PA-23-317 is a grant from the National Institutes of Health (NIH) that funds competing revisions and administrative supplements to existing NIH single-project research grants and cooperative agreements. The program supports researchers who need to expand the scope or add new dimensions to active NIH-funded projects, with clinical trial components optional.

Eligible applicants are current NIH grant recipients at participating institutes including NIAID, NIMH, NCI, NIDDK, NICHD, NIDA, NIEHS, and others. Applicants must have an active single-project research grant or cooperative agreement, and competing revision notices of special interest from individual institutes specify eligible activity codes.

PA-23-317: Competing Revisions to Existing NIH Single Project Research Grants and Cooperative Agreements (Clinical Trial Optional) 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. Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) Components of Participating Organizations NATIONAL INSTITUTES OF HEALTH ( NIH ) Fogarty International Center ( FIC ) National Human Genome Research Institute ( NHGRI ) National Institute on Alcohol Abuse and Alcoholism ( NIAAA ) February 29, 2024 - Participation Added ( NOT-AI-24-034 ) National Institute of Allergy and Infectious Diseases ( NIAID ) Eunice Kennedy Shriver National Institute of Child Health and Human Development ( NICHD ) National Institute of Diabetes and Digestive and Kidney Diseases ( NIDDK ) National Institute on Drug Abuse ( NIDA ) National Institute of Environmental Health Sciences ( NIEHS ) Participation Added June 10, 2024 ( NOT-ES-24-013 ) National Institute of Mental Health ( NIMH ) National Institute on Minority Health and Health Disparities ( NIMHD ) National Center for Complementary and Integrative Health ( NCCIH ) National Center for Advancing Translational Sciences ( NCATS ) National Cancer Institute ( NCI ) Aging ( NIA ) - August 14, 2024 - Participation added (NOT-AG-24-059) National Eye Institute ( NEI ) - January 13, 2025 - Participation added ( NOT-EY-25-005 ) National Institute of Dental and Craniofacial Research ( NIDCR ) - June 23, 2025 - Participation added ( NOT-DE-26-002 ) All applications to this funding opportunity announcement should fall within the mission of the Institutes/Centers.

The following NIH Offices may co-fund applications assigned to those Institutes/Centers.

Office of Data Science Strategy ( ODSS ) Funding Opportunity Title Competing Revisions to Existing NIH Single Project Research Grants and Cooperative Agreements (Clinical Trial Optional) Competing Revision Notices of Special Interest (NOSIs) issued by the respective ICOs will specify the single project research activity codes under which recipients can apply (e.g., R01, U01).

Notices of Special Interest associated with this funding opportunity June 23, 2025 - Notice of Participation of the National Institute of Dental and Craniofacial Research (NIDCR) in PA-23-317, Competing Revisions to Existing NIH Single Project Research Grants and Cooperative Agreements (Clinical Trial Optional).

See Notice NOT-DE-26-002 May 9, 2025 - Notice to Applicants That the Simplified Review Framework Will be Applied to All Relevant Applications for August/October 2025 Councils. See Notice NOT-OD-25-116 . 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. January 13, 2025 - NEI Notice of Participation in PA-23-317, "Competing Revisions to Existing NIH Single Project Research Grants and Cooperative Agreements (Clinical Trial Optional)". See Notice NOT-EY-25-005 April 04, 2024 - Overview of Grant Application and Review Changes for Due Dates on or after January 25, 2025.

See Notice NOT-OD-24-084 November 13, 2024 - Notice of Special Interest (NOSI): NIMH Funding for Competing Revisions to Existing NIH Single Project Research Grants and Cooperative Agreements. See Notice NOT-MH-25-010 . August 14, 2024 - Notice of Participation of the National Institute on Aging in PA-23-317, Competing Revisions to Existing NIH Single Project Research Grants and Cooperative Agreements (Clinical Trial Optional)".

See Notice NOT-AG-24-059 . June 10, 2024 - Notice of Participation of the National Institute of Environmental Health Sciences (NIEHS) in PA-23-317.. See Notice NOT-ES-24-013 February 29, 2024 - Notice of Participation of the National Institute of Allergy and Infectious Diseases (NIAID) in PA-23-317, Competing Revisions to Existing NIH Single Project Research Grants and Cooperative Agreements (Clinical Trial Optional) .

See Notices NOT-AI-24-034 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) Companion Funding Opportunity See Section III. 3.

Additional Information on Eligibility. Assistance Listing Number(s) 93. 310, 93.

273, 93. 279, 93. 242, 93.

213, 93. 350, 93. 172, 93.

865, 93. 394, 93. 307, 93.

855, 93. 989, 93. 866, 93.

867, 93. 121 Funding Opportunity Purpose The National Institutes of Health (NIH) hereby notifies NIH award recipients that funds may be available for revision applications to support the expansion of existing projects and/or programs within the awarding Institute or Center (IC) identified in the competitive revision Notice of Special Interest (NOSI).

Only applications submitted in response to a NOSI published by an NIH Institute or Center will be allowed to apply to this NOFO. Open Date (Earliest Submission Date) Letter of Intent Due Date(s) See the competitive revision NOSI for any applicable Application Due Dates. Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

AIDS Application Due Date(s) See competitive revision NOSI for scientific merit review information. See competitive revision NOSI for council review information. See competitive revision NOSI for information on start dates.

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. Workspace to prepare and submit your application and eRA Commons to track your application. Part 1.

Overview Information 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 National Institutes of Health (NIH) hereby notifies NIH award recipients that funds may be available for revision applications to support the expansion of existing projects and/or programs.

Only applications submitted in response to a Notice of Special Interest (NOSI) published by an NIH Institute, Center, or Office (ICO) will be allowed to apply to this NOFO. 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 The funding instrument will be the same as the parent award.

Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity. Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities.

See Section VI. 2 for additional information about the substantial involvement for this NOFO. Application Types Allowed Competitive revision applications to active NIH parent awards.

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this NOFO. 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 NIH appropriations and the submission of a sufficient number of meritorious applications. Specific budget limits may be specified in the competitive revision NOSI.

Application budgets must be reasonable and must reflect the actual needs of the proposed project. The project and budget periods must be within the currently approved project period for the existing parent award. Unless otherwise instructed in the competitive revision NOSI, applicants may request up to two years of support.

The parent award must have a minimum of two years remaining within the current project period at the time of application submission. 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 All organizations administering an eligible parent award may apply for a competitive revision under this opportunity unless otherwise stated in the terms and conditions of the parent award.

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 (Other than Small Businesses) City or Township Governments Special District Governments Indian/Native American Tribal Governments (Federally Recognized) Indian/Native American Tribal Governments (Other than Federally Recognized) Eligible Agencies of the Federal Government U.S. Territory or Possession 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 Non-domestic (non-U.S.) Entities (Foreign Organizations) Non-domestic (non-U.S.) Entities (Foreign Organizations) are eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply. Foreign components, as defined in the NIH Grants Policy Statement , are allowed. Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award.

All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Grants Policy Statement Section 2.

3. 9. 2 Electronically Submitted Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

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) Individual(s) must be designated as a PD/PI on an active grant or cooperative agreement award, and the research proposed in the competitive revision must be accomplished within the competitive segment of the active award. Individuals are encouraged to work with their organizations to develop applications for support.

For competitive revisions to parent awards that include multiple PDs/PIs, the competitive revision may be requested by any or all of the PDs/PIs (in accordance with the existing leadership plan) and submitted by the recipient organization of the parent award. Do not use this competitive revision application to add, delete, or change the PDs/PIs listed on the parent award.

Visit the Multiple Program Director/Principal Investigator Policy in the SF424 (R&R) Application Guide for more information. This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement unless otherwise specified in the competitive revision NOSI. 3.

Additional Information on Eligibility Unless otherwise specified in the competitive revision NOSI, applicant organizations may submit more than one application, provided that each is sufficiently distinct from any other application currently under consideration by the awarding NIH Institute or Center. 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 All applications must be submitted electronically using one of the submission methods listed in Part 1 of this NOFO and must be in response to the competitive revision NOSI that refers to this NOFO. All forms must be completed for the proposed new activities only and must not reflect funding or activities for the previously awarded parent award.

If presented with more than one form package, use the Competition ID and Competition Titles provided to determine the most appropriate application forms package for your situation. Prepare applications using the SF424 (R&R) forms associated with the chosen package. Please note that some forms marked optional in the application package are required for submission of applications for this NOFO.

Follow all instructions in the How to Apply - Application Guide and the competitive revision NOSI to ensure you complete all appropriate required and optional forms. Conformance to documented requirements is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

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.

All instructions in the How to Apply - Application Guide and competitive revision NOSI must be followed, with the following additional instructions: The NOSI number must be included in box 4b (Agency Routing Identifier) on the application face page to be considered under the revision NOSI and this NOFO. Select Revision in the Type of Application field.

The "Descriptive Title of the Applicant's Project" must match the title of the currently funded grant. SF424(R&R) Project/Performance Site Locations All instructions in the How to Apply - Application Guide and applicable competitive revision NOSI must be followed, with the following additional instructions: Include the primary site where the proposed supplement activities will be performed.

If a portion of the proposed supplement activities will be performed at any other site(s), identify the locations in the fields provided.

SF424(R&R) Other Project Information All instructions in the How to Apply - Application Guide and applicable competitive revision NOSI must be followed, with the following additional instructions: If applicable, attach PDF documents in the Other Attachments field indicating that the proposed research experience was approved by the Institutional Animal Care and Use Committee (IACUC) or human subjects Institutional Review Board (IRB) at the grantee institution.

Name the documents IACUC Documentation. pdf and/or IRB Documentation. pdf .

Adherence to the NIH policy for including women and minorities in clinical studies must also be ensured, if additional human subjects involvement is planned for the supplement. SF424(R&R) Senior/Key Person Profile All instructions in the How to Apply - Application Guide and applicable competitive revision NOSI must be followed. List the PD/PI as the first person (regardless of their role on the supplement activities).

List any other Senior/Key Personnel who are being added through this supplement, or for whom additional funds are being requested through this supplement; include a biographical sketch for each.

All instructions in the How to Apply - Application Guide and applicable competitive revision NOSI must be followed, as applicable based on the activity type, with the following additional instructions: Only include funds requested for the additional supplement activities.

All instructions in the How to Apply - Application Guide and applicable competitive revision NOSI must be followed, as applicable based on the activity type, with the following additional instructions: Only include funds requested for the additional supplement activities. PHS 398 Cover Page Supplement All instructions in the How to Apply - Application Guide and applicable competitive revision NOSI must be followed.

All instructions in the How to Apply - Application Guide and applicable competitive revision NOSI must be followed, as applicable based on the activity type, with the following additional instructions: At a minimum, the Research Strategy or Program Plan section, as applicable based on the activity type, should be completed and must include a summary or abstract of the funded parent award or project.

Other sections should also be included if they are being changed by the proposed supplement activities. Other Plan(s): Applicants must address a Data Management and Sharing (DMS) Plan based on the policy applicability and requirements of the parent award and are required to comply with the instructions for DMS Plans accordingly, as provided in the How to Apply - Application Guide and the competitive revision NOSI.

If applicable (i.e., when the parent award is already subject to the DMS Policy and an awarded competing revision changes the parent award’s approved approach to data management and sharing), an updated DMS Plan must be provided as part of the Just-In-Time submission. 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.

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the SF424 (R&R) Application Guide must be followed. PHS Assignment Request Form All instructions in the How to Apply - Application Guide and applicable competitive revision NOSI must be followed.

Foreign (non-U.S.) organizations must follow policies described in the NIH Grants Policy Statement , and procedures for foreign organizations described throughout the SF424 (R&R) Application Guide. 3. Unique Entity Identifier and System for Award Management (SAM) See Part 1.

Section III. 1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants. gov 4.

Submission Dates and Times As described in Part I. Overview Information , the NOSI will provide 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 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. Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

5. Intergovernmental Review (E. O.

12372) This initiative is not subject to intergovernmental review. 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 .

7. Other Submission Requirements and Information Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

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

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply Application Guide . If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile form . Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this NOFO for information on registration requirements.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide. See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review, NIH. Applications that are incomplete or non-compliant will not be reviewed. In order to expedite review, applicants are requested to notify the IC.

Referral Office by email when the application has been submitted. Please include the NOFO number and title, PD/PI name, and title of the application.

Requests of $500,000 or more for direct costs in any year Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact a Scientific/ Research Contact at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF424 (R&R) Application Guide.

Post Submission Materials Section V. Application Review Information Only the review criteria described below will be considered in the review process. Competitive revision applications will be reviewed using the criteria below, as applicable, based on the activity type.

Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

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

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

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?

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? 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? 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 NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex, 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 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, sex, 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 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