Full Text PAR-95-047 NATIONAL COOPERATIVE DRUG DISCOVERY GROUPS FOR THE TREATMENT OF HIV INFECTION (NCDDG-HIV) NIH GUIDE, Volume 24, Number 14, April 14, 1995 PA-95-047 P.T. Keywords: National Institute of Allergy and Infectious Diseases National Institute of Mental Health National Institute of Neurological Disorders and Stroke Application Receipt Date: July 1, 1995 Application Receipt Date: June 1, 1996 Application Receipt Date: June 1, 1997 PURPOSE The Division of AIDS (DAIDS), National Institute of Allergy and Infectious Diseases (NIAID), solicits applications on the discovery, preclinical efficacy evaluation, and development of novel agents and strategies that suppress HIV replication, interfere with disease progression, and ameliorate the consequences of infection. Responsive applications will involve creative and original research that emphasizes under- exploited facets of HIV infection. The National Institute of Mental Health (NIMH) solicits grant applications directed toward identifying the mechanisms underlying the cognitive and behavioral changes associated with HIV infection. The National Institute of Neurological Disorders and Stroke (NINDS) solicits grant applications directed toward studies on the neurological complications of HIV infection. Both institutes seek grant applications investigating potential CNS-targeted drug therapies that prevent or alleviate CNS dysfunction. Under this PA, applications in the following areas are not being solicited: (1) anti-viral agents and therapeutic strategies currently under intense investigation, (2) clinical studies, (3) studies of AIDS- related malignancies, and (4) studies of AIDS-associated opportunistic pathogens. Support under this PA will be provided to inter-related research consortia that include the private sector as one of its Group components. Applications funded in response to this PA will become part of the NCDDG-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 (PA), National Cooperative Drug Discovery Groups for the Treatment of HIV Infection (NCDDG-HIV), 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 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 for-profit and non-profit organizations, public and private institutions, such as universities, colleges, hospitals, laboratories, units of State and local governments, and eligible agencies of the Federal government. Foreign organizations are not eligible to apply. Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as Principal Investigators. MECHANISM OF SUPPORT The mechanism of support will be the program project (P01) grant. In previous years, the NCDDG-HIV program was supported under cooperative agreements solicited by Request for Applications (RFAs). Because of the continuing need for a drug discovery program and the maturity of the field, a program announcement for program projects is now being used. The program project mechanism supports multi- disciplinary research programs that have a well-defined research focus or objective. The program project grant consists of a minimum of three interrelated individual research projects that contribute to the program objective. An important feature of the program project is that the interrelationships of the individual scientifically meritorious projects will result in a greater contribution to the overall program goals than if each project were pursued individually. Consortia that include the private sector are of particular interest because of the unique capability of this sector to rapidly develop and advance promising therapeutic strategies to clinical studies. The program project grant can provide support for common resources termed cores. Each core should be utilized by two or more projects within the program project. Responsibility for the planning, direction, and execution of the proposed project will be that of the applicant. The total project period may not exceed four years. The earliest anticipated award date is January 1996. FUNDS AVAILABLE In fiscal year 1996, the NIAID plans to fund two to three new or competing renewal program projects related to this PA. The NIMH and NINDS each plan to support up to three additional program projects that focus on CNS-HIV related issues as described. This level of support is dependent upon the receipt of a sufficient number of applications of high scientific merit and programmatic relevance. NIH is limiting inflationary increases to no more than four percent per year. The current goal is to maintain an NCDDG-HIV program size of 8 to 12 groups. Funding in future years will depend on program size, quality of applications submitted, and availability of funds. PHS policies governing grants administration and management will apply. Awards pursuant to this PA are contingent upon the availability of funds for this purpose. RESEARCH OBJECTIVES Background Notwithstanding intense, multi-national efforts to halt the HIV epidemic, effective, long-term therapies are lacking, and the number of HIV-infected individuals and AIDS cases is increasing. As of June 1994, 401,749 cases of AIDS had been reported in the U.S. by the Centers for Disease Control (CDC) and more than 243,423 of these patients had died. Recent estimates indicate that 1,000,000 individuals in the U.S. are infected with HIV. The World Health Organization projection of worldwide HIV infection is placed at 30 to 40 million individuals by the year 2000. Research advances in recent years have yielded a wealth of information on HIV molecular biology, the pathogenic aspects of the infection, and the impact of disease progression on immune parameters. Concomitantly, seminal technological breakthroughs have been realized. However, development of effective HIV therapies has not been commensurate with this expansion: almost all antiretroviral therapies to date target either the viral reverse transcriptase (RT) or protease. Other viral genes identified to be critical for HIV replication remain largely under-exploited as therapeutic targets. In part, this is attributable to the fact that many single institutions do not have the critical mass, diverse scientific talents, and/or ancillary resources to translate basic discoveries to applied treatment entities. Research on HIV infection of the brain and potential CNS-targeted drug therapies are also not sufficiently addressed. The NCDDG-HIV program is an integral component of NIAID support of novel therapeutic opportunities and complements existing NIAID programs for treatment research in HIV disease. One of the principal goals of the NCDDG-HIV program is to fund research for the discovery of novel therapeutic strategies and their rapid translation to effective treatments suitable for clinical studies. This is accomplished by supporting multi- component research groups - comprising the academic and commercial sectors - with the needed scientific talents and development capabilities. This framework of multi-component research linked to the private sector will be used for this PA to fund groups that work in cooperative manner to discover and develop novel therapeutic modalities for HIV disease. Scope of Research The principal objective of this PA is the discovery and preclinical development of new and effective therapies for HIV disease. In line with this objective, this PA will support creative therapeutic strategies of sound scientific rationale that are not pursued or extensively studied. Such therapeutic approaches may have a greater risk-to-benefit quotient than currently funded research supported under the individual investigator initiated (R01) mechanism, but may also have a greater potential for effective, long-term therapeutic returns. As stated above, these efforts will be conducted in collaboration with the private sector, which has the infrastructure and resources required for the development of antiviral leads and strategies. Moreover, the private sector has the capabilities to mobilize additional resources rapidly as needed. Examples of responsive studies to be supported by this PA include, but are not limited to: o targeting new and/or under-explored viral functions; o interfering with viral functions required for replication (e.g. Nef, VPU, VPR, Vif) and cellular factors associated with their activity; o targeting cellular factors required for HIV function (e.g. NFkB; IkB) and effectors that modulate viral activity; o interfering with HIV/cell interaction (entry, subcellular transport, assembly, release); o creative strategies unlikely to be affected by emergence of escape mutants or drug resistant variants; strategies that target non-T cell compartments (e.g. dendritic cells, follicular dendritic cells, monocyte/macrophage, epithelial) involved in pathogenesis and virus dissemination; o cell and tissue based approaches to modulate organ damage; o mediators, factors, and neural receptors involved in HIV-penetration of the blood brain barrier and the resulting neural injury or neurological complications (unique to either pediatric or adult patients). Studies involving anti-viral agents (such as nucleoside analogue inhibitors of reverse transcriptase) and therapeutic strategies currently under intense investigation in the private or academic sector are excluded. A program project application as a whole, which must consist of three or more projects and include the private sector, must address the development of a specific strategy in a cohesive, concerted manner. Thus, responsive applications would be those in which each project provides information necessary to determine the utility of the single intervention strategy chosen as the overall program objective and/or develop the strategy. Each application must provide an experimental plan that details methods to evaluate the usefulness of the therapeutic approach, and must include a schedule or time table to be followed. Examples of confirmatory evaluation include: inhibition of infection or documented correlates of pathology in in vitro or in vivo model systems; design and validation of novel and predictive models amenable to efficacy testing; design and validation of assay systems amenable to large scale testing by the private sector component (excluding random screening, see below). Consortium arrangements should follow the NIH Guide outline in "Guidelines for Establishing and Operating Consortium Grants, January 1989." These are available from the individuals listed under INQUIRIES. SPECIAL REQUIREMENTS Patent Coverage Because the implementation of innovative, effective clinical therapies for HIV/AIDS is the principal goal of this PA and active involvement by the private sector is facilitated by the existence of adequate patent coverage, it is essential that applicants provide plans to ensure such coverage. Since several institutions may be involved, complex patent situations may arise. Each applicant Group must therefore provide a detailed description of (1) 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; and (2) the procedures to be followed for the resolution of legal problems that potentially 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. It is also noted that 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. The patent agreement among the institutions comprising the Group, signed and dated by the organizational officials authorized to enter into patent arrangements for each Group member and member institution, must be submitted with the application. If the Group wishes to place all inventions and discoveries resulting from these studies within the public domain, a letter to that effect must be submitted to Dr. Sarver in lieu of the patent agreement two weeks prior to submission of the application. The letter must be co-signed by the Principal Investigator, each of the Project Leaders, and each of the business officials representing the respective institutions. Federal regulation clause 37 CFR 401 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, NIH, Building 31, Room 5B41, 9000 Rockville Pike, Bethesda, MD 20892. The application should budget appropriate funds to allow key personnel to attend the annual meeting of the NCDDG-HIV, which is generally held in Bethesda. INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification is provided that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This new policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43) and supersedes and strengthens the previous policies (Concerning the Inclusion of Women in Study Populations, and Concerning the Inclusion of Minorities in Study Populations), which have been in effect since 1990. The new policy contains some provisions that are substantially different from the 1990 policies. All investigators proposing research involving human subjects should read the "NIH Guidelines For Inclusion of Women and Minorities as Subjects in Clinical Research," which have been published in the Federal Register of March 28, 1994 (FR 59 14508-14513) and printed in the NIH Guide for Grants and Contracts, Volume 23, Number 11, March 18, 1994. Investigators also may obtain copies of the policy from the program staff listed under INQUIRIES. Program staff may also provide additional relevant information concerning the policy. APPLICATION PROCEDURES Potential applicants are strongly encouraged to discuss their research concept with Dr. Nava Sarver (INQUIRIES below) before preparing applications. Applicants with a research focus on neurological complications of HIV infection affecting cognitive and/or motor function should discuss their proposed studies with Dr. Dianne Rausch, and applicants with a research focus on the neurological effects of HIV infection on the brain should discuss their proposed studies with Dr. A. P. Kerza-Kwiatecki before submitting an application (see INQUIRIES below). Applications are to be submitted on form PHS 398 (rev. 9/91), the standard application form for research grants. Application kits are available at most institutional offices of sponsored research and may be obtained from the Office of Grants Information, Division of Research Grants, National Institutes of Health, Westwood Building, Room 449, Bethesda, MD 20892, telephone 301/710-0267. Applicants must adhere to the format and requirements specified in the PHS 398 application kit. In addition, applicants are strongly advised to read the information brochure "NIAID Program Project Grants and Multi-project Cooperative Agreements", available from Dr. Nava Sarver at the address listed under INQUIRIES. For purposes of identification and processing, mark "YES" in item 2a on the face page of the application and type in the PA number PA-95-047 and the title "NATIONAL COOPERATIVE DRUG DISCOVERY GROUPS FOR THE TREATMENT OF HIV INFECTION (NCDDG- HIV)." The signed, typewritten original of the application, including the Checklist and five exact single-sided copies must be sent to: DIVISION OF RESEARCH GRANTS NATIONAL INSTITUTES OF HEALTH 6701 ROCKLEDGE DRIVE ROOM 1040 MSC 7710 BETHESDA MD 20892-7710 BETHESDA MD 20817 (for courier service) The entire address should appear in UPPER CASE letters without punctuation to allow optical scanners to read and sort mail. Concurrent submission of an R01 and a Component Project of a Multi-project Application Current NIH policy permits a component research project of a multi-project grant application to be concurrently submitted as a traditional individual research project (R01) application. If, following review, both the multi-project application and the R01 application are found to be in the fundable range, the investigator must relinquish the R0l and will not have the option to withdraw from the multi-project grant. This is an NIH policy intended to preserve the scientific integrity of a multi-project grant, which may be seriously compromised if a strong component project(s) is removed from the program. Investigators wishing to participate in a multi-project grant must be aware of this policy before making a commitment to the Principal Investigator and awarding institution. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by DRG. Incomplete applications will be returned to the applicant without further consideration. Applications will be assigned on the basis of established PHS referral guidelines. Applications will be evaluated for scientific and technical merit by an appropriate peer review group convened in accordance with the standard NIH peer review procedures. As part of the initial merit review, all applications will receive a written critique and undergo a process in which only those applications deemed to have the highest scientific merit, generally the top half of applications under review, will be discussed, assigned a priority score, and receive a second level review by the appropriate national advisory council or board. Applications determined to be non- competitive will be withdrawn from further considerations and the principal investigator and the official signing for the applicant organization will be promptly notified. Review Criteria Scientific Considerations The review criteria for P01 grant applications are the same as for large, multi-component, interdisciplinary program projects described in NIAID brochure "NIAID Program Project Grants and Multi-project Cooperative Agreements." The program project grant application should include a justification for using the P01 granting mechanism for the proposed project. In addition, the application must be directed toward (1) attaining the programmatic goals as stated under Research Objectives and Scope; and (2) as listed under AWARD CRITERIA, below. AWARD CRITERIA Funding decisions will be made on the basis of scientific and technical merit as determined by peer review, the availability of funds, and program balance, including relevance to the control of public health problems. In addition, for awards assigned to the NIAID, the following considerations will be included in the award criteria: o the novelty and appropriateness of the proposed research to the discovery of new entities and/or strategies for the treatment of HIV infection; o the likelihood that a therapeutic strategy will be developed that is suitable for clinical evaluation; o commitment of the PI and PLs to the program: a minimum of 20 per cent effort by the PI and each PL is deemed necessary for this effort; o For competitive renewal by currently funded groups: evidence of past accomplishment under the NCDDG-HIV program that fulfills the programmatic goals (e.g. design, formulation, or development therapeutic strategies/agents for the treatment of HIV infection). INQUIRIES Written and telephone inquiries concerning this PA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Requests for the brochure "NIAID Program Project Grants and Multi-project Cooperative Agreements," as well as inquiries regarding programmatic issues may be directed to: Nava Sarver, Ph.D. Division of AIDS, NIAID Solar Building, Room 2C01 6003 Executive Boulevard Bethesda, MD 20892 (301) 496-8197 FAX: (301) 402-3211 Email: ns18p@nih.gov For NIMH programmatic issues: Dianne Rausch, Ph.D. Office on AIDS NIMH Parklawn Building, Room 10-75 5600 Fishers lane Rockville, MD 20857 (301) 443-6100 FAX: (301) 443-9719 Email: drausch@aoamh2.ssw.dhhs.gov For NINDS programmatic issues: Dr. A. P. Kerza-Kwiatecki Division of Demyelinating, Atrophic, and Dementing Disorders, NINDS Federal Building, Room 804 7550 Wisconsin Ave. Bethesda, MD 20892 (301) 496-1431 FAX: (301) 402-2060 Email: ak64n@nih.gov Direct inquiries regarding fiscal matters to: Carol Alderson Division of Extramural Activities, NIAID Solar Building, Room 4C26 6003 Executive Boulevard Bethesda, MD 20892 (301) 496-5937 FAX: (301) 402-2638 Email: carol_alderson@nih.gov SCHEDULE Application Receipt Date: July 1, 1995 Scientific Review Date: October/November 1995 Earliest Date of Award: January 1996 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance, No. 93.856 - Microbiology and Infectious Diseases Research. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. The PHS strongly encourages all grant and contract recipients to provide a smoke-free work place and promote the non-use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routing education, library, day care, health care or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people. .
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