CHRONIC FATIGUE SYNDROME COOPERATIVE RESEARCH CENTERS NIH GUIDE, Volume 23, Number 16, April 29, 1994 RFA: AI-94-020 P.T. 04; K.W. 0715043, 0710030 National Institute of Allergy and Infectious Diseases Letter of Intent Receipt Date: September 15, 1994 Application Receipt Date: October 25, 1994 PURPOSE The Virology Branch (VB) of the Division of Microbiology and Infectious Diseases (DMID) of the National Institute of Allergy and Infectious Diseases (NIAID) invites applications for the continuation and/or establishment of high-quality Chronic Fatigue Syndrome Cooperative Research Centers (CFS CRCs) that provide a multi- disciplinary, systematic, sustained approach to the study of CFS. A nucleus of CFS CRCs dedicated to use of standardized methodologies and collaborative efforts was established in 1991. This is a recompetition to identify centers with capabilities to build on the initial effort in order to facilitate progress in this difficult research area. HEALTHY PEOPLE 2000 The Public Health Service 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), Chronic Fatigue Syndrome Cooperative Research Centers, is related to the priority area of chronic disabling diseases. 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, such as universities, colleges, hospitals, laboratories, units of State or local government, and eligible agencies of the Federal government. Foreign organizations are not eligible to apply. Domestic applications may not include international components. 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 (U01, 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 is the multiproject funding mechanism that will be used for applications comprised of three or more projects; the U01 mechanism will be used for applications with two 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. 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 entire project period for each application submitted in response to this RFA may not exceed five years. At present, the NIAID is administratively limiting the duration of cooperative agreements (U01, U19) to four years; this administrative limitation may change in the future. The NIAID has not yet determined whether and how this solicitation will be continued beyond the present RFA, but anticipates that there will be a renewed competition after four years contingent upon the continued availability of funds for this purpose. FUNDS AVAILABLE The NIAID plans to make at least three competing continuation and/or new awards under this RFA. The funds (direct and indirect costs) set aside for the first year of support will be $1.6 million. This level of support is dependent on the receipt of a sufficient number of applications of high scientific merit. The size of individual awards (estimated range, $350,000 to $650,000 total costs) will vary depending on the number of participating institutions and the complexity of the application. The usual PHS policies governing grants administration and management will apply. 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. RESEARCH OBJECTIVES Background Chronic fatigue syndrome (CFS) is a multisystem syndrome thought to be triggered by viral infection and characterized by months of debilitating fatigue frequently associated with myalgia, headache, sore throat, low grade fever, gastrointestinal symptoms, and tender lymph nodes. There have been reports of immunologic and, more recently, neuroendocrine parameters in CFS patients that on a group basis are different from those in healthy controls, but no single immunologic or neuroendocrine marker can be used to diagnose the syndrome. The cause and pathogenic mechanisms of the illness are unknown. Objectives and Scope The purpose of this RFA is to support a network of clinical centers of research excellence that use standardized methods for patient enrollment and data collection to pursue multidisciplinary coordinated projects to study etiology, natural history and/or pathogenesis of CFS. Expertise in fields of medicine, immunology, virology, physiology, psychology, clinical anthropology or clinical epidemiology may be helpful in furthering our understanding of CFS. It is not expected that expertise in all these areas be available at a single institution. Input from the NIAID Scientific Coordinator will facilitate technology transfer, assist in the identification of expert consultants, collaborators and resources, enhance communication among awardees and help to ensure that pilot studies funded through the CFS CRC program will complement and not unnecessarily duplicate existing or planned research endeavors. Well-designed studies with adequate sample sizes are needed to test biologically rational hypotheses concerning etiology or pathogenesis that will lead to improved diagnosis and effective interventions. Originality in concept and approach are encouraged. Examples of observations reported in the literature that merit further study to determine their biologic and/or epidemiologic basis and role in illness manifestation include, but are not limited to: o lymphocyte patterns suggestive of immune activation o low levels of cortisol and corticotropin-releasing hormone o low tolerance to physical exertion o demographic risk factors (gender, age, race, socioeconomic class) o reactivation of latent viruses o familial risk factors--including immunogenetic, behavioral and environmental factors o increased frequency of atopy o higher than normal frequency of brain scan abnormalities The development, standardization and evaluation of outcome measures for use in monitoring clinical status in natural history and therapeutic studies comprise another potential area for study. Medically and statistically sound therapeutic studies may be appropriate for testing certain hypotheses regarding pathogenesis, but it is not the intent of this RFA to support large-scale clinical trials. Budget and Related Issues In addition to support for personnel, supplies, travel to an annual CFS CRC workshop for CRC Director and Project Leaders (see "SPECIAL REQUIREMENTS") and other necessary costs justified in the application for conducting CRC research projects, award funds may be utilized to support the following research-related activities: o SHARED ADMINISTRATIVE, CLINICAL AND RESEARCH RESOURCES (CORES, pages 17-18 of brochure cited above): CFS CRCs may include funds for administration, equipment, supplies and services to expand and/or maintain clinical, laboratory, biostatistical, and data management facilities that are shared by research staff from at least two CRC research projects. Costs associated with patient and control recruitment, enrollment, follow-up and data entry would be appropriate for a core budget. Any research-related cost for patient and control subject enrollment that is not eligible for third-party payment should be included in the budget as PATIENT CARE COSTS. The amounts requested for Core support should be well justified and in keeping with the overall complexity and size of the budget. In any case, such costs may not duplicate or replace costs included in the institution's indirect cost base. Since the program cannot provide funds for new construction, adequate physical facilities must be available to meet the primary needs of the CRC. Please read pages 17-18 of the NIAID booklet on Program Project Grants and Multiproject Cooperative Agreements. o BIOSTATISTICAL SUPPORT: The budget must include adequate biostatistical support to ensure sound study design, data collection and data analysis procedures. o OTHER BUDGETABLE ITEMS: Budget requests may also include limited investigator travel and costs for publication. o DEVELOPMENTAL FUND FOR PILOT STUDIES: Applicants may request that $40,000 in direct costs be made available annually in a Developmental Fund for pilot studies. This Developmental Fund would be set aside and restricted solely to cover salaries and other research costs for small pilot studies to follow-up on new observations and novel hypotheses. It is envisioned that availability of funds for pilot studies would increase flexibility and responsiveness to important new scientific observations and medical reports. Pilot studies need not be restricted to the awardee institution. IT IS EMPHASIZED THAT INDIVIDUAL CRC RESEARCH PROJECTS ARE DISTINCT FROM PILOT STUDIES AWARDED FROM THE DEVELOPMENTAL FUND. The direct costs may not exceed $40,000 for any single pilot study. The duration of support for each study typically would be one year, but may be up to three years, unless the study is independently funded through a traditional research project grant (R01) or a FIRST (R29) award prior to the end of the three-year period. In these instances, the support of the pilot study from the Developmental Fund must be terminated, and unexpended funds must be returned to the Developmental Fund. Funds reserved for pilot projects may not be rebudgeted into other budget categories except in unusual circumstances and following approval from the Grants Management Specialist and the Scientific Coordinator. The CRC must maintain detailed records of disbursements and expenditures of the Developmental Fund. Procedures for soliciting and selection of pilot studies should be described, if developmental funds are requested. It is anticipated that pilot studies and their budgets recommended by the CFS CRC Director will be reviewed and selected by a local review committee. Studies involving Human Subjects will require prior approval by the Institutional Review Board like all other NIH supported projects. PILOT STUDIES PER SE, UNLIKE THE INDIVIDUAL CRC RESEARCH PROJECTS, SHOULD NOT BE DESCRIBED IN THE CRC APPLICATION. Only the solicitation process and selection method (institutional review process) and review criteria to be used need be described. Examples of criteria are scientific merit of the proposal, medical relevance and need for data to advance the research objectives of the CRC. The $40,000 annual direct costs should be entered in the OTHER category in the Consolidated Budget (see pages 15 and 21 in the accompanying brochure). SPECIAL REQUIREMENTS A. Study Organization The Cooperative Research Center Program requires cooperation between CRC Directors and the Scientific Coordinator to ensure that basic patient enrollment data under this program will be collected in a standardized manner and can be pooled in a computerized CRC database. Reports based on this pooled database are co-authored by CRC Directors. Patients are enrolled according to carefully specified criteria set forth by each CRC Director, but at a minimum all CRC CFS patients enrolled must meet inclusion and exclusion criteria comparable to those specified by CDC and NIH so that studies at different CRCs can be compared (Holmes, et al., Annals of Internal Medicine: 108, 387-389, 1988; Schluederberg, et al., Annals of Internal Medicine: 117, 325-331, 1992) (See also "Collaborative Responsibilities" under "Terms and Conditions of Award" below, and "SPECIAL REQUIREMENTS: Minimum Requirements for Application.") WORKSHOP PARTICIPATION: Successful applicants will be expected to participate in regularly scheduled workshops. These workshops will be held once a year in Bethesda, MD to provide the setting in which to share CFS research advances and to discuss CFS research needs and opportunities with the CRC Directors and other CRC principal investigators as well as with other investigators active in CFS research or working in relevant related areas. SUPPORT FOR TRAVEL TO THE WORKSHOP MUST BE INCLUDED IN THE CRC BUDGET REQUEST. B. 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. These 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 part 74 and 92, and other HHS, PHS, and NIH Grant Administration policy statements. The administrative and funding instrument used for this program is the cooperative agreement (U01, 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. 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 awardees 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 the NIAID Scientific Coordinator in those aspects of scientific and technical management of the project specified in 2 below. Specifically, awardees have primary responsibilities as described below. The CRC Director (the Principal Investigator for the CRC) will have ultimate responsibility for the coordination of efforts within the CRC and ensuring that the results obtained are analyzed appropriately and published in a timely manner. However, it will be the responsibility of each CRC Project Leader (the Principal Investigator for an individual research project within the CRC) to plan and conduct the research stipulated in the project proposal. NIAID may periodically review and generate internal reports from data and progress reports developed under this cooperative agreement. The data obtained will, however, be the property of the awardee. Awardees will retain custody of and have primary rights to the data developed under these awards, subject to Government rights of access consistent with current HHS, PHS and NIH policies. The multi-disciplinary and cooperative nature of the CFS CRCs creates an extraordinary opportunity for information exchange and scientific advancement in high quality CFS research. It is expected that Awardees will take advantage of this opportunity by participating in both formal events established expressly for this purpose and informal investigator-initiated dialogues. 2. NIAID Staff Responsibilities The NIAID Scientific Coordinator will be the Program Officer designated to administer the CFS CRC program, currently chief of the Virology Branch, DMID. During the award period, the NIAID Scientific Coordinator will work closely with the CRC Director TO FACILITATE, BUT NOT DIRECT, THE ACTIVITIES OF THE CRC. It is anticipated that decisions about cooperative CRC activities outlined within this RFA will be reached by consensus of the CRC Directors and the NIAID Scientific Coordinator. NIAID will facilitate research at CFS CRCs through the following: o assistance in overall research planning, data analysis and reporting; o facilitation of information exchange between CFS CRCs and other CFS grantees and investigators; o reduction of duplication of efforts by CFS CRCs and other NIAID awardees; o assistance in development of standardization procedures applicable to current and future CFS CRCs and to other grantees with regard to case definition, laboratory procedures, selection of reagents, etc; o facilitation of access to new research reagents and technologies; o assistance in review and selection of pilot studies o identification of experts and other important resources not otherwise available to the CFS CRCs; o assistance in locating potential replacements for key personnel vacancies including Principal Investigators, Project Leaders and Co- Investigators. 3. Collaborative Responsibilities The CRC Directors, Project Leaders, and NIAID Scientific Coordinator will communicate regularly by teleconference or at CFS related conferences, to review progress, plan, and design research activities, and establish CFS CRC priorities. As stated under "Study Organization," at a minimum, all CRC CFS patients enrolled must meet criteria comparable to those specified by CDC and NIH consensus reports so that studies at different CRCs can be compared and core data agreed upon by the CRC Directors can be entered into a common database. In addition, each year, NIAID staff will coordinate one workshop at the NIH in Bethesda, Maryland (or at a site designated by the NIAID). This workshop will provide a forum for CRC and other CFS research grant awardees to share research advances; to discuss CFS research needs and opportunities; and to develop collaborations. Funds for travel to these meetings must be included in the budget. 4. Release of Developmental Funds for Pilot Projects Release of funds for a pilot study may not occur until a written request is sent to the NIAID Scientific Coordinator with a copy to the Grants Management Specialist. A description of the proposed project, a summary of the deliberations of the local review committee, a committee roster and a budget countersigned by the institutional financial officer should accompany the letter of request. Funds may not be released until approved. 5. Arbitration 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 selected by the CRC Directors or by the individual awardee in the event of an individual disagreement, a second member selected by the NIAID, and the third member selected by the two prior members. This special arbitration procedure in no way affects the awardee's rights to appeal an adverse action that is otherwise appealable in accordance with the PHS regulations at 42 CFR part 50, subpart D and HHS regulation at 45 CFR part 16. 6. Therapeutic studies In the event that research supported by the Cooperative Agreement results in development of a therapeutic or other medical intervention, NIAID will retain the option to cross-file or independently file an application for an Investigational New Drug Application (INDA) to the United States Food and Drug Administration. Reports of data generated by the CRC or any of its members which are required for inclusion in INDAs and Clinical Brochures, and for cross-filing purposes will be submitted by the CRC Director 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 NIAID and may be augmented with test results from other Government sponsored projects prior to submission to the appropriate regulatory agency. 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 new 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 of March 18, 1994, Volume 23, Number 11. Investigators may obtain copies from these sources or from Dr. Schluederberg (listed in INQUIRIES below) who may also provide additional relevant information concerning the policy. LETTER OF INTENT Prospective applicants are asked to submit, by September 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). 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. Olivia Preble 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). These 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) 594-7248. 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 "CFS COOPERATIVE RESEARCH CENTERS" must be typed in. Before preparing the application, the applicant should carefully read the information brochure, "NIAID Program Projects and Multiproject Cooperative Agreements." Instructions outlined in the brochure for the formatting of the application must be followed carefully. Failure to follow the instructions may result in unnecessary delays in the review process. Investigators are urged to contact NIAID staff early in the development of the application (See program contact listed under INQUIRIES). Minimum Requirements for Application Particular attention should be given to the following areas when responding to the application instructions found in the brochure: o In describing the clinical and laboratory facilities available to the CRC, specific information should be included on the institution's present CFS patient load and projections for patients' willingness to participate in clinical investigations. A detailed account of case and control ascertainment procedures must be provided along with the inclusion and exclusion criteria to be used for enrollment. o A minimum of two projects must be proposed. The detailed description of each research project should demonstrate that it contributes to the attainment of the CRC's overall objectives. Preliminary results and evidence of feasibility should be provided if available. o Previously funded CRCs must submit a comprehensive progress report and carefully justify any plans for expansion. o In addressing the Organization and Administrative Structure of the CRC, the mutually reinforcing inter-relationships among the members of the CFS CRC and the contribution of each to fulfillment of CFS CRC objectives should be clearly described. This section must include an organizational chart showing the name, the organization, and the scientific discipline of the Program Director, the Project Leaders (principal investigators of individual research projects), and other key personnel for the projects. o The application must include a signed letter of agreement from each collaborator and/or consultant to the program indicating (1) willingness to participate in the program, and (2) the exact nature of the participation. o Also required is a plan to ensure the maintenance of close coordination and effective communication among members of the CFS CRC and between CRC members and the NIAID Scientific Coordinator. This plan should be co-signed by the CFS CRC Director and all Project Leaders to indicate acceptance of the participation of the NIAID Coordinator and to show commitment to the protocols of the proposed studies. o A written commitment by the sponsoring institution that explicitly defines the institution's willingness and preparedness to commit resources to ensure development, function, and maintenance of the proposed CFS CRC must be included in the application. This letter should be co-signed by the relevant departmental chairperson(s) and dean of the institution. Applications must be received by October 25, 1994. All components, subparts and sections of the application must be collated into the application, and the packages sent to the DRG and to the NIAID must each be complete in themselves. Applications that are not received by the receipt date or 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. The RFA label in the 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. 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, two additional exact copies of the grant application and all five sets of any appendix material must also be sent to Dr. Olivia Preble 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 could be included with the application. The Division of Research Grants (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 Review Method Upon receipt, applications will be reviewed for completeness by the NIH Division of Research Grants (DRG) 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 competition those applications judged to be non-competitive for award and will notify the Principal Investigators and institutional business officials. For applications found to be non-competitive, summary statements will be very brief and will generally contain a one paragraph resume, based on reviewers' comments, indicating the major reason(s) for the findings. 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. The second level of review will be provided by the National Advisory Allergy and Infectious Diseases Council. Review Criteria The review criteria for this RFA are the same as those for unsolicited research project grant applications: o scientific, technical, or medical significance and originality of proposed research; o appropriateness and adequacy of the experimental approach and methodology proposed to carry out the research; o qualifications and research experience of the Principal Investigator and staff, particularly but not exclusively in the area of the proposed research; o availability of resources necessary to perform the research; o appropriateness of the proposed budget and duration in relation to the proposed research; In addition, applicants are expected to address the issues identified under "SPECIAL REQUIREMENTS," as well as criteria specific to the objectives of this RFA. These criteria include: o CFS CRCs must offer a strong clinical facility with accessible patient populations that are appropriate for answering CFS research questions and are available for follow-up. o The value of studies of patients or their specimens will be directly related to the care exercised in selection and initial characterization of cases and controls. A detailed description of case recruitment procedures, the criteria to be used for case definition and the manner in which the criteria are to be applied must be included. Similar care should be given to descriptions of enrollment of comparison groups. o The CRC research program must focus on one or more aspects of CFS related to etiology, natural history or pathogenesis and involve the multidisciplinary expertise necessary to obtain meaningful results. o Each individual research project proposal must demonstrate the investigator's awareness of the requirements for hypothesis development and testing, and for sound data collection, management and analysis procedures. o The application must include evidence that the CRC Director and project directors have sufficient experience and expertise to make a significant contribution to the establishment of standardized procedures for studying CFS. AWARD CRITERIA Funding decisions will be made on the basis of scientific and technical merit as determined by peer review, program priorities 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: Ann Schluederberg, Sc.D. Division of Microbiology & Infectious Diseases National Institute of Allergy and Infectious Diseases Solar Building, Room 3A16 6003 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-7453 FAX: (301) 496-8030 Direct inquiries regarding review issues, address the letter of intent to, and mail two copies of the application and all five sets of appendices to: Olivia Preble, Ph.D. Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4C20 6003 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-8208 FAX: (301) 402-2638 Direct inquiries regarding fiscal matters to: Ms. Victoria Putprush Division of Extramural Activities National Institute of Allergy and Infectious Diseases Solar Building, Room 4B28 6003 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-7075 FAX: (301) 480-3780 Schedule Letter of Intent Receipt Date: September 15, 1994 Application Receipt Date: October 25, 1994 Scientific Review Date: February 1995 Advisory Council Date: June 1995 Earliest Award Date: September 1995 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.856, Microbiology and Infectious Diseases Research. Awards are made under authorization of the Public Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. The 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.