Full Text HD-96-008 SPECIALIZED COOPERATIVE CENTERS PROGRAM IN REPRODUCTION RESEARCH NIH GUIDE, Volume 25, Number 40, November 22, 1996 RFA: HD-96-008 P.T. 04 Keywords: Human Reproduction/Fertility Reproduction National Institute of Child Health and Human Development Letter of Intent Receipt Date: January 8, 1997 Application Receipt Date: May 15, 1997 PURPOSE The National Institute of Child Health and Human Development (NICHD) through the Reproductive Sciences Branch (RSB) in the Center for Population Research (CPR) provides funding for a limited number of research centers in the reproductive sciences. These centers provide an arena for multidisciplinary interactions among basic and clinical scientists interested in establishing high quality research programs in the reproductive sciences. Applications for these centers are sought from investigators willing to participate with the NICHD under a cooperative agreement in a multicenter cooperative research program. Center investigators will be expected to work with NICHD staff in facilitating research collaborations and interactions within and between centers. Such a cooperative program will form a national network that fosters communication, innovation and research excellence with the ultimate goal of improving human reproductive health through accelerated transfer of basic science findings into clinical practice. HEALTHY PEOPLE 2000 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2000," a PHS-led national activity for setting priority areas. This Request for Applications (RFA), Specialized Cooperative Centers Program in Reproduction Research, is related to the priority area of family planning. Potential applicants may obtain a copy of "Healthy People 2000" (Full Report: Stock No. 017-001-00474-0 or Summary Report: Stock No. 017-001-00473-1) through the Superintendent of Documents, Government Printing Office, Washington, DC 20402-9325 (telephone 202-512-1800). ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic for-profit and non-profit organizations, public and private, that meet the requirements stated in this RFA. Minority individuals, persons with disabilities, and women are encouraged to apply as Principal Investigators. The need for continuous and active communications and interactions among the awarded sites dictates that only domestic institutions in the United States will be eligible for these Center grant awards. MECHANISM OF SUPPORT The funding mechanism to be used to assist the scientific community in participating in this Centers Program will be the National Institutes of Health (NIH) cooperative specialized center (U54) mechanism. Funding will be provided by means of cooperative agreements established between the participating Centers and the NICHD. A cooperative agreement is not an "acquisition" mechanism. It is an "assistance" mechanism in which substantial NIH scientific and/or programmatic involvement with the awardee is anticipated during the performance of the activities conducted by the awardee. Under a cooperative agreement, the NIH purpose is to support, stimulate, and expedite the recipient's activities by jointly being involved with them. NIH staff work cooperatively with the award recipients in a partner role and do not assume direction, prime responsibility, or a dominant role in the activity. Details of the responsibilities, relationships, and governance of the activities to be funded under the cooperative agreements awarded for this Program are discussed later in this document under the section "Terms and Conditions." The total project period for an application submitted in response to this RFA is five years. The anticipated award date is April 1, 1998. Because the nature and scope of the research proposed in response to this RFA may vary, it is anticipated that the size of the awards will also vary within the funding limits available (see Description of a Center). It is expected that NICHD will solicit additional new or continuation center applications through annual issuance of an RFA. It is anticipated that at least three Centers will be funded in each subsequent annual competition contingent upon the availability of funds. FUNDS AVAILABLE Although this solicitation is included in the fiscal plans for FY 1998, support for these center grants is contingent upon the availability of funds for this purpose. The number of grants to be awarded is also contingent upon a sufficient number of applications deemed meritorious enough to be considered for an award. It is anticipated that an estimated total of $3,100,000 (including indirect and direct costs) will be available for the first year of the Program, which will support up to four Centers in FY 1998. RESEARCH OBJECTIVES Background The ultimate goals of biomedical research supported by the RSB are to develop new knowledge leading to clinical applications that will enable men and women to control their own fertility choices with methods that are safe, effective, inexpensive, reversible and acceptable to various population groups. Such research aims to develop new leads for contraception, procedures for alleviating infertility, and fertility preserving treatments for reproductive disorders that threaten fertility. The present day need for the availability of contraception options acceptable to diverse populations remains globally unmet. Among the 600 million women of reproductive age in today's world, as many as 228 million women are at risk of unintended pregnancy from the 39 trillion acts of intercourse that occur annually. Up to 64 percent of all worldwide pregnancies are unintended (mistimed or completely unwanted). Over 50 million abortions occur worldwide each year with minimal estimates of at least 100,000 abortion-related deaths annually. In the U.S., 3 million unintended pregnancies--57 percent of all pregnancies--occur annually with half resulting in abortion as an outcome. In half of the 1.3 million abortions occurring in the U.S. each year, a contraception method being used failed to prevent a pregnancy. Families, family values, and family planning form the cultural essence and cohesiveness of our existence as human societies. One of the most basic of human rights--the right to procreate-- is frustrated or denied by the occurrence of infertility in a couple desiring children. It has been estimated that infertility affects between 37 and 70 million married couples around the world. In U.S. studies described nearly 50 years ago, it was stated that up to 10 percent of married couples were 'sterile' with the remaining 90 percent having varying degrees of fertility. More recent and technically rigorous U.S. survey studies have conservatively identified that there are about 2.3 million infertile couples, which is about 9 percent of the domestic married couple population base with wives aged 15-44. In addition, such studies found that about 4.9 million U.S. women in this age range had an impaired ability to have children. At least 30-50 percent of infertility is attributable to male factor infertility for which the pathophysiology is either not understood at all or, at best, poorly understood. The prognosis for male infertility treatment outcomes is extremely poor at present. While analyses of the U.S. population base has not found alarming annual increases in the overall number of infertile couples or the overall prevalence of infertility, significant age-related increases in infertility coupled with delayed childbearing in the contemporary couple population base have been found in such studies. Physician office visits reflecting current societal life style requirements for infertility services have markedly increased from 1968 (600,000) to 1988 (1,350,000) with a projected U.S. peak estimated for 1995 approaching 1,800,000. Of the infertile couples seeking treatment for infertility, it has been estimated that up to one- half will be unsuccessful in achieving their desired outcome. In concert with the increased medical assistance sought, U.S. infertility service costs have risen to exceed a billion dollar annual medico-economic impact in the U.S. Reproductive disorders affecting fertility are associated with significant morbidity and a degree of mortality in some specific instances that cannot be ignored. During the past two decades, the incidence of ectopic pregnancy has increased from 4.5 to 16.1 per 10,000 pregnancies. The rate appears to be particularly increasing in young women aged 15-19, perhaps in relationship to the U.S. factors of earlier age of menarche and initiating sexual activity leading to encountering tubal disease factors earlier. In 1989, it was reported that 88,400 women experienced an ectopic pregnancy and 34 of them died as a direct consequence. While improved diagnostic procedures and early intervention protocols have resulted in markedly reducing mortality, surviving women are left with an 8-fold risk of reoccurrence and a 20 percent lowered chance of ever conceiving again. Accompanying the human costs of morbidities of reproductive tract disorders, as noted above, are the attendant substantial costs of the U.S. health care system involving the diagnosis, treatment, and follow-up services provided the patients, as well as the added costs to the patient and the U.S. economy of lost employment and family service hours. In reproductive aged couples, the obstructive sequelae of male accessory gland infections account for 8-12 percent of male partner diagnostic costs for fertility impairment. In reproductive aged females, it has been estimated that the general incidence of endometriosis is 5 to 15 percent. The incidence of endometriosis in females being surgically treated for infertility is known to be 30 to 50 percent. Among infertile females with no other known cause of their infertility, the incidence of endometriosis has been reported at 40 to 70 percent. A diagnosis of severe endometriosis often leads to hysterectomy-associated treatment. While the causative role of endometriosis in infertility remains poorly understood and its optimal diagnosis and treatment remain a goal--not an accomplishment--of contemporary medicine, the morbid impact of the associated pelvic pain has significant human cost and national economic costs. The etiology of polycystic ovary syndrome (PCOS), while identified more than 60 years ago by Stein and Leventhal, remains misunderstood despite 60 years of research. This insidious disease is currently the most common endocrine disorder of women of reproductive age. Recent prevalence rate estimates suggest at least 10 percent of the reproductive aged population of U.S. women suffer the full blown syndrome of hyperandrogenism, chronic anovulation and polycystic ovaries. While PCOS has been recognized to have a familial tendency consistent with a genetic factor in its etiology, few compelling studies clarifying this aspect have been forthcoming prior to this year. PCOS is a major cause of infertility, other reproductive system, and other tissue and organ system morbidities. Hysterectomy is a common patient outcome. PCOS is a major medical economic cost component in U.S. reproductive health care costs. Similarly, the role of dysfunctional uterine bleeding, either in the presence or the absence of uterine leiomyomata (fibroids), is not well understood despite its common occurrence and decades of research. It is a significant factor in noncompliant contraceptive use or discontinuance and, therefore, in the unintended pregnancy problem. Uterine myomata occur in nearly 20 percent of all reproductive aged women, are the single most common diagnosis from gynecological hospital admissions, may be the only abnormality observed in an infertile couple, and represent the most common medical indication for an unintended and often unwanted hysterectomy that prematurely ends a female's reproductive options. Hysterectomy to treat the morbidity of certain reproductive disorders is the second most common major surgery performed in the U.S., with greater than 500,000 hysterectomies reported each year prior to 1995, the year signifying the peak of 'baby boom' women in the population. If current hysterectomy rates had remained at the same pre-1995 prevalence level in the U.S., it is estimated that up to one- third of all women in the U.S. will have had a hysterectomy before the age of 60. The annual performance rate is not constant, however, with a projected level estimated at more than 800,000 annually beyond the 1995 marker year. Recognizing that the interactive needs of basic and clinical research necessary to address the above and related problems may be so complex that they cannot be solved by individual investigators working alone without the intellectual and fiscal resources of a cooperative specialized center program, it is the intention of the RSB, contingent upon the availability of funds, to initiate and maintain organized, multi-component reproductive extramural research programs of high quality that focus on topics deemed to be of high priority and significance because of their critically important relationship to the mission of the RSB. Objectives The objectives of this Centers Program are to support specialized reproductive research programs of high quality, and to facilitate and accelerate the translation of promising new preclinical or clinical leads into clinical practice. The RSB believes that the partnership developed between program staff and the award recipients through use of the cooperative agreement mechanism maximizes the ability of the RSB to promote, facilitate, and assist the research conducted by the awarded centers. This RFA is specifically designed to stimulate the reproductive sciences research community to organize and maintain research-based centers of outstanding quality that, serving as national research resources, form a cooperative network with NICHD that fosters communication, innovation and high quality reproductive research. Such networking as afforded by the cooperative nature of this Centers Program will ensure that the reproductive research community remains in the forefront of the development and utilization of new technologies which can be used to treat and ameliorate reproductive disorders, as well as to identify novel leads for fertility regulation. Research Scope The Specialized Cooperative Centers Program in Reproduction Research (SCCPRR) is composed of research-based center grants designed to support interactive groups of research projects and supporting core service facilities. The research activities included in these center grants must comprise, by definition, a multidisciplinary approach to biomedical problems addressing the specific research topic areas announced in this RFA (see below). These centers may have more than one theme, focus, or emphasis, but all of the subprojects involved must be responsive to one or more of the specific research areas of reproduction supported by the RSB. Furthermore, the translational objective of this Program requires that one of the subprojects be entirely or predominantly clinical. The following is a list of topics that are considered to be responsive to the research mission areas of the RSB. Additionally, these topics identify areas where research at the basic/clinical interface is deemed essential to the potential development of new leads or approaches to fertility control, as well as of diagnostic tools and procedures for the detection, treatment and effective management of reproductive disorders that impact on reproductive competence. Reproductive Biology and Physiology - gametogenesis, including nuclear and cytoplasmic mechanisms that direct germ cell mitosis and meiosis, and somatic cell-germ cell interactions which support gametogenesis; folliculogenesis, including studies addressing intraovarian control of follicle selection and atresia by growth factors, cytokines and their respective binding proteins and receptor antagonists; luteogenesis and luteolysis, including intraovarian mechanisms which control luteal lifespan; fertilization; early embryogenesis during the pre- to peri-implantation period; implantation, including cell-to-cell interactions regulating implantation. Reproductive Endocrinology - fundamental mechanisms of hormone synthesis, secretion, regulation and action in the context of reproduction, including intrapituitary mechanisms governing gonadotropin secretion, and intraneuronal mechanisms and glial- neuron interactions controlling pulsatile GnRH secretion; identification of elements and factors controlling gene transcription, and identification of signaling molecules and pathways mediating hormone action; interaction of the immune and neuroendocrine systems in controlling fertility; mechanisms by which nutritional modification alters the hypothalamo-pituitary- gonadal endocrine axis. Reproductive Medicine - pathophysiology, diagnosis and treatment of male or female infertility; relation of endometriosis to infertility, treatment of benign gynecologic diseases; improvement of existing and development of new approaches for assisted reproduction. Since this list is not meant to be all-inclusive, prospective applicants preparing either a competing new or continuation center grant application are encouraged to discuss program relevancy issues with the program staff contact cited under INQUIRIES in this RFA. However, applicants should note that the research scope of this RFA does not include studies in the area of reproductive oncology or reproductive epidemiology or studies dealing with post-implantation pregnancy and parturition. These topic areas are outside the purview of research areas supported by the RSB, and, therefore, will be deemed nonresponsive to this RFA. In addition, research proposals for projects or cores directly involving human in vitro fertilization and/or embryo transfer must be in compliance with NIH policies for such research and should not, therefore, include efforts or activities that create human embryos solely for research purposes. It is also not intended for the Centers to conduct large clinical trials. Guidance and Management Structures Overall coordination of the Centers Program consistent with the stated objectives set forth in the RFA (see Objectives) will be done by a Steering Committee consisting of all Center Principal Investigators and an NICHD staff Research Coordinator from the RSB, CPR. The Steering Committee will employ a consensus decision process to guide the Centers Program in evaluating the progress of member Center programs, their proposed new research initiatives within the general scope of the approved program, the need for collaborations either within or outside the Center network, and the need to redirect certain efforts of member Centers due to either sufficient data acquisition to permit conclusion, the acquisition of data supporting an alternative study initiative or experience proving that the proposed research is no longer feasible. In addition to the Steering Committee, smaller cooperative groups will be formed that consist of research components of member centers having common research interests addressing a specific basic and/or clinical research problem. These research focus groups will perform coordinated research activities as recommended by the Steering Committee. In turn, progress of the focus groups will further guide the Steering Committee in decision-making regarding changes in specific research directions, translational activities, and new research initiatives. The research focus group will consist of an NICHD staff Research Coordinator from the RSB, CPR, and Key Investigators of the relevant subproject and/or Core Directors. Further details of the guidance and management structures and processes may be found in the 'Terms and Conditions' section below. Description of a Center The minimal requirements for a Center described in this RFA are as follows (see sections on Review Criteria and Procedures and Award Criteria below): o Each center will propose a research plan that is responsive to the objectives of the Centers Program set forth in the RFA (see RESEARCH OBJECTIVES). o Each center will support at least three research subprojects that thematically address one or more research areas listed under Research Scope. It is required that one subproject be entirely or predominantly clinical in nature. For this Centers Program, the definition of clinical can involve patient studies or use of cultured human cells or tissue. Although not required, it is strongly encouraged that at least one basic science subproject be in a similar scientific area as the clinical subproject in order to facilitate transfer of information from bench to bedside. Alternatively, a project may be proposed that incorporates both basic and clinical approaches to a particular problem. o An administrative core unit which provides oversight to the Center that is located at the grantee institution, and is accessed only by budgeted center subprojects and cores. o A competent and experienced principal investigator who is committed to and directly involved in research dealing with mammalian reproduction; o Availability of competent and experienced scientific experts to direct individual research projects or cores associated with the proposed Center; o Availability of the technical resources and facilities necessary for the conduct of the experiments; o Access to properly managed animal facilities for projects conducting animal studies; o As appropriate, access to inpatient and outpatient reproductive health care units providing adequate numbers of patients for clinical research projects that require patient participation [Applications from institutions which have a General Clinical Research Center (GCRC) funded by the NIH National Center for Research Resources may wish to identify the GCRC as a resource for conducting the proposed research. In such a case, a letter of agreement from either the GCRC Program Director or Principal Investigator should be included with the application]. Optional components of the Center organization include the mix of subprojects and cores to be included in the Center. o The Principal Investigator may choose to organize the Center using collaborations of projects within the same institution. Alternatively, Centers may seek to maximize their scientific expertise and research capabilities by including in the application a subproject and/or a technical service core to be supported at other institutions through subcontracted consortium arrangements. No more than one consortium subproject and one consortium core service facility will be permissible in each Center. o The Principal Investigator may choose one of two center structure options regarding access to technical service core facilities. Closed Access Structure - In this center structure, administrative and all technical service cores will be utilized by budgeted center subprojects only. Consistent with NICHD guidelines for establishment of core facilities, utilization by three subprojects is required to justify a core technical service facility. Percent utilization by any one of the three subprojects justifying the core cannot exceed 50 percent or be less than 10 percent. The percent utilization of additional subprojects requiring core services can be less than 10 percent. Costs necessary to use a particular core facility can be incorporated into the budget of the core unit, and not in the budgets of the research subprojects per se. No internal chargeback system would be required. Open Access Structure - In this center structure, budgeted center subprojects as well as research projects external to the center (e.g., R01, R29, R03, P01 subproject) may have access to technical service cores. However, special consideration must be given to justification of a technical service core facility and the formal establishment of an effective chargeback system for all technical service cores. For each core service facility, at least one of the three projects used to justify a core must be a budgeted center subproject while the remaining project(s) used in justifying the core must be externally funded NICHD projects administered by the RSB. Percent utilization by any internally budgeted center subproject or externally-funded RSB project used to justify a particular core facility cannot exceed 50 percent or be less than 10 percent. If the minimum 30 percent utilization by three justifying budgeted center subprojects and externally- funded RSB projects is chosen, then up to seven additional federally-funded, peer-reviewed external research projects addressing program-relevant research areas of the RSB can access the core up to 100 percent of its service capacity. The 50/10 percent utilization requirement applies to this group of external projects. Centers must establish an internal management policy for evaluating the acceptability of proposed RSB program relevant external projects to access the core facilities. Approval of requests for core access privileges for external projects which would replace those described above must be made to RSB Program Staff who then will evaluate the extent to which the project is relevant to RSB mission research areas (see Research Scope), and render a decision accordingly. If centers choose to operate in an open access format, costs necessary to utilize a particular core facility by budgeted center subprojects must be incorporated into the budget of the subproject and not the core budget in order to accommodate participation in the required chargeback system. Core budgets will be justified and evaluated based on its access by budgeted center subprojects and external, program-relevant research projects as described above. Above and beyond this arrangement, technology-based core units can offer services to additional external projects addressing any area of research regardless of funding source only on a full payback (fee-for-service or in kind) basis. However, additional funds necessary to provide services to these external projects (e.g., technical support, supplies, etc.) must come from sources other than the center funding, such as the supply budgets of the external projects wishing to access the core facilities. In choosing to configure a center in an open-access center structure, the Principal Investigator must have in place and adequately described in the application management policies which ensure that budgeted center subprojects are given highest priority in receiving services provided by the core. Centers choosing to configure in an open-access center format may propose one or more technical service cores that will be utilized exclusively by budgeted center subprojects. These centers may, therefore, have a mix of open or restricted access technical service cores. On the other hand, administrative cores in open center structures may be accessed only by budgeted center subprojects. Once an award is made, centers configured as a closed-access center structure may, at a later time, choose to convert to an open access center structure by requesting such conversion in writing to the NICHD. Irrespective of the organizational mix selected by the Principal Investigator, each research subproject or core proposed for inclusion in the Center must be described independently using the PHS 398 application format as described in the document "Suggested Format for NICHD U54 Grant Applications," which is available from the program staff listed under INQUIRIES. For the individual projects or cores, the page limits stated in the PHS 398 instructions must be followed. The overall Center application must also use the PHS 398 format to provide at the beginning of the application an overall summary of the Center's organization and cumulative aggregate budgeting for the various budgetary categories. In both instances, all essential information for the evaluation of the application must appear in the body of the application rather than in an appendix. SPECIAL REQUIREMENTS Terms and Conditions of Award Cooperative agreements are assistance mechanisms and are subject to the same administrative requirements as grants. The following Terms and Conditions of Award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS, PHS, and NIH grant regulations, policies and procedures, with particular emphasis on HHS regulations at 45 CFR Part 74 and 92. Business management aspects of these awards will be administered by the NICHD Grants Management Branch in accordance with HHS, PHS, and NIH grant administration requirements. 1. The purpose of these cooperative agreements is to support a coordinated research program of specialized centers pursuing high quality reproductive research with the ultimate goal of facilitating and accelerating translation of basic science knowledge into clinical applications which can be used to regulate fertility or diagnose and treat infertility or reproductive disorders that impact on fertility. The primary authorities and responsibilities of the awardees are to participate cooperatively with the Steering Committee in the following activities: o Pursuit of research objectives consistent with the research scope of the RFA and research approved during the initial peer review; o Conduct experiments and collect the resulting data; o Analyze, interpret and present results and plans to the Steering Committee for approved activities; o Publish results, conclusions, and interpretation of the studies. The awardees will agree to: 1)accept the coordinating role of the Steering Committee which includes evaluating objectives and research goals of the Centers Program, and recommending modification, deletion or addition of protocols within the Centers Program; 2) follow any common protocols in which they participate for multicenter projects that are approved by the Steering Committee; and 3) accept the cooperative nature of the group process, including the establishment, where appropriate, of smaller collaborative groups comprised of interacting subprojects and/or cores focused on a particular reproductive research topic area. Awardees will retain custody of and primary rights to their data developed under the award subject to current government policies regarding rights of access as consistent with current HHS, PHS, and NIH policies. 2. The degree of programmatic involvement of the Research Coordinator is as follows: o Participating in the overall coordination of the Centers Program with the Steering Committee. This includes efforts to improve and strengthen inter- and intra-center cooperation amongst the research projects of the Centers, particularly as it pertains to translational research activities within and between centers. As a means of improving inter-center cooperation, the Research Coordinator will directly participate in the activities of the smaller collaborative groups established by the Steering Committee comprised of subprojects and/or cores focused on a particular reproductive research topic area. The Research Coordinator will also assist the research efforts of the Centers Program by facilitating access to fiscal and intellectual resources provided by industry, private foundations and NIH intramural scientists. The Research Coordinator will, as required, help reprogram research efforts, including options to modify or terminate them, by mutual consent between the Centers Program and NICHD. In the event of disagreements among the Program participants, the Research Coordinator will assist in forming an arbitration panel as discussed below. o Interacting with each individual center awardee evaluating objectives and research goals of that particular center, deciding optimal research approaches and protocol designs, and contributing to the adjustment of research protocols or approaches as warranted. The Research Coordinator will assist and facilitate this process and not direct it. The Research Coordinator will also provide assistance in reviewing and commenting on all major transitional changes of an individual center's activities prior to implementation to assure consistency with required goals of the Centers Program. o Retaining the option to recommend the withholding of support from a Center subproject or core materially failing to meet the technical performance requirements established by the Centers Program. This includes identifying jointly with participants of the Steering Committee the need to add additional research subprojects or service cores to Centers or to phase out a Center subproject or core when performance standards have not been met; and o Participating, where warranted, in data analyses, interpretations, and the dissemination of study findings to the research community and health care recipients including co- authorship of the publication of results of studies conducted by the Centers. 3. Overall Coordination of the Centers Program consistent with the stated intent of the RFA will be done by a Steering Committee consisting of the Principal Investigators from each of the participating Centers and one NICHD staff member from the RSB, CPR, NICHD, who will be the Research Coordinator. A member of the NICHD grants management staff will serve as a nonvoting advisor to the Committee. A chairperson for the Steering Committee will be chosen by a majority vote of the Principal Investigators. The Steering Committee meetings will be convened at least once per year. The purpose of these meetings is to share scientific information, assess scientific progress, identify new research opportunities and potential avenues of collaborations such as with industry, private foundations and/or NIH intramural scientists, establish priorities that will accelerate the translation of preclinical findings into clinical applications, reallocate resources and conduct the business of the cooperative research program. In anticipation that some centers will have common research interests that address a specific basic and/or clinical research problem, it is envisioned that research focus groups will be formed to conduct coordinated research activities recommended by the Steering Committee. The Steering Committee will approve multicenter protocols on specific research activities. As needed, the Steering Committee will develop a publication policy regarding joint authorship of research reports derived from such collaborative efforts. 4. Arbitration When agreement between an awardee and NICHD staff cannot be reached on scientific/programmatic issues that may arise after the award, an arbitration panel will be formed. The panel will consist of one person selected by the Principal Investigator, one person selected by NICHD staff, and a third person selected by these two members. The decision of the arbitration panel, by majority vote, will be binding. This special arbitration procedure in no way affects the right of an awardee 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. INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS It is the policy of the NIH that women and members of minority groups and their subpopulations must be included in all NIH-supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling rationale and justification is provided that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This new policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43) and supersedes and strengthens the previous policies (Concerning the Inclusion of Women in Study Populations, and Concerning the Inclusion of Minorities in Study Populations), which have been in effect since 1990. The new policy contains some provisions that are substantially different from the 1990 policies. All investigators proposing research involving human subjects should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research," which have been published in the Federal Register of March 28, 1994 (FR 59 14508-14513) and reprinted in the NIH Guide for Grants and Contracts, Volume 23, Number 11, March 18, 1994. Investigators also may obtain copies of the policy from the program staff listed under INQUIRIES. Program staff may also provide further discussion concerning the policy. LETTER OF INTENT Prospective applicants are asked to submit, by January 8, 1997, a letter of intent that includes a descriptive title of the proposed research, 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. Although a letter of intent is not required, is not binding, and does not enter into the review of subsequent applications, the information that it contains allows NICHD staff to estimate the potential review workload and to avoid conflict of interest in the review. The letter of intent is to be sent to Dr. Louis V. DePaolo at the address listed under INQUIRIES. APPLICATION PROCEDURES Contents of Applications A response to this RFA should consist of an application that includes: o A description of a Specialized Center in Reproduction Research consisting of multiple individual research subprojects, an Administrative Core and, if applicable, one or more technology- based core service facilities. For suggested formatting instructions see the document, "Suggested Format for NICHD U54 Grant Applications," available from the program staff listed under INQUIRIES. o A description of the capabilities of the Center to meet or exceed the minimal requirements stated below (see Description of a Center). o A proposed five-year research plan that presents the applicant's perception of the Center's organization and component functions. This plan should demonstrate the applicant's knowledge, ingenuity, practicality, and commitment in organizing a multiproject research infrastructure for conducting basic and clinical studies in the reproductive sciences. The research plan for the Center and all component subprojects must address the "Research Scope" described earlier. o The stated willingness of the Principal Investigator to cooperate in a coordinated cooperative program involving multiple Centers with the objective of developing research project and/or service core interactions between Centers. o Substantive evidence of departmental and institutional support for and commitment to the proposed Center. All applicants must document their ability to meet or exceed the minimum requirements as set forth in the 'Description of a Center'. This specifically includes understanding of and commitment to the cooperative nature of this Program. Applications from institutions that have a General Clinical Research Center (GCRC) funded by the NIH National Center for Research Resources may wish to identify the GCRC as a resource for conducting the proposed research, if appropriate. If so, a letter of agreement from either the GCRC program director or principal investigator could be included with the application. The research grant application form PHS 398 (rev. 5/95) is to be used in applying for these awards. Applications kits are available at most institutional offices of sponsored research and may be obtained from the Grants Information Office, Office of Extramural Outreach and Information Resources, National Institutes of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone 301/710-0267, email: ASKNIH@odrockm1.od.nih.gov. Additional suggestions for formatting the application into a Center grant application are provided in the document "Suggested Format for NICHD U54 Grant Applications," which is available from the program staff listed under INQUIRIES. The RFA label available in the PHS 398 (rev. 5/95) 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, the RFA title, SPECIALIZED COOPERATIVE CENTERS PROGRAM IN REPRODUCTION RESEARCH, and number, RFA HD-96-008, must be typed on line 2 of the face page of the application form and the YES box must be checked. Submit a signed, typewritten original of the application, including the Checklist, and three signed, photocopies, in one package to: DIVISION OF RESEARCH GRANTS NATIONAL INSTITUTES OF HEALTH 6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710 BETHESDA, MD 20892-7710 BETHESDA, MD 20817 (for express/courier service) At the time of submission, two additional copies of the application must be sent to: Susan Streufert, Ph.D. Division of Scientific Review National Institute of Child Health and Human Development Building 61E, Room 5E03 Bethesda, MD 20892 Bethesda, MD 20817 (for express/courier service) Applications must be received by May 15, 1997. The Division of Research Grants (DRG) will not accept any application in response to this RFA that is essentially the same as one already 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. The NICHD will not accept for review competing new or continuation applications that have been revised more than one time. If a revised competing continuation application is not selected for funding, the applicant institution may then only submit a new, substantially different application. Schedule Letter of Intent Receipt Date: January 8, 1997 Application Receipt Date: May 15, 1997 Initial Review Group Peer Review: October/November 1997 NACHHD Council Review: January 1998 Earliest Award Date: April 1, 1998 Budgets Applications from new center sites may not request more than $750,000 in direct costs for the first year, with incremental increases not exceeding four percent in each subsequent year. However, for currently existing RSB-supported center sites whose direct costs for the final year of the preceding project period as stated in the Notice of Grant Award are in excess of $750,000 in direct costs, the amount requested cannot exceed 120 percent of the direct costs awarded in the final competitive segment year of the preceding project period. A submitted application exceeding the budgetary limits specified above will be returned to the applicant unreviewed. In the event that an application submitted in response to this RFA is not funded, one revision of the application will be accepted in response to a subsequent RFA. Budgets for revised applications must be submitted in accord with the recommendations of the peer review group who evaluated the initial submission unless a different budget has been approved in advance by the NICHD. If a revised competing continuation application is not selected for funding, the applicant institution may then submit only a new, substantially different application that will be subject to the direct cost limit of $750,000. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by DRG and responsiveness to the RFA by NICHD staff. Incomplete applications will be returned to the applicant without further consideration. Any application that does not meet the minimum requirements as set forth in the 'Description of a Center' section of this RFA will be considered unresponsive to the RFA and returned to the applicant. This includes, but is not limited to, an evaluation by NICHD staff of the program relevancy of the proposed research subprojects and external projects being proposed to access core facilities. Applications that are complete and responsive to the RFA will be evaluated for scientific and technical merit by an appropriate peer review group convened by the NICHD in accordance with the review criteria stated below. As part of the initial merit review, a triage process may be used in which applications will be determined to be competitive or noncompetitive based on their scientific merit relative to other applications received in response to this RFA. Applications determined to be noncompetitive by the review committee will be withdrawn from further consideration, and the principal investigator will receive a summary statement reflecting the reviewers' evaluation. Applications judged to be competitive will be further discussed and assigned a priority score. They will then receive a second level review by the National Advisory Child Health and Human Development Council (NACHHD). Applications submitted in response to this RFA may also receive a site visit as part of the review process. However, applicants should assure that their applications are complete and can stand on their own. Review Criteria Evaluation of the applications will be based upon the following: 1. Research Plan o Scientific merit of the application with respect to its component subprojects and cores, as well as its overall strength as an organized center; o Significance of the application to the objectives of the Program outlined in this RFA; o Adequacy of plans to include both genders and minorities and their subgroups as appropriate for the scientific goals of the research. Plans for the recruitment and retention of subjects will also be evaluated. (See INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS) o Appropriateness of policies to ensure the protection of human subjects and the humane care and use of laboratory animals; and o Willingness to work and cooperate with other Centers and the NICHD in the manner summarized in this RFA. 2. Personnel o Scientific, clinical, and administrative abilities of the Principal Investigator and other key participants, particularly, but not exclusively, in the area of the proposed research; o Knowledge and experience of the Principal Investigator and other key investigators in areas relevant to the conduct of the experiments proposed; and o Documented commitment time for the proposed studies and the specifically stated and described willingness of the Principal Investigator and the key investigators to work and collaborate with other Centers and with NICHD assistance in the manner summarized in this RFA. 3. Facilities and Management o Adequacy of administrative, clinical, and technical capabilities to conduct the research proposed; o Adequacy of animal facilities and appropriateness of animal care management where animal work is proposed; o Adequacy of clinical facilities and appropriateness of patient care management where clinical work is proposed; and o Institutional assurance to provide support to the Center in such areas as fiscal administration, personnel management, space allocation, procurement, planning, and budgeting. 4. Budgeting Appropriateness of the proposed budget and duration in relation to the proposed research. AWARD CRITERIA The anticipated date of award is April 1, 1998. Applications approved by the NACHHD Council will be considered for award based on scientific and technical merit; program balance; and availability of funds. The NICHD will not support more than one SCCPRR center award involving departments or specialty units of a single grantee institution. In order to receive funding, an individual domestic institution's application for a Specialized Cooperative Center Grant must have three or more related, interactive, and high quality research subprojects that provide a multidisciplinary, yet thematic, approach to the problems to be investigated. At least one of the subprojects must be clinically oriented. Awards will not be made for applications with research activities focused exclusively on clinical research or exclusively on basic research or for applications or components thereof proposing epidemiological or large scale clinical trial research. INQUIRIES Written and telephone inquiries concerning this RFA are encouraged. The opportunity to clarify any issues or questions from potential applicants is welcome. Direct inquiries regarding programmatic issues and address the letter of intent to: Louis V. DePaolo, Ph.D. Center for Population Research National Institute of Child Health and Human Development Building 61E, Room 8B01 Bethesda, MD 20892-7510 Telephone: (301) 496-6515 FAX: (301) 496-0962 Email: depaolol@hd01.nichd.nih.gov Direct inquiries regarding fiscal matters to: Ms. Melinda Nelson Office of Grants and Contracts National Institute of Child Health and Human Development Building 61E, Room 8A17 Bethesda, MD 20892-7510 Telephone: (301) 496-5481 FAX: (301) 402-0915 Email: nelsonm@hd01.nichd.nih.gov AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance No. 93.864, Population Research. Awards are made under authorization of the PHS Act, Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and 285). These special Terms of Award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines administered under PHS grants policies and Federal Regulations 42 CFR 52 and 45 CFR Part 74. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. The PHS strongly encourages all grant and contract recipients to provide a smoke-free workplace and promote the non-use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people. .
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