Early Career Research (ECR) Award (R21)

Early Career Research (ECR) Award (R21) is sponsored by National Institute on Deafness and Other Communication Disorders (NIDCD). Supports early career scientists in research related to hearing, balance, taste, smell, voice, speech, or language.

PAR-25-120: NIDCD Early Career Research(ECR) Award (R21 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 Institute on Deafness and Other Communication Disorders ( NIDCD ) Funding Opportunity Title NIDCD Early Career Research(ECR) Award (R21 Clinical Trial Optional) R21 Exploratory/Developmental Research Grant Notices of Special Interest associated with this funding opportunity 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 NIDCD Early Career Research (ECR) Award (R21) is intended to support both basic and clinical research from scientists who are beginning to establish an independent research career. It cannot be used for thesis or dissertation research.

The research must be focused on one or more of the areas within the biomedical and behavioral scientific mission of the NIDCD: hearing, balance, smell, taste, voice, speech, or language.

The NIDCD ECR Award R21 grant mechanism supports different types of projects including secondary analysis of existing data; small, self-contained research projects; development of research methodology; translational research; outcomes research; and development of new research technology.

Irrespective of the type of project, the intent of the NIDCD ECR Award R21 is for the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) to obtain sufficient preliminary data for a subsequent R01 application. Open Date (Earliest Submission Date) 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 NIDCD Early Career Research (ECR) Award is different from other NIH R21 programs.

It is restricted to clinical and basic scientists who are transitioning to, or are already in the early stages of, their independent research career. The research should be focused on one or more of the areas within the biomedical and behavioral scientific mission of the NIDCD, specifically: hearing, balance, smell, taste, voice, speech, or language.

The expected outcome from projects funded under this mechanism is the acquisition of necessary preliminary data for a subsequent research project grant (R01) application. The proposed project may or may not be hypothesis-driven since the goal is to collect the necessary preliminary data sufficient to apply for an R01 grant. The project may aid in the formulation of hypotheses and may be milestone-driven or descriptive in scope.

Given that the goal is to collect preliminary data, R21 projects may be less immediately impactful or significant compared to the typical R01. It is not an expectation that this R21 project will likely "move the field forward" at this stage. Preliminary data are not required.

However, the project should be supported by sufficient information to give confidence to the reviewers that the proposed work is feasible and that data derived from the project would likely be suitable as preliminary data for a subsequent R01 application. If preliminary data are available, it is recommended that these be included.

The NIDCD ECR Award R21 may be used by beginning clinical scientists planning a future application for an NIDCD K08 or K23 mentored research career development award to demonstrate the feasibility of the research project to be proposed in their K-award application.

Applicants that have already received a K award from NIDCD may reduce their effort on the K-award to no less than 50% (6 person-months based on a 12 month calendar) during the last two years of the K-award in order to become PD/PI on the NIDCD ECR Award R21 (see NIH policy http://grants1. nih. gov/grants/guide/notice-files/NOT-OD-08-065.

html ). The PD/PI’s total level of effort must remain at 75% (9 person-months based on a 12 month calendar) or more across the K-award and the R21 award. Questions regarding eligibility should be addressed prior to beginning to prepare the application by contacting the training staff member listed in Section VII.

Agency Contacts. The Multiple PD/PI configuration is allowed for this NOFO. However, ALL of the PD/PIs MUST meet ALL of the ECR R21 eligibility criteria, 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 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.

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.

The combined budget for direct costs for the entire project period may not exceed $375,000. No more than $125,000 in direct costs may be requested in any single year. The scope of the proposed project should determine the project period.

The maximum period of support is 3 years. NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this NOFO. Section III.

Eligibility Information 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) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply. Foreign components, as defined in the NIH Grants Policy Statement , are allowed. 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. The Multiple PD/PI configuration is allowed for this NOFO. However, ALL of the PD/PIs MUST meet ALL of the ECR R21 eligibility criteria.

The PD/PI must be a U.S. citizen, permanent resident or valid U.S. visa holder. The PD/PI must be no more than 7 years beyond the date that the first professional, advanced professional, or terminal academic degree was awarded, whichever is most recent. The 7-year eligibility period will be calculated based on the MM/YYYY the degree was awarded.

The last application due date, not the application submission date, that falls within the 7-year eligibility period will be the last date an application may be submitted. Formal years of clinical training (Internship, Residency, and Fellowship) are not counted as part of the 7-year limit. In addition, exemption of years for clinical training is not limited to physicians.

For example, individuals with clinical training or clinical fellowship years in Clinical Molecular Genetics, Audiology, or Speech-Language Pathology are also eligible for an exemption. NIDCD will consider requests for a one time extension to the standard 7-year eligibility period. Each individual circumstance is different and as such, extension requests will be considered on a case by case basis.

The request for an extension must include a PD/PI statement describing the reason for the extension request and an independent statement from the Institutional Signing Official describing the timeframe over which productivity was significantly altered. The request must be signed by the PD/PI and co-signed and submitted by the Institutional Signing Official by email to the ECR R21 Program Coordinator listed in Section VII.

Agency Contacts. Extensions MUST be requested before the standard 7-year eligibility period has expired. All NIDCD decisions are final.

A resubmission application will be allowed even if the 7-year eligibility period has expired provided the resubmission application is received within 37 months from the original submission due date based on current NIH Guidelines ( NOT-OD-12-128 ). For further information please contact the NIDCD ECR Award (R21) program coordinator listed in Section VII. Agency Contacts.

The PD/PI may be an independent early stage investigator or a late-stage postdoctoral fellow still in their mentor's laboratory.

However, if still a postdoctoral fellow, there should be a letter from the mentor included with the application that clearly confirms a commitment to the provision of laboratory space and a clear indication that a transition away from the mentor is being initiated and that the research project will be transferable to another U.S. institution with the PD/PI.

Questions regarding eligibility should be addressed prior to beginning to prepare the application by contacting the appropriate staff member listed in Section VII. Agency Contacts.

Individuals who have served as PD/PI on any NIH research grant (including an R01, R03, R15, R21, K99/R00, SBIR/STTR, subprojects of program project or center grants) or any other federally-funded research grant (e.g., NSF, DOD, DOE, VA) are NOT eligible for the NIDCD ECR Award Grant Program.

However, former recipients of Federally-funded National Research Service Award fellowships and traineeships (i.e., F- and T- series awards) or mentored career development awards (i.e., K awards) are eligible for the NIDCD ECR Award grant program. Recipients of the K99/R00 award are not eligible to apply for the NIDCD ECR Award (R21). Replacement PD/PIs for an ECR R21 are NOT allowed.

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 ). Only one NIDCD ECR Award (R21) application may be submitted by a PD/PI per due date.

PD/PIs who successfully obtained an NIDCD Small Grant award are ineligible for the NIDCD ECR Award (R21). Applicants may not submit an NIDCD R01, R15 or R21 application for the same review cycle that the NIDCD ECR Award application is submitted. In such cases the NIDCD ECR Award application will be withdrawn.

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 SF424 (R&R) Application Guide must be followed. The effort dedicated to the NIDCD ECR Award R21 project must be commensurate with the aims of the project. At a minimum, the PD/PI is expected to commit 25% effort (i.e., 3 person-months based on a 12 month calendar) to the project unless a compelling justification for less is provided in the budget justification section of the application.

PD/PI effort may be as high as 100% (i.e., 12 person-months based on a 12 month calendar). Effort dedicated to the project reflects time commitment and may be more than the grant-supported salary committed. For example, the PD/PI may have a 25% time effort with only 10% of the PD/PI salary derived from the NIDCD ECR Award R21 with the rest coming from other sources.

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: If the PD/PI still a postdoctoral fellow, there should be a letter from the mentor included with the application.

Reviewers will determine whether or not there is a clear commitment to the provision of laboratory space and a clear indication that a transition away from the mentor is being initiated and that the research project will be transferable to another U.S. institution with the PD/PI.

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.

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. A change of PD/PI will not be allowed under the NIDCD ECR R21. 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 components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

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.

For this particular NOFO, note the following: The NIDCD ECR Award R21 grant is a mechanism supporting investigation of novel scientific ideas or new model systems, tools, or technologies that have the potential for significant impact on biomedical or biobehavioral research. An R21 grant application need not have extensive background material or preliminary information.

Accordingly, reviewers will focus their evaluation on the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data.

Preliminary data are not required for R21 applications; however, they may be included if available. An ECR Award grant application will not have the same level of detail or extensive discussion found in an R01 application.

The PD/PI should provide sufficient information to give confidence to the reviewers that the proposed work is feasible and that data derived from the project would likely be suitable as pilot data for a subsequent R01 application. It is not expected that at this stage these data will make a significant contribution to ‘drive’ or move the field forward.

Finally, the NIDCD ECR Award program is intended for investigators who are in the beginning stages of establishing an independent research career. These PD/PIs are not expected to have the same grant writing experience as a more senior R01 funded investigator. NIDCD ECR Award projects may be less immediately impactful or significant compared to an R01.

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

Importance of the Research (Significance and Innovation) 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