Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Funding Opportunity Title	Specialized Cooperative Centers Program in Reproduction and Infertility Research (U54)
Activity Code	U54 Specialized Center- Cooperative Agreements
Announcement Type	Reissue of RFA-HD-12-169
Related Notices	February 21, 2013 - This RFA has been reissued as RFA-HD-14-017.
Funding Opportunity Announcement (FOA) Number	RFA-HD-13-005
Companion FOA	None
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.865
FOA Purpose	The purpose of this funding opportunity announcement (FOA) is to announce the re-competition of the Specialized Cooperative Centers Program in Reproduction and Infertility Research (SCCPIR). The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) provides funding for a limited number of research centers in the reproductive sciences. These centers provide an arena for multidisciplinary interactions between basic and clinical scientists interested in establishing high quality translational research programs in the area of reproductive health and infertility. The centers also serve as a national resource for the training and career development of new scientists electing to pursue careers conducting translational research in high priority areas of reproduction and infertility. Finally, center investigators are expected to participate in important community outreach and education efforts to increase awareness and convey the importance and implications of their research activities to the general public.

Posted Date	January 4, 2012
Letter of Intent Due Date	May 27, 2012
Application Due Date(s)	June 27, 2012
AIDS Application Due Date(s)	Not Applicable
Scientific Merit Review	October/November 2012
Advisory Council Review	January 2013
Earliest Start Date(s)	April 2013
Expiration Date	June 28, 2012
Due Dates for E.O. 12372	Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the PHS398 Application Guide except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. While some links are provided, applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information
Part 2. Full Text of Announcement
Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

The Eunice Kennedy Shriver 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 translational research programs in the reproductive sciences. The centers also serve as national resources for the training and career development of young scientists electing to pursue careers conducting research in high priority areas of reproduction and infertility. Accordingly, the purpose of this FOA is to announce a re-competition of the Specialized Cooperative Centers Program in Reproduction and Infertility Research (SCCPIR). Applications 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 among centers. Such a cooperative program will form a national network that facilitates and accelerates bidirectional knowledge transfer between the laboratory and clinic with the ultimate goal of improving human reproductive health through enhanced communication, innovation and research excellence.

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 couples desiring children. It has been estimated that infertility affects between 37 and 70 million married couples around the world. In U.S. studies described over 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 nine percent of the domestic married couple population base with wives aged 15-44. According to the 2002 National Survey of Family Growth, 7.4 percent of married women, or about 2.1 million women were infertile (12 months or longer without birth control and without a pregnancy). This represents a significant decline from the prevalence of 8.4 percent reported in 1982. On the other hand, about 15% of married women or 4.3 million had an impaired ability to have children (impaired fecundity) in 2002 compared to 8.5% of married women 20 years earlier. This latter trend likely is indicative of the delay in childbearing found in the contemporary couple population base in which significant age-related increases in infertility and subfecundity have been reported.

Physician office visits reflecting current societal life style requirements for infertility services have markedly increased in the U.S. almost four fold between 1968 (600,000) and 2000 (2,100,000). Indeed, it is estimated that 13 percent of American women will receive infertility services during their lifetime. Interestingly, this represents only half the number of women who actually need infertility services. 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 several billion dollars annually.

In couples, at least 25-40 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. Indeed, whereas 80 percent of infertile women can be successfully treated, male infertility can be treated in only 10-20 percent of such men. However, the widespread use of assisted reproductive technologies such as intracytoplasmic sperm injection (ICSI) and its variants has enabled otherwise infertile men to father children, although possible genetic causes of the infertility are likely transmitted to the progeny.

Reproductive tract disorders affecting fertility are associated with significant morbidity and a degree of mortality in some specific instances that cannot be ignored. Accompanying the human costs of morbidities of reproductive tract disorders are the attendant substantial costs to the U.S. health care system involving the diagnosis, treatment, and follow-up services provided to 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 eight to 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 five to 15 percent, but can be as high as 50% in women with pelvic pain or infertility. 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 as well as national economic costs. Indeed, the health care burden of endometriosis has been estimated to be an astounding 22 billion dollars per year!

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 leiomyomata occur in nearly 20% percent of all reproductive-aged women, are the single most common diagnosis in 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. Fibroids disproportionately affect African Americans with some studies indicating a three-fold higher prevalence in this racial group than in the Caucasian population. Annual cost expenditures for this condition approximate 2.1 billion dollars.

Polycystic ovary syndrome (PCOS) is a major cause of female infertility, as well as of other reproductive system and other tissue and organ system morbidities. Identified more than 60 years ago by Stein and Leventhal, the etiology of PCOS remains misunderstood despite 60 years of research. This insidious disease is currently the most common endocrine disorder of reproductive-aged women, affecting between five and 10 percent of women aged 15-44 or more than four million women in the U.S. Most, if not all women with PCOS present with hyperandrogenemia, irregular menstrual cycles and polycystic ovaries. Often, these conditions are accompanied by obesity and insulin resistance. Indeed, the risk of type 2 diabetes mellitus among PCOS patients is five- to 10-fold higher than in the normal population, and the prevalence of the Metabolic Syndrome is nearly two-fold higher in PCOS women than in the general population. Considering the high prevalence of diabetes in PCOS women, a very recent study estimated that the total annualized cost of evaluating and providing care to PCOS women is a staggering $4.6 billion dollars.

Also poorly understood is the pathogenesis of premature ovarian failure that affects one in 100 women by age 40. Interestingly, 16 percent of women carrying the fragile X pre-mutation present with premature ovarian failure. The mechanism(s) underlying pre-mutation-based ovarian insufficiency is not known, but once known could provide critical insights into the basic biological processes regulating ovarian follicular growth, differentiation and atresia.

With the hopes that earlier diagnosis of these devastating infertility disorders will result in earlier intervention and amelioration of the condition, attention is now turning to the adolescent. Here, research efforts are needed to better define hormonal changes during normal progression of sexual maturation, particularly at the time of menarche. In this regard, initial menstrual cycles are often irregular and are anovulatory making it difficult to diagnose conditions such as PCOS. Likewise, endometriosis had been thought to occur rarely in adolescence, but it is being diagnosed more frequently in this population thanks to a greater awareness by the medical community. Even so, efforts to refine diagnostic criteria for children and adolescents so that effective interventional strategies can be employed are likely to pay enormous dividends in decreasing the incidence of disease and infertility in adulthood.

Data now firmly support the contribution of genetics and epigenetics in male and female infertility. In males, there is considerable evidence from breeding studies and gene knockout experiments in animals that mutation of over 100 separate genes results in infertility. More limited studies in humans show that a number of inherited diseases are associated with abnormal sperm morphology and function. These data suggest that a significant number of men with infertility may have one or more mutations that predispose to their condition. However, it is currently not possible to determine which men have genetic infertility. Similarly, it is estimated that 15-20 percent of human pregnancies are chromosomally abnormal as a result of division errors during oocyte meiosis or early embryonic cleavage. Such errors not only are the leading cause of birth defects, but may be the single most important factor contributing to human infertility. Finally, evidence is mounting to show that altered epigenetic modification of gene expression through histone modifications, methylation defects or RNA stability changes may underpin diseases such as endometriosis.

Regarding the male, it is becoming apparent that male infertility can be considered a marker for the general health of the individual, i.e., infertility is correlated with higher rates of cardiovascular disease, diabetes, and certain types of cancers. Furthermore, contrary to previous thinking, the sperm contributes more than its DNA to the oocyte as the epigenome has been shown to play a critical role in the developing embryo. Alterations in the establishment and/or maintenance of the various epigenetic marks have been shown to affect the fertility status of males.

An area of emerging public health interest is the preservation of fertility in individuals undergoing treatments for diseases such as cancer. Currently, there are more than 9 million cancer survivors in the U.S. of whom approximately 5% are under the age of 35. The chemical or radiological consequences of these treatments oftentimes target vital reproductive organs such as the gonads depleting the gamete stem cell pool thereby causing permanent infertility. Therefore, providing options for preserving fertility in men, women and children is not only an important reproductive health issue, but a quality of life issue as well.

Another high priority area for reproductive health is preconception care. This has its roots in the Barker Hypothesis which states that adult diseases have their origins prior to birth. To this point, most experimentation has examined possible adverse birth outcomes (e.g., low birth weight, intrauterine growth restriction, preeclampsia, pre-term birth, birth defects) and adult disease incidence as a result of perturbing the maternal-fetal environment. However, it is now clear once again from animal models that these adverse outcomes can occur during the embryonic period and even prior to implantation or conception itself. Thus, increased efforts are needed to define important developmental periods in which perturbations to normal physiological systems can result in poor pregnancy outcomes and to determine if these periods coincide with periods for important epigenetic modification of the genome.

Finally, the need for the availability of contraceptive 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. 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., more than three million unintended pregnancies, about 60 percent of all pregnancies, occur annually, with half resulting in abortion as an outcome. In half of the abortions occurring in the U.S. each year, a contraceptive method being used failed to prevent pregnancy.

The RSB recognizes 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. Therefore, it is the intention of the RSB, contingent upon the availability of funds, to continue and maintain organized, multi-component reproduction and infertility research programs of high quality that focus on topics of high priority and significance that are critically important to the mission of the RSB, and that address important reproductive health concerns of the American public.

A major objective of the SCCPIR is to support specialized translational reproductive research programs of high quality, and to facilitate and accelerate bidirectional transfer of knowledge between the laboratory and clinic. This process of translating research between the laboratory and clinic is a continuum that encompasses all aspects of knowledge transfer from non-human animal models to humans. For example, application of information from rodent species to non-human primates is considered part of the translational continuum. However, the ultimate goal of supporting translational research through the SCCPIR is to improve human reproductive health.

This FOA 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 reproduction and infertility 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 that can be used to diagnose, treat and ameliorate reproductive diseases and disorders, as well as to identify novel leads for fertility regulation.

The SCCPIR 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 FOA (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 objectives of this Program require that one of the subprojects be entirely or predominantly clinical and that all basic science subprojects be linked to the clinical component(s) of the center.

Topics that are considered to be responsive to the research mission areas of the RSB include but are not limited to those bulleted below. 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 regulation, as well as of diagnostic tools and procedures for the detection, treatment and effective management of reproductive disorders that impact on reproductive competence.

• Reproductive Developmental Biology: origins and differentiation of germ cells; the endocrine, paracrine and physiologic mechanisms involved in gametogenesis, including germ cell-somatic cell interactions, germ cell proliferation and apoptosis, blood-testis barrier formation and remodeling and germ cell transplantation; fertilization, including sperm motility and capacitation, zona pellucida binding and mechanisms to block polyspermy; pre-implantation embryonic development including zygotic gene activation, mechanisms regulating embryonic stem cell self-renewal and differentiation and maintenance of stem cell pluripotency including the importance of oocyte reprogramming factors; use of genetically modified stem cells to treat animal models of reproductive disorders impacting fertility.
• Reproductive Tract Biology and Physiology: 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 that control luteal life span; implantation, including cell-to-cell interactions and embryo-uterine communication; the role of angiogenesis in ovarian and endometrial function; correlation of segmental gene expression with structure and function of the oviduct and epididymis.
• Reproductive Endocrinology and Neuroendocrinology: fundamental mechanisms of hormone synthesis, secretion, regulation and action in the context of reproduction; developmental control of GnRH neuronal migration and targeting; intraneuronal mechanisms and glia-neuron interactions controlling pulsatile GnRH secretion; intrapituitary mechanisms governing gonadotropin secretion; identification of elements and factors controlling gene transcription including ensembles of co-activators and co-repressors, 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 Genetics and Epigenetics: genetics of sex determination including clarification of the functional interactions between the known sex determination genes; genes, pathways, and epigenetic mechanisms that are important in reproduction, including those involved in imprinting of genes, differential expression of maternally vs. paternally inherited alleles, and DNA methylation during gametogenesis and embryogenesis; and elucidation of the genes, genetic and epigenetic mechanisms responsible for normal and skewed X chromosome inactivation.
• Reproductive Medicine: etiology, pathophysiology, prevention and treatment of male or female infertility, with particular emphasis on defining those conditions that are either genetically based or may have a significant epigenetic component; relation of endometriosis and uterine leiomyomas to infertility, diagnosis, management and treatment of other benign gynecologic diseases; research leading to improved outcomes across the spectrum of assisted reproductive technologies, as well as development of new approaches for assisted reproduction; use of genomics and proteomics to develop novel diagnostics for reproductive diseases and disorders particularly in adolescents; role of parental health on gamete quality and function.

Because this list is not meant to be all-inclusive, prospective applicants preparing either a new or competing continuation center grant application are encouraged to discuss program relevance issues with the program staff contact cited below. However, applicants should note that the research scope of this FOA does not include studies in the area of reproductive oncology, reproductive toxicology or reproductive epidemiology, or studies dealing with post-implantation pregnancy and parturition. These topic areas are outside the scope of research supported by the RSB and, therefore, will be deemed non-responsive to this FOA. Further, applications proposing research activities focused exclusively on basic research, or applications or components thereof proposing epidemiological or large-scale clinical trial research, will not be considered responsive to this FOA.

The minimal structural requirements for a Center described in this FOA:

• Research Projects - At least three research projects that thematically address one or more research areas listed under Research Scope. It is required that at least one project be entirely or predominantly clinical in nature, and that all basic science projects be linked to the clinical component(s) of the center. According to the NIH definition, clinical research must be conducted with human subjects (or on material of human origin such as tissues and specimens) for which an investigator (or colleague) directly interacts with human subjects. Excluded from this definition are in vitro studies that utilize human tissues that cannot be linked to living individuals. For purposes of this FOA, studies involving use of NIH-approved human embryonic stem cell lines (http://escr.nih.gov) will be allowed. Projects must be in compliance with the Dickey-Wicker amendment.
• Administrative Core - An administrative core, located at the applicant institution and accessed only by budgeted Center research projects and cores, will provide oversight to the Center.

The budget for the Administrative Core must include $50,000 direct costs per year to support collaborative projects with investigators supported by other SCCPIR centers and/or pilot studies. In the case of pilot projects, centers are strongly encouraged to use the funds to support either New Investigators or investigators who are not already supported by the SCCPIR Center. New Investigators are those who have not previously competed successfully as PD(s)/PI(s) for a substantial NIH independent research award (http://grants.nih.gov/grants/new_investigators/index.htm#definition). Centers are also encouraged to utilize these funds for conduct of clinical research studies that could form the basis for conduct of large scale clinical trials through the NICHD Reproductive Medicine Network. A center can use these funds to support pilot studies even if a separate pilot project(s) was approved in the funded application (see below under Optional Components of the Center). These funds will be requested as part of the Administrative Core budget, and will be restricted for use to support collaborative and/or pilot projects pending an external peer review of the project, and approval by the SCCPIR Steering Committee and by NICHD. Applications should not include detailed proposals for pilot projects that request use of the restricted funds, although titles of potential projects may be provided. Support for a particular collaborative research activity or pilot project is limited to two years with an option to extend the project an additional year pending review of progress.

The Administrative Core budget should also include direct costs of $30,000 per year to provide translational research training experiences, both didactic and/or laboratory, for students, postdoctoral fellows or residents from other centers, and post-residency scholars supported under institutional K12 awards such as the CTSA, Women s Reproductive Health Research (WRHR), Male Reproductive Health Research (MRHR) and Building Interdisciplinary Research Careers in Women’s Health (BIRCWH) career development programs. These funds will be requested as part of the Administrative Core budget, and will be restricted for cross-center training experiences. Funds can be used to purchase supplies, course materials and travel. Center investigators are particularly encouraged to provide training experiences for under-represented minority groups, those with disabilities and those who wish to re-enter an active research career after taking time to care for children or attend to other family responsibilities. In addition to the $30,000, the NIH offers supplements to the parent award to support individuals representing these special populations. Guidelines on how to apply for these supplements are provided in PA-08-190, Research Supplements to Promote Diversity in Health-Related Research (http://grants.nih.gov/grants/guide/pa-files/PA-08-190.html).

• Outreach/Education Core - This core will have a separate budget of $75,000 direct costs per year to support activities related to community outreach and education. Investigators are required to develop a plan for disseminating information and providing awareness experiences for community members including students, families and other health-care professionals. Examples of activities that would address this important aspect of the center include development of a web site for the lay public that includes tutorials, laboratory-based learning experiences, seminars and involvement of the community on external advisory boards.

Optional components of the Center:

Optional components and organization include the mix of other research projects, pilot projects, and service cores to be included in the Center. The PD(s)/PI(s) may choose to organize the Center using a suite of research projects and cores within the same institution. Alternatively, Centers may seek to maximize their scientific expertise and research capabilities by including in the application research projects and/or technical service cores to be supported at other institutions through subcontracted consortium arrangements.

• Pilot Projects - Funds may be requested in the original application to provide support for one or more pilot projects in Years 01 and 02 relevant to the center’s goals. Pilot projects may be used to generate preliminary data for submission of an R01 application or center research project, to develop new technologies that further enhance the research efforts of the center or to support clinical research studies that could form the basis for conduct of large scale clinical trials through the NICHD Reproductive Medicine Network.

Support for a pilot project is limited to a two-year period. Funding may not exceed $100,000 direct costs per year. With NICHD staff approval, the period of support may be extended one additional year. Funds for pilot projects may be requested in either new or renewal applications. As such, the proposed research plan must be described in sufficient detail, comparable to the other research projects submitted in the application, to permit evaluation of the project using the review criteria listed under Section V. Application Review Information , with the exception that little or no preliminary data are required for a pilot project. If a pilot project is favorably recommended for an initial two-year period, funds will be included each year for the full five years. Funds requested in Years 03-05 will be contingent upon review and approval of additional pilot projects by NICHD staff. Funding levels in these out-years will be based on the level of funding for this purpose in Years 01 and 02.

• Core Units - If applicable, one or more technology-based core service facilities may be requested as part of the Center. Consistent with NICHD guidelines for establishment of core facilities, utilization by three research projects is required to justify a core technical service facility. The applicant 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 research projects only. Percent utilization by any one of the three research projects justifying the core may not exceed 50 percent or be less than five percent. The percent utilization of additional research projects requiring core services may be less than five percent. Costs necessary to use a particular core facility should be incorporated into the budget of the core unit, and not in the budgets of the research projects per se. No internal charge-back system would be required.

Open Access Structure - In this center structure, budgeted center research projects, as well as research projects external to the Center (e.g., R01, R03, R21, 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 charge-back 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 research project, 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 research project or externally funded RSB project used to justify a particular core facility may not exceed 50 percent or be less than five percent. An additional seven federally funded, peer reviewed external research projects addressing program relevant research areas of the RSB may access the core up to 100 percent of its service capacity. The 50/5 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 research projects must be incorporated into the budget of the project and not the core budget in order to accommodate participation in the required charge-back system. Core budgets will be justified and evaluated based on access by budgeted center projects and external, program relevant research projects as described above. Above and beyond this arrangement, technology based core units may 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 PD(s)/PI(s) must have in place, and adequately describe in the application, management policies that ensure that budgeted center research projects 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 research projects. These centers may, therefore, have a mix of open and restricted access technical service cores. On the other hand, administrative cores in open center structures may be accessed only by budgeted center research projects.

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.

Program Coordination and Management

Overall coordination of the SCCPIR, consistent with the stated objectives set forth in this FOA (see Objectives), will be done by a Steering Committee consisting of the PD(s)/PI(s), the Project Directors, and an NICHD Project Scientist from the RSB, CPR. The Steering Committee will employ a consensus decision process to guide the SCCPIR in evaluating the progress of member Center programs, their proposed new research initiatives within the general scope of the approved program, the need to provide the entire SCCPIR network of centers with access to new technologies, the need for collaborations either within or outside the SCCPIR 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, or, in the case of SCCPIR-wide resources, lack of utilization.

In addition to the Steering Committee, smaller cooperative Research Focus 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 SCCPIR Steering Committee, subject to peer review. In turn, progress of the Research Focus Groups will further guide the Steering Committee in decision making regarding changes in specific research directions, translational activities, collaborative research projects and support of new resources. The Research Focus Group will consist of an NICHD Staff liaison from the RSB, CPR, and Key Investigators of the relevant research project and/or Core Directors. Further details of the guidance and management structures and processes may be found under Section VI.2.A Cooperative Agreement Terms and Conditions of Award .

Funding Instrument	Cooperative Agreement
Application Types Allowed	New Renewal Resubmission Revision The OER Glossary and the PHS398 Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	The NICHD intends to commit approximately $3.5 million in total costs [Direct plus Facilities and Administrative (F & A) costs] in FY 2013 to fund up to two new and/or renewal applications in response to this FOA.
Award Budget	Overall Budget - An applicant for a center may request a project period of up to five years and a budget for direct costs not to exceed $1.4 million for the first year with incremental increases for recurring costs (i.e., personnel, consultants, supplies, travel and other expenses) not to exceed two percent in each subsequent year. Applications exceeding the budgetary limits specified above will be returned to the applicant without peer review. Increases in outyear budgets for recurring costs are subject to the availability of funds. Administrative Core - The budget for the Administrative Core must include $50,000 direct costs per year to support collaborative projects with investigators supported by other SCCPIR centers and/or pilot studies. The Administrative Core should also include funds in the amount of $30,000 direct costs per year to provide translational research training experiences, both didactic and/or laboratory, for students, postdoctoral fellows or residents from other centers, and post-residency scholars supported under institutional K12 awards such as the CTSA, Women s Reproductive Health Research (WRHR), Male Reproductive Health Research (MRHR) and Building Interdisciplinary Research Careers in Women’s Health (BIRCWH) career development programs. Outreach/Education Core - This core will have a separate budget of $75,000 direct costs per year to support activities related to community outreach and education. Pilot Projects (optional) - Up to $100,000 direct costs per year may be requested to provide support for one or more pilot projects relevant to the center’s goals in Years 01 and 02. Support for a pilot project is limited to a two-year period. However, the same level of funding may be requested for years 03-05. If a pilot project is favorably recommended for the initial two-year period, funds will be included each year for the full five years. Funds requested in Years 03-05 will be contingent upon review and approval of additional pilot projects by NICHD staff. Travel - PD(s)/PI(s) should request travel funds to support their participation in the annual Steering Committee Meeting as well as two research focus group meetings per year. Key Investigators of budgeted center research projects and Directors of technical service cores should request travel funds to support participation in two research focus group meetings per year.
Award Project Period	The maximum period of support is 5 years. Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. Although the financial plans of the IC provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

Subcontracts from domestic entities to foreign sites are permitted for research projects and cores.

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant organizations must complete the following registrations as described in the PHS398 Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

• Central Contractor Registration (CCR) must maintain an active registration, to be renewed at least annually
• eRA Commons

All Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least4-6 weeks prior to the application due date.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PD(s)/PI(s), visit the Multiple Program Director(s)/Principal Investigator(s) Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the PHS398 Application Guide. The multiple PD(s)/PI(s) option is allowed for the overall center and/or for individual research projects.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed. Resubmission applications may be submitted, according to the NIH Policy on Resubmission Applications from the PHS398 Application Guide.

Applicants are required to prepare applications according to the current PHS 398 application forms in accordance with the PHS 398 Application Guide.

It is critical that applicants follow the instructions in the PHS398 Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed research
• Name, address, and telephone number of the PD(s)/PI(s)
• Names of other key personnel
• Participating institutions
• Number and title of this funding opportunity

The letter of intent should be sent to:

Stuart B. Moss, PhD
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
6100 Executive Blvd. Room 8B01H
Bethesda, MD 20892-7510
(Fed Ex or courier use: Rockville, MD 20852
Telephone: 301-435-6979
Email: mossstua@mail.nih.gov

Applications must be prepared using the PHS 398 research grant application forms and instructions for preparing a research grant application. Submit a signed, typewritten original of the application, including the checklist, and three signed photocopies in one package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)

At the time of submission, two additional paper copies of the application and all copies of the Appendix files must be sent to:

Sherry Dupere, Ph.D.
Director, Division of Scientific Review
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institutes of Health (NIH)
6100 Executive Boulevard, Room 5B01, MSC 7510
Bethesda, MD 20892-7510
Rockville, MD 20852 (for express/courier service; non-USPS service)
Telephone: 301-451-3415
Email: duperes@mail.nih.gov

All page limitations described in the PHS398 Application Guide and the Table of Page Limits must be followed, with the following exceptions or additional requirements:

For New U54 applications, page limits are as follows:

• Overview of the Center (for overall U54) 12 pages
• Research Project Descriptions (each project)
  • Research Project Cover Page 1 page
  • Abstract 1 page
  • Specific Aims 1 page
  • Research Strategy (for Research Projects) 12 pages
  • Research Strategy (for optional Pilot Projects) 6 pages
• Core Descriptions (each Core)
  • Core Unit Cover Page 1 page
  • Abstract 1 page
  • Core Unit Structure, Administration, and Services 6 pages

For Resubmission or Revision applications, also include the following:

• Introductions (required for a resubmission or revision application)
  • For overall U54 1 page
  • For each Research Project 1 page
  • For each Core Unit 1 page

Resource Sharing Plan

Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the PHS398 Application Guide.

Appendix

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix (please note all format requirements) as described in the PHS398 Application Guide, with the following modifications:

• All paper PHS 398 applications must provide appendix material on CDs only.

Part I. Overview Information contains information about Key Dates.

Information on the process of receipt and determining if your application is considered on-time is described in detail in the PHS398 Application Guide.

Applicants may track the status of the application in the eRA Commons, NIH’s electronic system for grants administration.

This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

Applications must be received on or before the due dates in Part I. Overview Information. If an application is received after that date, it will not be reviewed.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review and responsiveness by the NICHD, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed.

Other submission requirements include:

• Availability of the technical resources and facilities necessary for the conduct of the research.
• Access to properly managed animal facilities for projects conducting animal studies.
• 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 that have a Clinical and Translational Science Award (CTSA) of General Clinical Research Center (GCRC) funded by the NIH National Center for Research Resources may wish to identify the CTSA or GCRC as a resource for conducting the proposed research. In such a case, a letter of agreement from either the CTSA or GCRC Program Director or Principal Investigator should be included with the application.]
• Willingness to cooperate in a coordinated cooperative research program involving other SCCPIR centers.

Applicants should use the following instructions for preparing the application:

Face Page (Form Page 1)

Complete all items on the application's face page. For Item 2, enter the number of this FOA and the title, "Specialized Cooperative Centers Program in Reproduction and Infertility Research (U54) . Number succeeding pages consecutively.

Description: Project Summary and Relevance, Project/Performance Site(s), Senior/Key Personnel, Other Significant Contributors, and Human Embryonic Stem Cells (Form Page 2 and 2-continued)

Describe briefly the proposed research program, indicate the research emphasis of the component Research Projects, and identify the purpose of the proposed Core units.

List all Senior/Key personnel and Other Significant Contributors engaged on the project. Use continuation pages as necessary, numbering consecutively.

Table of Contents (Form Page 3)

In lieu of the preprinted Table of Contents outline on Form Page 3 of PHS 398, a Table of Contents should be prepared listing all of the major sections described below and paginated to enable reviewers to find specific information easily. Identify each Research Project component and each Core unit by title. Assign each Research Project component a Roman numeral (I, II, III) and assign each Core unit a capital letter (A, B, C) that reflects the order in which they are presented.

Budget Instructions (Form Page 4 & 5):

Prepare a series of composite budget tables for the U54 grant as requested below, followed by a detailed budget for each Research Project component and each Core unit.

Composite Budget

• Use PHS-398 Form Page 4, "DETAILED BUDGET FOR INITIAL BUDGET PERIOD," to present the total budget for all requested support for the first year. For each category, such as "Personnel," "Equipment," etc., give the amount requested for each Research Project component and each Core unit, with subtotals.
• If consortium arrangements involving other institutions or organizations are anticipated, include total (direct and indirect) costs associated with such third-party participation in the Consortium/Contractual Costs category. Costs for purchased services should be itemized under the "Other Expenses" category.
• Use PHS-398 Form Page 5, "BUDGET FOR ENTIRE PROPOSED PROJECT PERIOD," to prepare a budget, by category, that provides totals for each year of requested support. Requests for any increases in succeeding years must be justified in the individual Research Project component and Core unit budgets.

Budgets for Individual Research Project Components and Core Components

• Detailed Budget for Initial Budget Period (use PHS-398 Form Page 4 for each).
• Budget for Entire Proposed Project (use PHS-398 Form Page 5 for each).
• Budget Justifications and Explanations: Describe the specific functions of all key personnel, consultants, collaborators, and support staff. For all years, explain and justify any unusual items such as major equipment or alterations and renovations. For additional years of support requested, justify any significant increases or decreases in any category over the first 12-month budget period. Identify such changes with asterisks against the appropriate amounts. If a recurring annual increase in personnel or other costs is anticipated, give the percentage; however, the maximum allowable escalation under this FOA is 2%. In addition, for RENEWAL applications, justify any significant increases in any category over the current level of support.
• PLEASE NOTE: Consortium budgets (if applicable) should be presented as described in Composite Budget, including budget for the entire proposed project period. Total direct and indirect costs of sub-awardee are to be shown under Consortium/Contractual costs on the individual component budget and a detailed sub-awardee budget is to be placed following the appropriate Research Project or Core budget.

Biographical Sketch (Biographical Sketch Format Page):

Follow the instructions on the Biographical Sketch Format Page. This section must contain the biographical sketches of all individuals listed as Senior/Key Personnel and Other Significant Contributors, following the order listed on Form Page 2. Biographical sketches are required for all key personnel participating in the Research Project components and Core units. Begin with the U54 overall PD(s)/PI(s) and thereafter, in alphabetical order, submit biographical sketches as described in the Instructions for Form PHS-398. Do not exceed four pages for each person.

Resources (Resources Format Page):

Complete the "Resources" page of PHS-398 for the overall project. Briefly describe the features of the institutional environment that are or would be relevant to the effective implementation of the proposed program. As appropriate, describe available resources, such as clinical and laboratory facilities, participating and affiliated units, patient populations, geographical distribution of space and personnel, and consultative resources.

All instructions in the PHS398 Application Guide must be followed, with the following additional instructions:

The Research Plan should include a general Overview of the Center, followed by individual sections for each Research Project and Core. Wherever possible, use the headings and subheadings specified below. Further information on the preparing NICHD U54 Cooperative Specialized Research Center Grant applications is available at http://www.nichd.nih.gov/funding/mechanism/u54_guide.cfm .]

Overview of the Center (12 pages)

History, Purpose, and Objectives

Describe the overall objectives and general plans for the proposed grant period, including the Center's research grant history with yearly funding level.

Administration, Organization, and Operation

Include information on the support and commitment of the parent institution for the program, the authority of the PD(s)/PI(s), the use of advisory committees, and space assignment. Describe organizational framework and provide an organizational chart.

Research Program

Discuss the proposed research program, highlighting its central theme. List by title and investigator's name the component Research Projects and Core units. Describe the relationship between the projects and the Core units and their relationship to the central theme.

Description of Assurances and Collaborative Agreements

Provide an overview and rationale for any collaborative and cooperative endeavors or subcontracts. Letters of agreement for these arrangements are included in Item 6. Letters of Assurance/agreement as described below.

Research Project Descriptions

• Identify each project by a Roman numeral (I, II, III...) and a title.
• A full description of each project is to be provided following the format and instructions for Form PHS-398 (http://grants.nih.gov/grants/funding/phs398/phs398.html).
• Begin the presentation of each Research Project component on a separate page (Cover Page).

Cover Page for Research Project (1 page; not the PHS398 Face Page) Include the following information:

• Title of Project
• Research Project Director (Principal Investigator), title, affiliation
• Other investigators, titles, affiliations

Abstract of Research Plan (1 page; use PHS-398 Form Page 2):

• Discuss the purpose and nature of the project and its relevance to the program's overall theme.
  

Content of Research Plan (Begin each section with a section header):

• Introduction to Application (Resubmission or Revision applications only; 1 page)
• Specific Aims (1 page)
• Research Strategy (12 pages for Research Projects; 6 pages for optional Pilot Projects): Start each section with the appropriate section heading Significance, Innovation, Approach. Cite published experimental details in the Research Strategy section and provide the full reference in the Bibliography and References Cited section. For new applications, include information on Preliminary Studies. For renewal/revision applications, provide a Progress Report within the 12 page research stategy limit. Indicate the Research Project's use of Core unit services, including why needed and the advantages and cost effectiveness of Core unit usage for the project.
• Inclusion Enrollment Report (renewal or revision applications only)
• Bibliography and References Cited, Progress Report Publication List
• Protection of Human Subjects
• Inclusion of Women and Minorities
• Targeted/planned Enrollment Table
• Inclusion of Children
• Vertebrate Animals
• Select Agent Research
• Consortium/contractual arrangements
• Letters of Support: Include pertinent letters of assurance and collaboration for the Research Project.
• For off-site projects, justification should be provided for the project's location, and plans for interaction and cooperation with the other components of the program should be addressed.
• Resource Sharing Plan

Core Unit Descriptions

• Identify each proposed Core unit by a letter (A, B, C...) and a title (e.g., Administrative Core, Molecular/Cellular Core, etc.).
• A full description of each Core unit is to be provided following the format below.
• Begin the presentation of each Core unit on a separate page (Cover Page).

Cover Page for Cores (1 page; not the PHS398 Face Page) Include the following information:

• Title of Core unit
• Core Director (Principal Investigator), title, affiliation
• Other investigators, titles, affiliations

Abstract (1 page; use PHS-398 Form Page 2): Include an Abstract that identifies and describes the purpose of the proposed Core unit. Summarize the Core unit's overall objectives; highlight the decision-making process for use of Core services and plans for cost-effectiveness and quality control.

Introduction (Resubmission or Revision applications only; 1 page)

Core unit Structure, Administration, and Services (6 pages)

• Administrative Core Unit
  • Objective
  • Organizational chart (if appropriate)
  • Staffing (Professional and Support)
  • Resources: provide description of space and physical resources
  • Services provided (current and projected use): describe services to other Core units and Research Projects
• Additional Core Unit(s)
  • Objective
  • Staffing (Professional and Support)
  • Resources: provide description of space and physical resources
  • Administration
  • Justification: describe services provided with their bearing on productivity and quality
  • Usage: Indicate past and/or current usage (e.g., assays performed, animals supplied, etc.) and list projects proposed for Core usage
  • Use of Core Units by Research Project Components
• Provide a summary for the first year of the proposed Center grant showing the percentage use of each Core unit by the Research Project components.

Multiple Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) Leadership Plan

For Center applications designating Multiple PD(s)/PI(s), a leadership plan must be included. The multiple PD(s)/PI(s) option is allowed for the overall center and/or for individual research projects. A rationale for choosing a multiple PD(s)/PI(s) approach should be described. The governance and organizational structure of the leadership team and the research project should be described, including communication plans, process for making decisions on scientific direction, and procedures for resolving conflicts. The roles and administrative, technical, and scientific responsibilities for the project or program should be delineated for the PD(s)/PI(s), including responsibilities for human or live vertebrate animal subject studies as appropriate. Do not submit a leadership plan if you are not submitting a Multiple PD(s)/PI(s) application. If budget allocation is planned, the distribution of resources to specific components of the project or the individual PD/PIs should be delineated in the Leadership Plan. In the event of an award, the requested allocations may be reflected in a footnote on the Notice of Award.

Progress Report Publication List (for Renewal applications only)

List publications prepared during current grant period (or the past five-year period) which report results of research supported by the grant.

Letters of Assurance/Agreement

Any arrangements for collaborative and cooperative endeavors or subcontracts should be highlighted. Include letters of agreement from consultants. For projects to be conducted off site, i.e., at an institution other than the applicant institution, a PHS-398 face page or other documentation, signed by the off-site institutional officials, must be submitted with the application.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

For this particular announcement, note the following:

For NICHD Center applications (U54), peer review of scientific and technical merit focuses on three areas: (1) review of the individual Research Projects and Pilot Projects; (2) review of the individual Core units; (3) review of the U54 Center as an integrated collection of research projects and cores oriented around a central theme as well as the overall merit of the program.

Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the Center to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the Center proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a Center that by its nature is not innovative may be essential to advance a field.

Significance

Does the Center address an important problem or a critical barrier to progress in the field? If the aims of the Center are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? Will the Center make an important contribution to high quality translational research in the area of reproductive health and infertility?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the Center? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD(s)/PI(s), do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the Center? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?

If the Center involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

As applicable for the center proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact/priority score, but will not give separate scores for these items.

Center as an Integrated Effort

The overall U54 Center will be evaluated as an integrated research effort focused on one or more research areas listed under Research Scope. The relationship and contributions of each Research Project and Core to the overall objectives will be discussed and evaluated. Reviewers will assign an impact/priority score based on assessment of the scientific and technical merit of the Center overall. The assessment will take into consideration all proposed Research Projects and Cores, including any with poor ratings. The review will assess the level of merit of the Center as an integrated effort, including the following criteria:

• Will there be coordination, interrelationships, cohesiveness, and synergy among the research projects and core components as they relate to the common theme of the Center?
• What are the advantages of conducting the proposed research as a program rather than through separate research efforts? Will the research efforts taken together have more impact on the field than each separate project conducted in isolation? Will the research proposed in individual projects be enhanced by the Center?
• Are there mechanisms proposed for regular communication and coordination among investigators in the Center?
• Are administrative structures in place for the day-to-day management of the Center, including arrangements for internal quality control of ongoing research?
• Does progress made during the previous funding period for renewal applications demonstrate an acceptable level of integration between the Center research projects?

Protections for Human Subjects

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children

When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewals

For Renewals, the committee will consider the following:

• Has sufficient progress made in the last funding period relative to the original goals of the Center and objectives of each research project and core?
• Has the center effectively conducted translational research where translation is defined as knowledge transfer from non-human models to humans?
• Has the center participated in collaborative research activities within the center network?

Revisions

For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project.

As applicable for the Center proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact/priority score.

Applications from Foreign Organizations

Not Applicable.

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genome Wide Association Studies (GWAS).

Budget and Period of Support

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a component project that by its nature is not innovative may be essential to advance a field.

Significance

Does the component project address an important problem or a critical barrier to progress in the field? If the aims of the component project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the component project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD(s)/PI(s), do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the component project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?

If the component project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

As applicable for the component project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact/priority score, but will not give separate scores for these items.

Protections for Human Subjects

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children

When the proposed component project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the component project.

Renewals

For Renewals, the committee will consider the progress made in the last funding period.

Revisions

For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the component project. If the Revision application relates to a specific line of investigation presented in the original application that was not for recommended approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

As applicable for the component project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact/priority score.

Applications from Foreign Organizations

Not Applicable.

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genome Wide Association Studies (GWAS).

Budget and Period of Support

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Reviewers will assign a score for each Core unit component, based on the assessment of each Core unit independently in terms of the specified review criteria for Cores (see below). Cores will not receive scores for the five standard criteria (significance, investigator(s), innovation, approach, environment).

For all Cores, the following review criteria will be used:

• Are the qualifications, experience, and commitment of the core director and other core personnel appropriate?
• Will the quality of services provided enable center investigators to achieve their research goals?
• Is there cost effectiveness in the core; will there be quality control measures taken for core procedures?
• Is the use of core services by the budgeted center projects and, if applicable, by external projects appropriate?
• Are plans for charge back and priority management procedures for core units offering services to external projects adequate?

For the Administrative Core, the following review criteria will be used:

• Does the core director have experience in research administration?
• Is there a decision-making process within the proposed center for the evaluation of research productivity, for allocation of funds and for management of the resources?
• What is the overall strength of the plan for center evaluation, including the use of any internal and external advisory groups?
• What is the overall strength of the internal data sharing and publication plan?
• Does the Center provide high-quality translational research training experiences for students, postdoctoral fellows or residents?

For the Outreach/Education Core, the following review criteria will be used:

• Does the applicant describe an effective plan for outreach/education activities?
• Will the activities result in a better comprehension by the community of the objectives and goals of the SCCPIR, a greater appreciation for research progress made as a result of funding and a better understanding of the implications of SCCPIR-supported research for reproductive health?
• Are efforts made to include community representatives on advisory committees?

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s), convened by NICHD, in accordance with NIH peer review policy and procedures, using the stated review criteria. Review assignments will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact/priority score.
• Will receive a written critique.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

Applications will be assigned to the appropriate NIH Institute or Center and will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Child Health and Human Development (NACHHD) Council. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

After the peer review of the application is completed, the PD(s)/PI(s) will be able to access his or her Summary Statement (written critique) via the eRA Commons.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to the DUNS, CCR Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

• Pursuing research objectives consistent with the research scope of the FOA and research favorably recommended by peer review;
• Conducting experiments and collecting the resulting data;
• Analyzing, interpreting and presenting results and plans to the Steering Committee for approved activities;
• Publishing 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 research projects and/or cores focused on a particular reproductive research topic area.
• Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

NICHD Project Scientist Roles:

• Participating in the overall coordination of the SCCPIR 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 they pertain to translational research activities within and between centers. As a means of improving inter-center cooperation, the Project Scientist will directly participate in the activities of the smaller collaborative groups established by the Steering Committee comprising research projects and/or cores focused on a particular reproductive research topic area. The Project Scientist will also assist the research efforts of the SCCPIR by facilitating access to fiscal and intellectual resources provided by industry, private foundations and NIH intramural scientists. The Project Scientist 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 Program participants, the Project Scientist will assist in forming an arbitration panel as discussed below.
• 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 Project Scientist will assist and facilitate this process and not direct it. The Project Scientist 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 SCCPIR.
• Retaining the option to recommend the withholding of support from a Center research project or core materially failing to meet the technical performance requirements established by this Centers Program. This includes identifying jointly with participants of the Steering Committee the need to add additional research projects or service cores to Centers or to phase out a Center project or core when performance standards have not been met; and
• 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 or results of studies conducted by the Centers.

NICHD Program Official Role:

• An NICHD Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

• Participating on a Steering Committee consisting of the PD/PIs from each of the participating centers and one NICHD staff member from the RSB, CPR, NICHD, who will be the Project Scientist. A non-NIH Chairperson for the Steering Committee will be chosen by a majority vote of the PD(s)/PI(s). Meetings of the Steering Committee will be convened 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.
• Each full member of the Steering Committee will have one vote. Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.

Dispute Resolution:

• Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

When multiple years are involved, awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-710-0267
TTY 301-451-5936
Email: GrantsInfo@nih.gov

eRA Commons Help Desk(Questions regarding eRA Commons registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Email: commons@od.nih.gov

Stuart B. Moss, PhD
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6979
Email: mossstua@mail.nih.gov

Sherry Dupere, Ph.D.
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-451-3415
Email: duperes@mail.nih.gov

Mr. Ted Williams
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-480-4782
Email: williate@mail.nih.gov

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.