Part 1. Overview Information

Key Dates

All applications are due by 5:00 PM local time of applicant organization. 

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.

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts).

Conformance to all requirements (both in the Application Guide and the NOFO) 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.



Table of Contents
Part 1. Overview Information
Key Dates
Part 2. Full Text of Announcement
Section I. Notice of 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. Notice of Funding Opportunity Description

Purpose

The purpose of this NOFO is to support and facilitate multidisciplinary research approaches for the development or improvement of technologies - including drugs, devices, products, or clinical practices - designed to improve fertility outcomes in patients dealing with infertility, particularly in the context of assisted reproductive technologies (ART).  This NOFO aims to position innovative and validated technologies for future clinical development.

Background

Infertility impacts about 15% of all couples, with males and females each contributing to roughly half of infertility cases.  Infertility is caused by a myriad of factors, including but not limited to genetic mutations/abnormalities, aging, acute and chronic conditions, and exposure to a variety of toxic agents.  According to the CDC, the use of ART has doubled over the last decade but is still significantly below demand.  Despite this increase in ART usage, ART only has a success rate of about 33%.  New, improved, and more cost-effective treatments for infertility need to be developed to address these issues. 

The NICHD is the world leader in reproductive health and infertility research.  Theme 2 of the NICHD Strategic Plan, - Titled Promoting Gynecologic, Andrologic, and Reproductive Health - explicitly calls for NICHD to “Identify biologic and environmental factors that can lead or contribute to infertility in males and females Apply this knowledge to expand technologies or methods for fertility stimulation, fertility preservation, and contraception.”  This initiative will directly address this goal in the NICHD Strategic Plan by funding projects focused on the development or improvement of drugs, products, devices, or changes in clinical practices to improve reproductive outcomes for those struggling with infertility.  

Phased Innovation Awards

This funding opportunity will use the R61/R33 phased award mechanism. Support will be provided for two years for the R61 phase, and up to three years of support may follow for the R33 phase.  Clinical trials will not be allowed in the R61 phase of the award, but will be allowed in the R33 phase of the award.

Research Scope

The purpose of this announcement is to support and facilitate multidisciplinary research for the development or improvement of products addressing infertility in both women and men.  For the purposes of this NOFO, “product” includes new, improved or repurposed drugs, devices, diagnostic tools, clinical laboratory tests, computer programs or apps, digital health platforms, protocols, technologies, or techniques.  This NOFO supports research on pre-clinical stages of development from proof-of-concept and safety through IND-enabling and IDE studies.

Examples of research in scope include (but are not limited to):

• Development of products designed to:
  1. Improve sperm quality/quantity
  2. Improve egg quality/quantity
  3. Improve gamete storage/vitrification/thawing
  4. Improve sperm/egg selection
  5. Improve/measure/optimize uterine receptivity
  6. Improve/optimize implantation window and/or implantation timing
• Development of an Artificial Intelligence/Machine Learning (AI/ML) model for ART applications such as:
  1. Semen analysis – concentration, morphology, motility, etc.
  2. Sperm selection
  3. Oocyte quality assessment and selection
  4. Embryo development annotation
  5. Ploidy prediction
  6. Embryo grading
  7. IVF outcome prediction
• Develop a diagnostic/screening tool, product, or protocol to improve fertility outcomes in patients with infertility - High priority for products that utilize reproductive fluids including semen, follicular fluid, menstrual effluent, and cervical/vaginal mucus 
• Improvements in existing technologies or protocols that significantly reduce IVF costs for patients

Utilization of animal models is allowed for this NOFO; however, the long-term goal of the project should be development of a product to address human infertility.

Application focused on the following areas are considered out of scope and will be considered non-responsive and will not be reviewed:

• Applications not focused on the development or improvement of products designed to address human infertility in the clinic - Animal studies are allowed if the ultimate goal of the project is the development/improvement of a product addressing human infertility.
• Applications focused on more than one product
• Applications focused on the development of products for non-reproductive gynecologic conditions (e.g. PCOS, endometriosis, uterine fibroids) unless the product has a primary goal of addressing infertility in these patients.
• Applications focused on menstrual management/tracking unless the product has a primary goal of improving outcomes for infertile patients.
• Applications developing a “Femtech” product NOT focused on improving fertility outcomes for infertile patients
• Applications focused on general gynecologic/pelvic pain not associated with infertility - Applications focusing on improving fertility outcomes of infertile patients with these conditions would be in scope.
• Applications focused on treatment of hypospadias, cryptorchidism, benign prostatic hyperplasia, epididymitis, prostitis, seminal vesiculitis, testicular torsion, hydrocoele, or varicocele
• Applications focused on cancer treatments/therapeutics
• Applications focused on improvements in reproductive surgeries
• Applications focused on new or improved contraceptive or multipurpose prevention products
• Applications focused on molecular or genetic targets for which there is no human ortholog
• Applications focused on the development of type I-II kinase inhibitors
• Applications that result in the creation of a human embryo or in which a human embryo is destroyed, discarded, or knowingly subjected to risk greater than that allowed on NIH funded research in fetuses in utero.

Applications that do not follow the administrative guidelines of this RFA will not be reviewed, including but not limited to: 

• Applications that do not provide a clear path to transition from the R61 to the R33 phase of the award 
• Applications that do not have a “Transition Milestones for the R61 Phase” section in the Research Strategy 
• Applications that do not provide measurable/quantifiable milestones for the transition from the R61 to the R33 phase of the award with go/no-go criteria (see Section IV.2)
• Applications proposing only the R61 phase or only the R33 phase 
• Applications proposing a budget for only the R61 or only the R33 phase 
• Applications that do not provide separate sections to describe the R61 and R33 phases 
• Applications that propose clinical trials in the R61 phase.

Transition from the R61 to the R33 phase 

No less than two months before the completion of the R61 phase, awardees may submit the R33 transition package, which includes the R61 progress report describing, in detail, progress towards the R61 milestones (negotiated with Program staff prior to award of the R61 phase) and a description of how research proposed for the R33 phase will be supported by the completion of the R61 phase milestones. These materials will be evaluated by NIH Program staff. R33 transition will be based on strong proof-of-concept, reasonable safety profile, transition milestone accomplishment, preparedness of candidate product/technology for further development (if applicable), whether Aims of the R33 phase continue to meet programmatic priorities in the context of the NOFO objectives, and availability of funds. Grants receiving a positive internal review will be transitioned to an R33 award without the need to submit a new application. It is anticipated that only a portion of the R61 awardees will be transitioned into the R33 phase. Priority may be given to awardees that successfully complete all transition milestones. Applicants must be aware that use of a no-cost extension at the end of the R61 period could jeopardize the award of the R33. 

Proof-of-concept

At the time of transition, grantees must provide evidence of proof-of-concept – i.e. compelling evidence must be shown that if the proposed research project is successful in achieving the modulation outlined in the application, the product will be a meaningful improvement or have significant differentiation over the current standard of care. 

• Proof-of-concept must be addressed in Research Strategy under the heading “Proof-of-concept”.  
  1. If evidence exists demonstrating proof-of-concept, this evidence should be presented in this section.
  2. If pursuing proof-of-concept in the R61 phase, outline the strategy to achieve this goal in this section.  At least one milestone must address the proof-of-concept if it is a goal of the R61 phase.
• If the application proposes a drug or gene therapy target, proof-of-concept must show that misregulation of the target gene/RNA/protein/etc. of interest 1) causes infertility/subfertility and 2) the proposed modulation is capable of rescuing fertility.
• If the application proposes a drug without a known molecular target, proof-of-concept must show that the proposed modulation is capable of rescuing fertility.
• If the application proposes a diagnostic or screening tool, validation must be as accurate or more accurate than current diagnostic or screening methodology OR provide a meaningful benefit (e.g. less invasive, less costly) while still providing actionable information relevant to addressing infertility.

Reasonable Safety Profile

To transition to the R33 phase, applicants must demonstrate that their proposed product has a reasonable safety profile – i.e. evidence must be provided to suggest that the product will likely impose no additional risk to patients beyond the current standard of care. Applicants who desire further discussion regarding this section are advised to consult the NICHD Scientific/Research contact.  

• The safety profile must be addressed in the Research Strategy section under the heading “Safety Profile”.  
  1. If there is already evidence showing a safety profile, this evidence should be presented in this section.
  2. At least one milestone must address this reasonable safety profile regardless of whethersupporting data is provided.
• As part of the reasonable safety profile, the applicants should address how their proposed product compares to the current standard of care.  A non-comprehensive list of examples addressing a reasonable safety profile could include, but are not limited to:
  1. For drugs or gene therapy products this could include toxicity studies, dose curves, specificity to target, and potential side effects
  2. For diagnostics/screening tools, this could address invasiveness, likelihood of false positives, and likelihood of false negatives
  3. For “at home” products/technologies designed for patient use/interface this could include potential misuse of the product, receiving potentially negative news without the presence of a medical professional, or potential use by non-patient household members

If the application proposes to utilize AI or ML tools, the applicants must address the composition of the training set and the applicability of the tool to the population of potential patients with a range of cause(s) of infertility. 

Milestones

All projects must be milestone-driven with clear go/no-go criteria. Milestones are deliverables for each specific aim of the R61 phase with quantifiable success metrics and include at minimum annual and/or intermediate quantitative criteria with key success metrics specifically defined. Proposed milestones must be quantitative in nature and will be specific for each project. Milestones must not be subjective in defining success criteria. Each milestone should have specific and quantifiable measures to evaluate achievement of the milestones. Go/no-go criteria, for the purpose of this NOFO, are defined as binary decision criteria at critical points to determine whether the referenced aspect of the project should proceed or not, and the “no-go” criteria are understood to be the inverse of the “go” criteria. The applicant must explicitly state go/no-go criteria for advancement to the R33 phase of the project. 

All projects should have at least one milestone addressing the safety profile.  If the R61 phase of the project will be collecting evidence to support proof-of-concept, appropriate quantitative milestones and go/no-go criteria must be present.  

The milestones will be evaluated by reviewers as additional review criteria (see the Review section).  Prior to funding an application, the NICHD Program Official will contact the applicant to discuss the proposed milestones and any changes recommended by peer review as well as additional feedback from NIH staff. The NICHD Program Official and the applicant will negotiate a final set of approved milestones that will be specified in the Notice of Award. 

• The milestones are part of the Research Strategy (and thus subject to the standard page limits) but should be in a separate section titled “Transition Milestones for the R61 Phase.” 
• All applications are strongly encouraged to include milestones related to intellectual property (e.g., patentability report). 

Representative examples of milestones for the research project types discussed in the Research Scope section: 

The following are example milestones that correlate to the research project types discussed in the Research Scope section above. In the following examples, “X” and “Y” are meant to be stand-ins for specific parameters chosen by the PI. This is not an exhaustive list or prescriptive as the desired values for all applicable projects may differ but are instead examples of the degree of quantitation and specificity expected by Program.  

I. Example milestones for drug/gene therapy: 

• Genetic or pharmacologic inhibition of target X shows at least a 20% improvement or rescue of fertility in genetic mouse model Y. 
• Drug/compound X shows 5-fold selectivity for target enzyme Y over other members of the same enzyme family.

II. Example milestones for device: 

• Wearable device X monitors estradiol and progesterone levels in the blood within a 10% margin of error over standard measurements Y. 
• At home testing kit X provides quantitative analysis of sperm motility that is within a 10% margin of error of standard sperm motility analysis Y.

III. Example milestones for Artificial Intelligence/Machine Learning: 

• Embryologists trained utilizing machine learning tool X show a 30% improvement in selecting euploid ooctyes compared to their pre-training selections.
• Embryos generated from sperm selected by AI selection tool X shows a 20% increase in the number of embryos that reached morula stage when compared to sperm selected by an embryologist (In a non-human primate model).

IV. Example milestones for improvement of an existing protocol: 

• Modification X to standard human cryopreservation technique Y results in a 20% reduction in DNA fragmentation. 
• X modifications to ovarian stimulation protocol Y results in a 15% increase in oocyte yield per cycle.

V. Example milestones for diagnostic/screening tool: 

• Novel screening tool X utilizing biomarker Y in the semen is able to predict microdissection testicular sperm extraction (mTESE) success with at least 90% confidence
• Novel screening tool X utilizing menstrual effluent to measure uterine receptivity is able to improve implantation rates over standard tool Y by 10%.

Leveraging Existing Research Resources

If applicable to their project, applicants are encouraged to consult existing research database resources, many of which have been developed with NIH or NICHD involvement. These databases (e.g., Knockout Mouse Project (KOMP), Contraceptive Infertility Target DataBase (CITDBase), Mammalian Reproductive Genetics Database V2, Geneshot, NIH Pharos, Open Targets, Calliope) are resources to gather hypothesis-generating information about a target of interest or find additional targets for study.  

Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs.

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

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions - Includes all types

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

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)

Local 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).

Federal Governments

• 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 Organizations)

Foreign Organizations/ International Collaborations

NIH will no longer issue awards (new, renewal, or non-competing continuation) to domestic or foreign entities that involve foreign subawards/subcontracts. All NIH-funded research involving foreign subawards/subcontracts must be submitted in response to a NOFO that is specifically designated for funded international collaborations. This new requirement was effective, May 1, 2025.

Applications involving foreign subawards/subcontracts submitted in response to this NOFO will be deemed noncompliant and will not be considered for funding. This policy applies to all monetary international collaborations resulting in foreign subawards/subcontracts, however, it does not preclude unfunded international collaborations or foreign components, funding for foreign consultants, or procurement of unique equipment or supplies from foreign vendors.

Non-domestic (non-U.S.) Entities (Foreign Organizations) 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.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the How to Apply- 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. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information.

• System for Award Management (SAM) – 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.
  • Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registrations; all registrations must be in place by time of submission. 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 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.

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 their organization to develop an application for 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 How to Apply-Application Guide.

2. Cost Sharing

This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1.2 Definition of Terms.

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, per NIH Grants Policy Statement Section 2.3.7.4 Submission of Resubmission Application. 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 NIH Grants Policy Statement 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this NOFO. 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 instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity 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.

Page Limitations

All page limitations described in the How to Apply- Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the How to Apply- Application Guide and should be used for preparing an application to this NOFO.

SF424(R&R) Cover

All instructions in the How to Apply - Application Guide must be followed.

SF424(R&R) Project/Performance Site Locations

All instructions in the How to Apply- Application Guide must be followed.

SF424(R&R) Other Project Information

All instructions in the How to Apply- Application Guide must be followed.

SF424(R&R) Senior/Key Person Profile

All instructions in the How to Apply- Application Guide must be followed.

R&R Budget

All instructions in the How to Apply- Application Guide must be followed.

R&R Subaward Budget

All instructions in the How to Apply-Application Guide must be followed.

PHS 398 Cover Page Supplement

All instructions in the How to Apply- Application Guide must be followed.

PHS 398 Research Plan

All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions:

Specific Aims: The specific aims for both the R61 phase and the R33 phase must be included in the Specific Aims attachment. Include headers indicating the R61 specific aims and the R33 specific aims.

Research Strategy:  Applicants must provide an overview of the proposed research, including milestones, feasibility, and timelines for completion of both phases. In preparing the R61/R33 application, investigators must consider that the application will be assigned a single overall impact score. Thus, clarity and completeness of the application regarding specific goals and the feasibility of each phase and the Transition Milestones are critical. Applicants must provide separate sections to describe the R61 and R33 phases. Applicants must not repeat information or details in the R33 section that are described in the R61 section unless they differ substantially.

In the Research Strategy, applicants must include:

• A description of the proof-of-concept status of the project at the time of submission.
  1. For projects without proof-of-concept, a plan to provide evidence of proof-of-concept by the end of the R61 phase must be proposed.
• A description of the reasonable safety profile status of the project at the time of submission.
  1. For projects without a reasonable safety profile, a plan to provide evidence of a reasonable safety profile by the end of the R61 phase must be proposed.
• A comprehensive Gantt chart for each phase outlining the proposed research and incorporating all proposed milestones and go/no-go criteria.
• A section titled "Transition Milestones for the R61 Phase." This section must be placed at the end of the R61 section within the Research Strategy. This section must include:
  1. Discussion of suitability of the proposed milestones to assess success in the R61 phase.
  2. Discussion of the implications of successful completion of these milestones for the proposed R33 phase.
  3. Milestones that are specific, quantifiable and scientifically justified; they must not be a simple restatement of the R61 phase specific aims.
  4. Go/no-go criteria integrated into the milestone criteria.
  5. Sufficiently scientifically rigorous milestones to assess progress in the R61 phase.
  6. For projects without proof-of-concept, one or more quantitative milestones for completing these studies.
  7. One or more quantitative milestones addressing a reasonable safety profile must be proposed.

Letters of Support: Letters of support must be provided for all collaborators and subcontractors. 

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply- Application Guide.

Other Plan(s): 

All instructions in the How to Apply-Application Guide must be followed, with the following additional instructions:

• All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.

Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the How to Apply- Application Guide.

• No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

PHS Human Subjects and Clinical Trials Information

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the How to Apply- 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 How to Apply- Application Guide must be followed.

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the How to Apply- Application Guide must be followed.

PHS Assignment Request Form

All instructions in the How to Apply- Application Guide must be followed.

Foreign Organizations

Foreign (non-U.S.) organizations must follow policies described in the NIH Grants Policy Statement, and procedures for foreign organizations described throughout the How to Apply- Application Guide.

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

See Part 2. 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. 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 Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

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 How to Apply-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 Section 7.9.1 Selected Items of Cost.

Applications must be submitted electronically following the instructions described in the How to Apply 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 How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. 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 form. 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 NOFO for information on registration requirements.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the How to Apply 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.

Recipients or subrecipients must submit any information related to violations of federal criminal law involving fraud, bribery, or gratuity violations potentially affecting the federal award. See Mandatory Disclosures, 2 CFR 200.113 and NIH Grants Policy Statement Section 4.1.35.

Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to the HHS Office of Inspector Grant Self Disclosure Program at [email protected].

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in the policy

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

For this particular announcement, note the following:

The R61/R33 phased innovation grant supports investigation of novel scientific ideas or new interventions, model systems, tools, or technologies that have the potential for significant impact on biomedical or behavioral and social sciences research. An R61/R33 grant application need not have preliminary data, extensive background material or preliminary information; however, they may be included if available. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Accordingly, reviewers will emphasize the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Reviewers will assign a single impact score for the entire application, which includes both the R61 and R33 phases. The rigor and appropriateness of the proposed milestones will be assessed and included as part of this impact score. 

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 scored review criteria and additional review criteria (as applicable for the project proposed). An application does not need to be strong in all categories to be judged likely to have a major scientific impact.

Reviewers will consider Factors 1, 2 and 3 in the determination of scientific merit, and in providing an overall impact score. In addition, Factors 1 and 2 will each receive a separate factor score. 

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

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.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the Center for Scientific Review, in accordance with NIH peer review policies and practices, 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 will receive a written critique.

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.

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

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 NOFO. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Child Health and Human Development Council. 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.

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 Section 2.5.1. Just-in-Time Procedures. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding.

Prior to making an award, NIH reviews an applicant’s federal award history in SAM.gov to ensure sound business practices. An applicant can review and comment on any information in the Responsibility/Qualification records available in SAM.gov. NIH will consider any comments by the applicant in the Responsibility/Qualification records in SAM.gov to ascertain the applicant’s integrity, business ethics, and performance record of managing Federal awards per 2 CFR Part 200.206 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.

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 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

A Notice of Award (NoA) is the official authorizing document notifying the applicant that an award has been made and that funds may be requested from the designated HHS payment system or office. The NoA is signed by the Grants Management Officer and emailed to the recipient’s business official.

In accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Any pre-award costs incurred before receipt of the NoA are at the applicant's own risk.  For more information on the Notice of Award, please refer to the NIH Grants Policy Statement Section 5. The Notice of Award and NIH Grants & Funding website, see Award Process.

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 and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

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

The following Federal wide and HHS-specific policy requirements apply to awards funded through NIH:

• The rules listed at 2 CFR Part 200, Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards.
• All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the terms and conditions in the Notice of Award (NoA). The NoA includes the requirements of this NOFO. 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, Recipients, and Activities.

All federal statutes and regulations relevant to federal financial assistance, including those highlighted in NIH Grants Policy Statement Section 4 Public Policy Requirements, Objectives and Other Appropriation Mandates.

Recipients are responsible for ensuring that their activities comply with all applicable federal regulations.  NIH may terminate awards under certain circumstances.  See 2 CFR Part 200.340 Termination and NIH Grants Policy Statement Section 8.5.2 Remedies for Noncompliance or Enforcement Actions: Suspension, Termination, and Withholding of Support. 

Pursuant to the Cybersecurity Act of 2015, Div. N, § 405, Pub. Law 114-113, 6 USC § 1533(d), the HHS Secretary has established a common set of voluntary, consensus-based, and industry-led guidelines, best practices, methodologies, procedures, and processes.

Successful recipients under this NOFO agree that:

When recipients, subrecipients, or third-party entities have:

1. ongoing and consistent access to HHS owned or operated information or operational technology systems; and 
2. receive, maintain, transmit, store, access, exchange, process, or utilize personal identifiable information (PII) or personal health information (PHI) obtained from the awarding HHS agency for the purposes of executing the award.

Recipients shall develop plans and procedures, modeled after the NIST Cybersecurity framework, to protect HHS systems and data. Please refer to NIH Post-Award Monitoring and Reporting for additional information. 

Not Applicable

Consistent with the 2023 NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

4. Reporting

When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement Section 8.4.1 Reporting. To learn more about post-award monitoring and reporting, see the NIH Grants & Funding website, see Post-Award Monitoring and Reporting.

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 Section 8.6 Closeout. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 2 CFR Part 200.301.

Section VII. Agency Contacts

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: https://www.era.nih.gov/need-help (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-480-7075

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

Travis Kent, PhD
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-2295
Email: [email protected]  
 

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

Mahasin Ingram
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-480-7460
Email: [email protected] 

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.

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 2 CFR Part 200.