Department of Health and Human Services

Part 1. Overview Information
Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

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

Funding Opportunity Title

Cooperative Multicenter Reproductive Medicine Network (U10)

Activity Code

U10 Cooperative Clinical Research – Cooperative Agreements

Announcement Type

Reissue of RFA-HD-06-008

Related Notices

None

Funding Opportunity Announcement (FOA) Number

RFA-HD-13-016

Companion Funding Opportunity

None

Number of Applications

See Section III. 3. Additional Information on Eligibility.

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

93.865 

Funding Opportunity Purpose

The purpose of this funding opportunity announcement (FOA) is to announce the recompetition of the Cooperative Multicenter Reproductive Medicine Network (RMN). The NICHD invites applications from investigators willing to participate, with the assistance of the NICHD under cooperative agreements, in an ongoing multicenter cooperative program designed to conduct clinical studies to investigate problems in reproductive medicine including female and male infertility, gynecologic and male reproductive system diseases and disorders that impact fertility, problems in andrology and endocrinology affecting reproduction. The objective of this program is to facilitate diagnostic and therapeutic solutions to these problems by maintaining a clinical research network of sites that use common protocols in large scale human trials to obtain answers to important clinical problems more rapidly than individual sites acting alone. This network benefits the public: infertile couples, individuals with reproductive diseases and disorders, and their health care providers.

Key Dates
Posted Date

July 30, 2010

Letter of Intent Due Date

September 29, 2012

Application Due Date(s)

November 29, 2012

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

February/March 2013

Advisory Council Review

May 2013

Earliest Start Date(s)

July 2013

Expiration Date

November 30, 2012

Due Dates for E.O. 12372

Not Applicable.

Required Application Instructions

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

Table of Contents

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

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Purpose

The purpose of this funding opportunity announcement (FOA) is to announce the recompetition of the Cooperative Multicenter Reproductive Medicine Network (RMN). The NICHD invites applications from investigators willing to participate, with the assistance of the NICHD under cooperative agreements, in an ongoing multicenter cooperative program designed to conduct clinical studies to investigate problems in reproductive medicine including female and male infertility, gynecologic and male reproductive system diseases and disorders that impact fertility, problems in andrology and endocrinology affecting reproduction. The objective of this program is to facilitate diagnostic and therapeutic solutions to these problems by maintaining a clinical research network of sites that use common protocols in large scale human trials to obtain answers to important clinical problems more rapidly than individual sites acting alone. This network benefits the public: infertile couples, individuals with reproductive diseases and disorders, and their health care providers.

Objectives

The NICHD supports scientific research aimed at alleviating human infertility, uncovering new contraceptive leads and expanding fundamental knowledge of processes that underlie human reproduction. To this end, the Reproductive Medicine Network (RMN) performs clinical and translational studies that will enhance the understanding of normal reproduction and reproductive pathophysiology, as well as enable the development of more effective strategies for the diagnosis, management and prevention of infertility. Applications are sought from investigators who are willing to participate, with the assistance of staff of NICHD under cooperative agreements, in an ongoing multicenter cooperative program designed to conduct clinical studies investigating problems in reproductive medicine, including conditions that cause, contribute to, or are associated with infertility, outcomes of infertility treatments, and gynecological diseases and disorders and those of the male reproductive system that affect fertility. Disorders in the endocrinological system that influence reproduction are also within the scope of investigation for the RMN. The objective of this program is to facilitate resolution of these problems by maintaining a network of sites that, by rigorous patient evaluation using common protocols, can study large numbers of patients and provide clinically meaningful and statistically valid answers more rapidly than individual sites acting alone.

The dissemination of study results is intended to replace empiric treatment, often used in many aspects of reproductive medical care today, with scientifically substantiated evidence-based, cost-effective, and patient-centered care. In addition, the RMN is a resource for the training of early career clinician scientists in reproductive medicine to become future clinical investigators through mentorship and by fostering involvement in ongoing clinical trials of the RMN. In turn, these junior investigators facilitate the conduct of trials by the RMN, increase patient and geographic diversity and enhance efforts by the network to advance clinical practice.

The NICHD invites applications from both current members of the RMN (renewal applications) and from prospective members (new applications).

Background

The RMN was established in 1989 to carry out large, multicenter clinical trials to address male and female infertility and reproductive diseases and disorders because of the paucity of medical evidence for most treatments of infertility and reproductive disorders. In the 15 years preceding the current funding period, the RMN conducted four trials on the efficacy of treatment of unexplained infertility with superovulation and intrauterine insemination, semen analysis as a measure of fertility, the utility of endometrial biopsy in the infertility evaluation, and the efficacy and safety of clomiphene citrate alone or in combination with metformin as a treatment for infertility associated with polycystic ovary syndrome (PCOS).

In the current funding period, the RMN has executed three comparative effectiveness trials simultaneously: the PPCOS II (Pregnancy in Polycystic Ovary Syndrome II) trial investigates the safety and efficacy of letrozole compared to clomiphene citrate for treatment of infertility in PCOS; the PhOx (The Effects of Physiologic Oxygen Tension on Clinical In Vitro Fertilization Outcomes) trial compares the efficacy and safety of two standards of practice( physiologic oxygen tension and room air) as culture conditions for in vitro fertilization (IVF); and the AMIGOS (Assessment of Multiple Intrauterine Gestations Following Ovarian Stimulation) trial investigates treatments for unexplained infertility to identify the most effective with the lowest risk of multiple gestations. Two additional male protocols have been fully developed, but not implemented, and ancillary studies have begun to address issues in male infertility. A Pregnancy Registry has been implemented as an observational study to evaluate early child outcomes associated with infertility treatments. Additionally behavioral outcomes and quality of life measures are being studied. The RMN has also established a bio-specimen repository to enable sharing of samples with investigators outside the network to facilitate ancillary studies to be undertaken with the well-characterized data sets and specimens collected.The RMN has also served as a resource for training new clinical investigators with the expansion of the network studies to include mentorship and collaboration with the Clinical Research Reproductive Scientist Training (CREST) program scholars.

Infertility affects approximately 12 % of reproductive-aged couples. Approximatey 2 million couples in the US and 6.1 million women have difficulty conceiving or staying pregnant. Women are delaying pregnancy until later age and medical visits for evaluation and treatment of infertility have increased. Unsubstantiated diagnostic and therapeutic methods have led to undeserved claims of efficacy and resulted in substantial costs, both psychological and economic. Causes of infertility are multifactorial involving both male and female factors, and may be modulated by environmental factors, such as exposure to chemicals or smoking; physical factors, such as endometriosis or obesity; and medications and supplements that impact production of sperm or mature eggs, and affect hormonal production. The development of new medications and technologies requires evaluation for safety and efficacy which is best achieved through the conduct of large clinical trials. As such, there continues to be a need for a clinical research network devoted to problems in infertility with the capability to undertake large scale human trials to answer questions with adequate statistical power for meaningful findings.

Many gynecologic conditions in women of reproductive age such as PCOS, endometriosis, leiomyomata uteri, and pelvic infection may adversely affect fertility. These conditions may interfere with function in the home and workplace, and reduce quality of life as well as fertility, resulting in billions of dollars in healthcare expenditures. Many of these conditions and co-morbidities disproportionately affect women of racial and ethnic minorities. There is a need to develop and assess alternative management strategies to improve treatment outcomes and quality of life in women and families.

Obesity has reached epidemic proportions and is a great public health concern. More than one-third of US adult men and women are obese. In observational trials, obesity is directly associated with ovulatory disturbances and early pregnancy loss, lower likelihood of conception from fertility treatments including assisted reproductive technologies and significantly reduced odds of live birth. Controversy exists as to whether obesity affects fertility in men. Safe and effective treatments are needed to improve reproductive outcomes in this population.

Treatment for infertility with IVF has been available in the US since 1981. Currently more than 1% of infants born are conceived with assisted reproductive technology (ART). Although highly successful, these treatments continue to result in high multiple pregnancy rates, increased pregnancy complications and preterm delivery of low and very low birth weight infants, even in ART singleton pregnancies. Methods that maintain high pregnancy and live birth rates but reduce multiple gestation and adverse perinatal outcomes are needed.

Scope

The NICHD plans to extend the RMN, through a competitive, peer-reviewed process, for an additional five years to support clinical trials in reproductive medicine. This initiative requires clinical sites with the infrastructure and clinical capacity to support clinical trials in reproductive medicine and which may collaborate with ancillary clinical sites, both foreign and within the US including NICHD intramural laboratories. Each RMN clinical site is expected to cooperate with the Data Coordinating Center (DCC) and NICHD staff to design and conduct clinical trials relevant to reproductive medicine.

Projects responsive to this solicitation should address clinical problems in reproductive medicine, including infertility, gynecological diseases and disorders, diseases and disorders of the male reproductive system, and disorders in reproductive endocrinology. Clinical issues which are considered to have high programmatic interest to the NICHD include but are not limited to those listed below:

Guidance and Management Structure of Clinical Sites

The Network will include "Reproductive Medicine Units" (RMUs) and a Data Coordinating Center (DCC). The RMUs are responsible for the identification of priority areas for research, with input from the Steering Committee (SC), the Advisory Board (AB) and NICHD staff; developing and implementing the Network protocols, recruitment, screening, and enrollment of subjects into approved protocols; conducting the protocols; collection and transmission of data to the DCC; and analysis of the data and timely publication of the results in peer-reviewed journals. The DCC will have primary responsibility for clinical trial management, data management and data analysis for each trial. A separate competition will be held for the DCC.

A member of NICHD program staff, serving as Project Scientist, will cooperate with the funded PD(s)/PI(s) in identifying research topics of high priority and in designing protocols appropriate to the evaluation of optimum management in these areas.

Steering Committee

The SC will consist of the PD(s)/PI(s) from each RMU, the PD(s)/PI(s) of the DCC, the NICHD staff Project Scientist, and a nongovernment chairperson to be designated by the SC. A member of the NICHD grants management staff will serve as an advisor to the SC. The SC will develop by consensus the protocols to be carried out under these cooperative agreements, and oversee the conduct of the studies.

Advisory Board

The AB is an external independent group that advises the SC on the scientific merit and impact of proposed studies. The AB also may suggest reproductive medicine topics to be studied by the RMN and advises the NICHD and SC of overall Network performance. The AB is composed of experts selected by the NICHD with the advice of the SC Chairperson, and may include members with expertise in the following: clinical trial design, biostatistics, epidemiology, reproductive endocrinology and infertility, gynecology and urology/andrology.

Data Safety and Monitoring Board

A DSMB convened by the NICHD will have responsibility for reviewing proposed clinical protocols, and for making a recommendation to the NICHD whether to accept, modify, or decline such proposed studies. The DSMB will enlist additional ad hoc scientific and/or clinical experts as needed to conduct each review. The DSMB will monitor data collection and analysis by the DCC, including any reports of adverse effects. When appropriate, the DSMB will conduct an interim evaluation of the data with respect to the need to terminate studies, either because the data suffice to answer the problems posed, data collection provides support for an alternative study initiative, or because experience has proven the research not to be feasible.

Time Sequence

It is anticipated that the Network will conduct its activities according to this general outline: Initially, the SC will review and identify issues of importance in reproductive medicine. It will consider items proposed for study by the Network from those listed above in "Scope" and others suggested by participating units. There will be two domains within the Network: Infertility/Andrology and Infertility/Gynecology which are intended to encompass male factor, female factor, and unknown cause. Ideally, the Network will identify a protocol from each domain, with one RMU acting as lead unit for each protocol. A protocol involving ART may be implemented as well. Within each of the Infertility/Andrology and Gynecology domains, the SC will rank by priority issues that are substantive, lie within the scope of existing technical capability, lend themselves to multicenter evaluation, involve sufficient numbers of participants to be of consequence in terms of morbidity, and comprise significant public health need.

From the list of important issues for each domain, the SC will generate diagnostic or treatment protocols and agree on lead units. Each protocol is to be acceptable to all the participants, adequate for appraisal of the research issues defined, and amenable to data collection in a common format. Protocol subcommittees may be constituted to develop protocols more efficiently. The protocols will be reviewed by the AB and the DSMB appointed by the NICHD prior to implementation.

Participating RMUs will recruit, screen and enroll subjects into the trials. The units will supervise the collection of data with adequate attention to the accuracy and quality of records and transcription, providing information in uniform data format for analysis. The mode of data transmission and analysis will be determined by the SC in conjunction with the recommendations of the DCC. Data summaries will be provided to the DSMB on a semi-annual basis, or as indicated by study protocol. Format and content of final reports and the dissemination of information to the scientific community will be determined by the SC.

SPECIAL REQUIREMENTS

Program Director(s)/Principal Investigator(s) [PD(s)/PI(s)]

Reproductive Medicine Units

Other Staff and Facilities

Department and Institutional Commitments

Concept Protocol

Because the protocols for investigation will not be written until after awards are made, it is not possible for RMU applicants to propose the exact work that they would actually carry out if funded. All applicants must submit a "concept" protocol for a new study that the site might expect to conduct as a participant in the Network. Applicants should note carefully that the "concept" study proposed may or may not actually be performed by the Network as one of its protocols, but is requested to serve as an indicator of the applicant's ability to participate in the development and design of protocols for cooperative clinical investigations. The concept protocol should describe one study that necessitates a multicenter approach, including background and significance, objectives, study design, and data analysis including considerations of sample size, power and statistical model. The protocol should estimate numbers of subjects potentially eligible at the applicant’s institution and should address the inclusion of women, minorities, and children as subjects. The research strategy section of the concept protocol will be limited to twelve pages and must summarize a project that could potentially be undertaken by the RMN. The SC may consider the "concept" protocols submitted by the funded RMU sites in its determination of topics for actual protocols.

For purposes of this FOA only, the "concept" protocol may address but is not limited to one of the following topics:

The choice of a "concept" topic from one domain (e.g., gynecology, andrology) will not necessarily limit the participation of an RMU in the other domain in the event that it is funded. The protocol should be written specifically for this Network, and will be a factor in evaluation of the application.

Access to Adequate Patient Population

Applications should indicate the numbers of patients seen annually for infertility overall and for the other categories of reproductive health diagnoses. The applicant should describe the demographics of the population from which they expect to recruit their clinical subjects and plans for recruitment of women, minorities, and children. The applicant should include a brief discussion of previous relevant efforts and their specific plans for recruitment and retention of research subjects.

New Applications

Prospective applicants must address their recent experience and participation in randomized clinical trials and other studies, preferably of a cooperative, multi-site nature. Specific roles should be described for each study and research presentations and publications should be listed.

Renewal Applications

Renewal applications should describe the site’s participation and contribution to the Network in detail, including subject enrollment in all studies, involvement in protocol development and their particular contribution to each study (e.g., PD/PI at site, participation on protocol and manuscript committees), collaborative Network activities, research presentations and publications.

The following requirements are highly desirable:

Intent to Participate

The RMN will be a collaborative effort that will require frequent interaction of awardees among themselves and the NICHD. Applicants must explicitly indicate their willingness to: participate in Steering Committee meetings (see Section VI, 2A, Cooperative Agreement Terms and Conditions of Award) and regular telephone conference calls; cooperate with other awardees in the development and design of research protocols; abide by common definitions, common methods for patient selection and enrollment, and common protocols, procedures, tests, as chosen by majority vote of the SC; comply with data reporting procedures and timelines; comply with study policies and quality assurance measures approved by the SC; agree to oversight of the study by a DSMB; report all adverse events in accordance with procedures established by the SC and NIH policies; and cooperate with other awardees in the publication of study results.

Section II. Award Information
Funding Instrument

Cooperative Agreement

Application Types Allowed

New
Renewal from RFA-HD-06-008

The OER Glossary and the PHS398 Application Guide provide details on these application types.

Funds Available and Anticipated Number of Awards

The NICHD intends to commit approximately $2.5 million in total costs [Direct plus Facilities and Administrative (F & A) costs] in FY 2013 to fund up to seven new and/or renewal applications in response to this FOA.

Award Budget

Overall Budget - An applicant for a RMU may request a project period of up to five years and a budget for direct costs not to exceed $200,000 for the first and second years with incremental increases for recurring costs (i.e., personnel, consultants, supplies, travel and other expenses), and direct costs not to exceed $250,000 in years 3 through 5 with incremental increases for recurring years. Applications exceeding the budgetary limits specified above will be returned to the applicant without peer review. Increases in outyear budgets for recurring costs are subject to the availability of funds.

Applicants should request funds to support:

  • PD/PI : 2.4 person-months (20 percent) effort
  • Co-investigators: up to 1.2 person-months (10 percent) effort each
  • Research Coordinator: 12 person-months (100 percent) effort
  • Travel (a total of three trips annually to Bethesda, MD for PD/PI, co-investigator and research coordinator and one trip annually for PD/PI to NICHD Center Director's meeting)
  • Supplies and advertising for protocol recruitment
  • The budget may also include infrastructure costs to support a half-time research coordinator at an ancillary clinical site starting in the third year.

Ongoing annual budgets for the RMN clinical sites will be based on individual protocols as approved by the SC with reimbursement of 'clinical trial research costs' based on a capitation system. Each RMN clinical site will be awarded base costs as described above in addition to funds from the Data Coordinating Center that represents per protocol costs, i.e. a flat fee for each subject successfully enrolled and completed for each study. The PD/PI will be required to project subject enrollment for each specific protocol during a specified time frame, although continuation and the level of funding will be based on actual enrollment.

Award Project Period

The maximum period of support is 5 years. Although the financial plans of the IC provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications.

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

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions

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

Nonprofits Other Than Institutions of Higher Education

For-Profit Organizations

Governments

Other

Foreign Institutions   

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

Required Registrations

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

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

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

Eligible Individuals (Program Director(s)/Principal Investigator(s))

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

For institutions/organizations proposing multiple PD(s)/PI(s), visit the Multiple Program Director(s)/Principal Investigator(s) Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the PHS398 Application Guide.

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application.

Section IV. Application and Submission Information

1. Address to Request Application Package

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

2. Content and Form of Application Submission

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

Letter of Intent

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

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

The letter of intent should be emailed to:

Esther Eisenberg, MD MPH
Project Scientist, Reproductive Medicine Network
Reproductive Sciences Branch
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Bethesda, MD 20892-7510
Email:eisenbes@mail.nih.gov

Application Submission

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

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

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

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

Page Limitations

All page limitations described in the PHS398 Application Guide and the Table of Page Limits must be followed,

Research Plan

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

Resource Sharing Plan

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

Appendix

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

3. Submission Dates and Times

Part I. Overview Information contains information about Key Dates. 

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

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

4. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

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

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

6. Other Submission Requirements and Information

Applications must be postmarked on or before the due dates in Part I. Overview Information.

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

Post Submission Materials

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

Section V. Application Review Information

1. Criteria

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

For this particular announcement, note the following:

For NICHD Reproductive Medicine Unit Clinical Site applications, peer review of scientific and technical merit  emphasizes (1) qualifications and experience of the PD(s)/PI(s), co-investigators and staff in conducting clinical trials, (2) the institutional environment; (3) review of the Concept protocol; (4) access and ability to recruit study populations; and (5) the scope and variety of the research strengths to enable a successful collaborative program.

Final selection of the Clinical Sites for funding may be partly based on the need for diversity, including geography and special populations.

Overall Impact - Overall

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

Scored Review Criteria - Overall

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a concept protocolt 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(s)/PI(s), collaborators, and other researchers well suited to the Network? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD(s)/PI(s), do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project? Do the PD(s)/PI(s) have experience in implementing, recruiting for and conducting clinical trials?  Do(es) the PD(s)/PI(s) have experience with multicenter clinical trials? Do the PD(s)/PI(s) have knowledge and experience in areas relevant to reproductive medicine?

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) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?   

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements? Department and institutional commitment: willingness and ability to participate in the Network, including applicant institution’s history of collaborative research, depth of commitment, willingness to randomize subjects, and ability to work with other Network sites.   

Additional Review Criteria - Overall

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

1) Qualifications and experience of the PD(s)/PI(s), co-investigator and staff: the expertise, training and experience of the PD(s)/PI(s) and the research team in the conduct of clinical trials, particularly cooperative, randomized clinical trials; commitment of staff time for the satisfactory conduct of Network activities; experience and qualifications of team members responsible for subject recruitment, enrollment, data collection and data management

2) Patient access and study population: plans for recruitment and retention of subjects; plans to ensure appropriate representation by ethnicity, age and gender

3) Institutional environment: adequacy of institutional resources including personnel, space, administrative support (fiscal management support, personnel management, procurement and budgeting);

4) Concept protocol: evaluation of the proposed protocol in terms of quality and relevancy of proposed hypotheses, background and significance, objectives, study design, and data analysis (including considerations of sample size, power and statistical model).

New Applications: level of experience and participation in randomized clinical trials including multicenter studies.

Renewal applications: evidence of successful past performance as a clinical site in the RMN. Reviewers will be asked to comment on the re-competing sites’ effectiveness at: site performance in past and current clinical trials, including protocol development, successful subject recruitment, data quality, and subject follow-up; presentation and publication record; and cooperation in a multi-center network, and the effectiveness of the PD(s)/PI(s) in providing site leadership and  cooperating with all aspects of the RMN.

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Children 

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

Vertebrate Animals

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

Biohazards

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

Resubmissions

Not Applicable.

Renewals

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

Revisions

Not Applicable.

Additional Review Considerations - Overall

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

Applications from Foreign Organizations

Not Applicable..

Select Agent Research

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

Resource Sharing Plans

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

Budget and Period of Support

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

2. Review and Selection Process

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

As part of the scientific peer review, all applications:

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

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

3. Anticipated Announcement and Award Dates

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

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

Section VI. Award Administration Information

1. Award Notices

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

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

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

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

2. Administrative and National Policy Requirements

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

Cooperative Agreement Terms and Conditions of Award

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

The administrative and funding instrument used for this program will be the cooperative agreement (NIH Cooperative Clinical Research for Clinical Sites [U10]), an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below

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

Identifying priority areas for research, with input from the Steering Committee, the Advisory Board and NICHD staff; developing and implementing common research protocols; recruitment, screening and enrolling subjects into multicenter protocols approved by the Steering Committee; implementation and conduct of common protocols, collecting and transmitting data to the Data Coordinating Center (DCC); and analyzing, interpreting, presenting and publishing the findings of the RMN. The awardee will agree to accept the participatory and cooperative nature of the Reproductive Medicine Network.

The PD(s)/PI(s) and co-Investigators will be members of the Steering Committee and will be required to participate in all Steering Committee activities and to follow the policies and procedures that are developed by the Steering Committee.

The Steering Committee will evaluate objectives and research goals of the RMN, and recommend modification, discontinuation or addition of protocols within the RMN; and accept the cooperative nature of the group process, including the establishment, where appropriate, of smaller collaborative groups to facilitate the goals of the Network.

Each RMN clinical site will have one vote in all Steering Committee matters. The clinical site PD(s)/PI(s) will be required to provide primary study data to the DCC for management, quality control and analysis.

In addition the PD(s)/PI(s) are encouraged to establish mentoring relationships with clinical investigators.

Each site will participate in the Data and Specimen Repository of the RMN.

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

NICHD Project Scientist Roles:

The Project Scientist will participate in the overall coordination of the RMN with the Steering Committee. This includes efforts to improve and strengthen cooperation of the RMN Sties and DCC. The Project Scientist will interface with each of the PD(s)/PI(s), the DCC, the Steering Committee Chair, the Committee Coordinator and directly participate in research protocol development by participating in the activities of the smaller collaborative groups established by the Steering Committee. The Project Scientist will provide progress reports to the Advisory Board and communicate recommendations, as well as assist the research efforts of the RMN 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 Steering Committee and NICHD. In the event of disagreements among Program participants, the Project Scientist will assist in forming an arbitration panels.

The Project Scientist will interact with each individual center awardee, evaluating objectives and research goals of the Network, 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.

Retaining the option to recommend the withholding of support from a research project materially failing to meet the technical performance requirements established by this RMN. This includes identifying jointly with participants of the Steering Committee the need to add additional research projects or to phase out a research project when performance standards have not been met; and participating in data analyses, interpretations, and the dissemination of study findings to the research community and health care recipients including co-authorship of the publication or results of studies conducted by the RMN.

NICHD Program Official Role:

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

Areas of Joint Responsibility for PD(s)/PI(s) and the NICHD Project Scientist include:

Participating on a Steering Committee consisting of the PD(s)/PI(s) from each of the participating centers and one NICHD staff member from the NICHD, who will be the Project Scientist. A non-NIH Chairperson for the Steering Committee will be chosen by a majority vote of the PD(s)/PI(s). Meetings of the Steering Committee will be convened regularly to be held in-person and by teleconference. The purpose of these meetings is to share scientific information, monitor progress, identify new research opportunities and potential avenues of collaborations such as with other clinical researchers, industry, private foundations and/or NIH intramural scientists, establish priorities that will accelerate the translation of preclinical findings into clinical applications, participate in planning and conduct the business of the cooperative research program. The Steering Committee will provide input and approve multicenter protocols. The Steering Committee will develop a publication policy regarding joint authorship of research reports derived from the Network and collaborative efforts.

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

Advisory Board

An Advisory Board (AB), convened by the NICHD, will advise the Steering Committee in the identification and prioritization of topics and protocols for the RMN. The AB will be composed of senior scientists, not part of the Network, with expertise in obstetrics and gynecology, andrology, biostatistics, epidemiology, human genetics and clinical trial design. The Chairperson of the Steering Committee and the NICHD Project Scientist will serve as ex officio members of the AB. Additional members will participate as necessary for specific expertise.

Data and Safety Monitoring Board

A Data and Safety Monitoring Board will monitor the safety of ongoing clinical trials and advise on their conduct. This committee will be established by NICHD and consist of individuals with expertise in obstetrics and gynecology, andrology, biostatistics, epidemiology, population genetics, clinical trial design and ethics. This committee will focus on safety, ethics, and scientific and statistical integrity of both proposed and ongoing trials.

Data Coordination and Management

The RMN DCC will carry out data coordination and management. As described, each participating clinical site will be responsible for providing primary study data to the DCC for management, quality control and analysis. Specific analyses to be performed will be directed by the Steering Committee. The results of those analyses will be delivered to the Steering Committee and the Steering Committee is responsible for determining how the results are interpreted, whether the results should influence ongoing data collection, and how the findings should be disseminated. All participating sites will have access to all data originating from their sites.

Publication and Presentation

Timely publication of findings is required. Publications and oral presentations of work performed under this agreement will require appropriate acknowledgement of the participating institutions and NICHD support. Review and approval by the Steering Committee will be required for all analyses prior to publication or presentation according to criteria that will be developed by the Steering Committee.

Collaboration with the Specialized Cooperative Centers Program in Reproduction and Infertility Research (SCCPIR)

The PD/PIs of the clinical sites will be required to attend the annual SCCPIR research meeting. The purpose of this meeting is to familiarize the Network investigators to the latest developments in basic investigations in reproductive science and thereby facilitate translational development. Additionally, the Network will be expected to present their latest research findings to the SCCPIR investigators at this same annual meeting. For some proposed studies, certain SCCPIR sites may be provided the resources to serve as additional recruitment sites for RMN initiated protocols.

Dispute Resolution:

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

3. Reporting

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

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

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

Section VII. Agency Contacts

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

Application Submission Contacts

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

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

Scientific/Research Contact(s)

Esther Eisenberg, MD MPH
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 615-343-1082
Email: eisenbes@mail.nih.gov 

Peer Review Contact(s)

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

Financial/Grants Management Contact(s)

Teri Pailen
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-7010
Email: pailent@mail.nih.gov

Section VIII. Other Information

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

Authority and Regulations

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


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