kristoff@GENBANK.BIO.NET (Dave Kristofferson) (03/02/90)
NIH GUIDE - Vol. 19, No. 9, March 2, 1990 - Page 12 FULL TEXT OF RFAs FOR ONLINE ACCESS REQUEST FOR COOPERATIVE AGREEMENT APPLICATIONS: RFA: 90-AI-04 AIDS CLINICAL TRIAL INFRASTRUCTURE COOPERATIVE AGREEMENT FOR MINORITY INSTITUTIONS P.T. 34, FF; K.W. 0715008, 0755015, 0404000, 0403004 NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES Letter of Intent: March 23, 1990 Application Receipt Date: April 26, 1990 The Division of AIDS, National Institute of Allergy and Infectious Diseases (NIAID), invites minority institutions to submit applications for cooperative agreements to support the establishment of an AIDS Clinical Trial infrastructure for the purpose of increasing the participation of underrepresented minority populations in AIDS Clinical Trials Group (ACTG) studies. There are no plans to reissue this Request for Applications (RFA) at any future time. I. BACKGROUND INFORMATION Infection with human immunodeficiency virus (HIV) and the Acquired Immunodeficiency Syndrome (AIDS) constitute a profound and increasing health problem for minority populations. Recent epidemiologic data indicate that minorities suffer disproportionately from AIDS. Blacks account for 27% of all adult cases of AIDS and 52% of pediatric cases, while Hispanics account for 15% of all adult cases and 23% of the pediatric cases, yet these groups comprise only 12 and 8%, respectively, of the population in the United States. Overall, the relative risk of AIDS for Black and Hispanic men is between two and ten times greater than for white men. The vast majority of these individuals are HIV-infected intravenous drug users (IVDUs) and more than 50% of their female sex partners are HIV seropositive. Of the adult cases of AIDS reported among females, 52% are Black, 11% are Hispanic and 29% are white, suggesting that AIDS is becoming a serious health problem for minority women as well. (Racial designation was not available for 8% of patients.) Since the initial recognition of AIDS in the early 1980s, NIAID has been fully committed to the struggle against this disease. This commitment has been characterized by the evolution of a multicenter network of institutions designated as the ACTG which is opening new avenues in evaluating therapies and methods to restore immune function and to treat opportunistic infections associated with AIDS. Although considerable progress has been made in bringing ACTG research to many individuals with HIV infection, there has been insufficient progress in bringing these studies to minorities. Despite the fact that several clinical trial sites are located in geographical areas with substantial minority populations, minorities with HIV infection are markedly underrepresented in ACTG research. Of 8,288 patients enrolled in ACTG studies as of November 13, 1989, 77.6% are white, 9.6% are Black, and 11.7% are Hispanic. Of the total number reported, 592 (7.6%) are women. These statistics are disturbing in that they do not accurately reflect the demographics of HIV infection in the overall population; moreover, they may suggest significant gaps in scientific knowledge about HIV infection in minority patients. To date, most ACTG studies evaluating treatment therapies have been conducted in homosexual and bisexual men and on a whole have involved relative small numbers of minorities with HIV infection, thus making the results of the studies of uncertain applicability as far as nationwide disease trends are concerned. While disparity in incidence and survival between majority and minority populations may be a reflection of our health care delivery system, underrepresentation of minorities in ACTG research may also reflect structural gaps in the existing system that limit participation in clinical trials and access to experimental therapeutic resources. One way to overcome these imbalances is to encourage greater participation of minority institutions and minority investigators in ACTG research. Currently, the ACTG is comprised of scientists and clinical researchers at 47 main AIDS Clinical Trials Units (ACTUs) and patients are enrolled in clinical research at 109 affiliated sites throughout the United States. These ACTUs were funded by the NIAID based on criteria relevant to institutional clinical trials research capabilities and availability of HIV-infected patients. Access and participation by minorities were not primary considerations for funding, particularly during the early years when the urgency to mobilize against this devastating disease was being felt. Now that the magnitude of HIV infection in minority populations has been fully realized, the NIAID is committed to improving access and participation among these groups and has given high priority to increased involvement in clinical trials for both minority patients with HIV infection and minority health professionals in AIDS research. NIAID realizes that while many minority institutions have access to the desired underrepresented minority populations and are in unique positions to address issues related to HIV infection in minorities, many of these institutions, for a myriad of reasons, experience difficulties in competing for research grants to conduct AIDS Clinical Trials. In this regard, NIAID plans to offer cooperative agreement grants to enable minority institutions to develop the capability and expertise necessary to establish and implement an AIDS Clinical Trial infrastructure and to participate more fully for competitive AIDS Clinical Trials research grants. II PURPOSE The purpose of this RFA is to provide a period of support of 3 years for minority institutions to establish an ACTU infrastructure and to acquire sufficient expertise in clinical trials for successful submission of a cooperative agreement to participate in ACTG research. These cooperative agreements are intended to provide a reasonable opportunity to demonstrate creativity and productivity and to assist in the preparation for competition for regular cooperative agreement support for conduct of ACTG research. III. DEFINITIONS MINORITY INSTITUTION - An institution that has more than 50% minority student enrollment, awards an M.D., D.D.S., D.V.M or other doctoral degree in the health professions. COOPERATIVE AGREEMENT - An assistance mechanism in which substantial NIH staff involvement with the recipient during the performance of the planned activity is anticipated. AIDS CLINICAL TRIALS GROUP (ACTG) - A network of institutions, investigators, NIAID personnel, and a Statistical and Data Analysis Center (SDAC), organized for the purpose of evaluating potential therapies for HIV infection and its sequelae. AIDS CLINICAL TRIALS UNIT - An institution that has been awarded an NIAID cooperative agreement to participate in ACTG clinical trials. PRINCIPAL INVESTIGATOR - The licensed physician who submits the single application in response to this RFA and who is responsible both scientifically and administratively for the performance of the participants as a whole. NIAID SCIENTIFIC COORDINATOR - A member of the NIAID extramural staff who assists and facilitates the partnership relationship between NIAID, the individual award recipients, and the ACTG as a whole. ARBITRATION PANEL - A group composed of an individual designated by the Principal Investigator of an individual minority institution cooperative agreement, one NIAID designee, and a third designee with expertise in the relevant area and chosen by the other two. Such panels may help resolve both scientific and programmatic issues that develop during the course of the work and restrict progress. The interaction of this panel is detailed in section VI, part D under "TERMS OF AWARD: NATURE OF PARTICIPATION OF NIAID STAFF". IV. MECHANISM OF SUPPORT Awards will be made as Cooperative Agreements. Assistance by Cooperative Agreement differs from the research grant in that the Government component (NIAID) awarding the Cooperative Agreement anticipates substantial involvement during the performance of the award. The nature of NIAID staff participation is described in section VI under "TERMS OF AWARD: NATURE OF PARTICIPATION OF NIAID STAFF." There is no intent, real or implied, for NIAID staff to direct an awardee's activities. The interaction of NIAID staff with the investigators is expected to assist and facilitate planning and development of an AIDS Clinical Trial capability. NIAID has set aside $3,632,000 in total costs for the initial year's funding to minority institutions. The NIAID plans to fund between 4 and 5 awards from this announcement. The starting date for the initial annual period will be on or before September 1990. Awards will be made for a period of 3 years with yearly evaluation involving competent consultants. Awardees are expected to develop an infrastructure and capabilities for AIDS Clinical Trials research and to submit a competitive grant application by the thirtieth month of operations under the award mechanism for conduct of AIDS Clinical Trials research. All policies and requirements that govern the grant program, Public Health Service, and the National Institutes of Health apply. Although this program is provided for in the financial plans of NIAID, the award of Cooperative Agreements pursuant to this RFA is also contingent upon the scientific merit of the applications received and the continuing availability of funds for this purpose. V. RESEARCH GOALS AND SCOPE The long-term objective of this RFA is to increase the involvement of underrepresented minority populations in AIDS Clinical Trials. The immediate goal is to provide funding to: o Plan and develop an AIDS Clinical Trial Unit infrastructure. o Acquire the necessary expertise in clinical trials needed for the successful submission of a cooperative agreement to participate in the ACTG. o Acquire the administrative and scientific training and skills to participate in AIDS Clinical Trials research. o Recruit professional and support staff. (See the fifth statement under section VI, Part B, "Participation of NIAID Staff in Cooperative Agreement Activities".) o Renovate existing structures or rental of space, at a cost not to exceed $85,000, for provision of suitable facilities for conduct of AIDS Clinical Trials research. NOTE: Funds will not be provided to establish new facilities (e.g., new virology or immunology laboratories). o Purchase of equipment, at a cost not to exceed $40,000, for conduct of AIDS Clinical Trials research. o Support travel and training activities related to AIDS Clinical Trials research. Long-term goals are to: o Encourage the participation of minority institutions and minority investigators in ACTG research and provide a basis for involving underrepresented populations in AIDS Clinical Trials studies. o Increase the scientific base of understanding the unique social and medical issues related to AIDS in minority populations. o Increase the understanding of the potential for adverse drug reactions in minority intravenous drug-using patient populations. The culmination of this effort will be the submission of a grant application for conduct of AIDS Clinical Trials. The Division of AIDS, NIAID, intends to support this planning initiative by awarding cooperative agreements to minority institutions. The institutions should be capable of developing a process to improve research capability and to begin protocol studies under the leadership of a qualified Principal Investigator sensitive to the needs and concerns of minority populations infected with HIV. Minimum Requirements for Applicants: Applicant institutions seeking funding must meet the following requirements: A. Have a student enrollment which is more than 50% minority and awards an M.D., D.D.S., D.V.M or other doctoral degree in the health professions. B. Demonstrate access, as evidenced by written documentation, to at least 100 minority individuals with HIV infection as proven by standard serologic methodologies such as ELISA, Western Blot, or p24 antigen determination. C. Provide written documentation of institutional commitment to participate fully in planning and developing the capability and expertise to conduct ACTG research and to submit a competitive application for conduct of AIDS Clinical Trials. D. Provide written documentation of the scientific, administrative/management, and organizational capabilities of the Principal Investigator and the existing, or to be recruited, professional and support personnel necessary to carry out the objectives of this grant. Applicant institutions should provide letters of commitment from qualified individuals who will be recruited. E. Provide evidence of an institutional plan and commitment to recruit and hire necessary and competent professional and paraprofessional staff to establish an ACTU and to conduct AIDS Clinical Trials research. F. Provide evidence of an institutional plan to provide adequate facilities and equipment to establish an ACTU and to conduct AIDS Clinical Trials research. G. Provide evidence of provision of health care for HIV-infected IVDUs. H. Provide a reasonable timetable for implementing plans related to organization, training (in conjunction with NIAID), personnel, facilities, and equipment for establishment of the necessary ACTU infrastructure. VI. TERMS OF THE AWARD: NATURE OF PARTICIPATION OF NIAID STAFF A. Responsibilities of the Awardees Assistance via 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 involvement during performance of the project. However, the awardee must define its objectives in accord with its own interests and perceptions of novel and exploitable approaches and develop the details of the project following the guidance given in this RFA. It is the primary responsibility of the awardee to appoint a Principal Investigator who is: a staff member of the awardee institution, available to devote at least 50% effort per year to the development of an ACTU, and ensure the development of the ACTU in a timely fashion. o Awardees will accept NIAID site visits and scientific and technical advice in all relevant areas to develop an effective and efficient system for conduct of AIDS Clinical Trials research. o Awardees will accept relevant training, when provided, for key personnel in the areas of data management, quality assurance/quality control, protocol development, etc., and regular interaction with ACTG investigators. o Awardees will accept input and advice regarding the selection of key personnel to fill positions which were not filled prior to this application. B. Participation of NIAID Staff in Cooperative Group Activities Through the NIAID Scientific Coordinator, the following support can be anticipated from the Treatment Research Program, Division of AIDS. o NIAID will maintain a close ongoing cooperation with cooperative agreement recipients. In this regard, NIAID staff will participate in site visits to facilitate this development activity. o NIAID will provide scientific and technical advice to awardee institution(s) in all areas relevant to the establishment and operation of an ACTU. o NIAID contractors will provide relevant training to key personnel for development of the expertise necessary for conduct of AIDS Clinical Trials in the areas of data management, quality assurance/quality control, intercommunication among participating institutions, protocol development, investigational drug management and distribution, and grant writing. o NIAID will provide linkage between awardee institutions and ongoing clinical trials efforts and epidemiologic and natural history studies by serving a referral function and providing baseline data when needed. o NIAID will provide logistical support for frequent and regular interaction among ACTG investigators and minority institutions. o NIAID will provide input and advice regarding the selection of key professional and support personnel to fill positions which were not filled prior to the review of application. C. The special "TERMS OF AWARD: NATURE OF PARTICIPATION OF NIAID STAFF" described in this section are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS Grant Administration Regulations at 45 CFR Part 74, and other HHS, PHS, and NIH grant administration policy statements. D. Inasmuch as certain of the activities described herein require approval by NIAID staff during performance of this Cooperative Agreement (e.g., training), NIAID will establish an arbitration process to resolve any differences of opinion. An arbitration panel, composed of one minority institution 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 administrative issue that is significantly restricting progress. This arbitration process in no way affects the right of an award recipient 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. VII. REVIEW PROCEDURES AND CRITERIA Applications that are incomplete or nonresponsive to this RFA will be withdrawn by the National Institute of Health (NIH) staff upon receipt and returned to the applicants without further consideration. Applications that are judged responsive will be reviewed in accordance with the usual NIH peer review procedures. They will first be reviewed for scientific and technical merit by the AIDS Research Review Committee of the Extramural Activities Program, organized by NIAID for this purpose. Following the initial review, the applications will be considered by the NIAID Advisory Council. Peer Review Criteria for Applicants: Acceptable applications for evaluation must be directed toward the attainment of programmatic goals as stated in Section V, "RESEARCH GOALS AND SCOPE." Listed below are the criteria that will be used by the AIDS Research Review Committee and the Advisory Council when reviewing the applications. A. Rationale Availability of patient population o Access to at least 100 minority persons with HIV infection as evidenced by the ELISA, Western Blot, or p24 antigen determination. o Proof of access to these numbers must be made available to the NIAID upon submission of the cooperative agreement application. o Clearly stated institutional plans for recruitment, follow up, and retainment of patients. B. Procedures and Plans for Organization Quality of a plan to develop the capabilities of the minority institution to establish an infrastructure for the conduct of AIDS Clinical Trials research and to integrate that unit within the existing ACTG structure. The plan should indicate how the following capabilities will be developed: o Clinical Activities; o Data Management; o Quality Assurance/Quality Control of data; o Investigational Drug Management; o Pharmacy support; o Immunologic Monitoring and Evaluation; * o Virologic Monitoring and Evaluation; * o Clinical Pharmacokinetics (optional); o Outreach and recruitment; o Social services support for infants born to women who are HIV infected; and, o Social, legal, and economic problems and other issues that will bear directly on the ability to conduct clinical trials in minority populations. *NOTE: The NIAID suggests that applicant institutions plan to have these tests performed by a certified ACTG laboratory. C. Plans for Training Merit of a plan for coordinating the training of key staff in areas of data management, quality assurance, protocol development, IND management, grant writing, and other training relevant to the development of a clinical trial unit. o Clearly stated training needs. o Suitability in terms of requests for the necessary training. o Practicability, especially with reference to the stated time- frame to acquire proficiency. D. Plans for Facilities and Major Equipment Adequacy of a plan to improve facilities and equipment for the development of the proposed AIDS Clinical Trials infrastructure. o An applicant institution should assess its existing infrastructure and provide a plan for modification or expansion, if necessary, in order to provide an appropriate environment for developing an ACTU. o Renovations or alterations of facilities, rental of space, and purchase of large equipment are justifiable when a description of their use or existing unmet needs are included in the plan. E. Investigators and Key Personnel Demonstrated qualifications, availability, competence, experience and an adequate mix of key professional and support personnel to develop this project as evidenced by: o Scientific and technical expertise of the Principal Investigator in the area of HIV infection. o Administrative/management competence of the Principal Investigator to develop an AIDS Clinical Trials infrastructure. o Expertise and time commitment of the Principal Investigator to assemble, coordinate, and manage a comprehensive planning and development team. NOTE: At the end of the funding period, awardees wishing to recompete for funds to conduct clinical trials will be required to submit an application detailing a relevant concept to the conduct of ACTG research. Applicants are advised to allow approximately 6-9 months for the development of a proposal. VIII. METHOD OF APPLYING A. Letter of Intent Prospective applicants are asked to submit, by March 23, 1990, a short letter of intent that includes a descriptive title(s) of the proposed research, and if possible, names of key members of the proposed group. The letter of intent is requested in order to provide an indication of the number and scope of applications to be reviewed. The letter of intent does not commit the sender to submit an application, nor is it a requirement for submission of an application. The letter of intent should be sent to: George W. Counts, M.D. Chief, Clinical Research Management Branch Treatment Research Program Division of AIDS Research National Institute for Allergy and Infectious Diseases 6003 Executive Blvd., Room 207P Bethesda, Maryland 20892 Telephone: (301) 496-8214 B. Receipt Date The deadline for receipt of application is April 26, 1990. In light of accelerated receipt to award processing requirements mandated by Section 2302 of the Title II (AIDS Amendment of 1988), there must be strict adherence to the receipt date announced in this RFA. No exceptions will be made. All applications received past the receipt date will be returned to the investigator. C. General 1. The regular research grant application form PHS-398 (rev. 10/88) must be used in applying. These forms are available at most institutional business offices or from the Division of Research Grants, National Institutes of Health, Bethesda, Maryland 20892. Submit a signed, typewritten original of the application, including the Checklist and four signed, exact, single-sided photocopies, in one package to: Division of Research Grants, NIH Westwood Building, Room 240 Bethesda, MD 20892** In addition, submit 19 exact, single-sided, photocopies of the application plus six copies of the appendices to: Sally Mulhern, Ph.D. AIDS Research Review Section Program and Project Review Branch National Institute of Allergy and Infectious Diseases National Institutes of Health Westwood Building, Room 3A-14 Bethesda, MD 20892 2. TO ASSURE PROPER IDENTIFICATION OF YOUR APPLICATION WITH THIS RFA, the applica- tion form should have "AIDS MINORITY INFRASTRUCTURE (RFA 90-AI-04)" typed on line 2 of the face page of the application form. THE RFA LABEL PROVIDED WITH THE INSTRUCTIONS MUST BE AFFIXED TO THE BOTTOM OF THE FACE PAGE. FAILURE TO USE THIS LABEL COULD RESULT IN DELAYED PROCESSING OF YOUR APPLICATION SUCH THAT IT MAY NOT REACH THE REVIEW COMMITTEE IN TIME FOR REVIEW. IX. SUMMARY OF TARGET DATES LETTER OF INTENT: March 23, 1990 APPLICATION RECEIPT DATE: April 26, 1990 REVIEW DATE: July 1990 COUNCIL DATE: September 1990 AWARD DATE: September 30, 1990 X. INQUIRIES Inquires of a Programmatic nature should be addressed to: George W. Counts, M.D. Chief, Clinical Research Management Branch Treatment Research Program Division of AIDS Research National Institute for Allergy and Infectious Diseases 6003 Executive Blvd., Room 207P Bethesda, Maryland 20892 Telephone: (301) 496-8214 B. Receipt Date Inquiries of the review process should be addressed to : Sally Mulhern, Ph.D. AIDS Research Review Section Program and Project Review Branch National Institute of Allergy and Infectious Diseases National Institutes of Health Westwood Building, Room 3A-14 Bethesda, Maryland 20892 Telephone: (301) 496-2550 Inquiries of a fiscal nature should be addressed to: Ms. Mary Kirker Grants Management Branch National Institute of Allergy and Infectious Diseases National Institutes of Health Westwood Building, Room 710 Bethesda, Maryland, 20892 Telephone: (301) 496-7075 Prospective applicants should request the brochure "Guidelines for Program Projects" from Dr. Mulhern before preparing an application. XI. PROGRAM DESCRIPTION This program is described in the Catalog of Federal Domestic Assistance 13.856-Microbiology and Infectious Diseases Research and 13.855-Immunology, Allergic and Immunologic Diseases Research. Cooperative agreements are awarded under the authority of the Public Health Service Act, Section 301 (42 USC 241) and administered under PHS grant policies and Federal Regulations 42 CFR Part 52 and 45 CFR part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. Request for Cooperative Agreement Applications: RFA-90-HD-04 COOPERATIVE MULTICENTER NETWORK OF MATERNAL-FETAL MEDICINE UNITS P.T. 34, FF, II; K.W. 0785135, 0775020, 0775025, 0785035, 0745020 National Institute of Child Health and Human Development Application Receipt Date: May 22, 1990 PURPOSE The National Institute of Child Health and Human Development (NICHD) invites applications from investigators to participate with the NICHD under a Cooperative Agreement in an ongoing multicenter clinical study designed to investigate problems in clinical obstetrics, particularly those related to prevention of low birth weight. The objective of this study is to facilitate resolution of these problems by establishing a network of centers that, by vigorous patient evaluation using common protocols, can study the required numbers of patients and can provide answers more rapidly than individual centers acting alone. The NICHD program staff will assist the principal investigators of the Maternal-Fetal Medicine Units (MFMUs) and the Advisory Board in identifying research topics of high priority, and in designing protocols appropriate to the evaluation of optimum management in these areas. It is anticipated that approximately 8 to 10 clinical centers will be involved in the program. The deadline for receipt of applications is May 22, 1990. Applications received after this date will not be considered. Only institutions in the United States will be eligible for participation. ADMINISTRATIVE BACKGROUND Modern obstetrical management, especially the management of high-risk pregnancies, has in some instances adopted principles of care, and at times employed pharmaceuticals and methodologies without rigorous use of the controlled observation necessary for their objective evaluation. Often the development of this medical specialty (and others as well) has been marked by the enthusiastic adoption of concepts and procedures followed by their modification or replacement, sometimes decades later, after extensive experience has failed to support their usefulness or shown unexpected consequences. Costs involved in instrument purchase and employment often have been large, and uncertainties embedded in such obstetrical practices have contributed at least partly to the rising incidence of cesarean delivery. Regional differences in practice have complicated the field. In an attempt to respond to the need for well-designed clinical trials in maternal-fetal medicine, NICHD established a Network of MFMUs in 1986. Seven university units were selected among respondents to a Request for Applications (RFA). The Network Steering Committee, which consists of representatives from each clinical center, NICHD staff, and data coordinating center staff, evaluated several controversial issues for study. It then selected certain priority areas on which to develop protocols for randomized clinical trials. Trials have actually been initiated on questions of postterm pregnancy, management of preterm labor, and prevention of preeclampsia. A Data Monitoring and Safety Committee also advises NICHD on research design issues, data quality and analysis, and ethical and human subject aspects of protocols. The NICHD expects that ongoing clinical trials dealing with preterm labor and preeclampsia prevention will continue into the continuation grant period for existing centers. Centers that might join the Network in the next award period (beginning April 1, 1991) would be expected to participate in the protocols ongoing at that time. NICHD intends to enable the Network to initiate new protocols within the first year of the next award period. The topics of these protocols will be decided cooperatively by the Steering Committee. Some areas of interest include: Doppler velocimetry; Cesarean birth; chronic (essential) hypertension during pregnancy; home uterine monitoring and other techniques in reducing the risk of preterm labor and birth. RESEARCH SCOPE NICHD invites applications both from current members of the MFMU Network (competitive continuation applications), as well as from prospective members (new applications). The minimum requirements for applicant investigators and their maternal-fetal research units, are as follows: 1. Professional staffing of the MFMU should include at least three maternal-fetal medicine subspecialists, each of whom would be available to take primary responsibility for one or more of the network protocols at the unit. 2. The application should identify one or more neonatologists at the center who would be designated to participate in protocol development and implementation. Such an individual(s) must have documented interest and experience with clinical trial research, and be willing to participate in the MFMU Network. 3. The applicant unit must demonstrate the existence of an established perinatal data system, preferably computerized, providing documentation of previous performance, e.g., in defining and quantitating patient populations for clinical studies. All successful applicants must be willing to provide complete, accurate, and timely data to the MFMU generic data base. 4. Applicant maternal-fetal units should have at least 2,500 births per year, with a minimum of 30 percent high-risk pregnancies. There must be evidence that a large majority of patients with obstetric complications use the prenatal, delivery, and postpartum care system affiliated with the hospital in which the unit is located. There should also be documentation of the proportion of various subgroups of the obstetric population that have been eligible for, and have been randomized, in previous, or ongoing, clinical trials. 5. Applicants should document the clinical capabilities of the unit, including antenatal fetal testing, intrapartum diagnosis, laboratory testing, and perinatal pathology, and indicate how these clinical services have been modified, if necessary, to support clinical research in the past. Also, the existence of a pharmacy capable of supporting clinical research should be documented. 6. The application should describe the neonatal intensive care unit in the same hospital, and document current collaborative relationships with the unit, in terms of patient care, teaching, and research. Specifically, the infant follow-up arrangements for NICU "graduates," and their rate of follow up for both clinical care and research should be described. 7. There should be a clearly expressed intent to participate in a cooperative manner with other units, the NICHD, and the data coordinating center, in all aspects of randomized clinical trials in obstetrics, within the context of this MFMU Network, as outlined in this RFA. 8. The departmental and institutional commitment to collaborative maternal-fetal research should be clearly documented by evidence of its research productivity (recruitment performance, publications, etc.) in past or present clinical trials. 9. The application must exhibit a preparedness to pursue capitation of operational costs for each protocol in the Network. (See Budget Section.) 10. The NICHD also funds clinical trials in a Neonatal Network whose applications will be due on May 22, 1990. NICHD encourages applications from institutions which propose participation in both the Maternal-Fetal and Neonatal Networks. DIRECTION AND MANAGEMENT OF THE NETWORK The management of the MFMU Network includes three committees whose functions are as follows: 1. A Steering Committee will be responsible for protocol development, assisted by the Advisory Board and the Data Safety and Monitoring Committee. The Steering Committee will have primary responsibility for the conduct of protocols and the preparation of publications. The Steering Committee will be composed of each principal investigator, one representative from the Data Center, and three NICHD staff. NICHD staff will comprise the Director of the Center for Research for Mothers and Children (CRMC), an obstetrician from the Pregnancy and Perinatology Branch, and a representative from the Epidemiology and Biometry Research Program. The MFMU program officer will be the only voting NICHD staff member of the Steering Committee. An outside chairman, who is not participating as a principal investigator, will be selected by the NICHD. 2. An Advisory Board will advise the Steering Committee in the identification and prioritization of topics for network research. The Advisory Board, chosen by the NICHD with the advice of the Steering Committee, will be composed of individuals with expertise in clinical trials, biostatistics, epidemiology, perinatology, and neonatology; the Chairman of the Steering Committee; and the Director of the CRMC and the MFMU program officer. Additional members will participate based on the need for specific expertise. 3. A Data Safety and Monitoring Committee will monitor the safety of ongoing clinical trials and advise on their conduct. It will be established by NICHD and will represent expertise in ethics, clinical trial design, perinatology, neonatology, and basic science. CONTENT OF APPLICATION The following information should be included in the application: 1. MFMU Staffing. Provide complete descriptions of the training and qualifications of the maternal-fetal medicine subspecialists (see minimum requirements under RESEARCH SCOPE). Specify their past and current involvement in clinical and basic research and their availability to take primary responsibility for one or more of the Network protocols at the unit. Detail the current pattern of research nurse staffing of clinical trials in the unit, including arrangements for recruitment into protocols during evening, nighttime, and weekend hours. Provide specific information on research nurses who would be available for Network assignment. 2. NICU Staffing. Document current collaborative relationships with neonatologists for patient care, teaching and research. Identify one or more neonatologists who would collaborate actively in protocol development and implementation for the MFMU Network. 3. Perinatal Data System. Describe the perinatal data system used by the maternal-fetal unit, and document how it has been used, and is being used, to plan and carry out clinical research. Include the data form as an appendix. 4. Available Population of Clinical Research Subjects. Applicants are encouraged to include minorities among study populations. If minorities are not included, a clear rationale for their exclusion should be provided. Characterize the patients served by the maternal-fetal medicine unit (see minimum requirements). Specify the proportions of various subgroups (by payment status, race, age, parity, etc.) that have been eligible for, and have actually been randomized, in previous or current clinical trials. 5. Clinical Strengths and Weaknesses of the MFMU. Describe in detail the clinical attributes of the MFMU, with special attention to ambulatory services, antenatal fetal testing, intrapartum diagnosis, laboratory testing, and perinatal pathology. Indicate how these clinical services have been modified, if necessary, to support clinical research in the past. Also, document the availability of an institutional pharmacy capable of supporting clinical research. Finally, discuss any perceived weaknesses in the MFMU clinical care system and review planned solutions. 6. Neonatal Intensive Care Unit. Describe the organization and service load of the neonatal intensive care unit (NICU) in the same hospital as the MFMU, including the existing follow-up program. 7. Intent to Participate. Based on your understanding of the MFMU Network's structure and function, indicate specific ways in which MFMU policies and procedures could be modified to allow effective participation in randomized, multi-center clinical trials. Specifically, indicate your preparedness to participate in network clinical trials according to the terms and conditions of this RFA. 8. Departmental and Institutional Commitment and Experience. Provide letters of commitment from all involved departments to ensure optimal cooperation for network protocols. Provide evidence of research productivity by the applicant unit in previous or present clinical trials, especially of a cooperative, multicentric nature. Describe allocations of office space, equipment, and faculty time to previous or present clinical trial research. Specifically, summarize your experience with a non-network clinical protocol, including preparation for the trial (retrospective studies, identification of the study population, funding applications, budget preparation), conduct of the trial (recruitment of patients, integration with other clinical research, assignment of costs to research versus clinical care), resolution of problems encountered, results, and their implications. (The actual protocol and IRB approval for the described trial should be appended.) Applicants who are current MFMU Network members and are reapplying should provide a description of their participation in the Network protocols to date. Include in this description numbers of patients enrolled and completed, percent enrollment of available patients, and the nature and extent of staff involvement as it affected performance. Also, current MFMU Network members should summarize how they have met the terms of award that accompanied the Notice of Award for their initial grant period. 9. Acceptance of Budgetary Mechanism. Provide a statement from the department and institutional office of sponsored programs assuring cooperation with the proposed plan to capitate operational costs for each protocol. Also, discuss innovative ideas for making the conduct of clinical trials within the MFMU Network more efficient and cost-effective. MECHANISM OF SUPPORT - Terms of Agreement The funding mechanism to be used to assist the scientific community in undertaking this system of clinical investigation will be a Cooperative Agreement between the participating units and NICHD. The major difference between a Cooperative Agreement and a research grant is that there will be substantial programmatic involvement of NICHD staff above and beyond the levels required for traditional program management of grants. Specifically, the role of the NICHD MFMU program officer will be to aid the awardees and the Steering Committee in the following ways: o Assistance in the identification of important areas of study. o Assistance in the development of study protocols. o Assistance in the development and review of capitation-based budgets, including the identification of study costs and special institutional needs. o Assistance in the review and evaluation of each stage of the program before subsequent stages are started, in conjunction with the Steering Committee, and the Advisory Board. o Assistance in reporting results to the community of investigators and health care recipients. Programmatic responsibility for review and oversight of these Cooperative Agreements will reside with the MFMU program officer. This role will include the following: o Assurance of the scientific merit of the trials, including the option to withhold support of a participating center if technical performance requirements such as protocol compliance, enrollment targets, or randomization of subjects are not met. o Assistance in the efficient conduct of the trials, including ongoing review of progress; possible redirection of activities to improve performance and cooperation; and frequent communication with other members of the Steering Committee. o Initiation of a decision to modify or terminate a study based on the advice of the Data Center, Data Safety and Monitoring Committee, and Advisory Committee with the mutual consent of the Steering Committee. The responsibilities and authorities of the awardees will be as follows: o Identification of priority issues for research. o Development and implementation of protocols. o Collection and transmission of accurate data in a timely manner. o Analysis of data and publication of results of the MFMU trials. All parties will agree to accept the coordinating role of the group and the participatory and cooperative nature of the group process. The support of awards pursuant to this RFA is contingent upon ultimate receipt of appropriated funds for this purpose. The number of awards will be influenced by the overall merit of the applying centers and by the amount of funds available to the Institute. It is anticipated that eight to ten meritorious applications will be funded. The specific terms, conditions, and details of arbitration procedures pertaining to the scope and nature of the interaction between NICHD and the participating MFMUs will be incorporated into the Notice of Grant Award. These procedures will be in addition to the customary programmatic and financial negotiations which occur in the administration of grants; they will be invoked only when agreement cannot be reached on issues that may arise after the award between the awardee and the MFMU program officer. In that event, an arbitration panel will be formed consisting of one person selected by the principal investigators, one person selected by Chief of the Pregnancy and Perinatology Branch, and a third person selected by these two members. The decision of the arbitration panel will be binding. The special terms of Award of Cooperative Agreement are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, DHHS grant administration regulations at 45 CFR Part 74 and other DHHS, PHS, and NIH grant administration policies. The NICHD review procedure in no way affects the right of a recipient of a cooperative agreement to appeal an adverse determination under the terms of PHS regulations at 42 CFR Part 50, Subpart D, and DHHS regulations at 45 CFR Part 16. Business management aspects of these awards will be administered by the NICHD Grants Management Section in accordance with DHHS, PHS, and NIH grant administration requirements. Program staff intend that the ongoing Cooperative Agreements will be recompeted every five years, depending on available funds. REVIEW CRITERIA AND PROCEDURES A. Review Procedures Applications that are incomplete or nonresponsive to this RFA will be withdrawn by the Division of Research Grants and NICHD staff upon receipt, and returned to the applicants without further consideration. Applications that are complete and responsive may be subjected to a preliminary evaluation by an NICHD peer review group to determine their scientific merit relative to the other applications received in response to this RFA (triage); the NICHD will withdraw from further consideration applications judged to be noncompetitive for award and promptly notify the principal investigator/program director and the official signing for the applicant organization. Those applications judged to be competitive will be further evaluated for scientific/technical merit by a special review committee convened specifically for this purpose by the Scientific Review Program, NICHD. This review will include an evaluation of past performance in the MFMU Network for current members followed by a second-level review by the National Advisory Child Health and Human Development Council. Final selection of clinical centers for funding may also be based on the need for diversity in the study population. B. Criteria for Review. Strengths and weaknesses will be considered in the following areas specified in the Content section: 1. Personnel - (Content items #1 and #2) 2. Facilities - (Content items #3, #4, #5, and #6) 3. Management Intent, Commitment, and Experience - (Content items #7 and #8) 4. Budget - (Content item #9) (See Appendix I) METHOD OF APPLYING Applications should be submitted on form PHS-398 (revised 10/88). The conventional presentation format for regular research grant applications should be used, with care taken to address the points identified under review criteria and eligibility for participation. The title "MFMU COOPERATIVE AGREEMENT APPLICATIONS, RFA 90-HD-04" should be typed in item 2 of the face page of the application. The RFA label included in the PHS 398 (rev. 10/88) application kit must be affixed to the bottom of the face page. Failure to use this label could result in delayed processing of your application such that it may not reach the review committee in time for review. The original and four copies of the application should be sent or delivered to: Application Receipt Office Division of Research Grants National Institutes of Health Room 240, Westwood Building Bethesda, MD 20892 Also send two copies to: Laurance S. Johnston, Ph.D. Scientific Review Program National Institute of Child Health and Human Development Executive Plaza North, Room 520 Bethesda, MD 20892 Applications must be received by May 22, 1990. Late applications will not be accepted. TIMETABLE Application Receipt Date: May 22, 1990 Initial Review Date: June-July, 1990 Review by Advisory Council: January 1991 Anticipated Award Date: April 1, 1991 Inquiries regarding this announcement may be directed to: Donald McNellis, M.D. Special Assistant for Obstetrics Pregnancy and Perinatology Branch Center for Research for Mothers and Children National Institute of Child Health and Human Development Executive Plaza North, Room 643 Bethesda, MD 20892 Telephone: (301) 496-5575 This program is described in the catalog of Federal Domestic Assistance No. 13.865, Research for Mothers and Children. Awards will be made under the authority of the Public Health Service Act, Section 301 (42 USC241), and administered under PHS grant policies and Federal Regulations 42 CFR Part 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency Review. APPENDIX I BUDGET The budget at the time of application will be limited to a BASE BUDGET with maximum allowances as follows: Principal/Co-Investigator component 10% effort Coordinator 100% effort Data Entry Clerk 50% effort Supplies and Small Equipment (itemized and justified) NTE $4,500 Travel (a total of 10 trips to Bethesda per Network team) as appropriate Other costs (itemized and individually justified) NTE $2,500 At such time as an application has been approved and is being considered for funding, the applicant will be required to complete protocol budgets for those studies underway within the network. These budgets will consist of specific protocol-related allowances and will be capitated on the anticipated number of subjects to be enrolled in the study at the applicant MFMU. Ongoing annual budgets of MFMU Network members will be based on individual protocols which will be funded through a capitation system. Each MFMU Network member will be given base costs (listed above), in addition to a flat fee per patient successfully enrolled and completed. The individual members will be required to project patient enrollment for a specific protocol during a specified time frame; continuation and level of funding will be based on actual recruitment.