Full Text AI-92-15 NATIONAL COOPERATIVE DRUG DISCOVERY GROUPS FOR THE TREATMENT OF OPPORTUNISTIC INFECTIONS ASSOCIATED WITH ACQUIRED IMMUNODEFICIENCY SYNDROME NIH GUIDE, Volume 21, Number 38, October 23, 1992 RFA: AI-92-15 P.T. 34 Keywords: AIDS Inhibitors Drug Design Pharmaceuticals Biotechnology Drug Resistance+ National Institute of Allergy and Infectious Diseases Letter of Intent Receipt Date: January 15, 1993 Application Receipt Date: March 10, 1993 PURPOSE The 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). The purpose of this Request for Applications (RFA) is to invite applications aimed at the discovery of new, more effective, selective, and diverse therapeutic agents to treat AIDS-associated opportunistic infections (OIs) caused by Mycobacterium tuberculosis, Mycobacterium avium, Cryptosporidium parvum, Toxoplasma gondii, Cryptococcus neoformans, Pneumocystis carinii, and Candida albicans. Applications that include research projects or core components from the private sector (e.g., pharmaceutical, chemical, or biotechnological companies) are encouraged. Organisms associated with additional OIs have not been included in this RFA reissuance in order to achieve programmatic balance among existing NCDDG-OI Groups. Investigators pursuing similar studies of other OIs are encouraged to apply through existing research support mechanisms. Research in the following areas is needed to provide the foundation for improvements in therapeutics for the OIs: selective drug targeting; unique metabolic activities for drug targeting; structure-function properties of microbial proteins; biochemistry and molecular mechanisms of OI-host interactions; improved culture methods for conducting metabolic studies on parasite-host interactions; inhibitors of enzymatic and regulatory functions, and of biochemical pathways; mechanisms of drug resistance; and discovery and biochemical characterization of promising natural products or synthetic chemical compounds. 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 drug discovery for the OIs associated with 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, 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 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 Awards will be made as Cooperative Agreements (U01s). The NIAID, in awarding a Cooperative Agreement, anticipates substantial programmatic staff involvement during performance of the award. The nature of NIAID staff participation is described in SPECIAL REQUIREMENTS - Terms of Award. 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. There is no intent, real or implied, for NIH staff to direct Group activities or to limit the freedom of investigators. 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. 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 making available to the Group biological materials for testing, by accessing appropriate data bases, by providing ancillary testing and other resources available under existing contracts. The interaction of academic and non-profit research institutions with commercial organizations and Government is strongly encouraged and is expected to favor expeditious discovery and preclinical development of agents active against OIs in AIDS patients and to facilitate their subsequent development for clinical trials. Under the Cooperative Agreement, a negotiated partner relationship between the recipient of the award and the NIAID exists in which the Group is responsive to the requirements and conditions set forth in this RFA. Specifically, the Principal Investigator defines the details for the project within the guidelines of the RFA, retains primary responsibility for the performance of the scientific activity, and agrees to accept close assistance in coordination, cooperation, and participation of NIAID staff in all aspects of scientific and technical management of the project in accordance with the terms formally and mutually agreed upon prior to the award. It is presently envisioned that the NIAID will be actively engaged in the coordination of scientific-programmatic components consisting of: o Cooperative participation in data analysis and reporting. o Prior approval of changes of key personnel including the Principal Investigator or Project Leaders. o Retention of the option to withhold support if the Principal Investigator or a Project Leader withdraws from the Group and a suitable replacement of key personnel is not obtained. All policies and requirements that govern the grant program of the Public Health Service and the National Institutes of Health (NIH) apply. FUNDS AVAILABLE The NIAID has set aside $3.5 million for the initial year's funding of this RFA. The amount spent will be dependent on the continuing availability of funds for this purpose and the quality and diversity of approved applications. Funding of five to seven awards is anticipated. It is anticipated that no more than one Group each will be funded for drug discovery against M. tuberculosis, T. gondii, P. carinii, C. parvum, M. avium, C. neoformans, and C. albicans as a result of this RFA. Applications focusing on C. albicans must study novel drug targets; further study of triazoles or polyene antibiotics will not be supported. Awards are subject to a first year limit of $650,000 in total costs (direct plus indirect costs). Subsequent years will be funded at a level no greater than the first year plus four percent. Applications with budgets in excess of $650,000 total (direct and indirect) costs will be returned without review. Funding duration will be three years for new applications and up to four years for competitive renewal applications. The anticipated starting dates for the initial annual periods will be December 1993. Previously funded NCDDG-OIs may compete for renewal or for supplemental support under this RFA. The NIAID plans to continue its support of the National Cooperative Drug Discovery Group program through RFA-initiated competitive renewals and new awards. Reissuance of this initiative in future years is anticipated but not certain. Although this program is provided for in the financial plans of NIAID, the award of Cooperative Agreements pursuant to this RFA is also contingent upon the continuing availability of funds for this purpose. RESEARCH OBJECTIVES Research Goals and Objectives of the NCDDG-OI Program The goals of the National Cooperative Drug Discovery Groups for the Treatment of Opportunistic Infections are: o The conceptualization, discovery, and preclinical development of drugs and strategies designed to effectively treat OIs in individuals infected with HIV. o The conduct of biological, biochemical, and pharmacological studies leading to selection of potential therapies. o The recommendation of therapies, entities or strategies for development in clinical trials. Applications for an NCDDG-OI should stress creative approaches to the discovery of effective therapies to treat opportunistic infections and should emphasize the following: o Specific objectives of the proposed NCDDG-OI. o Research rationale and approaches to the realization of objectives for proposed studies. o The scientific and technical expertise of the Principal Investigator and Project Leaders and the leadership ability of the Principal Investigator. The Group's objectives and goals should be relevant and compatible with NIAID program's missions and directions as stated in this RFA. Background and Summary Acquired Immunodeficiency Syndrome (AIDS) is a disease that destroys host immunological defenses against a variety of infections. As of June 30, 1992, 230,179 cases of AIDS had been reported to the Centers for Disease Control (CDC) and more than 152,153 (66.1 percent) 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 AIDS patients and are the principal reasons for hospitalization. Individuals infected with HIV are susceptible to a range of protozoal, fungal, viral, and bacterial infections. The actual incidence of these OIs over the lifetime of HIV-infected individuals far exceeds AIDS-defining statistics collected by the CDC, although medical history information on specific infections is not known with precision. Pneumocystis carinii pneumonia (PCP) is the most common opportunistic infection reported to the CDC for new cases of AIDS (approximately 50 percent of cases in 1990). Relapses of PCP and other opportunistic infections frequently occur later in the course of HIV infection concomitant with profound depletion of CD4+ T-lymphocytes. It is estimated that more than 50 percent of AIDS patients will have become massively infected with Mycobacterium avium at the time of death. Available drugs to treat these opportunistic infections have limited value because toxicity and other adverse reactions frequently occur in people with AIDS. Prolonged immunosuppression requires prolonged treatment and prophylaxis regimens which are often costly. There are no therapies proven effective for C. parvum and M. avium infections, and limited treatment options are available for infections caused by T. gondii, M. tuberculosis, P. carinii, C. neoformans, and C. albicans. Combined infection with HIV and M. tuberculosis have contributed to a public health crisis in many areas of the United States 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. Seven NCDDG-OIs were awarded in 1990, four were awarded in 1991, and four more are anticipated to be awarded in 1992. Five Groups are eligible for re-competition under this RFA. Within the currently funded NCDDG-OI program, the following approaches are presently being pursued for each organism: Pneumocystis carinii - cloning and expression of folate pathway genes, synthesis of anti-folate compounds, molecular modelling of chemical structures to inhibit enzymes of folate metabolism, lipid uptake and metabolism, and development of in vitro culture systems. Toxoplasma gondii - molecular biology, glycolytic enzymes, arprinocid analogs, purine salvage enzymes, macrolide transport and activity, animal models. Cryptosporidium - immunotherapy with monoclonal antibodies, interactions with host cells. Mycobacterium avium - cell wall biosynthesis enzymes, gene cloning, animal models, structure-activity relationships of candidate drugs. Candida albicans - inhibitors of protein N-myristoylation, cell wall biosynthesis, topoisomerases. Cryptococcus neoformans - cloning and expression of folate pathway genes, cationic peptides (defensins), interactions with human cells, immunotherapy, pheromones, mannitol metabolism, liposomes. Cytomegalovirus - synthesis and assay of nucleoside analogs, unique chemical classes, heterocyclics, cloning and expressing the UL97 gene product and DNA polymerase. Scientific Scope, Restrictions and Exclusions It is the intention of this RFA to encourage investigators to collaborate in new approaches to drug discovery against the OIs associated with AIDS and to complement and balance the efforts presently being pursued by existing NCDDG-OIs. 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 OIs associated with AIDS. Respondents to this RFA may include: new applications for a maximum period of three years support, competitive renewal applications from existing Groups for up to four years of support, and competitive supplements to currently funded NCDDG-OIs. No clinical trials will be supported under this RFA. Research efforts should be directed towards the discovery and preclinical evaluation of new entities with potential to control infections caused by the following pathogens: M. tuberculosis, T. gondii, C. parvum, P. carinii, M. avium, C. neoformans, and C. albicans (see restrictions below). It is not a requirement of this RFA that a complete development plan for new drugs be included, 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 drug target identification 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 therapies with potential for prophylaxis, practical administration to AIDS patients, and low toxicity. Applications focusing on the biochemical and metabolic activities of these microorganisms as drug targets are strongly encouraged. However, research focusing on anti-folates or sulfonamides for Pneumocystis or Toxoplasma infections or on triazoles or polyene antibiotics for C. albicans will not be supported under this RFA because of advances currently being pursued in this area. Other organisms causing infections which may be associated with AIDS have been excluded from this RFA due to competing priorities and in order to achieve programmatic balance within the NCDDG-OI program. 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, and R43 (Small Business Innovative Research Program) mechanisms. Research considered responsive to this RFA may include, but is not necessarily restricted to, the following: o Studies designed to discover therapeutic agents capable of producing selectively lethal effects on opportunistic infectious pathogens. o Studies to identify and characterize molecular and metabolic targets with potential for design of new therapeutic candidates and for development of practical prophylaxis agents. o Design of selective inhibitors using molecular modelling. o Identification of selected molecular functions which may be used to establish in vitro assay systems for discovery of active agents. o Improvements in in vitro culture or animal model systems with potential for acceleration of drug discovery, particularly for M. tuberculosis, Cryptosporidium, Toxoplasma bradyzoites, and Pneumocystis. It is anticipated that no more than one Group each will be supported to pursue drug discovery against M. tuberculosis, T. gondii, P. carinii, C. parvum, M. avium, C. neoformans, and C. albicans as a result of this RFA. Applications focusing on C. albicans must study novel drug targets. 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 will be withheld until compounds generated by the Group are available for animal efficacy studies. Testing of natural products, biologics and/or synthetic compounds must not exceed 25 percent of the total level-of-effort of the Group. Random or large scale screening of compounds will not 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 these developmental tasks. The NIH has a contract program for the preclinical development of compounds for the treatment of AIDS-associated opportunistic infections, including animal models. In addition, the NIAID supports AIDS Clinical Treatment Units (ACTUs) for Phase I, Phase II and Phase III clinical trials. It is envisioned that these ACTU cooperative agreements will be available for clinical studies of treatments discovered under this initiative, upon the recommendation of the NCDDG and concurrence of the AIDS Clinical Drug Development Committee, the Division of AIDS, and the ACTU investigators. DEFINITIONS ADMINISTRATIVE CORE - An administrative facility that provides support for the overall management of the cooperative agreement and services shared by the Group as a whole. The Administrative core will have in its budget travel costs for (1) one required annual Group meeting; (2) the NCDDG-OI annual meeting; and (3) travel expenses for the Scientific Advisor Panel (see below). The Administrative Core will be responsible for allocating required travel expenses to appropriate members of the Group. These travel expenses will be restricted to travel listed above. (For additional details of required travel see SPECIAL REQUIREMENTS - Terms of Award.) ARBITRATION PANEL - A group 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 VIII, "Terms of Award". COOPERATIVE AGREEMENT - An assistance mechanism in which substantial NIAID programmatic involvement with the recipient organization during the performance of the planned activity is anticipated. CORE COMPONENT - Facilities for equipment and services which are shared by two or more projects of the NCDDG-OI. Examples of core components are: biochemical studies, in vitro testing, animal model evaluations, toxicology studies, pharmacology studies, scale-up synthesis of drugs (10 grams or less). 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 same detail as research projects to enable the evaluation of its scientific and technical merit. DISCOVERY - The term "discovery" is used explicitly to limit activities of the NCDDG-OI to preclinical identification, design and development of new entities. 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. A minimum of two laboratory research projects representing diverse scientific disciplines and organizations that join together under a single Principal Investigator and that function as a unit with a common goal: the conceptualization, invention, and evaluation of new entities and strategies for the treatment of OIs. All applications must consist of at least two independent Projects conducted by at least two independent laboratories. For the purpose of this RFA, two (or more) projects within a single company or academic department will not be considered independent. A CORE COMPONENT cannot be used toward fulfillment of the two Projects requirement. NEW 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 OIs in AIDS patients. NIAID NCDDG-OI PROGRAM DIRECTOR - A Senior Scientist of the NIAID extramural staff who coordinates NIAID's participation in the NCDDG-OI program. This responsibility includes: (1) overseeing the entire NCDDG-OI program; (2) assuring that Groups' objectives are consistent with NIAID's mission and goals; (3) assigning Scientific Coordinators to appropriate Groups based on scientific expertise and compatibility with the Group research interests; (4) assuring overall scientific balance among Groups in the NCDDG-OI program; (5) networking and facilitating collaboration between Groups and industry to expedite development of promising anti-OI agents; (6) keeping the NCDDG-OI program current with regard to scientific developments and breakthroughs; and (7) identifying research gaps not adequately pursued. 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, based on his/hers scientific expertise, interests and compatibility with the Group's areas of research, is assigned to the Group by the NCDDG-OI program director, and is the immediate contact person for the Group. PRINCIPAL INVESTIGATOR - The person who assembles the NCDDG-OI, assembles a single application with the information provided by the Project Leaders and submits the application in response to this RFA and who is responsible for the performance of the Group as a whole and each of the Project Leaders. The Principal Investigator is strongly encouraged to lead one of the research projects of the Group and is expected to coordinate Group activities scientifically and administratively. The Principal Investigator's (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. PROJECT LEADER - The leader of one of the scientific research projects of the NCDDG-OI. 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 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. The Principal Investigator will invite the Scientific Coordinator to all meetings of the Panel, which may be combined with Group meetings. 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 six months of funding. The Panel will provide the Principal Investigator and the NIAID Scientific Coordinator with a comprehensive written review of Group's activity in years one, two, three, (and four, if applicable) of funding. These reviews will encompass timeliness of progress in individual projects relative to original projections; progress relative to Group's objectives and needs; continued relevance of a given project to Group's function; continued coordination of Group's objectives with the objectives of the NCDDG-OI program; and recommendations for new directions, as appropriate. SPECIAL REQUIREMENTS Composition of an NCDDG-OI The NCDDG-OI will consist of the following: o A Principal Investigator. o Project Leaders, each heading an independent research project. The research projects will utilize diverse scientific disciplines or alternative disciplines that are appropriate to the realization of Group objectives (e.g., microbiology, structural biology, biophysics, biochemistry, medicinal chemistry, organic chemistry, pharmacology, toxicology, drug delivery). Interdisciplinary projects are encouraged. o A Scientific Coordinator designated from the NIAID extramural staff. o An Administrative Core component that must provide for required travel and may also include support for the costs of administration, purchasing and secretarial services. o A Scientific Advisors Panel to be designated within six months of funding (see Definitions: Scientific Advirose Panel). This Panel will meet with the Group, evaluate and advise on the Group's progress, future goals, strategies and new directions, as appropriate. Panel members will not be affiliated with any of the institutions comprising the Group. o OPTIONAL - Core components that provide laboratory facilities, equipment and services to be shared by two or more projects. Items described above that are included in the institution's indirect cost rate are subject to negotiations, based on their applicability as direct or indirect charges. The Principal Investigator, in addition to providing scientific and administrative leadership, is strongly encouraged to have a research project. Project Leaders will be directly responsible to the Principal Investigator. The formation of the Group, the application in response to this RFA, the overall management of the Group, and the allocation of funds to the various laboratory projects will be the responsibility of the Principal Investigator and the Principal Investigator's institution in accordance with PHS policies. The composition of the Group and its research projects should depend on the talents required to accomplish its scientific and technical objectives as perceived by the Principal Investigator and Project Leaders. The major consideration in structuring an NCDDG-OI should be the mobilization of maximum intellectual talent and the ability to carry out the proposed research. An individual scientist may be proposed as a Project Leader by more than one applicant as part of a CORE COMPONENT. Project Leaders who do not have a core function will not be supported by more than one Cooperative Agreement awarded under this RFA unless the research is clearly delineated in separate NCDDG-OI applications. Individuals currently supported under an existing NCDDG-OI or other NCDDG programs (e.g., NCDDG-HIV) may be funded under this RFA provided there is no scientific or budgetary overlap in funded activities. More than one Project Leader of an NCDDG-OI may be enlisted from a single institution but at least two Projects Leaders must be from independent laboratories. However, the varied talents and commitment required for effective drug discovery are not usually present in most single institutions and it is anticipated that the Project Leaders within a Group will be "enlisted" from, or associated with several institutions. For the purpose of this RFA, two (or more) projects within a single company or academic department will not be considered independent. A minimum of two but no maximum number of research projects per Group is stipulated. However, the Principal Investigator could experience difficulty in providing the desirable level of guidance and Project Leaders might communicate and collaborate less efficiently if the Group were to contain more than five or six research projects. A CORE COMPONENT cannot be considered toward fulfilling the required two research projects per Group. In forming Groups, Principal Investigators should remain cognizant of the need for communication, including regular meetings of the members. While it is not a requirement of this RFA, the formation of Groups on a geographically regional basis may be advantageous. This is a particularly important factor to be considered by applicants from outside the United States or if the applicant proposes laboratory projects in foreign countries. An NCDDG is encouraged to include scientists from academia, non-profit institutions, and/or commercial organizations. The active participation of industry is encouraged because it will allow this sector of the scientific community to contribute its intellectual and material resources and will favor expeditious development of effective anti-OI therapies. Patent coverage Since the discovery of agents active against OIs in AIDS patients 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 multiple institutions involved, 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. All Group members can 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 and exclusive licensing arrangements. Applicants are encouraged to develop an arrangement that is most suitable for their own particular circumstances. The NIAID will not be a partner in any patents or royalties ensuing from this research. The patent agreement, signed and dated by the organizational officials authorized to enter into patent arrangements for each Group member and member institution, must be sent before the application deadline to: Dr. Barbara Laughon Developmental Therapeutics Branch Division of AIDS National Institute of Allergy and Infectious Diseases Solar Building Room 2C10 Bethesda, MD 20892 For express mail or courier services, the address is 6003 Executive Boulevard, Rockville, MD 20852. Federal regulation clause 37 CFR 401 and HHS Inventions regulations at 45 CFR Parts 6 and 8 require that the NIH be informed of inventions and licensing occurring under NIH funded research. Invention and licensing reports must be submitted to the Extramural Invention Reports Office, Office of Extramural Research, NIH, Building 31, Room 5B41, Bethesda, MD 20892, with a copy to Dr. Barbara Laughon at the address listed above. Terms of Award: Awardee Rights and Responsibilities and 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 component awarding the Cooperative Agreement anticipates substantial programmatic involvement during performance of the project. However, the applying Group must define its objectives and approaches in accord with its own interests and perceptions of novel and exploitable approaches to the discovery of effective anti-AIDS treatment and must develop the details of the research design following the guidance given in this RFA. It is the primary responsibility of the Principal Investigator to clearly state 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. The NIAID will participate as a member of the Group and will be represented by a Scientific Coordinator or the NCDDG-OI program director. The Coordinator will 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. The specific Terms of Award are detailed below and will be presented in the Notice of Award. Failure to abide by these Terms of Award may result in withholding of funds by the NIAID. Awardee Rights and Responsibilities o The Principal Investigator, Project Leaders, and the NIAID Scientific Coordinator will meet periodically to review progress, plan and design research activities, and establish priorities. The frequency of meetings (not less than two per year) shall be determined by the Principal Investigator who will be responsible for scheduling the time and place (generally at one of the performance sites), notifying the Scientific Coordinator at least thirty days prior to the meeting date. The NIAID Scientific Coordinator will participate but not chair Group meetings. The Principal Investigator will prepare concise (2-3 pages) minutes or summaries of the Group meetings that will be delivered to the members of the Group including the Scientific Coordinator within thirty days following the meeting. Funds for attending the one required Group meeting must be included in the Administrative Core budget for Project and Core Leaders, and will be restricted solely for this purpose. The application should also include plans for scheduling Group meetings, notifying Group members including the NIAID Scientific Coordinator, and documenting and disseminating Group meeting proceedings. o In addition to these two meetings, one meeting each year will be held at a site designated by the NIAID during which all Principal Investigators and Project Leaders will present significant findings in symposium format. The NCDDG-OI annual meeting is one of the central points for information flow among the Principal Investigators, Project Leaders, NCDDG-OI program director, the private sector, other drug development concerns, and the NIAID. The program director consults with the Groups' key personnel in formulating the overall agenda, selecting session Chairs and in identifying key topics for discussion. Session Chairs select the workshop participants who constitute the bulk of invited speakers. This forum is central for cross fertilization of ideas, integration of unique anti-OI strategies, and a critical source for updating NIAID and keeping it abreast of scientific and technological innovation toward the discovery of new anti-infective modalities. 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. It is expected that selected NIH staff, members of established committees and advisory boards, and others active in the process of discovery and development of therapies for AIDS will be invited to this meeting. The Principal Investigator will have control over the data and results presented by the Group. In addition to the two Group meetings discussed above, funds for attending the NCDDG-OI annual meeting must be included in the Administrative Core budget for the Principal Investigator, and Project and Core Leaders. These travel funds will be restricted for use to attend the annual NCDDG-OI meeting. Invited NCDDG-OI speakers will be expected to utilize budgeted travel funds to cover expenses incurred while attending the annual meeting. Funds to cover operating costs of the NCDDG-OI annual meeting will be contributed by one or more Groups. The NIAID will provide administrative supplements for this purpose, as needed. o Groups will designate a Scientific Advisors Panel within six months of funding. The Principal Investigator will convene a meeting, or meetings, of the Group with the Panel each year which may be in conjunction with the required Group meetings. 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 and the NIAID Scientific Coordinator with a comprehensive written review of the Group's activity each year. Members of the Panel will not be affiliated with any of the institutions comprising the Group. Funds to cover expenses incurred by the Panel should be included in the Administrative Core component of the application and will be restricted solely for this purpose. o A critical determinant of the Group's success will be the degree of communication among its members. Therefore, additional informal meetings among all participants as well as regular telephone and written communication will be important. o The Principal Investigator will be responsible for the timely submission 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 Leaders 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. o Each Progress Report should include 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. o Publication or oral presentations of work done under this Agreement is the responsibility of the Principal Investigator and appropriate Project Leaders. o 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 part by the NCDDG-OI program, cooperative agreement number U01-AI-12345, NIAID. NIAID Assistance in Implementation and Management of Research Activities o The NIAID Scientific Coordinator may assist the Group or other individual members in research planning, particularly with respect to (a) reduction of duplication of efforts conducted in other extramural projects; (b) provision of needed resources and information that may not be otherwise available to the Group; and (c) provision of data from testing conducted in resource contract laboratories. o 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 following is a list of some resources that may be available from the NIAID. These resources are intended for initial studies and may not be available on a continual basis: (a) reference compounds for standardization of test systems, as analytical standards and for related purposes; (b) materials for biological testing; (c) biochemical and cell-based laboratory testing capacity. Whenever appropriate and possible, current contract-based preclinical/therapy-related testing program will be used. On occasions, and under mutual agreements, NIAID will arrange for limited preclinical testing at other NCDDG-OI sites. The Groups are expected to provide sufficient test material for requested testing; (d) testing in appropriate animal model(s) when the occasional need arises in Groups whose main research activities do not require these resources on a regular basis. Groups whose experimental approach involves studies that require testing in animals on a regular basis must budget for costs to be paid from award funding. Requests for testing in NIAID's animal model program are contingent upon NIAID's recommendation and prioritization; (e) searches of NIAID's computer files of chemical structures and biological activity, if requests for such searches are sufficiently focused to avoid excessive costs and time. Information given to an NCDDG-OI will be restricted by the standard confidentiality agreements between the Government and suppliers of test materials to the Government; (f) computer processing and statistical evaluations if costs and time are not excessive; (g) chemical re-synthesis, analysis, formulation, and toxicology testing through existing pre-clinical development contracts (contingent upon NIAID's recommendation and prioritization); (h) 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. 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. o 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 has supplied the compounds for testing through the NIAID. o During performance of the award the NIAID Scientific Coordinator will provide appropriate assistance by participating in the design of Group activities; advising in the selection of sources or resources, replacement of staff, etc.; 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 the NIAID will be to facilitate rather than to direct the activities. It is anticipated that decisions in all activities outlined below will be reached by consensus of the Group and that the NIAID Scientific Coordinator 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. 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. o 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. Subsequent developmental work through private resources is encouraged. Alternatively, the Group may recommend that development be sponsored by the NIAID. In the latter case, it will be necessary for the Principal Investigator, appropriate Project Leaders and the NIAID Scientific Coordinator to collaborate in the analysis, summarization, preparation, and presentation of data to the appropriate NIAID staff and its advisory committees, such as the Animal Model Operating Committee or the AIDS Clinical Drug Development Committee. o The 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 the NIAID and may be augmented with test results from other Government sponsored projects prior to submission to the appropriate regulatory agency. o The NIAID will have access to data generated under this Cooperative Agreement and may periodically review the data and progress reports. Information obtained from the data may be used by the Scientific Coordinator for the preparation of internal reports on the Group's activities. However, the applicant will retain custody of and rights to the data, and timely publication of major findings is encouraged. Inasmuch as certain activities under "Terms of Award: NIAID Assistance in Implementation and Management of Research Activities" 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), the 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. The special "Terms of Award: NIAID Assistance in Implementation and Management of Research Activities" described in this section 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. NOTE: Failure to abide by any of the Terms of Award stipulated in this RFA may result in the withholding of funds by the NIAID until compliance with the Terms is restored. Minimum Requirements for Application Applicants seeking funding as a National Cooperative Drug Discovery Group for the Treatment of Opportunistic Infections must meet the following requirements. The application must be from a Group and must: Name a single Principal Investigator who is an employee of the applicant institution and who will be responsible for the application, for Group research activities, and for the support of Group activities through a Central Operations Office. Identify the single applicant organization (awardee institution) that will provide the Central Operations Office and be legally and financially responsible and be accountable for the use and disposition of funds awarded on the basis of this RFA; show availability of personnel and facilities capable of performing and supporting the administrative functions of the NCDDG-OI. 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 the proposed work. 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 that 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, Developmental Therapeutics Branch, Division of AIDS, NIAID, Solar Building, Bethesda Maryland, 20892 in advance of the application receipt date (see Patent Coverage above). Provide a clear, concise plan in narrative and diagrammatic form that depicts the interrelationships among the members of the Group and the contribution of each to fulfillment of Group objectives; provide an organizational chart of the Group showing the name, organization, and scientific discipline of the Principal Investigator and Project Leaders; provide an organizational chart for each laboratory project within the Group showing relationships among the key personnel. Provide a plan to assure the maintenance of close collaboration and effective communication among members of the Group which will include letters of commitment to this plan and a letter accepting the participation of the NIAID Scientific Coordinator, defined under Terms of Awards. Provide an introductory section that states the rationale of the research proposed in each project describing how it relates to drug discovery and the anticipated therapeutic approach which may result (see APPLICATION PROCEDURES). 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; show that total personnel of the Group are sufficient in quality and quantity to assure successful conduct of the proposed research. Other activities which are essential to maintaining or achieving the objectives of the stated research projects (e.g., large scale production of reagents, animal maintenance) should be included as subcontracts under the budget for core resources. Demonstrate that each component laboratory project, core facilities, and the Group as a whole have available the facilities required for conduct of the proposed research; demonstrate that appropriate biohazard facilities and safety procedures are in place for activities involving OIs and other pathogens and pathogen-producing cell lines as outlined in The Federal Register, Volume 49, Number 201, Tuesday, October 16, 1984, p. 40556; include a description of the Institutional Safety Guidelines and approval procedures for each proposed laboratory project. NOTE: The Principal Investigator will provide a narrative, supported by diagrammatic presentation(s) as needed, addressing the points raised above. This description should clearly demonstrate the interactive, cooperative, integrated and interdependent nature of each proposed project and core to the Group activities as a whole. The narrative is to be included under the Administrative Core: it will serve as one of the criteria used by the peer review group to evaluate and rate the ability of the Principal Investigator to assemble a comprehensive, interactive Group. 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, together with a rationale for its choice. 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 t 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 rational 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 limited to clinical studies. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissue cannot be identified or linked to individuals are excluded from the clinical research requirements. 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. In such a case, 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 January 15, 1993, a letter of intent that includes (maximum of two pages): o A descriptive title of the overall proposed research. o The name, address, telephone number, and institution of the Principal Investigator. o Names of prospective project leaders and other key investigators and their respective responsibilities. o Title, project leader, and institution for each component research project and brief descriptions of the proposed projects. o 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 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 process. The letter of intent is to be sent to: Barbara Laughon, Ph.D. Developmental Therapeutics Branch National Institute of Allergy and Infectious Diseases Solar Building, Room 2C10 Bethesda, MD 20892 Telephone: (301) 496-8197 FAX: (301) 402-3211 Applicants who use express mail or courier services are advised to follow the carrier's requirements for showing a street address. The address of the Solar Building is 6003 Executive Boulevard, Rockville, MD 20852. APPLICATION PROCEDURES It is important to follow the instructions in this RFA for preparing the application. Failure to do so may result in an application with insufficient information for appropriate scientific review. The prospective applicant is also urged to carefully read the sample application that accompanies this RFA. If additional information on how to prepare a multi-project application is required, the applicant may request the NIAID Information Brochure on Program Project and Center Grants, available from: Scientific Review Branch, DEA National Institute of Allergy and Infectious Diseases Solar Building Room 4C19 6003 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-0123 Questions concerning review requirements of a complete application may be directed to Dr. Diane Tingley, (301) 496-0818. Questions regarding responsiveness to the RFA may be directed to Dr. Barbara Laughon, (301) 496-8197. Receipt Date The deadline for receipt of applications is March 10, 1993. Applications received after this date will be considered as not responsive to this RFA and will be returned without review. General o 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 institution sponsored research offices and from the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone 301-496-7441. o Submit a signed, typewritten original of the application, including the Checklist, and three signed, exact, single-sided photocopies, in one package to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** 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. o To assure 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- 92-15) typed on item 2a of the face page of the application form. o Submit two exact copies of your application directly to: Diane Tingley, Ph.D. Chief, AIDS Scientific Review Section Scientific Review Branch, 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 Applicants who use express mail or a courier service are to use the city and the zip code of Rockville, MD 20852. Organization of Application and Suggested Modifications of form PHS 398 (rev. 9/91) This RFA requires the submission of a single application for the proposed National Cooperative Drug Discovery Group. Because of the multi-institutional nature of a NCDDG-OI and the special requirements in this RFA, additional instructions regarding format are contained in the NIAID Information Brochure on Program Project and Center Grants. The special requirements of this RFA will also necessitate the following modification. The Introductory Section should apply to the proposed NCDDG-OI as a whole with respect to goals, objectives, and overall research plan. The Introductory Section, not to exceed two pages, should contain any additional information about the proposed Principal Investigator or his/her institution as evidence of capability to carry out the scientific and administrative duties required in this RFA and the functions of the Central Operations Office. In addition, the Introductory Section must include the following elements to be considered responsive to minimum requirements o The name of a single Principal Investigator in accordance with the Minimum Requirements for Application in this RFA. o The name of the single applicant organization that will provide and operate the Central Operations Office in accordance with the Minimum Requirements for Application in this RFA. o A statement assuring adequate patent coverage of new inventions that may be issued as a result of Government funding in accordance with Patent Coverage. o A statement of acceptance of the provisions of the Terms of Award: Awardee Rights and Responsibilities; Nature of Participation of NIAID Staff. o A description of the interrelationships among members of the Group and organizational charts in accordance with the section on Composition of an NCDDG-OI. o A plan to assure maintenance of close collaboration and effective communication among members of the Group in accordance with the Minimum Requirements for Application in this RFA. o A rationale for the drug discovery approach(es) proposed and discussion of therapeutic approaches that may derive from the research projects. REVIEW CONSIDERATIONS 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) application kit will be judged non-responsive and will be returned to the applicant. 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 $650,000 total (direct and indirect) first year costs will be returned without review. Those applications that are complete and responsive may be subjected to a triage by an NIAID peer review group to determine their scientific merit relative to 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 judged to be competitive for award will be further reviewed for scientific and technical merit by a Review Committee convened by the Division of Extramural Activities, NIAID during June 1993. A second level of review will be provided by the National Advisory Allergy and Infectious Diseases Council. In the event of multiple highly qualified proposals, final funding recommendations will be based on highest Program priorities. REVIEW PROCEDURES AND CRITERIA Initial scientific review of applications will be conducted by the Scientific Review Branch, DEA, NIAID, by an appropriate committee. The application must be directed towards the attainment of the stated programmatic goals (see Research Goals and Objectives). The following factors will be considered in the scientific and technical review of the application: o Relevance of applicant's (Group) objectives to the discovery of new entities and strategies for the treatment of OIs in AIDS patients. o Scientific and technical significance, originality and uniqueness of proposed research. o Scientific and technical merit of research projects and core components for realization of drug discovery objectives. o Likelihood that new potential therapies will be identified during the course of the proposed study. o Specific competencies of the Principal Investigator and Project Leaders to conduct the proposed work: research experience, commitment, and time availability of Principal Investigator, Project Leaders, and other key personnel. While there is no maximum 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 (time) effort by the Principal Investigator and each Project Leader should be devoted to the study, unless there is compelling evidence to the contrary. o Accomplishments of the Group to date (for renewal and supplemental grant applications). o Technical merit of proposed methods for producing or obtaining test materials and for their evaluation. o Technical sufficiency of methods for evaluation of new discoveries, laboratory test systems, models, etc. o Administrative experience and competence of Principal Investigator in the development, implementation, and management of comprehensive research programs. o 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 as stipulated in Minimum Requirements for Application. 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. o Commitment to accept the assistance of NIAID staff in accordance with the guidelines outlined under Terms of Award: NIAID Assistance in Implementation and Management of Research Activities. o Mechanism for selecting and replacing key professional or technical personnel using the framework of the RFA. o Conformance to Minimum Requirements for Application. o Reasonableness of cost. 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 score each project and core within the application individually, followed by scoring of the application as a whole. INQUIRIES It is essential that prospective applicants obtain a copy of the RFA before preparing an application. Written and telephone requests for the RFA and the opportunity to clarify issues or questions from potential applicants are welcome. Direct requests for the RFA and inquiries regarding programmatic or scientific issues to: Dr. Barbara Laughon Developmental Therapeutics Branch Division of AIDS National Institute of Allergy and Infectious Diseases Solar Building, Room 2C10 Bethesda, MD 20892 Telephone: (301) 496-8197 FAX: (301) 402-3211 Inquiries regarding matters pertaining to the review of this application may be addressed to: Diane Tingley, Ph.D. Chief, AIDS Scientific Review Section Scientific Review Branch 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 Inquiries regarding fiscal matters may be addressed to: Jane Unsworth Chief, AIDS Grants Management Section Grants Management Branch Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4B22 Bethesda, MD 20892 Telephone: (301) 496-7075 FAX: (301) 480-3780 A separate request for Applications for the National Cooperative Drug Discovery Groups for the Treatment of Human Immunodeficiency Virus Infection (RFA AI-92-16) has been issued. To receive a copy, please contact Dr. Nava Sarver, Targeted Drug Discovery Section, Developmental Therapeutics Branch, Basic Research and Development Program, Division of AIDS, NIAID, 6003 Executive Boulevard, Bethesda, MD 20892, telephone: (301) 496-8197. AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance Nos. 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 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. .
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