NEI Clinical Research Study Planning Grant Program (R34 Clinical Trial Not Allowed) is sponsored by National Institutes of Health (NIH). Supports planning for clinical research studies, including those related to the impact of gambling on eye health.

PAR-25-358: NEI Clinical Research Study Planning Grant Program (R34 Clinical Trial Not Allowed) 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 Eye Institute ( NEI ) Funding Opportunity Title NEI Clinical Research Study Planning Grant Program (R34 Clinical Trial Not Allowed) Notices of Special Interest associated with this funding opportunity 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 4, 2024 - Overview of Grant Application and Review Changes for Due Dates on or after January 25, 2025.

See Notice NOT-OD-24-084 . August 31, 2022 - Implementation Changes for Genomic Data Sharing Plans Included with Applications Due on or after January 25, 2023. See Notice NOT-OD-22-198 .

August 5, 2022 - Implementation Details for the NIH Data Management and Sharing Policy. See Notice NOT-OD-22-189 . Funding Opportunity Number (FON) Companion Funding Opportunity See Section III.

3. Additional Information on Eligibility . Assistance Listing Number(s) Funding Opportunity Purpose The NEI supports large-scale clinical vision research projects, including randomized clinical trials and epidemiologic studies on eye/vision conditions.

At the time of submission, applications requesting support for these activities are expected to provide detailed information regarding the study rationale, design, analytic techniques, protocols and procedures, facilities and environment, organizational structure, and collaborative arrangements. This information is best conveyed in a Manual of Procedures (MOP), the development of which represents a costly and time-consuming activity.

This clinical research planning grant funding opportunity supports applicants in their planning efforts to conduct collaborative clinical research. The grant may be used to support the development of a MOP, as well as to conduct preliminary studies to refine study procedures or document recruitment potential. The grant must not be used to generate data on the effects of a proposed intervention.

This NEI FOA is applicable to both epidemiologic and clinical trial research studies. Funding Opportunity Goal(s) 1) To support eye and vision research projects that address the leading causes of blindness and impaired vision in the U.S. These include retinal diseases; corneal diseases; cataract; glaucoma and optic neuropathies; strabismus; amblyopia; and low vision and blindness rehabilitation.

2) To increase understanding of the normal development and function of the visual system in order to better prevent, diagnose, and treat sight-threatening conditions; and, to enhance the rehabilitation, training, and quality of life of individuals who are partially sighted or blind.

3) To support a broad program of basic vision research through grants and cooperative agreements; to encourage high quality clinical research, including clinical trials, other epidemiological studies, and health services research; to encourage research training and career development in the sciences related to vision; and to sponsor scientific workshops in high priority research areas to encourage exchange of information among scientists.

Open Date (Earliest Submission Date) The following table includes NIH standard due dates marked with an asterisk. Renewal / Resubmission / Revision (as allowed) AIDS - New/Renewal/Resubmission/Revision, as allowed 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 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 Eye Institute (NEI) clinical research planning grant is designed to facilitate activities central to the refinement of clinical research protocols and procedures for eye- and vision-related clinical trials or epidemiologic studies, including the development of a detailed study protocol and Manual of Procedures (MOP).

The planning grant may also support the conduct of preliminary studies to refine study procedures or document recruitment potential (i.e., to demonstrate feasibility). The grant, however, must not be used to generate data on the effects of a proposed intervention, i.e., applicants must not propose any research conducted as part of the planning process that meets the NIH definition of a clinical trial (as defined in NOT-OD-15-015 ).

The NEI Clinical Research Study Planning Grant is designed to (1) permit early peer review of the rationale for the proposed clinical trial or epidemiologic study, (2) provide support for the development of a complete study protocol and associated documents, including a detailed MOP and statistical analysis plan (SAP), (3) support the development of other essential elements of the clinical study.

If a clinical study is ready for implementation and readiness is adequately supported by documentation, submission of an R01, U01 or UG1 application may occur. Note that funding of the Clinical Research Study Planning Grant does not guarantee or imply funding of a subsequent full-scale clinical research study.

This NOFO supports timely planning activities and development of all materials required for the implementation of a future clinical study. Activities supported by this NOFO may include, but are not limited to, the following examples: Developing and/or finalizing the study protocol and MOP.

Basic elements in the protocol and MOP should include identification of the patient population; inclusion and exclusion criteria; adequate plans for recruitment and retention of participants; experimental design and protocols including definition of the study intervention and any comparator groups, if applicable; clear definition of the research hypothesis and outcome measures; quality control/assurance procedures; data management and analytical methods; sample size estimates with justification; administrative procedures, including regulatory approvals if necessary; collaborative arrangements; duties and responsibilities of the study chairperson, clinical sites, coordinating center, and other central resources such as a reading center; monitoring plans to assure patient protection and data integrity; and plans for addressing Federal inclusion and human subjects protection requirements.

When applicable, the MOP should describe procedures for tracking and monitoring stem cell function and integration in vivo; methods for in-depth stem cell characterization; and plans for sharing data and other resources after the full clinical trial is completed. Establishing and documenting collaborative arrangements.

Conducting administrative procedures necessary for obtaining regulatory authorization or approvals (such as pre-IND/IDE meetings with the FDA and other communications). Establishing methods for selecting cGMP compliant stem cell production, phase-appropriate GMP, and/or master cell banks; and for utilization of cGMP standards. Instituting means to assure standardization of procedures across sites and among staff.

Developing tools needed for data collection and data management. Developing and/or finalizing data and safety monitoring plans in the application. Do not name individuals for the Data and Safety Monitoring Committee (DSMC) or Data Monitoring and Oversight Committee (DMOC) but include areas of expertise that will be pertinent in forming these groups.

Developing plans for any training that is required to carry out the proposed study. This may include, for example, training of data collectors and individuals who will carry out the planned intervention. Standardized Ocular Imaging Expectations: The NEI encourages applicants to use common formats for files and metadata standards when incorporating ocular imaging in their research proposals (see NOT-EY-24-006 ).

This applies to both clinical and nonclinical research applications submitted in response to NOFOs where NEI is the issuing or participating organization.

It is anticipated the widespread adoption of standardized imaging formats will significantly advance the field by 1) simplifying streamlined digital workflows; 2) enhancing interoperability of large datasets; and 3) developing extensive and comprehensive training sets for artificial intelligence driven research.

By promoting these standards, the NEI’s goal is to create an environment where data can be seamlessly integrated and analyzed across different studies, thereby, amplifying the overall impact of vision research. To facilitate the exchange of health care information electronically the NEI encourages integration of FHIR (Fast Healthcare Interoperability Resources) ( https://hl7. org/fhir/us/cdmh/ ), OMOP ( https://www.

ohdsi. org/data-standardization/ ) common data model, FAIR (Findability, Accessibility, Interoperability, Reuse) principles ( https://www. go-fair.

org/fair-principles/ ) for all healthcare data, and DICOM (Digital Imaging and Communications in Medicine) standards ( https://www. dicomstandard. org/ ) for all imaging data.

The investigative teams are expected to develop milestones for measuring progress at each point in the clinical research planning process. Milestones should be quantifiable measures that reflect the degree of success of each step.

Applications Not Responsive to this NOFO The following types of applications will be considered non-responsive to this NOFO and will not be reviewed: Implementation of a clinical trial (i.e., conducting a research study as part of the planning process that meets the NIH definition of a clinical trial is not permitted on this NOFO) Collection of preclinical data (i.e., no preclinical/animal studies are permitted on this NOFO) Non-responsive applications will not be reviewed.

Applicants are encouraged to contact the NEI Scientific/Research Contacts listed at the end of this NOFO to discuss the programmatic priorities of the NEI prior to submission. See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information Grant: A financial assistance mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity. Application Types Allowed 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. Not Allowed: Only accepting applications that do not propose clinical trials. 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. The NEI permits direct costs up to $150,000 per year plus applicable F&A for consortia. The scope of the proposed project should determine the project period.

The maximum period is two 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 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 How to Apply- Application Guide to be eligible to apply for or receive an award.

All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference the NIH Grants Policy Statement Section 2.

3. 9. 2 Electronically Submitted Applications for additional information.

System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually . The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.

NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM. Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM. gov registration process.

The same UEI must be used for all registrations, as well as on the grant application. eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants. gov registrations; all registrations must be in place by time of submission.

eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application. Grants. gov – Applicants must have an active SAM registration in order to complete the Grants.

gov registration. Program Directors/Principal Investigators (PD(s)/PI(s)) All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons.

If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

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

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the How to Apply-Application Guide. This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1. 2 Definition of Terms .

3. Additional Information on Eligibility Applicant organizations may submit more than one application, provided that each application is scientifically distinct. The NIH will not accept duplicate or highly overlapping applications under review at the same time, per NIH Grants Policy Statement Section 2.

3. 7. 4 Submission of Resubmission Application .

This means that the NIH will not accept: A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application. A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.

An application that has substantial overlap with another application pending appeal of initial peer review (see NIH Grants Policy Statement 2. 3. 9.

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

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

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

Content and Form of Application Submission It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced.

Applications that are out of compliance with these instructions may be delayed or not accepted for review. 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 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. All instructions in the How to Apply- Application Guide must be followed. 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.

All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions: Please clearly address the following: If applicable, show how the study involves collaborations and/or input from community partners and relevant policy makers to inform the research and contribute to ensuring that the results have utility.

Show how the planned analyses and statistical approaches are appropriate for the proposed study design and methods. The procedures for data management and quality control must be standardized and applicable and there must be a plan to complete the data analysis within the proposed period of the award. If proposed, explain how the administrative and data coordinating activities are appropriate for the proposed study.

Also address the capability and ability to conduct research at the proposed site. If an international site is proposed, show how the application adequately addresses the complexity of executing the study. Provide milestones that support planning of a large-scale clinical vision research project.

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

All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan. Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the How to Apply- Application Guide.

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

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

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

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.

Foreign (non-U.S.) organizations must follow policies described in the NIH Grants Policy Statement , and procedures for foreign organizations described throughout the How to Apply- Application Guide. 3. Unique Entity Identifier and System for Award Management (SAM) See Part 2.

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

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

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

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

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

Applications that miss the due date and time are subjected to the NIH Grants Policy Statement Section 2. 3. 9.

2 Electronically Submitted Applications . Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission. Information on the submission process and a definition of on-time submission are provided in the How to Apply-Application Guide.

5. Intergovernmental Review (E. O.

12372) This initiative is not subject to intergovernmental review. All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement . Pre-award costs are allowable only as described in the NIH Grants Policy Statement Section 7.

9. 1 Selected Items of Cost. 7.

Other Submission Requirements and Information Applications must be submitted electronically following the instructions described in the How to Apply Application Guide. Paper applications will not be accepted. Applicants must complete all required registrations before the application due date.

Section III. Eligibility Information contains information about registration. For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply – Application Guide .

If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII. All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile form .

Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this NOFO for information on registration requirements.

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

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

Prior Consultation with NEI Consultation with NEI staff at least 10 weeks prior to the application due date is strongly encouraged for submission of the NEI Clinical Trial Planning Grant (R34) application, including new and resubmission applications.

Use of Common Data Elements in NIH-funded Research Many NIH ICs encourage the use of common data elements (CDEs) in basic, clinical, and applied research, patient registries, and other human subjects research to facilitate broader and more effective use of data and advance research across studies. CDEs are data elements that have been identified and defined for use in multiple data sets across different studies.

Use of CDEs can facilitate data sharing and standardization to improve data quality and enable data integration from multiple studies and sources, including electronic health records.

NIH ICs have identified CDEs for many clinical domains (e.g., neurological disease), types of studies (e.g. genome-wide association studies (GWAS)), types of outcomes (e.g., patient-reported outcomes), and patient registries (e.g., the Global Rare Diseases Patient Registry and Data Repository). NIH has established a “Common Data Element (CDE) Resource Portal" ( http://cde. nih.

gov/ ) to assist investigators in identifying NIH-supported CDEs when developing protocols, case report forms, and other instruments for data collection. The Portal provides guidance about and access to NIH-supported CDE initiatives and other tools and resources for the appropriate use of CDEs and data standards in NIH-funded research.

Investigators are encouraged to consult the Portal and describe in their applications any use they will make of NIH-supported CDEs in their projects. Recipients or subrecipients must submit any information related to violations of federal criminal law involving fraud, bribery, or gratuity violations potentially affecting the federal award. See Mandatory Disclosures, 2 CFR 200.

113 and NIH Grants Policy Statement Section 4. 1. 35 .

Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to the HHS Office of Inspector Grant Self Disclosure Program at [email protected] . Post Submission Materials Applicants are required to follow the instructions for post-submission materials, as described in the policy 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.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following scored review criteria and additional review criteria (as applicable for the project proposed). An application does not need to be strong in all categories to be judged likely to have a major scientific impact.

Reviewers will consider Factors 1, 2 and 3 in the determination of scientific merit, and in providing an overall impact score. In addition, Factors 1 and 2 will each receive a separate factor score. Factor 1.

Importance of the Research (Significance and Innovation) Evaluate the importance of the proposed research in the context of current scientific challenges and opportunities, either for advancing knowledge within the field, or more broadly. Assess whether the application addresses an important gap in knowledge in the field, would solve a critical problem, or create a valuable conceptual or technical advance.

Evaluate the rationale for undertaking the study, the rigor of the scientific background for the work (e.g., prior literature and/or preliminary data) and whether the scientific background justifies the proposed study. Evaluate the extent to which innovation influences the importance of undertaking the proposed research.

Note that while technical or conceptual innovation can influence the importance of the proposed research, a project that is not applying novel concepts or approaches may be of critical importance for the field. Evaluate whether the proposed work applies novel concepts, methods or technologies or uses existing concepts, methods, technologies in novel ways, to enhance the overall impact of the project. Factor 2.

Rigor and Feasibility (Approach) Evaluate the scientific quality of the proposed work. Evaluate the likelihood that compelling, reproducible findings will result (rigor) and assess whether the proposed studies can be done well and within the timeframes proposed (feasibility). Evaluate the potential to produce unbiased, reproducible, robust data.

Evaluate the rigor of experimental design and whether appropriate controls are in place. Evaluate whether the sample size is sufficient and well-justified. Assess the quality of the plans for analysis, interpretation, and reporting of results.

Evaluate whether the investigators presented adequate plans to address relevant biological variables, such as sex or age, in the design, analysis, and reporting. For applications involving human subjects or vertebrate animals, also evaluate: the rigor of the intervention or study manipulation (if applicable to the study design). whether outcome variables are justified.

whether the results will be generalizable or, in the case of a rare disease/special group, relevant to the particular subgroup. whether the sample is appropriate and sufficiently diverse to address the proposed question(s). For applications involving human subjects, including clinical trials, assess the adequacy of inclusion plans as appropriate for the scientific goals of the research.

Considerations of appropriateness may include disease/condition/behavior incidence, prevalence, or population burden, population representation, and/or current state of the science. Evaluate whether the proposed approach is sound and achievable, including plans to address problems or new challenges that emerge in the work.

For proposed studies in which feasibility may be less certain, evaluate whether the uncertainty is balanced by the potential for major advances. For applications involving human subjects, including clinical trials, evaluate the adequacy and feasibility of the plan to recruit and retain a study population that appropriately models the target population.

Additionally, evaluate the likelihood of successfully achieving the proposed enrollment based on age, race, ethnicity, and sex. For clinical trial applications, evaluate whether the study timeline and milestones are feasible. Evaluate whether successful conduct of the specific aims of the R34 application are appropriate to provide results that are both necessary and sufficient to make a final decision about the subsequent trial.

Assess the quality of the plans for how information learned will be used to inform decisions about the subsequent clinical