Full Text AI-94-014 NATIONAL COOPERATIVE DRUG DISCOVERY GROUPS FOR THE TREATMENT OF OPPORTUNISTIC INFECTIONS ASSOCIATED WITH TUBERCULOSIS IN AIDS NIH GUIDE, Volume 23, Number 12, March 25, 1994 RFA: AI-94-014 P.T. Keywords: National Institute of Allergy and Infectious Diseases Letter of Intent Receipt Date: July 15, 1994 Application Receipt Date: August 11, 1994 PURPOSE The National Institute of Allergy and Infectious Diseases (NIAID) invites applications for the establishment of National Cooperative Drug Discovery Groups for the Treatment of Opportunistic Infections and Tuberculosis Associated with Acquired Immunodeficiency Syndrome (NCDDG-OI). The Developmental Therapeutics Branch (DTB) of the Division of AIDS (DAIDS), NIAID, invites applications focused on the discovery and rational design of new therapies with potential to treat and/or prevent specific opportunistic infections (OIs) in individuals infected with HIV. Opportunistic pathogens targeted in this RFA are human cytomegalovirus (HCMV), Mycobacterium tuberculosis, Mycobacterium avium, Pneumocystis carinii, Cryptosporidium parvum, Toxoplasma gondii, the microsporidia (e.g., Enterocytozoon bieneusi, Septata intestinalis), and Cryptococcus neoformans. Research activities should be directed toward discovery of selective drugs or molecular strategies that are lethal to the pathogen with minimal toxicity for the host. Multidisciplinary approaches by scientists from consortia of academic, non-profit research, and commercial organizations, with the assistance of the NIAID, will be necessary to effectively accelerate discovery of new therapeutics for OIs associated with AIDS. Applications that include research projects or core components from the private sector (e.g., pharmaceutical, chemical or biotechnological companies) are encouraged. No clinical trials will be supported under this RFA. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This Request for Applications (RFA), National Cooperative Drug Discovery Groups for the Treatment of Opportunistic Infections Associated with AIDS (NCDDG-OI) Including Tuberculosis, is related to the priority area of HIV infection. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic for-profit and non-profit organizations, public and private organizations such as universities, colleges, hospitals, laboratories, units of State or local government, and eligible agencies of the Federal government. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT The administrative and funding mechanism to be used to undertake this program will be the Cooperative Agreement (U19), an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH scientific and/or programmatic involvement with the awardee is anticipated during the performance of the activity. Essential elements of the U19 mechanism include: (1) a minimum of three inter-related research projects organized around a central theme; (2) collaborative efforts and interaction among independent projects and their investigators to achieve a common goal; (3) a single Principal Investigator who will be scientifically and financially responsible for the use and disposition of funds awarded; and (4) support provided, as necessary, for "Core" resources or facilities, each of which is expected to be utilized by at least two research projects in order to facilitate the research effort. Under the cooperative agreement, the NIH purpose is to support and/or stimulate the recipient's activity by involvement in and otherwise working jointly with the award recipient in a partner role, but it is not to assume direction, prime responsibility, or a dominant role in the activity. Details of the responsibilities, relationships, and governance of a study funded under cooperative agreement(s) are discussed later in this document under the section "Terms and Conditions of Award." The total project period for applications submitted in response to the present RFA may not exceed four years. The anticipated award date is April/May 1995. At this time, the NIAID has not determined whether or how this solicitation will be continued beyond the present RFA. FUNDS AVAILABLE The estimated total funds (direct and indirect costs) available for the first year of support for awards under this RFA reissuance will be $5.6 million; estimated total project costs (direct and indirect) over the four-year period will be $23.8 million. Applications received with budgets in excess of $700,000 first-year total costs will be returned without review. In Fiscal Year 1995, the NIAID plans to fund approximately 7 to 9 applications, anticipating at least one group each for drug discovery against these high priority OIs: HCMV, Mycobacterium tuberculosis, Mycobacterium avium, Pneumocystis carinii, Cryptosporidium parvum, Toxoplasma gondii, the microsporidia (e.g., Enterocytozoon bieneusi, Septata intestinalis), and Cryptococcus neoformans. It is anticipated that ten existing NCDDG-OI Groups targeting antimycobacterial, antifungal, anti-toxoplasma, and anti-HCMV drugs will be eligible to recompete. Although this program is provided for in the financial plans of the NIAID, awards pursuant to this RFA are contingent upon the availability of funds for this purpose. The usual PHS policies governing grant administration and management will apply. This level of support is dependent on the receipt of a sufficient number of applications of high scientific merit. Funding beyond the first and subsequent years of the grant will be contingent upon satisfactory progress during the preceding years and availability of funds. RESEARCH OBJECTIVES Background The principal causes of morbidity and mortality in AIDS are opportunistic infections (OIs). Although HIV causes AIDS and is responsible for the progressive immunological deterioration seen in this disease, the OIs account for the vast majority of all AIDS-related deaths as well as diminishing quality of life. OIs are also the principal reasons for hospitalization. Individuals infected with HIV are susceptible to a range of viral, bacterial, protozoal, and fungal infections and the pathological consequences are retinitis (HCMV), tuberculosis (Mycobacterium tuberculosis), disseminated nontuberculosis mycobacterial disease (Mycobacterium avium), pulmonary disease (Pneumocystis carinii), encephalitis (Toxoplasma gondii), diarrhea (Cryptosporidium parvum, microsporidia), and meningitis (Cryptococcus neoformans). Available drugs to treat opportunistic infections (including tuberculosis) do not exhibit adequate potency to completely eradicate infecting organisms, and prolonged HIV-mediated immunosuppression requires prolonged treatment schedules and prophylaxis regimens against recurrence of infections. Overall, the management of OIs in AIDS patients is difficult and complicated due to: (1) simultaneous infections with other OIs; (2) toxicity and adverse side effects of therapeutic agents; (3) long-term drug use leading to patient intolerance or pathogen drug resistance; (4) occurrence of relapses after discontinuation of therapy; and (5) lack of effective therapies for newly emerging OIs. The NCDDG-OI program was launched in 1990 for the purpose of stimulating research for development and commercialization of therapeutic agents targeted against AIDS-associated OIs. The goals of the NCDDG-OI are: (1) the conceptualization, discovery and preclinical development of therapies designed to effectively treat OIs in individuals infected with HIV; (2) the conduct of biological, biochemical, and pharmacological studies leading to selection of potential therapies; and (3) the recommendation of therapies, entities or strategies for development in clinical trials. Objectives and Scope The purpose of this RFA is to foster multi-disciplinary research projects aimed at the discovery and rational design of new therapies against the OIs associated with AIDS. The objective is to stimulate drug discovery through original and innovative research focused on the microbiology, molecular biology, chemistry, computer-assisted drug design, drug delivery vehicles, and animal models that will lead to the identification of new drug targets. Additionally, this RFA will foster the development of improved in vitro assays for drug screening, predicting drug efficacy through animal models, and development of surrogate markers of efficacy to circumvent slow culture of organisms. Ultimately, this research should lead to the development of safe, well-tolerated, and effective new drug therapies for treatment and prophylaxis against the high priority OIs. Research objectives in this RFA reissuance include, but are not necessarily limited to: o the discovery and development of effective therapies to treat high priority opportunistic infections associated with AIDS; o identification and characterization of new molecular targets for exploitation toward selective virucidal, mycobactericidal, parasiticidal, and fungicidal therapeutic agents; o establishment and utilization of in vitro assays for selected molecular targets to identify active compounds and biologicals, and to guide synthesis of new compounds or analogs; o refinement of novel and innovative animal models to evaluate the therapeutic potential of new compounds and to compare efficacy in normal and immunocompromised models; o development of improved methodologies or surrogate markers for assessing therapeutic efficacy in animal models; and o elucidation of mechanisms of drug resistance and study of strategies to overcome such resistance. SPECIAL REQUIREMENTS A. Minimum Requirements for NCDDG-OI Application All applications must consist of at least three interrelated projects focusing on a unifying central theme conducted by at least three independent laboratories. For the purpose of encouraging new collaborations under this RFA, two (or more) projects within a single company will not be considered independent. Similarly, two (or more) projects within the same academic department will not be considered independent. This limitation on the number of independent projects from the same academic or private sector organization is intended to increase the diversity and multi-disciplinary expertise available to the Group from other than the parent institution or organization. Random or large scale screening as well as clinical trials will not be supported under this RFA. A minimum 10 percent (time) effort by the Principal Investigator and each Project Leader should be devoted to the study, unless there are compelling arguments to the contrary. B. Definitions 1. 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. Each group may consist of a number of scientific investigators from academic and/or non-profit research institutions as well as scientists from commercial organizations, performing research on interdependent projects. The minimum requirement is three independent laboratory research projects representing diverse scientific disciplines and organizations, which join together under a Principal Investigator and function as a unit with a common goal. A CORE COMPONENT cannot be used toward fulfillment of the three research projects requirement. 2. NIAID NCDDG-OI PROGRAM DIRECTOR: A Senior Scientist of the NIAID extramural staff who coordinates NIAID's participation in the NCDDG-OI program, oversees the entire NCDDG-OI program, maintains the overall scientific balance in the NCDDG-OI program commensurate with new research and therapeutic findings and emerging research opportunities, and who ensures that the NCDDG-OI program is consistent with NIAID's missions and goals. 3. NIAID SCIENTIFIC COORDINATOR: A Senior Scientist of the NIAID extramural staff who functions as a peer with the Principal Investigator and Project Leaders and who facilitates the partnership relationship between NIAID and each Group. The Scientific Coordinator is the immediate contact person to the Group and is assigned by the NCDDG-OI program director. 4. PRINCIPAL INVESTIGATOR: The person who assembles the NCDDG-OI, who is responsible for the performance of the Group as a whole, and who submits the single application in response to this RFA. The Principal Investigator will coordinate Group activities scientifically and administratively and should be project leader of one of the Research Projects of the Group. A minimum 10 percent (time) effort by the Principal Investigator should be devoted to the study. The Principal Investigator's institution establishes and operates the Central Operations Office that funds Group members and is legally and fiscally accountable for the disposition of funds awarded. 5. PROJECT LEADER: The leader of one of the scientific research projects of the NCDDG-OI who is directly responsible for the scientific conduct of that project and also directly responsible to the Principal Investigator. 6. RESEARCH PROJECT: A discrete, specified project with a separate budget that relates to the unifying central theme and objectives of the NCDDG-OI. 7. SCIENTIFIC ADVISORS PANEL: A panel comprised of two to three peers from the scientific community, whose mission is to provide the Principal Investigator with comprehensive review of the Group's activities and progress, consult on future goals and strategies, and recommend alternative directions, as appropriate. Selection and appointment of the Panel is the responsibility of the Principal Investigator. A Scientific Advisors Panel is required of all Groups. The composition of the designated Panel will be provided to the NIAID within the first year of funding; members of the Panel will not be affiliated with any of the institutions comprising the Group. 8. SCIENTIFIC SUPPORT CORE COMPONENT: Facilities for equipment and services which must be utilized by at least two research projects in order to facilitate the research effort. The Core can be defined as a component with established techniques and assays which perform a service function resulting in an economy of effort and savings in the overall costs of the NCDDG-OI. The Core unit is to be described in the research plan of the projects and in adequate detail to enable the evaluation of its scientific and technical merit. A CORE COMPONENT cannot be considered toward fulfilling the required minimum of three research projects per Group. C. Patent Coverage Because the discovery of innovative, effective drug therapies for OIs is the goal of this effort, and since active involvement by private sector laboratories is facilitated by the existence of adequate patent coverage, it is essential that applicants provide plans to ensure such coverage. With the potential for involvement of several institutions, the patent situation could be complicated. Each applicant Group must, therefore, provide a detailed description of the approach to be used for obtaining patent coverage and for licensing where appropriate, in particular where the invention may involve investigators from more than one institution. Each Group must provide a detailed description of the procedures to be followed for the resolution of legal problems that may develop. Attention is drawn to the reporting requirements of 35 U.S.C. Parts 200-212 and 37 CFR Part 401 or FAR 55.227-11. Instructions were also published in the NIH Guide for Grants and Contracts, Vol. 19, No. 23, June 22, 1990. Note that non-profit organizations (including universities) and small business firms retain the rights to any patent resulting from Government contracts, grants or cooperative agreements. It is also noted that a Presidential memorandum of February 18, 1983 extended to all business concerns, regardless of size, the first option to the ownership of rights to inventions as provided in P.L. 96-517. As a result of this memorandum, the relationships among industrial organizations and other participants are simplified, since all Group members can now be full partners in the research and in any inventions resulting therefrom. The specific patenting arrangements among institutions may vary, and could include joint patent ownership, exclusive licensing arrangements, etc. Applicants are encouraged to develop an arrangement that is most suitable for their own particular circumstances. Federal regulation clause 37 CFR 401 and HHS Inventions regulations at 45 CFR Parts 6 and 8 require that NIH be informed of inventions and licensing occurring under NIH funded research. Invention and licensing reports must be submitted to Extramural Invention Reports Office, Office of Extramural Research, Building 31, Room 5B41, NIH, 9000 Rockville Pike, Bethesda, Maryland 20892. D. Terms and Conditions of Award The following terms and conditions will be incorporated into the award statement and provided to the Principal Investigator as well as the institutional official at the time of award. The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS grant administration regulations at 45 CFR Parts 74 and 92 [Part 92 is applicable when State and local Governments are eligible to apply], and other HHS, PHS, and NIH grant administration policies The administrative and funding instrument used for this program is the Cooperative Agreement (U19), an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH scientific and/or programmatic involvement with the awardee is anticipated during the performance of the activity. The U19 must contain a minimum of three inter-related research projects organized around a central theme. A Core resource or facility must be utilized by at least two research projects. Under the Cooperative Agreement, the NIH purpose is to support and/or stimulate the recipient's activity by involvement in and otherwise working jointly with the award recipient in a partner role, but it is not to assume direction, prime responsibility, or a dominant role in the activity. Consistent with this concept, the dominant role and prime responsibility for the activity resides with the awardee(s) for the project as a whole, although specific tasks and activities in carrying out the study will be shared among the awardees and the NIAID Scientific Coordinator. 1. Awardee Rights and Responsibilities Awardees will have primary responsibility for defining the details for the project within the guidelines of the RFA and for performing the scientific activity, and agree to accept close coordination, cooperation, and participation of NIAID staff in those aspects of scientific and technical management of the project as described under "NIAID Staff Responsibilities". Specifically, awardees have primary responsibilities as described below: Meetings and Scientific Advisors Panel Two Group meetings are required per year. The Principal Investigator and Project and Core Leaders will meet to review progress, plan and design research activities, and establish priorities within the Group. The Principal Investigator will be responsible for scheduling the time and place (generally at one of the performance sites), for notifying the Scientific Coordinator at least thirty days prior to the meeting date, and for preparing concise (2-3 pages) minutes or summaries of the Group meetings which will be delivered to the members of the Group including the Scientific Coordinator within thirty days following the meeting. The NIAID Scientific Coordinator will participate but not chair Group meetings. One mandatory meeting of the entire NCDDG-OI program will be held each year at a site designated by NIAID during which all Principal Investigators and Project Leaders will attend and present significant findings in symposium format. Data presented at this meeting are selected by the individual presenters in consultation with their Principal Investigator, thus affording appropriate protection of proprietary or commercially sensitive information. Groups will designate a Scientific Advisors Panel within the first year of funding. The Principal Investigator will convene a meeting or meetings of the Group with the Panel during the second and third years which may be in conjunction with the required Group meetings. The Panel will meet with the Group and advise the Principal Investigator on the Group's progress, future goals, strategies and new directions, as appropriate. The Panel will provide the Principal Investigator with a comprehensive written review (2-3 pages) of the Group's activity each year. Members of the Panel will not be affiliated with any of the institutions comprising the Group. Publications and Presentation of Findings Early publication of major findings is encouraged. The Principal Investigator will be responsible for the timely submission to the Scientific Coordinator of all abstracts, manuscripts, and reviews (co)authored by members of the Group and supported in part or in total under this Agreement. The Principal Investigator and Project Leader are requested to submit manuscripts to the Scientific Coordinator within three weeks of acceptance for publication so that an up-to-date summary of program accomplishments can be maintained. Publications or oral presentations of work done under this Agreement are the responsibility of the Principal Investigator and appropriate Project Leader. All publications (abstracts, peer reviewed manuscripts, reviews) and oral presentations of work supported in part or in total by the NCDDG-OI cooperative agreement must be acknowledged as part of the presentation and will include the mechanism, cooperative agreement number and Institute, for example, "This work was supported in whole (or in part) by the NCDDG-OI program, cooperative agreement number U19-AI-1234, NIAID." Progress Reports An annual Progress Report will be submitted with the Application for Continuation Grant which must include significant experimental data obtained and a complete and cumulative list of all publications (abstracts, manuscripts, reviews) (co)authored by Group members and supported in part or in total under this Agreement. Each Progress Report should 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 assays). Inter-Group collaboration with other NCDDG-OIs should be specified, where applicable. Interaction with the Scientific Coordinator and the NIAID during the reporting period should be described. The Progress Report must also include basic information as instructed with PHS 2590 Noncompeting Continuation Application forms. Rights to Data While the NIAID Scientific Coordinator has a right of access to the data, the applicant will retain custody of and rights to the data. Information obtained from the data may be used by the Scientific Coordinator for the preparation of internal reports on the Group's activities. The NIAID Scientific Coordinator may assist the Groups by providing them with compounds for voluntary initial and confirmatory testing. In testing compounds supplied by the NIAID, the Groups agree to abide by any confidentiality agreement between the NIAID and a third party who may have supplied the compounds for testing through NIAID. 2. NIAID Staff Responsibilities The NIAID shall participate as a member of the Group and shall be represented by a Scientific Coordinator or the NCDDG-OI program director. The Scientific Coordinator shall be selected from the Developmental Therapeutics Branch of the Division of Acquired Immunodeficiency Syndrome, or from the Division of Microbiology and Infectious Diseases, which are extramural programs of the NIAID. The NIAID Scientific Coordinator will have substantial scientific/programmatic involvement during the conduct of this activity through technical assistance, advice and coordination such as participating in the design of Group activities, advising in the selection of sources or resources, coordinating or participating in collection and/or analysis of data, advising in management and technical performance, or participating in the preparation of publications. However, the role of NIAID will be to facilitate and not to direct the activities. It is anticipated that decisions in all activities will be reached by consensus of the Group and that NIAID staff will be given the opportunity to offer input to this process. The manner of reaching this consensus and the final decision-making authority will rest with the Principal Investigator. The Scientific Coordinator may serve as a resource for information, laboratory testing, and biological supplies, when such resources are not a normal requirement of the Group's day-to-day research activities, but may be required on an occasional basis. The NIAID has a contract program for the preclinical development of compounds for the treatment of AIDS-associated opportunistic infections, including animal models. These resources are intended for initial studies and may not be available on a continual basis. Examples of potential assistance include: reference compounds for standardization of test systems, facilitation of confirmatory testing at research sites including other NCDDG-OI Groups, limited testing in appropriate animal model(s), focused searches of NIAID's computer files of chemical structures and biological activity, chemical re-synthesis, analysis, formulation, and toxicology testing through existing pre-clinical development contracts (contingent upon NIAID's recommendation and prioritization), and networking with other NIH staff, NCDDGs, other collaborators, and other Government and non-Government researchers who may provide guidance, expertise or resources to facilitate development of therapies identified by the Group. 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. The NIAID supports Phase I, Phase II and Phase III clinical trials through a variety of mechanisms. These clinical development resources are available to study promising therapies brought forward from sources such as the NCDDG-OI program. It is understood that the Government provides its consulting and testing services in the interest of promoting experimental anti-infective agents through pre-clinical 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. 3. Arbitration Process Any disagreement that may arise on scientific/programmatic matters (within the scope of the award), between award recipients and the NIAID may be brought to arbitration. An arbitration panel will be composed of three members -- one Group designee, one NIAID designee, and a third designee with expertise in the relevant area and chosen by the other two. This special arbitration procedure in no way affects the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations 42 CFR Part 50, Subpart D and HHS regulation at 45 CFR Part 16. STUDY POPULATIONS 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 new policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43) and supersedes and strengthens the previous policies (Concerning the Inclusion of Women in Study Populations, and Concerning the Inclusion of Minorities in Study Populations), which have been in effect since 1990. The new policy contains some provisions that are substantially different from the 1990 policies. All investigators proposing research involving human subjects should read the "NIH Guidelines For Inclusion of Women and Minorities as Subjects in Clinical Research," which have been published in the Federal Register of March 9, 1994 (FR 59 11146-11151) and reprinted in the NIH Guide for Grants and Contracts, Volume 23, Number 11, March 18, 1994. Investigators also may obtain copies of the policy from the program staff listed under INQUIRIES. Program staff may also provide additional relevant information concerning the policy. (NOTE: When the proposed study or studies in the RFA or PA involves a gender specific study or a single or limited number of minority population groups, this should also be stated to inform potential applicants and reviewers.) NOTE: Peer review groups need adequate information about the composition of proposed study populations in all applications involving human subjects. To avoid delays in review of such applications, the NIAID therefore requires that, as a minimum, the application must contain demographic data about the clinic and/or in-patient population from which the study subjects will be drawn: average hospital admissions per year; percentage distribution of black/hispanic/other minority/non-minority populations; gender; etc. Studies using non-hospital populations, such as community-based studies, should provide similar data about populations in the area or region from which the study subjects will be drawn. In the absence of current data, historical demographic information and/or previous recruitment data for similar studies from the proposed sites should be provided. LETTER OF INTENT Prospective applicants are asked to submit, by July 15, 1994, a letter of intent that includes a descriptive title of the overall proposed research, the name, address and telephone number of the Principal Investigator, the number and title of this RFA, and a list of the key investigators and their institution(s) and projects. Although the letter of intent is not required, is not binding, does not commit the sender to submit an application, and does not enter into the review of subsequent applications, the information that it contains allows NIAID staff to estimate the potential review workload and to avoid conflict of interest in the review. The letter of intent is to be sent to Dr. Dianne Tingley at the address listed under INQUIRIES. APPLICATION PROCEDURES Applications are to be submitted on the standard research grant application form PHS 398 (rev. 9/91). For purposes of identification and processing, item 2a on the face page of the application must be marked "YES" and the RFA number and the words "NATIONAL COOPERATIVE DRUG DISCOVERY GROUP FOR TREATMENT OF OPPORTUNISTIC INFECTIONS (NCDDG-OI)" must be typed in. Applications must be received by August 11, 1994. Applications from multi-component consortia must contain a single face page. an overall budget page, and separate budget pages for each institution involved. Each consortium institution is allowed 25 pages for the research plan if different plans are proposed by the different member institutions. Because of the multi-institutional nature of and the special requirements in this RFA, additional instructions regarding format are contained in NIAID POLICY ON MULTIPROJECT APPLICATIONS (PROGRAM PROJECT GRANTS AND MULTIPROJECT COOPERATIVE AGREEMENTS), which is available from the program staff listed under INQUIRIES. If a conflict exists between instructions as presented in the program policy guidelines and this RFA, this RFA takes precedence. The application forms may be obtained from the institution's office of sponsored research or its equivalent, and from the Office of Grants Information, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone (301) 710-0267. Applications must address the requirements below as outlined in the section "SPECIAL REQUIREMENTS." A. Composition of First Section of the Application 1. It is suggested that applications provide a clear, concise plan in narrative and diagrammatic form that depicts the interrelationships among the members of the NCDDG-OI and the contribution of each to fulfillment of Group objectives that meets the scope of this RFA. 2. It is suggested that applications provide an organizational chart of the NCDDG-OI showing the name, organization, and scientific discipline of the investigators comprising the Group. 3. Applications are to provide a plan to ensure maintenance of close collaboration and effective communication among members of the Group. The application should include plans for scheduling Group meetings, notifying Group members including the NIAID Scientific Coordinator, and documenting and disseminating Group meeting proceedings. 4. Applications must include letters of commitment to the overall plan and acceptance of the participation of the NIAID Scientific Coordinator. 5. Applications are to provide a rationale for the drug discovery approach(es) proposed and discussion of the therapeutic approaches which may derive from the research projects. 6. Applications should present the anticipated unique advantages to be expected from the Group operating within the proposed collaborative efforts, how the projects are mutually reinforcing, and how collectively they will further the stated goals of the proposed research. B. Organizational and Administrative Structure of the NCDDG-OI The application should describe in detail and by diagram the chain of responsibility for decision-making and administration beginning at the level of the Principal Investigator and including the different research Project Leaders and other investigators. Where in the chain of responsibility advisory groups will be used should be indicated and their role in establishing quality control of the research efforts should be described. C. Consortium Arrangements An application that includes research activity involving institutions other than the sponsoring organization is considered a consortium effort. It is imperative that care be taken in preparing any consortium application so that the programmatic, fiscal, and administrative considerations are fully explained. The policy governing consortia is described in the NIH Guide for grants and Contracts (Vol. 14, No. 7, June 21, 1985), which should be available at the sponsoring institution's business office, or in the Office of Grants Inquiries' publication entitled "Guidelines for Establishing and Operating Consortium Grants", January 1989, which may be obtained by calling (301) 710-0267. D. Patent Coverage Agreement 1. The application should provide a description of the Group's plan for assuring adequate patent coverage of new inventions that may arise as a result of Government funding of this U19. "Invention" is defined as a new drug or innovative treatment that is or may be patentable under Title 35 of the United States Code. A copy of the proposed patent plan among the institutions comprising the Group must be submitted with the application. This patent agreement, signed and dated by the organizational officials authorized to enter into patent arrangements for each Group member and member institution, must be delivered two weeks prior to submission of the application to Dr. Barbara Laughon at the address listed under INQUIRIES. 2. Should the Group wish to place all inventions and discoveries resulting from these studies within the public domain, a letter to that effect must be submitted to Dr. Laughon in lieu of the patent agreement prior to submission of the application. The letter must be co-signed by the Principal Investigator, Project Leaders, and each of the business officials representing the respective institutions. E. Individual Research Projects 1. The strength of the complete application package will be judged mainly on the basis of the quality of each research project. Reviewers will expect each project to be described in the same detail as for a regular research grant application to enable the reviewers to judge the technical and scientific merit solely on the basis of the written applications. 2. The portion of the application for each component research project should be prepared in the same manner as an R01 application, following carefully the instructions found in the grant application form PHS 398 (rev. 9/91). F. Scientific Core Support 1. The application should describe the role and importance of the core as a resource to the NCDDG-OI as a whole and the specific service(s) such core support will provide and the projects it will serve. The facilities, techniques, and professional skills that the core will provide should be described. The role of the Core Leader and each of the key participants should be described. The portion of the application describing each scientific core should be prepared with the same level of detail as an R01 application in order for the technical merit and appropriateness of each core to be evaluated. 2. Core support may be provided as consortia if performed at institutions different from that of the Principal Investigator. 3. The budget for each scientific core should be presented according to the instructions of the form PHS 398 (rev. 9/91); see also NIAID POLICY ON MULTIPROJECT APPLICATIONS (PROGRAM PROJECT GRANTS AND MULTIPROJECT COOPERATIVE AGREEMENTS). All components, subparts and sections of the application must be collated into the application, and the packages sent to the Division of Research Grants (DRG) and to the NIAID must each be complete in themselves. Applications that are not received as a single package from the Principal Investigator and that do not conform to the instructions contained in PHS 398 (rev. 9/91) applications kit will be judged nonresponsive and will be returned to the applicant. The RFA label in the application form PHS 398 must be affixed to the bottom of the face page of the application. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2a of the face page of the application form and the YES box must be marked. Submit a signed, typewritten original of the application, including the checklist; and three signed, exact, single-spaced photocopies in one package to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** At the time of submission, also submit two additional exact copies of the application, and five sets of the appendix and reprints directly to Dr. Dianne Tingley at the address listed under INQUIRIES. Applicants from institutions that have a General Clinical Research Center (GCRC) funded by the NIH National Center for Research Resources may wish to identify the GCRC as a resource for conducting the proposed research. If so, a letter of agreement from either the GCRC program director or Principal Investigator should be included with the application. Applications must be received by August 11, 1994. If an application is received after that date, it will be returned to the applicant without review. The DRG will not accept any application in response to this RFA that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. The DRG will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of a substantial revision of an application already reviewed, but such applications must include an introduction addressing the previous critique. REVIEW CONSIDERATIONS General Considerations All applications will be judged on the basis of the scientific and technical merit of the proposed projects and the documented ability of the investigators to meet the RESEARCH OBJECTIVES of the RFA. Applications with first year total costs (direct and indirect) in excess of $700,000 will be returned without review. Upon receipt, applications will be reviewed for completeness by the NIH Division of Research Grants and for responsiveness by NIAID staff. Incomplete applications will be returned to the applicant without further consideration. If the application is not responsive to the RFA, it will be returned without further consideration. Those applications that are complete and responsive may be subjected to a triage by a peer review group to determine their scientific merit relative to other applications received in response to this RFA. The NIAID will withdraw from further competition those applications judged to be noncompetitive for award and will notify the Principal Investigator and institutional business official. Those applications judged by the reviewers to be competitive for award will undergo further scientific merit review by an appropriate peer review group convened by the Division of Extramural Activities, NIAID. The second level of review will be provided by the National Advisory Allergy and Infectious Diseases Council. Review Criteria Scientific Considerations 1. The scientific and technical merit of the application as a whole as well as that of each individual research project and core components, for the realization of drug discovery objectives. Evaluations will be based on originality, novel and unique ideas, and the incorporation of state-of-the-art approaches and methodologies of the proposed project towards the attainment of the stated programmatic goals. Each project must be supportable on its own merit; 2. Relevance of the Group's objectives to the discovery of new entities and strategies for the treatment of opportunistic infections and the likelihood that innovative preclinical therapeutic strategies will be identified during the course of the proposed project. Groups that are recompeting must demonstrate and document progress as defined by the goals of the program; 3. The cohesiveness, multi-disciplinary and multifaceted scope of the application and the coordination and interdependence of the individual projects and core(s) to the common theme; 4. The justification for and the usefulness to the various research projects of the core facilities. The relationship of each core to the central focus of the overall project. Each core unit must provide essential facilities or service for two or more individual research projects; 5. The leadership, scientific ability, and administrative competence of the Principal Investigator for the development, implementation, and management of the research program; and the Principal Investigator's commitment to devote sufficient time and effort to the program; 6. The qualifications, experience, and commitment of the investigators responsible for the individual research projects (Project Leaders) or core(s) (Core Leaders) and their contribution to the program, including their ability to devote adequate time and effort to the Group. It is anticipated that, due to the complexity and time required to maintain a well-coordinated and productive research effort, a minimum 10 percent (time) effort by the Principal Investigator and each Project Leader should be devoted to the study, unless there are compelling arguments to the contrary; 7. Research training, experience and accomplishments of other participating investigators and support personnel in the Group in the research areas outlined in the RFA; 8. Provisions for the protection of human subjects and the humane care of animals; adequacy of biohazard containment facilities; 9. Adequate representation of women and/or minorities in clinical research populations. Administrative Considerations 1. Academic environment and resources in which the research will be conducted, including the availability of space, equipment, human subjects, animals, or other resources as required, and the potential for interaction with scientists from other departments and/or participating institutions; 2. Documented commitment of Institutions represented by Group members; documented capability of the Principal Investigator's Institution to serve as the Central Operations Office for the Group; 3. Soundness of the administrative and organizational structure that facilitates attainment of the objective(s) of the program; 4. Institutional strength, stability, and commitment to research and to the program, including fiscal responsibility and management capability to assist the Principal Investigator and staff in following DHHS, PHS, and NIH policies; 5. Administrative planning and leadership capability to provide for internal quality control of on-going research, allocation of funds, day-to-day management, internal communications and cooperation among the investigators involved in the program, contractual agreements, and replacement of the Principal Investigator, if required, on an interim or permanent basis; 6. Documented commitment of the sponsoring institution to the cooperative agreement and willingness to accept the participation and assistance of NIAID staff (Scientific Coordinator); 7. Appropriateness of the budget in relation to the proposed program. The initial review group can make recommendations regarding appropriateness of the applicant's 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, in order to strengthen applications. The initial review group will review each project and core within the application individually, followed by scoring of the application as a whole. Council Review Stage The second level review will be conducted by the National Advisory Allergy and Infectious Diseases Council. Factors that will be considered in this review include: 1. Results of the initial scientific and technical merit review; 2. Significance to NIAID program goals in microbiology, infectious diseases, allergy, transplantation immunology, immunologic diseases, or AIDS; 3. National needs and NIAID program balance; 4. Policy and budgetary considerations. AWARD CRITERIA Award criteria will be made on the basis of scientific and technical merit as determined by peer review, program needs and balance, and the availability of funds. INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues to: Barbara Laughon, Ph.D. Division of AIDS National Institute of Allergy and Infectious Diseases Solar Building, Room 2C35 6003 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 402-2304 FAX: (301) 401-3211 Direct letters of intent, and inquiries regarding application preparation and review to: Dianne Tingley, Ph.D. Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4C16 6003 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-0818 FAX: (301) 402-2638 Direct inquiries regarding fiscal matters to: Ms. Jane Unsworth Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4B22 6003 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-7075 FAX: (301) 480-3780 Schedule Letter of Intent Receipt Date: July 15, 1994 Application Receipt Date: August 11, 1994 Scientific Review Date: November 1994 Advisory Council Date: February 1995 Anticipated Award Date: April/May 1995 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance, No. 93.856 - Microbiology and Infectious Diseases Research and No. 93.855 - Immunology, Allergic and Immunologic Diseases Research. Awards will be 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 Parts 52 and 45 CFR Part 74 [and Part 92 when applicable for State and Local governments]. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. The Public Health Service strongly encourages all grant recipients to provide a smoke-free workplace and promote the non-use of all tobacco products. This is consistent with the PHS mission to protect and advance the physical and mental health of the american people. .
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Office of Extramural Research (OER) |
National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892 |
Department of Health and Human Services (HHS) |
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