NEI Collaborative Clinical Vision Research Project: Resource Center Grant (UG1 Clinical Trial Required)

NEI Collaborative Clinical Vision Research Project: Resource Center Grant (UG1 Clinical Trial Required) is sponsored by National Institutes of Health. Funds resource centers to support collaborative clinical vision research projects.

Expired PAR-23-201: NEI Collaborative Clinical Vision Research Project: Resource Center Grant (UG1 Clinical Trial Required) This notice has expired. For NIH, in limited situations, applications may be accepted on a case-by-case basis for a short period after expiration to accommodate NIH late or continuous submission policies . Contact the eRA Service Desk for any submission issues.

Check the NIH Guide for active opportunities and notices. Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) Components of Participating Organizations National Eye Institute ( NEI ) Funding Opportunity Title NEI Collaborative Clinical Vision Research Project: Resource Center Grant (UG1 Clinical Trial Required) UG1 Clinical Research Cooperative Agreements - Single Project Notices of Special Interest associated with this funding opportunity February 10, 2026 - Notice of Change to Key Dates for PAR-23-209, PAR-23-204, PAR-23-201 NEI Collaborative Clinical Vision Research Grants (UG1 Clinical Trial Required).

See Notice NOT-EY-26-001 January 28, 2026 - NIH Removing AIDS Application Due Dates from NOFOs. See Notice NOT-OD-26-029 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 04, 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 8, 2022 - New NIH "FORMS-H" Grant Application Forms and Instructions Coming for Due Dates on or after January 25, 2023 - See Notice NOT-OD-22-195. August 5, 2022 - Implementation Details for the NIH Data Management and Sharing Policy - see Notice NOT-OD-22-189 .

Notice of Funding Opportunity (NOFO) Number Companion Funding Opportunity Clinical Research Cooperative Agreements - Single Project Clinical Research Cooperative Agreements - Single Project See Section III. 3. Additional Information on Eligibility.

Assistance Listing Number(s) Funding Opportunity Purpose The NEI uses UG1 cooperative agreement awards to support investigator-initiated large-scale clinical trials, human gene-transfer, stem cell therapy trials, and other complex or high resource- or safety-risk clinical trials.

These projects are multifaceted and of high public health significance requiring clear delineation of study organization including roles and responsibilities and require careful performance oversight and monitoring.

For purposes of this Notice of Funding Opportunity (NOFO), the proposed study must be intended to evaluate interventions aimed at screening, diagnosing, preventing, or treating vision disorders, or to compare the effectiveness of two or more established interventions.

The NEI UG1-supported studies are typically funded as a group of single-component companion grant awards including the Chair’s Grant, the Coordinating Center, and Resource Centers, when appropriate. Specifically, this NOFO encourages applications for the Resource Center grant which provides imaging, laboratory, or other requisite services for a multi-center clinical trial or other complex or high-risk clinical trial.

Open Date (Earliest Submission Date) Letter of Intent Due Date(s) The following table includes NIH standard due dates marked with an asterisk.

Dates in bold and italics reflect changes per NOT-EY-26-001 Application Due Dates Review and Award Cycles New Renewal / Resubmission / Revision (as allowed) AIDS Scientific Merit Review Advisory Council Review Earliest Start Date July 13, 2023 July 13, 2023 September 07, 2023 * November 2023 January 2024 April 2024 September 25, 2023 * September 25, 2023 * January 07, 2024 * March 2024 May 2024 July 2024 January 25, 2024 * January 25, 2024 * May 07, 2024 * July 2024 October 2024 December 2024 May 25, 2024 * May 25, 2024 * September 07, 2024 * November 2024 January 2025 April 2025 September 25, 2024 * September 25, 2024 * January 07, 2025 * March 2025 May 2025 July 2025 January 25, 2025 * January 25, 2025 * May 07, 2025 * July 2025 October 2025 December 2025 May 25, 2025 * May 25, 2025 * September 07, 2025 * November 2025 January 2026 April 2026 September 25, 2025 * September 25, 2025 * January 07, 2026 * March 2026 May 2026 July 2026 January 25, 2026 * January 25, 2026 * May 07, 2026 * July 2026 October 2026 December 2026 May 25, 2026 * May 25, 2026 * Not Applicable November 2026 January 2027 April 2027 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.

Required Application Instructions It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) 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 purpose of this Notice of Funding Opportunity (NOFO) is to provide a framework for applicants seeking a Resource Center Grant.

The Resource Center Grant provides imaging, laboratory, or other requisite services for a multi-center or other complex or high-risk vision research clinical trial. The NEI UG1-supported studies are typically funded as a group of companion grant awards including the Chair’s Grant, the Coordinating Center, and the Resource Centers, as appropriate.

For less organizationally complex projects, details pertaining to data management and statistical analysis, resource center and recruitment activity may be included as part of the Chair's Grant application. Separate applications may be submitted for Chair's or Coordinating Centers under the following respective UG1 companion NOFOs: PAR-23-209 NEI Collaborative Clinical Vision Research Project: Chair's Grant.

(The Chair's Grant provides the clinical, scientific, and technical leadership to the study) PAR-23-204 NEI Collaborative Clinical Vision Research Project: Coordinating Center Grant.

(The Coordinating Center proposes a role of statistical and methodologic leadership, logistical coordination and trial support, and safety monitoring including support of the Data and Safety Monitoring Committee) Scope of this Notice of Funding Opportunity: The scope of this NOFO is to encourage grant applications for investigator-initiated clinical trials to establish the efficacy or compare the effectiveness of screening, diagnostic, preventative or therapeutic interventions.

Renewal applications that request additional years or funds to complete the original aims of a clinical trial will be accepted under this NOFO. Renewal applications may also be submitted to request support to extend follow-up of clinical trial cohorts after completion of the primary study goals to gather information on longer-term outcomes.

As applicable, this NOFO may support laboratory work associated with study product manufacture, repackaging, and distribution; quality assurance (i.e., identity, potency, or other aspects of product integrity); and participants safety.

Applications Not Responsive to this NOFO: The following types of activities remain outside of the scope of this NOFO, and applications proposing such activities will be considered non-responsive to this NOFO and will be withdrawn without review: Applications involving a clinical experiment that is not directly intended to evaluate a screening, diagnostic, preventative, or therapeutic intervention, or compare the effectiveness of established interventions, are not suitable for this NOFO.

Applications that are not complex or of high resource-or safety-risk are not suitable for this NOFO. Preclinical, developmental, or preparatory studies for gene transfer and stem cell therapy are not supported under this NOFO. NIH-defined clinical trial applications proposing basic experimental studies with humans (BESH) and/or minimal risk studies are not supported under this NOFO.

Applicants are strongly encouraged to contact Scientific/Research staff as plans for an application are being developed (see Section VII, Agency Contacts), and no later than 12 weeks prior to the anticipated application submission date. 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 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 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. Required: Only accepting applications that 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. Application budgets are not limited but need to reflect the actual needs of the proposed project.

The scope of the proposed project should determine the project period. The maximum period is five 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 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 Institutions) Non-domestic (non-U.S.) Entities (Foreign Institutions) 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 Policy on Late Submission of Grant 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 registration; 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 SF424 (R&R) Application Guide. This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement. 3.

Additional Information on Eligibility 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 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 2. 3.

9. 4 Similar, Essentially Identical, or Identical Applications ) Section IV. Application and Submission Information 1.

Requesting an Application Package The application forms package specific to this opportunity must be accessed through ASSIST, Grants. gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.

gov Workspace are available in Part 1 of this NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution. 2.

Content and Form of Application Submission It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) 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. All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed. Instructions for Application Submission The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this NOFO.

All instructions in the SF424 (R&R) Application Guide must be followed. SF424(R&R) Project/Performance Site Locations All instructions in the SF424 (R&R) Application Guide must be followed. SF424(R&R) Other Project Information All instructions in the SF424 (R&R) Application Guide must be followed.

The following must be included as an attachment: Resource Center Methods (required) – Provide a detailed description of the Resource Center's methods for Grading, analyses, or study product manufacture, as applicable; and De-identifying images or specimens, as applicable to enable resource sharing. The filename "ResourceCenterMethods. pdf" should be used and will be reflected in the final image bookmarking for easy access to reviewers.

Applications that lack appropriate attachment(s) are incomplete, will not be reviewed, and will be withdrawn. SF424(R&R) Senior/Key Person Profile All instructions in the SF424 (R&R) Application Guide must be followed. All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed. PHS 398 Cover Page Supplement All instructions in the SF424 (R&R) Application Guide must be followed. All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions: Specific Aims: This section should outline the responsibilities and operations of the Resource Center.

Research Strategy: Provide a detailed description of the Resource Center, including the following, as applicable: Personnel available to perform the necessary work Independent accreditations, certifications, and facility audit processes Overall structure of the resource center team Plans for communications with the Chair’s Center and Coordinating Center Protocols for the timely receipt, inventory, routing, processing, analysis, storage, retrieval and archiving of requisite images and/or biological samples and related data Protocols for the timely production, inventory, storage and transfer of study product or materials Training and certification of study clinic personnel in image capture, specimen collection or local laboratory procedures and product handling Transmission of resource center data to the coordinating center Transmission of study product to the clinical center(s) Standardization and ongoing quality control Preparation of resource center reports Organizing and conducting of on-site and off-site monitoring of resource center procedures as needed Scientific experience and expertise of the team as a whole to contribute to project leadership and to study manuscripts and presentations Letters of Support: Letters of support from institutions with a key role in the study must be provided.

Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide. With the following modification: Describe plans for supporting timely publication and dissemination of study findings Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions: All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan.

All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan. Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

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

PHS Human Subjects and Clinical Trials Information When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions: If you answered “Yes” to the question “Are Human Subjects Involved?

” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record. Study Record: PHS Human Subjects and Clinical Trials Information All instructions in the SF424 (R&R) Application Guide must be followed.

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

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

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

Submission Dates and Times Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission.

When a submission date falls on a weekend or Federal holiday , the application deadline is automatically extended to the next business day. Organizations must submit applications to Grants. gov (the online portal to find and apply for grants across all Federal agencies).

Applicants must then complete the submission process by tracking the status of the application in the eRA Commons , NIH’s electronic system for grants administration. NIH and Grants. gov systems check the application against many of the application instructions upon submission.

Errors must be corrected and a changed/corrected application must be submitted to Grants. gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

Applications that miss the due date and time are subjected to the NIH 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.

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 Applicants are required to follow the instructions for post-submission materials, as described in the policy In addition, for this PAR, applicants may submit a 1-2 page document providing update on the clinical trial as post-submission materials, up to 30 days prior to the review meeting.

This update could include information on recruitment of enrollment centers, recruitment of key personnel, obtaining the drug, access to the device, FDA and other regulatory approvals, and IRB approvals. Section V. Application Review Information 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: 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.

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? 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?

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?

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) as required by statute, 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?

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