kristoff@GENBANK.BIO.NET (Dave Kristofferson) (04/08/90)
REQUEST FOR COOPERATIVE AGREEMENT APPLICATIONS SEXUALLY TRANSMITTED DISEASES COOPERATIVE RESEARCH CENTERS RFA: AI-90-03 P.T. 04; K.W. 0715182, 0710030, 0715125, 0404000, 0785035, 0403004 National Institute of Allergy and Infectious Diseases Letter of Intent Receipt Date: August 1, 1990 Application Receipt Date: October 10, 1990 I. SUMMARY The Sexually Transmitted Diseases (STD) Branch of the Division of Microbiology and Infectious Diseases (DMID) of the National Institute of Allergy and Infectious Diseases (NIAID) invites grant applications for the establishment of a network of Sexually Transmitted Diseases Cooperative Research Centers (STD CRCs). Establishment of STD CRCs reflects the Institute's recognition that although each sexually transmitted disease presents unique diagnostic, therapeutic and prevention challenges, all STDs share a common mode of transmission and, therefore, a research approach that addresses these diseases as a group is likely to be highly productive in yielding important insights. The CRCs will provide a multi-disciplinary, systematic, sustained approach to sexually transmitted diseases research. The intent of this approach is to bridge the basic research, clinical, and epidemiologic research arenas; to facilitate intervention-oriented behavioral research for prevention and control of STDs; to foster interaction with both local medical and lay communities; to develop potential sites for future multi-center clinical trials; and to provide opportunities for interaction, dialogue and planning among STD investigators through STD Branch coordination of regularly scheduled workshops. Successful applicants funded under this Request for Applications (RFA) will be supported through Cooperative Agreements. This type of funding mechanism is utilized when it is desired to encourage investigator-initiated research projects in areas of special importance to the National Institutes of Health (NIH) and when substantial programmatic assistance by NIH staff is anticipated. This RFA solicitation represents a single competition with a specified deadline for receipt of applications. Although there are no present plans to reissue this request for applications, NIAID intends to invite competitive renewal applications upon expiration of the initial funding period, contingent on the continued availability of funds for this purpose. Support is authorized by the Public Health Service Act, Public Law 78-410, as amended. The Catalog of Federal Domestic Assistance citation is Sec. 13.856, Microbiology and Infectious Diseases Research. Awards will be administered under PHS grant policies and Federal Regulations 42 CFR Part 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review of Executive Order 12372 or health system agency review. II. BACKGROUND INFORMATION During the last half of this century there have been dramatic increases in STDs in the United States. * Annually, approximately 2 million new cases of gonorrhea occur at an estimated cost of almost $1 billion; 25% of these cases are in teenagers. In addition, four new types of antibiotic resistance have emerged in the last decade. * The annual incidence of chlamydial infection is approximately 4 million cases at a comprehensive cost estimated to exceed $2.18 billion. Control of chlamydial infection is complicated by the frequency of asymptomatic disease, the cost and technical difficulty of available diagnostic tests, and the absence of effective single dose therapy. * In 1987, the largest single-year increase in infectious syphilis in more than a quarter of a century was reported. The increase in women was followed by a 21% increase in the rate of congenital cases. * Since 1980, the annual incidence of chancroid has increased more than 500% due to multiple outbreaks across the country. * Approximately 30 million Americans are afflicted with genital herpes (HSV), a painful, recurrent, incurable disease with annual costs of roughly $68 million. * In the United States, approximately 24 million people are infected with human papillomavirus (HPV), a virus which remains extremely difficult to detect and eradicate. The multiple, long-term, devastating consequences of STDs disproportionately affect women and infants. These consequences are particularly common among minority populations. * Untreated or inadequately treated gonococcal and chlamydial infections result in approximately 1 million cases of pelvic inflammatory disease (PID) each year. In 1990, estimated PID health care costs will total $3.5 billion. Consequences of PID include scarring of fallopian tubes leading to infertility, life-threatening ectopic pregnancy, and chronic pelvic pain syndromes. * In one quarter to two thirds of acutely infected pregnant women, STDs are preventable causes of adverse outcomes of pregnancy such as fetal wastage, low birth weight, and congenital infection. * Several biotypes of HPV are associated with cervical carcinoma, which is responsible for the death of approximately 5000 American women yearly. * In both men and women, STDs, particularly genital ulcer diseases such as syphilis, herpes, and chancroid, markedly increase the risk of human immunodeficiency virus (HIV) transmission. III. RESEARCH OBJECTIVES AND SCOPE The purpose of this RFA is to stimulate exceptionally high quality, multi-disciplinary, collaborative STD research efforts. This will be accomplished by collaborations among the disciplines from the basic research, clinical and epidemiological, and behavioral arenas. Appropriate collaborations may include, but are not limited to, the following disciplines: molecular biology, immunology, microbiology, cytopathology, pharmacology, animal modeling, obstetrics and gynecology, gynecological oncology, neonatology, pediatrics, adolescent medicine, dermatology, infectious diseases, social and clinical psychology, sociology, medical anthropology, health education, health care financing, biostatistics, computer modeling, and epidemiology. Interdisciplinary collaborations should both link disciplines within a single arena (e.g., molecular biology and immunology) and reach across to link disciplines in two different arenas (e.g., microbiology and social/clinical psychology). In addition to the importance of utilizing a multi-disciplinary approach, specific programmatic requirements are as follows: * DEFINITION OF RESEARCH SCOPE: Research must focus on a minimum of three STD pathogens or syndromes, each of which should be approached through multi-disciplinary collaborations. STD CRC applications must include at least two projects that link disciplines within a single arena and at least one project that links disciplines in two different arenas. Applications must, therefore, include a minimum of three research projects. Applicants are strongly encouraged, however, to propose three or more projects linking disciplines within a single arena and two or more projects linking disciplines across two different arenas for a total of at least five projects. * CLINICAL FACILITY: In order to bridge the basic research and clinical arenas, STD CRCs must offer a strong clinical facility with accessible patient populations that are appropriate to answering STD research questions. Adolescents, inner city minority groups, and antenatal, family planning and STD clinic patients are examples of potentially relevant populations. To further integrate clinical and basic biomedical research initiatives, it is also permissible for projects to include post-residency personnel who spend a maximum of one third of their time in clinical activities related to the research focus of the project. Applications must also include at least one of the following components. It should be emphasized, however, that no single application is expected to include all of these components. Other creative approaches may be proposed in addition to, but not instead of, these components. * INCLUSION OF A STRONG, INNOVATIVE, BEHAVIORAL COMPONENT TO STD CRC RESEARCH PROJECTS: Much STD research to date has focused on diagnosis, treatment, and vaccine development without integrating approaches to modify the sexual, drug and alcohol-use, or health-care seeking behaviors that are risk factors for acquisition of STDs or for development of their sequelae. STD CRCs, because of their multi-disciplinary approach, are in a unique position to design and evaluate behavioral interventions by examining microbiologic as well as behavioral outcomes. * OUTREACH ACTIVITIES TO THE LAY AND THE LOCAL MEDICAL COMMUNITIES: STD CRCs are an effective vehicle by which to stimulate an increased awareness of the prevention, diagnosis, and treatment of STDs in both the lay and the local medical communities, through outreach activities to both of these communities. Outreach activities 1) may be nonhealth-care facility based, 2) should usually focus on non-patient populations, and 3) must include an evaluation component. These activities may take many different forms including educational programs to community groups or hospital personnel, or demonstration projects involving local schools. Design of these activities should take advantage of the opportunity to institute and examine creative approaches to augment awareness of STD prevention and control issues in these communities. * LONG-TERM, ONGOING COLLABORATIONS WITH FOREIGN INSTITUTIONS IN DEVELOPING COUNTRIES: The high prevalence of STDs such as chancroid, syphilis, and HIV infection in some third-world countries provides scientifically valuable STD research opportunities. Proposals for development of long-term, ongoing collaborations between STD CRCs and foreign institutions in developing countries will, therefore, be considered. The collaboration not only must be beneficial to the foreign country but also must offer the potential for collection of STD data that are pertinent to U.S. populations and that could not be generated as effectively in the United States. Collaborations may include, but are not limited to, investigator exchanges, data collection, data analysis and/or cleaning, and specimen analysis. An optional component that may also be helpful in achieving STD CRC research goals is a developmental funds pool: * DEVELOPMENTAL FUNDS FOR NEW INVESTIGATOR OR PILOT PROJECTS: Within budget proposals, applicants may request developmental funds for new investigator projects or pilot projects. It is hoped that this type of support may be used for objectives such as the rapid, "pilot" exploration of new ideas and approaches, the generation of preliminary data for traditional NIH grant applications, or the development of new "programs." This area is discussed further in Section IV - "MECHANISM OF SUPPORT." In designing specific projects, applicants are encouraged to consider research proposals that focus on important, yet underserved, areas of STD investigation. Areas and organisms of particular interest include: * SEQUELAE OF STDs IN WOMEN: In non-pregnant women, underserved areas of research include studies elucidating the pathogenesis of complications of PID, such as infertility, ectopic pregnancy, and chronic pelvic pain syndromes, and interventions to reduce the incidence and severity of these complications. In pregnant women, areas for additional study include the epidemiology and pathogenetic mechanisms linking specific STDs with adverse outcomes of pregnancy. * GENITAL ULCER DISEASE: Underserved research topics include the epidemiology, pathogenesis, and natural history of chancroid and syphilis; studies that explore mechanisms by which genital ulcers and other STDs facilitate HIV transmission; and conversely, studies of the impact of HIV infection on the natural history, diagnosis, and treatment of other STDs. * HUMAN PAPILLOMAVIRUS (HPV): The pathogenesis, natural history and management of HPV infection require additional research efforts. Specific gaps in our knowledge include the role of HPV and the host immune response in the development and clinical manifestations of cervical disease, the role of HPV in transmission of HIV, the development of relevant animal models of genital HPV infection, and improved methods for detection and treatment of HPV infection. STD VACCINE DEVELOPMENT also continues to be an important priority. Ongoing basic research directed towards vaccine development, particularly for pathogens such as N. gonorrhoeae, C. trachomatis, T. pallidum, and herpes simplex virus type 2 (HSV-2) are research areas of interest. In order to make critical advances in this area, functional collaborations between immunologists and microbiologists focused on pathogenesis will be extremely important. WORKSHOP PARTICIPATION: Successful applicants will be expected to participate in regularly scheduled workshops. These workshops will be held at least twice yearly to share STD research advances; to discuss STD research needs and opportunities; and to develop new collaborative protocols which may include multi-center studies. MULTI-CENTER TRIALS: Because the STD CRCs will form the nucleus of a network of high-quality STD research environments, STD CRC applicants are strongly encouraged to be receptive to future participation in the development of multi-center trials. It should be emphasized that STD CRC applications are not expected to include proposals for multi-center trials at this time. It is likely, however, that STD CRCs will be asked, in the future, to consider developing proposals for multi-center studies. These studies might, for example, evaluate vaccine efficacy, examine new therapeutic interventions, or explore the natural history of STD syndromes and their sequelae. Opportunities for development and execution of collaborative trials will be facilitated by the regularly scheduled STD CRC workshops discussed above. Participation in multi-center trials will require submission of a separate NIH application which will undergo the standard NIAID peer review. IV. MECHANISM OF SUPPORT Awards will be made as COOPERATIVE AGREEMENTS. These are interactive assistance relationships in which an ongoing collaborative relationship exists between NIAID staff and the investigative team as outlined under Section V - "TERMS OF AWARD: AWARDEE RIGHTS AND RESPONSIBILITIES; NATURE OF PARTICIPATION OF NIAID STAFF." NIAID anticipates making two to four awards as a result of this RFA. The final number of awards to be made is dependent upon the availability of funds. It is estimated that the initial year's direct and indirect costs will not exceed $1.2 million for each award. Awards will be made for a project period of up to five years. The earliest possible award date is July 1, 1991. Funding beyond the first and subsequent years of the award will be contingent upon satisfactory progress during the preceding years and upon availability of funds. Award funds may be utilized to support the following research-related activities: * Scientific and Professional Personnel Costs: The requested percentage of an individual's salary may not exceed the percentage of effort devoted specifically to activities associated with the CRC. Information substantiating this level of effort must be included in the application. * Administrative Costs: This category includes the costs necessary for the central administration and fiscal management of the CRC, such as salaries of the STD CRC Chief Administrator and secretarial support. Those costs may not duplicate or replace costs included in the institution's indirect cost base. * Shared Research Resources (Cores): STD CRCs may include funds for equipment, supplies and services to expand and/or maintain clinical, laboratory, biostatistical, or behavioral facilities which are shared by research staff from at least two research projects. * Planning and Evaluation: Costs of planning and evaluating the effectiveness of individual research projects as well as the overall operation of the CRC are allowable. Budgets may, therefore, include costs of ad hoc scientific and technical consultants providing needed expertise and/or technical assistance in planning and evaluation for the STD CRC. * Developmental Funds For New Investigator Pilot Projects: In addition to the traditional cores discussed above, applicants may request that a limited pool of developmental funds also be available as a core (Developmental Funds Core). These funds would be set aside and restricted solely to cover salaries and research costs for small pilot projects proposed by new investigators or by investigators newly recruited into the parent institution. Eligible investigators are those who are employed by the awardee institution and who have not previously been principal investigators (PI) on an NIH R01 grant or on any other type of grant or contract with direct costs in excess of $37,500 The annual total amount for each of these awards may not exceed $40,000. Funds awarded under this section may be used for salary, technical support, laboratory supplies, and equipment. However, supplies and equipment expenditures for each award may not exceed $20,000 annually. Projects and investigators funded under the developmental funds core will not be eligible for subsequent awards from the developmental funds pool. The duration of support will be limited to three years unless the investigator achieves independent funding through a traditional research grant (R01) or a FIRST (R29) award prior to the end of the three-year period. In these instances, the award must be terminated, and unexpended funds must be returned to the developmental funds award pool. THIS PORTION OF THE STD CRC APPLICATION WILL BE REVIEWED PRIMARILY ON THE BASIS OF THE MERIT OF THE PROPOSED SELECTION CRITERIA FOR APPLICANTS FOR DEVELOPMENT FUNDS. The selection method and criteria for awards must be thoroughly described. A local review committee consisting of, at a minimum, the STD CRC Director, the Principal Investigators of the research projects and cores, and the NIAID Scientific Coordinator (Program Officer) will be responsible for reviewing and selecting proposals. Suggested criteria to be used by the local review committee include: 1) the scientific merit of the proposal, 2) the responsiveness of the proposal to areas of STD investigation which are currently underserved, and 3) the interdigitation of the proposed research with existing projects. Potential awardees, pilot projects, and specific research initiatives to be pursued need not be identified in the CRC application. However, in order to facilitate NIH review of this section, in addition to the selection method and criteria mentioned above, a synopsis of the kind of project that the CRC would expect to fund under this mechanism should be submitted. The synopsis should be no longer than one page. Approval of the developmental funds portion of the STD CRC application does not in any way commit the investigators to execution of the sample project. It is the NIAID's intent that developmental funding provide a flexible means for the STD CRC Director and the PI's of the CRC projects to achieve the short-and long-term goals of the STD CRC. There is no ceiling on the total dollar amount of the developmental funds pool which can be requested. Applicants are, however, reminded that funds requested for developmental projects constitute a restricted portion of the total CRC budget and will thus not be available for other CRC activities. The CRC must maintain detailed records of disbursements and expenditures of developmental funds to facilitate peer review of future competitive renewal applications. In addition to the above categories, budget requests may also include research-related costs for patient involvement and medical care, funds for limited investigator travel, and costs of publication. Since the program cannot provide funds for new construction, adequate physical facilities must be available to meet the primary needs of the project. However, limited alteration or renovation of clinical or laboratory facilities, which is fundamental to meeting the objectives of the proposed research and which is systematically justified, may be considered. In light of the frequency of the required STD CRC meetings and the desire to develop an integrated infra-structure to address STD research needs in the United States, applications will be limited to domestic institutions. Applications from domestic academic, non-profit, or for-profit research institutions are eligible for awards. Awards will be made to a group of investigators on behalf of a CRC Director who will be responsible for the coordination of STD CRC scientific and administrative activities. Support of all CRC activities will be coordinated through a Central Operations Office located within the applicant organization. It is the desire of NIAID to fund applications in a manner which will promote a geographic distribution of awards within the United States. Although this program is provided for in the financial plans of NIAID, the award of Cooperative Agreements pursuant to this RFA is also contingent upon the continuing availability of funds for this purpose. All policies and requirements of the Public Health Service (PHS), and NIH apply to applications submitted in response to this RFA. V. TERMS OF AWARD: AWARDEE RIGHTS AND RESPONSIBILITIES; NATURE OF PARTICIPATION OF NIAID STAFF Under the Cooperative Agreement, a partnership relationship exists between the recipient of the award and NIAID in which successful applicants are responsive to the guidelines and conditions set forth in the RFA. At the same time, investigators are expected to define research objectives and approaches in accord with their own interests and perceptions of novel and exploitable approaches to the research which ultimately is likely to result in improved prevention and control of STDs. It is the primary responsibility of each Principal Investigator to clearly state the objectives and approaches of the project, to plan and conduct the research stipulated in the proposal and to ensure that the results obtained are analyzed and published in a timely manner. 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. The multi-disciplinary and collaborative nature of the STD CRCs creates an extraordinary opportunity for information exchange and scientific advancement in high quality STD research. It is expected that PIs will take advantage of this opportunity by participating in both formal events established expressly for this purpose and informal investigator-initiated dialogues. The NIAID staff will work closely with the CRC Director and shall be represented by a Scientific Coordinator (Program Officer). The Scientific Coordinator will be the Chief of the STD Branch of NIAID or a staff member designated by the Chief of the STD Branch. During the award period, the NIAID Scientific Coordinator may provide appropriate assistance, advice, and guidance in: the design of research group activities; the selection of resources and replacement staff; the coordination, collection and/or analysis of data; the technical and management performance of CRC activities; and the preparation of publications. However, it is again emphasized that the role of NIAID will be to facilitate and not to direct the activities of the STD CRC. It is anticipated that decisions in all activities outlined within this RFA will be reached by consensus of the investigators and that the NIAID Scientific Coordinator will be given the opportunity to offer input to this process. NIAID will support and facilitate coordination among the STD CRCs through the following types of assistance: * cooperation in overall research planning, data analysis and reporting; * coordination of communication and facilitation of information exchange between STD CRCs; * reduction of duplication of efforts both between STD CRCs and with other extramural projects; * provision of new research reagents and technologies or of other important resources and information that may not otherwise be available to the STD CRCs; * coordination of research reagents and technologies to achieve standardization among CRCs; * assistance in selection of candidates for award of developmental funds; * authorization of key personnel changes including the Principal Investigators, Project Leaders and Co-Investigators. The Principal Investigators, Project Leaders, and NIAID Scientific Coordinator will meet periodically to review progress, plan and design research activities, and establish STD CRC priorities. In addition, each year, NIAID staff will coordinate at least two workshops at the NIH in Bethesda, Maryland (or at a site designated by NIAID). These workshops will provide a forum for Principal Investigators to share STD research advances; to discuss STD research needs and opportunities; and to develop collaborations and multi-center studies. Funds for travel to these meetings should be included in the budget. An extremely critical element of the STD CRCs' success is the degree of communication among its members. Therefore, additional informal meetings among participants from different CRCs as well as regular telephone and written communication will be important and encouraged. In the unlikely event that a scientific or programmatic dispute should arise which is resistant to productive negotiation between the STD CRC and NIAID, the decision of a three-member arbitration team will be binding. One member of this team will be chosen by the Principal Investigator and the second will be chosen by the NIAID Scientific Coordinator. These two members of the arbitration team will select the third member. These special arbitration procedures, however, do not in any way affect the awardee's right to appeal an adverse action in accordance with PHS regulations at 42 CFR Part 50, Subpart D, and HHS regulations at 45 CFR Part 16. 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 investigational clinical trial; i.e. 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 Principal Investigator to the Scientific Coordinator upon request. Such reports will be in final draft form and include background information, methods, results, and conclusion. 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. The special "TERMS OF AWARD: AWARDEE RIGHTS AND RESPONSIBILITIES; NATURE OF PARTICIPATION OF NIAID STAFF" described in this section are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS Grant Administration Regulations at 45 CFR Part 74, and other HHS, PHS, and NIH grant administration policy statements. VI. MINIMUM REQUIREMENTS FOR APPLICATION Before preparing an application, the applicant should carefully read the information brochure which accompanies each RFA: Program Project and Center Grants, NIAID. Instructions outlined in the brochure for the formatting of the application should be followed carefully. Failure to follow the instructions may result in unnecessary delays in the review process. Particular attention should be given to the following areas when responding to the application instructions found in the brochure. * The detailed description of each research project should demonstrate that it contributes to the attainment of the CRC's overall objectives. * In describing the clinical and laboratory facilities available to conduct each project, specific information should be included on the institution's present patient load and projections for patient involvement in clinical investigations as well as on the availability of appropriate biohazard facilities and safety procedures. Applicants are urged to give added attention where feasible and appropriate to the inclusion of females and of minorities in study populations for STD CRCs. If either females or minorities are not included in a given study, a clear rationale for their exclusion should be provided. * Included in information under the "Other Support" section must be an explicit written plan which explains how applicant Principal Investigators who also hold Principal Investigator status on grants unrelated to the STD CRC application (particularly on Program Project, Training, or Center grants) will be able to successfully and fully meet the responsibilities demanded by both endeavors. * In addressing the Organization and Administrative Structure of the CRC, the mutually reinforcing inter-relationships among the members of the STD CRC and the contribution of each to fulfillment of STD CRC objectives should be clearly described. This section must include an organizational chart showing the name, the organization and the scientific discipline of the Principal Investigator, the Project Leaders, and the key personnel for the projects and cores. * 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. * Also required is a plan to assure the maintenance of close collaboration and effective communication among members of the STD CRC. This plan should be co-signed by the Principal Investigator and all Project Leaders to indicate acceptance of the participation of NIAID Staff and to show commitment to the collaborative organization and protocols of the proposed studies. * A written commitment by the sponsoring institution which explicitly defines the institution's willingness and preparedness to commit resources to ensure development, function and maintenance of the proposed STD CRC must be included in the application. This letter should be co-signed by the relevant departmental chairperson and dean of the institution. VII. REVIEW PROCEDURES AND PEER REVIEW CRITERIA REVIEW PROCEDURES: Applications that are judged to be incomplete or non-responsive to this RFA will be withdrawn by NIAID staff upon receipt and returned to the applicant without further consideration. Those applications that are complete and responsive to the RFA may be subjected to triage review by an NIAID peer review group to determine their scientific merit relative to the other applications received in response to the RFA. The NIAID will withdraw from competition those applications judged by the triage peer review group to be noncompetitive for award and will notify the applicant and the institutional business office. Those applications considered to be competitive for award will be reviewed for scientific and technical merit on or about February 1991, by a committee convened by the Division of Extramural Activities, NIAID. The second level of review will be provided by the National Advisory Allergy and Infectious Disease Council in May 1991. The earliest award date is July 1, 1991. PEER REVIEW CRITERIA: It is again emphasized that prospective applicants should read carefully the information brochure "PROGRAM PROJECT AND CENTER GRANTS, NIAID" which is available from Dr. Wasserheit (see X. INQUIRIES). The brochure describes program projects and other large, multi-disciplinary grants; outlines review criteria for such programs; and includes other important information that will aid in formatting the application. The review criteria outlined in the brochure are the review criteria to be used by the peer review group in the evaluation of applications received in response to this RFA. Specifically, proposals will be evaluated for scientific merit including the originality, uniqueness and technical excellence of the research projects. Programmatic relevance and overall responsiveness to the research objectives stated within this RFA will, of course, also be considered. In addition to the review criteria stated above, proposals must satisfy the previously mentioned specific programmatic requirements that are summarized below. These requirements appear in greater detail in Section III - "RESEARCH OBJECTIVES AND SCOPE" and applicants are urged to review this section carefully. * Research must focus on a minimum of three STD pathogens or syndromes, each of which should be approached through multi-disciplinary collaborations. * Applications must include at least two projects which link disciplines within a single arena and at least one project which links disciplines in two different arenas. * Applications must therefore include a minimum of three research projects. * Successful applicants will be expected to participate in regularly scheduled workshops. * STD CRCs must offer a strong clinical facility with accessible patient populations that are appropriate to answering STD research questions. Applications must also include at least one of the following components. Other creative approaches may be proposed in addition to (but not instead of) these components. * Research which includes a strong, innovative, behavioral component. * Outreach activities which may be nonhealth-care facility based, which should usually focus on non-patient populations, and which must include an evaluation component. * Long-term, ongoing collaborations between foreign institutions in developing countries and the STD CRC. As explained in detail under Section IV - MECHANISM OF SUPPORT, applications that include requests for developmental funds are advised to include a description of the selection method and criteria for awards and a one-page synopsis of the kind of project expected to be funded under this mechanism. VIII. METHOD OF APPLYING LETTER OF INTENT: Prospective applicants are asked to submit, by August 1, 1990, a short letter of intent that includes a descriptive title and the names and affiliation(s) of proposed key investigators for each of the proposed research projects. The letter of intent is requested in order to provide an indication of the number and scope of applications to be reviewed. The letter of intent does not commit the sender to submit an application, nor is it a requirement for submission of an application. The letter of intent should be sent to: Dr. Olivia Preble Acting Chief, Microbiology and Immunology Review Section Program and Project Review Branch National Institute of Allergy and Infectious Diseases National Institutes of Health Westwood Building - Room 3A10 Bethesda, Maryland 20892 Telephone: (301) 496-8208 FORMAT OF APPLICATIONS: Applications must be submitted on form PHS 398 (Rev. 10/88), the application form for research grants. Application kits are available at most institutional business offices or may be obtained from the Office of Grants Inquiries, Room 449, Westwood Building, Division of Research Grants, National Institutes of Health, Bethesda, Maryland, 20892. The format and detail applicable to regular research grant applications should be followed, and the requirements specified under Section VII - "REVIEW PROCEDURES AND PEER REVIEW CRITERIA" must be fulfilled. APPLICATION PROCEDURE: A signed, typewritten original of the application, including the checklist, and four (4) signed, exact, single-sided copies should be sent or delivered, in one package, to: Division of Research Grants National Institutes of Health Westwood Building - Room 240 Bethesda, Maryland 20892** TWO ADDITIONAL COPIES MUST ALSO BE SENT DIRECTLY TO DR. OLIVIA PREBLE AT THE ADDRESS GIVEN ABOVE. The RFA label available in the form PHS-398 (rev. 10/88) must be affixed to the bottom of the face page of the original signed application. Failure to use this label could result in delayed processing of the application such that it may not reach the committee in time for review. To assure the identification of your application with this RFA, the application must have "SEXUALLY TRANSMITTED DISEASES COOPERATIVE RESEARCH CENTER" RFA AI-90-03 typed on item 2 of the face page and check the "YES" box. IX. CONSEQUENCES OF LATE APPLICATIONS To ensure their review, applications must be received by both DRG and Dr. Olivia Preble by October 10, 1990. Applications received after October 10, 1990 will be returned without review. The DRG will not accept any application in response to this announcement that is the same as one currently being considered by any other NIH awarding unit. X. INQUIRIES Investigators seeking information relevant to this RFA should contact: Dr. Judith Wasserheit Chief, Sexually Transmitted Diseases Branch Westwood Building - Room 749 Division of Microbiology and Infectious Diseases National Institute of Allergy and Infectious Diseases National Institutes of Health 9000 Rockville Pike Bethesda, MD 20892 Telephone: (301) 402-0443 Questions regarding review procedures should be addressed to Dr. Preble, at the address given above. Questions regarding fiscal matters should be addressed to: Mr. Todd Ball Grants Management Branch Division of Extramural Activities NIAID, NIH Westwood Building - Room 726 Bethesda, Maryland 20892 Telephone: (301) 496-7075