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

Long-Term Outcomes of Medically Assisted Reproduction (R21) 

Activity Code

R21 Exploratory/Developmental Research Grant

Announcement Type

New

Related Notices

None

Funding Opportunity Announcement (FOA) Number

PAR-14-273

Companion Funding Opportunity

PAR-14-272, R01 Research Project Grant  

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

93.865 

Funding Opportunity Purpose

Assisted Reproductive Technologies (ART) and Non-IVF Fertility Treatments (NIFT) have revolutionized the field of human reproduction for the past 3 decades. Millions of children have been born worldwide through the utilization of these technologies.  An analysis of the long-term outcomes in the children is crucial for understanding the inherent risks or benefits of these procedures.  The outcomes of children conceived after ART include data from nationally-maintained registries in different countries around the world. There is no uniformity in the collection and analysis of data, and most registries lack information on long-term health and developmental outcomes. NIFT has been in use for much longer than ART, and there is lack of national registries for outcomes of NIFT across the world. Long-term biological, physical, and social outcomes of offspring conceived by ART or NIFT may be different depending upon the methods or approaches used in ART or NIFT. The underlying cause of parental infertility may also contribute to the outcomes. This funding opportunity announcement encourages the innovative and high-risk/impact studies for assessing the long-term outcomes and development of registries for documenting data on ART and NIFT procedures.   

Key Dates
Posted Date

July 3, 2014

Open Date (Earliest Submission Date)

August 30, 2014  

Letter of Intent Due Date(s)

30 days before application due date   

Application Due Date(s)

September 30, 2014; September 30, 2015; September 30, 2016, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on these dates.

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

February/March 2015, February/March 2016, February/March 2017  

Advisory Council Review

May 2015, May 2016, May 2017   

Earliest Start Date

July 2015, July 2016, July 2017 

Expiration Date

October 1, 2016  

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the 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.


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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

This FOA is intended to encourage innovative and high risk/impact in the area of human medically assisted reproduction. The research proposed under this program can propose novel approaches for the assessment of long-term consequences of ART and NIFT; improve upon the existing evaluating approaches that were used for birth outcomes in ART-born children; and development of registries for documenting long-term outcome data; or initiate research on long-term health assessment with any of the ART or NIFT procedures upon which significant new research can be built. ART primarily includes the technique of in vitro fertilization (IVF), i.e., oocyte retrieval, oocyte culture, in vitro insemination, intracytoplasmic sperm injection (ICSI), embryo culture, embryo transfer into the uterus, cryopreservation of embryos, and subsequent thaw and embryo transfer. NIFT consists of various other medical interventions that include ovarian stimulation with pharmacological agents such as selective estrogen receptor modulators (clomiphene citrate), aromatase inhibitors (letrozole), gonadotropins as well as human chorionic gonadotropin, gonadotropin-releasing hormone analogs and antagonists, with or without intrauterine insemination. In addition, hormonal supplementation of the luteal phase and early pregnancy with progesterone and hormonal preparation of the endometrium for embryo receipt or replacement is practiced. The use of medically-assisted conception (includes both ART and NIFT) is increasing worldwide. This is attributed to increases in the size of the population requiring fertility services and advances in ART and NIFT technologies.  ART alone now accounts for 1.5 percent of all births in the United States (over 61,564 newborns in 2010) and there is lack of information on births associated with NIFT procedures. Both ART and NIFT have the potential to affect the long-term health, biologically, physically, and emotionally.  Variability in the practiced procedures and the underlying infertility/subfertility in the parents possibly will confound the assessment of the contribution of these procedures to long-term health of the offspring.

During the last decade, studies were focused on birth outcomes of ART-conceived children due to the availability of large registries of IVF, ICSI, embryo donation, and cryopreservation in different countries especially in US and a few European nations. These outcomes include multiple births, preterm birth, prematurity, low birth-weights, and a few developmental defects. Although not well documented, it is well known that NIFT is also associated with substantial proportion of multiple births, prematurity, low birth weight, and birth defects. These birth outcomes may impact the long-term health of both ART- and NIFT-conceived children as their age advances.

There has been limited research on the long-term health of ART and NIFT children, and it is unknown whether these children will have normal growth, development, and health as they progress into adulthood and reproductive-age individuals. Thus, this FOA calls for novel approaches for assessment and documenting of long-term health effects of ART and NIFT. While minimal or no preliminary data are expected to be described, applications should clearly indicate the significance of the proposed research and/or that the approach is scientifically sound, that the qualifications of the investigators are appropriate, and that the resources available to the investigators are adequate.

The R21 grant mechanism is used to support the following types of research:

  • Exploratory, novel studies that break new ground or extend previous discoveries towards new directions or applications
  • High risk/high reward studies that may lead to a breakthrough in a particular area, or result in novel techniques, agents, methodologies, or applications that will impact biomedical, behavioral, or clinical research/practice.
  • Projects should be distinct from those supported through the traditional R01 mechanism.

Background

Infertility affects 10-15% of couples of child-bearing age. More and more of these couples are seeking medical assistance to conceive. Medically Assisted Reproduction consists of Assisted Reproduction technologies (ART) and Non-In Vitro Fertilization Fertility Treatments (NIFT). Although the use of NIFT started earlier than ART in the clinical practice, tremendous advances in Assisted Reproductive Technologies (ART) have been made resulting in the birth of over five million babies worldwide since 1978 when the first ART baby was born. In fertility clinics all around the world, both NIFT and ART are being used to achieve the ultimate goal of conception. ART refers to the advanced techniques in which both eggs and sperm are handled in the laboratory. These techniques include In Vitro Fertilization (IVF), Intra-Cytoplasmic Sperm Injection (ICSI), Gamete Intra-Fallopian Transfer (GIFT), Zygote Intra-Fallopian Transfer (ZIFT), and Frozen Embryo Transfer (FET). NIFT refers to ovulation induction, ovarian stimulation (without retrieval) and intrauterine insemination. The use of ART and NIFT continues to increase due to technical advances in ART and NIFT procedures, increased supply of fertility clinics and practitioners, and increased demand for these services, largely due to trends in delayed child bearing and the consequential impact of aging on fertility. However, very little is known about whether and how much these methods of conception impact the long-term health and development of the resulting children.

In its recent Assisted Reproductive Technology Surveillance Report (United States Department of Health and Human Services, Centers for Disease Control and Prevention, 2010) published in 2013, ART has been correlated with increase in the probability of twinning or higher order pregnancies. Although ovulation induction and ovarian stimulation are included as part of the IVF process, they are also used as a treatment for infertile couples either with timed intercourse or intrauterine insemination to establish pregnancy independently of IVF. These non-IVF fertility treatments have also been shown to account for more multiple births than IVF, but are not well-documented since there is no national registry for documenting non-IVF ART outcomes.

The above ART Surveillance Report indicates that more than 30% of ART pregnancies are multiple pregnancies in the United States and more than half of all ART newborns are the products of multifetal gestations. Among infants conceived with ART, 46% were born as multiple-birth infants compared with only 3% of infants among the general population. Correspondingly, 31.6% of ART conceived infants were low birthweight compared with 8% among the general population. In addition, 36.6% of ART-conceived infants were born preterm compared to 12% among the general birth population. Among singleton pregnancies, ART is associated with greater risks of complications during pregnancy, labor and delivery. ART singleton pregnancies show increased incidences of perinatal complications such as small for gestational age, preterm delivery and perinatal mortality.

In September 2005, NICHD sponsored a workshop on “Infertility Treatment and Adverse Pregnancy Outcomes” in partnership with the Office of Rare Diseases, NIH, and the Office of Research on Women’s Health, NIH. Although most ART children appear to be healthy and developing normally, there are reports of adverse outcomes in both mothers and offspring. The workshop recommended closing knowledge gaps in three key areas: 1) identification of the risks for adverse pregnancy and child health outcomes associated with ART using suitable methodologies for the analysis of correlated treatment and outcome data; 2) devising a standardized counseling strategy to discuss risks of ART with prospective couples; and 3) developing a basic research agenda in addition to clinical and epidemiological research. An important data gap identified at the workshop was the need to determine whether any of the apparently adverse outcomes of ART are actually due to the underlying infertility itself, rather than the ART. A report from the President’s Council on Bioethics in 2004 had already called attention to the need for improved monitoring of ARTs and outcomes, long term studies to assess ART and child health concerns, and attention to the decision-making processes for parents and practitioners. This was followed by Congressional report language for Fiscal Year 2008 that urged the NICHD to support the establishment of a multi-cohort study on ART to investigate outcomes.

Knowledge gained from research supported by this FOA and the companion FOA (R01) should answer the following questions:

1. Does ART or NIFT affect the general health status of the children as they progress into young adults and during adulthood?

2. Are there differences in the incidence and type of outcomes in young adults and adults born from ART and NIFT procedures?

3. Do ART and NIFT lead to chronic pathological conditions such as respiratory, cardiac, ocular, metabolic or psychiatric illnesses during adolescence or in adulthood?

4. What is the impact of ART and NIFT on the fertility status of the reproductive age group adults born out of ART/NIFT? Can it be correlated with the infertility/subfertility status of the parents?

5. Do birth outcomes such as preterm, prematurity, low birth weight, born as singleton or multiple offspring lead to different long-term outcome in the health status? What is the impact of ART or NIFT on height and weight of the body during adolescence and in adult life?

6. What is the impact of individual ART or NIFT procedure on the long-term health of offspring born out of assisted conception?

Research Scope

The scope of this FOA includes, but is not limited to, the following topics and approaches:

  • Studies using longitudinal methods to model the effects of ART and NIFT on life course health trajectories, adult onset diseases, and fertility of the offspring. Existing demographic, clinical, or epidemiological studies using population-based birth cohort designs or retrospective cohort designs could be used for the prospective or longitudinal follow-up of ART and NIFT offspring.

  • Studies on long-term health outcomes of specific ART and NIFT procedures: These studies could be follow-up studies of infants born with any of the following ART or NIFT procedures into adolescence or adulthood, or new studies of adolescents or adults born out of ART or NIFT with appropriate controls. ART and NIFT procedures suitable for study include, but are not limited to the following: hormonal stimulation protocols, ovulation induction protocols, hormonal treatments postimplantation, in vitro culture to promote differentiation and maturation of sperm and oocytes, cryopreservation of oocytes, sperm, and embryos, in vitro fertilization, intracytoplasmic sperm injection, preimplantation embryo culture and culture media formulations, preimplantation genetic diagnosis and screening, blastocyst hatching, embryo transfer, noninvasive assessment of human oocytes and preimplantation embryos.

  • Research designed to determine whether long-term outcomes of ART and NIFT are specifically related to the ART or NIFT procedures or whether they are complicated by factors underlying infertility that are parentally mediated. Multi-cohort studies, particularly those that are population-based in order to ensure the statistical power required for assessing multiple types of ART and NIFT simultaneously, are consistent with the intent of this FOA. Applications may also include donor gamete populations to tease apart causality.

  • Research on the impact of ART and NIFT on cognitive outcomes: Long-term studies on cognitive outcomes in adolescents and adults born out of assisted conception. These studies could be follow-up studies from birth to early childhood (if data is available) to adolescence or adulthood, or new studies designed to assess cognitive outcomes with appropriate age-matched and gender-matched controls.

  • Research using animal models: Animal models can be used, for example, to conduct mechanistic studies on the direct impact of ART and NIFT for the examination of outcomes of ART and NIFT that extend into adulthood and perhaps into subsequent generations. Proposed evaluations may draw from the full range of genomic, proteomic, epigenetic, biophysical, biochemical, physiological, immunological, morphological, or systems biology approaches.

  • Design and establishment of registries for documenting use of ART and NIFT procedures and offspring outcomes at the site of performance of these procedures with an eventual purpose of establishing a national registry.
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
Resubmission
Revision

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

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.

Award Budget

Direct costs are limited to $275,000 over a two-year period, with no more than $200,000 in direct costs allowed in any single year.  

Award Project Period

The total project period may not exceed two years.  

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

Section III. Eligibility Information
1. Eligible Applicants
Eligible Organizations

Higher Education Institutions

  • 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)
  • Eligible Agencies of the Federal Government
  • U.S. Territory or Possession

Other

  • Independent School Districts
  • Public Housing Authorities/Indian Housing Authorities
  • Native American Tribal Organizations (other than Federally recognized tribal governments)
  • Faith-based or Community-based Organizations
  • Regional Organizations
  • Non-domestic (non-U.S.) Entities (Foreign Institutions)
Foreign Institutions

Non-domestic (non-U.S.) Entities (Foreign Institutions) are  eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are 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.

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).

In addition, the NIH will not accept a resubmission (A1) application that is submitted later than 37 months after submission of the new (A0) application that it follows.  The NIH will accept submission:

  • To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;
  • Of an investigator-initiated application that was originally submitted to an RFA but not paid; or
  • Of an application with a changed grant activity code.
Section IV. Application and Submission Information
1. Requesting an Application Package

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the “Apply for Grant Electronically” button in this FOA or following the directions provided at Grants.gov.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions 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:

Ravi (Neelakanta) Ravindranath, PhD
Fertility and Infertility Branch (FIB)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
6100 Executive Boulevard, Rm8B01G, MSC 7510
Bethesda, MD 20892
Rockville, MD 20852 (for express/courier service; non-USPS service)
Telephone: 301-435-6889
Fax: 301-480-2389
Email: ravindrn@mail.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.  

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.  

SF424(R&R) Senior/Key Person Profile

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

R&R or Modular Budget

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

R&R Subaward Budget

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

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: 

Research Strategy: While minimal or no preliminary data are expected to be described, applications should clearly indicate the significance of the proposed research and/or that the technology is scientifically sound.

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 SF424 (R&R) Application Guide, with the following modification:

  • All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Appendix:  Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

Planned Enrollment Report

When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.  

PHS 398 Cumulative Inclusion Enrollment Report

When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide. 

Foreign Institutions

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

3. Submission Dates and Times

Part I. Overview Information contains information about Key Dates. 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.

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.  If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

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.

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 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.

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 by the Center for Scientific Review, NIH. Applications that are incomplete will not be reviewed.

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.

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:

The R21 exploratory/developmental grant supports investigation of novel scientific ideas or new model systems, tools, or technologies that have the potential for significant impact on biomedical or biobehavioral research. An R21 grant application need not have extensive background material or preliminary information. Accordingly, reviewers will focus their evaluation on the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Preliminary data are not required for R21 applications; however, they may be included if available.

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

Innovation

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

Approach

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

If the project involves 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?  

Environment

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

Additional Review Criteria

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.

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Children 

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

Vertebrate Animals

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

Biohazards

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

Resubmissions

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

Renewals

Not Applicable

Revisions

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

Additional Review Considerations

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

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

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 CSR,  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.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. 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

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.

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

Not Applicable

3. Reporting

When multiple years are involved, awardees will be required to submit the annual Non-Competing Progress Report (PHS 2590 or RPPR) 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

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

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact CenterTelephone: 800-518-4726
Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: support@grants.gov

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

Scientific/Research Contact(s)

Ravi (Neelakanta) Ravindranath, PhD 
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6889
Email: ravindrn@mail.nih.gov

Peer Review Contact(s)

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Financial/Grants Management Contact(s)

Bryan S. Clark, MBA Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6975
Email: clarkb1@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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