The purpose of this funding opportunity announcement (FOA) is to invite applications for a broad range of research efforts in computational genomics, data science, statistics, and bioinformatics relevant to one or both of basic or clinical genomic science, and broadly applicable to human health and disease. This FOA supports fundamental genomics research developing innovative analytical methodologies and approaches, early-stage development of tools and software, and refinement or hardening of software and tools of high value to the biomedical genomics community. Work supported under this FOA should be enabling for genomics and be generalizable or broadly applicable across diseases and biological systems. All applications should address how the methods would scale to address increasingly larger data sets.

Funding Opportunity Number: PAR-25-228. Assistance Listing: 93.172,93.879. Funding Instrument: G. Category: ED,HL.

PAR-25-228: Investigator Initiated Innovation in Computational Genomics and Data Science (R01 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 Human Genome Research Institute ( NHGRI ) National Library of Medicine ( NLM ) Funding Opportunity Title Investigator Initiated Innovation in Computational Genomics and Data Science (R01 Clinical Trial Not Allowed) R01 Research Project 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 Exploratory/Developmental Grants See Part 2, Section III. 3.

Additional Information on Eligibility. Assistance Listing Number(s) Funding Opportunity Purpose The purpose of this renewing Notice of Funding Opportunity (NOFO) is to support investigator-initiated research efforts fostering innovation in computational genomics, data science, statistics, bioinformatics, and data visualization and exploration.

This NOFO supports development of innovative analytical methodologies and approaches and early-stage tools and software for genomics, rather than incremental advances or modification and application of existing approaches. Projects should be enabling for genomics research, broadly applicable to human health and disease, and generalizable across diseases and biological systems.

Funding Opportunity Goal(s) NHGRI supports the development of resources and technologies that will accelerate genome research and its application to human health and genomic medicine. 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 NHGRI 2020 Vision for improving human health at the forefront of genomics highlights genomic data science as an essential part of sustaining and improving a robust foundation for genomics.

The scale of genomic data and the commitment of researchers and the NIH to open science and responsible sharing of digital data resources necessitate continual advances in genomic data processing, storage, organization, and access. Efficient management, querying and visualization of increasingly complex genomic datasets require innovation in both traditional and advanced methods.

Democratization of genomics depends on advances toward truly user-friendly software, scalable systems for data management and automated metadata capture, and intuitive methods for visualization of multi-modal data. The exponential growth of genomic data demands new scalable algorithms and new solutions for making genomic data findable, accessible, interoperable, and reusable (FAIR).

Advancing our understanding in genomics requires the continued development and improvement of computational, analytical, statistical and bioinformatic approaches, from processing raw sequencing signals and assembling genomes, to deriving insight from population sequencing studies and implementing genomics in clinical settings.

Through this NOFO, NHGRI seeks applications that propose highly innovative research efforts in computational genomics through developing novel data science, statistics, and bioinformatics approaches that are broadly applicable to human health and disease.

Examples of research topics that may be appropriate for this NOFO include development of innovative computational, bioinformatics, statistical, or analytical approaches, tools, or software, such as: Tools for visualization of large genomic data sets Development of genetically informed causal inference methods Machine learning and artificial intelligence (AI) methods for genomics research, including development of generative AI and estimation of model power, validation and benchmarking Privacy-preserving technologies to access and compute on controlled-access human genomic, phenotypic, and clinical research data Improving efficiency and scalability of compute-intensive genomic data analysis applications, including novel methods to reduce the size of large models or cross-model training Tools to improve synergy between genomic data generation and computation, including integrating AI in experimental workflows to automate or optimize data gathering Methodology development for federated learning on distributed genomic data, computing resources, and models from multiple sites Applicants are encouraged to propose creative and innovative research topics that go beyond the examples listed above.

All applicants are strongly encouraged to contact the scientific research contact listed below or other NHGRI Program Staff to discuss the alignment of their proposed work with the goals of this NOFO prior to submitting an application. NHGRI encourages all investigators with innovative ideas aligned with the goals of this NOFO to submit applications.

NHGRI especially encourages applicants who are new investigators, experienced investigators who are new to genomic science, and investigators from demographic groups or institutions that are generally underrepresented in genomic science.

Applications where the central goal is to utilize or incrementally update existing approaches for genomics research, rather than to develop innovative approaches in computational genomics and data science, should be submitted in response to the parent R01/R21/R15 announcements ( PA-20-185 , PA-20-195 , PAR-24-152 , PAR-22-060 ).

Projects with the following properties will be considered non-responsive, and will not be reviewed: Work focused on microbial genomics or the microbiome Development, maintenance, extension, or curation of existing genomic resources, repositories, knowledgebases, or platforms.

Applicants considering developing such resources are directed to the Genomic Community Resources (U24) program ( PAR-23-085 ) and the trans-NIH Biomedical Data Repositories ( PAR-23-079 ) and Knowledgebases ( PAR-23-078 ) funding opportunities.

Research that is not broadly generalizable or that is relevant to only one or a few diseases or biological systems; research utilizing a small number of disease models or biological systems for proof-of-concept studies may be acceptable when the resulting methods, tools, approaches, or software are generalizable Development and application of ontologies or controlled vocabularies, or manual curation efforts Basic data science research that is not developed for genomics Research with most effort or resources devoted to experimental data generation; applicants may propose up to 10% of the total budget to support experimental work for evaluation of computational approaches Approaches not clearly pertaining to computational genomics and data science and/or lacking relevance to human health and diseases 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. Application budgets are limited to less than $500,000 in direct costs per year and need to reflect the actual needs of the proposed project.

The scope of the proposed project should determine the project period. The maximum project period is 5 years. NHGRI typically funds early-stage investigators for 5 years and established investigator R01s for 4 or fewer 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: Applicants should explain how the proposed research will advance our understanding of genomic science, and how the approach will be broadly applicable to human health and diseases.

As part of the Significance section, applicants should describe the generalizability and broader relevance of the proposed research beyond any specific disease(s)/biological system(s)/ancestries utilized in the study. NHGRI is interested in development of methods, tools, and approaches that are forward-thinking and highly innovative and could be catalytic for genomics.

Applicants should describe in the Innovation section how their research will address a critical gap, be distinct from existing research efforts in this area, or significantly outperform current approaches in this area.

Applicants should describe in detail plans for rigorous validation, benchmarking, comparisons with existing methodologies/tools, and/or evaluations that will be performed to assess the quality or utility of the developed approaches. Where applicable, applicants may describe plans for up to 10% of the total budget to support experimental work for evaluation of computational approaches.

Applicants should describe how their proposed approaches are scalable with the size of the data sets to be analyzed or processed, able to run on data residing on a variety of storage systems and data sources, or be deployed on them.

Applicants should also describe how tools and approaches or resulting outputs or analyses are interoperable with other methods, including plans for using existing data and metadata standards and ontologies already in use in the community. NHGRI supports development of methods, tools, and technologies that can be broadly utilized by biomedical researchers.

Applicants should describe how the methods, tools, or approaches will be developed such that they are robust, well documented, and can be readily adopted, applied, and extended or modified by other biomedical researchers. Applicants should describe plans to enable broad uptake of developed methods, including portable solutions and thorough documentation. See also the Resource Sharing section below.

Where appropriate, applicants should describe how the methods or software they are developing will protect any human subjects data while allowing access to those data by qualified users. To facilitate sharing of ideas and methods and accelerate advances in computational genomics and data science, grantees will be required to participate actively and openly in one grantee meeting per year that will be convened by NHGRI.

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. The Resource Sharing Plan should summarize whether and how resources (e.g., educational materials; methods; models; physical products, materials, and reagents; protocols; research findings and products; and software) will be made available.

Applicants should include a description of the format, an indication of who will be responsible for implementation and plans for long-term maintenance, whether there will be opportunities for community input and feedback, platform(s) or mechanism(s) that will be used to make resources publicly accessible, and proposed timeline for implementing the Resource Sharing Plan.

Resource Sharing Plans should not duplicate other sections of the main Research Plan but should refer to them when appropriate. After initial review, NHGRI program staff may negotiate revisions of this plan with the prospective awardee. The final negotiated version of this plan will become a term and condition of the award.

For more guidance on writing a Resource Sharing Plan, see https://genome. gov/resource-sharing. Where applicable, software sharing is recommended to follow the FAIR for Research Software ( FAIR4RS ) principles to promote and encourage the findability, accessibility, interoperability, and reusability (FAIR) for software management and stewardship.

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 Data Management and Sharing Policy.

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.

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 NHGRI, 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 Any instructions provided here are in addition to the instructions 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 announcement, please note the NOFO-specific review criteria listed for Factors 1 and 2 below.

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.

Evaluate whether the application clearly outlines the computational innovation compared with state-of-the-art methods. Evaluate whether the proposed method or algorithm is likely to be widely adopted by the relevant research community, considering factors including computational power needed and size of training data required. 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. Assess whether the algorithms/approaches are theoretically sound and well-justified.

Assess the plans for enabling model reuse including sharing models and parameters. Evaluate plans for rigorous benchmarking, validation, comparisons with existing methodologies/tools, and/or evaluations to assess the quality or utility of the developed approaches described. Factor 3.

Expertise and Resources (Investigator(s) and Environment) Evaluate whether the investigator(s) have demonstrated background, training, and expertise, as appropriate for their career stage, to conduct the proposed work. For Multiple Principal Investigator (MPI) applications, assess the quality of the leadership plan to facilitate coordination and collaboration.

Evaluate whether the institutional resources are appropriate to ensure the successful execution of the proposed work. Additional Review Criteria As applicable for the project proposed, reviewers will consider the following additional items while determining scientific and technical merit, but will not give criterion scores for these items, and should consider them in providing an overall impact score.

Protections for Human Subjects For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to