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) and the Gynecological, Health and Disease (GHD) Branches, provides funding for a limited number of research centers in the reproductive and gynecological sciences. For the purpose of this FOA, reproductive health includes both fertility/infertility and gynecological health. These centers provide an arena for multidisciplinary interactions among basic and clinical scientists interested in establishing high quality translational research programs in these scientific areas. The centers also serve as national resources for the training and career development of junior scientists electing to pursue biomedical research careers in reproductive health. 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.

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 and gynecological health through research excellence and innovation.

For this FOA, applications that address the epigenetic bases of reproductive health 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 are responsive to many of the scientific mission areas of the FI and the GHD Branches will be accepted, meritorious applications addressing the epigenetic bases of reproductive health and disease will receive priority in making funding decisions. Up to three meritorious centers will be awarded, one of which may be within the scientific mission of the GHD Branch.

P50 NCTRI reproductive centers supported by FI and GHD branches of the NICHD may only be renewed for two additional five-year periods. Applications for support beyond the second renewal period must be submitted as "New" applications and must include significant changes in scope and direction and, when appropriate, changes in individual project leadership. For NCTRI centers presently in year 15 or greater, one final renewal will be allowed.

Since 1994, the Eunice Kennedy Shriver National Institute of Child Health and Human Development NICHD has been directed by federal law to establish research centers 'for the purpose of improving methods of diagnosis and treatment of infertility' (42 USC 285-5).

Fertility/Infertility: 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 worldwide. A recent U.S. survey conservatively estimated that there are approximately 2.0 million infertile couples (12 months or longer without birth control and without a pregnancy) with wives aged 15-44 in the U.S., which is about nine percent of the domestic married couple population base for that age group. Furthermore, 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 upward trend likely is indicative of the delay in childbearing where significant age-related increases in infertility and subfecundity have been reported.

It is estimated that 12 percent of American women aged 15-44 have received infertility services at some point during their lifetime, with costs of several billion dollars annually. Of couples seeking treatment, it is likely that up to one half will be unsuccessful in achieving a pregnancy. While the infertility can be treated successfully in 80 percent of infertile women, male infertility can be treated only 10-20 percent of the time. This latter figure is even more concerning because at least 30-40 percent of infertility in couples is attributable to male factor infertility for which the pathophysiology is either not or poorly understood. Even though assisted reproductive technologies such as intracytoplasmic sperm injection can, in many cases, circumvent male infertility, the process is expensive, both from a monetary and a psychological standpoint for the couple. Furthermore, 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.

Polycystic ovary syndrome (PCOS), a disorder characterized by irregular menstrual cycles, hyperandrogenism, and polycystic ovaries, is a major cause of female infertility. It is 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. The infertility is due to the associated oligo-anovulation. Identified more than 60 years ago, the etiology of PCOS still remains poorly understood. Often accompanied by obesity and insulin resistance, the risk of type 2 diabetes mellitus among PCOS patients is five- to 10-fold higher than in the non-PCOS population. Considering the high prevalence of diabetes in PCOS women, a recent study estimated that the total annualized cost of evaluating and providing care to PCOS women is $4.6 billion dollars.

Premature loss of gametes may occur spontaneously or be iatrogenic (i.e., due to treatments for diseases such as cancer). Premature ovarian insufficiency (POI), defined as loss of ovarian function before age 40, affects approximately 1 in 100 women. The underlying etiology is unknown in the majority of cases. Interestingly, 16 percent of women carrying the Fragile X pre-mutation present with POI. A better understanding of the mechanism(s) underlying pre-mutation-based ovarian insufficiency may provide critical insights into the basic biological processes regulating ovarian follicular growth, differentiation, and atresia.

Currently, there are more than 9 million cancer survivors in the U.S., of whom approximately 5% are under the age of 35. Chemotherapy or local radiation treatments in these patients may deplete the gamete stem cell pool and cause permanent infertility. The ability to cryopreserve a testicular or ovarian biopsy prior to treatment may provide the opportunity later 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.

Gynecological Health: A number of benign gynecologic conditions are associated with substantial morbidity beyond infertility which further impact women’s health. For the purpose of this FOA, these conditions are fibroids, endometriosis, and adenomyosis. Uterine leiomyoma (fibroids) are benign, monoclonal tumors of the uterine smooth muscle which occur in 20-30% percent of all reproductive-aged women, with nearly 70 percent of white women and over 80 percent of black women having developed at least one fibroid by age 50. Extremely heterogeneous in their number, size, and location, a clear racial disparity exist with fibroids presenting earlier and with greater severity in African American women. The presence of symptomatic fibroids is the most common medical indication for an unwanted hysterectomy that prematurely ends a female's reproductive options outside of uterine surrogacy.

An estrogen-dependent inflammatory disease, endometriosis affects approximately 10-15% of all reproductive-aged women and is found in 50-60% of women with chronic pelvic pain and infertility. Adenomyosis is a related disorder defined by the presence of ectopic endometrial glands and stroma within the myometrium, leading to adjacent smooth muscle hyperplasia and hypertrophy. While endometriosis and adenomyosis share common features and may coexist, the current thinking is that they should be considered distinct entities due to differences in pathogenesis, risk factors and clinical presentation. While the prevalence of adenomyosis is unknown, adenomyosis has been identified in 25% of women undergoing hysterectomies for chronic pelvic pain.

These three gynecologic conditions are associated with an array of symptoms which substantially impact women’s health. Depending on the disorder and its severity, location, and other factors, symptoms may include abnormal uterine bleeding, dysmenorrhea, dyspareunia, noncyclic pelvic pain, pressure symptoms, infertility and pregnancy loss. Additional studies are critically needed to further elucidate the pathophysiology, diagnosis, and optimal management of these disorders beyond an understanding of the mechanisms by which they impact fertility.

Reproductive Health in the Adolescent: Attention is now turning to the adolescent with the hopes that earlier diagnosis and treatment of these devastating reproductive disorders will improve long-term health including the preservation of fertility in adulthood. Research efforts are needed to better refine diagnostic criteria for children and adolescents and to define hormonal changes during normal progression of sexual maturation so that effective interventional strategies can be employed. In this regard, initial menstrual cycles are often irregular and anovulatory, making it difficult to diagnose conditions such as PCOS. Dysmenorrhea is often interpreted as normal for adolescents despite clear demonstration that endometriosis and, more rarely, adenomyosis may present in this age group. The development of new biomarkers, including glycoproteins, cytokines, and noncoding RNAs, as well as novel diagnostic imaging approaches should prove particularly valuable for these patients.

Genetics and Epigenetics in Reproductive Health: Data now firmly support the contribution of genetics in both male and female infertility and to the development of benign gynecological disorders. It has been estimated that a large number of genes (1 in 25 of all mammalian genes) are specifically expressed in the male germline. Furthermore, animal studies indicate that mutations in over 100 separate genes result in male infertility. More limited studies in humans show that a number of inherited diseases associated with abnormal sperm morphology and function are likely polygenic. This genomic complexity contributes to the more than 40 percent of male infertile cases being classified as idiopathic. 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. For endometriosis, genome-wide association studies (GWAS) have implicated genetic variants involved in steroid hormone metabolism, inflammation, angiogenesis, WNT/ -catenin signaling, and estrogen-induced cell growth, migration, adhesion, and invasion. Genetic mutations have been identified for fibroids, including complex chromosomal rearrangements, mediator complex subunit 12 (MED12), and fumarate hydratase (FH) inactivation.

In addition to the DNA sequence, an array of so-called epigenetic mechanisms may be important for the development of infertility or gynecologic disorders. These mechanisms include DNA methylation, post-translational histone modifications, RNA modifications (epitranscriptomics), and the action of non-coding RNAs (microRNAs, long non-coding RNAs). Unlike alterations to the DNA that are fixed , epigenetic changes 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 or at the epigenome-wide level (e.g., eFORGE).

Epigenetics is controlled by families of enzymatic 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. 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). Although specificity remains an issue, some of these inhibitors already are in clinical trials for various cancers and may be found to be relevant to the reproductive field.

It is also becoming increasing apparent that interactions between genetic and epigenetic mechanisms and the environment are involved in the development and progression of complex diseases, including those affecting reproductive health (e.g., PCOS, endometriosis). Preliminary studies suggest a correlation between certain foods and the development of endometriosis, with a decreased risk in women with diets high in fruits and vegetables, fish oil, omega-3 fatty acids, and dairy products rich in calcium and vitamin D. Conversely, exposure to environmental toxins, particularly dioxin-like compounds, are also suspected to play a role in the development of endometriosis.

Contrary to previous thinking, the sperm contributes more than 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.

Reproductive Status and Overall Health: 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 and gynecological disorders are 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 reproductive status can act as a marker for overall health. Both male and female reproductive function have been associated with the presence of cancer, as well as conditions of the cardiovascular, metabolic, and 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. Similarly, gynecologic disorders may be markers of an increased risk for other medical disorders, such as the reported link between endometriosis and ovarian cancer or coronary artery disease.

The Fertility and Infertility (FI) and the Gynecology Health and Disease (GHD) Branches recognize that interaction between basic and clinical research paradigms will be necessary to address these problems and that these requirements may be too complex to be solved by individual investigators working alone. Therefore, it is the intention, 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 to the mission of the FI and GHD Branches, and that address important reproductive health concerns of the American public.

The NCTRI is composed of research-based centers designed to support interactive groups of research projects and supporting core service facilities. The research activities included in these centers 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 research supported by the FI or GHD Branches. Only those centers which address fibroids, endometriosis, or adenomyosis outside of their impact on fertility will be given consideration as a potential gynecologic center. Other gynecologic/fertility disorders such as PCOS will be deemed responsive as an infertility center. 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 and gynecological health and disease will be strongly encouraged and, if deemed meritorious, can receive priority when making funding decisions.

The 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 reproductive health, as well as of diagnostic tools and procedures for the detection and effective management of disorders that impact on reproductive and gynecological health and competence.

• Reproductive Developmental Biology: differentiation of germ cells including gametic stem cells; the endocrine, paracrine and physiologic mechanisms involved in gametogenesis; fertilization and pre-implantation embryonic development; embryonic stem cell self-renewal and differentiation and maintenance of stem cell pluripotency; the use of genetically modified stem cells to treat animal models of reproductive disorders impacting fertility.
• Reproductive Tract Biology and Physiology: folliculogenesis; luteogenesis and luteolysis; implantation; trophoblast differentiation and function including the role of the immune system; angiogenesis in ovarian and endometrial function; sperm maturation in the epididymis and in the female reproductive tract; pathophysiology of FOA-relevant gynecologic disorders utilizing current concepts in engineering, neurobiology, smooth muscle biology, vascular biology, immunology and cell biology, including the role of extracellular matrix and cell-cell interactions.
• Reproductive Endocrinology and Neuroendocrinology: hormone synthesis and secretion in the context of reproduction; developmental control of GnRH neuronal migration, targeting and pulsatile secretion; intrapituitary mechanisms governing gonadotropin secretion; systems approaches to identify factors controlling gene transcription 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; investigation of the genome, epigenome, and/or transcriptome as they impact development, progression, and/or treatment response in relevant gynecologic conditions; interaction between environmental factors and genetic and/or epigenetic markers.
• 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; novel non-invasive diagnostics such as biomarkers or imaging technologies for gynecologic disorders with a focus on early detection; novel non-surgical approaches to the treatment of gynecologic disorders including non-hormonal pharmacologic therapies and gene therapy; endogenous stem cells in the etiology and pathophysiology of gynecologic conditions and/or projects that develop stem cell based therapeutics.

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 Contacts indicated in Section VII. Agency Contacts.

However, applications will be deemed non-responsive to this FOA if they intend to investigate topic areas outside the scope of research supported by the FI or GHD branches. For the FI branch, non-responsive topics would include reproductive oncology, reproductive toxicology or reproductive epidemiology. Studies must not focus on post-implantation pregnancy and parturition; however, they can be included as part of research projects that are studying other reproductive health topics that have to include pregnancy, e.g., transgenerational inheritance. For the GHD branch, non-responsive topic areas include pelvic pain syndromes (except as pain relates to the disorders of interest), vulvodynia, pelvic floor disorders (including pelvic organ prolapse, urinary and fecal incontinence), and gynecologic malignancies. Furthermore, 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. Applications proposing to use human fetal tissue will not be considered responsive to this FOA.

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 and gynecological 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 research in reproductive and gynecological 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. 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 and gynecological health. Support beyond the second renewal period must be submitted as "New" applications and must include significant changes in scope and direction and, when appropriate, changes in individual project leadership. For NCTRI centers presently in year 15 or greater, one final renewal will be allowed.

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 from this FOA.

Higher Education Institutions

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

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

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

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, 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, PhD
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
EducOutreach Core (use for Education/Outreach Core)	6
Tech Service Core (use for Technical Services Core)	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 Projects: required; minimum 3, maximum 5.
• Pilot Project: 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 for day-to-day management of the center and provide an organizational chart. Discuss the mechanisms for regular communication and coordination among investigators in the Center.

• Research Program

Discuss the proposed research program, highlighting its central theme. Discuss how the center is an integrated research effort with each project and core contributing to the synergy of the overall center. Discuss the advantages of conducting the proposed research as a program rather than through separate research efforts.

• 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 include a Data Sharing Plan. The Data Sharing Plan will be considered during peer review and by program staff as award decisions are being made as appropriate and consistent with achieving the goals of the program. It is expected that the results of NICHD-funded research will be shared with the wider scientific community in a timely manner.

Awardees are strongly encouraged to deposit large-scale, human genetic data in the database for Genotype and Phenotype dbGaP (https://www.ncbi.nlm.nih.gov/gap). For other data and biospecimens from human genetic or non-genetic studies, awardees are encouraged to use the NICHD Data and Specimen Hub DASH (https://dash.nichd.nih.gov/) or other equivalent broad-sharing data and/or biospecimen repositories.

The following resource describing Common Data Elements may be helpful during the planning phases of a project when considering ways to optimize data collection in order to facilitate broad data sharing: https://www.nlm.nih.gov/cde/.

Appendix:

Limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide;

PHS Human Subjects and Clinical Trials Information (Overall)

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed. For a given study, the PHS Human Subject and Clinical Trial study record form should only be completed once. The PHS Human Subjects and Clinical Trial study record form for each study should be placed in the most relevant section of the application, e.g., Research Project, Education and Outreach Core (if applicable).

Delayed Onset Study

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

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 Core 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 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.

PHS 398 Research Plan (Administrative Core)

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 experience of Core director in research administration. 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. Description of the process by which pilot/collaborative projects will be selected and evaluated for potential funding.
• 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:

Limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide

PHS Human Subjects and Clinical Trials Information (Administrative Core)

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

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.

SF424 (R&R) Cover (Education/Outreach Core)

Complete only the following fields:

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

PHS 398 Cover Page Supplement (Education/Outreach Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Education/Outreach Core)

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.

Project /Performance Site Location(s) (Education/Outreach Core)

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.

Research & Related Senior/Key Person Profile (Education/Outreach Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core 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 (Education/Outreach Core)

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

This core must 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.

PHS 398 Research Plan (Education/Outreach Core)

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. If appropriate, describe efforts to include community representative on advisory committees.
• 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:

Limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

PHS Human Subjects and Clinical Trials Information (Education/Outreach Core)

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

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.

SF424 (R&R) Cover (Technical Service Core)

Complete only the following fields:

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

PHS 398 Cover Page Supplement (Technical Service Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Technical Service Core)

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.

Project /Performance Site Location(s) (Technical Service Core)

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.

Research & Related Senior/Key Person Profile (Technical Service Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core 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 (Technical Service Core)

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.

PHS 398 Research Plan (Technical Service Core)

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 FI or GHD Branch. Percent utilization by any internally budgeted Research Project or externally funded FI or GHD Branch project used to justify a particular core facility may not exceed 50 percent or be less than five percent. Additional federally funded, peer reviewed external research projects addressing program relevant research areas of the FI or GHD Branches may access the core up to 100 percent of its service capacity. Centers must establish an internal management policy for evaluating the acceptability of proposed FI or GHD Branch 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 FI or GHD Branch Program Staff who then will evaluate the extent to which the project is relevant to FI or GHD Branch 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:

Limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

PHS Human Subjects and Clinical Trials Information (Technical Service Core)

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

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

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.

SF424 (R&R) Cover (Research Project)

Complete only the following fields:

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

PHS 398 Cover Page Supplement (Research Project)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Research Project)

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.

Project /Performance Site Location(s) (Research Project)

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.

Research & Related Senior/Key Person Profile (Research Project)

• 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 (Research Project)

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.

PHS 398 Research Plan (Research Project)

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 Research 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 expectations of the NIH Data Sharing Policy and the NIH Genomic Data Sharing Policy.

Appendix:

Limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

PHS Human Subjects and Clinical Trials Information (Research Project)

Use only for applications with due dates on or after January 25, 2018. When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

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

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

SF424 (R&R) Cover (Pilot Project)

Complete only the following fields:

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

PHS 398 Cover Page Supplement (Pilot Project)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Pilot Project)

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.

Project /Performance Site Location(s) (Pilot Project)

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.

Research & Related Senior/Key Person Profile (Pilot Project)

• 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 (Pilot Project)

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.

PHS 398 Research Plan (Pilot Project)

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 expectations of the NIH Data Sharing Policy and the NIH Genomic Data Sharing Policy.

Appendix:

Limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

PHS Human Subjects and Clinical Trials Information (Pilot Project)

When involving NIH-defined human subjects research, clinical research, and/or clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

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. Any instructions provided here are in addition to the instructions 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.

In addition, for applications involving clinical trials:

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

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?

In addition, for applications involving clinical trials:

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

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?

In addition, for applications involving clinical trials:

With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

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?

In addition, for applications involving clinical trials:

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

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?

In addition, for applications involving clinical trials:

Does the application adequately address the following, if applicable?

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

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?

In addition, for applications involving clinical trials:

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

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?
• Are there clear 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 effective day-to-day management of the Center, including arrangements for internal quality control of ongoing research?

Study Timeline

Specific to applications involving clinical trials:

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

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).

In addition, for applications involving clinical trials:

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

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?

In addition, for applications involving clinical trials:

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

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?

In addition, for applications involving clinical trials:

With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

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?

In addition, for applications involving clinical trials:

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

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?

In addition, for applications involving clinical trials:

Does the application adequately address the following, if applicable?

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

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?

In addition, for applications involving clinical trials:

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

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.

Study Timeline

Specific to applications involving clinical trials:

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

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 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).

In addition, for applications involving clinical trials:

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

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?

In addition, for applications involving clinical trials:

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

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?

In addition, for applications involving clinical trials:

With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

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?

In addition, for applications involving clinical trials:

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

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?

In addition, for applications involving clinical trials:

Does the application adequately address the following, if applicable?

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

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?

In addition, for applications involving clinical trials:

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

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.

Study Timeline

Specific to applications involving clinical trials:

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

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.

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.

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 expects 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.
• The Human Subjects and Clinical Trials Information must be part of prior approval.

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.

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

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

Susan Parker
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-7006
Email: susanparker@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.