Department of Health and Human Services


Part 1. Overview Information
Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Funding Opportunity Title

Specialized Cooperative Centers Program in Reproduction and Infertility Research (U54)

Activity Code

U54 Specialized Center- Cooperative Agreements

Announcement Type

Reissue of RFA-HD-13-005

Related Notices

None

Funding Opportunity Announcement (FOA) Number

RFA-HD-14-017

Companion Funding Opportunity

None

Number of Applications

See Section III. 3. Additional Information on Eligibility.

Catalog of Federal Domestic Assistance (CFDA) Number(s)

93.865  

Funding Opportunity Purpose

The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), through the Fertility and Infertility Branch (FIB), provides funding for a limited number of research centers in the reproductive sciences.  These centers provide an arena for multidisciplinary interactions among basic and clinical scientists interested in establishing high quality translational research programs in the reproductive sciences.  The centers also serve as national resources for the training and career development of young scientists electing to pursue careers conducting research in high priority areas of reproduction and infertility.  Accordingly, the purpose of this FOA is to announce the competition of the Specialized Cooperative Centers Program in Reproduction and Infertility Research (SCCPIR).  Applications are sought from investigators willing to participate with the NICHD under a cooperative agreement in a multicenter cooperative research program. Center investigators will be expected to work with NICHD staff in facilitating research collaborations and interactions within and among centers.  Such a cooperative program will form a national network that facilitates and accelerates bidirectional knowledge transfer between the laboratory and clinic with the ultimate goal of improving human reproductive health through enhanced communication, innovation and research excellence.

Key Dates
Posted Date

February 21, 2013

Letter of Intent Due Date(s)

June 25, 2013

Application Due Date(s)

July 25, 2013    

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

October/November 2013

Advisory Council Review

January 2014

Earliest Start Date

April 2014

Expiration Date

July 26, 2013 

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the PHS 398 Application Guide except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. While some links are provided, applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Looking ahead: NIH is committed to transitioning all grant programs to electronic submission using the SF424 Research and Related (R&R) format and is currently investigating solutions that will accommodate NIH’s multi-project programs. NIH will announce plans to transition the remaining programs in the NIH Guide to Grants and Contracts and on NIH’s Applying Electronically website.

Table of Contents

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

Part 2. Full Text of Announcement


Section I. Funding Opportunity Description


Purpose

The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), through the Fertility and Infertility Branch (FIB), provides funding for a limited number of research centers in the reproductive sciences.  These centers provide an arena for multidisciplinary interactions among basic and clinical scientists interested in establishing high quality translational research programs in the reproductive sciences.  The centers also serve as national resources for the training and career development of young scientists electing to pursue careers conducting research in high priority areas of reproduction and infertility.  Accordingly, the purpose of this FOA is to announce the competition of the Specialized Cooperative Centers Program in Reproduction and Infertility Research (SCCPIR).  Applications are sought from investigators willing to participate with the NICHD under a cooperative agreement in a multicenter cooperative research program.  Center investigators will be expected to work with NICHD staff in facilitating research collaborations and interactions within and among centers.  Such a cooperative program will form a national network that facilitates and accelerates bidirectional knowledge transfer between the laboratory and clinic with the ultimate goal of improving human reproductive health through enhanced communication, innovation and research excellence.

Background

Families, family values, and family planning form the cultural essence and cohesiveness of our existence as human societies. One of the most basic of human rights - the right to procreate - is frustrated or denied by the occurrence of infertility in couples desiring children.  It has been estimated that infertility affects between 37 and 70 million married couples around the world.  In studies described over 50 years ago, it was stated that up to 10 percent of U.S. married couples were sterile, with the remaining 90 percent having varying degrees of fertility.  More recent and technically rigorous U.S. survey studies have conservatively identified that there are approximately 2.0 million infertile couples, which is about nine percent of the domestic married couple population base with wives aged 15-44.  According to the 2010 National Survey of Family Growth, 6.0 percent of married women were infertile (12 months or longer without birth control and without a pregnancy).  This represents a significant decline from the prevalence of 8.4 percent reported in 1982. On the other hand, about 11% of married women had an impaired ability to have children (impaired fecundity) in 2010 compared to 8.5% of married women in 1982.  This latter trend likely is indicative of the delay in childbearing found in the contemporary couple population base in which significant age-related increases in infertility and subfecundity have been reported.

Physician office visits reflecting current societal life-style requirements for infertility services have markedly increased in the U.S. over four fold between 1968 and 2010 (>2,000,000 visits annually).  Indeed, it is estimated that 12 percent of American women aged 15-44 have received infertility services at some point during their lifetime.  Interestingly, this represents only half the number of women who actually need infertility services.  Of the infertile couples seeking treatment for infertility, it has been estimated that up to one half will be unsuccessful in achieving their desired outcome.  In concert with the increased medical assistance sought, U.S. infertility service costs have risen to exceed several billion dollars annually.

In couples, at least 25-40 percent of infertility is attributable to male factor infertility for which the pathophysiology is either not understood at all or, at best, poorly understood.  The prognosis for male infertility treatment outcomes is extremely poor at present.  Indeed, whereas 80 percent of infertile women can be successfully treated, male infertility can be treated in only 10-20 percent of such men.  Even though artificial reproductive technologies such as intracytoplasmic sperm injection can, in most cases, circumvent male infertility, the process is expensive, both from a monetary and psychological standpoint for the couple.  Furthermore, while ICSI and other assisted reproductive technologies have enabled otherwise infertile men to father children, these technologies may bypass genetic or epigenetic causes of infertility that may also be linked to other health problems that will negatively impact the life of the unborn child (and possibly later generations).

Reproductive tract disorders affecting fertility are associated with significant morbidity and a degree of mortality in some specific instances that cannot be ignored.  Accompanying the human costs of morbidities of reproductive tract disorders are the attendant substantial costs to the U.S. health care system involving the diagnosis, treatment, and follow-up services provided to the patients, as well as the added costs to the patient and the U.S. economy of lost employment and family service hours.  In reproductive-aged couples, the obstructive sequelae of male accessory gland infections account for eight to 12 percent of male partner diagnostic costs for fertility impairment.  In reproductive-aged females, it has been estimated that the general incidence of endometriosis is five to 15 percent, but can be as high as 50% in women with pelvic pain or infertility.  While the causative role of endometriosis in infertility remains poorly understood and its optimal diagnosis and treatment remain a goal not an accomplishment of contemporary medicine, the morbid impact of the associated pelvic pain has significant human cost as well as national economic costs.  Indeed, the health care burden of endometriosis has been estimated to be an astounding 22 billion dollars per year!  Similarly, the role of dysfunctional uterine bleeding, either in the presence or the absence of uterine leiomyomata (fibroids), is not well understood despite its common occurrence and decades of research.  It is a significant factor in noncompliant contraceptive use or discontinuance and, therefore, in the unintended pregnancy problem.

Uterine leiomyomata occur in 20-30% percent of all reproductive-aged women.  Uterine fibroids are the single most common diagnosis in gynecological hospital admissions, may be the only abnormality observed in an infertile couple, and represent the most common medical indication for an unintended and often unwanted hysterectomy that prematurely ends a female's reproductive options.  Fibroids disproportionately affect African Americans with some studies indicating a three-fold higher prevalence in this racial group than in the Caucasian population, exacting a profound health care burden on a population of women that often times lack good health care coverage or any coverage at all.  Annual cost expenditures for this condition have recently been estimated to be between 6 and 34 billion dollars.

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

Also poorly understood is the pathogenesis of premature ovarian insufficiency (POI) that affects one in 100 women by age 40.  Interestingly, 16 percent of women carrying the fragile X pre-mutation present with POI.  The mechanism(s) underlying pre-mutation-based ovarian insufficiency is not known, but once known could provide critical insights into the basic biological processes regulating ovarian follicular growth, differentiation and atresia.  The scientific ‘dogma’ that oocytes progressively decline in number until exhausted as women age and cannot be renewed has been called recently into question.  Furthermore, dietary interventions may delay ovarian aging and improve oocyte (and sperm) quality as aging advances.

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

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

It is becoming increasingly apparent that male infertility can be considered a marker for the general health of the individual, i.e., infertility is correlated with higher rates of cardiovascular disease, diabetes, and certain types of cancers.  Furthermore, contrary to previous thinking, the sperm contributes more than its DNA to the oocyte as the epigenome has been shown to play a critical role in the developing embryo.  Alterations in the establishment and/or maintenance of the various epigenetic marks have been shown to affect the fertility status of males.  Of particular importance is the demonstration that environmental factors such as toxicants and diet promote multi- and transgenerational inheritance of adult-onset disease.  Epigenetic alterations are generated in the male gamete and then stably passed to subsequent generations, where the result can be e.g., insulin sensitivity and infertility.

An area of emerging public health interest is the preservation of fertility in individuals undergoing treatments for diseases such as cancer.  Currently, there are more than 9 million cancer survivors in the U.S. of whom approximately 5% are under the age of 35.  The chemical or radiological consequences of these treatments oftentimes target vital reproductive organs such as the gonads, depleting the gamete stem cell pool and causing permanent infertility.  For example, more than 1 in 5000 men of reproductive age who are childhood cancer survivors suffers from infertility or sub-fertility.  However, in the future the ability to cryopreserve a testicular biopsy prior to treatment, followed by expansion of the spermatogonial stem cells and transplantation back into the testis may afford the opportunity to generate normal offspring without contaminating malignant cells and epigenetic and/or genetic errors.  Providing options for preserving fertility in men, women and children is not only an important reproductive health issue, but a quality of life issue as well. 

Another high priority topic for reproductive health is preconception care.  This area has its roots in the Barker Hypothesis which states that adult diseases have their origins prior to birth.  To this point, most experimentation has examined possible adverse birth outcomes (e.g., low birth weight, intrauterine growth restriction, preeclampsia, pre-term birth, birth defects) and adult disease incidence as a result of perturbing the maternal-fetal environment.  However, it is now clear 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 important epigenetic modification of the genome.

Finally, the need for the availability of contraceptive options acceptable to diverse populations remains globally unmet.  Among the 600 million women of reproductive age in today's world, as many as 228 million women are at risk of unintended pregnancy. Up to 64 percent of all worldwide pregnancies and approximately one-third of pregnancies in the U.S. are unintended (mistimed or never wanted).  About 40-50 million abortions occur worldwide each year, with minimal estimates of at least 100,000 abortion-related deaths annually.  In the U.S., more than three million unintended/unwanted pregnancies occur annually, with half resulting in abortion as an outcome.  In half of the abortions occurring in the U.S. each year, a contraceptive method being used failed to prevent pregnancy.  Clearly, new innovative strategies are needed for pregnancy prevention.  As such, discovery of novel contraceptive targets remains a high priority research area for the institute.

The Fertility and Infertility Branch recognizes that the interactive needs of basic and clinical research necessary to address the above and related problems may be so complex that they cannot be solved by individual investigators working alone.  Therefore, it is the intention of the FIB, contingent upon the availability of funds, to continue and maintain organized, multi-component reproduction and infertility research programs of high quality that focus on topics of high priority and significance that are critically important to the mission of the FIB, and that address important reproductive health concerns of the American public.

Objectives

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

This FOA is specifically designed to stimulate the reproductive sciences research community to organize and maintain research-based centers of outstanding quality that, serving as national research resources, form a cooperative network with NICHD that fosters communication, innovation and high quality reproduction and infertility research.  Such networking as afforded by the cooperative nature of this Centers Program will ensure that the reproductive research community remains in the forefront of the development and utilization of new technologies that can be used to diagnose, treat and ameliorate reproductive diseases and disorders, as well as to identify novel leads for fertility regulation.

Research Scope

The SCCPIR is composed of research-based center grants designed to support interactive groups of research projects and supporting core service facilities.  The research activities included in these center grants must comprise, by definition, a multidisciplinary approach to biomedical problems addressing the specific research topic areas announced in this FOA (see below).  These centers may have more than one theme, focus or emphasis, but all of the research projects involved must be responsive to one or more of the specific research areas of reproduction supported by the FIB.  Furthermore, the objectives of this Program require that one of the research projects be entirely or predominantly clinical and that all basic science projects be linked to the clinical project (s) of the center.

Topics that are considered to be responsive to the research mission areas of the FIB include but are not limited to those bulleted below.  Additionally, these topics identify areas where research at the basic/clinical interface is deemed essential to the potential development of new leads or approaches to fertility regulation, as well as of diagnostic tools and procedures for the detection, treatment and effective management of reproductive disorders that impact on reproductive competence.

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

Section II. Award Information
Funding Instrument

Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH staff will assist, guide, coordinate, or participate in project activities.

Application Types Allowed

New
Renewal
Resubmission
Revision

The OER Glossary and the PHS 398 Application Guide provide details on these application types.

Funds Available and Anticipated Number of Awards

The NICHD intends to commit approximately $3,500,000 in total costs [Direct + Facilities and Administrative (F&A) costs] in FY 2014 to fund up to two new and/or renewal applications in response to this FOA.

Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. Although the financial plans of the IC provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications.

Award Budget

An application for a center may request a budget for direct costs of no more than $1.4 million per year, excluding third party F&A.  For future year expenses, applications may request up to a two percent cost escalation.  The provision of committed money for costs escalations is subject to the availability of funds. Applications exceeding the budgetary limits will be returned to the applicant without peer review.

Administrative Core - The budget for the Administrative Core must include $50,000 direct costs per year to support collaborative projects with investigators supported by other SCCPIR centers and/or pilot studies.  The Administrative Core should also include funds in the amount of $30,000 direct costs per year to provide translational research training experiences, both didactic and/or laboratory, for students, postdoctoral fellows or residents from other centers, and post-residency scholars supported under institutional K12 awards such as the CTSA, Women’s Reproductive Health Research (WRHR), Male Reproductive Health Research (MRHR) and Building Interdisciplinary Research Careers in Women’s Health (BIRCWH) career development programs.  

Outreach/Education Core - This core will have a separate budget of $75,000 direct costs per year to support activities related to community outreach and education.

Pilot Projects (optional) - Up to $100,000 direct costs per year may be requested to provide support for one or more pilot projects relevant to the center’s goals in Years 01 and 02.  Support for a pilot project is limited to a two-year period.  However, the same level of funding may be requested for years 03-05.  If a pilot project is favorably recommended for the initial two-year period, funds will be included each year for the full five years.  Funds requested in Years 03-05 will be contingent upon review and approval of additional pilot projects by NICHD staff. 

Award Project Period

The maximum period of support is 5 years.

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

Section III. Eligibility Information


1. Eligible Applicants


Eligible Organizations

Higher Education Institutions

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

Nonprofits Other Than Institutions of Higher Education

For-Profit Organizations

Governments

Other

Foreign Institutions

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.

Required Registrations

Applicant organizations must complete the following registrations as described in the PHS 398 Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

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

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

Eligible Individuals (Program Director/Principal Investigator)

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 PHS 398 Application Guide.  

2. Cost Sharing

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

3. Additional Information on Eligibility


Number of Applications

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

NIH will not accept any application that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for submission:

Section IV. Application and Submission Information


1. Address to Request Application Package

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

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the PHS 398 Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Letter of Intent

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:

The letter of intent should be sent to:

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

Application Submission

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

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

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

Page Limitations

All page limitations described in the PHS 398 Application Guide and the Table of Page Limits must be followed, in addition to the following page limitations to the Research Strategy section of each component of the application.

Supplemental Instructions for the Preparation of Multi-Component Applications

The following section supplements the instructions found in Form PHS 398 for preparing a multi-component grant application. Additional instructions are required because the Form PHS 398 is designed primarily for individual, free-standing research project grant applications, and has no specific instructions for multi-component applications.  All applications must be submitted on Form PHS 398. 

The multi-component grant application should be assembled and paginated as one complete document in the following order:

Overview of the Center (Overall)

Follow all instructions in the PHS398 Application Guide for a single project application, but note the additional instructions provided below.

Face Page (Form Page 1)

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

Description, Project/Performance Sites, Senior/Key Personnel, Other Significant Contributors, and Human Embryonic Stem Cells (Form Page 2)

Follow all instructions in the Application Guide, but note the following additional instructions:

Senior/Key Personnel: List key scientific and key technical personnel participating in the U54 Center. Use continuation pages as necessary, numbering consecutively.

Table of Contents (Form Page 3)

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

Detailed Budget for Initial Budget Period and Budget for Entire Proposed Period of Support

This FOA uses non-modular budget formats described in the PHS 398 application instructions (see http://grants.nih.gov/grants/funding/phs398/phs398.html).

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

Composite Budget

Use PHS-398 Form Page 4, "Detailed budget for initial budget period,"  to present the total budget for all requested support for the first year. For each category, such as "Personnel," "Equipment," etc., give the amount requested for each Research Project component and each Core unit, with subtotals.

If consortium arrangements involving other institutions or organizations are anticipated, include total (direct and indirect) costs associated with such third-party participation in the Consortium/Contractual Costs category.

Use PHS-398 Form Page 5, "Budget for entire proposed project period," to prepare a budget, by category, that provides totals for each year of requested support. Requests for any increases in succeeding years must be justified in the individual Research Project component and Core unit budgets.

Budgets for Individual Research Project Components and Core Components  

Detailed budget for initial budget period:  (use PHS-398 Form Page 4 for each).  Note the specific budget requirements for the Pilot Projects, Administrative Core, and Outreach/Education Core budget as described below.

Pilot Projects (optional):  Funds may be requested in the original application to provide support for one or more Pilot Projects in areas relevant to the center’s goals.  Funds for Pilot Projects may be requested in either new or renewal applications.  Pilot projects may be used to generate preliminary data for submission of an R01 or center Research Project, to develop new technologies that further enhance the research efforts of the center or to support clinical research studies that could form the basis for conduct of large scale clinical trials through the NICHD Reproductive Medicine Network.  Funding for Pilot Projects may not exceed $100,000 direct costs per year.  Support for any particular Pilot Project is limited to a two-year period.  With NICHD staff approval, the period of support may be extended one additional year.  If a Pilot Project component is favorably recommended for an initial two-year period, funds will be included each year for the full five years based on the level of funding for this purpose in Years 01 and 02.   Funds requested in Years 03-05 will be contingent upon review and approval of additional Pilot Projects by NICHD staff. 

The Administrative Core must include funds in the amount of $30,000 direct costs per year to provide translational research training experiences, both didactic and/or laboratory, for students, postdoctoral fellows or residents from other centers, and post-residency scholars supported under institutional K12 awards such as the CTSA, Women’s Reproductive Health Research (WRHR), Male Reproductive Health Research (MRHR) and Building Interdisciplinary Research Careers in Women’s Health (BIRCWH) career development programs.  These funds will be restricted for cross-center training experiences.  Funds can be used to purchase supplies, course materials and travel. 

Note:  Total direct and indirect costs of any sub-awardee are to be shown under Consortium/Contractual costs on the individual component budget and a detailed sub-awardee budget is to be placed following the appropriate Research Project or Core budget. Costs for purchased services should be itemized under the "Other Expenses" category.

Budget for entire proposed project: use PHS-398 Form Page 5 for each.

Budget Justifications and Explanations: Describe the specific functions of all key personnel, consultants, collaborators, and support staff. For all years, explain and justify any unusual items such as major equipment or alterations and renovations. For additional years of support requested, justify any significant increases or decreases in any category over the first 12-month budget period. Identify such changes with asterisks against the appropriate amounts. If a recurring annual increase in personnel or other costs is anticipated, give the percentage; however, the maximum allowable escalation under this FOA is 2%. In addition, for renewal applications, justify any significant increases in any category over the current level of support.

Biographical Sketches

Biographical sketches are required for all senior/key scientific and key technical personnel participating in the overall Center, the Core Components, and the specific Research Component project(s). Beginning with Center Director, and following in alphabetical order, submit biographical sketches as described in the "Instruction Sheet for Form PHS-398," using the sample format on the Biographical Sketch Format Page.

Resources

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

Research Plan (Overall)

All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions:

Center organization may include a mix of research projects and cores to be included in the Center, given the minimal requirements for projects and cores as specified below.  The applicant may choose to organize the Center using a suite of projects and cores within the same institution. Alternatively, Centers may seek to maximize their scientific expertise and research capabilities by including in the application research projects and/or technical service cores to be supported at other institutions through subcontracted consortium arrangements.

Introduction:  Resubmission applications should include an Introduction as described in the PHS398 Application Guide.

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 as outlined in Section I.  Funding Opportunity Description.  Explain the strategy for achieving the goals defined for the overall program and how each Core and Research Component relate to that strategy. Explain how the different aspects of the organization, including key personnel, will interact, why they are essential to accomplishing the overall goal of the research, and how combined resources create a Center 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:

Protection of Human Subjects. Provide an overview of the human subjects considerations for the Center as a whole.  List the components of the application that involve human subjects and page numbers for the relevant human subjects sections. 

Vertebrate Animals. Provide an overview of the vertebrate animal considerations for the Center as a whole. List the components of the application that involve live vertebrate animals and page numbers for the relevant sections.

Letters of Assurance/Agreement: Provide an overview and rationale for any arrangements for collaborative and cooperative endeavors or subcontracts. Include letters of agreement from consultants. For projects 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.  Applicants are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the PHS 398 Application Guide, with the following modifications:

Research Projects and Pilot Project(s)

Follow all instructions in the PHS398 Application Guide for a single project application, but note the additional instructions provided below.

Face Page (Form Page 1)

Do not use the PHS398 Face Page. For each Research Project and optional Pilot Project, include a single cover page listing the title of the Project, the name of the PD/PI, and names of any other Key Personnel (with titles and affiliations). Identify each project  with a Roman numeral (I, II, III…) and a descriptive title.  

Description, Project Performance Sites, Senior/Key Personnel, Other Significant Contributors, and Human Embryonic Stem Cells (Form Page 2)

Provide the description and other requested information for each Research Project and Pilot Project.

Table of Contents (Form Page 3)

Do not complete this form for the Research Projects or Pilot Projects.  

Detailed Budget for Initial Budget Period and Budget for Entire Proposed Period of Support

Do not complete these pages for the Research Projects or Pilot Projects.  See instructions under Budget for the Center overall.

Biographical Sketches

Do not complete this form page for the Research Projects or Pilot Projects.

Research Plan for Research Projects and Pilot Project(s)

The application must include at least three Research Projects that thematically address one or more research areas listed under Research Scope.  It is required that at least one project be entirely or predominantly clinical in nature, and that all basic science projects be linked to the clinical component(s) of the center.  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 (http://escr.nih.gov). 

Pilot Projects may be proposed for Years 01 and 02 to generate preliminary data for submission of an R01 or center research project, to develop new technologies that further enhance the research efforts of the center, or to support clinical research studies that could form the basis for conduct of large scale clinical trials through the NICHD Reproductive Medicine Network.  The proposed Research Plan must be described in sufficient detail, comparable to the other Research Projects submitted in the application, to permit evaluation of the Pilot Project(s) using the review criteria listed under Section V “Application Review Information” with the exception that little or no preliminary data are required for a Pilot Project. 

Introduction:  Resubmission applications should include an Introduction for each Research Project and Pilot Project as described in the PHS398 Application Guide.

Specific Aims:  Describe the Specific Aims for the Research Project or Pilot Project(s) following the instructions in the PHS398 Application Guide.

Research Strategy: Organize the Research Strategy for each Research Project and Pilot Project as described in the PHS398 Application Guide and using the instructions provided below. Start each section with the appropriate section heading—Significance, Innovation, Approach.  Each Research Project and Pilot Project should clearly describe the project's overall objective and explain its relevance to the Center's theme.  Specify the overall 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.

Applications must provide information regarding access to inpatient and outpatient reproductive health care units providing adequate numbers of patients for clinical Research Projects that require patient participation. [Applications from institutions that have a Clinical and Translational Science Award (CTSA) or General Clinical Research Center (GCRC) may wish to identify the CTSA or GCRC as a resource for conducting the proposed research.  In such a case, a letter of agreement from either the CTSA or GCRC Program Director or PD/PI should be included with the application.]

NOTE:  Each specific Research Project and optional Pilot Project will be peer reviewed for scientific and technical merit, as well as for the appropriateness of the project's use of Core services and relevance to the goals of the Center.

Protection of Human Subjects: If the Research Project or Pilot Project  involves human subjects, describe the risks, protections, potential benefits, importance of knowledge to be gained, and data and safety monitoring for clinical trials, as required in PHS398 application instructions.  If Pilot Projects are to be selected administratively after the initial award, describe the internal institutional plans and procedures to ensure that all projects supported from this award will comply fully with all applicable Federal regulations, policies, and guidelines for research involving human subjects, including the evaluation of risks and protections in project proposals, appropriate ethical oversight and funded projects, and plans for data and safety monitoring for clinical trials, if applicable.

Inclusion of Women, Minorities and Children. If appropriate for the Research Project or Pilot Project, describe the composition of the human subjects and the proactive plan to recruit women, minorities, and children. Follow PHS 398 Instructions in preparing this section.

Vertebrate Animals: If the Research Project or Pilot Project(s) involve live vertebrate animals, include a description of the use of live vertebrate animals 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.

Resource Sharing Plan.  Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the PHS 398 Application Guide. 

Core Components

Follow all instructions in the PHS398 Application Guide for a single project application, but note the additional instructions provided below.

Face Page (Form Page 1)

Do not use the PHS398 Face Page. For each Core Component, include a single cover page listing the title of the Core, the name of the Core Director, and names of any other Key Personnel (with titles and affiliations). Identify each proposed Core unit by a letter (A, B, C…) and a title (e.g., Administrative Core, Outreach/Education Core, Molecular/Cellular Core, etc.).

Description, Project Performance Sites, Senior/Key Personnel, Other Significant Contributors, and Human Embryonic Sttem Cells (Form Page 2)

Provide the description and other requested information for each Core Component.

Table of Contents (Form Page 3)

Do not complete this form page for the Core Components.

Detailed Budget for Initial Budget Period and Budget for Entire Proposed Period of Support

Do not complete these pages for the Core Components.  Budgets for Core Components should be prepared as described for the Center Overall.  

Biographical Sketches

Do not complete this form page for the Core Components.

Research Plan for Core Components

Introduction:  Resubmission applications should include an Introduction for each Core as described in the PHS398 Application Guide.

Research Strategy:  For the required Administrative Core and Outreach/Education Core, and for any optional Cores, provide the following information:

Note the following requirements for specific Core components.  Applications should address these Core requirements and functions in describing the Research Plan.

Administrative Core:  Each Center must include an Administrative Core, located at the applicant institution, that provides oversight to the Center and is accessed only by budgeted Center Research Projects and Cores.

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

Technical Service Cores (optional):  The applicant may choose one of two center structure options regarding access to technical service core facilities:

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.

Protection of Human Subjects:  If the Core services involve human subjects, describe the risks, protections, potential benefits, importance of knowledge to be gained, and data and safety monitoring for clinical trials, as required in PHS398 application instructions. If all of the individual projects accessing the Core have their own Human Subjects sections, this should be clearly stated in this section.

Inclusion of Women, Minorities and Children.  If applicable for this Core Component, describe the composition of the human subjects and the proactive plan to recruit women, minorities, and children. Follow PHS 398 Instructions in preparing this section.

Vertebrate Animals: If Core services involve live vertebrate animals, include a description of the use of live vertebrate animals 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. If all of the individual projects accessing the Core have their own vertebrate animal assurances, this should be clearly stated in this section.

Resource Sharing Plan

Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the PHS 398 Application Guide.

Appendix

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix (please note all format requirements) as described in the PHS 398 Application Guide.

3. Submission Dates and Times

Part I. Overview Information contains information about Key Dates. 

Information on the process of receipt and determining if your application is considered “on-time” is described in detail in the PHS 398 Application Guide.

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

4. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

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.

6. Other Submission Requirements and Information

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

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

Post Submission Materials

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

Section V. Application Review Information


1. Criteria

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

For this particular announcement, note the following:  

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

Overall Impact - Overall

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).

Scored Review Criteria - Overall

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

Significance

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

Investigator(s)

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

Innovation

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

Approach

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

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

Environment

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

Additional Review Criteria - Overall

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

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Children 

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

Vertebrate Animals

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

Biohazards

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

Resubmissions

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

Renewals

For Renewals, the committee will consider the following: 

Revisions

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

Additional Review Considerations - Overall

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.

Applications from Foreign Organizations

Not Applicable.

Select Agent Research

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

Resource Sharing Plans

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

Budget and Period of Support

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

Review Criteria for Research Projects and Pilot Project(s)
 
Overall Impact - Research Projects and Pilot Project(s)

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the Research Project or Pilot Project(s) 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).

Scored Review Criteria- Research Projects and Pilot Projects

Reviewers will also consider each of the five review criteria below in the determination of scientific and technical 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 Research Project address an important problem or a critical barrier to progress in the field? If the aims of the Research Project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Investigator(s)

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

Innovation

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

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the Research Project? Are potential problems, alternative strategies, and benchmarks for success presented? If the Research Project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? If the Research Project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the Research Project proposed? Will the Research Project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements? Is the Research Project well-integrated into the Center as a whole?

Additional Review Criteria-Research Projects and Pilot Projects

As applicable for the Research Project or Pilot Project(s) proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Children

When the proposed Reseach Project or Pilot Project(s) involve clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

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

Biohazards

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

Resubmissions

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

Renewals

For Renewals, the committee will consider the following: 

Revisions

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

Additional Review Considerations-Research Projects and Pilots

As applicable for the Research Project or Pilot 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) Genome Wide Association Studies (GWAS).

Budget and Period of Support

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

Review Criteria for Core Components
 
Overall Impact - Cores

Reviewers will assign an Impact Score based on the assessment of each Core Component in terms of the following review criteria.

Additional Review Criteria-Cores

As applicable for each individual Core, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall Impact Score, but will not give separate scores for these items.

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Children

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

Vertebrate Animals

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

Biohazards

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

Resubmissions

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

Renewals

For Renewals, the committee will consider the following: 

Revisions

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

Additional Review Considerations-Cores

As applicable for the Cores 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) Genome Wide Association Studies (GWAS).

Budget and Period of Support

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

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s), convened by the 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:

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

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

3. Anticipated Announcement and Award Dates

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

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

Section VI. Award Administration Information


1. Award Notices

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

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

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

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

Prior Approval of Pilot Projects

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.

2. Administrative and National Policy Requirements

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.

Cooperative Agreement Terms and Conditions of Award

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

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

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

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

Areas of Joint Responsibility include:

Dispute Resolution:

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

3. Reporting

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

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

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

Section VII. Agency Contacts

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

Application Submission Contacts

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-435-0714
TTY 301-451-5936
Email: GrantsInfo@nih.gov

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

Scientific/Research Contact(s)

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

Peer Review Contact(s)

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

Financial/Grants Management Contact(s)

Mr. Ted Williams
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-326-6450
Email: williate@mail.nih.gov

Section VIII. Other Information

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.

Authority and Regulations

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


Weekly TOC for this Announcement
NIH Funding Opportunities and Notices


Office of Extramural Research (OER) - Home Page Office of Extramural
Research (OER)
  National Institutes of Health (NIH) - Home Page National Institutes of Health (NIH)
9000 Rockville Pike
Bethesda, Maryland 20892
  Department of Health and Human Services (HHS) - Home Page Department of Health
and Human Services (HHS)
  USA.gov - Government Made Easy
NIH . . . Turning Discovery Into Health

Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files.