initiated grants program. FUNDS AVAILABLE Approximately $750,000 in total costs per year for three years will be committed to fund applications submitted in response to this RFA. It is anticipated that the funds will be able to support two phase III awards, four phase II awards, or some combination thereof. RESEARCH OBJECTIVES Solid tumors potentially relevant to this RFA account for significant cancer incidence, morbidity, mortality and expense. This RFA is intended to promote phase II and III evaluation of minimal access surgery in the management of patients with solid tumors. This RFA is not intended to duplicate or supplement support for any phase II or phase III trials supported by any other mechanism. Phase III studies will evaluate minimal access surgery versus standard surgical technique, including cancers of the brain, lung, stomach, pancreas, colon, ovary, endometrium and cervix. Developmental phase II studies will be aimed at broadening the applicability of minimal access surgery for specific tumor sites by evaluating the practicality and safety of this approach. Each application is expected to focus on a specific solid tumor. An applicant institution may submit more than one application. In addition, an individual scientist, individual institution, or consortium of institutions may be included on more than one application (or tumor site). All institutions accruing patients must be able to document adequate surgical experience with minimal access surgery as well as adequate patient accrual to complete a phase II or III trial in a timely manner. For phase III trials, outcomes of interest include morbidity (acute and chronic), mortality, efficacy of treatment, length of hospital stay, time to return to normal activities, quality of life, and cost. Applications should include an analysis of what outcomes are expected to vary importantly between minimal access surgery and conventional surgery. It is recommended that costs be measured in terms of health-related resource utilization, such as hospital days, operating room time, office visits, days until resumption of normal activities, etc. Applications should include documentation of a cost-related data source that is comprehensive and available to the researcher. Applications must include a statistical section describing plans for analysis of data designed to test the hypotheses, as well as a power/sample size analysis for cost and clinical endpoints. It is possible that collection of data on cost from a subset of patients may be adequate. For phase III trials, or phase II trials focusing on rare tumors, investigators are encouraged to work with multi-center organizations or form a consortium of institutions in order to access sufficient number of patients to test the proposed hypotheses. SPECIAL REQUIREMENTS The RFA describes the complete terms for this cooperative agreement including definitions, conditions of award, responsibilities of the awardees, responsibilities of NCI staff, collaborative responsibilities and the arbitration process to resolve disputes. The RFA is available from the Program Director listed under INQUIRIES. STUDY POPULATIONS SPECIAL INSTRUCTIONS FOR INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDIES For projects involving clinical research, NIH requires applicants to give special attention to the inclusion of women and minorities in study populations. If women or minorities are not included in the study populations for clinical studies, a specific justification for this exclusion must be provided. Applications without such documentation will not be accepted for review. LETTER OF INTENT Prospective applications are asked to submit, by October 20, 1993, a letter of intent that includes a descriptive title of the proposed research, the name and address of the Principal Investigator, the names of key personnel, participating institutions, and the number and title of the RFA in response to which the applications may be submitted. This letter of intent is not required, is not binding, and does not enter into the review of subsequent applications. The letter of intent is to be sent to Dr. Roy S. Wu at the address listed under INQUIRIES. APPLICATION PROCEDURES Applications must be received by December 22, 1993. If an application is received after that date, it will be returned. The research grant application form PHS 398 (rev. 9/91) is to be used in applying for cooperative agreements. 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 the NCI Program Director named below. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed by the Division of Research Grants (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 NCI program staff function. Applications that are judged non-responsive will be returned to the applicant by the NCI. AWARD CRITERIA The anticipated date of award is July 1, 1994. In addition to the scientific and technical merit of the application, NCI will consider how well the applicant institution meets the goals and objectives of the program as described in the RFA, availability of resources, and study population. INQUIRIES Written and telephone requests for the RFA and the opportunity to clarify any issues or questions from potential applicants are welcome. Direct inquiries regarding scientific issues to: Edward L. Trimble, M.D., M.P.H. Division of Cancer Treatment National Cancer Institute Executive Plaza North, Suite 741 Bethesda, MD 20892 Telephone: (301) 496-2522 FAX: (301) 402-0557 Direct inquiries regarding programmatic issues and address the letter of intent to: Roy S. Wu, Ph.D. Grants Program Director Division of Cancer Treatment National Cancer Institute Executive Plaza North, Room 734 Bethesda, MD 20892 Telephone: (301) 496-8866 FAX: (301) 480-4663 Direct inquiries regarding fiscal matters to: Ms Carolyn Mason Grants Administration Branch National Cancer Institute Executive Plaza South, Room 242 6120 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-7800, ext. 59 FAX: (301) 496-8601 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.395, Cancer Treatment Research. Awards are made under the authorization of the Public Health Service Act, Tile IV Sections 301, 410, and 411, Part A (Public Law 78-410, 42 USC 241 as amended, Public Law 99-158, 42 USC 285a) and administered under PHS grant policies and Federal Regulation at 42 CFR Part 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems agency review. $$R4 END ************************************************************ $$R5 BEGIN CA-93-040 FULL-TEXT ************************************** IMMUNOBIOLOGY OF AIDS LYMPHOMA NIH GUIDE, Volume 22, Number 33, September 17, 1993 RFA AVAILABLE: CA-93-040 P.T. 34; K.W. 0715008, 0715035, 0710070 National Cancer Institute Letter of Intent Receipt Date: November 15, 1993 Application Receipt Date: January 7, 1994 THIS IS A NOTICE OF AVAILABILITY OF A REQUEST FOR APPLICATIONS (RFA); IT IS ONLY AN ABSTRACT OF THE RFA. POTENTIAL APPLICANTS MUST REQUEST THE COMPLETE RFA, WHICH CONTAINS ESSENTIAL INFORMATION FOR THE PREPARATION OF AN APPLICATION, FROM THE CONTACT LISTED IN "INQUIRIES" BELOW. FAILURE TO FOLLOW THE INSTRUCTIONS IN THE COMPLETE RFA MAY RESULT IN AN INCOMPLETE APPLICATION, WHICH WILL BE RETURNED TO THE APPLICANT WITHOUT REVIEW. PURPOSE The intent of this initiative is to stimulate basic research on biologic and immunologic mechanisms involved in the development of lymphomas in AIDS patients. Specifically, this initiative will encourage development and testing of hypotheses about the mechanisms of lymphomagenesis in the unique immune environment induced by HIV infection. Before effective therapies can be designed, it is necessary to understand the basic mechanism of lymphomagenesis in AIDS. 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, Immunobiology of AIDS Lymphoma, is related to the priority area of cancer. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Research grant applications may be submitted by domestic and foreign for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of state and local governments, and eligible agencies of the Federal government. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT Support of this program will be through the National Institutes of Health (NIH) research project grant (R01). Applicants will be responsible for the planning, direction, and execution of the proposed project. Except as otherwise stated in this RFA, awards will be administered under PHS grants policy as stated in the Public Health Service Grants Policy Statement DHHS Publication No. (OASH) 90-50,000, revised October 1, 1990. This RFA is a one-time solicitation. Generally, future unsolicited competing renewal applications will compete with all investigator-initiated R01 applications and be reviewed according to the customary peer review procedures by the Division of Research Grants (DRG). However, if the NCI determines that there is a sufficient continuing program need, a request for renewal applications will be announced. Only recipients of awards under this RFA will be eligible to apply. FUNDS AVAILABLE Approximately $1,500,000 in total costs per year for four years will be committed to fund applications that are submitted in response to this RFA. It is anticipated that at least six to eight individual R01 grant awards will be made. This level of support is dependent on the receipt of a sufficient number of applications of high scientific merit. Although this program is provided for in the financial plans of the NCI, awards pursuant to this RFA are contingent upon the availability of funds for this purpose. RESEARCH OBJECTIVES This RFA is intended to encourage and promote research into the basic immunologic mechanisms that underlie lymphomagenesis in AIDS patients. Since there are many factors that affect B-cell lymphomagenesis it is important to elucidate the inter-relationships between cellular and molecular mechanisms in AIDS-associated lymphomagenesis. While the use of patient-derived material may be the most direct approach to this problem, the use of animal models of AIDS lymphoma or other human immunodeficiencies may be appropriate and is encouraged. The proposed studies should include cellular and molecular approaches and may include collaborations between basic and clinical scientists. Applicants who propose to use tissues or cells from AIDS patients must document that they have adequate access to these resources to perform the proposed studies. Applicants who do not demonstrate this access will have their applications returned without review. STUDY POPULATIONS SPECIAL INSTRUCTIONS FOR INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDIES 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. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale must be provided. Applications without this documentation will not be accepted for review. LETTER OF INTENT Prospective applicants are asked to submit, by November 15, 1993, a letter of intent that includes a descriptive title of the proposed research, the name and address of the Principal Investigator, the names of other key personnel and participating institutions, and the number and title of the RFA in response to which the application may be submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information that it contains is helpful in planning for the review of applications. It allows NCI staff to estimate the potential review workload and to avoid conflict of interest in the review. The letter of intent is to be sent to Dr. John F. Finerty at the address listed under INQUIRIES. APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 9/91) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research and from the Office of Grants Information, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone 301/594-7248. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed by NIH staff for completeness and responsiveness. Those applications judged to be both responsive and competitive will be further evaluated according to the review criteria stated in the RFA. INQUIRIES Written and telephone inquiries concerning this RFA are encouraged and may be directed to the program director listed below. NCI program staff welcome the opportunity to clarify any issues or questions from potential applicants. Direct inquiries regarding programmatic issues and requests for the RFA to: Dr. John F. Finerty Division of Cancer Biology, Diagnosis, and Centers National Cancer Institute Executive Plaza North, Room 501 6130 Executive Boulevard Bethesda, MD 20892-9904 Telephone: (301) 496-7815 FAX: (301) 496-8656 Direct inquiries regarding fiscal matters to: Mr. Robert Hawkins Grants Management Branch National Cancer Institute Executive Plaza South, Room 243 Bethesda, MD 20892 Telephone: (301) 496-7800, ext. 13 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.396. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$R5 END ************************************************************ ONGOING PROGRAM ANNOUNCEMENTS $$P1 BEGIN PA-93-109 ************************************************ DEVELOPMENT OF HIGH CONNECTIVITY NONMAMMALIAN MODELS NIH GUIDE, Volume 22, Number 33, September 17, 1993 PA NUMBER: PA-93-109 P.T. 34; K.W. 0755020, 0755043, 0780015, 1004005 National Center for Research Resources PURPOSE The Biological Models and Materials Research Program (BMMRP) of the National Center for Research Resources (NCRR) is reissuing this announcement to encourage the submission of applications for the development of high connectivity nonmammalian models for biomedical research. ELIGIBILITY REQUIREMENTS Applications may be submitted by foreign and domestic, for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State or local governments, and eligible agencies of the Federal government. Foreign institutions are not eligible for the First Independent Research Support and Transition (FIRST) (R29) award. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT The support mechanism for this program will be the individual investigator-initiated research grant (R01) or the FIRST Award (R29), as applicable. Under these mechanisms the applicant will plan, direct, and carry out the research program. The proposed project period during which the research will be conducted should adequately reflect the time required to accomplish the stated goals and be consistent with the policy for grant support. 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 vary also. RESEARCH OBJECTIVES The objective of this announcement is to stimulate research on the development of high connectivity, nonmammalian models for biomedical research as follows: o Organismic, including all poikilotherms, but not homeotherms, lower organisms (such as fishes, invertebrates, and microorganisms). o In vitro systems, such as established cell lines from any species, or cell or tissue culture from poikilothermic sources. o Mathematical or computer models, in particular when closely coupled to biological experimentation. There are opportunities for mathematical modeling in many areas of biomedical research and at all levels of biological organization. A high connectivity model is one in which: o the body of knowledge about the system is large, and has resulted in extensive cross information, or connection, with other systems. Examples of organisms that have many characterized properties include, but are not limited to, Drosophila melanogaster, Caenorhabditis elegans, Escherichia coli, Aplysia sp., Xenopus sp., Arabidopsis sp., and sea urchins. o a function or property is broadly retained across many taxa. Examples of functions include cytoskeletal structure, cell adhesion, cytochrome c, hormones, hormone receptors, and genetic regulation. o the research involves broad intertaxonomic projects. 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, i.e., February 1, June 1, and October 1. Application kits are available at most institutional offices of sponsored research and may be obtained from the Office of Grants Information, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone (301) 594- 7248. 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. To identify the application as in response to this announcement, check "YES" in Item 2a on the face page of the application and enter the PA number and the title, "HIGH CONNECTIVITY NONMAMMALIAN MODELS." The completed original application and five legible copies must be sent or delivered to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** REVIEW PROCEDURES Applications will be received by the National Institutes of Health (NIH), Division of Research Grants (DRG), and referred to an appropriate Initial Review Group (IRG) for scientific and technical review. Institute assignment decisions will be governed by normal programmatic considerations as specified in the NIH Referral Guidelines. Some applications may receive secondary assignments. Following the initial scientific review, the applications will be evaluated by the National Advisory Research Resources Council or another appropriate Institute/Center (IC) council/board. AWARD CRITERIA Applications will compete for available funds with all other approved applications assigned to that IC. The following will be considered when 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: Louise E. Ramm, Ph.D. or Elaine Young, Ph.D. Biological Models and Materials Research Program National Center for Research Resources Westwood Building, Room 854 5333 Westbard Avenue Bethesda, MD 20892 Telephone: (301) 594-7906 Direct inquiries regarding fiscal matters to: Ms. Mary V. Niemiec Office of Grants and Contracts Management National Center for Research Resources Westwood Building, Room 849 Bethesda, MD 20892 Telephone: (301) 594-7955 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.198. Awards are made under authorization of the Public Health Service Act, Title III, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$P1 END ************************************************************ $$P2 BEGIN PA-93-110 ************************************************ HEALTH CARE SERVICES FOR PERSONS WITH HIV INFECTION NIH GUIDE, Volume 22, Number 33, September 17, 1993 PA NUMBER: PA-93-110 P.T. 34; K.W. 0715008, 0730050 Agency for Health Care Policy and Research National Institute on Alcohol Abuse and Alcoholism National Institute on Drug Abuse National Institute of Mental Health PURPOSE The Agency for Health Care Policy and Research (AHCPR), National Institute on Alcohol Abuse and Alcoholism (NIAAA), the National Institute on Drug Abuse (NIDA), and the National Institute of Mental Health (NIMH) support and conduct extramural research and evaluations of health care services and health care systems. This program announcement (PA) focuses on research related to care for persons with Acquired Immune Deficiency Syndrome (AIDS) and other Human Immunodeficiency Virus (HIV)-related diseases. The continued growth of the HIV epidemic has created an urgent need to better understand the public policy implications of providing care for persons with HIV infection. Critical issues include: the epidemic's expansion into new populations, the availability of new treatment modalities, the recognition of HIV-related illness as a chronic disease, the interaction of HIV infection with substance abuse and with the resurgence of tuberculosis, the passage and implementation of the Ryan White Comprehensive AIDS Resources Emergency (CARE) Act, and health care reform. This PA emphasizes a need for short-term research to better inform decision-makers developing public policy concerning the delivery of health care services to people with HIV-related 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, Health Care Services for Persons with HIV Infection, is related to the services and protection objectives of several priority areas including HIV infection, sexually transmitted diseases, and immunization and infectious diseases. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0 or 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, public and private, including universities, clinics, units of State and local governments, and foundations. The AHCPR by law can support only non-profit organizations; the NIAAA, NIDA, and NIMH can support for-profit as well. Applications from minority and women investigators are encouraged. MECHANISM OF SUPPORT This program announcement will use the research project grants (R01) mechanism. Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. Projects should be accomplished in one to three years. RESEARCH OBJECTIVES Background. The AIDS epidemic has spread to previously unaffected populations and has placed an increased burden on individuals with HIV infection and their families, providers of health care, communities, and governments. Although HIV infection is spreading to new populations, the difficulties in obtaining health care and supportive services faced by people with HIV infection continue to focus attention on gaps and inequities in the health care system. New treatments have caused HIV-related illnesses to shift from acute, fatal ailments to chronic illnesses with which individuals may live asymptomatically for long periods. However, the response of the health care delivery system remains oriented to acute care, rather than preventive and primary care; and continues to be based on hospital and medical services that often do not complement community outreach, social support services, and long-term care. The divergence between the acute-care based health care system and the chronic care paradigm of HIV infection is generating new health care policy questions. The frequent association of HIV infection with homelessness, mental illness, poverty, and substance abuse requires that the study of the HIV epidemic occur in conjunction with analyses of socioeconomic and other conditions. The resurgence of tuberculosis (TB), often in persons with HIV infection, creates new challenges for those seeking to improve care of the dually infected population. Public policy concerning HIV infection also must address the distinct needs of special populations such as minorities; women; adolescents; children, including abandoned and orphaned children; residents of rural communities; and prisoners. Research Issues. Research is needed to build the scientific foundation necessary for development of informed HIV-related health care policy recommendations. Some research questions require long-term study; however, the intent of this PA is to encourage research designs and methods that produce results quickly. The AHCPR, NIAAA, NIDA, and NIMH have identified five service research areas as priorities: (1) cost and financing of HIV/AIDS treatments and services; (2) organization and delivery of services; (3) characteristics and interactions of providers and patients; (4) co-morbidity; and (5) special populations. The questions raised within these research areas often are interdependent and may be applicable to topics in other areas. Applicants need not limit themselves to these questions. 1. Cost and Financing of HIV/AIDS Treatments and Services To focus the debate on future financing and organization of HIV-related care, information is needed about costs of care, the variation of costs within different health care settings, the relation of costs to health needs and outcomes, and the relative roles of private and public sectors in financing care. Efforts are required to discern how changes in health care systems, such as those being implemented in several States, will address the needs of persons with HIV infection, and affect reimbursement, financing, and expenditures for HIV-related care. Examples of research questions are: o What are the current and projected unmet needs and service demands, utilization patterns, and costs of providing health and mental health care, substance abuse treatment, and support services for individuals with HIV disease and their families over the duration of the illness? o How do different levels and mechanisms of State and Federal financing such as enhanced Medicaid reimbursement for AIDS care, funding of HIV treatment centers, use of Medicaid waivers, and Medicaid payment of private insurance premiums affect availability, accessibility, and outcomes of HIV-related care? o What are the relationships among community-based services, including home health care and other forms of supportive and long-term care, and the utilization and costs of ambulatory, inpatient, emergency room, and nursing home services? 2. Organization and Delivery of Services Research is required to ascertain how HIV service delivery systems function in different communities to enhance the effectiveness, reduce the cost of the services delivered, maximize the individual's dignity and autonomy, and integrate HIV-related care into the mainstream of health care services. While case management has been a key organizational component in the response of many communities to the challenge of caring for individuals with HIV-related diseases, many research issues remain. Establishing effective health care delivery systems requires an understanding of the availability of different service providers and the extent to which they coordinate their services. Examples of questions of interest include: o What is the effect of HIV case management on clinical outcomes, patient and caregiver satisfaction, access to and utilization of services, costs of care, and quality of life? o What is the effect of different delivery settings such as public vs. private, inpatient vs. outpatient, home care vs. various housing and intermediate care options, and substance abuse treatment setting options on cost, utilization, treatment effectiveness, patient and provider satisfaction, perceived quality of care, and quality of life? o How do multi-professional, one-stop shopping approaches, and other organizational models affect the delivery of HIV-related clinical services, mental health care, substance abuse treatment, early intervention, and support services to HIV-infected persons? 3. Characteristics and Interactions of Providers and Patients To address the many different needs of persons with HIV infection, a complex array of formal and informal care providers has evolved. With HIV infection increasingly recognized as a chronic disease, questions are raised about the linkage between the provision of acute and long-term care services. Analyses of the elements defining appropriate and effective care and a better understanding of the actions of the care provider and the consequences of those actions for the patient are essential to the further improvement of HIV care delivery systems. Some questions are: o What are the attitudes and actual behaviors of providers regarding the provision of services to patients with HIV? o What characteristics of providers and their provision of services are associated with patient satisfaction and effective use of and adherence to prescribed regimens? o How effective are various early interventions in preventing acute phases of HIV-related disease, enhancing health outcomes and quality of life, and reducing health care costs? 4. Issues Related to Co-morbidity Increasingly, persons with HIV infection have several conditions of co-morbidity, such as TB, mental illness, alcoholism, and drug abuse that affect individual health outcomes and disease transmission and call attention to the need for coordination of care delivery. Research is needed to clarify the relationship between these conditions and HIV-related illness, morbidity, health care utilization, organizational characteristics of delivery systems, and costs and financing of care. Some questions are: o What services are available to address health care and related needs for the drug-using population with HIV infection? How can health services be integrated with substance abuse treatment, HIV testing, and mental health and social support services? o What is the economic effect of TB and multi-drug resistant (MDR) TB on the cost of HIV-related care? What is the cost effectiveness of various TB treatment strategies for persons with HIV infection. o To what extent do treatment practices of health care providers lead to poor adherence and development of MDR-TB in HIV infected patients? 5. Special Populations The AHCPR, NIAAA, NIDA, and NIMH are interested in studies of the preceding four research areas that target the unique concerns of drug abusers in and out of treatment, sex partners and families of drug abusers, minorities, native Americans, homosexual populations, women, adolescents, children including abandoned and orphaned children, the indigent, the homeless, prisoners, and residents of rural communities. Examples of research needs are: o How can rural health care systems establish coordinated, comprehensive, and quality patient care programs for patients with HIV-related illness? o What are the additional services, such as day care for children, psychosocial services, or drug treatment, required to enhance access to HIV-related treatment for women and their families? What are the social and financial burdens of families caring for more than one HIV infected family member? o How does utilization of HIV-related care vary among women, children, adolescents, and others? What is the role of socioeconomic and cultural factors in the transmission of HIV, the disease process, and early and continuous access to care among these populations? STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS CONCERNING INCLUSION OF WOMEN AND MINORITIES IN RESEARCH STUDY POPULATIONS The AHCPR and the National Institutes of Health (NIH) require 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 and NIH will not award grants for applications which do not comply. If the application does not contain the required information, it will be returned without review. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues should be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information should be included in the form PHS 398 in Sections 1 to 4 of the Research Plan and summarized in Section 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, the AHCPR and NIH recognize that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., American Indians/Alaskan Natives, Asian/Pacific Islanders, African Americans, Hispanics). Where appropriate, the applicant must provide the rationale for studies on single minority population groups. For foreign awards, the policy on inclusion of women applies fully. Since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. Peer reviewers will address specifically whether the applicant's research plan conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific 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. APPLICATION PROCEDURES Applications are to be submitted on the grant application form PHS 398 (rev. 09/91), and will be accepted at the standard AIDS application deadlines as indicated in the application kit. (State and local governments may use form PHS 5161 and follow those requirements for copy submission.) Application kits 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 the Scientific Review Branch, Agency for Health Care Policy and Research, 2101 East Jefferson Street, Suite 602, Rockville, MD 20852, telephone 301-594-1449. The title and number of the PA must be typed in Section 2a on the face page of the application. The completed original application of form PHS 398 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** The Division of Research Grants (DRG) will not accept any application in response to this announcement that is essentially the same as one pending initial review, unless the applicant withdraws the pending application. The DRG will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of substantial revisions of applications already reviewed, but such applications must include an introduction addressing the previous critique. Applications for R01 grants must be received by the Division of Research Grants, NIH. The first application receipt date for this PA is January 2, 1994. Thereafter, the deadline dates for HIV applications are May 1, September 1, and January 2 of each year. Applicants are encouraged to apply by the earliest possible submission date. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by the referral office, DRG. Incomplete applications will be returned to the applicant without further consideration. Review criteria for AHCPR, NIAAA, NIDA, and NIMH grant applications are significance and originality from a scientific and technical viewpoint; adequacy of the method to carry out the project; availability of data or the proposed plan to collect data required for the project; qualifications and experience of the Principal Investigator and proposed staff; adequacy of the plan for organizing and carrying out the project; reasonableness of the proposed budget; and adequacy of the facilities and resources available to the applicant. Applications will be reviewed for scientific and technical merit by an initial review group (IRG) 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. For NIH, by law, only applications recommended by the Council for consideration for funding may be supported. Summaries of IRG recommendations are sent to applicants as soon as possible following IRG review. AWARD CRITERIA Applications will compete for available funds with all other 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. The earliest possible dates of award for applications are six months from the date of submission. INQUIRIES Those considering an application in response to this PA are strongly encouraged to discuss their project with AHCPR, NIAAA, NIDA, and/or NIMH program staff before formal submission. Staff members of these respective agencies welcome the opportunity to clarify any issues or questions from potential applicants. Copies of a Grant Announcement based upon this PA will be available in the Fall from the AHCPR Publications Clearinghouse, P.O. Box 8547, Silver Spring, MD 20907, (1-800-358-9295); or NIAAA, NIDA, and NIMH program staff listed below. Applicants may direct inquiries regarding programmatic issues to: Melford J. Henderson, M.P.H, M.A. Center for General Health Services Extramural Research Agency for Health Care Policy and Research 2101 East Jefferson Street, Suite 502 Rockville, MD 20852-4908 Telephone: (301) 594-1354, ext. 122 Kendall Bryant, Ph.D. Division of Clinical and Prevention Research National Institute of Alcohol Abuse and Alcoholism 5600 Fishers Lane, Room 13C-06 Rockville, MD 20857 Telephone: (301) 443-1677 Harry W. Haverkos, M.D. National Institute on Drug Abuse 5600 Fishers Lane, Room 10A-38 Rockville, MD 20857 Telephone: (301) 443-6697 Leonard Mitnick, Ph.D. Office on AIDS National Institute of Mental Health 5600 Fishers Lane, Room 15-99 Rockville, MD 20857 Telephone: (301) 443-7281 Direct inquiries regarding fiscal matters to: Ralph Sloat Grants Management Branch Agency for Health Care Policy and Research 2101 East Jefferson Street, Suite 601 Rockville, MD 20852-4908 Telephone: (301) 594-1447 Joseph Weeda Grants Management Branch National Institute on Alcohol Abuse and Alcoholism 5600 Fishers Lane, Room 16-86 Rockville, MD 20857 Telephone: (301) 443-4703 Jack Manischewitz Grants Management Branch National Institute on Drug Abuse 5600 Fishers Lane, Room 8A-54 Rockville, MD 20857 Telephone: (301) 443-6710 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 Nos. 93.226, 93.242, 93.273, and 93.279. Awards are made under authorization of Section 301 and Titles IV and IX of the Public Health Service Act. Awards are administered under the PHS Grants Policy Statement; and Federal Regulations 42 CFR 67 Subpart A, 42 CFR 52, 45 CFR Part 74 (45 CFR Part 92 for State and local governments), 45 CFR Part 46, and 42 CFR Part 2. This program is not subject to the intergovernmental review requirements of Executive Order 12372. $$P2 END ************************************************************ $$P3 BEGIN PA-93-111 ************************************************ PARTNER NOTIFICATION TO HIV-INFECTED DRUG USERS NIH GUIDE, Volume 22, Number 33, September 17, 1993 PA NUMBER: PA-93-111 P.T. 34; K.W. 0715008, 0404009, 0715182 National Institute on Drug Abuse PURPOSE The purpose of this program announcement is to encourage research on comprehensive partner notification programs targeted to HIV-positive drug users and their sexual and/or needle-sharing partners. Support will be provided for the development of new community-based methodologies/strategies for client and third-party notification, the selection/adaption of existing notification models, and the subsequent implementation, testing, and evaluation of effectiveness of the methodologies in terms of identification of partners, reduction in risk behavior, and prevention of spread of HIV. 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, Partner Notification to HIV-Infected Individuals, is related to the priority area of alcohol and other drugs. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0 of Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by foreign and domestic, for-profit and non-profit, public and private organizations such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Women and minority investigators are encouraged to apply. Applicants are especially encouraged from State and municipal governments with outreach units and/or State and municipal governments collaborating with university-based research units. MECHANISM OF SUPPORT This program announcement will use the National Institutes of Health (NIH) individual research grant (R01). Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. Support will be provided for a period of up to five years (renewable for subsequent periods) subject to continued availability of funds and progress achieved. Because the nature and scope of the research proposed in response to this program announcement may vary, it is anticipated that the size of an award will vary also. RESEARCH OBJECTIVES Summary Following initial exploratory investigations on issues related to the process of HIV-seropositivity disclosure and its consequences, carefully controlled studies are sought to implement and determine: (1) which strategies are most effective in reaching seropositive drug users and motivating them to disclose their serostatus to their sexual/needle-sharing partners; (2) the effects of combining partner notification with current HIV outreach/prevention activities; and (3) evaluation of new and existing methodologies for patient and third-party partner notification models for drug users. Sub-objectives include: (a) evaluation of different notification strategies on voluntary HIV testing for at-risk needle-sharing injection drug users and/or sexual partners; (b) identifying subgroup characteristics as a function of which partner notification model is selected; (c) assessing the degree to which index individuals are compliant with the selected model; (d) analyzing the changes in behavioral risk reported among individuals with different risk behaviors (e.g., type of partner--needle-sharing versus high-risk sexual contacts) as a function of selected model and subsequent compliance; (e) extent to which identified sexual/needle-sharing partners seek HIV counseling and testing; (f) analyzing the changes in behavioral risk reported by informed partners with different risk behaviors (needle-sharing versus high-risk sexual contacts); (g) evaluating the extent and duration of psychological and social impact of HIV seropositive partner notification on both index and partners' drug-using, needle-sharing and sexual relationships; and (h) determining risk factors and rates of HIV transmission in serologically discordant injection partners receiving risk reduction. Applicants may focus on and recruit drug users from a variety of settings including individuals who are currently involved in traditional drug treatment programs or drug users who cannot or do not wish to currently access drug treatment and are identified through community-based outreach efforts. There exists a paucity of data regarding issues related to disclosure and its consequences. As a result, it may be necessary to obtain data from exploratory studies to address issues surrounding the process of HIV-seropositivity disclosure using qualitative strategies and methodological approaches to better understand this process prior to program development, implementation, and evaluation. It is also important to explore and understand the consequences of disclosure and determine the differential impact on risk behaviors for men and women and across various racial/ethnic groups. Background The National Institute on Drug Abuse (NIDA) recognizes the importance of understanding the extent to which HIV prevention efforts exist or can exist for drug users at risk for HIV infection. It is particularly important to demonstrate the extent to which drug users will voluntarily obtain HIV testing and counseling, as well as to ascertain their willingness and ability to inform drug users with whom they have shared needles or sexual partners of their HIV antibody seropositivity. It is also important to: (1) understand the barriers, processes, and consequences of such disclosure; (2) determine the differential impact of disclosure for men and women and across various racial/ethnic groups; and (3) ultimately, to determine the impact of disclosure on the spread of HIV infection to others. Between June 1981 and June 30, 1993, more than 300,000 AIDS cases in the U.S. were reported to the Centers for Disease Control and Prevention (CDC). Approximately 30 percent of the AIDS cases are among injecting drug users. Heterosexual IDUs account for 23 percent of AIDS cases, whereas homosexual and bisexual IDUs account for an additional six percent. Nineteen percent of all male cases were heterosexuals who reported using needles for self-injecting of drugs not prescribed by a physician at least once prior to developing AIDS. Half of all females with AIDS also reported a self-injection drug-use history. Although AIDS diagnoses among homosexual and bisexual men and among injecting drug users are projected to reach a plateau during this decade, the number of AIDS diagnoses among persons whose HIV infection is attributed to heterosexual transmission of HIV is likely to continue to increase through 1994. Outcome data from studies investigating seroprevalence among persons identified as sex or needle-sharing partners of HIV-infected individuals show HIV positive rates ranging from 11 percent to 39 percent (Vernon et al., 1988). In analyzing data from the first cohort of study sites involved in NIDA's Cooperative Agreement for AIDS Community-Based Outreach/Intervention Research Program, almost 29 percent of HIV positive drug users reported giving their used From owner-sci-resources@net.bio.net Thu Sep 16 23:00:00 1993 Path: biosci!net.bio.net From: kristoff@net.bio.net (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 22, no. 33, pt. 4, 17 September 1993 Message-ID: Date: 17 Sep 93 02:00:43 GMT Sender: kristoff@net.bio.net Lines: 445 Approved: biosci-moderator@net.bio.net $$XID RFA CA93040 CA-93-040 P1O1 *************************************** IMMUNOBIOLOGY OF AIDS LYMPHOMA NIH GUIDE, Volume 22, Number 33, September 17, 1993 RFA: CA-93-040 P.T. 34; K.W. 0715008, 0715035, 0710070 National Cancer Institute Letter of Intent Receipt Date: November 15, 1993 Application Receipt Date: January 7, 1994 PURPOSE The intent of this initiative is to stimulate research on biologic and immunologic mechanisms involved in the development of lymphomas in AIDS patients. Specifically, this initiative will encourage development and testing of hypotheses about the mechanisms of lymphomagenesis in the unique immune environment induced by HIV infection. This environment is characterized by defects in immune regulation, loss of specific immune cell subsets, presence of abnormal cytokine levels, changes in the architecture of germinal centers and other lymphoid tissues, and an apparent loss of immune surveillance. Any or all of these factors may play a role in the high incidence and distinctive characteristics of AIDS-associated lymphoma. The dysregulation may lead to an increase in the rate of generation of transformed lymphocytes and/or to enhanced capacity of these cells to escape surveillance and cause disease. Before effective therapies can be designed, it is necessary to understand the basic mechanism of lymphomagenesis in AIDS. 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), Immunobiology of AIDS Lymphoma, is related to the priority area of cancer. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Research grant applications may be submitted by domestic and foreign for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of state and local governments, and eligible agencies of the Federal government. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT Support of this program will be through the National Institutes of Health (NIH) research project grant (R01). Applicants will be responsible for the planning, direction, and execution of the proposed project. Except as otherwise stated in this RFA, awards will be administered under PHS grants policy as stated in the Public Health Service Grants Policy Statement DHHS Publication No. (OASH) 90-50,000, revised October 1, 1990. This RFA is a one-time solicitation. Generally, future unsolicited competing renewal applications will compete with all investigator-initiated R01 applications and be reviewed according to the customary peer review procedures by the Division of Research Grants (DRG). However, if the NCI determines that there is a sufficient continuing program need, a request for renewal applications will be announced. Only recipients of awards under this RFA will be eligible to apply. FUNDS AVAILABLE Approximately $1,500,000 in total costs per year for four years will be committed to fund applications that are submitted in response to this RFA. It is anticipated that at least six to eight individual R01 grant awards will be made. This level of support is dependent on the receipt of a sufficient number of applications of high scientific merit. Because the nature and scope of the research proposed in response to this RFA may vary, it is anticipated that the size of an award may vary also. The earliest start date for the initial award will be July 1, 1994. Although this program is provided for in the financial plans of the NCI, awards pursuant to this RFA are contingent upon the availability of funds for this purpose. RESEARCH OBJECTIVES The incidence of Non-Hodgkin's Lymphoma (NHL) has increased steadily during the past decade, with the most dramatic increase occurring in the AIDS-associated B-cell lymphomas. As AIDS patients are living longer, NHL has emerged as a major clinical problem in AIDS. The causes of this are poorly understood. Yet, during the same decade, tremendous progress was made in elucidating mechanisms of B and T lymphocyte regulation in both normal and immunodeficient patients. Initially, the emphasis was focused on elucidating the cellular and molecular mechanisms that govern the function of the immune system in normal individuals. Comparisons have been made between immune mechanisms in non-immunodeficient and immunodeficient individuals. It is obvious that deficiencies in the functioning components of the immune system, e.g., B or T cells, could readily account for the lack of resistance to infectious diseases in immunodeficient animals and patients. But no such explanation is readily available to explain the etiology and pathogenesis of AIDS-associated lymphomas. Studies have shown that similar immune abnormalities exist among congenitally immunodeficient, iatrogenically suppressed and AIDS patients. For example, low numbers of CD4+ T cells can be found in the peripheral circulation of all three groups of patients. Similarly, abnormal cytokine levels are detected in both non-AIDS and AIDS patients. This is best exemplified by high levels of interleukin 6 (IL-6) detected in the common-variable immunodeficiency (CVI) syndrome and AIDS patients. This apparently reflects lack of normal B cell function in both groups of patients. However, other studies have shown distinct differences between AIDS patients and patients with other immunodeficiencies. For example, Epstein-Barr Virus (EBV) was reported to induce essentially all of the B lymphomas in post-transplant recipients whereas EBV appears to play a lesser role in AIDS-associated lymphomas. Other studies indicated that HIV and other retroviruses do not play a direct role in inducing AIDS lymphomas. The NCI-sponsored workshop entitled "Biology of AIDS Lymphoma," held in Bethesda in May 1992, provided a forum for discussing the current state of research into the biologic and immunologic mechanisms that underlie the development of AIDS lymphoma. There was general agreement that while AIDS lymphoma is a heterogeneous collection of diseases, there are unique features that distinguish AIDS lymphomas from lymphomas in other immunodeficiency states and lymphomas in the general population. Participants identified numerous factors that might contribute to the unique pattern of lymphomagenesis, but no consensus was possible at the current state of knowledge on a mechanistic model for AIDS lymphoma development. On one level, the factors that lead to lymphomagenesis in AIDS are understandable, but the data that support this understanding are largely correlative and details are lacking. Factors that have been suggested to play a role in AIDS lymphomagenesis include, but are not limited to, loss of immune surveillance, infection by EBV and other viruses, chronic antigenic stimulation, high levels of stimulatory cytokines (especially IL-6), low levels of inhibitory cytokines, oncogene activation, other increases in DNA damage and alterations in DNA repair mechanisms. For every factor, important questions remain unanswered and will remain so until incisive, mechanistic studies are undertaken. Applicants should understand that the focus of this initiative is on the basic mechanisms leading to lymphomagenesis in AIDS patients. Thus, studies designed to test new forms of immunotherapy or other treatment modalities for AIDS lymphoma are outside the scope of this initiative and applications with a primary focus on designing new treatments for AIDS lymphoma will not be considered responsive to this initiative and these applications will be returned. It is anticipated that the majority of applications submitted in response to this RFA will propose experiments requiring access to cells and/or tissues from AIDS patients. Because such patient material is not readily available, applicants who propose such experiments must document that they have adequate access to these resources to carry out the proposed studies. Applicants who do not demonstrate this access will have their applications returned without review. The intent of this RFA is to elucidate the mechanisms underlying lymphomagenesis in AIDS patients. While the most direct route to understanding these mechanisms is to study AIDS patients or patient-derived material, it is recognized that studies of animal models of AIDS lymphoma or studies involving comparison to lymphomagenesis in other human immunodeficiency states may yield important insights into relevant mechanisms. Such studies might be designed to shed light on factors such as abnormal cytokine production in immunodeficient individuals, CD4+ T cell depletion and subsequent effects on B cell lymphomagenesis, the overall immune dysfunction in B and T cells and effects on dendritic cells, B cell lymphomagenesis in immunodeficient individuals, post-transplant lymphoproliferative disease (PTLD) and lymphomagenesis, immune surveillance and malignant B cell proliferation, the role of HIV-infected follicular-dendritic cells within germinal centers, the germinal center microenvironment and immunoregulatory effects on B cells and the role of chronic polyclonal B-cell stimulation in lymphoma development. Studies primarily involving animal models of AIDS or humans with immunodeficiency states other than AIDS will be considered responsive only if the intent is to derive a testable hypothesis concerning lymphomagenesis in AIDS patients and if the application contains a clear and compelling plan to apply the results obtained in a direct study of AIDS lymphoma. It is clear that the Epstein-Barr virus (EBV) plays a predominant role in lymphomagenesis in post-transplant recipients and a somewhat lesser, but still major, role in AIDS lymphomagenesis. However, the direct involvement of EBV and/or retroviruses in AIDS lymphomagenesis was the subject of a previous NCI RFA (RFA CA-90-15). Therefore, applications where the sole focus is on EBV-induced or retrovirus-induced lymphomagenesis in iatrogenically immunosuppressed individuals (animals or humans) will not be considered responsive to this initiative and these applications will be returned. However, studies that include, but are not limited to, retroviral-oncogene activation of immune cells or retroviral models of AIDS employing naturally occurring immunodeficient individuals where the intent is to derive a testable hypothesis of lymphomagenesis with application to the human disease will be considered responsive to the initiative. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements are required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder, or condition under study; special emphasis must be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to males and females of all ages. If women or minorities are excluded or inadequately represented in clinical research, particularly in proposed population-based studies, a clear compelling rationale must be provided. The composition of the proposed study population must be described in terms of gender and racial/ethnic group. In addition, gender and racial/ethnic issues must be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information must be included in the form PHS 398 in the Research Plan, parts 1-4, AND summarized in part 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations (i.e., Native Americans [including American Indians or Alaskan Natives], Asian/Pacific Islanders, Blacks, Hispanics). The rationale for studies on single minority population groups should be provided. For the purpose of this policy, clinical research is defined as human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including but not limited to clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded. However, every effort should be made to include human tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. For foreign awards, the policy on inclusion of women applies fully; since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. If the required information is not contained within the application, the application will be returned. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. LETTER OF INTENT Prospective applicants are asked to submit, by November 15, 1993, a letter of intent that includes a descriptive title of the proposed research, the name and address of the Principal Investigator, the names of other key personnel and participating institutions, and the number and title of the RFA in response to which the application may be submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information that it contains is helpful in planning for the review of applications. It allows NCI staff to estimate the potential review workload and to avoid conflict of interest in the review. The letter of intent is to be sent to Dr. John F. Finerty at the address listed under INQUIRIES. APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 9/91) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research and from the Office of Grants Information, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone 301/594-7248. The RFA label available in the PHS 398 application form must be affixed to the bottom of the face page of the application. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2a of the face page of the application form and the YES box must be marked. Submit a signed, typewritten original of the application, including the Checklist, and three signed, single-sided photocopies, in one package with the appendices to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** At the time of submission, two additional copies of the application must also be sent to: Ms. Toby Friedberg Division of Extramural Activities National Cancer Institute Executive Plaza North, Room 636 6130 Executive Boulevard Bethesda, MD 20892 Applications must be received by January 7, 1994. If an application is received after that date, it will be returned to the applicant without review. The Division of Research Grants (DRG) will not accept any application in response to this announcement that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. The DRG will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of substantial revisions of applications already reviewed, but such applications must include an introduction addressing the previous critique. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed by NIH staff for completeness and responsiveness. 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 NCI program staff function. Applications that are judged non-responsive to this RFA will be returned to the applicant by the NCI. An application judged to be non-responsive to this RFA may be submitted as a traditional research project grant (R01), or as a component of a program project grant (P01), with modification in accordance with either the R01 or P01 guidelines. The application would then not be considered a response to an RFA. If the number of applications submitted is large compared to the number of awards to be made, the NCI may conduct a preliminary scientific peer review (triage) to eliminate those that are clearly not competitive. The NCI will remove from further competition those applications judged to be non-competitive for award and notify the applicant Principal Investigator and institutional official. Those applications judged to be both responsive and competitive will be further evaluated according to the review criteria stated below for scientific and technical merit by an appropriate peer review group convened by the Division of Extramural Activities, NCI. The second level of review will be by the National Cancer Advisory Board. Review criteria for this RFA will be: o extent to which the proposed research addresses the goals of the RFA o scientific, technical, or medical significance and originality of proposed research o appropriateness and adequacy of the experimental approach and methodology proposed to carry out the research o where applicable, appropriateness of the model system chosen for the experiments proposed and potential relevance of the model system to AIDS lymphoma o demonstrated expertise in both the appropriate basic and clinical sciences of the PI and key personnel, particularly but not exclusively in the area of the proposed research o demonstration of availability and access to appropriate human tissue necessary to perform the proposed research o where applicable, availability of clinical information associated with human samples o adequacy of provision for the protection of human subjects and the humane treatment of animals o adequacy of the plans for inclusion of females and minorities o adequacy of available facilities The reviewers will also judge the appropriateness of the proposed budget and duration in relation to the proposed research. AWARD CRITERIA The earliest anticipated date of award is July 1, 1994. In addition to technical merit of the application, the NCI will consider the level of total cost requested. Only highly-rated projects will be funded. INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. NCI program staff welcome the opportunity to clarify any issues or questions from potential applicants. Direct inquiries regarding programmatic issues and address the letter of intent to: Dr. John F. Finerty Division of Cancer Biology, Diagnosis, and Centers National Cancer Institute Executive Plaza North, Room 501 6130 Executive Boulevard Bethesda, MD 20892-9904 Telephone: (301) 496-7815 FAX: (301) 496-8656 Direct inquiries regarding fiscal matters to: Mr. Robert Hawkins Grants Management Branch National Cancer Institute Executive Plaza South, Room 243 Bethesda, MD 20892 Telephone: (301) 496-7800, ext. 13 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.396. 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 Mon Sep 20 23:00:00 1993 Path: biosci!stc.nato.int From: scheurwe@stc.nato.int (Chris Scheurweghs) Newsgroups: bionet.announce,bionet.sci-resources Subject: INFO FROM NATO HQ: NATOSCI Message-ID: <199309211417.AA20537@stc.nato.int> Date: 21 Sep 93 14:17:01 GMT Sender: kristoff@net.bio.net Reply-To: Chris.Scheurweghs@stc.nato.int Lines: 30 Approved: bionews-moderator@net.bio.net Xref: biosci bionet.announce:707 bionet.sci-resources:814 Organisation: Defence Research Group, NATO HQ COMING SOON - COMING SOON - COMING SOON In addition to the information on various topics though NATODATA, NATO will shortly make available through NATOSCI information on the NATO Science Programme and the Environmental projects of the CCMS (Committee on the Challenges of Modern Society). It is planned to introduce this service around 27th September. Following initial descriptions of the activities and the possibilities of support for collaborative projects, updates will be posted on an occasional basis, and a quarterly newsletter and tri-annual list of scientific meetings will be provided. To subscibe to NATOSCI send an email message to LISTSERV@CC1.KULEUVEN.AC.BE or LISTSERV@BLEKUL11.BITNET (for Bitnet users), with the text 'subscribe NATOSCI Firstname Lastname'. -------------------------------------------------------------------------- NATO - OTAN Tel.: (32)-2-728.4599 INFORMATION / PRESS FAX : (32)-2-728.5248 NATO CENTRALIZED MEDIA SERVICE (32)-2-728.4579 Chris SCHEURWEGHS E-MAIL: Scheurwe@stc.nato.int Leopold III laan Scheurweghs@shape.nato.int 1110 BRUSSEL Belgium --------------------------------------------------------------------------- From owner-sci-resources@net.bio.net Thu Sep 23 23:00:00 1993 Path: biosci!NET.BIO.NET!kristoff From: kristoff@NET.BIO.NET (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NSF - Summary of new documents on STIS - 19 September 1993 Message-ID: Date: 24 Sep 93 05:04:07 GMT Sender: kristoff@net.bio.net Distribution: bionet Lines: 87 Approved: sci-resources-moderator@net.bio.net ** NEW DOCUMENTS ON STIS ** Document Type: News Title: NPR 93-a Report of the National Performance Review File size (bytes): 523437 STIS Filename: npr93a Title: TIPS 93-A U.S. ANTARCTIC PROGRAM LAUNCHES 37TH RESEARCH SEASON File size (bytes): 5411 STIS Filename: tips93a Document Type: Press Release Title: PR 93-68 U.S. ANTARCTIC PROGRAM LAUNCHES 37TH RESEARCH SEASON File size (bytes): 10949 STIS Filename: pr93-68 Document Type: Program Guideline Title: NSF 93-141 - Research on Digital Libraries File size (bytes): 23137 STIS Filename: nsf93141 Document Type: Recruit Title: Biologist (Science Assistant) File size (bytes): 4392 STIS Filename: vex9328 ------------------------------------------------------------------------ ** UPDATES TO EXISTING STIS DOCUMENTS ** Document Type: Phone Book Title: NSF Alphabetical Listing File size (bytes): 90852 STIS Filename: phnalpha Title: NSF Organizational Directory File size (bytes): 99905 STIS Filename: phnorg ------------------------------------------------------------------------ ** FOR YOUR REFERENCE ** ------------------------------------------------------------------------ HOW TO OBTAIN DOCUMENTS The above files can be retrieved in electronic form using the STIS system. If you don't know how to use STIS, send an E-mail message to stisinfo@nsf.gov (Internet) or stisinfo@NSF (BITNET). You will receive a copy of the STIS flyer via E-mail. If you are already using STIS, you can use the information above to retrieve these files: Documents via E-mail: Send a message to stisserv@nsf.gov (Internet) or stisserv@NSF (BITNET). Use the "STIS Filename" shown above in the "get" command. For example, to retrieve phnorg, the text of your message should be as follows: get phnorg Anonymous FTP: FTP to stis.nsf.gov. Use the "STIS Filename" shown above to retrieve a file. For example, to retrieve phnorg, you would enter: ftp> get phnorg WAIS or Gopher: Do a word search on the filename as shown in the summary. If you want a *printed* copy of a document: Send your name and postal mailing address, and the document title and number to "firstop@nsf.gov" (Internet) or "firstop@nsf" (BITNET). If you have problems with the above procedures: Send a message to "stis@nsf.gov" (Internet) or "stis@NSF" (BITNET). From owner-sci-resources@net.bio.net Sun Sep 26 23:00:00 1993 Path: biosci!NET.BIO.NET!kristoff From: kristoff@NET.BIO.NET (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NSF - Summary of new documents on STIS - 26 September 1993 Message-ID: Date: 27 Sep 93 17:11:49 GMT Sender: kristoff@net.bio.net Distribution: bionet Lines: 90 Approved: sci-resources-moderator@net.bio.net ** NEW DOCUMENTS ON STIS ** Document Type: Program Guideline Title: NSF 93-135 LMER Land-Margin Ecosystems Research File size (bytes): 12797 STIS Filename: nsf93135 Title: NSF 93-137 BIO Research Training Groups Program File size (bytes): 21497 STIS Filename: nsf93137 Title: NSF 93-134 RIDGE-Ridge Activities File size (bytes): 34808 STIS Filename: nsf9314 Document Type: Recruit Title: Director, Division of Human Resource Management File size (bytes): 7119 STIS Filename: vep937 Document Type: SRS Data Brief Title: DB 93-318 U.S. Expenditures on R&D Expected To Increase in 1993 File size (bytes): 4828 STIS Filename: db93318 ------------------------------------------------------------------------ ** UPDATES TO EXISTING STIS DOCUMENTS ** Document Type: Committees Title: NSF Advisory Committee Meetings File size (bytes): 1601 STIS Filename: cmpublic Document Type: Phone Book Title: NSF Alphabetical Listing File size (bytes): 91172 STIS Filename: phnalpha Title: NSF Organizational Directory File size (bytes): 100504 STIS Filename: phnorg ------------------------------------------------------------------------ ** FOR YOUR REFERENCE ** ------------------------------------------------------------------------ HOW TO OBTAIN DOCUMENTS The above files can be retrieved in electronic form using the STIS system. If you don't know how to use STIS, send an E-mail message to stisinfo@nsf.gov (Internet) or stisinfo@NSF (BITNET). You will receive a copy of the STIS flyer via E-mail. If you are already using STIS, you can use the information above to retrieve these files: Documents via E-mail: Send a message to stisserv@nsf.gov (Internet) or stisserv@NSF (BITNET). Use the "STIS Filename" shown above in the "get" command. For example, to retrieve phnorg, the text of your message should be as follows: get phnorg Anonymous FTP: FTP to stis.nsf.gov. Use the "STIS Filename" shown above to retrieve a file. For example, to retrieve phnorg, you would enter: ftp> get phnorg WAIS or Gopher: Do a word search on the filename as shown in the summary. If you want a *printed* copy of a document: Send your name and postal mailing address, and the document title and number to "firstop@nsf.gov" (Internet) or "firstop@nsf" (BITNET). If you have problems with the above procedures: Send a message to "stis@nsf.gov" (Internet) or "stis@NSF" (BITNET). From owner-sci-resources@net.bio.net Mon Sep 27 23:00:00 1993 Path: biosci!net.bio.net From: kristoff@net.bio.net (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 22, no. 34, pt. 1, 24 September 1993 Message-ID: Date: 28 Sep 93 01:58:23 GMT Sender: kristoff@net.bio.net Lines: 1159 Approved: biosci-moderator@net.bio.net NOTE: The NIH Guide may be split into more than one mail message to avoid truncation during e-mail distribution. The first message always begins with the RFP/RFA summary sections followed by the appended texts of the full RFP/RFAs. ---------------------------------------------------------------------- $$XID NIHGUIDE 19930924 V22N34 P1O1 ************************************ X-comment: RFAs described: AR-94-002, AI-93-023 NIH GUIDE - Vol. 22, No. 34 - September 24, 1993 $$INDEX BEGIN ******************************************************* NOTICES $$INDEX N1 ********************************************************** NATIONAL ANIMAL WELFARE EDUCATION WORKSHOPS National Institutes of Health INDEX: NATIONAL INSTITUTES OF HEALTH $$INDEX N2 ********************************************************** NATIONAL ANIMAL WELFARE EDUCATION WORKSHOPS National Institutes of Health INDEX: NATIONAL INSTITUTES OF HEALTH $$INDEX N3 ********************************************************** NATIONAL HUMAN SUBJECTS PROTECTION WORKSHOPS National Institutes of Health Food and Drug Administration INDEX: NATIONAL INSTITUTES OF HEALTH; FOOD AND DRUG ADMINISTRATION NOTICES OF AVAILABILITY (RFPs AND RFAs) $$INDEX R1 12/21/93 ************************************************* OSTEOPOROSIS/RELATED BONE DISEASES INFORMATION RESOURCE CENTER (RFA AR-94-002) National Institute of Arthritis and Musculoskeletal and Skin Diseases INDEX: ARTHRITIS, MUSCULOSKELETAL, SKIN DISEASES $$INDEX R2 02/18/93 ************************************************* TUBERCULOSIS DIAGNOSTICS (RFA AI-93-023) National Institute of Allergy and Infectious Diseases INDEX: ALLERGY, INFECTIOUS DISEASES ONGOING PROGRAM ANNOUNCEMENTS $$INDEX P1 ********************************************************** AUTOIMMUNE ENDOCRINE DISEASE (PA-93-114) National Institute of Diabetes and Digestive and Kidney Diseases National Institute of Allergy and Infectious Diseases INDEX: DIABETES, DIGESTIVE, KIDNEY; ALLERGY, INFECTIOUS DISEASES This publication is available electronically to institutions via BITNET or INTERNET and is also on the NIH GOPHER. Alternative access is through the NIH Grant Line using a personal computer (data line 301/402-2221). Contact Dr. John James at 301/594-7270 for details. $$INDEX END ********************************************************* NOTICES $$N1 BEGIN ********************************************************** NATIONAL ANIMAL WELFARE EDUCATION WORKSHOPS NIH GUIDE, Volume 22, Number 34, September 24, 1993 P.T. 42; K.W. 0201011, 1014003 National Institutes of Health The National Institutes of Health (NIH), Office for Protection from Research Risks (OPRR) announces the postponement of an animal welfare education workshop. The Southeastern Animal Welfare Education Workshop cosponsored by Louisiana State University Medical Center and Xavier University of Louisiana scheduled for December 2-3, 1993, at the Monteleone Hotel in New Orleans, LA, has been postponed and will be rescheduled in 1994. Announcements for the proposed date will appear in the NIH Guide for Grants and Contracts and similar publications. INQUIRIES For further information concerning this workshop and future NIH/OPRR Animal Welfare Education Workshops, contact: Ms. Darlene Marie Ross Office for Protection from Research Risks National Institutes of Health Building 31, Room 5B63 Bethesda, MD 20892 Telephone: (301) 496-8101 $$N1 END ************************************************************ $$N2 BEGIN ********************************************************** NATIONAL ANIMAL WELFARE EDUCATION WORKSHOPS NIH GUIDE, Volume 22, Number 34, September 24, 1993 P.T. 42; K.W. 0201011, 1014003 National Institutes of Health The National Institutes of Health (NIH), Office for Protection from Research Risks (OPRR), is continuing to sponsor workshops on implementing the Public Health Service Policy on Humane Care and Use of Laboratory Animals. Each of the workshops scheduled for FY 1993 will focus on a specific theme. The workshops are open to institutional administrators, members of Institutional Animal Care and Use Committees, laboratory animal veterinarians, investigators, and other institutional staff who have responsibility for high-quality management of sound institutional animal care and use programs. Ample opportunities will be provided to exchange ideas and interests, through question and answer sessions and informal discussions. SOUTHWESTERN REGION DATES: September 27-29, 1993 LOCATION Oklahoma City Hilton Northwest 2945 N.W. Expressway Oklahoma City, OK 73112 Telephone: 1-800-445-8667 FAX: (405) 842-4328 SPONSOR University of Oklahoma Health Sciences Center REGISTRATION Ms. Marilyn Perry, Assistant to Director for Compliance Division of Animal Resources BMSB, Room 203 University of Oklahoma Health Sciences Center Oklahoma City, OK 73190 Telephone: (405) 271-5185 FAX: (405) 271-3032 FEE: $140; Graduate Students and Post-Docs $90.00 TOPIC: THE PRESENT AND FUTURE USE OF FARM ANIMALS IN BIOMEDICAL RESEARCH AND EDUCATION DATES: September 28 (Afternoon); September 29 (Morning) LOCATION Oklahoma City Hilton Northwest (Same as above) SPONSOR University of Oklahoma Health Sciences Center REGISTRATION Ms. Marilyn Perry (address as above) TOPIC: USDA OPEN FORUM ON FARM ANIMAL ISSUES UNDER THE ANIMAL WELFARE ACT INQUIRIES For further information concerning these workshops and future NIH/OPRR Animal Welfare Education workshops, contact: Ms. Roberta Sonneborn Office for Protection from Research Risks National Institutes of Health Building 31, Room 5B59 Bethesda, MD 20892 Telephone: (301) 496-7163 FAX: (301) 402-2803 $$N2 END ************************************************************ $$N3 BEGIN ********************************************************** NATIONAL HUMAN SUBJECTS PROTECTION WORKSHOPS NIH GUIDE, Volume 22, Number 34, September 24, 1993 P.T. 42; K.W. 0783005 National Institutes of Health Food and Drug Administration The National Institutes of Health (NIH) and the Food and Drug Administration (FDA) are continuing to sponsor a series of workshops on responsibilities of researchers, Institutional Review Boards (IRBs), and institutional officials for the protection of human subjects in research. The workshops are open to everyone with an interest in research involving human persons and those currently serving or about to begin serving as a member of an IRB. Issues discussed at these workshops are relevant to all other Public Health Service agencies. The current schedule includes: WESTERN WORKSHOP DATES: November 4-5, 1993 LOCATION Radisson Hotel Denver South, Denver, CO SPONSORS University of Colorado Health Sciences Center, Denver, CO University of Southern Colorado, Pueblo, CO REGISTRATION Ms. Mary Peratt, Secretary IRB University of Colorado Health Sciences Center 4200 East Ninth Avenue (Box C-290) Denver, CO 80262 Telephone: (303) 270-7960 TITLE: Medical Research: Protection of Vulnerable Subjects DESCRIPTION: IRBs are confronted with a complexity of questions and ethical issues that seldom have defined answers or ready resolve. Some of the more perplexing clinical research protocols presented for review are studies involving human subjects in overt, at-risk groups. This human subjects workshop will address protections of highly vulnerable and protected human populations. Discussions will focus on the ethical principles, protective measures, and definitions of criteria for informed consent that are tantamount for IRB reviews when members of these vulnerable groups are subjects of research studies. Subject groups and protocols to be covered will be focused on prisoners, children, mentally compromised, AIDS and HIV-infected, geriatric, and emergency room. The conference program is designed to be of value to physicians, nurses, pharmacists, scientific investigators, pharmaceutical and medical device company representatives, and other health care professionals. All IRB members, faculty, and students in health care areas and administrators will benefit from the conference. Critical attention will be given to Federal regulations governing these special groups, professional judgment, real and perceived elements of "implied," "second," and "third" party consents. Conference emphasis will be placed on the assessment of risks and protection of the vulnerable subject with the application of medical, legal, psychosocial and ethical standards and principles. The conference format is structured to promote the optimum exchange of ideas and discussion through small and large group, topic-defined, informal, and provocative sessions. WEST COAST WORKSHOP DATES: January 23-24, 1994 LOCATION Doubletree Hotel, Pasadena, CA SPONSORS City of Hope National Medical Center, Duarte, CA Charles R. Drew University of Medicine and Science, Los Angeles, CA REGISTRATION Ms. Donna Pearce Administrative Secretary, IRB City of Hope National Medical Center Beckman Research Institute Duarte, CA 91010 Telephone: (818) 359-8111, ext. 2700 TITLE: Ethical Issues in Human Subject Research: Catastrophic Diseases and Minorities DESCRIPTION: This workshop is intended for physicians, nurses, pharmacists, and other health care professionals as well as administrators, members of Institutional Review Boards, students, ethicists and legal experts, and lay persons with interest and concern for human subject research. The program will address the following issues: (1) new governmental policies on human subject research; (2) resolving ethical principles in clinical research on AIDS, gene transfer, and cancer prevention trials involving catastrophic illnesses; (3) drug trials and parallel track protocols; (4) minorities as research subjects; and (5) the uncertain fate of clinical research in the current era of health care reform. SOUTH COAST CENTRAL WORKSHOP DATES: February 17-18, 1994 LOCATION Fairmont Hotel, New Orleans, LA SPONSORS University of New Orleans - Lakefront, New Orleans, LA Xavier University of Louisiana, New Orleans, LA REGISTRATION Ms. Anne O'Hearn Jakob Office of Conference Services University of New Orleans - Lakefront New Orleans, LA 70148 Telephone: (504) 286-7118 TITLE: Recent Trends in Human Subjects Research DESCRIPTION: The purpose of this conference is to explore recent issues and trends related to the protection of human subjects in research. It will provide discussions and opportunities among participants to share views on NIH's new guidelines on fetal research, the inclusion of women and minorities in research, and FDA's recent policy on enrolling women of childbearing age in drug trials. Workshops and meetings will be conducted by faculty of more than 25 national experts whose research interests include alzheimer's disease, environmental research, women's health, human genome research, biomedical research, and others. INQUIRIES For further information regarding these workshop and future NIH/FDA National Human Subject Protections Workshops, contact: Ms. Darlene Marie Ross Office for Protection from Research Risks National Institutes of Health Building 31, Room 5B63 Bethesda, MD 20892 Telephone: (301) 496-8101 $$N3 END ************************************************************ NOTICES OF AVAILABILITY (RFPs AND RFAs) $$R1 BEGIN AR-94-002 FULL-TEXT ************************************** OSTEOPOROSIS/RELATED BONE DISEASES INFORMATION RESOURCE CENTER NIH GUIDE, Volume 22, Number 34, September 24, 1993 RFA AVAILABLE: AR-94-002 P.T. 16; K.W. 0715031, 0710095, 0745027, 0745070, 0502017 National Institute of Arthritis and Musculoskeletal and Skin Diseases Letter of Intent Receipt Date: November 1, 1993 Application Receipt Date: December 21, 1993 THIS IS A NOTICE OF AVAILABILITY OF A REQUEST FOR APPLICATIONS (RFA); IT IS ONLY AN ABSTRACT OF THE RFA. POTENTIAL APPLICANTS MUST REQUEST THE COMPLETE RFA, WHICH CONTAINS ESSENTIAL INFORMATION FOR THE PREPARATION OF AN APPLICATION, FROM THE CONTACT LISTED IN "INQUIRIES," BELOW. FAILURE TO FOLLOW THE INSTRUCTIONS IN THE COMPLETE RFA MAY RESULT IN AN INCOMPLETE APPLICATION, WHICH WILL BE RETURNED TO THE APPLICANT WITHOUT REVIEW. PURPOSE The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) invites applications for the purpose of establishing a resource center for osteoporosis, Paget's disease, and related bone disorders to facilitate and enhance knowledge and understanding on the part of health professionals, patients, and the public through effective dissemination of information. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This RFA, Osteoporosis/Related Bone Diseases Resource Center, is related to the priority area of educational and community-based programs. 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 individuals representing domestic or foreign non-profit entities involved in activities regarding the prevention and control of osteoporosis and related bone disorders. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT This RFA will use the National Institutes of Health (NIH) Education Project Grant (R25). Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. The total project period for applications submitted in response to the present RFA may not exceed four years. The anticipated award date is June 30, 1994. Future competitions will be announced by a new RFA. FUNDS AVAILABLE The estimated funds (total costs) available for the first year of support are $500,000 total cost. The NIAMS expects to make one award. RESEARCH OBJECTIVES Osteoporosis is an important public health problem in which weakened bones are easily fractured. More than 1.3 million fractures each year are attributable to osteoporosis. Other secondary types of osteoporosis, Paget's disease, osteogenesis imperfecta, and other bone diseases, are also important problems. In the past decade there have been extraordinary advances in the understanding of basic bone biology, leading to very targeted approaches both in the prevention and effective treatment of several types of osteoporosis and related bone diseases, but wide application to clinical care has lagged behind. Further education of health care professionals, patients, and the public at large is needed. In particular, the teaching of osteoporosis prevention to children and adolescents and the need to reach all segments of an ethnically, economically, and geographically diverse American population have been identified as priorities. The National Institutes of Health Revitalization Act of 1993 [P.L. 103-43] provided for "the establishment of an information clearinghouse on osteoporosis and related bone disorders to facilitate and enhance knowledge and understanding on the part of health professionals, patients, and the public through the effective dissemination of information." The law further requires that such a clearinghouse be established through "a grant, cooperative agreement, or contract with a non-profit private entity involved in activities regarding the prevention and control of osteoporosis and related bone disorders." The objectives of this RFA are to establish an information resource center to reach health professionals, patients and the public with state-of-the-art information on the prevention and treatment of osteoporosis and related bone diseases. This will include evaluation of the Center's ability to effect beneficial changes in one or more of the target groups who receive the information. STUDY POPULATIONS SPECIAL INSTRUCTIONS FOR INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDIES For projects involving clinical research, NIH requires applicants to give special attention to the inclusion of women and minorities in study populations. If women or minorities are not included in the study populations for clinical studies, a specific justification for this exclusion must be provided. Applications without such documentation will not be accepted for review. LETTER OF INTENT Prospective applicants are asked to submit, by November 1, 1993, a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, the identities of other key personnel and participating institutions, and the number and title of the RFA in response to which the application may be submitted. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information that it contains allows NIAMS 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. Tommy Broadwater at the address listed under APPLICATION PROCEDURES. 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 program administrator named below. The RFA label available in the PHS 398 (rev. 9/91) application form must be affixed to the bottom of the face page of the application. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2a of the face page of the application form and the YES box must be marked. Submit a signed, typewritten original of the application, including the Checklist, and three signed, photocopies, in one package to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** At the time of submission, two additional copies of the application must also be sent to: Dr. Tommy Broadwater Review Branch National Institute of Arthritis and Musculoskeletal and Skin Diseases Westwood Building, Room 404 Bethesda, MD 20892 Applications must be received by December 21, 1993. If an application is received after that date, it will be returned to the applicant without review. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by DRG and responsiveness by the NIAMS. Incomplete applications will be returned to the applicant without further consideration. If the application is not responsive to the RFA, ICD staff will contact the applicant to determine whether to return the application. Applications may be triaged by the NIAMS peer review group on the basis of relative competitiveness. The NIH will withdraw from further competition those applications judged to be non-competitive for award and notify the applicant Principal Investigator and institutional official. Those applications judged to be competitive will undergo further scientific merit review. Those applications that are complete and responsive will be evaluated in accordance with the criteria stated below for scientific/technical merit by an appropriate peer review group convened by the ICD. The second level of review will be provided by the National Arthritis and Musculoskeletal and Skin Diseases Advisory Council. Review criteria for RFAs are generally similar to those for unsolicited investigator-initiated research grant applications. AWARD CRITERIA Applications will compete for available funds with all other applications responsive to this RFA. The anticipated date of award is June 30, 1994. INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Dr. Joan McGowan Bone Biology and Bone Diseases Branch National Institute of Arthritis and Musculoskeletal and Skin Diseases Westwood Building, Room 403 Bethesda, MD 20892 Telephone: (301) 594-9957 FAX: (301) 594-9673 Direct inquiries regarding fiscal matters to: Ms. Carol G. Clearfield Grants Management Branch National Institute of Arthritis and Musculoskeletal and Skin Diseases Westwood Building, Room 725B Bethesda, MD 20892 Telephone: (301) 594-9973 FAX: (301) 594-9950 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.846, Arthritis, Musculoskeletal and Skin Diseases Research. Awards will be made under authorization of the Public Health Service Act, Title III, Section 301 (Public Law 410, 78th Congress, as amended, 42 USC 241) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. $$R1 END ************************************************************ $$R2 BEGIN AI-93-023 FULL-TEXT ************************************** TUBERCULOSIS DIAGNOSTICS NIH GUIDE, Volume 22, Number 34, September 24, 1993 RFA AVAILABLE: AI-93-023 P.T. 34; K.W. 0715165, 0745020, 0710040, 0760003, 0755020, 0710070 National Institute of Allergy and Infectious Diseases Letter of Intent Receipt Date: January 7, 1994 Application Receipt Date: February 18, 1994 THIS IS A NOTICE OF AVAILABILITY OF A REQUEST FOR APPLICATIONS (RFA); IT IS ONLY AN ABSTRACT OF THE RFA. POTENTIAL APPLICANTS MUST REQUEST THE COMPLETE RFA, WHICH CONTAINS ESSENTIAL INFORMATION FOR THE PREPARATION OF AN APPLICATION, FROM THE CONTACT LISTED IN "INQUIRIES," BELOW. FAILURE TO FOLLOW THE INSTRUCTIONS IN THE COMPLETE RFA MAY RESULT IN AN INCOMPLETE APPLICATION, WHICH WILL BE RETURNED TO THE APPLICANT WITHOUT REVIEW. PURPOSE The Respiratory Diseases Branch, Division of Microbiology and Infectious Diseases (DMID), National Institute of Allergy and Infectious Diseases (NIAID) invites applications for innovative basic or applied research leading to the development of diagnostics for tuberculosis (TB). It is anticipated that new and reformed diagnostic tools to assist in the detection, prevention, and treatment of tuberculosis will improve the speed, sensitivity, specificity, and/or reliability of existing diagnostic procedures. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This RFA, Tuberculosis Diagnostics, is related to the priority areas of diagnostics and infectious diseases. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Domestic and foreign, non-profit and for-profit organizations and institutions, State and local governments and their agencies, are eligible to apply. Foreign institutions are not eligible for the First Independent Research Support and Transition (FIRST) (R29) award. Minorities and women are encouraged to apply. Applications from or involving minority institutions or women's institutions are encouraged. MECHANISM OF SUPPORT This RFA will use the National Institutes of Health (NIH) individual research project grant (R01), and the FIRST (R29) award. Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. The total project period for applications submitted in response to this RFA may not exceed five years. The earliest anticipated award date is September 1994. This RFA is a one-time solicitation. Future unsolicited competing applications will compete with investigator-initiated applications and be reviewed according to customary review procedures. FUNDS AVAILABLE The estimated minimum total funds (direct and indirect costs) available for the first year of this program will be $2,000,000. In fiscal year 1994, the NIAID plans to fund at least eight R01s and/or R29s. This level of support is dependent on the receipt of a sufficient number of applications of high scientific merit. RESEARCH OBJECTIVES Background On April 23, 1993, the World Health Organization declared tuberculosis a global public health emergency, a distinction never accorded another disease. Once believed by health officials to be contained, tuberculosis is now recognized as out of control in many parts of the world. Yet, the disease is not confined by national boundaries. In the United States, after decades of successful control and decreasing rates of disease, tuberculosis is making a comeback. About 10 million people in the U.S. are infected by the tuberculosis bacillus. The vast majority of these individuals are not sick and they are not infectious but remain at risk to develop active disease. During 1992, 26,678 cases of active tuberculosis were reported to the Centers for Disease Control, up 20 percent from 1985 when resurgence of the disease began. The link between HIV and tuberculosis is anticipated to be a major factor in the spread of tuberculosis. It is the only AIDS-associated infection readily transmitted to non-HIV-infected persons. HIV infection also accelerates the progression of tuberculosis. TB diagnostics need to be improved. Many available tests are too slow and/or lack sensitivity. Active tuberculosis is currently diagnosed using an assortment of techniques, symptoms, and clinical signs. These techniques include the chest X-ray, microscopy, and culture of the organism from clinical samples, typically sputum. Diagnosis based on symptoms, X-ray, or even microscopy is not definitive. The current gold standard is culture. Objectives The purpose of this RFA is to stimulate and encourage high quality innovative research leading toward a greater understanding of microbiological and immunological response to infection and advancing to improvements in the diagnosis of tuberculosis. These areas may include, but are not limited to, studies to: o Develop improved methods for rapid, sensitive, specific, and reliable identification of M. tuberculosis in clinical samples, especially samples containing limited numbers of organisms, i.e., paucibacillary disease. o Develop improved methods for rapid, reliable identification of drug-sensitive and drug-resistant strains of M. tuberculosis, including MDRTB, in clinical specimens and in laboratory cultures. o Develop rapid methods for reliable identification of M. tuberculosis, including MDRTB, in clinical specimens other than sputum, including blood and spinal fluid. o Develop methods to distinguish latent and active tuberculosis infections. o Identify low molecular weight compounds or metabolites that may serve as specific markers for active or latent tuberculosis infection and/or reflect the extent of the bacterial burden. o Develop improved in vitro or animal models for evaluation of diagnostics. o Characterize cell surface antigens, including those expressed exclusively, or primarily, during intracellular growth and develop their use for diagnosis of active disease. o Define and characterize immune mechanisms associated with latent tuberculosis infections and the mechanisms by which M. tuberculosis persists in a quiescent state, and develop for use in the diagnosis of latent infection. o Define and characterize immune mechanisms associated with latent tuberculosis infections and the mechanisms by which M. tuberculosis persists in a quiescent state, and develop for use in the diagnosis of latent infection. SPECIAL REQUIREMENTS NIAID program staff will organize annual meetings that Principal Investigators and other key members (as designated by the Principal Investigators) of the projects will be invited to attend to discuss progress. Funds for travel to these meetings should be included in the budget. STUDY POPULATIONS SPECIAL INSTRUCTIONS FOR INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDIES For projects involving clinical research, NIH requires applicants to include minorities and women in study populations. 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. Applications without such documentation will not be accepted for review. LETTER OF INTENT Prospective applicants are asked to submit, by January 7, 1994, a letter of intent that includes a descriptive title of the proposed research, the name, address, and telephone number of the Principal Investigator, the identities of other key personnel and participating institutions, and the number and title of the RFA in response to which the application may be submitted. The letter of intent is not required. It allows NIAID 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. Olivia Preble at the address listed under INQUIRIES. APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 9/91) is to be used in applying for these grants. These forms are available at most institutional offices of sponsored research and from the Office of Grants Information, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892. Applicants for FIRST (R29) awards must attach three reference letters (in sealed envelopes) to the face page of the original application. Applicants from institutions that have a General Clinical Research Center (GCRC) funded by the NIH National Center of Research Resources may wish to identify the Center as a resource for conducting the proposed research. If so, a letter of agreement from the GCRC Program Director must be included in the application material. The RFA label available in the PHS 398 (rev. 9/91) of the 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 (TUBERCULOSIS DIAGNOSTICS) and number (AI-93-023) must be typed on line 2a of the face page of the application. The typed original signed original application package and three exact single-sided 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 At the time of submission, two additional exact copies must be sent to Dr. Olivia Preble at the address listed under INQUIRIES. 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 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 exclude the submission of substantial revisions of application already reviewed. These applications must, however, include an introduction addressing the previous critique. REVIEW CONSIDERATIONS Upon receipt, applications and supporting material will be reviewed by the DRG for completeness and by the NIAID staff for responsiveness to the RFA. Incomplete applications will be returned without further consideration. If the application is not responsive to the RFA, NIAID staff will contact the applicant to determine whether to return the application or submit it for review in competition with unsolicited application at the next review cycle. Applications may be triaged by an ICD peer review group on the basis of relative competitiveness. The NIH will withdraw from further competition those applications judged to be non-competitive for award and notify the applicant Principal Investigator and institutional official. Those applications that are complete and responsive will be evaluated in accordance with the criteria stated in the RFA for scientific/technical merit by an appropriate peer review group convened by the NIAID. The second level of review will be provided by the National Advisory Allergy and Infectious Diseases Council. AWARD CRITERIA The anticipated date of award is September 30, 1994. The NIAID will consider for funding all R01s and R29s rated by peer review as having significant and substantial scientific merit. Awards are subject to the availability of funds. INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. The opportunity to clarify issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues and request for the RFA to: Dr. John Foulds Division of Microbiology and Infectious Diseases National Institute of Allergy and Infectious Diseases Solar Building, Room 3B10 Bethesda, MD 20892 Telephone: (301) 496-5305 FAX: (301) 496-8030 E-Mail: Jfoulds@exec.niaid.pc.niaid.nih.gov Direct inquiries regarding the review of applications and address the letter of intent to: Dr. Olivia Preble Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4C19 Bethesda, MD 20892 Telephone: (301) 496-8208 FAX: (301) 402-2638 Direct inquiries regarding fiscal matters to: Mr. Todd Ball Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4B35 Bethesda, MD 20892 Telephone: (301) 496-7075 AUTHORITY AND REGULATIONS This program is supported under authorization of the Public Health Service Act, Sec. 301 (c), Public Law 78-410, as amended. The Catalogue of Federal Domestic Assistance Citation is Sec. 93.856, Microbiology and Infectious Diseases Research. Awards will be administered under PHS grant policies and Federal Regulations 42 CFR Part 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems review. $$R2 END ************************************************************ ONGOING PROGRAM ANNOUNCEMENTS $$P1 BEGIN PA-93-114 ************************************************ AUTOIMMUNE ENDOCRINE DISEASE NIH GUIDE, Volume 22, Number 34, September 24, 1993 PA NUMBER: PA-93-114 P.T. 34; K.W. 0715015, 0785050, 0755030, 0765033, 0755020, 1002008 National Institute of Diabetes and Digestive and Kidney Diseases National Institute of Allergy and Infectious Diseases PURPOSE The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the National Institute of Allergy and Infectious Diseases (NIAID) invite investigator-initiated research grant applications specifically targeted to study of the causes, etiology, pathogenesis, and treatment of autoimmune endocrine diseases, and in particular autoimmune thyroid disease and insulin-dependent diabetes mellitus. 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, Autoimmune Endocrine Disease, is related to the priority area of research on women's 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, for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, laboratories, units of State or local governments, and eligible agencies of the Federal government. Applications from minorities and women are encouraged. MECHANISM OF SUPPORT The mechanism of support for this program will be the research project grant (R01). The policies that govern the research grant programs of the National Institutes of Health will prevail. Support for this solicitation is contingent upon receipt of appropriated funds. Since a variety of approaches would represent valid responses to this solicitation, it is anticipated that there will be a range of costs among individual grants awarded; however, it is anticipated that awards will average approximately $200,000 per year in total costs. With respect to post-award administration, the current policies and requirements that govern the research grant programs of the NIH will prevail. RESEARCH OBJECTIVES The purpose of this initiative is to stimulate basic and clinical research applications that will further the understanding of the causes and therapeutic modalities of autoimmune endocrine diseases. Background Autoimmune endocrine diseases, including those involving the thyroid (Graves' disease, Hashimoto's thyroiditis), insulin dependent diabetes mellitus (IDDM), and Addison's disease are among the most prevalent or common endocrine disorders. These disorders often strike young people, resulting in considerable loss of productivity and long-term increases in health care costs. Several of these autoimmune endocrine diseases also have a higher incidence among women, especially the autoimmune thyroid diseases, and in particular Hashimoto's disease, the most common thyroid autoimmune disorder, which has a four-fold greater incidence in women. People with one autoimmune endocrine disease are at increased risk for another of these disorders, as are family members of patients with autoimmune endocrine disease. A recent NIDDK workshop entitled "Autoimmune Thyroid Disease" brought together experts in autoimmune disease to exchange state-of-the-art information in this field and identify areas of scientific opportunity. As a result of this workshop several key research issues relevant to autoimmune endocrine diseases were identified, including the underlying nature of autoimmunity, the basis of increased incidence in women, and potential therapeutic approaches to autoimmune diabetes and thyroid disease. Recent observations have delineated many of the pathways that regulate thyroid hormone release and metabolism. This, together with improved assays for thyroid stimulating hormone (TSH), thyroid autoantibodies, and an enhanced understanding of mechanisms of signal transduction involving thyroid hormones has greatly improved the laboratory and clinical assessment of thyroid function. Nevertheless, for autoimmune endocrine diseases considerable questions exist regarding the etiology, pathogenesis, and potential treatments directed at the autoimmune basis of these diseases. For autoimmune thyroid diseases, several of the antigens that are involved in the immune system responses, including the TSH receptor for Graves' disease and thyroid peroxidase (TPO) for Hashimoto's thyroiditis, have been identified. For IDDM, several potential antigens have been identified, including glutamic acid decarboxylase (GAD). In both instances, factors associated with autoimmune diseases, including T-cell, B-cell, and HLA markers have been implicated in disease initiation and progression. Possible therapeutic interventions have focused on immune system interventions. Nevertheless, the putative role(s) played by such antigens in eliciting and/or contributing to autoimmune disease is not known. Clearly, a fuller understanding of the autoimmune basis of these endocrine disorders is necessary to open the way for more effective immune (and other) system approaches to disease treatment and/or prevention. Scope Some examples of research topics that would be considered responsive to this solicitation include, but are not limited to, the following: o the etiology, pathogenesis and treatment of autoimmune endocrine diseases, including IDDM, autoimmune thyroid disease, and Addison's disease o the cellular and molecular basis of autoimmune endocrine diseases o the molecular basis for the increased prevalence of autoimmune endocrine diseases in women o the role of cytokines and growth factors in the etiology and/or pathophysiology of autoimmune endocrine diseases o the mechanism of increased susceptibility to more than one autoimmune endocrine disease o postpartum thyroiditis o experimental animal or tissue culture models for autoimmune endocrine disorders o the role of islet cell antigens and antibodies and other potential antigens in IDDM o extrathyroidal manifestations of autoimmune thyroid disease o potential therapeutic approaches to autoimmune endocrine diseases These areas of interest are not listed in any order or priority. They are only suggested examples of areas of research. Applicants are encouraged to propose other areas that are related to the objectives and scope described above. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS It is the NIH policy that women and minorities must be included in clinical study populations unless there is a good reason to exclude them, and the study design must seek to identify any pertinent gender or minority population differences. For foreign awards, the policy on inclusion of women applies fully; since the definition of minority differs in other countries, the applicant must discuss the relevance of research involving foreign population groups to the United States' populations, including minorities. If the required information is not contained within the application, the application will be returned. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and will be reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. APPLICATION PROCEDURES Applications are to be submitted on form PHS 398 (rev. 9/91), which is available from an applicant institution's office of sponsored research and the Office of Grants Information, Division of Research Grants, National Institutes of Health, Westwood Building, Room 240, Bethesda, MD 20892, telephone 301/594-7248. Use the conventional format for research project grant applications and ensure that the points identified in this program announcement in the section REVIEW PROCEDURES AND CRITERIA are fulfilled. To identify the application as a response to this Program Announcement, check "YES" on item 2a of page one of the application and enter the title "Autoimmune Endocrine Disease" and the program announcement number: PA-93-114. Applications will be accepted in accordance with the announced receipt dates for new applications (see receipt dates and review schedule in application kits). The original and five copies of the application must be sent or delivered to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** REVIEW CONSIDERATIONS Applications will be received by the NIH, Division of Research Grants (DRG), referred to an appropriate Initial Review Group (IRG) for scientific merit review, and assigned to individual Institutes for possible funding. Referral decisions will be governed by normal programmatic considerations as specified in the Referral Guidelines of the PHS. Some applications may receive dual assignment. Applications will first be reviewed for scientific and technical merit by an IRG composed primarily of non-federal scientific consultants. 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 assigned to NIDDK or NIAID. The factors to be considered in making funding decisions include: 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: Ronald N. Margolis, Ph.D. Division of Diabetes, Endocrinology and Metabolic Diseases National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 621 Bethesda, MD 20892 Telephone: (301) 594-7549 FAX: (301) 594-9011 Elaine Collier, M.D. Division of Allergy, Immunology, and Transplantation National Institute of Allergy and Infectious Diseases/NIH Solar Building, Room 4A-20 Bethesda, MD 20892 Telephone: (301) 496-7985 FAX: (301) 402-2571 Direct inquiries regarding fiscal matters to: Ms. Kim Law Grants Management Branch National Institute of Diabetes and Digestive and Kidney Diseases Westwood Building, Room 549D Bethesda, MD 20892 Telephone: (301) 594-7543 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance Nos. 93.847 and 93.855. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under 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 ************************************************************ From owner-sci-resources@net.bio.net Mon Sep 27 23:00:00 1993 Path: biosci!net.bio.net From: kristoff@net.bio.net (Dave Kristofferson) Newsgroups: bionet.sci-resources Subject: NIH Guide, vol. 22, no. 34, pt. 2, 24 September 1993 Message-ID: Date: 28 Sep 93 01:58:57 GMT Sender: kristoff@net.bio.net Lines: 508 Approved: biosci-moderator@net.bio.net $$XID RFA AI93023 AI-93-023 P1O1 *************************************** TUBERCULOSIS DIAGNOSTICS NIH GUIDE, Volume 22, Number 34, September 24, 1993 RFA: AI-93-023 P.T. 34; K.W. 0715165, 0745020, 0710040, 0760003, 0755020, 0710070 National Institute of Allergy and Infectious Diseases Letter of Intent Receipt Date: January 7, 1994 Application Receipt Date: February 18, 1994 PURPOSE The Respiratory Diseases Branch, Division of Microbiology and Infectious Diseases (DMID), National Institute of Allergy and Infectious Diseases (NIAID) invites applications for innovative basic or applied research leading to the development of diagnostics for tuberculosis. It is anticipated that new and improved diagnostic tools to assist in the detection, prevention, and treatment of tuberculosis will improve the speed, sensitivity, specificity, and/or reliability of existing diagnostic procedures. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This Request for Applications (RFA), Tuberculosis Diagnostics, is related to the priority areas of immunity, infectious diseases, 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 Domestic and foreign, non-profit and for-profit organizations and institutions, State and local governments and their agencies, are eligible to apply. Foreign institutions are not eligible for the First Independent Research Support and Transition (FIRST) (R29) award. Minorities and women are encouraged to apply. Applications from or involving minority institutions or women's institutions are encouraged. MECHANISM OF SUPPORT This RFA will use the National Institutes of Health (NIH) individual research project grant (R01) and the FIRST (R29) award. Responsibility for the planning, direction, and execution of the proposed project will be solely that of the applicant. The total project period for applications submitted in response to this RFA may not exceed five years. The earliest anticipated award date is September 1994. This RFA is a one-time solicitation. Future unsolicited competing applications will compete with investigator-initiated applications and be reviewed according to customary review procedures. FUNDS AVAILABLE The estimated minimum total funds (direct and indirect costs) available for the first year of this program will be $2,000,000. In fiscal year 1994, the NIAID plans to fund at least eight R01s and/or R29s. This level of support is dependent on the receipt of a sufficient number of applications of high scientific merit. RESEARCH OBJECTIVES Background On April 23, 1993, the World Health Organization declared tuberculosis a global public health emergency, a distinction never accorded another disease. Once believed by health officials to be contained, tuberculosis is now recognized as out of control in many parts of the world. The London School of Hygiene and Tropical Medicine estimates that tuberculosis will claim more than 30 million lives during the coming decade unless efforts to control its transmission and deliver treatment in a timely fashion are improved. Most of these deaths will occur in persons aged 20 to 30 upon whom both younger and older persons rely for their support. Tuberculosis is responsible for an estimated 26 percent of all avoidable deaths in the 5 to 59 years age group. This increases the economic burden of the disease that remains the world's leading cause of death from any infectious agent. Most tuberculosis cases occur in developing countries where poor, crowded living conditions and inadequate nutrition prevail, and where public health programs are limited. Yet, the disease is not confined by national boundaries. In the United States, after decades of successful control and decreasing rates of disease, tuberculosis is making a comeback. About 10 million people in the U.S. are infected by the tuberculosis bacillus. The vast majority of these individuals are not sick and they are not infectious but remain at risk to develop active disease. During 1992, 26,678 cases of active tuberculosis were reported to the Centers for Disease Control up 20 percent from 1985 when resurgence of the disease began. This trend continues, among those with AIDS, the homeless, chronic alcohol or drug-abuse, those living in long-term care facilities (nursing homes, jails, etc.) and especially among certain minorities. During 1991, more than 56 percent of the active cases of tuberculosis were reported among Hispanic or African Americans. The resurgence of tuberculosis is a matter of grave concern for physicians and other health care workers, especially those charged with care of patients with active disease. These workers must treat the patient and limit transmission of an airborne infectious agent. Role of HIV Epidemic and the Emergence of Multiple-Drug-Resistant Disease The difficulties associated with early diagnosis and successful treatment of tuberculosis are compounded by two evolving developments: (1) the impact of the HIV epidemic on tuberculosis and (2) the recent accumulation in the number of isolates of multi-drug-resistant Mycobacterium tuberculosis (MDRTB). The link between HIV and tuberculosis is anticipated to be a major factor in the spread of tuberculosis. It is the only AIDS-associated infection readily transmitted to non-HIV-infected persons. Tuberculosis and HIV have been identified as synergistic. HIV infection increases the chance of primary tuberculosis and activation of latent tuberculosis infections. Recent reports show HIV-infected tuberculosis patients may become super infected with a second, drug-resistant tuberculosis strain, reducing the potential for cure and increasing both treatment costs and the chance of further transmission. HIV infection also accelerates the progression of tuberculosis. Among HIV-infected persons, tuberculosis can result in death during the first month of treatment or even before diagnosis. Finally, HIV+, TB+ patients may remain infectious due to difficulties in diagnosing tuberculosis. This increases the likelihood of transmission and poses additional challenges for public health authorities. The transmission of MDRTB poses a major threat, especially to health care workers, social workers, prison personnel, and other contacts at risk. Treatment of MDRTB infections is difficult, expensive, and often unsuccessful. Successful treatment of tuberculosis, especially MDRTB, depends upon early diagnosis. At present, it may take as long as 13 weeks to diagnose tuberculosis and determine the antibiotic susceptibility of the organism. This information is critical. Treated effectively, both HIV+ and HIV- tuberculosis patients rapidly become non-infectious. MDRTB response to appropriate treatment is markedly improved by early diagnosis. These circumstances support the need for urgent development of more rapid diagnostic testing in M. tuberculosis infections. The skin test, also called the Mantoux test, is used to determine primary infection by M. tuberculosis. This test will show a positive result for most people who have been exposed to tuberculosis. Other tests are required to determine the presence of active disease. A recent conversion to a positive skin test suggests the start of a new infection. Yet this test is not reliable for HIV infected persons. Patients with dual HIV and tuberculosis infections often do not respond to the skin