NIH’s new Application Submission System & Interface for Submission Tracking (ASSIST) is available for the electronic preparation and submission of multi-project applications through Grants.gov to NIH. Applications to this FOA must be submitted electronically using ASSIST or an institutional system-to-system solution; paper applications will not be accepted. ASSIST replaces the Grants.gov downloadable forms currently used with most NIH opportunities and provides many features to enable electronic multi-project application submission and improve data quality, including: pre-population of organization and PD/PI data, pre-submission validation of many agency business rules and the generation of data summaries in the application image used for review.

It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts) and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. 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 the 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 Fertility and Infertility (FI) Branch, 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 this scientific area. The centers also serve as national resources for the training and career development of young scientists electing to pursue biomedical research careers in reproduction and infertility. Finally, center investigators develop and participate in community outreach and education efforts to increase awareness and convey the importance and implications of their research activities to the general public. Accordingly, the purpose of this FOA is to announce the re-competition of the National Centers for Translational Research in Reproduction and Infertility (NCTRI). The NCTRI will be administered through the Specialized Research Center (P50) award mechanism. These centers 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 research excellence and innovation.

With the issuance of this FOA, applications that address the epigenetic bases of reproductive health and disease will be strongly encouraged. Particular emphasis will be on applications that go beyond correlative studies to address possible causality and contributions of epigenomic variants to inherited reproductive health and disease. Although applications that address the scientific mission areas of the Fertility and Infertility Branch will continue to be accepted, meritorious applications addressing the epigenetic bases of reproductive health and disease will receive priority in making funding decisions.

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 studies described over 50 years ago, it was stated that up to 10 percent of U.S. 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 approximately 2.0 million infertile couples, which is about nine percent of the domestic married couple population base with wives aged 15-44. According to the 2012 National Survey of Family Growth, 6.0 percent of married 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. Interestingly, the prevalence of infertility using a current duration (time to pregnancy) was recently estimated to be ~15%, indicating the importance of definition and methodologic approach for estimating the prevalence of infertility. On the other hand, about 11% of married women had impaired fecundity, i.e., the biological capacity to reproduce in 2010 compared to 8.5% of married women in 1982. This trend likely is indicative of the delay in childbearing found in the couple population base in which significant age-related increases in infertility and subfecundity have been reported.

Physician office visits for infertility services have markedly increased over four-fold between 1968 and 2010 in the U.S. (>2,000,000 visits annually). It is estimated that 12 percent of American women aged 15-44 have received infertility services at some point 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. This increase in medical assistance has led to a rise in infertility service costs to more than several billion dollars annually.

In couples, at least 30-40 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. Even though artificial reproductive technologies such as intracytoplasmic sperm injection can, in most cases, circumvent male infertility, the process is expensive, both from a monetary and a psychological standpoint for the couple. Furthermore, while ICSI and other assisted reproductive technologies have enabled otherwise infertile men to father children, these technologies may bypass genetic or epigenetic causes of infertility that may also be linked to other health problems that will negatively impact the life of the unborn child (and possibly later generations).

Reproductive tract disorders affecting fertility are associated with significant morbidity and a degree of mortality in some instances. 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. Because the causative role of endometriosis in infertility remains poorly understood and its optimal diagnosis and management has not been achieved, the health care burden of endometriosis has been estimated to be an astounding 22 billion dollars per year.

Uterine leiomyomata occur in 20-30% percent of all reproductive-aged women. Uterine fibroids 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, exacting a profound health care burden on a population of women that often times lack good health care coverage. Annual societal cost expenditures for this condition have recently been estimated to be between 6 and 34 billion dollars.

Polycystic ovary syndrome (PCOS) is a major cause of female infertility. Identified more than 60 years ago, the etiology of PCOS still remains misunderstood. It 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 $4.6 billion dollars.

Also poorly understood is the pathogenesis of premature ovarian insufficiency (POI) that affects one in 100 women by age 40. Interestingly, 16 percent of women carrying the fragile X pre-mutation present with POI. 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. 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. 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 in both male and female infertility. In males, there is considerable evidence from animal studies that mutations in over 100 separate genes result in infertility. More limited studies in humans show that a number of inherited diseases associated with abnormal sperm morphology and function are likely polygenic. 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.

It is becoming increasing apparent that for complex diseases including those affecting reproductive health (e.g., PCOS, endometriosis) both genetic and non-genetic factors are involved. These non-genetic factors, collectively referred to as epigenetic mechanisms, include DNA methylation, RNA modifications (epitranscriptomics), post-translational histone modifications, and non-coding RNAs (microRNAs, long non-coding RNAs). In fact, although diseases such as cancer typically have been thought of as genetic disease, they actually may be a disease of the 'epigenome' (why doesn t everyone with a specific mutation get cancer?). Unlike alterations to the DNA that are fixed , epigenetic mechanisms are bidirectional, e.g., a histone may alternate between being acetylated or not depending on the transcriptional state of its associated gene. These epigenetic mechanisms are responsible for how the genome interacts with the environment and changes in the epigenome are sporadic and differ from cell-to-cell. This heterogeneity makes analyses difficult, although techniques now exist that permit the epigenome to be interrogated at the single cell level. Similar to GWAS studies, epigenome-wide association studies (e.g., eFORGE) that will provide insight into disease etiology are now possible.

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. Of particular importance is the demonstration that environmental factors such as toxicants and diet promote multi- and transgenerational inheritance of adult-onset disease through epigenetic alterations in both males and females.

Epigenetics is controlled by families of proteins called 'writers',' readers', and 'erasers'; writers add a particular mark to DNA, RNA or protein, readers translate the signal carried by the mark into a particular phenotype, and erasers remove the mark. Ten or 15 years ago there was relatively little known of these enzymes and the metabolites that are required for their action. As more of these enzymes have been identified, great interest has arisen in controlling gene expression via small molecule inhibitors of various epigenetic mechanisms (e.g., lysine methyltransferases, histone deacetylases). For example, JQ1 is a potent inhibitor of the BET (bromodomain and extraterminal domain) family of bromodomain proteins and has been shown to affect memory formation in neurons. Although specificity is an issue, some of these inhibitors already are in clinical trials for various cancers. It is hoped that because of the large number of proteins that make up the families of enzymes that modify the epigenome, it will be possible to achieve specificity of action.

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 often times target vital reproductive organs such as the gonads, depleting the gamete stem cell pool and causing permanent infertility. For example, more than 1 in 5000 men of reproductive age who are childhood cancer survivors suffers from infertility or sub-fertility. However, in the future the ability to cryopreserve a testicular biopsy prior to treatment, followed by expansion of the spermatogonial stem cells and transplantation back into the testis may afford the opportunity to generate normal offspring without contaminating malignant cells and epigenetic and/or genetic errors. 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.

The importance of preconception care has its basis in the Barker Hypothesis that states that adult diseases have their origins prior to birth. Most experimentation has examined the relationship between 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 from animal models that these adverse outcomes can occur during the embryonic period and even prior to implantation or conception itself (and can even be due to the paternal contribution). 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 epigenetic modification of the genome.

Data suggest that infertility is not necessarily a unique disease of the reproductive axis, but is often physiologically or genetically linked with other diseases and conditions. Although it is well-established that many chronic diseases and conditions can impair fertility, less is known about the extent to which fertility status can act as a marker for overall health. Many recent epidemiologic studies demonstrate a link between fertility status and various somatic diseases and disorders, and suggest that fertility status can be a window into overall health. The findings include both male and female reproductive function, and their association with cancer, as well as conditions of the cardiovascular, metabolic, and the immune systems. Validation of the premise that fertility status can be a window into overall health would provide a valuable opportunity to affect future health during fertility evaluation, allowing early intervention in serious, chronic diseases.

The Fertility and Infertility Branch (FIB) 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 FIB, 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 FIB, and that address important reproductive health concerns of the American public.

A major objective of the NCTRI 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 NCTRI 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 centers program that fosters communication, innovation and high quality reproduction and infertility research. To facilitate networking, investigators will have opportunities to participate in various Research Focus Groups (RFGs), comprised of investigators from multiple centers who have similar research interests, e.g., male infertility. The RFGs themes will be determined during the first meeting of the Center Directors depending on the scientific areas of the reproductive centers. are organized by the NICHD program staff depending on the scientific areas of the reproductive centers. It is expected that PD/PIs from all reproductive centers participate in the most scientific-appropriate RFGs (and should request travel funds to attend the yearly meetings). Each RFG elects a leader who organizes the meetings and the agenda. These RFGs meet at least once a year in-person and maintain contact throughout the year via webinars, meeting at Scientific meetings etc. Such networking 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 NCTRI 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 discussed in this FOA. These centers may have more than one focus or emphasis, but all of the research projects involved must address one or more of the specific research areas of reproduction supported by the FIB. Furthermore, the objectives of this Program require that one of the research projects be entirely or predominantly clinical, and that all basic science projects be linked to the clinical project (s) of the center. As noted above, applications that focus on the epigenetic bases of reproductive health and disease will be strongly encouraged and, if deemed meritorious, can receive priority when making funding decisions.

These topics listed below 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 and effective management of reproductive disorders that impact on reproductive competence.

• Reproductive Developmental Biology: origins and differentiation of germ cells including gametic stem 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; fertilization, including sperm motility and capacitation, zona pellucida binding and mechanisms to block polyspermy in animal models; pre-implantation embryonic development including zygotic gene activation in animal models; 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 and cytokines; luteogenesis and luteolysis, including intraovarian mechanisms that control luteal life span; implantation, including cell-to-cell interactions and embryo-uterine communication; trophoblast differentiation and function in relation to fertility and pregnancy, including the role of the immune system; the role of angiogenesis in ovarian and endometrial function; sperm maturation in the epididymis and acquisition of hyperactivated motility in the female reproductive tract.
• Reproductive Endocrinology and Neuroendocrinology: 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; systems approaches to identify factors controlling gene transcription, and identification of signaling molecules and pathways mediating hormone action; interaction of the immune and neuroendocrine systems in controlling fertility; mechanisms by which nutritional modification alters the hypothalamo-pituitary-gonadal endocrine axis including the role of the microbiome.
• Reproductive Genetics and Epigenetics: genetics of sex determination; genetics and epigenetic mechanisms important in reproduction, including those involved in genomic imprinting and X chromosomal inactivation; mechanisms involved in DNA methylation, RNA modification, post-translational modifications of histones, and small non-coding RNAs during gametogenesis and embryogenesis; mechanisms underlying transgenerational epigenetic inheritance.
• Reproductive Medicine: etiology, pathophysiology, prevention and management of male or female infertility, with particular emphasis on defining those conditions that are either genetically based or may have a significant epigenetic etiology beyond correlation; relation of endometriosis and uterine leiomyomas to infertility; research on preserving fertility including cryopreservation of gametes and embryos; use of genomics, epigenomics and proteomics to develop novel diagnostics for reproductive diseases and disorders; 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 renewal center grant application are encouraged to discuss program relevance issues with the Scientific/Research Contact indicated in Section VII. Agency Contacts. 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 FIB 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.

See Section VIII. Other Information for award authorities and regulations.

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:

o Hispanic-serving Institutions

o Historically Black Colleges and Universities (HBCUs)

o Tribally Controlled Colleges and Universities (TCCUs)

o Alaska Native and Native Hawaiian Serving Institutions

o Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

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)
• 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

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

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
• NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons.If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

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 PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

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.

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

Individuals involved in NIH-funded clinical trials must meet the requirements for documented ICH-Good Clinical Practice (GCP) training. Documented means GCP training that provides a certification/documentation of completion indicating that the training requirement has been successfully completed. Appropriate personnel are those individuals responsible for the design or conduct of the study, including all personnel of participating consortia and performance sites participating in the clinical trial. The description of GCP training for new key personnel or GCP refresher training for other personnel should be part of the progress report submitted as a prerequisite to award. GCP refresher training should occur every 3 years for the length of the trial. The GCP training of choice must meet the GCP Principles of ICH E6.

A button to access the online ASSIST system is available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

Most applicants will use NIH’s ASSIST system to prepare and submit applications through Grants.gov to NIH. Applications prepared and submitted using applicant systems capable of submitting electronic multi-project applications to Grants.gov will also be accepted.

It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. 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.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

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 activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Stuart B. Moss, Ph.D.
Telephone: 301-435-6979
Fax: 301-480-2389
Email: mossstua@mail.nih.gov

Component Types Available in ASSIST	Research Strategy/Program Plan Page Limits
Overall	12
Admin Core: (Use for Administrative Core)	6
Project: (Use for Research Project)	12
Educ Outreach Core: (Use for Education/Outreach Core)	6
Tech Service Core: (Use for Technical Service Cores)	6
Pilot Project	6

Additional page limits described in the SF424 Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the SF424 (R&R) Application Guide, and should be used for preparing a multi-component application.

The application should consist of the following components:

• Overall: required
• Administrative Core: required; maximum 1
• Educ/Outreach Core: required; maximum 1
• Tech Service Core: Optional; minimum 0, maximum 3.
• Research Project: required; minimum 3, maximum 5. (http://escr.nih.gov).
• Pilot Projects: optional; minimum 0, maximum 1.

When preparing your application in ASSIST, use Component Type Overall .

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

Complete entire form.

Note: Human Embryonic Stem Cell lines from other components should be repeated in cell line table in Overall component.

Follow standard instructions.

Enter primary site only.

A summary of Project/Performance Sites in the Overall section of the assembled application image in eRA Commons compiled from data collected in the other components will be generated upon submission.

Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this FOA) for the entire application.

A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.

The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover.

A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.

Introduction to Application: For Resubmission applications, an Introduction to Application is required in the Overall component.

Specific Aims: Include Specific Aims for the overall P50 project.

Research Strategy: Describe the major themes of the overall Center, its goals and objectives, background information and the overall importance of the research to the theme of this program. Explain the strategy for achieving the goals defined for the overall program and how each Research Project and Core relate to that strategy. Explain how the different aspects of the organization, including key personnel, will coordinate and communicate, why they are essential to accomplishing the overall goal of the research, and how the combined resources create an overall program that is more than the sum of its parts. Include all necessary tables, graphs, figures, diagrams and charts in this section. In addition, provide the following information:

History, Purpose, and Objectives of the Program

Discuss the overall program's objectives and general plans for the proposed grant period, including research grant history (as a P50 and/or U54 center) with yearly funding level, if appropriate.

Administration, Organization, and Operation

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

Research Program

Discuss the proposed research program, highlighting its central theme. Describe the relationship and synergy between the Research Projects and the Cores 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 Support for these arrangements are included as described below

Letters of Support: Include letters of support/agreement for any collaborative/cooperative arrangements, subcontracts, or consultants. Letters of support for the overall Center should be included with the Overall Component. Letters of support for individual Research Projects or Cores should be included with those components of the application. For program activities to be conducted off site, i.e., at an institution other than the applicant institution, a letter of assurance or comparable documentation, signed by the collaborator as well as the off-site institutional officials, must be submitted with the application.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan. Investigators are encouraged to utilize the NICHD Data and Specimen Hub (DASH), a centralized resource for researchers to store and access de-identified data from NICHD-funded studies (https://dash.nichd.nih.gov/). The website provides guidance for storing data in DASH. Submission of data to the NICHD DASH is one way that grantees may meet the requirements of the NIH Data Sharing Policy and the NIH Genomic Data Sharing Policy.

The final data set should be made publicly available after the date of acceptance of the first publication using the primary result or no longer than one year after the final collection and analysis of the data set, whichever comes first.

Appendix:

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

All instructions in the SF424 (R&R) Application Guide must be followed.

When preparing your application in ASSIST, use Component Type Admin Core.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget forms appropriate for the specific component will be included in the application package.

The budget for the Administrative Core must include $50,000 direct costs per year to support collaborative pilot projects with investigators supported by other NCTRI centers and/or pilot studies. These pilot/collaborative projects are different from the optional Pilot Projects component listed below.

Funds should be allocated for the PD(s)/PI(s) of the center and the Leads of the Projects and Cores to attend up to two meetings a year, one a meeting of the most appropriate Research Focus Group (a group of investigators from multiple centers with similar research interests, e.g., male infertility), and one the Research Meeting or the Center Directors' meeting, occurring in alternative years.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for each component.

Specific Aims: Include a brief list of Specific Aims outlining the objectives and functions of the Administrative Core.

Research Strategy: The Administrative Core will provide oversight for the Cores and Research Projects, and will promote coordination and collaboration within the program and with investigators and organizations outside the program. The Research Strategy should describe the planning and coordination of research activities, the integration of cross-disciplinary research, allocation of funds, management of resources and quality control, the maintenance of ongoing communication, and plans for evaluation of the Center Project by internal or external advisory committees. Indicate who will be responsible for each of these activities. Include a description of the process by which pilot/collaborative projects will be selected and evaluated for potential funding. For example, are the various advisory committees, both internal and external consulted during this process? Are pilot projects from new investigators particularly encouraged?

For the Administrative Core, provide the following information:

• Objectives of the Administrative Core
• Staffing: Description of administrative, scientific, technical, and support staff who are not designated as Key Personnel.
• Resources: Description of how Administrative Core resources will contribute to the objectives of the Research Projects.
• Services provided: Description of the services provided to other Cores and Research Projects.
• Administration: Description of the strategies and processes that will be used to manage the Center and achieve the overall goals.
• Use of advisory committees, Do not list specific members for any external advisory committees. This list should only include the type of expertise needed to advise Key Personnel of the Program Project. If the center is funded, the PD(s)/PI(s) will be asked to name an external advisory committee.
• Method of determining Core access and space assignments.
• Describe structures for day-to-day management of the Center, including arrangements for internal quality control of ongoing research.

Letters of Support: Include Letters of Support specific to the Administrative Core.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

Do not include a Resource Sharing Plan for this component. Any resources to be developed under this component should be included with the Resource Sharing Plan for the Overall Component.

Appendix:

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

PHS Inclusion Enrollment Report (Administrative Core)

When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

When preparing your application in ASSIST, use Component Type Educ Outreach Core.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget forms appropriate for the specific component will be included in the application package.

This core will have a separate budget of $50,000 direct costs per year to support activities related to community outreach and dissemination

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for each component.

Specific Aims: Include a brief list of Specific Aims outlining the objectives and functions of the Education/Outreach Core.

Research Strategy: Provide the following information:

Objectives of the Core: This core provides funds to support activities related to community outreach and education.

Staffing: Description of scientific, technical, and support staff who are not designated as Key Personnel.

Resources and Services provided: Investigators are required to describe 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 public that includes tutorials, laboratory-based learning experiences, seminars and involvement of the community on external advisory boards.

Management: Description of overall management of the Core, decision-making process for use of Core services, and plans for cost-effectiveness and quality control.

Utilization of Core: Provide a description of the activities and target audiences for the required Education/Outreach Core.

Letters of Support: Include Letters of Support specific to the Core.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

Do not include a Resource Sharing Plan for this component. Any resources to be developed under this component should be included with the Resource Sharing Plan for the Overall Component.

Appendix:

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

When preparing your application in ASSIST, use Component Type Tech Service Core

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for each component.

Specific Aims: Include a brief list of Specific Aims outlining the objectives and functions of the Core.

Research Strategy: Provide the following information:

• Objectives of the Core
• Staffing: Description of scientific, technical, and support staff who are not designated as Key Personnel.
• Resources and Services provided: Description of current and projected services to other Core and Research Components, as well as the process for prioritizing requests for use of Core facilities by the various Research Projects. If a Core already exists, include a description of past services provided, new technologies developed, changes in protocols or Core administration, and other significant developments. Describe how the quality of services provided will allow investigators to achieve their research goals.
• Management: Description of overall management of the Core, decision-making process for use of Core services, and plans for cost-effectiveness and quality control.
• Utilization of Core: Provide a summary of past and/or projected usage of Core services (e.g., assays performed, animals supplied, etc.). Include estimates of the percentage use of each Core unit by the affiliated Research Project components.
• 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. Consistent with NICHD guidelines for establishment of core facilities, utilization by three research projects is required to justify a Technical Service Core facility. 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 projects requiring core services may be less than five percent. Costs necessary to use a particular core facility may 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 may be externally funded NICHD projects administered by the FIB. Percent utilization by any internally budgeted Research Project or externally funded FIB 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 FIB 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 FIB 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 FIB Program Staff who then will evaluate the extent to which the project is relevant to FIB mission research areas (see Research Scope), and render a decision accordingly.

If centers choose to operate in an open access format, the PD/PI 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. 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.

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, the Administrative Core in open center structures may be accessed only by budgeted center 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.

Letters of Support: Include Letters of Support specific to the Core.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

Do not include a Resource Sharing Plan for this component. Any resources to be developed under this component should be included with the Resource Sharing Plan for the Overall Component.

Appendix:

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

When preparing your application in ASSIST, use Component Type Projects

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

One of the projects must be entirely or predominantly clinical; all basic science projects must be related to the clinical project(s) of the center. For purposes of this FOA and consistent with 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. An exception to this definition of clinical research for this FOA will be studies involving use of NIH-approved human embryonic stem cell lines

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget forms appropriate for the specific component will be included in the application package.

There should be at least 1.8 person months effort on the part of the Project Lead and at least a total of 2.4 person months effort for the PD/PI of the center.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for each component.

Specific Aims: Include a brief list of Specific Aims outlining the objectives and functions of the Research Project.

Research Strategy: Following the instructions in the SF424 (R&R) Application Guide, start each section with the appropriate section heading Significance, Innovation, Approach. Cite published experimental details and provide the full reference in the Bibliography and References Cited section of the Other Project Information form. Clearly describe the project's objectives and explain its relevance to the overall program's theme. Specify the underlying scientific premise and biomedical significance of the work proposed. As part of the Research Strategy, include information on preliminary studies, data, and/or prior experience pertinent to this application. Discuss rigor and reproducibility of the study. Provide a consideration of sex and other biological variables. For renewal applications, provide a Progress Report. Describe the Research Project's use of Core services, including why the services are needed and the advantages and cost effectiveness of Core usage for the Project.

Letters of Support: Include Letters of Support specific to the Core.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan. As discussed, investigators are encouraged to utilize the NICHD Data and Specimen Hub (DASH), a centralized resource for researchers to store and access de-identified data from NICHD-funded studies (https://dash.nichd.nih.gov/). The website provides guidance for storing data in DASH. Submission of data to the NICHD DASH is one way that grantees may meet the requirements of the NIH Data Sharing Policy and the NIH Genomic Data Sharing Policy.

Appendix:

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

When preparing your application in ASSIST, use Component Type Pilot Project.

A Pilot Project may be proposed to generate data or develop new technologies that further enhances the research efforts of the Center Project.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget forms appropriate for the specific component will be included in the application package.

Up to $100,000 direct costs per year may be requested to provide support for one pilot project relevant to the center’s goals in Years 01 and 02. Support for a pilot project is typically limited to a two-year period, although a third year of funding may be requested during the pilot, if appropriate. In the application, the same level of funding should be requested for years 03-05 for additional pilot projects. If a pilot project is favorably recommended for the initial two-year period as part of the center, funds will be included each year for the full five years. Funds requested in Years 03-05 will be contingent upon notification of the NICHD of additional institutionally-approved pilot projects.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for each component.

Specific Aims: Include a brief list of Specific Aims outlining the objectives and functions of the Pilot Project.

Research Strategy: Following the instructions in the SF424 (R&R) Application Guide, start each section with the appropriate section heading Significance, Innovation, Approach. Cite published experimental details and provide the full reference in the Bibliography and References Cited section. Clearly describe the project's objectives and explain its relevance to the overall program's theme. Specify the underlying scientific premise and biomedical significance of the work proposed. Discuss rigor and reproducibility of the study. Provide a consideration of sex and other biological variables. Although little or no preliminary data are required for a Pilot Project, any relevant studies or data that establish the feasibility and rationale for the project may be included. Describe the Pilot Project's use of Core services, including why the services are needed and the advantages and cost effectiveness of Core usage for the project. If additional Pilot Projects are to be supported after the onset of the P50 award, the application must describe the process for reviewing and selecting those projects.

Letters of Support: Include Letters of Support specific to the Pilot Project.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan. As discussed, investigators are encouraged to utilize the NICHD Data and Specimen Hub (DASH), a centralized resource for researchers to store and access de-identified data from NICHD-funded studies (https://dash.nichd.nih.gov/). The website provides guidance for storing data in DASH. Submission of data to the NICHD DASH is one way that grantees may meet the requirements of the NIH Data Sharing Policy and the NIH Genomic Data Sharing Policy.

Appendix:

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov.

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies) using ASSIST or other electronic submission systems. Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

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 submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

For information on how your application will be automatically assembled for review and funding consideration after submission go to: http://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) and component Project Leads must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management (SAM). Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in the policy.

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.

Reviewers will provide an overall impact 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.

Does the center address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? 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?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the center? If Early Stage Investigators or those 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/PI , do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

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?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the center? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? 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? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the center involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?

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 score, but will not give separate scores for these items.

Center as an Integrated Effort

The overall P50 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 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 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?

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 Guidelines for the Review of Human Subjects.

When the proposed center involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

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.

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.

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

Not applicable

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 score.

Not applicable

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).

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) Genomic Data Sharing Plan .

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

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

As applicable for each individual Core, reviewers will provide an assessment of its strengths and weaknesses. In particular, the following items should be evaluated while determining scientific and technical merit, and in providing an overall Impact Score for the core; however, separate scores will not be given for these items.

• Are the qualifications, experience, and commitment of the core director and other core personnel appropriate?
• For the Administrative Core:
• Does the Core director have sufficient 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?
• Is there a plan for center evaluation, including the use of any internal and external advisory groups?
• Is there an effective process by which pilot/collaborative projects will be selected and evaluated for potential funding?
• For the Education/Outreach Core:
• 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 NCTRI, a greater appreciation for research progress made as a result of funding and a better understanding of the implications of NCTRI-supported research for reproductive health?
• Are efforts made to include community representatives on advisory committees?
• For the Technical Service Cores:
• Will the quality of services provided enable center investigators to achieve their research goals?
• Is there cost effectiveness in the core; will quality control measures be 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?

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the Project 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 Project 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 Project that by its nature is not innovative may be essential to advance a field.

Significance

Does the Project address an important problem or a critical barrier to progress in the field? Is the study rooted in a strong scientific premise? If the aims of the 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 Project Leads, collaborators, and other researchers well suited to the Project? If Early Stage Investigators or those 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/PI, 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 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? Is the study designed to be rigorous and reproducible? Is there a consideration of sex and other biological variables?

If the Project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion 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 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 Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Children

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

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 been made in the last funding period relative to the original goals of the project?
• Has the project contributed to the translational goals of the center, defined as knowledge transfer from non-human models to humans as well as humans to non-human models?

As applicable for the 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 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) Genomic Data Sharing Plan.

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 provide an overall impact score to reflect their assessment of the likelihood for the Pilot Project 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 Project 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 Pilot Project that by its nature is not innovative may be essential to advance a field.

Significance

Does the Project address an important problem or a critical barrier to progress in the field? Is the study rooted in a strong scientific premise? If the aims of the 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 Project Leads, collaborators, and other researchers well suited to the Project? If Early Stage Investigators or those 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/PI , 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 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? Is the study designed to be rigorous and reproducible? Is there a consideration of sex and other biological variables?

If the Project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion 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 Pilot Project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact 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 Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Children

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

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

Not Applicable

Revisions

Not Applicable

As applicable for the 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 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) Genomic Data Sharing Plan.

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.

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. Assignment to a Scientific Review Group 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 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. Applications 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/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

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 terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

Additionally, ICs may specify any special reporting requirements for a proposed clinical trial to be included under IC-specific terms and conditions in the NoA. For example: If a proposed clinical trial has elevated risks, ICs may require closer programmatic monitoring and it may be necessary to require the awardee to provide more frequent information and data as a term of the award (e.g., to clarify issues, address and evaluate concerns, provide documentation). All additional communications and information related to programmatic monitoring must be documented and incorporated into the official project file. Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA. ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain applicable clinical trials on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH encourages registration of all trials whether required under the law or not. For more information, see http://grants.nih.gov/ClinicalTrials_fdaaa/.

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that the application as well as all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

Awardee-selected projects that involve {clinical trials or studies involving greater than minimal risk to human subjects} require prior approval by NIH prior to initiation.

• The awardee institution will provide NIH with written study protocols that address risks and protections for human subjects in accordance with NIH s Instructions for Preparing the Human Subjects Section of the Research Plan.
• The awardee institution will provide NIH with specific plans for data and safety monitoring, and will notify the IRB and NIH of serious adverse events and unanticipated problems, consistent with NIH DSMP policies.

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.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

Not Applicable

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement. Progress reports should briefly describe status of pilot projects, including data and safety monitoring, and should notify NIH of serious adverse events and unanticipated problems.

A final RPPR, 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.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573

Stuart B. Moss, Ph.D.
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

Margaret Young
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-642-4552
Email: margaret.young@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 Part 75.