RFA-FD-26-012.pdf

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Department of Health and Human Services Part 1. Overview Information Participating Organization(s)

U.S. Food and Drug Administration (FDA)

NOTE: The policies, guidelines, terms, and conditions stated in this Notice of Funding Opportunity (NOFO) may differ from those used by the NIH. Where this NOFO provides specific written guidance that may differ from the general guidance provided in the grant application form, please follow the instructions given in this NOFO.

The FDA does not follow the NIH Page Limitation Guidelines or the NIH Review Criteria. Applicants are encouraged to consult with FDA Agency Contacts for additional information regarding page limits and the FDA Objective Review Process.

Components of Participating Organizations

Center for Biologics Evaluation and Research (CBER) Center for Drug Evaluation and Research (CDER)

Funding Opportunity Title

Use of Digital Health Technologies in Clinical Investigations to Support Drug and Biological Product Development (U01) Clinical Trials Optional

Activity Code

U01 Research Project Cooperative Agreements

Announcement Type

New

Related Notices

None

Number (FON)

RFA-FD-26-012

Companion Funding Opportunity

None http://www.fda.gov/ http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CBER/default.htm http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/default.htm http://grants.nih.gov/grants/funding/ac_search_results.htm?text_curr=u01&Search.x=0&Search.y=0&Search_Type=Activity

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Number of Applications

See Part 2, Section III. 3. Additional Information on Eligibility.

Assistance Listing Number(s)

93.103

Purpose

The purpose of this Notice of Funding Opportunity (NOFO) is to address topics related to the use of digital health technologies (DHTs) for remote data acquisition in clinical investigations to support drug development.

Goals

The overarching goal of this notice of funding opportunity (NOFO) is to explore the role of DHTs (e.g., actigraphy, photography, contactless sensors) in drug development. These projects may involve engagement with researchers from academia, the biopharmaceutical industry, patient groups, and other stakeholders. The objectives of these projects are to advance DHTs for clinical drug development, expand the ability to capture early manifestations of chronic diseases, determine outcomes in populations with unmet medical needs and enhance convenience for trial participants by allowing for remote data acquisition in clinical investigations. The scope includes, but is not limited to, projects that focus on:

• Comparing digital measurements to traditional measurements in clinical trials to evaluate drugs

• Developing and evaluating novel endpoints using DHTs to address unmet needs for drug clinical trials (e.g., use of contactless room sensors to capture apnea in pediatric patients)

• Comparing metrics to evaluate continuous measurements (e.g., maximum activity and stamina)

• Capturing early manifestations of chronic diseases (e.g., non-memory related signs of dementia) through the use of DHTs (e.g., tests of balance or slowed reaction time)

Key Dates Posted Date

July 20, 2026

Open Date (Earliest Submission Date)

July 20, 2026

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Letter of Intent Due Date(s)

Not Applicable.

Application Due Date(s) August 20, 2026

All applications are due by 11:59 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.

No late applications will be accepted for this Notice of Funding Opportunity (NOFO).

AIDS Application Due Date(s) Not Applicable

Expiration Date

August 21, 2026

Advisory Council Review

Due Dates for E.O.

12372

Required Application Instructions Conformance to all requirements, both in the the Research (R) Instructions How to Apply - Application Guide and in the NOFO, is required and strictly enforced. Applicants must read and follow all application instructions in the How to Apply - Application Guide as well as any program-specific instructions noted in Section IV of this NOFO or an applicable related Notice posted to the Guide for Grants and Contracts.

When the program-specific instructions deviate from those in the How to Apply - Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

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 https://grants.nih.gov/grants/guide/url_redirect.htm?id=82400 https://grants.nih.gov/grants/guide/url_redirect.htm?id=82400 https://grants.nih.gov/grants/guide/url_redirect.htm?id=82400 http://grants.nih.gov/grants/guide/url_redirect.htm?id=11164 https://grants.nih.gov/grants/guide/url_redirect.htm?id=82400

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Section VII. Agency Contacts Section VIII. Other Information

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

The Food and Drug Administration (FDA) protects the public health by ensuring that medical products intended to be marketed in the United States are safe and effective for their intended use. FDA stakeholders are exploring innovative approaches to produce scientific evidence in support of regulatory submissions, including the development of new data sources, study designs, methodologies, and technologies. FDA encourages and facilitates the use of such innovative approaches while ensuring that the scientific evidence supporting marketing approvals meet our high evidentiary standards.

The Prescription Drug User Fee Act VII (PDUFA VII) commitment letter represents the product of discussions between the FDA, regulated industry, and public stakeholders, as mandated by Congress. The performance and procedural goals and other commitments specified in the PDUFA VII commitment letter apply to aspects of the human drug review program that are important for facilitating timely access to safe, effective, and innovative new medicines for patients. The commitment letter includes goals relating to the use of digital health technologies (DHTs) to support drug development and review. A DHT is a system that uses computing platforms, connectivity, software, and/or sensors, for health care and related uses. DHTs for remote data acquisition in clinical investigations can include hardware and/or software to perform one or more functions. DHTs may rely on or work with other technologies that support their operation, such as general-purpose computing platforms (e.g., smartphones) and communication networks.

Among other activities relating to the use of DHTs, FDA has established a Framework for the Use of DHTs in Drug and Biological Product Development to guide the use of DHT-derived data in regulatory decision-making for drugs (hereinafter Framework). The Framework highlights FDA’s DHT efforts including workshops and demonstration projects; engagement with stakeholders; establishment of internal processes to support the evaluation of DHTs for use in drug development; promotion of shared learning and consistency regarding DHT-based policy, procedure, and analytic tool development; and publication of guidance documents. In addition, FDA’s webpage DHTs for Drug Development (available at:

https://www.fda.gov/science-research/science-and-research-special-topics/digital-health-technologies-dhts-drug-development) provides an overview of the ongoing DHT efforts, including demonstration projects.

A variety of project types are welcomed under this NOFO, applicable to drugs and biologics (not devices).

FDA is particularly interested in projects that evaluate the use of DHTs in drug development.

Project Objectives

The overarching goal of this notice of funding opportunity (NOFO) is to explore the role of DHTs (e.g., actigraphy, photography, contactless sensors) in drug development. These projects may involve engagement with researchers from academia, the biopharmaceutical industry, patient groups, and other stakeholders. The objectives of these projects are to advance DHTs for clinical drug development, expand the ability to capture early manifestations of chronic diseases, determine outcomes in populations with unmet medical needs and enhance convenience for trial participants by allowing for remote data acquisition in clinical investigations. The scope includes, but is not limited to, projects that focus on:

• Comparing digital measurements to traditional measurements in clinical trials to evaluate drugs https://www.fda.gov/science-research/science-and-research-special-topics/digital-health-technologies-dhts-drug-development https://www.fda.gov/science-research/science-and-research-special-topics/digital-health-technologies-dhts-drug-development

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• Developing and evaluating novel endpoints using DHTs to address unmet needs for drug clinical trials (e.g., use of contactless room sensors to capture apnea in pediatric patients)

• Comparing metrics to evaluate continuous measurements (e.g., maximum activity and stamina)

• Capturing early manifestations of chronic diseases (e.g., non-memory related signs of dementia) through the use of DHTs (e.g., tests of balance or slowed reaction time) See Section VIII. Other Information for award authorities and regulations.

Investigators proposing FDA-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

Cooperative Agreement: A financial assistance mechanism used when there will be substantial Federal scientific or programmatic involvement. See Section VI.2 for additional information about the substantial involvement for this NOFO.

Application Types Allowed

New 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?

Funds Available and Anticipated Number of Awards

The number of awards is contingent upon FDA appropriations and the submission of a sufficient number of meritorious applications. Award will provide 1 (one) year of support and include future recommended support for up to 1 (one) additional year contingent upon annual appropriations, availability of funding and satisfactory recipient performance.

CDER intends to commit up to $2.2 million in FY 2026 to fund up to 2 (two) awards.

Award Budget

Application budgets are not limited but need to reflect the actual needs of the proposed project and should not exceed the following in total costs (direct and indirect):

YR 01: $1,100,000

YR 02: $1,100,000

https://researchmethodsresources.nih.gov/ http://grants.nih.gov/grants/guide/url_redirect.htm?id=11116 https://grants.nih.gov/grants/guide/url_redirect.htm?id=82370

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Award Project Period

The scope of the proposed project should determine the project period.

The maximum project period is 2 (two) years.

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

Section III. Eligibility Information 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)

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 not 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 HHS Grants Policy Statement for additional information https://www.hhs.gov/sites/default/files/hhs-grants-policy-statement-oct-2025.pdf http://grants.nih.gov/grants/guide/url_redirect.htm?id=11118 https://grants.nih.gov/grants/guide/url_redirect.htm?id=82400 https://www.hhs.gov/sites/default/files/hhs-grants-policy-statement-oct-2025.pdf

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• 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.

The PD/PI should be an established investigator in the scientific area in which the application is targeted and capable of providing both administrative and scientific leadership to the development and implementation of the proposed program. The PD/PI will be expected to monitor and assess the program and submit all documents and reports as required.

2. Cost Sharing This NOFO does not require cost sharing as defined in the HHS Grants Policy Statement.

3. Additional Information on Eligibility Number of Applications Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The FDA will not accept duplicate or highly overlapping applications under review at the same time.

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.

https://grants.nih.gov/grants/guide/url_redirect.htm?id=82390 http://grants.nih.gov/grants/guide/url_redirect.htm?id=11176 https://grants.nih.gov/grants/guide/url_redirect.htm?id=11123 http://grants.nih.gov/grants/guide/url_redirect.htm?id=82300 https://grants.nih.gov/grants/guide/url_redirect.php?id=82400

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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 How to Apply - 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.

For this specific NOFO, the Research Strategy section is limited to 12 pages.

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.

Applications requesting multiple years of support must complete and submit a separate detailed budget breakdown and narrative justification for each year of financial support requested.

If an applicant is requesting indirect costs as part of their budget, a copy of the most recent Federal indirect cost rate or F&A agreement must be provided as part of the application submission. This agreement should be attached to the RESEARCH & RELATED Other Project Information Component as line #12 'Other Attachments'.

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:

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.

All applicants planning research (funded or conducted in whole or in part by FDA) 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.

https://grants.nih.gov/grants/guide/url_redirect.htm?id=82400 https://grants.nih.gov/grants/guide/url_redirect.htm?id=82400 https://grants.nih.gov/grants/guide/url_redirect.htm?id=82400 https://grants.nih.gov/grants/guide/url_redirect.htm?id=82400 https://grants.nih.gov/grants/guide/url_redirect.htm?id=61134 https://grants.nih.gov/grants/guide/url_redirect.htm?id=82400 https://grants.nih.gov/grants/guide/url_redirect.htm?id=82400 https://grants.nih.gov/grants/guide/url_redirect.htm?id=82400 https://grants.nih.gov/grants/guide/url_redirect.htm?id=82400 https://grants.nih.gov/grants/guide/url_redirect.htm?id=82400 https://grants.nih.gov/grants/guide/url_redirect.htm?id=82400 https://grants.nih.gov/grants/guide/url_redirect.htm?id=82400 https://grants.nih.gov/grants/guide/url_redirect.htm?id=82400

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

Not applicable.

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 FDA-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, FDA's electronic system for grants administration. FDA 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 FDA Policy on Late Application Submission.

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

https://grants.nih.gov/grants/guide/url_redirect.htm?id=82400 https://grants.nih.gov/grants/guide/url_redirect.htm?id=82400 https://grants.nih.gov/grants/guide/url_redirect.htm?id=82400 https://grants.nih.gov/grants/guide/url_redirect.htm?id=82400 https://grants.nih.gov/grants/glossary.htm#DelayedOnsetStudy https://grants.nih.gov/grants/guide/url_redirect.htm?id=82400 https://grants.nih.gov/grants/guide/url_redirect.htm?id=82400 https://grants.nih.gov/grants/guide/url_redirect.html?id=82380 http://grants.nih.gov/grants/guide/url_redirect.htm?id=11128 http://grants.nih.gov/grants/guide/url_redirect.htm?id=11123

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Information on the submission process and a definition of on-time submission are provided in the How to Apply - Application Guide.

6. Funding Restrictions All activities proposed in your application and budget narrative must align with applicable law, including but not limited to statutes, executive orders, federal regulations, and applicable judicial holdings.

Accordingly, discretionary awards shall not be used to fund, promote, encourage, subsidize, or facilitate:

racial preferences or other forms of racial discrimination by the recipient, including activities where race or intentional proxies for race will be used as a selection criterion for employment or program participation; denial by the recipient of the sex binary in humans, or the belief that sex is a chosen or mutable characteristic; illegal immigration; or any other initiatives that compromise public safety. If an application does not align, the application will not receive funding to the extent permitted by law and applicable court orders.

Additional funding restrictions may be part of the Notice of Award.

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 the FDA. 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 assigned FDA Grants Management Specialist and responsiveness by components of participating organizations. 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.

Not applicable.

Section V. Application Review Information

1. Criteria https://grants.nih.gov/grants/guide/url_redirect.htm?id=82400 https://grants.nih.gov/grants/guide/url_redirect.htm?id=82400 https://grants.nih.gov/grants/guide/url_redirect.htm?id=82400 https://grants.nih.gov/grants/guide/url_redirect.htm?id=82400 https://grants.nih.gov/grants/guide/url_redirect.htm?id=82400 https://grants.nih.gov/grants/how-to-apply-application-guide/due-dates-and-submission-policies/dealing-with-system-issues.htm https://grants.nih.gov/grants/how-to-apply-application-guide/due-dates-and-submission-policies/dealing-with-system-issues.htm https://grants.nih.gov/grants/guide/url_redirect.htm?id=82400 http://grants.nih.gov/grants/guide/url_redirect.htm?id=11146 http://grants.nih.gov/grants/guide/url_redirect.htm?id=82299 http://grants.nih.gov/grants/guide/url_redirect.htm?id=82299

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

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

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

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

Significance

Maximum Points: 20

Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

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

Investigator(s)

Maximum Points: 20

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

In addition, for applications involving clinical trials With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

Innovation

Maximum Points: 25

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions?

Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

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

Approach

Maximum Points: 25

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Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed?

Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

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

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

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

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

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

Environment

Maximum Points: 10

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Will the scientific environment in which the work will be done contribute to the probability of success?

Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

In addition, for applications involving clinical trials If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

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

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

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

Study Timeline Specific to applications involving clinical trials

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified?

Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

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

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, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

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

Vertebrate Animals http://grants.nih.gov/grants/guide/url_redirect.htm?id=11175 http://grants.nih.gov/grants/guide/url_redirect.htm?id=11175

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The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following three points: (1) a complete description of all proposed procedures including the species, strains, ages, and total numbers of animals to be used; (2) justifications that the species is appropriate for the proposed research and why the research goals cannot be accomplished using an alternative non-animal model; and (3) interventions including analgesia, anesthesia, sedation, palliative care, and humane endpoints that will be used to limit any unavoidable discomfort, distress, pain and injury in the conduct of scientifically valuable research.

Methods of euthanasia and justification for selected methods, if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals, is also required but is found in a separate section of the application. For additional information on review of the Vertebrate Animals Section, please refer to the Worksheet for Review of the Vertebrate Animals Section.

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

Resubmissions Not Applicable

Renewals Not Applicable

Revisions Not Applicable

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

Applications from Foreign Organizations Not Applicable.

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

Resource Sharing Plans Reviewers will comment on whether the Resource Sharing Plan(s) (i.e., Sharing Model Organisms) or the rationale for not sharing the resources, is reasonable.

Authentication of Key Biological and/or Chemical Resources:

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

Budget and Period of Support Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Applications will be evaluated for scientific and technical merit by (an) appropriate Objective Review Committee convened by the FDA, using the stated review criteria. Assignment to an Objective Review Committee will be shown in eRA Commons.

http://grants.nih.gov/grants/guide/url_redirect.htm?id=11150 https://sharing.nih.gov/other-sharing-policies/model-organism-sharing-policy#policy-overview

FDA OCT _ 2026 Page 16 of 21

As part of the objective review, all applications will receive a written critique.

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

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 compete for available funds with all other recommended applications submitted in response to this NOFO. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by objective review.

• Availability of funds.

• Relevance of the proposed project to program priorities.

3. Anticipated Announcement and Award Dates Successful applicants will be notified of additional information that may be required or other actions leading to an award. The decision not to award a grant, or to award a grant at a particular funding level, is discretionary and is not subject to appeal to any FDA or HHS official or board.

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

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 HHS Grants Policy Statement.

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 FDA-funded studies, the recipient must provide FDA copies of documents related to all major changes in the status of ongoing protocols.

Individual awards are based on the application submitted to, and as approved by, the FDA 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). The FDA expects registration and results reporting of all trials whether required under the law or not. For more information, see the HHS Grants Policy Statement.

Data and Safety Monitoring Requirements: The FDA policy for data and safety monitoring requires oversight and monitoring of all FDA-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 the HHS Grants Policy Statement and in the application instructions (SF424 (R&R) and PHS 398).

https://grants.nih.gov/grants/policy/nihgps/html5/section_2/2.4.2_appeals_of_initial_scientific_review.htm https://www.hhs.gov/sites/default/files/hhs-grants-policy-statement-oct-2025.pdf https://grants.nih.gov/grants/guide/rfa-files/RFA-OD-25-003.html#FundingRestrictionsanchor https://www.hhs.gov/sites/default/files/hhs-grants-policy-statement-oct-2025.pdf https://register.clinicaltrials.gov/ https://www.hhs.gov/sites/default/files/hhs-grants-policy-statement-april-2025.pdf https://www.hhs.gov/sites/default/files/hhs-grants-policy-statement-april-2025.pdf

FDA OCT _ 2026 Page 17 of 21

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 As of October 1, 2025, HHS has adopted 2 CFR Part 200, with some modifications included in 2 CFR Part

300. These regulations replace those in 45 CFR Part 75.

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

• The rules listed at 2 CFR Part 200, Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards.

• All FDA grant and cooperative agreement awards include the HHS Grants Policy Statement as part of the terms and conditions in the Notice of Award (NoA). The NoA includes the requirements of this NOFO.

All federal statutes and regulations relevant to federal financial assistance, including those highlighted in the HHS Grants Policy Statement.

Recipients are responsible for ensuring that their activities comply with all applicable federal regulations.

FDA may terminate awards under certain circumstances. See 2 CFR Part 200.340 Termination and HHS Grants Policy Statement.

Successful recipients under this NOFO agree that:

Where the award funding involves implementing, acquiring, or upgrading health IT for activities by any funded entity, recipients and subrecipient(s) are required to: Use health IT that meets standards and implementation specifications adopted in 45 CFR part 170, Subpart B, if such standards and implementation specifications can support the activity.