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

Reproductive Medicine Collaborative Clinical Trials Program (Collaborative R01 Clinical Trial Required)

Activity Code

 Collaborative R01 Research Project Grant

Announcement Type

New

Related Notices
Funding Opportunity Announcement (FOA) Number

RFA-HD-19-022

Companion Funding Opportunity

None   

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

93.865  

Funding Opportunity Purpose

The NICHD invites applications from investigators to develop a multi-site project designed to conduct clinical trials to investigate problems in reproductive medicine, female and male infertility, and gynecologic and male reproductive system diseases and disorders that impact fertility. This funding opportunity announcement (FOA) is intended to support multi-site clinical research consortia devoted to evaluating safety and efficacy of new medications, treatments and technologies addressing questions in infertility.  The objective of this program is to advance scientific research that facilitates diagnostic and therapeutic solutions to infertility by using common protocols in large scale human trials to obtain answers more rapidly than individual sites acting alone. This program benefits the public: infertile couples, individuals with reproductive diseases and disorders, and their health care providers.

This FOA supports trials that require participation of two or more collaborative sites for completion of the study.  Accordingly, the collaborating sites share a specific protocol across the sites and are organized to increase sample size, accelerate recruitment, or increase sample diversity and representation.  Each site has its own Program Director/Principal Investigator (PD/PI) and each consortium includes a mechanism for coordination, implementation and monitoring of the protocol across sites, quality control, database management, statistical analysis, and reporting.

Key Dates
Posted Date

October 24, 2018

Open Date (Earliest Submission Date)

December 18, 2018

Letter of Intent Due Date(s)

December 18, 2018

Application Due Date(s)

January 18, 2019, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on this date.

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

AIDS Application Due Date(s)

Not Applicable  

Scientific Merit Review

March 2019

Advisory Council Review

May 2019

Earliest Start Date

July 2019

Expiration Date

January 19, 2019

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.


There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

  1. Use the NIH ASSIST system to prepare, submit and track your application online.
  2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.

  3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.
  4. Table of Contents

    Part 1. Overview Information
    Part 2. Full Text of the Announcement

    Section I. Funding Opportunity Description
    Section II. Award Information
    Section III. Eligibility Information
    Section IV. Application and Submission Information
    Section V. Application Review Information
    Section VI. Award Administration Information
    Section VII. Agency Contacts
    Section VIII. Other Information

    Part 2. Full Text of Announcement
    Section I. Funding Opportunity Description
    Purpose  

    The purpose of this funding opportunity announcement is intended to support a collaborative program of linked clinical trial sites including data coordination. These linked sites will be referred to as 'consortia'. Each consortium will consist of at least two linked clinical sites, all of which will carry out a unique clinical protocol designed to facilitate advances in diagnostic and therapeutic solutions to infertility, and of which at least one site includes data coordination expertise and functional capability, and who have agreed to oversee and implement the same protocol. 

    Infertility, defined as the inability to conceive after 12 months of trying, affects approximately 7-15% of reproductive-aged couples.  Most interventions to treat infertility, especially those pertaining to male infertility and in vitro fertilization, have been empirical with insufficient evidence-based research to support the approach.  Well-designed multi-site clinical trials provide a means to develop high-quality evidence addressing important questions in male and female infertility and translate new discoveries into the clinical arena. Moreover, the development of new medications and technologies requires evaluation for safety and efficacy that is best achieved through large-scale clinical trials.  This, in turn, will result in scientifically substantiated, safe, more efficient, and cost-effective care.

    Previously, NICHD Program staff cooperatively assisted in identifying research topics of high priority and in designing and implementing protocols to evaluate the optimal management in the areas targeted for research. As the NICHD Reproductive Medicine Network has matured, the current program seeks PD(s)/PI(s) that have self-identified and have congruent interests to develop a common protocol to answer important questions regarding diagnosis or treatment of female and male infertility, which they seek to implement. The objective of this program is to support the conduct of multi-site trials in reproductive medicine by establishing linked research awards to form clinical research consortia that can perform rigorous patient evaluation, recruit adequate numbers of patients, and collect and analyze large data sets to provide answers more rapidly than individual sites acting alone.  The diagnostic and intervention research covered under this announcement is explicitly focused on practice-relevant questions with the goal to provide evidence that guides clinical practice.    

    Background

    The Reproductive Medicine Network (RMN) was established by NICHD in 1989 to address the need for large, multicenter clinical trials to study infertility and reproductive diseases and disorders that impact fertility, in order to increase the evidence-base for infertility treatments. In the last 30 years, the RMN has made significant advances in addressing the gap in evidence-based medical approaches.  Yet, in this time of rapidly evolving scientific knowledge specifically in the realms of genetics, genomics and precision medicine, the need to conduct trials that evaluate new diagnostic methods and identify the most effective interventions for both male and female infertility still remains. 

    For the current award period which commenced in 2013, three trials have been/are being conducted:  1. Active Treatment or No Treatment: Optimal Treatment for Women with a Persisting Pregnancy of Unknown Location - A Randomized Clinical Trial of Women at Risk for an Ectopic Pregnancy (ACTorNOT), 2. Improving Reproductive Fitness with Pretreatment with Lifestyle Modification in Obese Women with Unexplained Infertility (FIT-PLESE), and 3. Males, Antioxidants and Infertility (MOXI). Observational studies undertaken by the RMN have addressed Psychological Family Issues and Outcomes of Multiple Gestations (PsyFI).  In addition, the ENDOmarker study is establishing a biorepository of well-characterized patient data and samples for future use to develop serum or tissue biomarkers for the diagnosis of endometriosis. In prior funding cycles, studies addressed new medications for ovulation induction in infertile women with polycystic ovary syndrome (PCOS), compared two existing standards of care utilized in in vitro fertilization (IVF), and evaluated existing treatments for unexplained infertility on the primary outcome of multiple gestations. (See https://publichealth.yale.edu/c2s2/rmn/).

    As a byproduct of conducting these trials, the RMN has also collected additional data, including behavioral outcomes and quality of life measures, and biospecimens during the conduct of the clinical trials that serve as a resource to the scientific community at large by providing access for scientific studies through the RMN biorepository via the NICHD Data and Specimen Hub (DASH).  The RMN has also supported a Pregnancy Registry replete with follow-up information from offspring born from NICHD-funded infertility trials. 

    The RMN also provided a platform for exposing interested clinicians to clinical research by collaborating with the Clinical Research Reproductive Scientist Training (CREST) Program which is funded by an R25 grant.  While not a main goal of the program, it is envisioned that these consortia will continue to serve as a resource for the training of CREST scholars by enabling them to utilize the intellectual and research infrastructure to become familiar with performing clinical research, performing secondary data analyses and interpreting results from those trials.

    Scope

    This FOA is intended to support a collaborative program of clinical trial sites (i.e, consortia) to advance the scientific research on new medications, interventions and approaches addressing the diagnosis, prevention and treatment of infertility.  A consortium requires participation of two or more collaborative sites for completion of the study. Accordingly, the collaborating studies share a common protocol across the sites and are organized to increase sample size, accelerate recruitment, and increase sample diversity and representation. Each site has its own Program Director/Principal Investigator (PD/PI) and each consortium provides a mechanism for cross-site coordination, quality control, database management, statistical analysis, and reporting. This initiative requires that each clinical site within a self-identified consortium have the resources, infrastructure and clinical capacity to support clinical trials in reproductive medicine.

    Topic areas of high program relevance include but are not limited to:

    1. Trials that can contribute to advancing the personalization of reproductive health care and include collection of clinical and biological variables (e.g., blood for genetic analysis, other potential biomarkers), as appropriate, that might be used to inform or test algorithms to foster personalized treatment strategies;

    2. Trials that address medical management of mild male factor infertility/subfertility;

    3. Trials that address comparative effectiveness of current standards of care in IVF to optimize singleton live birth rates while minimizing multiple births;

    4. Evaluation of cost-effective alternatives to current diagnostic methods and interventions for infertility and early pregnancy loss;

    5. Investigation of interventions that maximize fertility and live birth outcomes in women with underlying conditions such as endometriosis, uterine fibroids, or prior pelvic infection;

    6. Investigation of the immunologic aspects of infertility.

    Effectiveness of the program will be assessed by: 1) timely completion of clinical trials that address public health concerns in the area of infertility; 2) the tempo of recruitment and synergy of multiple primary sites; 3) the quantity (numbers of publications) and quality (impact on clinical practice) of publications emanating from the trials, and, to a lesser extent, 4) further use of resources generated from trials (i.e., biospecimens, data) by outside investigators that contributes to advancing scientific knowledge and improving health care.

    Investigators

    Applications for this FOA should include investigators who possess the knowledge and expertise in conducting clinical trials in the field of reproductive medicine, with expertise in female and/or male infertility and/or reproductive diseases and disorders that impact fertility. 

    Investigators should have sufficient expertise, commitment of effort, organizational structure, and operational effectiveness to successfully implement a plan for this undertaking. It is expected that within each consortium, investigators will be from a variety of professional backgrounds and have interdisciplinary research expertise . Examples of the kinds of investigators who could be included in the consortium include reproductive endocrinologists, reproductive urologists, andrologists, endocrinologists, bioinformation specialists, epidemiologists, biostatisticians, clinical trialists, gynecologists, radiologists, pelvic surgeons, and psychologists, to name a few.

    A multiple Program Director/Principal Investigator model of leadership may be proposed if warranted.

    Organization

    Applicants are expected to propose a consortium of investigators that span multiple institutions, linked by a common clinical trial protocol. A successful consortium will likely have an organizational structure that effectively addresses the proposed aims and integrates the personnel, resources, and infrastructure across institutions. Examples of the organizational components that could contribute to a successful consortium include a leadership or steering body composed of the PDs/PIs of the linked sites to coordinate planning, evaluation, resource allocation, and administrative oversight. The consortium may identify a mentorship committee that facilitates involvement of junior investigators into the research activities of the consortium and a dissemination committee that coordinates timely and effective information sharing with relevant stakeholders. Applicants may also consider establishment of an external advisory committee. These are merely examples and are not intended to prescribe a specific organizational structure. Investigators may propose the components and functions that best suit the aims of the consortium.

    The consortium must identify one site that will provide data coordination functions.  These functions include: 1) assistance in the implementation of the clinical protocol, monitoring of clinical sites and distribution of protocol (capitation) costs to the clinical sites; 2) provision of clinical and scientific knowledge to facilitate data collection and analyses and drafting of case report forms, consent forms, annual reports by the consortium and other reports and documents as needed to support the goals of the consortium clinical sites and this program; 3) facilitation of regulatory requirements such as adverse event reporting and coordination of serious adverse event reporting and resolution between the clinical consortium sites and Data and Safety Monitoring Board (DSMB); 4) provision of scientific knowledge necessary to facilitate IND submissions and communications with the FDA; 5) provision of logistical services to the consortium members as required by the multi-site research program; 7) assistance with the preparation of single IRB submissions, amendments and reports, and 8) preparation and coordination of DSMB reports and regular DSMB meetings.

    The consortium through the data coordination body is expected to have procedures and capabilities for standardization and exchange of data, as well as housing informatics resources, biospecimens, and other research resources. As such, a mechanism should be proposed for the following: 1) providing patient care costs to clinical sites and monitoring expenditures by sites and forming and issuing sub-contractual arrangements to ancillary recruitment sites; 2) facilitating the centralization and standardization of the data that are derived from collaborative studies and putting the data into a common format for use by the consortium member sites, as well as preparation of data into a format to be deposited into the NICHD data repository DASH, 3) facilitating the transfer and the archiving of data generated to preserve the data for future secondary analyses and for access by the outside community through deposit of data into the NICHD DASH.

    Applications should include plans for coordination, communication, publishing and data sharing.  They should also describe the functions of the coordination site, how the DSMB will be constituted and plans for the single IRB.

    A webinar with NIH staff will be planned to provide prospective applicants the opportunity to receive information and ask questions about the scientific scope of this announcement and technical details for applying.  We anticipate the webinar will be held late November or early December 2018.

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

    Section II. Award Information
    Funding Instrument

    Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.

    Application Types Allowed

    New
    Renewal 

    The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.

    Clinical Trial?

    Required: Only accepting applications that propose clinical trial(s)

    Need help determining whether you are doing a clinical trial?

    Funds Available and Anticipated Number of Awards

    The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

    NIH intends to fund up to three linked award consortia, corresponding to a total cost level of $4.1 million for fiscal year 2019. Subsequent year funding has been estimated at $5.4 million total costs for four additional years subject to the availability of funds.

    Award Budget

    Direct costs per year of each clinical site are limited to $250,000 for recruitment infrastructure (personnel, travel, etc.) and up to $600,000 direct costs for sites that provide data coordination infrastructure in addition to recruitment infrastructure. These latter sites should also request protocol (capitation) costs, i.e. a flat fee for each subject successfully enrolled and completed for each study. These costs should not exceed a maximum of $1.2M in year 1 and $2.5M in years 2-5 (in general, capitation costs are not subject to facilities and administrative costs). Direct costs allotted to support functions of a single IRB cannot exceed $100,000.

    Award Project Period

     The maximum project period is 5 years.

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

    Section III. Eligibility Information
    1. Eligible Applicants
    Eligible Organizations

    Higher Education Institutions

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

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

    • Hispanic-serving Institutions
    • Historically Black Colleges and Universities (HBCUs)
    • Tribally Controlled Colleges and Universities (TCCUs)
    • Alaska Native and Native Hawaiian Serving Institutions
    • Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

    Nonprofits Other Than Institutions of Higher Education

    • Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
    • Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

    For-Profit Organizations

    • Small Businesses
    • For-Profit Organizations (Other than Small Businesses)

    Governments

    • State Governments
    • County Governments
    • City or Township Governments
    • Special District Governments
    • Indian/Native American Tribal Governments (Federally Recognized)
    • Indian/Native American Tribal Governments (Other than Federally Recognized)
    • U.S. Territory or Possession

    Other

    • Independent School Districts
    • Public Housing Authorities/Indian Housing Authorities
    • Native American Tribal Organizations (other than Federally recognized tribal governments)
    • Faith-based or Community-based Organizations
    • Regional Organizations
    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

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

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

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

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

    Eligible Individuals (Program Director/Principal Investigator)

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

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

     This FOA supports linked applications. Multiple PDs/PIs are allowed on any single application. Because the FOA already supports a team approach between groups of experts across sites and collaborating applications, the designation of multiple PDs/PIs on a single application may be less likely to apply. PD(s)/PI(s) from each linked application should not be designated as multiple PDs/PIs on each application of a collaborative set.

    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.

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

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

    Applicant organizations may submit more than one application with different linked organizations, but the common clinical trial protocol must be unique for each consortium of linked organizations proposed.   

    Section IV. Application and Submission Information
    1. Requesting an Application Package

    Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

    2. Content and Form of Application Submission

    It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) 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.

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

    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:

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

    The letter of intent should be sent to:

    Louis V. DePaolo, PhD
    Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) 
    Telephone: 301-435-6970
    Email: ld38p@nih.gov

    Page Limitations

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

    Instructions for Application Submission

    The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

    SF424(R&R) Cover

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

    Descriptive Title of Applicant's Project: To allow NIH to identify a group of applications as a related consortium of linked applications, the titles for each application in the set must have the following format: a “1/N” indicator + Identical Title (e.g., “1/3”, where the 1/3 means this is site 1 of 3 sites in the set. The other sites will be labeled 2/3, etc.) Titles may not exceed 200 characters in length, including the tag, e.g., 1/3, at the beginning of the title.

    Cover Letter Attachment: The Cover Letter is one pdf file only. The following information is required in the Cover Letter: a listing of all the applications that are a part of the linked sites in the consortium  being submitted, including for each: 1) the PD/PI(s) name(s), 2) the Title (including the tag, e.g., “1/3”), and 3) the Applicant Institution. Each site should submit an identical listing.

    SF424(R&R) Project/Performance Site Locations

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

    SF424(R&R) Other Project Information

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

    Facilities and Other Resources:

    Facilities

    The description of the resources and environment should address how the study utilizes existing infrastructure (e.g., CTSAs, practice-based research networks, electronic medical records, administrative data bases, patient registries) or utilizes other available resources to increase the efficiency of participant recruitment and data collection or provide a justification if such efficiencies cannot be incorporated. 

    A site must have a history of previous successful clinical research, and expertise in research design,

    biostatistics, and the implementation of clinical protocols. Ability to enroll sufficient numbers of diverse patients in clinical trials and demonstration of excellence in the collection and communication of clinical data should be documented.

    Laboratory facilities must be available for appropriate testing of patients and subjects, such as clinical

    pathology, hematology, blood chemistry, endocrinology, microbiology, radioimmunoassay, and andrology.

    Appropriate imaging services must be available, including ultrasound, contrast studies, and other

    radiological and related techniques that may be required to diagnose and follow the conditions under study.

    If an institution includes multiple, non-contiguous clinics, then applicants should include appropriate staffing levels to cover all sub-sites and include a detailed plan for how to manage recruitment, study implementation, data collection, data entry, and data editing among the sub-sites.  

    A clinical site should be in an institution with access to infertility services. 

    Population Available for Clinical Trials

    Applicant clinical sites must have academically-oriented divisions of reproductive medicine and adequate clinical volume to recruit the requisite numbers of study subjects in a timely manner. Sites should provide evidence of the ability to follow study subjects after establishment of pregnancy during ongoing obstetrical care and delivery to facilitate accrual of live-birth and outcome data. 

    Applicants should provide the specific information regarding the population available for study at the clinical site(s), include information regarding annual visits, new and returning visits and/or admissions. 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.

    If a site has a long standing, well-documented collaboration and interaction with other linked sites, this should be clearly stated in the application, including the investigator responsible at the collaborating site.

    Special Strengths

    Applicants are encouraged to describe special or unique resources. This can include state-of-the art scientific capabilities such as modern imaging and assessment techniques, proteomics, genomics, micro analysis, pathology, or clinical pharmacology as examples which may be available to develop secondary studies and expand the scientific productivity of the consortium.

    Special administrative strengths or experience and participation in administrative aspects of clinical research (e.g., institutional review boards, data and safety monitoring committees, advisory board for clinical research, clinical research committees) should be highlighted. 

    SF424(R&R) Senior/Key Person Profile

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

    As appropriate, Senior/Key Personnel should demonstrate their experience and expertise at collaborating with other investigators and community practice partners/provider to implement and complete clinical studies.

    The PD/PI must be a practicing board certified physician with additional board certification in either reproductive endocrinology and infertility or urology with a specialization in male reproduction, and should describe his/her clinical, research, administrative and academic commitments in the Biosketch.

    The PD/PI should demonstrate access to an appropriate patient population and ability to recruit

    successfully to clinical studies. The PD/PI should be able to devote the required time to the supervision, implementation, and management of the clinical study at his/her site and have experience participating in multisite clinical trials.

    In addition to the named PD/PI, the applicant must include at least one board-certified physician co-investigator, to be designated as an Alternate PD/PI, who is able to serve in the absence of the PD/PI. An additional co-investigator may be included with expertise in a content area that enhances multidisciplinary investigation (i.e., internal medicine, behavioral medicine, economic analysis, andrology, pathology, radiology, endocrinology, social medicine, biostatistics and/or epidemiology).

    The PD/PI must devote at least 1.8 person-months (15 percent) effort to the project, and the other co-investigators may devote up to 1.2 person-months (10 percent) effort. A Biosketch should be submitted with the application for these co-investigators.

    Clinical research coordinators, totaling no less than 1.0 FTE and up to 1.5 FTEs can be designated as key personnel, with biographical sketches included as part of the application. Additional research nursing and support staff should be available.

    Previous Clinical Trial Experience - Applicants must describe their recent experience and participation in clinical studies and trials. Specific roles [PD(s)/PI(s)], participating site, steering committee, writing committee, trial design and development] should be described for each study. They should also provide evidence of research productivity by the clinical site in previous or ongoing clinical studies and trials, especially those of a collaborative or multisite design. Contributions in key areas of research development and design, patient recruitment, retention and study completion, data collection and analysis, and track record of publications should be included in the application. Publications that resulted from participation in these studies should be listed

    R&R Budget

    All instructions in the SF424 (R&R) Application Guide must be followed. Each applicant should submit infrastructure budget estimates and protocol cost estimates for all years. 

    Applicants should request funds to support:

    • PD/PI: 1.8 person-months (15 percent) effort
    • Alternate PD/PI, additional investigator or additional PD/PI support: up to 1.2 person-months (10 percent) effort each.
    • Research Coordinators: total of 18 person-months (150 percent) effort divided among at least 2 coordinators including those coordinators at ancillary recruiting sites if applicable
    • Data Entry Clerk: 6 person-months (50 percent) effort
    • Supplies and small equipment (itemized and justified): Not to exceed $5,000
    • Travel: A total of 4 in-person meetings of up to 3 site key personnel to one of the consortium sites or the Washington DC area annually. The PD/PI or designee and Research Coordinator are encouraged to attend these meetings.  For sites providing the data coordination infrastructure for the consortium, funds should also be requested for travel of a Project Manager to linked clinical sites for training of research coordinators and quality control. 
    • Other costs (itemized and individually justified) including:  Supplies and advertising for protocol recruitment, publication costs, single IRB functions (cost should be encumbered by one of the linked sites), etc.

    The clinical site that supports data coordinating functions should indicate funds that represent protocol costs, i.e. a flat fee for each subject successfully enrolled and completed for each study. The PD/PI of that clinical site will be required to project subject enrollment at each linked clinical site during a specified time frame, although continuation and the level of funding will be based on actual enrollment.  Funds from this site should also be budgeted for storage of biospecimens.

    Total funding for clinical sites depends on the base awards and reimbursements from the data coordination site for approved protocol-related expenses.  The overall provision of money is subject to the availability of NICHD funding.

    R&R Subaward Budget

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

    The PD/PI may identify ancillary sites that may serve as additional recruitment sites.

    PHS 398 Cover Page Supplement

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

    PHS 398 Research Plan

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

    Specific Aims:

    The Specific Aims should include an Overview section that is identical for all applications within a consortium that are linked together. The overview should provide an overall rationale for applying as a collaborative study, the role of each site, the approach to project management, and elements unique to any of the sites.

    Research Strategy:

    The application from each site must contain a Research Strategy that clearly describes those aspects of the project that are common to all sites of the collaboration. All variations in the Research Strategy between sites, no matter how minor, should be highlighted in a subsection of the Research Strategy with the heading "Elements Unique to This Site." In this subsection, PDs/PIs should describe, for example, how the research site has a unique role in the collaboration, such as data coordination, statistical analyses, etc. The site that provides data coordination should include a detailed description of all the functions that will be performed for clinical trial implementation, monitoring, data analysis, data and biospecimen storage and reporting and coordination of the study. This site will be responsible for issuing payments for the approved protocol expenses including a per patient capitation. 

    Applications from each site must describe a feasible mechanism for scientific integration of research procedures, overall managerial and administrative responsibilities, and cross-site comparability of training to assure reliability and quality control. A clear plan of operation and communication should be provided for the administrative structure and proposed interactions amongst the investigators.  The PDs/PIs may or may not wish to designate a Steering Committee or other decision-making body or identify one individual as the contact person for the group as a whole for purposes of NICHD correspondence. Plans for ensuring access to data by all sites, analytic resources, publication and authorship rights, the possibility of public use research materials and data, or other means of distributing research materials to the wider scientific community, and a means of arbitrating disagreements on publication and other issues should be included in the application.

    Any site that contracts out some portions of this work should list this fact under "Elements Unique to This Site," and provide a full description of the nature, purpose and oversight of this contractual arrangement.

    Significance

    Justify the  intervention in terms of the estimated hypothesized effect size (in terms of key outcomes, such as clinical benefit, safety/tolerability, value and efficiency, or scalability), compared with already available approaches and the clinical meaningfulness of the anticipated increment in outcome compared to existing approaches. 

    Innovation

    Highlight how innovative research strategies and design/analytic elements (e.g., adaptive sequential randomization, equipoise stratification), if any, are incorporated, as appropriate, to enhance the study’s potential for yielding practice-relevant information.

    Single IRB

    Provide a single IRB plan in the PHS Human Subjects and Clinical Trial Information form, section 3.2.

    Letters of Support:

    The departmental and institutional commitments to reproductive medicine research and this program should be clearly documented with letters of support from appropriate individuals. Evidence of past support can also be cited. Support in areas of grants management, personnel provision and management, space allocation, procurement, equipment as well as general support of the research should be described as well as evidence of past research support.

    The clinical site(s) should be located in an institution with resources for evaluation and management of infertility patients. A letter of assurance of cooperation with the policy for capitation of research costs as outlined below should be provided from the departmental and institutional offices of sponsored research programs.

    The site with data coordination role will be responsible for issuing payments for the approved protocol expenses including a per patient capitation. These funds may be used to fund staff positions listed above and other research staff and expenses required by the protocol.  To receive reimbursements, a funded clinical site must set up an agreement with the coordination site. 

    Applications from institutions that have a Clinical and Translational Science Award (CTSA) funded by NIH or other funded research centers as resources for conducting the proposed research should provide a letter of agreement that identifies the level and type of support from the PD/PI or the CTSA program director.  

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

    All applications, regardless of the amount of direct costs requested for any one year, should include a Data Sharing Plan.  The Data Sharing Plan will be considered during peer review and by program staff as award decisions are being made as appropriate and consistent with achieving the goals of the program.  It is expected that the results of NICHD-funded research will be shared with the wider scientific community in a timely manner. 

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

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

    To accomplish the goal of data sharing, it will be important to formulate a) an enrollment strategy that will obtain the information necessary to enable data sharing for each participant, and b) a budget strategy that will cover the costs entering and preparing data that can be readily shared upon study completion. Investigators are expected to certify the quality of all data generated by grants funded under this FOA prior to submission to DASH and review their data for accuracy after submission. Submission of all data related to the clinical trial is expected at the time of publication, or prior to the end of the grant, whichever occurs first.

    Appendix:

    Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

    PHS Human Subjects and Clinical Trials Information

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

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

    Study Record: PHS Human Subjects and Clinical Trials Information

    All instructions in the SF424 (R&R) Application Guide must be followed with the following additional instructions:

    Section 2 - Study Population Characteristics

    2.5 Recruitment and Retention Plan

    Applications must provide a clear description of:

    1. Recruitment and Referral sources, including detailed descriptions of the census/rate of new cases and anticipated yield of eligible participants from each source;

    2. Procedures that will be used to monitor enrollment and track/retain participants for follow-up assessments;

    3. Strategies that will be used to ensure a diverse, representative sample;

    4. Potential recruitment/enrollment challenges and strategies that can be implemented in the event of enrollment shortfalls (e.g., additional outreach procedures, alternate/back-up referral sources);

    5. Strategies to assess risks to study participants once they are enrolled;

    6. Evidence to support the feasibility of enrollment, including descriptions of prior experiences and yield from research efforts employing similar referral sources and/or strategies.

    2.7 Study Timeline

    Applications must provide a timeline for reaching important study benchmarks such as: (1) finalizing the study procedures and training participating clinical site staff; (2) finalizing the intervention manual and assessment protocols, including fidelity measures/procedures, where applicable; (3) enrollment benchmarks; (4) completing all subject assessments and data collection activities, including data quality checks; (5) analyzing and interpreting results; and (6) preparing de-identified data and relevant documentation to facilitate data sharing, as appropriate.

    Section 3 – Protection and Monitoring Plans

    3.2 Is this a multi-site study that will use the same protocol to conduct non-exempt human subjects research at more than one domestic site?

    If yes, describe the single IRB plan

    Single IRB Plan. In view of the multi-site clinical studies solicited by this FOA, applications from each site should describe the Single IRB to be used and previous experience of this single IRB in the conduct of multicenter clinical trials.  Exceptions to the Single IRB policy will be made for Native American or foreign sites as stipulated within the Single IRB policy. Each site requesting an sIRB exception should also provide evidence of local IRB support, and, if applicable, processes for local IRB approval and how the approval process will be coordinated with the single IRB approval process.

    Section 5 - Other Clinical Trial-related Attachments

    5.1 Other Clinical Trial-related Attachments

    Applicants must upload the attachments for Intervention Manual/Materials as separate files, as applicable. Applicants must use the “Intervention Manual/Materials” (appended with 1, 2, 3, etc. if needed) to name these other attachments files. As appropriate, this may include screenshots of mobile interventions, technological specifications, training manuals or treatment algorithms.

    Delayed Onset Study

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

    PHS Assignment Request Form

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

     
    3. Unique Entity Identifier and System for Award Management (SAM)

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

    4. Submission Dates and Times

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

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

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

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

    5. Intergovernmental Review (E.O. 12372)

    This initiative is not subject to intergovernmental review.

    6. 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.

    7. Other Submission Requirements and Information

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

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

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

    Important reminders:

    All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

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

    See more tips for avoiding common errors.

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

    Additional Information about Linked Applications

    Applications must be submitted as a linked group or set of R01s, usually one R01 per participating PD/PI.  For each set of linked collaborative R01 applications, it is expected that each application/site will involve recruitment and enrollment of participants and executing a common protocol. It is expected that each application will be coordinated and interlocked with the others as each application will contribute an essential component to the overall study.  However, there are likely to be elements unique to some sites (e.g., data coordination, fidelity assessment, statistical analyses).  

    Post Submission Materials

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

    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.

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

    Overall Impact

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

    Scored Review Criteria

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

    Significance

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

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

    Investigator(s)

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

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

    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?

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

    Approach

    Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects? 

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

    Does the application adequately address the following, if applicable?

    Study Design

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

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

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

    Data Management, Statistical Analysis and Biospecimen Storage

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

    Has a biospecimen storage facility been identified?  Have funds been budgeted to support this facility?  For both data and biospecimens, is there a discussion of ownership of both data and biospecimens and a succession plan for ownership once federal support of the project has run out?

    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? 

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

    Does the application adequately address the capability and ability to conduct the trial at the proposed site(s)? Are the plans to add ancillary recruitment sites, as needed, appropriate?

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

    Is there evidence of the ability of the individual site to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure? 

    Additional Review Criteria

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

    Study Timeline

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

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

    Interactive Processes

    Collaboration and Coordination

    Does the application justify the need for a collaborative multi-site project using this FOA? Are sufficient and feasible mechanisms in place to ensure coordination, communication and collaboration across sites to achieve scientific integration of research procedures, overall managerial and administrative responsibilities, appropriate quality control and reliability assurance, and planning for data management, analysis and reporting of results? Are there adequate plans for shared decision making among PDs/PIs regarding personnel, clinical decisions, changes in study protocol, and authorship?

    Data and Safety Monitoring Board (DSMB)

    Is there a description of how the DSMB will be constituted?  Does the description indicate the frequency and format of the DSMB meetings, and is this appropriate? Are there plans for how meetings of the DSMB will be coordinated and meeting minutes distributed?  Does the application present a strategy for adverse event reporting and timelines for communicating serious adverse events to the DSMB? Is there a process in place for termination of a protocol by the DSMB and communication of that decision to NICHD staff?

    Single IRB Protocol Review

    Is there a description of the process for single IRB review?  Have funds been budgeted to support the functions of a single IRB?  If applicable, has a process been developed for coordination of single and local IRB review?

    Protections for Human Subjects

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

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

    Inclusion of Women, Minorities, and Children 

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

    Vertebrate Animals

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

    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

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

    Applications from Foreign Organizations

    Not Applicable

    Select Agent Research

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

    Resource Sharing Plans

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

    Authentication of Key Biological and/or Chemical Resources:

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

    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 NICHD, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

    As part of the scientific peer review, all applications:

    • May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
    • Will receive a written critique.

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

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

    • Scientific and technical merit of the proposed project as determined by scientific peer review.
    • Availability of funds.
    • Relevance of the proposed project to program priorities.
    3. Anticipated Announcement and Award Dates

    After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

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

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

    Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA. 

    ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain “applicable clinical trials” on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration of all trials whether required under the law or not. For more information, see http://grants.nih.gov/ClinicalTrials_fdaaa/.   

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

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

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

    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.

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

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

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

    Cooperative Agreement Terms and Conditions of Award

    Not Applicable

    3. Reporting

    When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

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

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

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

    Section VII. Agency Contacts

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

    Application Submission Contacts

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

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

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

    Scientific/Research Contact(s)

    Louis V. DePaolo, PhD
    Eunice Kennedy Shriver National Institute of Child Health and Human Development
    Telephone: 301-435-6970
    Email: ld38p@nih.gov

    Peer Review Contact(s)

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

    Financial/Grants Management Contact(s)

    Alesia Brody
    Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
    Telephone: 301-435-0267
    Email: alesiabrody@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 Part 75.

NIH Office of Extramural Research Logo
Department of Health and Human Services (HHS) - Home Page
Department of Health
and Human Services (HHS)
USA.gov - Government Made Easy
NIH... Turning Discovery Into Health®


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