Full Text AI-92-12 WOMEN'S INTERAGENCY HIV STUDY NIH GUIDE, Volume 21, Number 41, November 13, 1992 RFA: AI-92-12 P.T. 34, II Keywords: AIDS Vaccine Risk Factors/Analysis Community/Outreach Programs Clinical Medicine, General National Institute of Allergy and Infectious Diseases Letter of Intent Receipt Date: January 11, 1993 Application Receipt Date: February 18, 1993 PURPOSE The Vaccine Trials and Epidemiology Branch (VTEB) of the Division of AIDS (DAIDS) of the National Institute of Allergy and Infectious Diseases (NIAID) invites applications for cooperative agreements for the establishment of a Women's Interagency HIV Study (WIHS) to investigate the clinical, laboratory, and psychosocial impact of human immunodeficiency virus (HIV) infection in women. The WIHS will use a multi-site, prospective study design to gather data on the clinical, immunological and behavioral aspects of HIV infection and disease in women. This study will investigate the full spectrum of clinical disease caused by HIV infection in women. It also will seek to determine the immunological factors and the cofactors which may be associated with HIV disease progression in women. 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), Women's Interagency HIV Study, 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. 017-001-10473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic non-profit and for-profit research institutions; public and private organizations such as universities, colleges, hospitals or laboratories; units of State and local governments; and eligible agencies of the Federal government. Applications from minority individuals and women are encouraged. Applicants must demonstrate the capability to recruit and maintain a minimum of 300 HIV-infected women and 75 HIV seronegative women with high risk behaviors for HIV; the proposed study cohort should reflect the socioeconomic, racial, and ethnic female populations infected with HIV in the US. MECHANISM OF SUPPORT Successful applicants funded under this RFA will be supported through Cooperative Agreements (U01). This type of funding mechanism is used when it is desired to encourage investigator-initiated research projects in areas of special importance to the NIAID and when programmatic assistance and involvement of NIAID staff would be beneficial to attain the desired research goals. This RFA represents a single competition with a specified deadline for receipt of applications. Reissuance of this RFA will be dependent on the state of science and findings at the completion of this cooperative agreement as well as the availability of funds. It is estimated that the total annual cost for an awardee with a study population of 300 HIV-seropositive women and 75 HIV-seronegative women could approach $1,000,000. It may be advantageous for applicants (including institutional consortia) to recruit significantly more than the minimum number of women when it would be cost effective. Awards will be made annually for a period of up to four years. Continuation of funding for each new annual budget period will be contingent on availability of funds, and will be based on satisfactory performance in recruitment and retention, success in protocol performance, and scientific productivity. Annual progress reports will be required and will include reports on recruitment, retention, and scientific productivity. Funding adjustments may be made based on study performance and changing NIAID research priorities. FUNDS AVAILABLE Approximately $5,000,000 will be available for funding the total costs of the WIHS during its initial year. The earliest possible award date is July 1993. The NIAID anticipates making two to five awards as a result of this RFA. The final number of awards to be made is dependent upon receipt of a sufficient number of applications of high scientific merit and the continuing availability of funds. RESEARCH OBJECTIVES Background The number of cases of Acquired Immunodeficiency Syndrome (AIDS) diagnosed in women has increased rapidly since 1985. As of December 1991, more than 21,000 cases of AIDS in women had been reported to the Centers for Disease Control (CDC) in sharp contrast to the approximately 1,100 women reported by the end of 1985. Approximately 100,000 American women are estimated to be infected with HIV-1. These numbers are expected to continue to increase throughout the 1990s. Major deficiencies remain in understanding the clinical, immunological, and virological spectrum of HIV disease and AIDS in women. Gynecological manifestations of HIV infection have not been sufficiently studied despite early results indicating their importance. There is also a growing body of evidence that other female genital and reproductive tract infections, such as vaginal candidiasis, pelvic inflammatory disease (PID), syphilis, herpes simplex virus-2 (HSV-2), and other sexually transmitted infections, are more severe and/or more common in women with HIV-induced immune dysfunction than in comparable groups of HIV-negative women. The rate and pattern of decline of CD4+ cells and factors which affect immune function in HIV-infected women have not been well-characterized. On the basis of these early reports, women-specific disease outcomes have been identified suggesting the need for a large-scale prospective study of HIV infection and disease in women to address the multiplicity of research questions within a single research design. Such information is critically important in designing and interpreting medical intervention research including trials of therapeutic interventions and vaccines. These data will be important in designing programs to improve access to and use of medical services by HIV-infected women. The primary purpose of this RFA is to develop a cooperative multi-site prospective epidemiologic study of the clinical, immunologic, virologic and behavioral aspects of HIV disease progression in women. The NIAID and CDC have jointly developed an organizational working arrangement for the HERS and for the transition phase incorporating the NIAID-funded WIHS sites. This organizational structure of an Executive Committee and Working Groups is intended to enable the NIAID WIHS sites expedite implementation of their cooperative agreements, while protecting the autonomy implicit in an assistance mechanism. The NIAID continues to play an active role in facilitating the HERS. The CDC and the NIAID have initiated the initial phase of this interagency prospective study of HIV-infected and uninfected women through the CDC's 1991 program announcement #115 (Federal Register, vol. 56, no. 65, Thursday, April 4, 1991), the HIV Epidemiology Research Study (HERS). Cooperative agreements have been awarded by the CDC to four clinical sites. For purposes of clarity in this RFA AI-92-12, the HERS sites will be referred to as the "CDC HERS sites", though it should be understood that they are part of the WIHS initiative. Accordingly, awardees of this RFA will be referred to as the "NIAID WIHS sites," and will be named by the WIHS Principal Investigators themselves after the cooperative agreements are awarded. A pilot study manual for this phase of the study has been developed by the CDC, NIAID, the four currently funded clinical sites, and an interim data center. Pilot studies of draft data collection instruments and procedures have been initiated including: (1) study subject identification and enrollment; (2) patient sociodemographic and health history; (3) physical examination; and (4) laboratory specimen collection and procedures. The current version of these materials will be provided to potential applicants upon written request to Dr. Sandra Melnick, Division of AIDS, NIAID (see INQUIRIES for address and FAX numbers). A Request for Proposals (RFP) for a Statistical and Clinical Coordinating Center (SACCC), which will support WIHS and other NIAID prospective studies, has recently been announced. So that applicants for cooperative agreements under this WIHS RFA are aware of the services to be provided by the SACCC, each prospective applicant will also be provided with a copy of the statement of work from the SACCC RFP. When new sites are awarded under this RFA, the awardees will review the study protocols to arrive at data collection procedures and instruments compatible with those of the HERS sites, and contribute to the development of new studies and procedures. The final study design could be a modular study design that may include both standardized modules (separate study protocols on a particular topic, consisting of standardized physical exam procedures and a questionnaire) to be used at all CDC HERS sites and NIAID WIHS sites, as well as separate modules for CDC HERS sites that differ from those modules used by the NIAID WIHS sites. During the course of the four-year study period, there may also be modules carried out at a single site. Plans for such site-specific modules are encouraged in this application (see Site-Specific Research Studies). Sample Size Goal The goal of the entire WIHS research effort is 2,500 HIV-seropositive women and a comparison group of 775 HIV-seronegative women who engage in activities that place them at high risk of acquiring HIV. The following table shows the sample size goals for the NIAID WIHS sites and the CDC HERS sites. NIAID WIHS sites CDC HERS sites Total 1,700 HIV(+) women 800 HIV(+) women 2,500 375 HIV(-) 400 HIV(-) 775 high risk women high risk women 2,075 women 1,200 women 3,275 RESEARCH OBJECTIVES The overall objectives of WIHS are to: o Determine the spectrum and course of the clinical manifestations of HIV infection in women, including those affecting the genital tract and oral cavity. o Determine the pattern and rate of decline of CD4+ cells in women and the relationship of CD4+ changes to other immunologic and virologic parameter, and to the clinical manifestations of HIV. o Investigate factors (e.g., infectious, treatment-related, nutritional, socioeconomic, drug-use related) that may delay or accelerate HIV-induced immune dysfunction and specific manifestations of HIV-associated clinical disease. o Study the factors influencing the length of survival and quality of life of women with HIV infection. Although the emphasis of this study is not on HIV transmission, follow-up of the initially seronegative group of women will be important to: o Determine the rate of incident HIV seroconversion and identify the factors that may increase the risk of incident HIV infection among a smaller cohort of high-risk women who are HIV-antibody negative at the time of study enrollment. o Access the feasibility of HIV vaccine trial initiation in high-risk HIV-seronegative women by assessing willingness to participate in vaccine efficacy trials. All applicants should provide plans and other evidence describing their capability to participate in this multicenter collaborative study. The Research Plan should be based on the approaches the applicant would take to participate in the WIHS including recommendations to refine the draft HERS procedures being provided to applicants. The Research Plan should address separately three components of WIHS: 1. Cohort Studies including o Recruitment, Retention, and Service Linkages. o Study Visits and Data Collection Including Interviews, Medical Histories, and Physical Examinations. o Laboratory Specimen Collection, Testing, and Storage. 2. WIHS Organization, Management, and Communications 3. Site-Specific Research Studies Each WIHS component is discussed separately in the following paragraphs. Cohort studies o Recruitment, Retention, and Service Linkages The applicant should provide a recruitment and retention plan with information regarding their access to, and ability to enroll and retain, a minimum of 300 HIV-infected women and 75 HIV-uninfected but high risk women into a prospective study of HIV-related disease outcomes. Adolescents (ages 15 to 18) may be recruited depending on local Institutional Review Board (IRB) requirements and applicable State laws. The suggested enrollment ratio of HIV-infected women to uninfected high risk women is five to one. Uninfected women should meet criteria for high-risk of acquiring HIV infection including current or recent injection drug or crack cocaine use and/or engaging in high risk sex (e.g., as a commercial sex worker, as a sexual partner to an injection drug user, and/or engaging in frequent heterosexual encounters that are not for money). Applicants should demonstrate their capability to enroll at least 300 HIV infected women and 75 uninfected high risk women by 18 months. At least 50 percent of the HIV infected women should be in later stages of HIV disease. The applicant's recruitment and retention plan should address the following elements: o Plans for community outreach, screening for cohort enrollment, HIV testing and counseling, and informed consent. o Evidence of capability to work with women who have substance abuse problems. o Identification of sources of study subjects, e.g., inpatient or outpatient units providing primary care or substance abuse treatment, HIV clinics and testing sites, referrals from community-based physicians or agencies, sexually transmitted disease clinics, and community-based clinics. o Description of procedures for assistance with and referral for non-protocol-related care. A strategy for interaction with community health care providers or agencies to handle referral of HIV-infected women in this study should be incorporated into the application. The cultural, ethnic, and language expertise of the staff to interact with community-based organizations and with women in their communities, or alternatively, the ability of the staff to interact with community-based organizations and with women in a culturally sensitive manner, should be described. o Provision of a detailed and specific plan for retention of study subjects, including, for example, a patient advocate or study nurse who provides continuity of care at visits, a small cash award, or reimbursement/vouchers for transportation expenses, on-site child care arrangements, culturally sensitive research staff, etc. Collaboration with community-based organizations is strongly encouraged to facilitate retention of women, particularly from socioeconomically disadvantaged backgrounds. All applicants should describe how clinical care will be provided to study participants, and describe the amount of primary care, if any, that will be provided by the research study staff to the study population. Clinical care costs directly associated with the WIHS protocols can be paid for under this award, when these are not covered by other sources. Proposed clinical facilities should have demonstrated experience in providing services to, or effective referral services for low-income cultural and ethnic minority groups and chemically dependent women. Applicants are encouraged to form linkages with other AIDS-related studies and services. Applications should include letters of agreement in the application that should be co-signed by the Principal Investigator of the applicant institution and each cooperating site. All letters should be explicit as to the intended purpose and role of the collaborating site or organization. See Appendices 5-13 for listings of contacts for AIDS-related services and studies, including: Contact List Appendix AIDS Clinical Trial Units (ACTUs), which comprise the AIDS Clinical Trials Group (ACTG) 5 Community Programs for Clinical Research on AIDS (CPCRA) 6 General Clinical Research Centers (GCRCs) 7 Research Centers at Minority Institutions (RCMIs) 8 Centers for AIDS Research (CFAR) 9 National Institute on Drug Abuse (NIDA) Cooperative Agreement Awardees 10 American Foundation for AIDS Research (AmFAR) Community-based Clinical Trials Network 11 AIDS Vaccine Evaluation Units (AVEUs) which comprise the AIDS Vaccine Evaluation Group (AVEG) 12 Health Resource and Services Administration (HRSA) Ryan White CARE Act Titles I & II Grantees 13 Applicants should describe plans for establishing, within two months of award, a Community Advisory Board (CAB). The purpose of the CAB is to foster interaction between the WIHS staff and HIV-infected women in the community, health care and other service providers, and other related community-based groups. (If an appropriate CAB is already in place, it is not necessary to establish a separated CAB for this project). Applications should describe the role and relationship of the CAB to the applicant institution. Applications should also specify the composition of the CAB, functions it will perform for the WIHS, and a proposed meeting schedule. Inclusion on the CAB of women, particularly those representing minority populations, to reflect the demographics of HIV-infected women in the catchment area may ensure representation of concerns of community members and patient advocates. o Study Visits and Data Collection including Interviews, Medical Histories, and Physical Examinations The applicant should submit a plan for initial and follow-up study visits. As stated above, the enrollment goal is at least 300 HIV-infected women and 75 uninfected women in the first 18 months of the study. The applicant should assume that the final WIHS procedures and data collection forms will be completed by the WIHS Executive Committee and Working Groups (see "2. WIHS Organization, Management, and Communication" below) within the first nine months after award of the WIHS cooperative agreements. The applicant's plan should be based on (1) the six WIHS objectives stated above and the associated suggested areas for study-wide data collection stated in Appendix 2 to this RFA and (2) a review the HERS study visit procedures and data collection instruments. The applicant's plan should address each of the six objectives and should include the applicant's recommendations for refinement of these HERS procedures and data collection instruments. Based on the HERS pilot study materials and possible refinements, a typical initial study visit could entail: (1) an interview; (2) a physical examination; (3) laboratory specimen collection; and (4) medical record extraction. The applicant should address their plans for conducting these initial visits as efficiently as possible. The applicants should base their plans for follow-up visits on the following considerations: (1) follow-up visits should be conducted every six months for all study participants; and (2) additional contacts (which may be short visits or phone calls) should be made to collect data on major clinical events between the regular 6-month visits for women who (a) have fewer than 350 CD4+ cells/ul at their last 6-month visit, (b) have AIDS-related clinical conditions, and/or (c) are pregnant. The applicant should discuss potential approaches to obtaining data between the regular six month visits. In preparing their plans and budgets for study visits, the applicants should consider possible attrition rates, reasons for attrition, and the implications for the study and study budgets. The applicant should assume that no study visits will be conducted during the final six months of the four year award period; that six month period will be devoted to ensuring that all study data have been completed, validated, and submitted to the SACCC. o Laboratory Specimen Collection, Testing, and Storage Applicants should submit a plan and budget for the collection and processing of WIHS study specimens. Certain specimens may be analyzed at the clinical research site and funded through this cooperative agreement. Other specimens may be obtained and shipped to central laboratories to establish consistency across sites. Applicants should review the draft HERS Laboratory Procedures and Data Collection Instruments and two appendices to this RFA: Appendix 3 for suggested components of the Laboratory Protocol and Appendix 4 for local and central processing of specimens (Appendix 4 is a summary of information from Appendix 3). Awardee laboratories will be required to participate in a quality assurance (QA) program. Funds are not available in this RFA for new laboratory equipment or for the expansion of facilities. Applicants are encouraged to make arrangements with other institutions if necessary to have adequate laboratory capabilities. The laboratory studies plan should provide documentation of the following: (1) prior experience with each proposed laboratory procedure; (2) facilities available for performance of laboratory procedures; (3) current quality assurance programs; (4) experience with multi-institutional prospective studies; and (5) facilities and processes for the storage and shipment of study specimens. The applicant's budget should be based on the information in RFA Appendices 3 and 4 and in the HERS draft procedures and data collection instruments. The applicant should address possible changes or improvements in the laboratory efforts that could be incorporated into WIHS with the approval of the WIHS Executive Committee. Site-specific research studies Access to significant numbers of clinical specimens from well-characterized study subjects will be a important resource for the support of research studies of HIV and AIDS-related issues. Applicants should propose site-specific research studies that will investigate issues associated with one or more of the major objectives of WIHS (stated above) and the associated suggested areas for study-wide data collection presented in Appendix 2 of this RFA. These proposed research studies should take advantage of samples and data generated under the WIHS protocols. Research that does not require the use of WIHS samples, WIHS data, or WIHS study subjects will not be supported by this RFA; applicants for such research are encouraged to seek funding through other funding sources and mechanisms. SPECIAL REQUIREMENTS Terms and conditions Special Requirements Under the Cooperative Agreement Successful applicant(s) funded under this RFA will be supported through Cooperative Agreements. Within a cooperative agreement, a partnership relationship exists between the recipient of the award and the NIAID. Each party to this partnership within the WIHS will have rights and responsibilities as well as a defined working relationship. Awardee Rights and Responsibilities The WIHS Principal Investigators will be responsible for directing the research efforts of the WIHS, as well as the conduct of the studies performed at their respective clinical sites. As a group (the Executive Committee), WIHS investigators will identify scientific objectives and research hypotheses, arrive at mutually-agreed upon data collection instruments and physical exam protocols, and verify that the data collection instruments will meet the objectives and produce high quality data. Investigators will implement the protocols and the data collection instruments, and be responsible for ensuring patient accrual. WIHS investigators will hold leadership positions in the Executive Committee, on the Working Groups, and ad hoc committees, thereby providing the direction for the study. These responsibilities will also include overseeing study design, data analyses, and presentation of results according to Executive Committee policies. WIHS site performance during each budget period will determine the subsequent budget awards. Applicant institutions are reminded that adequate protection for human subjects in research is an essential requirement for the NIH. Awardee institutions, each subordinate entity to the Awardee, and each performance site, whether institutions or independent investigators, should agree that the rights and welfare of human subjects involved in research under this cooperative agreement shall be protected in accordance with 45 CFR 46. As a condition of award, not as a condition of application, applicants and affiliated performance sites are required to designate an Institutional Review Board (IRB) and possess an applicable assurance of compliance which has been approved by the Office for Protection from Research Risks (OPRR) of the NIH. Applicants will be notified if additional information is required on this matter. NIAID Rights and Responsibilities The NIAID staff will assist the WIHS Principal Investigators through a Program Official who will be designated by the Chief of the Vaccine Trials and Epidemiology Branch of NIAID's Division of AIDS. The NIAID Program Official will have overall responsibility to assure the scientific and technical integrity of the project on behalf of the Institute. It is again emphasized that the role of NIAID will be to act as a facilitator and not to direct the activities of the WIHS investigators. It is anticipated that decisions aimed towards achieving the research objectives of the WIHS project will be made by the Executive Committee. NIAID staff will assist the WIHS awardees by o Providing scientific and technical assistance in the development of research plans, data collection methods, analyses and reporting. o Providing technical support in areas including statistical and data collection, analysis, and publication through the SACCC. o Providing logistical and other support services for meetings of the Executive Committee and Working Groups. o Preventing duplication of efforts among WIHS sites, other WIHS grantees, and other related NIAID projects by overseeing efforts of all the sites, and other NIAID projects. o Coordinating research reagents and technologies used by WIHS sites to achieve standardization. The NIAID will establish an arbitration process to resolve any difference of opinion between the awardee and the NIAID with regard to programmatic decisions on scientific-technical matters. An arbitration panel, composed of one WIHS awardee designee, one NIAID designee, and a third designee with expertise in the relevant area and chosen by the other two, will be formed to review any scientific or programmatic issue that is significantly restricting progress. While the decisions of the Arbitration Panel are binding, these special arbitration procedures will in no way affect the awardee's right to appeal an adverse action in accordance with PHS regulations at 42 CFR Part 50, subpart D, and HHS regulations at 45 CFR Part 16. Cooperative Agreements are subject to the administrative requirements outlined in OMB circulars. All pertinent HHS, PHS, and NIH grant regulations, policies and procedures, with particular emphasis on PHS regulations at 42 CFR Part 52 and HHS regulations at 45 CFR Parts 74 and 92, are applicable. These special terms and conditions pertaining to the scope and nature of the interaction between NIAID and the investigators will be incorporated in the Notice of Grant Award. However, these terms will be in addition to, not in lieu of, the customary programmatic and financial negotiations which occur in the administration of cooperative agreements. WIHS Organization, Management, and Communication The planned organizational structure for WIHS and the current organizational structure for HERS are presented in Appendix 1 to this RFA. In that appendix, the roles of the Executive Committees and Working Groups for both WIHS and HERS are outlined. Executive Committee. To ensure that the WIHS addresses questions of the highest scientific priority and to provide leadership and direction for the study, WIHS Principal Investigators, and the NIAID WIHS Program Official will be members of the Executive Committee with voting privileges. The Principal Investigator from the SACCC and one program official from each Federal agency contributing funds to the project will participate as ex officio members of the Executive Committee. This organizational structure of an Executive Committee and Working Groups is intended to enable the NIAID WIHS sites to expedite implementation of their cooperative agreements while protecting the autonomy implicit in an assistance mechanism. The Executive Committee will develop general WIHS policies concerning: subcommittee or Working Group structure and membership; publications; access to data; interim data monitoring; agendas for group meetings; protocol and questionnaire development; evaluation of WIHS performance; and schedule and content of WIHS meetings. Most importantly, the Executive Committee will be charged with the establishment of overall scientific priorities. Working Groups. Within this cooperative framework, clinical staff may participate in study-wide Working Groups and contribute to the broader study goals outside of the sphere of their own clinical center. These Working Groups will have responsibility for the development of a research agenda for specific topic areas, for developing and modifying modules (specific clinical physical examination and laboratory specimen collection procedures) to address that agenda, assess the progress in specific topic areas, and publish the results of collaborative study findings. These activities will be conducted according to procedures and standards developed and/or overseen by the Executive Committee. While the CDC HERS sites and NIAID WIHS sites will each have their own Executive Committee, it is the intention of NIAID and CDC Program Officials to encourage the merger of the two Executive Committees, or develop other collaborative arrangements, as soon as is practical and desirable. Applicants should review the material in Appendix 1 with particular reference to the Working Groups which have been established for the HERS study. Given the objectives and scope of WIHS, applicants are requested to recommend Working Groups for WIHS, to state why these specific Working Groups will be needed, and to identify which proposed staff would be recommended as members of each Working Group. Applicants are also asked to recommend an approach which could be taken during the first nine months after the award of WIHS to use the Executive Committee and Working Groups structure to develop final data collection procedures and instruments. Study-wide data management issues Data Management and Study Coordination The WIHS will be assisted by the SACCC, contracted by the NIAID, to provide extensive technical and logistical support. This contract will: 1) provide statistical expertise and data analysis, in conjunction with the Executive Committee; 2) establish and administer an effective and responsive data management system; and 3) assist with the design and implementation of educational and training activities involving data quality assurance, including clinical training for the staff performing physical examinations at the WIHS clinical sites. Each applicant will be sent a copy of the work statement from the Request for Proposals (RFP) for the SACCC so that the applicant can be aware of the full range of services to be provided by the SACCC. Applicants may plan for either: o On-site data entry, using a data entry module that will be developed by the SACCC. Computer tapes or diskettes containing files of the data entered on site will be sent to the SACCC. OR o Central data entry by photocopying and retaining copies of completed data collection instruments on site, and sending the originals to the SACCC for data entry. Inconsistencies discovered by the SACCC and reported to the sites will be the responsibility of the sites to resolve regardless of whether they elect on-site or central data entry. Selection of either option does not preclude the participation of the site investigators in any of the above activities, including statistical analyses of their own data. At a minimum, applicants should have equipment available for computer-to- computer electronic mail communications and report generation. This equipment should be dedicated for WIHS-related operations, and should include: o IBM compatible 386/33 microcomputer. o Monochrome or color VGA display. o Minimum of 40 megabyte hard disk, 2 megabyte memory, (dual 3.5" and 5" drives are recommended). o Hayes compatible 9600 baud modem. o Hewlett-Packard IIIP or comparable laser printer. o WordPerfect word processing software, version 5.1. o ProComm Plus or compatible communications software. Reporting Requirements, Access to Data, and Publication of Research Findings In addition to the reporting requirements currently in existence for awardees of traditional NIH research project grants, the following apply: o Site-Specific Data WIHS awardee institutions will generate data that will be submitted to the SACCC as explained above. In most cases, these institutional data will represent a subset of the total database for a given protocol. These data may have limited value or may have substantial independent scientific value for specific research questions. The WIHS Executive Committee may establish policies encouraging or limiting publication of such site-specific institutional data as appropriate for a given circumstance. These institutional data will remain the property of the awardee. o Study-Wide Data The total database for the WIHS core protocol will come from all funded sites, including the HERS sites. While physically located at the SACCC, the use and publication of the data will be governed by policies established by the Executive Committee. Working groups will be established to define research questions of interest, coordinate data analyses, and determine publication policies and dissemination of findings. NIAID Program staff, in collaboration with the EC, (or Program staff from other Federal funding agencies) may have access to data generated under this cooperative agreement. Information obtained from the data may be used by NIAID for the preparation of internal reports on WIHS activities. However, the awardees will retain rights to the data. Publication policies will be established by the Executive Committee. Publication of major findings is the responsibility of the Executive Committee in accordance with these policies. Publication or oral presentation of work performed under this agreement will require appropriate acknowledgement of NIAID support. Specific instructions This section supplements the instructions for preparing a grant application, form PHS 398 (rev. 9/91). Additional information is provided on the organization of the application to accommodate a multi-component studies. The cooperative agreement application should be assembled and paginated as one complete application. Research Plans Separate research plans are required for each of the three WIHS components: (1) Cohort Studies; (2) WIHS Organization, Management, and Communications; and (3) Site-Specific Research Studies. o Component 1 - Cohort Studies. As part of items 1-4 of the Research Plan section of the PHS 398 form, applicants should present their plans for the required cohort studies including: (a) recruitment, retention, and service linkages; (b) study visits and data collection; and (c) laboratory specimen collection, testing, and storage (see pages 14-18 of the RFA). This section may not exceed 20 pages in length. A separate PHS 398 page 2, titled "Component 1 - Cohort Studies", should precede this section. o Component 2 - WIHS Organization, Management, and Communications. In place of items 1-4 of the Research Plan section of the PHS form 398, applicants should present their plans for participation in central WIHS activities (see RFA pages 21-22. This section may not exceed five pages in length. A separate PHS 398 page 2, titled "Component 2 - WIHS Organization, Management, and Communications" should precede this section. o Site-Specific Research Studies. For each proposed research study, the applicant should complete the Research Plan section of the PHS 398 (see RFA page 18). Items 1-4 of the Research Plan should be limited to 10 pages with emphasis on "1. Specific Aims" and "4. Research Design and Methods" since much of the background and significance will be discussed in the cohort studies section of the application. A separate PHS 398 page 2, with the title of each proposed research study, should precede each proposed study. Budgets An overall composite budget for all components of WIHS must be submitted by the applicant on pages 4 and 5 of the PHS 398 form. The composite budget must be the sum of separate itemized budgets for each component of WIHS; the itemized budgets for each component should immediately follow the composite budget. A separate itemized budget (PHS 398 form pages 4 and 5, renumber appropriately) must be completed for the following components of WIHS: o Cohort Studies. The budget for the cohort studies should be based on (a) the applicants proposed number of study subjects including estimated retention rates; (b) the visits, exams, and laboratory studies presented in the draft HERS protocols; (c) supplies to carry out the study activities; and (d) computer equipment. NOTE: Budget justification should include a breakdown of laboratory costs (i.e., cost per test). On-site laboratory costs charged to this grant must be the actual cost of the test. Applicants must include cost of shipping those tests that will be processed at a central laboratory (see Appendix 4). NOTE: Although applicants are encouraged to recommend refinements in the HERS protocols, the budget should be based on the current HERS design. o WIHS Organization, Management, and Communications. The budget for this component should address personnel involved in carrying out study activities, and travel/meeting information should be based on the assumptions presented on pages 26 and 27 of the RFA. Travel costs for meetings other than those related to the conduct of the WIHS will not be covered by this award. o Site-Specific Research Studies. A separate budget must be prepared for each proposed research study, using pages 4 and 5 of the PHS 398 kit (renumbered appropriately). For budget purposes, applicants should assume the following: Executive Committee. While the actual number and scheduling of the Executive Committee will be determined by the Principal Investigators, for budgetary purposes, assume there will be two one-day meetings per year of the Executive Committee during the first nine months of WIHS to develop, review, and make final WIHS policies and procedures prior to, or during the initial phase of, enrollment of the study subjects. Assume that there will be a third one-day meeting of the Executive Committee at the end of the first year of WIHS. Assume that three of the meetings will be held in Bethesda, MD and two will be held in Atlanta, GA. Assume that participants from each awardee will include the Principal Investigator and one other senior staff member. For the second through fourth years of WIHS study, assume there will be three one-day Executive Committee meetings per year. Assume that two of the meetings will be held in Bethesda, MD and one in Atlanta, GA. These meetings are intended to provide a forum for the Executive Committee(s) and working groups (see below) to review research findings, define research activities, and discuss and resolve issues. Meetings will include the Principal Investigator and one other senior staff member from each funded site. Assume that the Executive Committee will also hold conference calls twice monthly for the duration of the project. Working Groups. While the actual number and content of the Working Groups will be decided by the Executive Committee, assume there will be seven Working Groups. Assume that each awardee will have one staff member from his/her clinical sites on each Working Group. During the first nine months of the WIHS awards, assume that each Working Group will meet two times for two-day meetings; one meeting to be held in Bethesda, MD and one meeting to be held in Atlanta, GA. Although the purposes of these meetings will be specifically determined by the Executive Committee, the general goal will be to provide a forum to review and discuss refinements and changes to the protocols for approval by the Executive Committee. Assume an additional two-day meeting will take place at the end of the first year of the WIHS in Bethesda, MD. During the second through fourth years of the WIHS study, assume there will be three two-day meetings annually of each Working Group. In addition, assume all working groups will hold conference calls twice monthly. STUDY POPULATIONS SPECIAL INSTRUCTIONS TO APPLICANTS REGARDING IMPLEMENTATION OF NIH POLICIES CONCERNING INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH STUDY POPULATIONS NIH policy is that applicants for NIH clinical research grants and cooperative agreements will be required to include minorities and women in study populations so that research findings can be of benefit to all persons at risk of the disease, disorder or condition under study; special emphasis should be placed on the need for inclusion of minorities and women in studies of diseases, disorders and conditions which disproportionately affect them. This policy is intended to apply to adult males and females. 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 should be described in terms of racial/ethnic group. In addition, racial/ethnic issues should be addressed developing a research design and sample sizes appropriate for the scientific objectives of the study. This information should be included in the form PHS 398 in Sections 1-4 of the Research Plan AND summarized in Section 5, Human Subjects. Applicants are urged to assess carefully the feasibility of including the broadest possible representation of minority groups. However, NIH recognizes 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., Asian and Pacific Islanders, African Americans/Blacks, Hispanics/Latinos, and Native Americans, which includes American Indians and Alaskan Natives). 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 tissues from racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. If the required information is not contained within the application, the application will be returned without further review or consideration by the NIH. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of 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 elements will not award grants or cooperative agreements that do not comply with these policies. NOTE: This study fully meets the requirements for inclusion of women because it is exclusively comprised of female subjects. LETTER OF INTENT Prospective applicants are asked to submit, by January 11, 1993, a letter of intent that includes a descriptive title of the proposed research and the name, address, and telephone number of the Principal Investigator; the identities of other key personnel and participating institutions; and the number and title of the RFA in response to which the application may be submitted. 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 is to be sent to: Dr. Sandra L. Melnick Vaccine Trials and Epidemiology Branch Division of AIDS National Institute of Allergy and Infectious Diseases Solar Building Room 2A28 6003 Executive Boulevard Bethesda, MD 20892 APPLICATION PROCEDURES The research grant application form PHS 398 (rev. 9/91) is to be used in applying for these cooperative agreements. These forms are available from the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, Maryland, 20892, telephone 301/496-7441. The RFA label available in the PHS 398 application form 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, WOMEN'S INTERAGENCY HIV STUDY, RFA AI-92-12 should be typed on line 2a of the face page of the application form and the "YES" box should be marked. Submit a signed, typewritten original of the application, including the checklist, and three signed, identical single-sided photocopies, in one package, to: Division of Research Grants National Institutes of Health Westwood Building, Room 240 5333 Westbard Avenue Bethesda, MD 20892** At the time of submission, two additional copies must also be sent directly to: Dr. Dianne Tingley Division of AIDS Division of Extramural Activities National Institutes of Allergy and Infectious Diseases Solar Building, Room 4C16 6003 Executive Boulevard Bethesda, MD 20892 Applications must be received by both the Division of Research Grants (DRG) and Dr. Tingley by February 18, 1993. Applications received after February 18, 1993 will be returned to the applicant without review. The DRG will not accept any application in response to this announcement that is virtually identical to 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, however, the submission of substantial revisions of previously reviewed applications which are suitably tailored to the guidelines and requirements expressed in this RFA. Applications that are not received as a single package from the principal investigator will be judged non-responsive and will be returned to the applicant. Applications must also conform to the instructions contained in PHS 398 (rev. 9/91), with the exceptions that the research plan and page length limitations for the usual grant applications are modified as stated in the RFA. Applications that do not follow the prescribed font sizes outlined in form 398 will be judged non-responsive and will be returned to the applicant. Applicants should use standard, easily readable printer/typewriter fonts; it is not in the self-interest of an applicant to submit an application that is hard to read or that exceeds the above page length limitations. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed DRG for completeness and by NIAID review staff for responsiveness. Incomplete applications will be returned to the applicant without further consideration. If the application is complete, but is judged not responsive to the RFA, it will be returned to the applicant without further consideration, though the applicant may then submit a revision, within page length limitations of PHS 398 (rev. 9/91), for review as unsolicited, investigator-initiated research at the next DRG review cycle. A triage may be performed by a peer review group to determine relative competitiveness of applications responding to this RFA. The NIH will withdraw from further competition those applications judged to be non-competitive for award and notify the applicant Principal Investigator and institutional official. Those applications judged to be competitive for award will be evaluated in accordance with the criteria stated below for scientific/technical merit by an appropriate peer review group convened by the NIAID. The second level of review will be provided by the National Advisory Allergy and Infectious Disease Council in June 1993. The earliest possible award date is July 1993. The following criteria will be considered in the review of the applications: o Demonstration of the applicant's willingness and capability to participate in this multicenter study. o Adequacy of applicant's plan for achieving the recruitment and retention goals. o Adequacy of the plans for linkages with and utilization of other AIDS-related studies and services, including the requisite plans for establishing or utilizing a Community Advisory Board. o Adequacy of applicant's plan for refining and implementing HERS study visit procedures and data collection forms. o Adequacy of applicant's plan for collecting and distributing or analyzing laboratory specimens. o Adequacy of applicant's plan for participation in central WIHS activities (Executive Committee and Working Groups). o Adequacy of applicant's plan for any site-specific studies. Applicant must demonstrate that each proposed site-specific research study will use WIHS study participants, specimens, or data, alone or in some combination. o The professional qualifications and the scientific experience of the Principal Investigator and key personnel responsible for various aspects of the clinical and research investigations proposed. o Adequacy of the administrative and organizational structure that facilitates attainment of the objectives of the program, including arrangements for internal quality control, allocation of funds, day-to-day management, internal communications, and cooperation among the investigators, contractual agreements, and replacement of the Principal Investigator on an interim or permanent basis. INQUIRIES Direct inquiries pertaining to programmatic issues and for copies of HERS materials and the statement of work from the SACCC RFP, and the Appendices of the RFA to: Dr. Sandra Melnick Vaccine Trials and Epidemiology Branch Division of AIDS National Institute of Allergy and Infectious Diseases Solar Building, Room 2A28 6003 Executive Boulevard Bethesda, MD 20892 FAX: (301) 402-1506 Direct inquiries pertaining to fiscal and policy matters to Ms. Jane Unsworth Chief, AIDS Grants Management Section/GMB/DEA National Institutes of Allergy and Infectious Diseases Solar Building, Room 4B25 6003 Executive Boulevard Bethesda, MD 20892 Telephone: (301) 496-7075 FAX: (301) 480-3780 Direct inquiries pertaining to the review process and review requirements to Dr. Dianne Tingley Division of AIDS 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 AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.856, Microbiology and Infectious Disease Research and No. 93.855 Immunology, Allergic and Immunologic 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, 45 CFR Part 74, and 45 CFR Part 92. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. .
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