This Trailblazer Award is an opportunity for NIH-defined New and Early Stage Investigators (https://grants.nih.gov/policy/early-investigators/index.htm) to pursue research programs that integrate engineering and the physical sciences with the life and/or biomedical sciences. A Trailblazer project may be exploratory, developmental, proof of concept, or high risk-high impact, and may be technology design-directed, discovery-driven, or hypothesis-driven. Importantly, applicants must propose research approaches for which there are minimal or no preliminary data.A distinct feature for this FOA is that no preliminary data are required, expected, or encouraged. However, if available, minimal preliminary data are allowed. Preliminary data are defined as material which the applicant has independently produced and not yet published in a peer-reviewed journal. All preliminary data should be clearly marked and limited to one-half page, which may include one figure. Applications including data more than one-half page or more than one figure will be considered noncompliant with the FOA instructions and will not go forward to review.

PA-25-169: Trailblazer Award for New and Early Stage Investigators (R21 Clinical Trial Optional)

March 31, 2025

This funding opportunity was updated to align with agency priorities. Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission.

Part 1. Overview Information

Participating Organization(s) National Institutes of Health (NIH)

Components of Participating Organizations

• National Institute of Biomedical Imaging and Bioengineering (NIBIB)
• National Eye Institute (NEI)
• National Institute on Aging (NIA)

Funding Opportunity Title Trailblazer Award for New and Early Stage Investigators (R21 Clinical Trial Optional)

Activity Code R21 Exploratory/Developmental Research Grant

Announcement Type Reissue of PAR-24-022

Related Notices See Notices of Special Interest associated with this funding opportunity

• June 16, 2025 - Notice of Change to PA-25-169, "Trailblazer Award for New and Early-Stage Investigators (R21 Clinical Trial Optional)". See Notice NOT-EB-25-007.
• March 31, 2025 - This funding opportunity was updated to align with agency priorities. Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission.
• April 4, 2024 - Overview of Grant Application and Review Changes for Due Dates on or after January 25, 2025. See Notice NOT-OD-24-084.
• August 31, 2022 - Implementation Changes for Genomic Data Sharing Plans Included with Applications Due on or after January 25, 2023. See Notice NOT-OD-22-198.
• August 5, 2022 - Implementation Details for the NIH Data Management and Sharing Policy. See Notice NOT-OD-22-189.

Funding Opportunity Number (FON) PA-25-169

Companion Funding Opportunity None

Number of Applications See Section III. 3. Additional Information on Eligibility

Assistance Listing Number(s) 93.286, 93.866, 93.867

Funding Opportunity Purpose This Trailblazer Award is an opportunity for NIH-defined New and Early Stage Investigators (https://grants.nih.gov/policy/early-investigators/index.htm) to pursue research programs that integrate engineering and the physical sciences with the life and/or biomedical sciences. A Trailblazer project may be exploratory, developmental, proof of concept, or high risk-high impact, and may be technology design-directed, discovery-driven, or hypothesis-driven. Importantly, applicants must propose research approaches for which there are minimal or no preliminary data.

A distinct feature for this NOFO is that no preliminary data are required, expected, or encouraged. However, if available, minimal preliminary data are allowed. Preliminary data are defined as material which the applicant has independently produced and not yet published in a peer-reviewed journal. All preliminary data should be clearly marked and limited to one-half page, which may include one figure.

Applications including data more than one-half page or more than one figure will be considered noncompliant with the NOFO instructions and will not go forward to review.

Key Dates

| Date Type | Date
Posted Date: January 08, 2025 Open Date (Earliest Submission Date): January 16, 2025

The following table includes NIH standard due dates marked with an asterisk. Dates in bold and italics reflect changes per NOT-EB-25-007.

• 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.

Expiration Date New Date: May 08, 2026 per NOT-EB-25-007 (Prior Date January 08, 2026).

Due Dates for E.O. 12372 Not Applicable

Required Application Instructions 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.

• Use the NIH ASSIST system to prepare, submit and track your application online.
• 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.
• 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

The rapid evolution and vitality of the biomedical sciences benefit from the contributions and creativity of investigators in the early stages of their careers, and a continuous infusion of new ideas, techniques, and perspectives from other fields. This Trailblazer Award is an opportunity for New and Early Stage Investigators to pursue research programs at the interface of engineering and/or the physical sciences with the biomedical sciences. Applicants are encouraged to contact the appropriate NIBIB Program Director assigned to their specific scientific program area (https://www.nibib.nih.gov/research-funding) to discuss the appropriateness of the project before submission. This Notice of Funding Opportunity (NOFO) employs an R21 Exploratory/Developmental Research Grant mechanism enhanced to provide $400,000 in direct costs over three years, allowing expanded time and resources to pursue a new or emerging research program.

All applicants to this NOFO must meet the NIH definition of New or Early Stage Investigator (https://grants.nih.gov/policy/new_investigators/index.htm).

The application of principles and techniques from engineering and the quantitative sciences, such as physics, mathematics, chemistry, and computer sciences, is providing innovative technologies and novel methods to accelerate the pace of biomedical research, producing new understanding of disease mechanisms and translating these new discoveries to improve human health. The Trailblazer Award seeks to catalyze the development of transdisciplinary research approaches with the potential to open new areas of biomedical investigation.

A Trailblazer project may be exploratory, developmental, proof of concept or have high risk-high impact goals. Importantly, the proposed research for this NOFO may be technology design-directed and may or may not be hypothesis-driven. In the context of this NOFO, innovation encompasses approaches to address well-defined, unmet biomedical research needs through the development of new methods, ideas, or technologies; early steps along the path toward delivery of a new capability or method; and the integration of existing components in a previously unproven format. High-impact projects should transform our understanding or practice by applying an innovative approach to an important biomedical challenge. For projects supported by a Trailblazer Award, successful results should provide a solid foundation for further research under other funding mechanisms, such as the R01. Applicants will be considered ineligible for this funding opportunity if they have submitted an R01, R15 or any other R21 application, with a participating IC as the primary IC within the same review cycle. An awardee may not hold concurrent Trailblazer awards.

Trailblazer approaches are expected to differ substantially from current thinking or practice, therefore, extensive preliminary data demonstrating feasibility is an indication that the project is beyond the scope of this NOFO. Reviewers’ determinations of merit will rely instead on the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge, understanding or practice. Applicants can provide appropriate justification for the proposed work through literature citations, data from other publicly available sources, or analytical and computational models. The proposed research will likely involve considerable risk that the work may not be successful, so applicants should clearly explain the significance of the work to allow the reviewers to determine whether the potential impact justifies these risks.

Preliminary Data: Trailblazer applications are meant to be exploratory, novel, and non-incremental. We encourage the submission of high-risk, high-reward projects. A distinct feature for this FOA is that no preliminary data are required, expected, or encouraged. However, if available, some minimal preliminary data is allowed. Preliminary data are defined as material which the applicant has independently produced and not yet published in a peer-reviewed journal. Such evidence, if provided, should not represent work involving the aims of the Trailblazer application. All preliminary data must be clearly marked and limited to one-half page, which may include one figure.

Applications including data more than one-half page or more than one figure will be considered noncompliant with the NOFO instructions and not go forward to review.

Figures containing published data must include citations within the figure legend. Published data that is included in the research plan, biographical sketch or elsewhere in the application must be cited adjacent to each occurrence. Data that is published must be unambiguously identified as such within the application. References and data from widely available preprints that have a Digital Object Identifier (DOI) are considered published.

Clinical Trials: For applications submitted that propose clinical trials, this NOFO will only support applications proposing early-stage clinical trials through Phase I, first-in-human, safety, feasibility, or other small clinical trials that inform the early-stage technology development in the submitted application. This NOFO will not support applications proposing Phase II, III, IV or pivotal clinical trials, or trials in which the primary outcome is efficacy, effectiveness, or a post-market concern.

Applicants are strongly encouraged to contact the Scientific/Research contact for this NOFO for guidance in advance of submitting an application to ensure their proposed project is in compliance with new NIH human subjects research and clinical trials policies (https://grants.nih.gov/policy/clinical-trials.htm) and consistent with the types of clinical trial projects that each IC supports.

Not all research endeavors will be suitable for this NOFO. Projects from New and Early Stage Investigators that are supported by extensive preliminary data should be submitted to the Parent R01 Clinical Trial Not Allowed FOA (https://grants.nih.gov/grants/guide/pa-files/pa-20-185.html) or the Parent R01 Clinical Trial Required FOA (https://grants.nih.gov/grants/guide/pa-files/pa-20-183.html) or Stephen I. Katz Early Stage Investigator Research Project Grant (R01 Clinical Trial Not Allowed) (https://grants.nih.gov/grants/guide/pa-files/PAR-21-038.html). Established investigators proposing exploratory and developmental projects should consider the Parent R21 Clinical Trial Not Allowed FOA (https://grants.nih.gov/grants/guide/pa-files/PA-20-195.html) or the Parent R21 Clinical Trial Required FOA (https://grants.nih.gov/grants/guide/pa-files/PA-20-194.html). Projects of limited cost or scope that use widely accepted approaches and methods within well-established fields should be submitted to the Parent R03 FOA (https://grants.nih.gov/grants/guide/pa-files/PA-20-200.html). Projects that propose incremental improvements in well-established areas of investigation are not appropriate for this NOFO.

Specific Research Objectives and Scope

Each institute has specific areas of research interest.

National Institute of Biomedical Imaging and Bioengineering (NIBIB) NIBIB interests include the development and integration of advanced engineering, imaging, and computational technologies with life sciences for the improvement of human health and medical care. An application is not within the NIBIB mission and will be withdrawn from consideration if its principal focus is development of technologies whose goal is to understand basic biological function or mechanisms. Additionally, NIBIB only supports projects whose technology would ultimately be applicable to a broad spectrum of disorders and diseases rather than being limited to only a single tissue, organ, or physiological condition. However, applicants may propose research that utilizes only a single tissue, organ or physiological condition as a model system to facilitate the development of what is expected to be a more broadly applicable emerging technology. An application is not within the NIBIB mission and will be withdrawn from consideration if the proposed technology or approach has limited application to a single disease, organ, or physiological condition.

For this Funding Opportunity Announcement, if an application proposes a clinical trial, NIBIB funding of clinical trials will be in accordance with NOT-EB-21-005 "NIBIB Guidance for Support of Clinical Trial Applications." Briefly, NIBIB will only support mission-focused (see NIBIB's program areas) early stage clinical trial applications, i.e., feasibility, Phase I, first-in-human, safety, or other small clinical trials, that inform early stage technology development. NIBIB will not support applications proposing pivotal, Phase II, III, IV, or trials in which the primary outcome is efficacy, effectiveness, or a post-market concern. Also, mechanistic trials are not supported unless the primary focus of the project is on technology development.

Applicants are strongly encouraged to contact the NIBIB Scientific Contact listed in this FOA for guidance in advance of submitting an application that includes human subjects research to ensure their proposed project is in compliance with new NIH human subjects research and clinical trials policies (https://grants.nih.gov/policy/clinical-trials.htm) and consistent with the types of clinical trial applications that NIBIB supports.

National Eye Institute (NEI) NEI leads the federal government in conducting and supporting research in vision research. The mission of the National Eye Institute (NEI) is to eliminate vision loss and improve quality of life through vision research. The NEI has framed its current strategic plan around this mission which addresses multiple opportunities as challenges in the vision field.

NEI will support applications that address or seek fundamental knowledge related to vision sciences, including, but not limited to: cellular and molecular neuroscience, imaging, genetics, development, basic/translational research on vision including how the visual system works from the eyes to the brain in health and disease. The overarching goal is to reduce visual impairment and blindness and thus resulting in an improvement in the quality of life for people of all ages. In all these areas and related areas of vision sciences research, NEI encourages an emphasis on understanding and addressing health disparities that are experienced by underserved populations.

For this funding opportunity, only the following trials will be supported by NEI:

• Mechanistic trials defined as studies designed to understand a biological or behavioral process, the pathophysiology of a disease, or the mechanism of action of an intervention (i.e., HOW an intervention works, but not IF it works or is safe).

Clinical trials that seek to answer specific questions about safety, tolerability, clinical efficacy, effectiveness, clinical management, and/or implementation of pharmacologic, biologic, surgical, or device (invasive or non-invasive) interventions, preventive, therapeutic, and services interventions will not be supported under this NOFO. Please refer to https://www.nei.nih.gov/grants-and-training/funding-opportunities to find the appropriate NIH or NEI-specific NOFO for such clinical trials.

Applications considered for funding by the NEI must fall within the areas of emphasis detailed in the NEI Strategic Plan. ( NEI Strategic Plan: Vision for the Future (PDF 22.5 MB) )

To determine if your research fits within the NIBIB mission, please contact the appropriate Program Director in your scientific program area of interest (https://www.nibib.nih.gov/research-funding).

National Institute on Aging (NIA) NIA leads the federal government in conducting and supporting research on aging and the health and well-being of older people. To fulfill its mission, NIA supports technologies which aim to increase the research community's understanding of the aging process, as well as diseases, conditions, and needs associated with growing older, in order to extend the healthy, active years of life. Studies of interest to NIA include, but are not limited to, the following:

• Technology development for imaging modalities and visualization tools as applied to aging
• Applications of artificial intelligence, machine learning, or health monitoring technologies to the study of aging biology or age related diseases
• Bioinformatic, statistical, and computational approaches in aging biology research
• Novel sensors and biomarkers for monitoring age-related changes and diseases
• Less invasive and more ubiquitous ways of collecting biological and diagnostic data
• Systems biology of aging
• Other emerging technologies that may benefit aging research and reflect new directions, such as new imaging technologies or novel biophysical approaches
• Tissues-, organs- and organ systems-on-a-chip technologies
• Imaging of any of the pillars or hallmarks of aging which include protein homeostasis, nuclear and DNA integrity, metabolism and mitochondrial quality control, cellular senescence, autophagy and cell death, and other hallmarks as described in the literature

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

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

Section II. Award Information

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

Application Types Allowed

• New
• Resubmission
• Revision

The OER Glossary and the How to Apply Application Guide provide details on these application types. Only those application types listed here are allowed for this NOFO.

Clinical Trial? Optional: Accepting applications that either propose or do not propose clinical trial(s).

Need help determining whether you are doing a clinical trial? https://grants.nih.gov/policy/clinical-trials/defining-clinical-trials.htm

Funds Available and Anticipated Number of Awards The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

Award Budget Application budgets may not exceed $400,000 direct costs over a maximum three-year funding period. No more than $200,000 direct costs may be requested in any single year.

Award Project Period The scope of the proposed project should determine the project period. The maximum project period is 3 years.

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

Eligible Organizations

• Higher Education Institutions
  • 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

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

Required Registrations

Applicant Organizations Applicant organizations must complete and maintain the following registrations as described in the 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.

Eligible Individuals (Program Director/Principal Investigator) Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with 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.

This FOA targets New and Early Stage Investigators integrating engineering and physical sciences with the biomedical sciences. Eligible individuals must be a) NIH-defined Early Stage Investigators; or b) NIH-defined New Investigators (https://grants.nih.gov/policy/early-investigators/index.htm). For applications with multiple PDs/PIs, all PDs/PIs must be eligible to apply for this award.

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).

Applicants will be considered ineligible for this funding opportunity if they have submitted an R01, R15 or any other R21 application, with a participating IC as the primary IC within the same review cycle. Applicants may not hold concurrent Trailblazer awards.

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.

Instructions for Application Submission 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 or Modular 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:
  • Research Strategy: Trailblazer R21 applications only allow minimal preliminary data. Consequently, determinations of merit and feasibility will rely instead on the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Applicants are encouraged to provide justification for the proposed work through literature citations, data from other publicly available sources, analytical and computational models, or when available, from a limited amount of investigator-generated data. Since Trailblazer grant applications could involve considerable risk that the proposed work may not be successful, applicants are encouraged to clearly explain the significance of the proposed work, to allow the reviewers to determine whether the potential impact outweighs these risks. Trailblazer applications are meant to be exploratory, novel, and non-incremental. We encourage the submission of high-risk, high-reward projects. Applications for Trailblazer R21 awards should describe projects distinct from those supported through the traditional R01 mechanism, which are generally longer-term systematic investigations supported by extensive preliminary data. Projects should have well-defined goals with the potential for future development. Applicants should explain how success in this project could lead to further development under other funding mechanisms, such as the R01.
  • Preliminary Data: Preliminary data are defined as material which the applicant has independently produced and not yet published in a peer-reviewed journal. Such evidence, if provided, should not represent work involving the aims of the Trailblazer application. All preliminary data must be clearly marked and limited to one-half page, which may include one figure. Applications including data more than one-half page or more than one figure will be considered noncompliant with the FOA instructions and not go forward to review. Figures containing published data must include citations within the figure legend. Published data that is included in the research plan, biographical sketch or elsewhere in the application must be cited adjacent to each occurrence. Data that is published must be unambiguously identified as such within the application. References and data from widely available preprints that have a Digital Object Identifier (DOI) are considered published.
• 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.

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.

7. Other Submission Requirements and Information

• 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, NIH. Applications that are incomplete or non-compliant will not be reviewed.

Mandatory Disclosure 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 General Grant Self Disclosure Program at oig.hotline@hhs.gov.

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:

Overall Impact Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following 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.

Scored Review Criteria Reviewers will evaluate 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 criterion score.

• Factor 1. Importance of the Research (Significance and Innovation)

  • Significance Evaluate the importance of the proposed research in the context of current scientific challenges and opportunities, either for advancing knowledge within the field, or more broadly. Assess whether the application addresses an important gap in knowledge in the field, would solve a critical problem, or create a valuable conceptual or technical advance. Evaluate the rationale for undertaking the study, the rigor of the scientific background for the work (e.g., prior literature and/or preliminary data) and whether the scientific background justifies the proposed study.
  • Innovation Evaluate the extent to which innovation influences the importance of undertaking the proposed research. Note that while technical or conceptual innovation can influence the importance of the proposed research, a project that is not applying novel concepts or approaches may be of critical importance for the field. Evaluate whether the proposed work applies novel concepts, methods or technologies or uses existing concepts, methods, technologies in novel ways, to enhance the overall impact of the project.

• Factor 2. Rigor and Feasibility (Approach)

  • Approach Evaluate the scientific quality of the proposed work. Evaluate the likelihood that compelling, reproducible findings will result (rigor) and assess whether the proposed studies can be done well and within the timeframes proposed (feasibility).
    • Rigor: Evaluate the potential to produce unbiased, reproducible, robust data. Evaluate the rigor of experimental design and whether appropriate controls are in place. Evaluate whether the sample size is sufficient and well-justified. Assess the quality of the plans for analysis, interpretation, and reporting of results. Evaluate whether the investigators presented adequate plans to address relevant biological variables, such as sex or age, in the design, analysis, and reporting. For applications involving human subjects or vertebrate animals, also evaluate:
      • the rigor of the intervention or study manipulation (if applicable to the study design).
      • whether outcome variables are justified.
      • whether the results will be generalizable or, in the case of a rare disease/special group, relevant to the particular subgroup.
      • whether the sample is appropriate and sufficiently diverse to address the proposed question(s). For applications involving human subjects, including clinical trials, assess the adequacy of inclusion plans as appropriate for the scientific goals of the research. Considerations of appropriateness may include disease/condition/behavior incidence, prevalence, or population burden, population representation, and/or current state of the science.
    • Feasibility: Evaluate whether the proposed approach is sound and achievable, including plans to address problems or new challenges that emerge in the work. For proposed studies in which feasibility may be less certain, evaluate whether the uncertainty is balanced by the potential for major advances. For applications involving human subjects, including clinical trials, evaluate the adequacy and feasibility of the plan to recruit and retain a study population that appropriately models the target population. Additionally, evaluate the likelihood of successfully achieving the proposed enrollment based on age, race, ethnicity, and sex. For clinical trial applications, evaluate whether the study timeline and milestones are feasible.

• Factor 3. Expertise and Resources (Investigator(s) and Environment)

  • Investigator(s) Evaluate whether the investigator(s) have demonstrated background, training, and expertise, as appropriate for their career stage, to conduct the proposed work. For Multiple Principal Investigator (MPI) applications, assess the quality of the leadership plan to facilitate coordination and collaboration.
  • Environment Evaluate whether the institutional resources are appropriate to ensure the successful execution of the proposed work.

Additional Review Criteria 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.

• Protections for Human Subjects For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects; 2) adequacy of protection against risks; 3) potential benefits to the subjects and others; 4) importance of the knowledge to be gained; and 5) data and safety monitoring for clinical trials. For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, evaluate: 1) the justification for the exemption; 2) human subjects involvement and characteristics; and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.
• Vertebrate Animals When the proposed research includes Vertebrate Animals, evaluate the involvement of live vertebrate animals according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animals Section.
• Biohazards When the proposed research includes Biohazards, evaluate whether specific materials or procedures that will be used are significantly hazardous to research personnel and/or the environment, and whether adequate protection is proposed.
• Resubmissions As applicable, evaluate the full application as now presented.
• Renewals As applicable, evaluate the progress made in the last funding period.
• Revisions As applicable, evaluate the appropriateness of the proposed expansion of the scope of the project.

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

• Authentication of Key Biological and/or Chemical Resources For projects involving key biological and/or chemical resources, evaluate the brief plans proposed for identifying and ensuring the validity of those resources.
• Budget and Period of Support Evaluate whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

2. Review and Selection Process Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by Center for Scientific Review, 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.

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 appropriate national Advisory Council or Board. The following will be considered in making funding decisions:

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

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.
• 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 Laws and Regulations Enforced by 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.
• 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.

Cooperative Agreement Terms and Conditions of Award 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 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.

Application Submission Contacts

• 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