Part I Overview Information

Department of Health and Human Services

Participating Organizations
National Institutes of Health (NIH) (http://www.nih.gov)

Components of Participating Organizations
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (http://www.nichd.nih.gov)

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

Announcement Type
This is a reissue of RFA-HD-08-001

Update: The following update relating to this announcement has been issued:

• November 19, 2010 - This RFA has been reissued as (RFA-HD-12-169).
• December 2, 2009 - This FOA has been updated to reflect the new requirements from NIH’s Enhancing Peer Review Initiative. The new requirements are effective for submissions intended for due dates January 25, 2010 and beyond. If submitting an application intended for a due date of January 25, 2010 and beyond, follow the guidance below and be sure to use the 06/2009 version of the PHS 398 application forms and instructions. If applying for a due date before January 25, 2010, follow the guidance in the archived version of this FOA and be sure to use the 11/2007 version of the PHS 398 application forms and instructions.

Key Dates
Release Date: September 3, 2009
Letters of Intent Receipt Date: April 5, 2010
Application Receipt Date: May 5, 2010
Peer Review Date(s): October/November 2010
Council Review Date: January 2011
Earliest Anticipated Start Date: April 1, 2011
Additional Information to Be Available Date (Url Activation Date): Not applicable
Expiration Date: May 6, 2010

Due Dates for E.O. 12372

Not Applicable

Additional Overview Content

Executive Summary

• Purpose. The purpose of this FOA is to announce the re-competition of the Specialized Cooperative Centers Program in Reproduction and Infertility Research (SCCPIR). The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) provides funding for a limited number of research centers in the reproductive sciences. These centers provide an arena for multidisciplinary interactions between basic and clinical scientists interested in establishing high quality translational research programs in the area of reproduction and infertility. The centers also serve as national resources for the training and career development of new scientists electing to pursue careers conducting translational research in high priority areas of reproduction and infertility. Finally, center investigators will participate in important community outreach and education efforts to increase awareness and convey the importance and implications of their research activities to the general public.
• Mechanism of Support. This FOA will utilize the NIH Specialized Cooperative Center (U54) award mechanism grant mechanism.
• Funds Available and Anticipated Number of Awards. The NICHD intends to commit approximately $5.5 million in total costs in FY 2011 to fund up to three new and/or renewal applications in response to this FOA.
• Budget and Project Period. The total project period for an application submitted in response to this FOA may not exceed five years. Direct costs are limited to $1,400,000 for the first year.
• Eligible Institutions/Organizations. Institutions/organizations listed in Section III, 1.A. are eligible to apply.
• Eligible Project Directors/Principal Investigators (PDs/PIs). Individuals with the skills, knowledge, and resources necessary to carry out the proposed research are invited to work with their institution/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.
• Number of Applications. Applicant institutions may submit more than one application, provided they are scientifically distinct and based in different departments or units.
• Resubmissions. Applicants may submit a resubmission application, but such application must include an Introduction addressing the previous peer review critique (Summary Statement). See new NIH policy on resubmission (amended) applications (NOT-OD-09-003, NOT-OD-09-016).
• Renewals. Renewal applications are permitted in response to this FOA.
• Application Research Strategy Length: The Research Strategy section may not exceed 12 pages for each project and 6 pages for each core and pilot project, including tables, graphs, figures, diagrams and charts.
• Application Materials. See Section IV.1 for application materials.
  All applications, including resubmission, revision and renewal, submitted for due dates January 25, 2010 and beyond, must utilize the current forms and instructions.
• Hearing Impaired. Telecommunications for the hearing impaired are available at: TTY: (301) 451-5936.

Table of Contents

Part I Overview Information

Part II Full Text of Announcement

Section I. Funding Opportunity Description
1. Research Objectives

Section II. Award Information
1. Mechanism(s) of Support
2. Funds Available

Section III. Eligibility Information
1. Eligible Applicants
A. Eligible Institutions
B. Eligible Individuals
2.Cost Sharing or Matching
3. Other - Special Eligibility Criteria

Section IV. Application and Submission Information
1. Address to Request Application Information
2. Content and Form of Application Submission
3. Submission Dates and Times
A. Receipt, Review and Anticipated Start Dates
1. Letter of Intent
B. Sending an Application to the NIH
C. Application Processing
D. Application Assignment
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements

Section V. Application Review Information
1. Criteria
2. Review and Selection Process
A. Additional Review Criteria
B. Additional Review Considerations
C. Resource Sharing Plan(s)
3. Anticipated Announcement and Award Dates

Section VI. Award Administration Information
1. Award Notices
2. Administrative and National Policy Requirements
A. Cooperative Agreement Terms and Conditions of Award
1. Principal Investigator Rights and Responsibilities
2. NIH Responsibilities
3. Collaborative Responsibilities
4. Arbitration Process
3. Reporting

Section VII. Agency Contact(s)
1. Scientific/Research Contact(s)
2. Peer Review Contact(s)
3. Financial/ Grants Management Contact(s)

Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement

Section I. Funding Opportunity Description

1. Research Objectives

Purpose

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

Families, family values, and family planning form the cultural essence and cohesiveness of our existence as human societies. One of the most basic of human rights -- the right to procreate -- is frustrated or denied by the occurrence of infertility in couples desiring children. It has been estimated that infertility affects between 37 and 70 million married couples around the world. In U.S. studies described over 50 years ago, it was stated that up to 10 percent of married couples were sterile, with the remaining 90 percent having varying degrees of fertility. More recent and technically rigorous U.S. survey studies have conservatively identified that there are about 2.3 million infertile couples, which is about nine percent of the domestic married couple population base with wives aged 15-44. According to the 2002 National Survey of Family Growth, 7.4 percent of married women, or about 2.1 million women were infertile (12 months or longer without birth control and without a pregnancy). This represents a significant decline from the prevalence of 8.4 percent reported in 1982. On the other hand, about 15% of married women or 4.3 million had an impaired ability to have children (impaired fecundity) in 2002 compared to 8.5% of married women 20 years earlier. This latter trend likely is indicative of the delay in childbearing found in the contemporary couple population base in which significant age-related increases in infertility and subfecundity have been reported.

Physician office visits reflecting current societal life style requirements for infertility services have markedly increased in the U.S. almost four fold between 1968 (600,000) and 2000 (2,100,000). Indeed, it is estimated that 13 percent of American women will receive infertility services during their lifetime. Interestingly, this represents only half the number of women who actually need infertility services. Of the infertile couples seeking treatment for infertility, it has been estimated that up to one half will be unsuccessful in achieving their desired outcome. In concert with the increased medical assistance sought, U.S. infertility service costs have risen to exceed a several billion dollars annually.

In couples, at least 25-40 percent of infertility is attributable to male factor infertility for which the pathophysiology is either not understood at all or, at best, poorly understood. The prognosis for male infertility treatment outcomes is extremely poor at present. Indeed, whereas 80 percent of infertile women can be successfully treated, male infertility can be treated in only 10-20 percent of such men. However, the widespread use of assisted reproductive technologies such as intracytoplasmic sperm injection (ICSI) and its variants has enabled otherwise infertile men to father children, although possible genetic causes of the infertility are likely transmitted to the progeny.

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

Similarly, the role of dysfunctional uterine bleeding, either in the presence or the absence of uterine leiomyomata (fibroids), is not well understood despite its common occurrence and decades of research. It is a significant factor in noncompliant contraceptive use or discontinuance and, therefore, in the unintended pregnancy problem.

Uterine leiomyomata occur in nearly 20% percent of all reproductive-aged women, are the single most common diagnosis in gynecological hospital admissions, may be the only abnormality observed in an infertile couple, and represent the most common medical indication for an unintended and often unwanted hysterectomy that prematurely ends a females reproductive options. Fibroids disproportionately affect African Americans with some studies indicating a three-fold higher prevalence in this racial group than in the Caucasian population. Annual cost expenditures for this condition approximates 2.1 billion dollars.

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

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

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

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

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

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

Finally, the need for the availability of contraceptive options acceptable to diverse populations remains globally unmet. Among the 600 million women of reproductive age in todays world, as many as 228 million women are at risk of unintended pregnancy. Up to 64 percent of all worldwide pregnancies are unintended (mistimed or completely unwanted). Over 50 million abortions occur worldwide each year, with minimal estimates of at least 100,000 abortion-related deaths annually. In the U.S., more than three million unintended pregnancies, about 60 percent of all pregnancies, occur annually, with half resulting in abortion as an outcome. In half of the abortions occurring in the U.S. each year, a contraceptive method being used failed to prevent pregnancy.

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

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

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

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

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

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

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

See Section VIII, Other Information - Required Federal Citations, for policies related to this announcement.

Section II. Award Information

1. Mechanism of Support

This funding opportunity will use the NIH Specialized Cooperative Research Center (U54) award mechanism. The Project Director/Principal Investigator (PD/PI) will be solely responsible for planning, directing, and executing the proposed project.

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

This funding opportunity will use a cooperative agreement award mechanism. In the cooperative agreement mechanism, the Project Director/Principal Investigator (PD/PI) retains the primary responsibility and dominant role for planning, directing, and executing the proposed project, with NIH staff being substantially involved as a partner with the Principal Investigator, as described under the Section VI. 2. Administrative Requirements, "Cooperative Agreement Terms and Conditions of Award". At this time, the NICHD plans to reissue this FOA on an annual basis.

2. Funds Available

The NICHD intends to commit approximately $5.5 million in total costs [Direct plus Facilities and Administrative (F & A) costs] in FY 2011 to fund up to three new and/or renewal applications in response to this FOA. An applicant for a center may request a project period of up to five years and a budget for direct costs not to exceed $1.4 million for the first year with incremental increases for recurring costs (i.e., personnel, consultants, supplies, travel and other expenses) not to exceed three percent in each subsequent year. Applications exceeding the budgetary limits specified above will be returned to the applicant without peer review. Furthermore, increases in outyear budgets for recurring costs are subject to the availability of funds.

The estimated amount of funds available for support of three projects awarded as a result of this announcement is $5.5 million for fiscal year 2011. Future year amounts will depend on annual appropriations.

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(s) 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.

Facilities and administrative costs requested by consortium participants are not included in the direct cost limitation see NOT-OD-05-004.

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

1.A. Eligible Institutions

The following organizations/institutions are eligible to apply:

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education
• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Nonprofits 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 (Other than Small Businesses)
• State Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribally Designated Organizations
• U.S. Territory or Possession
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Regional Organizations
• Non-domestic (non-U.S.) Entities (Foreign Organizations) are not eligible to apply as a P.I. However, subcontracts from domestic entities to foreign sites are permitted.

1.B. Eligible Individuals

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research as the PD/PI is invited to work with his/her institution 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.

2. Cost Sharing or Matching

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

3. Other-Special Eligibility Criteria

Number of Applications. Applicants may submit more than one application, provided they are scientifically distinct and based in different departments or units.

Resubmissions. Applicants may submit a resubmission application, but such application must include an Introduction addressing the previous peer review critique (Summary Statement). Beginning with applications intended for the January 25, 2009 official submission due date, all original new applications (i.e., never submitted) and competing renewal applications will be permitted only a single amendment (A1). See http://grants.nih.gov/grants/guide/notice-files/NOT-OD-09-003.html and NOT-OD-09-016. Original new and competing renewal applications that were submitted prior to January 25, 2009 will be permitted two amendments (A1 and A2). For these grandfathered applications, NIH expects that any A2 will be submitted no later than January 7, 2011, and NIH will not accept A2 applications after that date.

Renewals. Renewal applications are permitted in response to this FOA.

Section IV. Application and Submission Information

1. Address to Request Application Information

The PHS 398 application instructions are available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. Applicants must use the currently approved version of the PHS 398. For further assistance contact GrantsInfo, Telephone (301) 710-0267, Email: [email protected].

Telecommunications for the hearing impaired: TTY 301-451-5936.

2. Content and Form of Application Submission

Applications must be prepared using the most current PHS 398 research grant application instructions and forms. Applications must have a D&B Data Universal Numbering System (DUNS) number as the universal identifier when applying for Federal grants or cooperative agreements. The D&B number can be obtained by calling (866) 705-5711 or through the web site at http://www.dnb.com/us/. The D&B number should be entered on line 11 of the face page of the PHS 398 form.

The title and number of this funding opportunity must be typed in item (box) 2 only of the face page of the application form and the YES box must be checked.

Applications for the U54 grant are to be prepared in a manner consistent with the information presented in the NICHD U54 Cooperative Specialized Research Center Grant Guidelines, available from the contacts listed below and at http://www.nichd.nih.gov/funding/mechanism/u54_guide.cfm.

Additional information is available in the PHS 398 grant application instructions.

3. Submission Dates and Times

Applications must be received on or before the receipt date described below (Section IV.3.A). Submission times N/A.

3.A. Receipt, Review and Anticipated Start Dates
Letters of Intent Receipt Date: April 5, 2010
Application Receipt Date: May 5, 2010
Peer Review Date(s): October/November 2010
Council Review Date: January 2011
Earliest Anticipated Start Date: April 1, 2011

3.A.1. Letter of Intent

Prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed research
• Name, address, and telephone number of the Principal Investigator
• Names of other key personnel
• Participating institutions
• Number and title of this funding opportunity

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.

The letter of intent is to be sent by the date listed in Section IV.3.A.

The letter of intent should be sent to:

Louis V. DePaolo, Ph.D.
Reproductive Sciences Branch
Center for Population Research
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
6100 Executive Boulevard, Room 8B01A, MSC 7510
Rockville, MD 20852 (for express/courier service; non-USPS service)
Telephone: (301) 435-6970
FAX: (301) 496-0962
Email: [email protected]

3.B. Sending an Application to the NIH

Applications must be prepared using the forms found in the PHS 398 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)

Personal deliveries of applications are no longer permitted (see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-040.html).

At the time of submission, two additional copies of the application and all copies of the appendix material must be sent to:

Robert Stretch, Ph.D.
Director, Division of Scientific Review
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institutes of Health (NIH)
6100 Executive Boulevard, Room 5B01, MSC 7510
Bethesda, MD 20892-7510
Rockville, MD 20852 (for express/courier service; non-USPS service)
Telephone: 301-496-1485
FAX: 301-402-4104
Email: [email protected]

3.C. Application Processing

Applications must be received on or before the application receipt date) described above (Section IV.3.A.). If an application is received after that date, the application may be delayed in the review process or not reviewed. Upon receipt, applications will be evaluated for completeness by the CSR and for responsiveness by the reviewing Institute Incomplete and/or non-responsive applications will not be reviewed.

The NIH will not accept any application in response to this funding opportunity that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. However, when a previously unfunded application, originally submitted as an investigator-initiated application, is to be submitted in response to a funding opportunity, it is to be prepared as a NEW application. That is, the application for the funding opportunity must not include an Introduction describing the changes and improvements made, and the text must not be marked to indicate the changes from the previous unfunded version of the application.

Information on the status of an application should be checked by the Principal Investigator in the eRA Commons at: https://commons.era.nih.gov/commons/.

4. Intergovernmental Review

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. The Grants Policy Statement can be found at NIH Grants Policy Statement.

Pre-award costs are allowable. A grantee may, at its own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new or renewal award if such costs: 1) are necessary to conduct the project, and 2) would be allowable under the grant, if awarded, without NIH prior approval. If specific expenditures would otherwise require prior approval, the grantee must obtain NIH approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new or renewal award.

The incurrence of pre-award costs in anticipation of a competing or non-competing award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project (see NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part6.htm.)

6. Other Submission Requirements

Applications for the U54 grant are to be prepared in a manner consistent with the information presented in the NICHD U54 Cooperative Specialized Research Center Grant Guidelines, available from the contacts listed below and at http://www.nichd.nih.gov/funding/mechanism/u54_guide.cfm.

At minimum, an application in response to this FOA should include:

• A description of a Specialized Center in Reproduction and Infertility Research consisting of multiple individual research subprojects, an Administrative Core, an Outreach/Education Core and, if applicable, one or more technology-based core service facilities.
• A description of the capabilities of the Center to meet or exceed the minimal requirements for a Center stated in this FOA (see Description of a Center).
• A proposed five-year research plan that presents the applicant's perception of the Center's organization and component functions. This plan should demonstrate the applicant's knowledge, ingenuity, practicality, and commitment in organizing a multi-project research infrastructure for conducting basic and clinical studies in the reproductive sciences and integrating those studies to accomplish the translational research objectives of this Centers Program. The research plan for the Center and all component subprojects must address the Research Scope described above.
• A statement describing the willingness of the Principal Investigator to cooperate in a coordinated cooperative program involving multiple Centers with the objective of developing research project and/or service core interactions between Centers.
• Substantive evidence of departmental and institutional support for and commitment to the proposed Center.
• For renewal applications, evidence during the previous funding period of: 1) having met the Terms and Conditions of the award; 2) translational research activities within the center and/or in conjunction with other Centers, and 3) cooperative research activities with other centers.

All applicants must document their ability to meet or exceed the minimum requirements as set forth in this FOA. This specifically includes understanding of and commitment to the cooperative nature of this Program, and willingness to meet the Terms and Conditions of Award.

Description of a Center

The minimal requirements for a Center described in this FOA are as follows (see sections on Review Procedures and Award Criteria below):

• A research plan that is responsive to the objectives of the Centers Program set forth in this FOA (see Research Objectives).
• At least three research subprojects that thematically address one or more research areas listed under Research Scope. It is required that at least one subproject be entirely or predominantly clinical in nature, and that all basic science subprojects 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).
• An Administrative Core unit that provides oversight to the Center, located at the applicant institution and accessed only by budgeted Center subprojects and cores.
• Funds in the amount of $50,000 direct costs per year to support collaborative projects with investigators supported by other SCCPIR centers and/or pilot studies. In the case of pilot projects, it is encouraged that the center use the funds to support new investigators (new investigators are defined as individuals who have not been a Principal Investigator on any prior NIH research grant except K01, K08, K22, K23, R03 and R15). Centers are encouraged to also utilize these funds for conduct of clinical research studies that could form the basis for conduct of large scale clinical trials through the NICHD Reproductive Medicine Network. A center can use these funds to support pilot studies even if a separate pilot project(s) was approved in the funded application (see below under Optional Components of the Center). These funds will be requested as part of the Administrative Core budget, and will be restricted for use to support collaborative and/or pilot projects pending an external peer review of the project, and approval by the SCCPIR Steering Committee and by NICHD. Support for a particular collaborative research activity or pilot project is limited to two years.
• 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, Womens Reproductive Health Research (WRHR), Male Reproductive Health Research (MRHR) and Building Interdisciplinary Research Careers in Womens Health (BIRCWH) career development programs. These funds will be requested as part of the Administrative Core budget, and will be restricted for cross-center training experiences. Funds can be used to purchase supplies, course materials and travel. Center investigators are particularly encouraged to provide training experiences for under-represented minority groups, those with disabilities and those who wish to re-enter an active research career after taking time to care for children or attend to other family responsibilities. For these individuals, and in addition to the $30,000, the NIH offers supplements to the parent award to support individuals representing these special populations. Guidelines on how to apply for these supplements are provided in PA-05-015, Research Supplements to Promote Diversity in Health-Related Research (http://grants.nih.gov/grants/guide/pa-files/PA-05-015.html).
• An Outreach/Education Core unit that 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 to support these activities. 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.
• A competent and experienced Principal Investigator who is committed to and directly involved in research dealing with mammalian reproduction.
• Availability of competent and experienced scientific experts to direct individual research projects or cores associated with the proposed Center.
• Availability of the technical resources and facilities necessary for the conduct of the research.
• Access to properly managed animal facilities for projects conducting animal studies.
• As appropriate, access to inpatient and outpatient reproductive health care units providing adequate numbers of patients for clinical research projects that require patient participation. [Applications from institutions that have a Clinical and Translational Science Award (CTSA) of General Clinical Research Center (GCRC) funded by the NIH National Center for Research Resources may wish to identify the CTSA or GCRC as a resource for conducting the proposed research. In such a case, a letter of agreement from either the CTSA or GCRC Program Director or Principal Investigator should be included with the application.]
• Plans for data and resource sharing. These plans should be listed under the Research Plan. See Section IV-6 Resource Sharing Plans for guidance.
• Substantive evidence of departmental and institutional support for and commitment to the proposed center.
• Willingness to cooperate in a coordinated cooperative research program involving other SCCPIR centers.

Optional components of the Center organization include the mix of subprojects and cores to be included in the Center:

• The Principal Investigator may choose to organize the Center using a suite of subprojects and cores within the same institution. Alternatively, Centers may seek to maximize their scientific expertise and research capabilities by including in the application subprojects and/or a technical service cores to be supported at other institutions through subcontracted consortium arrangements.
• Funds may be requested in the original application to provide support for one or more pilot projects in Years 01 and 02 relevant to the centers goals. Pilot projects may be used to generate preliminary data for submission of an R01 or center subproject, to develop new technologies that further enhance the research efforts of the center or to support clinical research studies that could form the basis for conduct of large scale clinical trials through the NICHD Reproductive Medicine Network. Support for a pilot project is limited to a two-year period. Funding may not exceed $100,000 per year. With NICHD staff approval, the period of support may be extended one additional year. Funds for pilot projects may be requested in either new or renewal applications. As such, the proposed research plan must be described in sufficient detail, comparable to the other subprojects submitted in the application, to permit evaluation of the project using the review criteria listed under Section V Application Review Information with the exception that little or no preliminary data are required for a pilot project. If a pilot project is favorably recommended for an initial two-year period, funds will be included each year for the full five years. Funds in Years 03-05 will be contingent upon review and approval of additional pilot projects by NICHD staff. Funding levels in these out-years will be based on the level of funding for this purpose in Years 01 and 02.
• The Principal Investigator may choose one of two center structure options regarding access to technical service core facilities:

Closed Access Structure: In this center structure administrative and all technical service cores will be utilized by budgeted center subprojects only. Consistent with NICHD guidelines for establishment of core facilities, utilization by three subprojects is required to justify a core technical service facility. Percent utilization by any one of the three subprojects justifying the core may not exceed 50 percent or be less than five percent. The percent utilization of additional subprojects 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 subprojects per se. No internal charge-back system would be required.

Open Access Structure: In this center structure, budgeted center subprojects, as well as research projects external to the Center (e.g., R01, 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 subproject, while the remaining project(s) used in justifying the core must be externally funded NICHD projects administered by the RSB. Percent utilization by any internally budgeted center subproject or externally funded RSB project used to justify a particular core facility may not exceed 50 percent or be less than five percent. An additional seven federally funded, peer reviewed external research projects addressing program relevant research areas of the RSB may access the core up to 100 percent of its service capacity. The 50/5 percent utilization requirement applies to this group of external projects. Centers must establish an internal management policy for evaluating the acceptability of proposed RSB program relevant external projects to access the core facilities. Approval of requests for core access privileges for external projects which would replace those described above must be made to RSB Program Staff who then will evaluate the extent to which the project is relevant to RSB mission research areas (see Research Scope), and render a decision accordingly.

If centers choose to operate in an open access format, costs necessary to utilize a particular core facility by budgeted center subprojects must be incorporated into the budget of the subproject 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 subprojects and external, program relevant research projects as described above. Above and beyond this arrangement, technology based core units may offer services to additional external projects addressing any area of research regardless of funding source only on a full payback (fee for service or in-kind) basis. However, additional funds necessary to provide services to these external projects (e.g., technical support, supplies, etc.) must come from sources other than the center funding, such as the supply budgets of the external projects wishing to access the core facilities. In choosing to configure a center in an open access center structure, the Principal Investigator must have in place, and adequately describe in the application, management policies that ensure that budgeted center subprojects are given highest priority in receiving services provided by the core.

Centers choosing to configure in an open access center format may propose one or more technical service cores that will be utilized exclusively by budgeted center subprojects. These centers may, therefore, have a mix of open and restricted access technical service cores. On the other hand, administrative cores in open center structures may be accessed only by budgeted center subprojects.

Once an award is made, centers configured as a closed access center structure may, at a later time, choose to convert to an open access center structure by requesting such conversion in writing to the NICHD.

Program Coordination and Management Structure

Overall coordination of the SCCPIR, consistent with the stated objectives set forth in this FOA (see Objectives), will be done by a Steering Committee consisting of all Center Principal Investigators and an NICHD Project Scientist from the RSB, CPR. The Steering Committee will employ a consensus decision process to guide the SCCPIR in evaluating the progress of member Center programs, their proposed new research initiatives within the general scope of the approved program, the need to provide the entire SCCPIR network of centers with access to new technologies, the need for collaborations either within or outside the SCCPIR network, and the need to redirect certain efforts of member Centers due to either sufficient data acquisition to permit conclusion, the acquisition of data supporting an alternative study initiative or experience proving that the proposed research is no longer feasible, or, in the case of SCCPIR-wide resources, lack of utilization.

In addition to the Steering Committee, smaller cooperative groups will be formed that consist of research components of member centers having common research interests addressing a specific basic and/or clinical research problem. These Research Focus Groups will perform coordinated research activities as recommended by the SCCPIR Steering Committee, subject to peer review. In turn, progress of the Research Focus Groups will further guide the Steering Committee in decision making regarding changes in specific research directions, translational activities, collaborative research projects and support of new resources. The Research Focus Group will consist of an NICHD Staff liaison from the RSB, CPR, and Key Investigators of the relevant subproject and/or Core Directors.

Further details of the guidance and management structures and processes may be found under Section VI.2.A Cooperative Agreement Terms and Conditions of Award.

Travel to Meetings

Principal Investigators should request travel funds to support their participation in the annual Steering Committee Meeting as well as two research focus group meetings. Key Investigators of budgeted center subprojects and Directors of technical service cores should request travel funds to support participation in two research focus group meetings.

Research Strategy Page Limitations

The Research Strategy section may not exceed 12 pages for each project and 6 pages for each core and pilot project, including tables, graphs, figures, diagrams and charts.

Appendix Materials

All paper PHS 398 applications submitted must provide appendix material on CDs only. Include five identical CDs in the same package with the application. See http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-031.html.

Do not use the Appendix to circumvent the page limitations. An application that does not observe the required page limitations may be delayed in the review process.

NIH considers the sharing of unique research resources developed through NIH-sponsored research an important means to enhance the value of, and advance research. When resources have been developed with NIH funds and the associated research findings published or provided to NIH, it is important that they be made readily available for research purposes to qualified individuals within the scientific community. If the final data/resources are not amenable to sharing, this must be explained in Resource Sharing section of the application. See http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm.

(a) Data Sharing Plan: Investigators seeking $500,000 or more in direct costs in any year are expected to include a brief 1-paragraph description of how final research data will be shared, or explain why data-sharing is not possible. Applicants are encouraged to discuss data-sharing plans with their NIH program contact. See Data-Sharing Policy or http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html.

(b) Sharing Model Organisms: Regardless of the amount requested, all applications where the development of model organisms is anticipated are expected to include a description of a specific plan for sharing and distributing unique model organisms and related resources, or state appropriate reasons why such sharing is restricted or not possible. See Sharing Model Organisms Policy, and NIH Guide NOT-OD-04-042.

(c) Genome-Wide Association Studies (GWAS): Regardless of the amount requested, applicants seeking funding for a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible. A genome-wide association study is defined as any study of genetic variation across the entire genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight) or the presence or absence of a disease or condition. For further information see Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088, and http://grants.nih.gov/grants/gwas/.

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process.

2. Review and Selection Process

Applications that are complete and responsive to the FOA will be evaluated for scientific and technical merit by an appropriate peer review group convened by NICHD and in accordance with NIH peer review procedures (http://grants1.nih.gov/grants/peer/), using the review criteria stated below.

As part of the scientific peer review, all applications will:

• 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 impact/priority score.
• Receive a written critique.
• Receive a second level of review by the National Advisory Child Health and Human Development Advisory Council.

The following will be considered in making funding decisions:

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

The mission of the NIH is to support science in pursuit of knowledge about the biology and behavior of living systems and to apply that knowledge to extend healthy life and reduce the burdens of illness and disability. As part of this mission, applications submitted to the NIH for grants or cooperative agreements to support biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

Individual Research Projects

Overall Impact. Reviewers will provide an overall impact/priority 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 five core review criteria, and additional review criteria (as applicable for the project proposed).

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

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

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

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

If the project involves clinical research, are the plans for 1) Protections for Human Subjects, 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?

Core Units

• Are the qualifications, experience, and commitment of the core director and other core personnel appropriate?
• Will the quality of services provided enable center investigators to achieve their research goals?
• Is there cost effectiveness in the core; Will there be quality control measures taken for core procedures?
• Is the use of core services by the budgeted center projects and, if applicable, by external projects appropriate?
• Are plans for charge back and priority management procedures for core units offering services to external projects adequate?
• For the Administrative Core: Does the core director have experience in research administration? Is there a decision-making process within the proposed center for the evaluation of research productivity, for allocation of funds and for management of the resources? Is there a plan for center evaluation, including the use of any internal and external advisory groups?
• For the Outreach/Education 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 SCCPIR, a greater appreciation for research progress made as a result of funding and a better understanding of the implications of SCCPIR-supported research for reproductive health? Are efforts made to include community representatives on advisory committees?

NIH considers the following in evaluating Center grant applications:

• The scientific and technical merit of the proposed program;
• The qualifications and experience of the center director and other key personnel;
• The statutory and program purposes to be accomplished;
• The extent to which the various components of the proposed program would be coordinated into one multi-disciplinary effort within the center;
• The extent to which the center's activities would be coordinated with similar efforts by other organizations;
• The administrative and managerial capability of the applicant; and
• Other factors which the awarding IC considers appropriate in light of its particular statutory mission

Center as an Integrated Effort

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

For Renewal Applications:

• Has the center effectively conducted translational research where translation is defined as knowledge transfer from non-human animal models to humans?
• Has the center participated in collaborative research activities within the center network?

Additional Review Considerations

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

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

Select Agents 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).

Applications from Foreign Organizations. Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

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 (http://grants.nih.gov/grants/policy/data_sharing/data_sharing_guidance.htm); 2) Sharing Model Organisms (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-042.html); and 3) Genome Wide Association Studies (GWAS) (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html).

3. Anticipated Announcement and Award Dates

Not applicable

Section VI. Award Administration Information

1. Award Notices

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.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization. The NoA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NoA will be generated via email notification from the awarding component to the grantee business official.

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. See Also Section IV.5. Funding Restrictions.

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 (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part4.htm) and Part II Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part9.htm).

The following Terms and Conditions will be incorporated into the award statement and will be provided to the Principal Investigator as well as to the appropriate institutional official, at the time of award.

2.A. Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS 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.

2. A.1. Principal Investigator Rights and Responsibilities

The Principal Investigator will have the primary responsibility for:

• Pursue research objectives consistent with the research scope of the FOA and research favorably recommended by peer review;
• Conduct experiments and collect the resulting data;
• Analyze, interpret and present results and plans to the Steering Committee for approved activities;
• Publish results, conclusions, and interpretation of the studies. The awardees will agree to: 1) accept the coordinating role of the Steering Committee which includes evaluating objectives and research goals of the Centers Program, and recommending modification, deletion or addition of protocols within the Centers Program; 2) follow any common protocols in which they participate for multicenter projects that are approved by the Steering Committee; and 3) accept the cooperative nature of the group process, including the establishment, where appropriate, of smaller collaborative groups comprised of interacting subprojects and/or cores focused on a particular reproductive research topic area.

Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.

2. A.2. NIH Responsibilities

An NIH Project Scientist will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below.

• Participating in the overall coordination of the SCCPIR with the Steering Committee. This includes efforts to improve and strengthen inter- and intra-center cooperation amongst the research projects of the Centers, particularly as it pertains to translational research activities within and between centers. As a means of improving inter-center cooperation, the Project Scientist will directly participate in the activities of the smaller collaborative groups established by the Steering Committee comprising subprojects and/or cores focused on a particular reproductive research topic area. The Project Scientist will also assist the research efforts of the SCCPIR by facilitating access to fiscal and intellectual resources provided by industry, private foundations and NIH intramural scientists. The Project Scientist will, as required, help reprogram research efforts, including options to modify or terminate them, by mutual consent between the Centers Program and NICHD. In the event of disagreements among the Program participants, the Project Scientist will assist in forming an arbitration panel as discussed below.
• Interacting with each individual center awardee evaluating objectives and research goals of that particular center, deciding optimal research approaches and protocol designs, and contributing to the adjustment of research protocols or approaches as warranted. The Project Scientist will assist and facilitate this process and not direct it. The Project Scientist will also provide assistance in reviewing and commenting on all major transitional changes of an individual center's activities prior to implementation to assure consistency with required goals of the SCCPIR.
• Retaining the option to recommend the withholding of support from a Center subproject or core materially failing to meet the technical performance requirements established by this Centers Program. This includes identifying jointly with participants of the Steering Committee the need to add additional research subprojects or service cores to Centers or to phase out a Center subproject or core when performance standards have not been met; and
• Participating, where warranted, in data analyses, interpretations, and the dissemination of study findings to the research community and health care recipients including co-authorship of the publication of results of studies conducted by the Centers.

Additionally, an NICHD Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

2.A.3. Collaborative Responsibilities (optional)

Overall Coordination of the Centers Program consistent with the stated intent of the RFA will be done by a Steering Committee consisting of the Principal Investigators from each of the participating Centers and one NICHD staff member from the RSB, CPR, NICHD, who will be the Project Scientist. A member of the NICHD grants management staff will serve as a nonvoting advisor to the Committee. A non-NIH chairperson for the Steering Committee will be chosen by a majority vote of the Principal Investigators. The Steering Committee meetings will be convened at least once per year. The purpose of these meetings is to share scientific information, assess scientific progress, identify new research opportunities and potential avenues of collaborations such as with industry, private foundations and/or NIH intramural scientists, establish priorities that will accelerate the translation of preclinical findings into clinical applications, reallocate resources and conduct the business of the cooperative research program. In anticipation that some centers will have common research interests that address a specific basic and/or clinical research problem, it is envisioned that research focus groups will be formed to conduct coordinated research activities recommended by the Steering Committee. The Steering Committee will approve multicenter protocols on specific research activities. As needed, the Steering Committee will develop a publication policy regarding joint authorship of research reports derived from such collaborative efforts.

Each full member will have one vote. Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.

2.A.4. Arbitration Process

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 arbitration. An Arbitration 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 arbitration procedure in no way affects the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations 42 CFR Part 50, Subpart D and HHS regulations 45 CFR Part 16.

3. Reporting

Awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and Financial Status Report are required when an award is relinquished when a recipient changes institutions or when an award is terminated.

Section VII. Agency Contacts

We encourage your inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into three areas: scientific/research, peer review, and financial or grants management issues:

1. Scientific/Research Contacts:

Louis V. DePaolo, Ph.D.
Reproductive Sciences Branch
Center for Population Research
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
6100 Executive Boulevard, Room 8B01, MSC 7510
Bethesda, MD 20892-7510
Rockville, MD 20852 (for express/courier service; non-USPS service)
Telephone: (301) 435-6970
FAX: (301) 480-2389
Email: [email protected]

2. Peer Review Contacts:

Robert Stretch, Ph.D.
Director, Division of Scientific Review
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institutes of Health (NIH)
6100 Executive Boulevard, Room 5B01, MSC 7510
Bethesda, MD 20892-7510
Rockville, MD 20852 (for express/courier service; non-USPS service)
Telephone: 301-496-1485
FAX: 301-402-4104
Email: [email protected]

3. Financial or Grants Management Contacts:

Ms. Cecilia Bruce
Grants Management Branch
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
6100 Executive Boulevard, Room 8A17L, MSC 7510
Bethesda, MD 20892-7510
Rockville, MD 20852 (for express/courier service; non-USPS service)
Telephone: (301) 496-1304
FAX: (301) 480-4782
Email: [email protected]

Section VIII. Other Information

Required Federal Citations

Vertebrate Animals:
Recipients of PHS support for activities involving live, vertebrate animals must comply with PHS Policy on Humane Care and Use of Laboratory Animals (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf) as mandated by the Health Research Extension Act of 1985 (http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA Animal Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm) as applicable.

Human Subjects Protection:
Federal regulations (45CFR46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

Data and Safety Monitoring Plan:
Data and safety monitoring is required for all types of clinical trials, including physiologic toxicity and dose-finding studies (phase I); efficacy studies (Phase II); efficacy, effectiveness and comparative trials (Phase III). Monitoring should be commensurate with risk. The establishment of data and safety monitoring boards (DSMBs) is required for multi-site clinical trials involving interventions that entail potential risks to the participants (NIH Policy for Data and Safety Monitoring, NIH Guide for Grants and Contracts, http://grants.nih.gov/grants/guide/notice-files/not98-084.html).

Sharing Research Data:
Investigators submitting an NIH application seeking $500,000 or more in direct costs in any single year are expected to include a plan for data sharing or state why this is not possible (http://grants.nih.gov/grants/policy/data_sharing).

Investigators should seek guidance from their institutions, on issues related to institutional policies and local IRB rules, as well as local, State and Federal laws and regulations, including the Privacy Rule. Reviewers will consider the data sharing plan but will not factor the plan into the determination of the scientific merit or the impact/priority score.

Policy for Genome-Wide Association Studies (GWAS):
NIH is interested in advancing genome-wide association studies (GWAS) to identify common genetic factors that influence health and disease through a centralized GWAS data repository. For the purposes of this policy, a genome-wide association study is defined as any study of genetic variation across the entire human genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight), or the presence or absence of a disease or condition. All applications, regardless of the amount requested, proposing a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible. Data repository management (submission and access) is governed by the Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088. For additional information, see http://grants.nih.gov/grants/gwas/.

Access to Research Data through the Freedom of Information Act:
The Office of Management and Budget (OMB) Circular A-110 has been revised to provide access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are (1) first produced in a project that is supported in whole or in part with Federal funds and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this funding opportunity in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award.

Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with Federal funding pursuant to the Bayh Dole Act (see the NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/index.htm). All investigators submitting an NIH application or contract proposal, beginning with the October 1, 2004 receipt date, are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.

Inclusion of Women, Minorities, and Children:
It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH-supported clinical research projects unless a clear and compelling justification is provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing clinical research should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the new PHS Form 398; and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences.

Inclusion of Children as Participants in Clinical Research:
The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all clinical research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them.

All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines" on the inclusion of children as participants in research involving human subjects (http://grants.nih.gov/grants/funding/children/children.htm).

Required Education on the Protection of Human Subject Participants:
NIH policy requires education on the protection of human subject participants for all investigators submitting NIH applications for research involving human subjects and individuals designated as key personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

Human Embryonic Stem Cells (hESC):
Criteria for federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-09-116.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (http://escr.nih.gov). It is the responsibility of the applicant to provide in the project description and elsewhere in the application as appropriate, the official NIH identifier(s) for the hESC line(s) to be used in the proposed research.

NIH Public Access Policy Requirement:
In accordance with the NIH Public Access Policy (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-033.html) investigators must submit or have submitted for them their final, peer-reviewed manuscripts that arise from NIH funds and are accepted for publication as of April 7, 2008 to PubMed Central (http://www.pubmedcentral.nih.gov/), to be made publicly available no later than 12 months after publication. As of May 27, 2008, investigators must include the PubMed Central reference number when citing an article in NIH applications, proposals, and progress reports that fall under the policy, and was authored or co-authored by the investigator or arose from the investigators NIH award. For more information, see the Public Access webpage at http://publicaccess.nih.gov/.

Standards for Privacy of Individually Identifiable Health Information:
The Department of Health and Human Services (DHHS) issued final modification to the "Standards for Privacy of Individually Identifiable Health Information", the "Privacy Rule", on August 14, 2002. The Privacy Rule is a federal regulation under the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable health information, and is administered and enforced by the DHHS Office for Civil Rights (OCR).

Decisions about applicability and implementation of the Privacy Rule reside with the researcher and his/her institution. The OCR website (http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including a complete Regulation Text and a set of decision tools on "Am I a covered entity?" Information on the impact of the HIPAA Privacy Rule on NIH processes involving the review, funding, and progress monitoring of grants, cooperative agreements, and research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. For publications listed in the appendix and/or Progress report, internet addresses (URLs) must be used for publicly accessible on-line journal articles. Unless otherwise specified in this solicitation, Internet addresses (URLs) should not be used to provide any other information necessary for the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site.

Healthy People 2010:
The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This FOA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

Authority and Regulations:
This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive Order 12372. 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 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The NIH Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.

The PHS strongly encourages all grant recipients to provide a smoke-free workplace and discourage the use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care, or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.

Loan Repayment Programs:
NIH encourages applications for educational loan repayment from qualified health professionals who have made a commitment to pursue a research career involving clinical, pediatric, contraception, infertility, and health disparities related areas. The LRP is an important component of NIH's efforts to recruit and retain the next generation of researchers by providing the means for developing a research career unfettered by the burden of student loan debt. Note that an NIH grant is not required for eligibility and concurrent career award and LRP applications are encouraged. The periods of career award and LRP award may overlap providing the LRP recipient with the required commitment of time and effort, as LRP awardees must commit at least 50% of their time (at least 20 hours per week based on a 40 hour week) for two years to the research. For further information, please see: http://www.lrp.nih.gov.

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