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.

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Purpose

The purpose of this notice of funding opportunity (NOFO) is to support and facilitate multidisciplinary research approaches for the development of novel nonsteroidal contraceptive products for men and women that act prior to fertilization using high molecular weight polymers, biologics, and devices. This NOFO aims to position innovative and validated methods for future clinical development. 

Background

Nearly half of all pregnancies in the United States are unintended. There is a critical need for fertility regulation methods that fit the needs of women and men throughout their reproductive lives. This NOFO supports the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) in its mission to develop novel, safe, and effective contraceptive methods for men and women. 

An important component of any early stage product development project is to conduct the necessary research to demonstrate that if the proposed modulation is successful (e.g., inhibition of a specific enzyme), the desired result will be achieved (e.g., infertility). This is commonly referred to as “validation.” When a specific and defined molecule is targeted for modulation to affect a reproductive process resulting in the desired biological outcome (e.g., inhibition of a specific enzyme essential for sperm motility, resulting in a contraceptive effect), the specific molecule is referred to as a “target” and the validation process is referred to as “target validation.” If more than one specific molecule is targeted (e.g., two related enzymes), the same principles apply for the two molecules (i.e., demonstration that a well characterized modulation of both molecules will achieve the desired result). If the contraceptive product does not act on a defined molecular target or the molecular target is unknown (e.g., high molecular weight polymer), “validation” remains defined as demonstrating that if the proposed modulation is successful (e.g., sperm aggregation), the desired result will be achieved (e.g., infertility). In addition to supporting contraceptive development research on validated modulations, this NOFO encourages innovative ideas and supports early stage, high-risk projects lacking validation by allowing validation during the R61 phase. 

Phased Innovation Awards

This funding opportunity will use the R61/R33 phased award mechanism. Support will be provided for one year for the R61 phase, and up to three years of support may follow for the R33 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 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 funding decisions will be based on transition milestone accomplishment, preparedness of candidate product/technology for further development (if applicable), whether Aims of Phase II (R33 phase) continue to meet programmatic priorities in the context of the NOFO objectives, and availability of funds. Grants receiving a positive R33 funding decision will be transitioned to an R33 award without the need to submit a new application. It is anticipated that not all 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. 

Validation

The purpose of validation is to provide evidence that if the proposed research project is successful in achieving the modulation outlined in the application, the contraceptive method will be effective. Validation, as defined in this NOFO, is the demonstration in a mammalian species that the modulation proposed in the application to achieve a contraceptive effect, whether specific (e.g., neutralizing antibody against a known target) or non-specific (e.g., sperm motility inhibition by exposure to a high molecular weight polymer), results in infertility with a reasonable safety profile. 

• Validation should be discussed as part of the Research Strategy (and thus subject to the standard page limits) but must be in a separate section titled “Validation of Technology.”
• If the modulation proposed is validated, the “Validation of Technology” section should discuss how validation was determined, and if it is not validated, this section should include the plan for achieving validation in the R61 phase.
• If the application proposes a modulation by a biologic, high molecular weight polymer, or device to achieve contraceptive effect that is not validated, the milestones in the R61 phase must include one or more milestones that address the outcome of the validation studies. 
• If validation results solely from inhibition of sperm motility in vitro, it must be demonstrated in both human sperm and sperm from an appropriate model species for pharmaceutical development. 
• If the contraceptive target, product or device was not validated at the time of initial application, validation must be demonstrated in the transition package for transition to the R33 phase. 
• Validation is not required for applications focused on the development of delivery technologies for high molecular weight polymers or biologics. 
• Subfertility is not sufficient to constitute validation. (Subfertility as defined in this NOFO is the generation of live animals from in vivo mating trials and/or an in vivo or in vitro fertilization rate greater than zero.) 
• Reversibility does not need to be demonstrated as part of the validation process. 

Examples of research project types and acceptable forms of validation

For applications focused on modulation of defined molecular targets:  

The proposed contraception research project focuses on the modulation of specific molecular interactions between an administered molecule (e.g., antibody) and defined molecular target(s) (e.g., cell surface molecule) to achieve a defined response against the target (e.g., agglutination, inhibition) leading to a contraceptive effect (i.e., infertility). 

• Examples include but are not limited to: 
  • Targeted deletion of the gene encoding the target to be modulated results in infertility. 
  • Development of an antibody that binds specifically to the target and inhibits fertility in a concentration-dependent manner in a relevant model (e.g., in vitro fertilization). 
  • Specific inhibition of RNA corresponding to target to be modulated, leading to inhibition of gametogenesis or loss of gamete function as demonstrated by histology, mating studies or in vitro fertilization. 

For high molecular weight polymers: 

It is generally accepted that natural or synthetic high molecular weight polymers that interact with cells and inhibit transport (e.g., sperm motility) act via multiple non-specific binding events. Validation of these molecules requires (1) supporting evidence that their action is mediated by non-specific binding, (2) demonstration that the agent can achieve a contraceptive effect, and (3) a demonstrated and reasonable safety profile. See below for a discussion of reasonable safety profile. Program recommends a lack of toxicity at >50× the dose for the duration of contact expected to be used to achieve contraceptive effect in a relevant model. 

• Examples include but are not limited to: 
  • Use of the agent in a mammalian animal model results in infertility. 
  • Use of the agent to inhibit sperm motility in vitro to a level consistent with infertility at concentrations consistent with expected in vivo use. 
  • Use of the agent to inhibit in vitro fertilization when the product is at concentrations consistent with in vivo use. 

For projects focused on the development or improvement of delivery technologies for nonsteroidal contraceptive agents: 

• Validation is not required for delivery technologies for nonsteroidal contraceptive agents. 

Reasonable Safety Profile

To transition to the R33 phase, applicants must demonstrate that their proposed modulation is validated. A component of that validation is a reasonable safety profile. The application should define research to demonstrate in vivo safety parameters consistent with the intended dose/duration used in vitro or in vivo to achieve a contraceptive effect. There must be an appropriate differential between efficacy (e.g., IC₅₀) and safety (e.g., TC₅₀) sufficient to justify supporting further development. These parameters will vary by target, route of administration (e.g., PO, IV) and local versus systemic administration. Program recommends a lack of toxicity at >50× the dose for the duration of contact expected to be used to achieve contraceptive effect in a relevant model. Applicants should consider addressing toxicity as part of the transition milestones. Applicants who desire further discussion regarding this section are advised to consult the NICHD Scientific/Research contact. 

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. 

Research Scope

The purpose of this announcement is to support and facilitate multidisciplinary research approaches to the development of novel nonsteroidal contraceptive methods for men and women that act prior to fertilization using high molecular weight polymers, biologics (e.g., antibodies, nucleic acids), and medical devices. This NOFO supports research on pre-clinical stages of development from target validation through IND-enabling studies. This NOFO also supports the development of multipurpose prevention technologies (MPTs) with both contraceptive and anti-infective properties.

Contraception development research projects appropriate for this NOFO are limited to the following: 

• Male or female contraceptive development of high molecular weight polymers, biologics and devices based on nonsteroidal action 
• Male and/or female pre-coital on-demand contraception using high molecular weight polymers, biologics and devices based on nonsteroidal action 
• Male or female contraceptive device development
• MPT products based on nonsteroidal action with both contraceptive and anti-infective properties 
• Development or improvement of delivery technologies for nonsteroidal contraceptive agents including but not limited to vaginal films and microneedles 

Applications focused in the following areas are considered not responsive and will not be reviewed: 

• Applications not focused on the development of high molecular weight polymers, biologics (e.g., antibodies, nucleic acids), or medical devices for contraceptive or MPT use 
• Applications not focused on the development of a contraceptive product or delivery system 
• Applications focused on molecular targets for which there is no human ortholog 
• Applications based on mechanisms of contraceptive action that may act post-fertilization 
• Applications that focus on the development of methods that act via disruption of gamete travel through the oviduct or uterus, unless they act by occlusion of a segment of the reproductive tract
• Applications focused on the development of molecules or devices that disrupt/perturb the blood-testis and/or blood-epididymal barriers 
• Applications for the development of molecules for male or female contraception that act via steroid receptors 
• Applications for the development of contraceptive methods that require the administration of one or more exogenous steroidal molecules that act via nuclear steroid receptors 
• Applications focused on the development of delivery technologies for molecules that are not high molecular weight polymers or biologics
• Applications focused on condom development 
• Applications based on the following targets or target classes: 
  • Kinases 
  • CatSper 
  • Retinoic acid receptor alpha (RARα) 
• Applications for the development of the following molecules and/or their chemical derivatives: 
  • Gamendazole/H2-Gamendazole 
  • Adjudin 
  • Gossypol 
  • alpha-Chlorohydrin 
  • Inorganic elements (e.g., copper, zinc) 

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 propose clinical trials 
• 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 do not provide milestones for the transition from the R61 to the R33 phase of the award with go/no-go criteria and a Gantt chart (see Section IV.2) 

Milestones

All projects must be milestone-driven with clear go/no-go criteria. Milestones are deliverables for each specific aim of the project 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 unique 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. 

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 NICHD 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 may include milestones related to intellectual property (e.g., patentability report). 
• All applicants should consider addressing toxicity as part of the transition milestones. 

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. 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. For high molecular weight polymers: 

• Example milestones: 
  • Administration of compound in 3-day mouse mating study resulted in zero pups. 
  • Inhibition of sperm progressive motility in the presence of 4% polymer by >90% compared to no-polymer control. 

II. For biologics: 

• Example milestones: 
  • Antibody and antibody:antigen thermostability >37 °C. 
  • Antibody binding affinity K_D < 0.1 nM. 

III. For projects focused on the development or improvement of delivery technologies for nonsteroidal contraceptive agents: 

• Example milestone: 
  • Viability of cells treated with molecule of interest will be >90% of the control cell population after 7 days and show <10% caspase-1 activity versus control in an inflammasome activity.?

Subcontracting of Research Facilities

PDs/PIs may sub-contract portions of their research they are not able to conduct at their facility or institute to outside vendors (e.g., animal studies, protein production, stable cell line production, and x-ray crystallography). Applicants interested in subcontracting facilities must obtain agreement in advance, provide for the services in the budget, and include a letter of support in the application (see Section IV.2). Applicants who desire assistance in identifying subcontractors for animal studies or drug development services are advised to consult the NICHD Scientific/Research contact.

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

• 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)

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)

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 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. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference 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. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019.

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

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:

Leigh Allen, PhD
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-594-9151
Email: [email protected] 

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 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.

Facilities and Other Resources

If a subcontractor is proposed, provide relevant details on the subcontractor's research environment.

SF424(R&R) Senior/Key Person Profile

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

R&R Budget

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

Meetings (required) - Funds should be allocated for the PI(s) of the R61/R33 to attend an annual contraception research and development meeting. The US-based location and host of the meeting may vary, but air travel and hotel costs should be budgeted. 

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:

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 separate sections to describe the R61 and R33 phases. 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 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 validation status of the project at the time of submission.
• For non-validated projects, a plan to validate the target must be proposed in the R61 phase.
• For applications focused on development of a treatment containing two or more identified molecules, a discussion addressing potential compound interactions (i.e., drug:drug interactions).
• A comprehensive Gantt chart for each phase outlining the proposed research and incorporating all proposed milestones and go/no-go criteria.
• For projects that are in or have completed the optimization phase, a description of potential routes of delivery/administration.
• A discussion of current intellectual property status and strategy. 
• For MPT projects, discussion of the anti-infective strategy, the proposed delivery method, and the potential impact on public health.
• 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:
  • For non-validated projects, one or more quantitative milestones for completing validation studies.
  • Milestones that are specific, quantifiable, and scientifically justified; they must not be a simple restatement of the R61 phase specific aims.
  • Go/no-go criteria integrated into the milestone criteria.
  • Sufficiently scientifically rigorous milestones to assess progress in the R61 phase.
  • Discussion of suitability of the proposed milestones to assess success in the R61 phase.
  • Discussion of the implications of successful completion of these milestones for the proposed R33 phase.

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 SF424 (R&R) Application Guide.

Other Plan(s): Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages.

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

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 SF424 (R&R) Application Guide must be followed.

PHS Assignment Request Form

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

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

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

4. Submission Dates and Times

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

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

7. Other Submission Requirements and Information

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

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

For assistance with your electronic application or for more information on the electronic submission process, visit 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 SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

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

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.

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).

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.

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.

Specific to this NOFO: Transition Milestones - Are the proposed Transition Milestones well defined with quantifiable measures that are appropriate for assessing the success of the R61 phase of the awards? Is it clear how the R33 phase of the study will develop and expand once the R61 Transition Milestones are achieved? If the project requires validation, is the validation plan sufficient to address validation and reasonable to perform in time for transition to the R33 phase? Do the Gantt charts appropriately reflect the milestones? Are appropriate go/no-go criteria integrated into the milestone criteria?

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

As part of the scientific peer review, all applications 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 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 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 (NACHHD). The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities (e.g., branch research priorities, achievement of a balanced product development portfolio). 

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

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 recipient's business official.

Recipients must comply with any funding restrictions described in Section IV.6. 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 NOFO 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.

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that 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.

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: Generaland Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:

• Federalwide Standard Terms and Conditions for Research Grants
• Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
• Acknowledgment of Federal Funding

If a recipient is successful and receives a Notice of Award, 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.

If a recipient receives an award, the recipient must follow all applicable nondiscrimination laws. The recipient agrees to this when registering in SAM.gov. The recipient must also submit an Assurance of Compliance (HHS-690). To learn more, see the HHS Office for Civil Rights website.

HHS recognizes that NIH research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this NOFO.

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

Not applicable.

3. Data Management and Sharing

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.

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. 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.

The Federal Funding Accountability and Transparency Act of 2006 as amended (FFATA), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later.  All recipients 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 the threshold.  See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 2 CFR Part 200.113 and Appendix XII to 2 CFR Part 200, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period.  The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS).  This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313).  As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available.  Full reporting requirements and procedures are found in Appendix XII to 2 CFR Part 200 – Award Term and Condition for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

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

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]

Leigh Allen, PhD
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-594-9151
Email: [email protected]

Joanna Kubler-Kielb, PhD
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 301-435-6916
Email: [email protected]

Melissa Copeland
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Telephone: 240-401-3847
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.