Full Text AI-92-13 WOMEN AND INFANTS TRANSMISSION STUDY (WITS II) NIH GUIDE, Volume 21, Number 36, October 9, 1992 RFA: AI-92-13 P.T. 34, AA, II Keywords: AIDS Infectious Diseases/Agents Epidemiology Diagnosis, Medical National Institute of Allergy and Infectious Diseases Letter of Intent Receipt Date: October 26, 1992 Application Receipt Date: January 14, 1993 PURPOSE The Vaccine Trials and Epidemiology Branch of the Division of AIDS (DAIDS) of the National Institute of Allergy and Infectious Diseases (NIAID) announces a Request for Applications (RFA) for funding the continuation of the Women and Infants Transmission Study (WITS). The purpose of this RFA is a competitive renewal of WITS I, a multi-site epidemiologic cohort study of HIV infected pregnant women and their offspring. New sites not participating in WITS I are encouraged to apply, as are current WITS I sites. Specific aims are: (1) to assess the effects of pregnancy on HIV disease progression, (2) determine maternal cofactors related to maternal-infant transmission and timing of transmission, (3) assess early diagnostic techniques to identify HIV-infected fetuses and infants, (4) evaluate the natural history of HIV infection among infants during an era of antiretroviral and other therapeutic modalities, and (5) assess the feasibility of future vaccine trials in this population. 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 RFA, Women and Infants Transmission Study (WITS II), 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, laboratories, units of State and local governments, and eligible agencies of the Federal government. Applications from minority individuals and women are encouraged. MECHANISM OF SUPPORT Applicants funded under this RFA will be supported through National Institutes of Health (NIH) Cooperative Agreements (U01). Cooperative Agreements are awarded to institutions to encourage investigator-initiated research in areas of special importance to the NIH and if substantial programmatic involvement by NIH staff is anticipated. The interaction of NIAID staff with the investigators is expected to assist and facilitate the research. There is no intent, real or implied, for staff to direct a research site's activities or to limit the freedom of investigators. This RFA solicitation represents a onetime competition for a four year award with a specified deadline for receipt of applications. Program intents for extensions beyond the initial competitive segments are uncertain. If, by the end of the third year of award, NIAID has not announced an intention to reissue the RFA, awardees who plan to apply for continuing support should contact NIAID program officials for advice on how to recompete. FUNDS AVAILABLE Approximately $5,000,000 will be available for funding the total costs for the initial year of awards made pursuant to this RFA. NIAID anticipates making four to eight 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 availability of funds. Awards will be made for a 12-month budget period within a total project period of four years. Continuation of funds for each new budget period will be contingent on availability of funds and will be made on the basis of satisfactory performance in the areas of recruitment, retention, success in carrying out the WITS protocols, collaborative efforts with the other WITS sites, and scientific productivity. Annual progress reports will be required and should include a report on scientific, recruitment, and technical progress. Funding adjustments may be made related to both study performance and changing NIH research priorities. The earliest anticipated award dates will be July 1993. Under a separate and distinct initiative, the National Institute of Child Health and Human Development (NICHD) intends to independently support one or more clinical sites. Principal Investigators at those sites will collaborate with the NIAID sponsored sites in planning and carrying out the research agenda of WITS II. RESEARCH OBJECTIVES Background The growing magnitude of the HIV epidemic among women of child-bearing age and their infants is becoming apparent in many areas of the United States. The percentages of AIDS cases among women and children are increasing more rapidly than for any other risk groups. In the 1990s, the AIDS epidemic will continue to attack African American and Hispanic women and children in disproportionately high numbers. To date, more than 80 percent of pediatric AIDS cases have been caused by maternal-infant transmission. Moreover, virtually all new cases of pediatric HIV infection in infants and children will be due to maternal-infant transmission. In the face of this growing epidemic among women and their offspring, there are a number of critical and unanswered questions related to HIV infection during pregnancy and maternal-infant transmission. These include the impact of pregnancy on the health of HIV-infected women, mechanisms and timing of vertical HIV transmission, rates of maternal-infant transmission (overall and among different subpopulations of at-risk pregnant women), as well as understanding cofactors related to HIV transmission. In addition, major research issues appropriate therapeutic interventions include: (1) evaluating the impact of prenatal and intrapartum, (2) determining as early as possible which infants are HIV infected, (3) defining risk factors associated with rapid progression of disease among infants, and (4) understanding the natural history of pediatric HIV infection. The scientific and medical complexity of conducting valid epidemiologic studies of HIV-infected pregnant women and their offspring, in a way that addresses these research questions, is considerable. For example, to address research questions regarding maternal cofactors related to transmission, a cohort of approximately 1,000 pregnant HIV infected women and their offspring must be recruited. In addition, the laboratory techniques involved in HIV research are complex and rapidly evolving, requiring research efforts that can flexibly respond to expanding knowledge in this area. The Women and Infants Transmission Study II will continue and expand the Women and Infants Transmission Study (WITS I) that began in 1988. WITS I is co-sponsored by the NIAID and the NICHD. The current WITS study is conducted at five sites: a consortium of hospitals in the Boston, Worcester, Massachusetts area administered by Brigham and Women's Hospital in Boston, The Presbyterian Hospital in New York City, The State University of New York Health Sciences at Brooklyn, University of Illinois in Chicago, and University of Puerto Rico in San Juan. Anticipated final accrual for WITS I includes 500 HIV positive pregnant women, 400 infants born to these women, and 200 HIV positive nonpregnant women. WITS II will continue and expand this prospective natural history cohort study of HIV positive pregnant women and their offspring. It will rely heavily on the core protocols already in place for WITS I, but will also encourage new projects that may shed light on our understanding of maternal-infant HIV transmission and early diagnosis of fetal or infant HIV infection. New applicants should have a copy of the WITS I protocol summary and objectives of WITS I to aid them in preparing the RFA application. This information may be obtained from Dr. Mary Glenn Fowler, at the address listed under INQUIRIES. The research efforts of WITS II will complement a number of AIDS Clinical Trial Group (ACTG) perinatal and pediatric clinical trials currently underway or being planned. WITS II will also complement the Women's Interagency HIV Study funded by the NIAID and the Centers for Disease Control, which is evaluating the natural history of disease progression among HIV infected women. WITS II will have three major foci: o Continued evaluation of maternal cofactors related to maternal-infant HIV transmission including timing of transmission. o Assessment of promising early diagnostic techniques to rapidly identify HIV-infected infants. o Determination of the natural history of HIV infection among infants and children in an era of antiretroviral, prophylactic, and immunotherapy. Identification of infants at risk for rapid HIV disease progression will be an important element of this research. This component will be accomplished through follow up of infants currently enrolled in WITS I as well as infants born to pregnant HIV positive women enrolled in WITS II. Specific objective of WITS II are: o Determine maternal cofactors related to maternal-infant transmission, including assessment of mechanisms and timing of transmission. o Determine the impact of pregnancy on the natural history of HIV infection among women through the post partum period, including immunologic and virologic changes in pregnant HIV positive women. o Evaluate early diagnostic tests to determine infant HIV infection status as rapidly as possible. o Determine the natural history of HIV infection among congenitally exposed infants and children in light of antiretroviral, prophylactic, and immune-based therapy. o Assess the feasibility of future vaccine trials in a cohort of HIV infected pregnant women by evaluating their attitudes and potential willingness to take part in future clinical vaccine trials for themselves or their infants. To achieve the objectives of WITS II, the NIAID seeks applicants to help develop and carry out this continuing epidemiologic natural history study of pregnant HIV women and their children. New prospective sites as well as current WITS I sites are encouraged to apply. The template for this study will be the research protocols designed for WITS I, which includes a schedule of research visits with designated evaluations and data collection instruments (medical history questionnaires, physical exam forms, laboratory specimen collection procedures). In addition, specific new research studies are also encouraged that may provide critical information directed toward the primary research aims of WITS II. Applicants who are not current WITS sites may contact Dr. Mary Glenn Fowler (301/496-6177) to obtain a summary of the research protocol and objectives of WITS I. The applicants for this RFA should provide information that demonstrates scientific, technical, and operational capabilities to plan, implement, and participate effectively in a multi-site collaborative interdisciplinary research study. These capabilities will enable the applicant to respond to the urgent need to determine factors related to maternal-infant transmission; identify early diagnostic techniques to determine HIV status of infants; evaluate the natural history of HIV infection among infants and children; and assess feasibility of carrying out future vaccine trials. The application should demonstrate, at a minimum, the following capabilities: o Recruit and retain at least 30 and ideally over 50 HIV pregnant women and their children to fulfill the objectives of the WITS II study (See Specific Instructions, Section 1, Accrual and Retention Plan). Women should be recruited as early in pregnancy as possible. Demonstrated linkages with a Community Advisory Board will be required and linkages with other community based groups are strongly encouraged. (See Specific Instructions, Section 1, Linkages) o Carry out cohort studies of HIV infected pregnant women to evaluate factors related to maternal-infant transmission; determine mechanisms and timing of transmission; and assess early diagnostic studies to determine HIV status of infants born to HIV positive women. This effort will involve refinement and continuation of the current WITS I core protocols. o Implement follow up studies for the cohort of infants born to HIV positive women who are enrolled in WITS I and WITS II. Such studies would include assessment of survival, morbidity, growth and development, and quality of life for these children. Depending on the final selection of WITS II sites, successful new sites may subcontract with some current WITS I sites, if these sites do not recompete or secure a new award, to follow up infants currently enrolled in WITS I. Modification and refinement of existing WITS I protocols will be the template for this follow up. o Propose budgets, based on per patient capitation costs, to carry out the WITS protocols. o Carry out virologic, immunologic, and other laboratory studies relevant to the WITS protocols either on site or through linkages with an ACTU laboratory. Laboratory evaluations carried out on site must meet NIAID quality assurance requirements. o Coordinate and oversee specimen collection for the timely processing, storage, and retrieval of laboratory specimens as needed for WITS II studies. This would include the ability to transfer certain specimens to a central repository and transfer of other specimens to designated labs for early diagnostic and other specific laboratory studies. Structural Arrangements of the WITS II Cooperative Agreement WITS Steering Committee and Meetings The WITS II Steering Committee (WSC) will develop general WITS policies concerning subcommittee or working group structure and membership, publications, access to data, interim data monitoring, agendas for working group meetings, and developing and/or refining WITS protocols. Membership in the WSC will consist of one Principal Investigator from each WITS study site; the Principal Investigator of the Statistical and Clinical Coordinating Center (SACCC), which is responsible for central data management of the WITS study; and a program coordinator from the NIAID and the NICHD. The WSC will be chaired by an awardee Principal Investigator. The Chief of the Perinatal Transmission and Pediatric Section of the Vaccine Trials and Epidemiology Branch of the NIAID will serve as the NIAID program coordinator and the Special Assistant for Obstetrics in the Pediatric, Adolescent, and Maternal AIDS Branch, NICHD will serve as the NICHD program coordinator. The Program Coordinators together will have one vote on the WSC. The program coordinators and SACCC will assist in coordinating four WSC meetings per year in the Bethesda, Maryland area to discuss and define research activities with an agenda based on input from all WSC members. At the WSC meetings members will be responsible for suggesting and defining new inter-institutional studies as offered by the applicants consistent with Specific Instructions - Section 2 of the RFA, thus having been peer-reviewed and evaluated. The WSC will have a Publications Subcommittee and Working Groups set up as part of the infrastructure. Interim conference calls and/or meetings will be utilized by working groups and subcommittees. Data Access, and Publication In addition to the standard reporting requirements currently in existence for awardees of NIH research cooperative agreements, the following apply: It is the primary responsibility of the WITS Principal Investigators to clearly state the objectives and approaches of WITS II, to plan and conduct the research stipulated in WITS II, and to ensure that the results obtained are analyzed and published in a timely manner. The data obtained will be the property of the awardees. The NIAID and NICHD program coordinators will have access to the data generated under these cooperative agreements and may periodically review the progress by interim analyses. Information obtained from the data may be used by NIH program coordinators for the preparation of internal reports on WITS activities. WITS II publication policies will closely follow those established for WITS I, with the Principal Investigators taking the lead role in presentation and publication of scientific data generated by the WITS study. Specific publication policies will cover combined data from WITS I and WITS II, and will ensure that both WITS I and WITS II investigators contributions as well as those of the NIH program coordinators and the SACCC are appropriately acknowledged in terms of authorship and publications. All published (abstracts, peer reviewed manuscripts, reviews) and oral presentations of work supported in part or in total by the cooperative agreement must be acknowledged in the presentation and will include the mechanism, cooperative agreement number and Institute; for example, "This work was supported in part by the cooperative agreement number AI-92-13, NIAID." WITS awardee institutions will generate data that will be submitted to the SACCC. The total database for the WITS core protocols will include data from all funded sites. The use and publication of the data will be governed by policies established by the WITS investigators through the WSC. Final approval of publications will be by the WSC. Working groups and subcommittees such as a publication subcommittee, will be established by the WSC to coordinate efforts including, but not limited to, definition of research questions of interest, analysis of data, and publication of findings. The WSC will determine at the completion of WITS II whether or not to make the data from WITS II available to the public. These data could be made available through the National Technical Information Service. Data requestors would be asked to explicitly acknowledge the WITS research project and specific Principal Investigators or their designees in any publication or presentation involving the WITS data. Defined Working Relationship Within a Cooperative Agreement Assistance via a Cooperative Agreement differs from the traditional research grant in that in addition to the normal programmatic and administrative stewardship responsibilities, the component awarding the Cooperative Agreement anticipates substantial programmatic involvement during performance of the project. Within a cooperative agreement, a partnership relationship exists between the recipient of the award and NIAID. Each party to this partnership within WITS II will have rights and responsibilities as well as a defined working relationship. To be responsive to this cooperative agreement, an applicant must indicate willingness to work collaboratively with other WITS II investigators, with the assistance of the NIAID and NICHD program coordinators, in carrying out the WITS II research agenda. Awardee rights and responsibilities WITS II investigators will be responsible for overall conduct of the study including design of new studies, patient accrual and retention, production of high-quality data, and the analysis and publication of the research findings. WITS II investigators with the assistance of NIAID and NICHD program coordinators will establish and serve on the WSC and all working groups. NIH rights and responsibilities The NIAID and NICHD program coordinators, Chief of Vaccine Trials and Epidemiology Branch of NIAID and the Chief of the Pediatric, Adolescent and Medicine AIDS Branch, will assist the WITS II Principal Investigators. In addition, these coordinators, when appropriate, may designate other NIH staff to offer specific expertise on subjects determined by the WSC. It is again emphasized that the role of NIH will be to facilitate and not to direct the activity of the WITS II investigators. To ensure that the scientific research in WITS II is of the highest caliber and is directed appropriately to meet the objectives of WITS II, the NIH program coordinators may convene an external advisory scientific panel to review the WITS II protocol within the first year of the study. SPECIAL REQUIREMENTS Specific Instructions - Section 1 As part of items 1-4 of the research plan of PHS Form 398, applicants for the RFA awards should demonstrate the following minimum requirements Proficiency in conduct of epidemiologic research or clinical trials (5 page limit recommended) The applicant should describe the extent and scope of previous experience in carrying out epidemiologic or clinical trial studies; complications for women, infants and children and participation or capability to participate in multi-site clinical studies. The following should be done to permit an evaluation of performance: o Describe the epidemiologic research or clinical trials experience of key personnel in terms of kinds of studies and numbers and description of patients. o For current WITS sites, describe the total accruals to date, from the beginning of the study to the present, missed visits and retention data. In addition, applications from current WITS I sites should include information on data forms completion rates, data entry turn around time, and information on proportion of required repository specimen volumes that were actually collected, summarized across all patients by visit. For new sites, describe the anticipated potential accrual per year of pregnant HIV infected women. o Describe the level of scientific contribution in such studies (i.e., protocol design, cooperative efforts in carrying out the WITS protocols, oversight, handling of laboratory specimens, data management, publication contributions). o Describe the capability and willingness to administer a subcontract to follow up infants and children from the WITS I cohort who might be enrolled at a WITS I site that did not successfully recompete for WITS II. Assume semi-annual visits including physical and neuropsychological evaluations, and immunologic and virologic laboratory studies. Organizational Structure for Conduct of Epidemiologic or Clinical Trials (6-page limit recommended) The applicant should detail the essential features present at their site for the performance of multi-site clinical studies, including qualifications of key personnel and facilities. The narrative must specifically address the following: o Personnel - describe in detail, the qualifications of other staff (other than those key personnel already mentioned above in 1a), who would help conduct the study, as well as personnel for delivery of ancillary services. Culturally sensitive individuals reflective of local demographics should be represented among key staff as well as personnel for ancillary services. o Facilities - describe facilities and resources available for conducting the clinical studies and ancillary services (e.g., obstetrical, perinatal, and pediatric care facilities, outreach and social services, child care, transportation). Accrual and Retention Plan (6-page limit recommended, plus supporting letters) Applicants should document the capability to access a population of HIV pregnant women and their offspring. The applicant should document their potential ability to recruit a minimum of at least 30 and ideally 50 or more pregnant HIV infected women in the first year, a number that will help define the size of the first year budget. Especially useful is an assessment of local data derived from HIV prevalence newborn screening surveys. The application should describe: o The primary source(s) of WITS study subjects. o The demographic features of the HIV-positive pregnant women in the catchment area including HIV seroprevalence data, race/ethnicity, and risk transmission categories. o A plan for outreach to pregnant HIV women, including strategies for interaction with community health care providers or agencies that are likely to lead to referral of HIV-infected pregnant women into the WITS study. The number, background, and experience of staff who are culturally sensitive to the needs of these women should be described and provisions made for training to increase the sensitivity of WITS staff. o Policies and procedures for accessing referral patients, such as communication, provision of ancillary services, outreach and non-study related care, follow-up by research staff or primary care providers, and amount of primary care provided by the research study staff to the populations, should be mentioned. Letters of agreement to document, describe, and support interactions with specific referral sites must be provided. All applicants should present a plan to provide or refer WITS enrollees for comprehensive clinical care including substance abuse treatment when appropriate. Linkages (5-page limit recommended, plus supporting letters) The following support linkages are either REQUIRED as specified or strongly ENCOURAGED when not specified: o Community Advisory Board (REQUIRED). A Community Advisory Board (CAB) associated with each site should be established within two months of award. The purpose of the CAB is to foster interaction between the WITS personnel and HIV infected individuals in the community, community health providers, community leaders, and advocacy groups. (If an appropriate CAB is already in place, it is not necessary to establish a separated CAB for the WITS). Applicants may contact the WITS NIAID Program Coordinator, Dr. Mary Glenn Fowler, 301-496-6177, to clarify any questions regarding the CAB. o AIDS Clinical Trials Unit (ACTU): An establishment of linkage with a ACTU funded by the NIAID or the NICHD, if one is located within the same geographic area, is encouraged, and a letter of agreement describing the relationship should be included. (See Appendix 1 for listing). o Clinical Programs for Clinical Research on AIDS (CPCRA): An establishment of linkage with a CPCRA site if one is located within the same geographic area is encouraged, and a letter of agreement describing the relationship should be included. (See Appendix 2 for listing). o General Clinical Research Center (GCRC): Applicants from institutions that have a GCRC funded by the NIH National Center for Research Resources are encouraged to identify the GCRC as a resource for conducting the proposed research. A letter of agreement from either the GCRC Program Director or the Principal Investigator should be included with the application. (See Appendix 3 for listing). o Research Centers at Minority Institutions (RCMI): An establishment of linkage with an RCMI- funded or cofunded by the NIAID, if one is located within the same geographic area, is encouraged, and a letter of agreement describing the relationship should be included. (see Appendix 4 for listing) o Centers for AIDS Research (CFAR): An establishment of linkage with a CFAR funded by the NIAID, if one is located within the same geographic area, is encouraged and a letter of agreement describing the relationship should be included. (See Appendix 5 for listing) o National Institute on Drug Abuse (NIDA) Treatment and Research Centers: An establishment of linkage with a NIDA project, if one is located within the geographic area, is encouraged, and a letter of agreement describing the relationship should be included. (See Appendix 6 for listing) o American Foundation for AIDS Research Community-based Clinical Trials (CBCT) Network: An establishment of linkage with a CBCT, if one is located within the geographic region, is encouraged, and a letter of agreement describing the relationship should be included. (See Appendix 7 for listing) o AIDS Vaccine Evaluation Group (AVEG, NIAID): An establishment of linkage with an AVEG funded by NIAID, if one is located within the same geographic area, is encouraged and a letter of agreement describing the relationship should be included. (See Appendix 8 for listing) o Health Resources Services Administration (HRSA) AIDS Demonstration Project: An establishment of linkage with a HRSA AIDS Demonstration Project, if one is located within the same geographic area, is encouraged, and a letter of agreement describing the relationship should be included. (See Appendix 9 for listing) Applicants are encouraged to form other linkages, including, but not limited to, community-based organizations that serve populations at increased risk for HIV infection, designated State/County/Public Health AIDS Centers, and community-based AIDS clinics. A letter of agreement for each linkage should be included with the application. All letters of agreement should be explicit about the intended purpose and role of the collaborating site or organization, referencing prior successful collaborations. Laboratory Capabilities (5-page limit recommended) Applicants should demonstrate a capability to collect and process blood and cervical specimens for laboratory analyses including, but not limited to, immunology, virology assays and cultures, cervical cultures, serology, chemistry, and hematology studies. This capability could be either in the applicants' own laboratories, by a ACTG-certified laboratory, or other laboratories likely to be deemed suitable by peer reviewers and by NIAID staff. Funds will not be provided to support equipment, personnel, or facilities for the establishment of new laboratories, although funds may be requested for supplementary equipment at existing laboratories. Detailed justification is required. Awardee laboratories will be required to participate in a quality assurance (QA) program supported by the NIAID. A key part of the WITS protocols includes collection, transfer, and storage of designated laboratory specimens (urine and blood samples) at a central NIAID-supported specimen repository.The purpose is to permit future nested studies in which technologies, sample sizes, or hypotheses are not currently known or available. Applicants should indicate in their application (1) their agreement to transfer designated specimens; (2) describe their abilities to collect, store, and transfer required quantities of designated specimens to a central repository; and (3) their experience in similar activities. Data Coordination (5-page limit recommended) The WITS will be assisted by a Statistical and Clinical Coordinating Center (SACCC), contracted by the NIAID to provide extensive technical and logistical support for data analyses. This contract will: (1) provide statistical leadership; (2) establish and administer an effective and responsive data management system; (3) design and implement educational/training assistance to WITS investigators and quality assurance with respect to WITS data; and (4) facilitate communications, meetings, conference calls, publications, and study-related coordination between the clinical sites and the government. Applicants should present capabilities to do either (a) on-site data entry using SACCC-produced data entry modules or (b) photocopying and sending data collection instruments and sending them to the SACCC for data entry. If specific required hardware/software equipment for data entry is not available at an applicant site doing on-site data entry, it may be proposed in the budget. However, applicants are strongly encouraged to use existing facilities and data entry equipment already available to them at their site. For on-site data entry, computer tapes or diskettes that contain files of the site data will be sent to the SACCC. Inconsistencies found by the SACCC and reported to the sites will be the responsibility of the sites to resolve, irrespective of whether sites enter their own data or send hard copies to SACCC for data entry. The SACCC staff will support the WITS investigators in their analyses of the findings from WITS II. Each applicant will be sent a copy of the Request for Proposals for the SACCC so that the applicant can be aware of the full range of services to be provided by the SACCC. Specific Instructions - Section 2 - Development Research Component (Optional) The essential research for WITS II will be based on refinement of the WITS I protocols. However, WITS II also wishes to encourage a limited number of new research protocols to address the objectives of WITS II in light of the most current scientific knowledge available. Interested investigators may briefly describe (3-6 single spaced pages) specific research projects that they would propose to be added to WITS II that address specific research objectives of WITS II. Research areas of particular interest to the NIAID include evaluation of maternal-infant pairs with respect to genotypic sequencing, host effects related to transmission, placental and other studies which may shed light on timing and mechanisms of transmission, TB related studies, new diagnostic studies that might identify HIV infected infants in the newborn period or prenatally; and HIV vaccine feasibility studies. Applicants responding to this optional section should also complete a separate budget for this section using pages 3 and 4 of the budget section of PHS 398 application form (rev.9/91). Although the scientific merit of applications in this section will be peer reviewed and evaluated, this review will not be used in the overall scoring of the application. Specific Instructions for Preparing an Application Budget This section supplements the instructions for preparing a grant application form PHS 398 (rev. 9/91). Applicant budgets should follow the instructions contained in the PHS 398 (rev. 9/91) to complete the budget pages for Sections 1 and for Section 2 separately. In addition, for Section 1, applicants should include as additional budgetary attachments, worksheets showing the breakdown of separate budgets for the following components of the study: o A core budget that includes (1) personnel costs for the Principal Investigator and other key personnel (study coordinator, research assistant,); (2) travel for meetings to include four meetings of the study Principal Investigators to be held in the Bethesda, Maryland area, one national meeting, and one international meeting; (3) supplies--laboratory, data management, and other supplies needed to carry out the study; (4) community based efforts for recruitment of pregnant HIV infected women. Budgets should indicate funds allocated for support of community based personnel who would help with recruitment and retention, counselling and other logistic support. o Annual costs for recruitment and evaluation of pregnant women at a site, based on total estimated accrual per year, number of visits per year, clinical assessments, and laboratory costs per visit (See Appendix 10 for specific information regarding number of visits, costs anticipated for lab tests, and costs for shipping three urines and two pap smears per patient per year). Costs for ancillary services such as transportation, child care, and incentive costs related to patient visits should also be itemized in the budget worksheet. o Annual costs for evaluations of the offspring born to the HIV infected women enrolled in WITS II, based on total estimated accrual per year, number of visits per year, staff, clinical and neuropsychologic evaluations, and laboratory costs per visit. (See Appendix 11 for specifics on number of visits, and estimated costs for laboratory tests). Costs for ancillary services such as transportation, child care,and incentive costs related to patient visits should also be itemized in the budget worksheet. 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 are 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 must 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 both genders and all ages. Because this RFA addresses research on the effects of HIV infection among women and their infants, many of whom are from minority race/ethnicity groups, it is anticipated that women and minorities will be adequately represented in applications for this RFA. Because the research in this RFA is directed at the effects of HIV infection on women and their infants, the noninclusion of adult males in submitted proposals is justified. The composition of the proposed study population must be described in terms of racial/ethnic groups. In addition, racial/ethnic issues must be addressed in developing a research design and sample size appropriate for the scientific objectives of the study. This information must be included in the application Under SPECIAL INSTRUCTIONS, STUDY POPULATIONS. 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 U.S. racial/ethnic minority populations (i.e., Native American Indians or Native Alaskans, Asian/Pacific Islanders, African-American, Hispanics/Latinos). The rationale for studies on single minority population groups should be provided. For the purpose of this policy, clinical research is defined as 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 PHS/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 may be exempted from these usual PHS/NIH policies. However, every effort would be made to include human tissues from women and racial/ethnic minorities when it is important to apply the results of the study broadly, and this should be addressed by applicants. If the required information is not contained within the application as determined by NIAID program coordinator, the application will be returned. Peer reviewers will address specifically whether the research plan in the application conforms to these policies. If the representation of minorities in the proposed study design is inadequate to answer the scientific question(s) addressed AND the justification for the selected study population(s) is inadequate, it will be considered a scientific weakness or deficiency in the study design and reflected in assigning the priority score to the application. All applications for clinical research submitted to NIH are required to address these policies. NIH funding components will not award grants or cooperative agreement that do not comply with these policies. LETTER OF INTENT Prospective applicants are asked to submit, by October 26, 1992, 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 to provide an indication of the number and scope of applications to be reviewed. The letter of intent is not binding, 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: Mary Glenn Fowler, M.D., M.P.H. Vaccine Trials and Epidemiology Branch Division of AIDS National Institute of Allergy and Infectious Diseases 6003 Executive Boulevard, Room 2A24 Bethesda, MD 20892 (for express mail or courier, use Rockville, MD 20852) APPLICATION PROCEDURES The research grant application form PHS 398 (revised 9/91) is to be used in applying for these cooperative agreements. These forms are available from most institutional offices of sponsored research; the Office of Grants Inquiries, Division of Research Grants, National Institutes of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892, telephone 301/496-7441; and from the NIH program coordinator named below. 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 AND INFANTS TRANSMISSION STUDY", RFA AI-92-13 must be typed on line 2a of the face page of the application form and the "YES" box must be marked. Submit a signed, typewritten original of the application, including the Checklist, and three signed, exact, single-sided 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 copies must also be sent directly to: Dr. Dianne Tingley AIDS Scientific Review Branch Division of Extramural Activities National Institute of Allergy and Infectious Diseases 6003 Executive Boulevard, Room 4C16 Bethesda, MD 20892 If sending the application by overnight mail or courier service use "Rockville, Maryland 20852". Applications must be received by both DRG and Dr. Tingley by January 14, 1993. Applications received after January 14, 1993 will be returned to the applicant without review. If the application submitted in response to this RFA is substantially similar to a grant application already submitted to the NIH for review, but has not yet been reviewed, the applicant will be asked to withdraw either the pending application or the new one. Simultaneous submission of identical applications will not be allowed, nor will essentially identical applications be reviewed by different review committees. Therefore, an application cannot be submitted in response to this RFA that is essentially identical to one that has already been reviewed. This does not preclude the submission of substantial revisions of applications already reviewed, but such applications must include an introduction addressing the previous critique. Applications that are not received as a single package from the Principal Investigator and that do not conform to the instructions contained in PHS 398 (rev. 9/91) and the specific instructions including the page guidelines to not exceed 32 pages for section 1 of this RFA will be judged non-responsive and will be returned to the applicant. Upon receipt, applications will be reviewed by DRG staff for completeness and NIAID staff for responsiveness. Incomplete applications will be returned to the applicant without further consideration. If the application is not responsive to the RFA, NIAID staff will contact the applicant to determine whether to return the application to the applicant or submit it for review in competition with unsolicited applications at the next review cycle. Applications may be triaged by a NIAID peer review group to determine their relative competitiveness. The NIAID will withdraw from further competition those applications judged to be non-competitive for award and will notify the Principal Investigator and institutional official. Those applications judged to be competitive will be evaluated in accordance with the criteria stated below for scientific/technical merit by an appropriate peer review group convened by the AIDS Review Section, DEA, NIAID. The second level of review will be provided by the National Advisory Allergy and Infectious Diseases Council in June 1993. The earliest possible award date is July 1993. Applications will be evaluated for scientific merit including the originality, feasibility, and technical excellence of the research projects. REVIEW CONSIDERATIONS This application must be directed at and address the research objectives identified in this RFA; that portion of the application corresponding to this research plan should follow in form the specific instructions given in this RFA. The primary factors that will be considered in the review of the application will be demonstrated ability or potential to recruit adequate numbers of HIV pregnant women into the study; capability to carry out the clinical and laboratory studies of WITS II including commitment to a multi-site research collaborative effort; and cost efficiency in carrying out the research protocols. The following specific factors will be considered in the review of the application: Section 1 o Prior success or demonstrated potential of the applicant to recruit adequate numbers of HIV pregnant women for the study. (To be competitive an applicant site should demonstrate the capability to recruit and retain at least 30 and ideally over 50 HIV pregnant women annually.) o Capability to carry out the clinical, and laboratory studies of WITS II, including adequacy of available physical facilities to accommodate conduct of physical examination, phlebotomy, interviewing, counselling, neurodevelopmental testing of infants and children, handling of laboratory specimens, and data management. o Potential for original research bearing on the research objectives of WITS II. o The professional qualifications and the scientific expertise of the Principal Investigator and key personnel in research areas emphasized by the study. This includes experience in multi-site collaborative efforts and adequacy of proposed staffing levels to meet the research objectives of the RFA. o The establishment and adequacy of community support linkages. o Evidence of institutional commitment to the study as demonstrated by administrative experience and capabilities and listing of resources that will be dedicated to the study. o Efficiency in terms of costing, and utilization of available resources. Section 2 Scientific merit of the proposed optional research study. AWARD CRITERIA Awards will be made on the basis of high scientific and technical merit, adequacy of funds and program relevance. However, after applications have been approved by the National Advisory Allergy and Infectious Diseases Council, NIAID staff reserve the right to give consideration to the following factors in the final selection of applications to be funded: WITS II sites reflect the racial/ethnicity and socioeconomic characteristics of the nation-wide HIV epidemic among women and infants and reflect the HIV-AIDS incidence/geographic distribution of the epidemic among U.S. women and their infants. 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 concerning programmatic issues to: Mary Glenn Fowler, M.D., M.P.H. Vaccine Trials and Epidemiology Branch Division of AIDS National Institute of Allergy and Infectious Diseases 6003 Executive Boulevard, Room 2A24 Bethesda, MD 20892 Telephone: (301) 496-6177 FAX: (301) 402-1506 or (301) 480-5703 Direct inquiries concerning fiscal and policy issues to: Jane Unsworth Chief, AIDS Grants Management Section Grants Management Branch Division of Extramural Activities National Institute of Allergy and Infectious Diseases 6003 Executive Boulevard, Room 4B25 Bethesda, MD 20892 Telephone: (301) 496-7075 FAX: (301) 480-3780 Direct inquiries concerning the review process and review requirements to: Dr. Dianne Tingley AIDS Scientific Review Branch National Institute of Allergy and Infectious Diseases 6003 Executive Boulevard, Room 4C16 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 Nos. 93.856 and 93.855. 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 Public Health Service Act 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. .
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Office of Extramural Research (OER) |
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National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892 |
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Department of Health and Human Services (HHS) |
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