$$XID RFA AI9111 AI-91-11 P1O1 ***************************************** REQUEST FOR APPLICATIONS RFA: AI-91-11 PROGRAM PROJECTS ON NEW METHODS OF IMMUNE INTERVENTION P.T. 34; K.W. 0710070, 0745045, 0715015, 0715110, 0715026 National Institute of Allergy and Infectious Diseases Letter of Intent Receipt Date: August 22, 1991 Application Receipt Date: November 19, 1991 BACKGROUND The Basic Immunology Branch, Division of Allergy, Immunology and Transplantation, of the National Institute of Allergy and Infectious Diseases (NIAID) supports fundamental research that expands recent, major advances in the field of immunology and leads to the clinical application of those advances. The remarkable progress in understanding the immune system in health and disease has created a wealth of potential for the treatment and prevention of human illness. It is also evident that a void exists between the new information and new experimental approaches generated by basic research and the effective use of recent information to develop methods and procedures for clinical application. This Request for Applications (RFA) is intended to encourage the submission of applications from collaborating investigators that include prospective clinical significance as a factor in the design and execution of the research. The ultimate goal of these program project grants is to develop new approaches to the treatment and/or prevention of human autoimmune, allergic, and inflammatory diseases. RESEARCH GOALS AND SCOPE Major, recent advances in our knowledge have indicated that, for example, immunodominant (Class I- and Class II-reactive) peptides and idiotypes of T-cell receptors (prospective "vaccines"), and cell adhesion molecules and lymphocyte homing receptors may be valuable tools in treating illness. The prospects for the use of immunodominant major histocompatibility complex peptides, idiotypic peptides, and anti-idiotype monoclonal antibodies or T-cell clones to treat autoimmune diseases are particularly promising. The reason for optimism is that, in several experimental autoimmune disease models, the disease results from the autoaggressive actions of a highly restricted number of T-cell clones. There likewise appear to be opportunities to employ cell adhesion molecules and lymphocyte homing receptors to treat inflammation, various infections, and asthma. An approach that appears unusually promising in altering the course of autoimmune and allergic diseases is the induction of oral tolerance by appropriate tolerogenic substances. The scope of these program project grants includes all aspects of research concerned with the treatment or prevention of model experimental autoimmune, allergic, and inflammatory disorders. Studies involving valid in vitro models are appropriate. Investigations that involve human subjects or human materials are welcome. SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH and ADAMHA policy is that applicants for NIH/ADAMHA 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 Section 2, A-D of the Research Plan AND summarized in Section 2, E, Human Subjects. Applicants/offerors are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes that it may not be feasible or appropriate in all research projects to include representation of the full array of United States racial/ethnic minority populations [i.e., Native Americans (including American Indians or Alaskan Natives), Asian/Pacific Islanders, Blacks, Hispanics]. The rationale for studies on single minority population groups should be provided. For the purpose of this policy, clinical research includes human biomedical and behavioral studies of etiology, epidemiology, prevention (and preventive strategies), diagnosis, or treatment of diseases, disorders or conditions, including, but not limited to, clinical trials. The usual NIH policies concerning research on human subjects also apply. Basic research or clinical studies in which human tissues cannot be identified or linked to individuals are excluded. However, every effort should be made to include human tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of women or minorities in a study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population is inadequate, it will be considered a scientific weakness or deficiency in the study design and will be reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreements that do not comply with these policies. If the required information is not contained within the application, the application will be returned. MECHANISM OF SUPPORT Program project (P01) grants are awarded to an institution on behalf of a program director for the support of a broadly based, multidisciplinary, long-term research program that has a specific major goal or basic theme. A program project involves the organized efforts of groups of investigators that conduct research projects related to the overall program goal. The grant can provide support for the projects and for certain basic resources shared by individuals in the program project if sharing facilitates the total research effort. Each project supported under a program project grant is expected to contribute to and be directly related to the common theme of the program. The projects, under the direction of a Principal Investigator, must demonstrate an essential element of unity and interdependence. The application must clearly explain how the projected multidisciplinary integrated program will accomplish the stated goals more efficiently and effectively than could a series of independent, individual research projects. Designation of a program director must be based upon accomplishment and experience as a scientist, the ability to assume both the leadership of the research group and the responsibility for scientific, professional, and administrative functions, and the commitment of a significant amount of his/her time to the project. Each project in the program must have a designated project leader with a record of accomplishment in clinical immunology or one of the basic science disciplines or clinical specialties relevant to the particular subject of investigation. However, the participation of one junior investigator whose project is an integral part of the overall program, and whose work would be closely related to that of the senior scientist leaders of the other projects is encouraged by the NIAID. Support for a competing program project in New Methods in Immune Intervention will be limited to a maximum of five years. Competing renewals may be submitted in response to an RFA or as an unsolicited application. Funding beyond the first and subsequent years of the grant will be contingent upon satisfactory progress during the preceding years and availability of funds. In Fiscal Year 1992, the NIAID plans to award at least two program project grants submitted in response to this RFA and, depending on availability of funds and scientific merit of the applications, more than two. Budgetary requests must be limited to no more than $500,000 direct costs. Grant funds may be utilized to support the research activities of scientific and professional personnel, administration, consultation services, central support services, equipment, supplies, travel, and publication costs. Support for research-related costs of patient involvement and medical care may be authorized. No funds will be provided for new construction; therefore, adequate physical facilities must be available for the primary needs of the project. However, moderate alterations or renovations to enhance clinical or laboratory facilities may be allowed if they are necessary to meet the objectives of the proposed program. ELIGIBILITY Only domestic institutions are eligible to apply. REVIEW PROCEDURES AND CRITERIA The NIAID Information Brochure on Program Project and Center Grants contains special instructions and information for multiproject applications for program project grants regarding review procedures and criteria. Before proceeding, the prospective applicant should read this brochure. Applications will be examined 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. Those applications that are complete and responsive may be subjected to a triage by an NIAID peer review group before or during the scientific review meeting to determine their scientific merit relative to other applications received in response to this RFA. The NIAID will withdraw from competition those applications judged to be non-competitive for award and will notify the applicant and institutional business official. Those applications judged by the reviewers 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 February or March. The second level of review will be provided by the National Advisory Allergy and Infectious Disease Council in May 1992. July 1, 1992 will be the earliest start date for successful applicants. METHOD OF APPLYING In addition to following the format instructions contained in the Information Brochure for the development of a program project grant application, include the expanded material listed below: o A brief overview of the intended program project as well its components; o A description of available laboratory and clinical facilities available for use by the proposed project; o Ongoing relevant research studies, identifying existing projects and sources of support; o Past research by members of the proposed investigative group relevant to the proposal; o Specific information on the institution's present patient load and projections for patient involvement in clinical investigations; o The academic positions and major research interests of the program director and his/her professional staff who will be involved in the work of the program project; o Collaborative arrangements with other laboratories and investigators and delineation of the role and manner of anticipated participation and interaction of the Principal Investigators, consultants, and collaborators; o Justification for the use of the PO1 mechanism as opposed to submission of individual RO1 projects. The receipt date for applications is November 19, 1991. APPLICATIONS NOT RECEIVED AS A SINGLE PACKAGE FROM THE APPLICANT ORGANIZATION BY NOVEMBER 19, 1991, OR THAT DO NOT CONFORM TO THE INSTRUCTIONS CONTAINED IN FORM PHS 398 (rev. 10/88) APPLICATION KIT, WILL BE JUDGED TO BE NON-RESPONSIVE AND WILL BE RETURNED TO THE APPLICANT. Use the standard research grant application form PHS 398 (rev. 10/88). For purposes of identification and processing, the words "PROGRAM PROJECTS ON NEW METHODS OF IMMUNE INTERVENTION" and the RFA number must be typed in item 2 on the face page of the application. THE RFA LABEL AVAILABLE IN THE 10/88 REVISION OF APPLICATION FORM PHS 398 MUST BE AFFIXED TO THE BOTTOM OF THE FACE PAGE. FAILURE TO USE THIS LABEL COULD RESULT IN DELAYED PROCESSING OF THE APPLICATION SUCH THAT IT MAY NOT REACH THE REVIEW COMMITTEE IN TIME FOR REVIEW. Application kits may be obtained from the institution's office of sponsored research and from: Office of Grants Inquiries Division of Research Grants National Institutes of Health Westwood Building, Room 449 Bethesda, MD 20892 Submit a signed, typewritten original of the application, including the Checklist, and four signed, exact, single-sided photocopies, in one package to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 Bethesda, MD 20892** In addition, mail two exact copies of the application and six copies of the appendices directly to Dr. Olivia Preble at the following address: Olivia T. Preble, Ph.D. Chief, Microbiology & Immunology Review Section National Institute of Allergy and Infectious Diseases National Institute of Health Westwood Building, Room 3A-10 Bethesda, MD 20892 Telephone: (301) 496-8208 LETTER OF INTENT Prospective applicants are asked to submit by August 22, 1991, a letter of intent that includes a descriptive title of the overall proposed research, the name of the Principal Investigator, and a list of the names of key investigators and their institution(s). The letter of intent is requested in order to provide an indication of the number and scope of applications to be reviewed to allow early preparations for review, as well as to promote early interactions between applicants and NIAID staff. The letter of intent is not binding and does not commit the sender to submit an application, nor is it a requirement for submission of an application. The letter of intent is to be directed to Dr. Preble at the address given above. In addition, it is highly recommended that the Chief of the Basic Immunology Branch be contacted in the early stages of preparation of the application: Joseph F. Albright, Ph.D. Chief, Basic Immunology Branch Division of Allergy, Immunology and Transplantation National Institute of Allergy and Infectious Diseases National Institutes of Health 5333 Westbard Avenue, Room 757 Bethesda, MD 20892 Telephone: (301) 496-7551 Telefax: (301) 402-0175 INQUIRIES Inquiries concerning the programmatic aspects of this RFA and the NIAID Information Brochure may be addressed to Dr. Albright at the address given above. Inquiries regarding the review of these applications may be addressed to Dr. Preble at the address given above. Inquiries regarding fiscal matters may be addressed to: Mr. Jeffrey Carow Chief, Immunology Grants Management Section GMB, DEA National Institute of Allergy and Infectious Diseases Westwood Building, Room 726 Bethesda, MD 20892 Telephone: (301) 496-7075 This program is described in the Catalog of Federal Domestic Assistance No. 93.855, Immunology, Allergic and Immunologic Diseases Research. Awards will be made under the authority of the Public Health Service Act, Title III, Section 301 (Public Law 78-410, as amended; 42 USC 241) and administered under PHS grants policies and Federal Regulation 42 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review.