This is a one time solicitation. This PA expires after June 27, 2001. INTEGRATED PRECLINICAL/CLINICAL PROGRAM FOR HIV TOPICAL MICROBICIDES Release Date: March 29, 2001 Receipt Date: June 27, 2001 PA NUMBER: PA-01-075 National Institute of Allergy and Infectious Diseases (http://www.niaid.nih.gov/) National Institute of Child Health and Human Development (http://www.nichd.nih.gov/) APPLICATIONS IN RESPONSE TO THIS PROGRAM ANNOUNCEMENT (PA) MUST BE PREPARED USING A MULTI-PROJECT GRANT APPLICATION FORMAT; SPECIFIC INSTRUCTIONS FOR COMPLETING THE APPLICATION ARE IN THE NIAID BROCHURE ENTITLED "INSTRUCTIONS FOR APPLICATIONS FOR MULTI-PROJECT AWARDS. PURPOSE The National Institute of Allergy and Infectious Diseases (NIAID) and the National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH) invite multi-project, multi- disciplinary applications whose goal is to advance novel topical microbicides and microbicide combination strategies to prevent the sexual transmission of HIV from preclinical to clinical studies. For the purposes of this Program Announcement (PA), topical microbicides are defined as vaginally or rectally applied biomedical products with or without contraceptive activity that directly or indirectly inactivate HIV or prevent HIV infection or spread from initial target cells. The Integrated Preclinical/Clinical Program for HIV Topical Microbicides (IPCP-HTM) described in this PA links research with product development and initial clinical evaluation by supporting diverse research activities from multidisciplinary groups spanning advanced preclinical optimization and development through early clinical trials. Applications that aim to further an innovative topical microbicide may propose to initiate research at one of the following points: (1) preclinical optimization of a lead microbicide candidate/combination and advanced preclinical development, (2) preclinical research that transitions to iterative clinical/laboratory research directed toward refinement of the microbicide candidate/combination during the award period, or (3) iterative clinical/laboratory research in which a pilot clinical trial will be implemented within the first year of award. In combining these activities into a single PA, the IPCP-HTM provides a spectrum of research opportunities for collaborative groups pursuing any aspect of advanced development of new topical microbicides. For applications in which clinical studies are proposed, the participation of industry is required. For applications limited to advanced preclinical optimization and development, participation of industry is strongly urged. Responsive applications will advance microbicide development with innovative microbicide research. Excluded from this PA is research on, or development of, marketed spermicidal products and/or discovery of potential microbicides. HEALTHY PEOPLE 2010 The PHS is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS led national activity for setting priority areas. This PA, Integrated Preclinical/Clinical Program for HIV Topical Microbicides, is related to the focus area of HIV Infection and Sexually Transmitted Diseases. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople. 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. Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as Principal Investigators (PIs). The involvement of industry is required for applications proposing clinical studies and strongly urged for preclinical applications because of the established and proven infrastructure and capital resources it brings to the program and its proficiency in rapidly mobilizing resources and expertise to move promising leads through the development pathway. Investigators from the private sector are eligible to participate as PIs, Project or Core Leaders (PLs or CLs), or as collaborators. MECHANISM OF SUPPORT Program Project grants (P01) will be used to support projects in response to this announcement. Program Project grants support broadly based, multi-disciplinary research programs that have a well-defined, central research focus or objective. An important feature is that the integrated approach of the individual scientifically meritorious projects will result in a greater contribution to the overall program goals than if each project were pursued independently. Normally, the program project grant consists of a minimum of three interrelated individual research projects that contribute to the program objective. However, for the purposes of this PA, the minimum number of individual research projects is two. It is important to note that applications for programs consisting of only 2 projects must have 2 fundable projects remaining as recommended for consideration for funding after the review is complete. This type of award also can provide support for certain common resources termed cores. Such resources should be utilized by two or more projects within the award. Examples of cores include administrative, formulation or animal model cores. The total project period for an application submitted in response to this PA that proposes clinical studies at any time during the award period may not exceed 5 years. The total project period for an application limited to advanced preclinical optimization and development may not exceed 4 years. NIAID and NICHD intend to support the following research groups through this PA: (1) groups focusing exclusively on advanced preclinical optimization and IND-directed development of new topical microbicides [i.e., appropriately synthesized and manufactured microbicide products that will undergo safety testing as per U.S. Food and Drug Administration (FDA) Investigational New Drug (IND) guidelines], and (2) groups positioned to implement a pilot clinical study during the award period. Pilot clinical studies are defined as early Phase I studies with small numbers of participants, exclusive of formal Phase I through Phase III clinical trials. P01 applications submitted in response to this PA may not request in excess of $750,000 first-year direct costs for research involving preclinical studies, or $1,300,000 first-year direct costs, exclusive of Facilities & Administrative (F & A) costs for consortium arrangements for translational research involving clinical studies. Budgets exceeding these levels must be strongly justified and pre-approved for submission by the Program contact person listed under INQUIRIES. Applications with budgets exceeding these levels that are submitted without prior Program approval will be returned without review. Groups proposing to transition from preclinical to clinical studies during the award period should submit a budget for each phase that reflects the limits given above. The level of support for clinical research under this PA may be insufficient to provide all the funds necessary to conduct the proposed clinical study. Prospective groups are encouraged therefore to develop plans to use existing infrastructure and organizational support to complement the award [including NIH-sponsored General Clinical Research Centers (GCRC), Centers for AIDS Research (CFAR), the HIV Prevention Trials Network (HPTN), the Adolescent Medicine Trials Network (ATN), the Contraceptive Clinical Trials Network (CCTN) and the Comprehensive International Program for Research on AIDS (CIPRA)]. These plans should be included in the application. Responsibility for the planning, direction, and execution of the proposed research for all applicable mechanisms of support will be solely that of the applicant. Applicants for P01 grants must follow special application guidelines in the NIAID Brochure entitled INSTRUCTIONS FOR APPLICATIONS FOR MULTI- PROJECT AWARDS (August 2000); this brochure is available via the WWW at: http://www.niaid.nih.gov/ncn/grants/multibron.htm. RESEARCH OBJECTIVES Background In the absence of a fully effective HIV vaccine, topical microbicides represent an important potential strategy for preventing the transmission of HIV through sexual intercourse, the predominant mode by which HIV is transmitted worldwide. In particular, the number of women with HIV infection and AIDS has been increasing steadily worldwide and according to the World Health Organization (WHO), 15.7 million women are living with HIV/AIDS worldwide, accounting for 46 percent of the 32.4 million adults living with HIV/AIDS. The vulnerability of women of all ages for acquiring HIV infection - including older, postmenopausal women as well as adolescents - demands the development of effective and acceptable female-controlled chemical and physical barrier methods, including topical microbicides, to reduce HIV transmission. In addition, recent statistics from several major cities in the U.S. show an increase in unsafe sexual practices as indicated by an increase in rectal gonorrhea. Yet no effective anti-HIV topical microbicide is currently available. Few products have been entered into clinical trials and only nonoxynol-9 (N-9)-containing products have advanced to efficacy trials. Results from Phase III trials of vaginal N-9-containing products have indicated that N-9 does not provide protection against the sexual transmission of HIV. Candidate microbicides currently under investigation include products that kill or inactivate HIV nonspecifically, those that inhibit HIV entry and cell fusion, and those that inhibit post-fusion events early in the viral replication cycle. The nonspecific candidate products fall predominantly into the category of surfactants and detergents, whereas most products targeted against specific steps in the HIV life cycle have been developed exclusively as potential therapeutics. In addition, no combination of microbicides has yet been evaluated in animal or human trials. Therefore, there is a critical need to promote the advanced development of novel microbicides and combinations and to provide support for translational studies to advance existing/new candidates and combinations into early clinical trials. This PA will support multi-project, multi-disciplinary research groups whose goal is to advance topical microbicides and microbicide combination strategies from preclinical to clinical studies by assembling the diverse scientific expertise and ancillary resources needed to translate basic discoveries to innovative applied entities. Scope The purpose of the IPCP-HTM is: 1) to encourage advanced optimization and development of lead topical microbicide candidates and combinations, and 2) to foster translation of new microbicides/combinations from preclinical studies to pilot clinical studies. The ultimate goal of this research is the development and exploratory clinical evaluation of new and potentially effective microbicides for the prevention of HIV sexual transmission. Such research is expected to increase the array of approaches and availability of potential candidates and combinations suitable for evaluations of safety and effectiveness in human clinical studies. In line with this objective, the PA will support diverse and creative microbicides/combinations with sound scientific rationale that are new and innovative or understudied. The PA provides a continuous spectrum of research opportunities for interdisciplinary research groups to conduct, from preclinical to pilot clinical studies. Examples of microbicide candidates of interest to the IPCP-HTM include, but are not limited to: o Development of combination microbicides containing a cocktail of active agents with diverse mechanisms of action, including those addressed below. o Development of microbicides that target viral or host elements essential for (i) HIV entry, including attachment, receptor engagement or fusion; (ii) early post-entry events in the HIV life cycle prior to and including reverse transcription, such as uncoating or translocation of the pre-integration complex into the nucleus; and/or (iii) HIV capture by, and dissemination from, initial target cells o Development of microbicides that enhance or stimulate naturally occurring healthy mucosal defense mechanisms o Development of innovative virucidal agents that inactivate infectious HIV-1 particles or HIV-1-infected cells in the absence of host cell toxicity. Preclinical Research The preclinical component of the IPCP-HTM supports the advanced optimization and development of topical microbicides and combination microbicide approaches. A new microbicide or combination, including pre-existing non-detergent microbicides, should have relevance and future application to clinical evaluation. Advanced optimization may involve identification of the most favorable formulation for delivery or determination of the optimum concentrations of individual active agents in a candidate combination microbicide. As part of an integrated approach to the critical path development of a specific candidate product and advancement into pilot clinical trials, applications may incorporate research in the areas of formulation science and development of new and/or improved ex vivo (e.g., tissue explants) and in vivo animal models for evaluating the safety and efficacy of new microbicides, including models for reproductive toxicity. In addition, IND-enabling preclinical studies must comply with Good Laboratory Practice (GLP) regulations, as well as production and manufacture of microbicide products according to Good Manufacturing Practice (GMP) regulations, to be considered responsive to this PA. A successful group proposing preclinical studies would move a candidate microbicide, or combination, through advanced preclinical development where it would be poised for clinical evaluation during the course of the award period. Applicants seeking to transition from preclinical to clinical research during the award period must detail the goals and milestones considered necessary to enter the clinical phase. These goals and milestones should also include plans and a timetable for obtaining the required institutional and government approvals [Institutional Review Board (IRB), Office of Human Research Protection (OHRP), FDA]. The peer review group will review the appropriateness of the goals and milestones. When a request to transition to the clinical phase is made, these goals and milestones will also be used to determine the successful completion of the preclinical development phase. Release of funds for clinical research will be contingent upon the documented successful completion of the proposed and peer-reviewed goals and milestones. Clinical studies The clinical portion of the IPCP-HTM exploits interdependent, iterative clinical/laboratory research designed to evaluate and optimize a microbicide. Research in the areas of identification of markers to establish product use compliance and assessment of state-of-the-art technologies to measure bio-adhesive and bio-dispersion characteristics may be included as part of an integrated approach to advance a specific microbicide candidate. Examples of other scientific areas appropriate for pilot clinical studies include, but are not limited to, evaluation of pharmacokinetics and tissue distribution of the proposed microbicide candidate, and preliminary evaluation of potential activity on viral load (if relevant to the proposed mechanism of action) recovered in vaginal and rectal mucosal specimens. Proposals with projects focusing on new strategies that exploit pre-existing non-detergent microbicides, especially as combination microbicides, would also be considered responsive. A successful application proposing clinical studies would develop and optimize a microbicide candidate to the point of determining its merits for further clinical evaluation. A clinical application must be based on a strategy in an advanced stage of preclinical development that is suitable for evaluation in a small number (6-12) of subjects in a pilot clinical study. [When merited by the study, a larger number of subjects may be considered; prior approval by the Program Officer (see INQUIRIES, below) is required.] Conventional Phase I through Phase III clinical trials are not supported by this Program Announcement. The application should include (1) a detailed plan of the iterative clinical and laboratory research to be conducted to optimize the proposed strategy, (2) a timetable to be followed, (3) plans for clinical studies, including a clinical concept, outline of a clinical protocol, or the clinical protocol, and (4) institutional and government approvals (IRB, FDA, OHRP), where applicable. SPECIAL REQUIREMENTS IPCP-HTM Group Scientific Advisory Panel Each IPCP group will establish a Scientific Advisory Panel ("Panel") of 2-3 investigators not affiliated with any of the institutions comprising the group. Applicants must not name the prospective Advisory Panel members in their applications nor should prospective members be contacted by applicants prior to completion of review of applications. However, a proposal should include identification of the proposed expertise to be represented on the panel. The Panel will attend one or more of the IPCP group meetings each year, review the group's activities, and evaluate progress, adherence to the original time frame of activities, and the continued relevance of each project to the group's overall goals. The Panel will recommend new directions as appropriate and will provide the PI with a comprehensive written evaluation of the group's activities and recommendations after each meeting. A copy of the report is to be sent to the NIAID or NICHD Coordinator, as appropriate, within 30 days of the meeting. [The Coordinator for each group will be the equivalent of a Program Officer, having medical and/or scientific research expertise depending on the preclinical and/or clinical focus of the project.] Meetings and travel All awardees will be strongly encouraged to attend a scientific conference of IPCP-HTM investigators, organized by NIH and held every 12-18 months in the Washington, D.C. area. Applicants should include estimated travel expenses for one such meeting per year to the applicant organization or the Washington, D.C. metropolitan area in the application budget. Estimated expenses for travel of the Scientific Advisory Panel members should be based on one group meeting per year and should also be included in the budget. No additional travel funds will be provided to attend other domestic or foreign meetings. TERMS AND CONDITIONS OF AWARD Patent Coverage Since an application may include several institutions, including the private sector, complex patent situations may arise. To avoid delays related to intellectual property issues, each multi-project group is required to provide, as part of the application, a plan detailing (1) the approach agreed to by all parties for obtaining patent coverage and licensing, where appropriate; and (2) 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 for intellectual property issues. 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 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 there from. 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 the group’s 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, should be submitted to Dr. Roberta Black (listed under INQUIRIES) prior to review. The patent agreement should not 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. Black in lieu of the patent agreement. The letter must be co-signed by the PI, each of the PLs, and each of the business officials representing the respective institutions. Awards Including Clinical Studies When clinical studies or trials are a component of the research proposed, NIAID policy requires that studies be monitored commensurate with the degree of potential risk to study subjects and the complexity of the study. Terms and Conditions of Award will be included with awards. NIAID policy was announced in the NIH Guide on February 24, 2000 and is available at: http://grants.nih.gov/grants/guide/notice-files/NOT-AI-00-003.html. The full policy including terms and conditions of award is available at: http://www.niaid.nih.gov/ncn/pdf/clinterm.pdf Groups seeking to transition from preclinical to clinical studies during the award period must include a long-range development plan that details the preclinical, transitional, and clinical phases of the proposed studies, and a budget appropriate to each phase. Funds to accommodate the potentially more costly clinical study should be budgeted in the application. The group must articulate a set of objectives and milestones to be completed prior to transition to clinical research and include the clinical site(s) and clinical investigators to be involved. For purposes of peer review, the application must include, at a minimum, a clinical concept for a future protocol or an outline of a clinical protocol (as an Appendix to the application) based on research findings available at the time of submission (although it is understood that the concept/protocol may evolve as work progresses). The concept/outline must contain information regarding the design of the protocol including objectives and rationale, the size and characteristics of the patient population, medical (including safety) and site monitoring plans, statistical analysis, if appropriate, and a list and time course for associated laboratory evaluations. All the above components - the development plan, objectives and milestones, clinical concept/protocol outline, clinical site and clinical investigators - will be essential elements of the initial review by the peer review group. The NIAID and NICHD will review requests to transition to clinical research and will use the Division of AIDS (DAIDS) Prevention Sciences Review Committee (PSRC) to review the clinical protocol and budget and to assist in determining whether the group requesting transition is positioned to proceed to clinical studies. Release of funds for clinical research will be contingent on successful accomplishment of milestones and criteria stated in the original application as reviewed and approved by the peer review group, and include compliance with all applicable laws and regulations. To initiate clinical studies awardees must have IRB, FDA, and OHRP approvals. Funds for clinical studies will be withheld until the required approvals are obtained and copies provided to NIAID (Dr. Roberta Black, listed under INQUIRIES) or NICHD (Dr. Patricia Reichelderfer, listed under INQUIRIES), as appropriate. Additional details for applications that include a clinical component are listed as follows. The PI is responsible for: o Assuming responsibility for developing protocols and monitoring study performance; participant recruitment and follow-up; interim data and safety analysis and monitoring. All protocols will be submitted by the PI to the NIAID (Dr. Roberta Black, listed under INQUIRIES) for review for safety issues by the DAIDS PSRC prior to implementation. The PI will be responsible for reporting recruitment, retention, and other similar information to DAIDS, NIAID (or Center for Population Research, NICHD, as appropriate) at six-month intervals, on January 1 and July 1 of each year. Adverse event reports will be forwarded to Dr. Black or Dr. Reichelderfer at the same time as to the FDA. o Establishing procedures to comply with FDA regulations for studies involving investigational agents and strategies and to comply with the requirements of 45 CFR Part 46 for the protection of human subjects. Terms of award for any human clinical trial component will be developed to ensure volunteer safety and monitoring of compliance with regulations and Good Clinical Practices. NIAID and NICHD staff will provide guidance and technical advice on meeting FDA requirements for investigational agents. INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of the NIH that women and members of minority groups and their subpopulations must be included in all NIH supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification is provided that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing research involving human subjects should read the UPDATED "NIH Guidelines For Inclusion of Women and Minorities as Subjects in Clinical Research," published in the NIH Guide for Grants and Contracts on August 2, 2000 http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-048.html. The revisions relate to the NIH-defined Phase III clinical trials and require: a) all applications or proposals and/or protocols to provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) all investigators to report accrual, and to conduct and report analyses, as appropriate, by sex/gender and/or racial/ethnic group differences. INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of NIH that children (i.e., individuals under the age of 21) must be included in all human subjects research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them. This policy applies to all initial (Type 1) applications submitted for receipt dates after October 1, 1998. All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines on the Inclusion of Children as Participants in Research Involving Human Subjects" that was published in the NIH Guide for Grants and Contracts, March 6, 1998, and is available at the following URL address: http://grants.nih.gov/grants/guide/notice-files/not98-024.html Investigators may obtain copies from these sources or from Dr. Roberta Black (listed in INQUIRIES below) who may also provide additional relevant information concerning the policy. URLS IN NIH GRANT APPLICATIONS OR APPENDICES All applications and proposals for NIH funding must be self-contained within specified page limitations. Unless otherwise specified in an NIH solicitation, internet addresses (URLs) should not be used to provide information necessary to the review because reviewers are under no obligation to view the Internet sites. Reviewers are cautioned that their anonymity may be compromised when they directly access an Internet site. APPLICATION PROCEDURES Applicants for P01 grants must follow special application guidelines in the NIAID Brochure entitled INSTRUCTIONS FOR APPLICATIONS FOR MULTI- PROJECT AWARDS (August 2000); this brochure is available via the WWW at: http://www.niaid.nih.gov/ncn/grants/multibron.htm Applications are to be submitted on the grant application form PHS 398 (rev. 4/98) and will be accepted up to and including the application receipt date as indicated in this PA. Application kits are available at most institutional offices of sponsored research and may be obtained from the Division of Extramural Outreach and Information Resources, National Institutes of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone 301/710-0267, email: GrantsInfo@nih.gov. In addition, applications are available at the following URL: http://grants.nih.gov/grants/forms.htm. Applications that are not received as a single package on the receipt date or that do not conform to the instructions contained in PHS 398 (rev. 4/98) Application Kit (as modified in, and superseded by, the NIAID BROCHURE ENTITLED "INSTRUCTIONS FOR APPLICATIONS FOR MULTI- PROJECT AWARDS"), will be judged non-responsive and will be returned to the applicant. For purposes of this PA, the following procedures and policies will apply. Applicants planning to submit a grant application requesting in excess of $750,000 in direct costs if preclinical research is proposed, or in excess of $1,300,000 in direct costs if a clinical trial is proposed, for any year, are advised that he or she must contact the Institute or Center (IC) program staff listed in INQUIRIES below, before submitting the application, i.e., as plans for the study are being developed. Furthermore, the applicant must obtain agreement from the IC staff that the IC will accept the application for consideration for award. Finally, the applicant must identify, in a cover letter sent with the application, the staff member and Institute or Center who agreed to accept assignment of the application. This policy requires an applicant to obtain agreement for acceptance of both any such application and any such subsequent amendment. Refer to the NIH Guide for Grants and Contracts, March 20, 1998 at http://grants.nih.gov/grants/guide/notice-files/not98-030.html For purposes of identification and processing, item 2a on the face page of the application must be marked YES , and the PA number and the words, INTEGRATED PRECLINICAL/ CLINICAL PROGRAM FOR HIV TOPICAL MICROBICIDES must be typed in. Submit a signed, typewritten original of the application, including the checklist, and three signed, exact, single-sided photocopies in one package to: CENTER FOR SCIENTIFIC REVIEW NATIONAL INSTITUTES OF HEALTH 6701 ROCKLEDGE DRIVE, ROOM 1040, MSC 7710 BETHESDA, MD 20892-7710 BETHESDA, MD 20817 (for express/courier service) At the time of submission, two additional exact copies of the grant application and all five sets of any appendix material must be sent to Dr. Vassil St. Georgiev at the address listed under INQUIRIES. 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 R01 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 PI and awarding institution. Applicants from institutions that have a GCRC funded by the NIH National Center for Research Resources or an HIV Prevention Trials Unit (HPTU), a CFAR, or a CIPRA award funded by NIAID or an ATN or CCTN award funded by NICHD may wish to identify the GCRC, HPTU, CFAR, ATN, CCTN or CIPRA as a resource for conducting the proposed research. If so, a letter of agreement from either the GCRC program director or PI for the other relevant program(s) should be included with the application. REVIEW CONSIDERATIONS Review Procedures Upon receipt, applications will be reviewed for completeness by the NIH Center for Scientific Review. Incomplete applications will be returned to the applicant without further consideration. P01 applications that are complete and responsive to this PA will be evaluated for scientific and technical merit by an appropriate peer review group convened by the NIAID. Review Criteria Applicants should see the NIAID brochure "INSTRUCTIONS FOR APPLICATIONS FOR MULTI-PROJECT AWARDS (August 2000) for review criteria for P01 applications. Additional review criteria specific to this PA that the initial review group will also examine are: the adequacy of plans to include children, and both genders and minorities and their subgroups, as appropriate for the scientific goals of the research, and plans for the recruitment and retention of subjects; the provisions for the protection of human and animal subjects; and the safety of the research environment. It may be beneficial to contact staff for advice regarding human subjects concerns prior to submission. The reviewers will be asked to comment on specific criteria as detailed in the brochure for multi-project applications in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. These specific criteria are: o The biomedical significance and originality of the project. o The likelihood that the research will open new directions in the prevention of HIV sexual transmission or containment of HIV infection, demonstrate a capacity to be translated to clinical practice, or merit evaluation in IND-directed clinical trials for safety and proof-of- concept. o Appropriateness of the experimental approach, development plan, and methodology proposed, including laboratory capabilities (preclinical and/or clinical). o The PI's and PLs' commitment to devote substantial time and effort to the program. [Due to the complexity and time required to maintain a well coordinated and productive research effort, a minimum 20% (time) commitment by the PI and PLs is strongly suggested.] Each of these review criteria will be addressed and considered by the reviewers in assigning the overall score, weighting them as appropriate for each application. Note that the application does not need to be strong in all categories to be judged likely to have a major scientific impact and thus deserve a high priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to move a field forward. In addition to (not in lieu of) the review criteria detailed in the instruction brochure (see above), review criteria specific to this PA (mainly bearing to the review of the individual preclinical and clinical projects) include an evaluation of the following: For groups focusing on preclinical research: o Choice of the microbicide target or strategy, its contribution to the diversity of potential microbicides, and the likelihood that the microbicide candidate can be developed (e.g., following a prescribed preclinical development plan; selecting a clinical candidate) during the award period. o Likelihood that work will progress through advanced development during the award period For groups proposing clinical research: o Adequacy and validity of the proposed milestones for determining the readiness of the group to transition to clinical research; iterative research plan to develop and optimize the proposed microbicide candidate; protocol design (clinical and scientific); short and long term development plans; contingency plans addressing the specific objectives; plans to guard the safety of subjects; plans to evaluate outcome even if unanticipated; and provisions to obtain the required institutional and regulatory approvals (IRB, FDA, OHRP) to conduct the clinical study. o Experience of the PI and PLs in the planning, design, and conduct of small pilot clinical studies in healthy individuals and/or in the conduct of topical microbicide clinical trials, availability of a GCRC, CFAR, CIPRA, HPTN clinical site, ATN site, CCTN site or other additional source of institutional support and/or statistical support; the infrastructure required for the conduct of safe and efficient clinical research; and short and long range plans that will result in the successful implementation of clinical studies during the award period. In addition to evaluating the scientific merit of the application, all multi-project applications are also assessed for the soundness of the administrative and organizational structure that facilitates attainment of the objective(s) of the program. Thus, the Administrative Core should detail the short and long term management of the Program such as: communication, group meetings, sharing and transmission of information and reagents, awareness of development of other projects within the program, progress, problems and how will they be addressed, engagement of the Scientific Advisory Panel and NIAID and NICHD, as appropriate, in the group's research activities/meetings, consideration and integration of scientific input/recommendation from the Scientific Advisory Panel and NIAID and NICHD, as appropriate, into scientific direction and decision-making, timely reporting as required in the Terms of Award (provided at the time of award), Health and Human Services, NIH Office of Biotechnology Activities - Recombinant Advisory Committee (OBA-RAC), and FDA as applicable, and other aspects relevant to the cohesiveness and interactive nature of group activities. In addition to the above criteria, in accordance with NIH policy, all applications will also be reviewed with respect to the following: o The reasonableness of the proposed budget and duration in relation to the proposed research AWARD CRITERIA The following will be considered in making funding decisions: quality of the proposed project as determined by peer review, program balance among research areas of the announcement, balance of preclinical and clinical studies, and availability of funds. INQUIRIES Written and telephone inquiries are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Requests for the NIAID brochure INSTRUCTIONS FOR APPLICATIONS FOR MULTI-PROJECT AWARDS as well as inquiries regarding programmatic (research scope, eligibility and responsiveness) issues may be directed to: Roberta Black, Ph.D. Division of AIDS National Institute of Allergy and Infectious Diseases Room 4110, MSC-7628 6700-B Rockledge Drive Bethesda, MD 20892-7628 Telephone: (301) 496-8199 FAX: (301) 402-3684 Email: rblack@niaid.nih.gov Requests for inquiries related to the NICHD contraceptive microbicide research interests may be directed to: Patricia Reichelderfer, Ph.D. Contraception and Reproductive Health Branch (CRH) National Institute of Child Health and Human Development 6100 Executive Boulevard, Room 8B13G, MSC 7510 Bethesda, MD 20892-7510 Telephone: (301) 496-1661 FAX: (301) 480-1972 Email: pr20f@nih.gov Direct inquiries regarding review issues to: Vassil St. Georgiev, Ph.D. Division of Extramural Activities National Institute of Allergy and Infectious Diseases Room 2102, MSC-7616 6700-B Rockledge Drive Bethesda, MD 20892-7616 Telephone: (301) 496-8206 FAX: (301) 402-2638 Email: vg8q@nih.gov Direct inquiries regarding fiscal matters to: Ms. Celeste Kerner Division of Extramural Activities National Institute of Allergy and Infectious Diseases Room 2248, MSC-7614 6700-B Rockledge Drive Bethesda, MD 20892-7614 Telephone: (301) 402-6213 FAX: (301) 480-3780 Email: ck103k@nih.gov AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.856 and 93.864. Awards are made under authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and administered under NIH grants policies and Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. The PHS strongly encourages all grant and contract recipients to provide a smoke-free workplace and promote the non-use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.


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NIH Funding Opportunities and Notices



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