PRIMED-AI Validation Center

PRIMED-AI Validation Center is sponsored by National Institutes of Health (NIH). Seeks applications for a center to independently verify, validate, and quantify uncertainty in AI-enabled tools developed under the PRIMED-AI program.

RFA-RM-27-014: Validation Center for Precision Medicine with AI: Integrating Imaging with Multimodal Data (PRIMED-AI) (U54 Clinical Trials Not Allowed) Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) Components of Participating Organizations Office of Strategic Coordination ( Common Fund ) This Notice of Funding Opportunity (NOFO) is developed as a Common Fund Initiative ( https://commonfund. nih. gov/ ) through the Office of the NIH Director, Office of Strategic Coordination ( https://commonfund.

nih. gov/ ). All NIH Institutes and Centers participate in Common Fund initiatives.

The NOFO will be administered by the National Institute of Biomedical Imaging and Bioengineering (NIBIB) on behalf of the NIH. Note: Not all NIH Institutes, Centers, and Offices (ICOs) participate in Announcements. Applicants should carefully note which ICOs participate in this announcement and view their respective areas of research interest at the ICO-Specific Scientific Interests website .

ICOs that do not participate in this announcement will not consider applications for funding. Funding Opportunity Title Validation Center for Precision Medicine with AI: Integrating Imaging with Multimodal Data (PRIMED-AI) (U54 Clinical Trials Not Allowed) U54 Specialized Center- Cooperative Agreements Check for any recent Notices of NIH Policy Changes that may impact application requirements.

January 23, 2026 - NIH Pause on New Submissions to the NIH Human Embryonic Stem Cell Registry and Request for Information on Reducing Reliance on Human Embryonic Stem Cells in NIH-Supported Research. See Notice, NOT-OD-26-031 .

Funding Opportunity Number (FON) Companion Notice of Funding Opportunity Research Project (Cooperative Agreements) Phase 1 Exploratory/Developmental Cooperative Agreement/Exploratory/Developmental Cooperative Agreement Phase II Phase 1 Exploratory/Developmental Cooperative Agreement/Exploratory/Developmental Cooperative Agreement Phase II Resource-Related Research Project (Cooperative Agreements) See Section III. 3.

Additional Information on Eligibility.

Assistance Listing Number(s) Notice of Funding Opportunity Purpose The overarching goal of this notice of funding opportunity (NOFO) and its companion opportunities is to establish the Precision Medicine with AI: Integrating Imaging with Multimodal Data (PRIMED-AI) Program to support development of innovative, reliable, cost-effective, and sustainable multimodal AI-based clinical decision support (CDS) tools.

PRIMED-AI CDS tools are based on the integration of clinical imaging with other types of multimodal health data to enhance care for patients with a wide range of health conditions. The PRIMED-AI Program seeks to catalyze the adoption of AI-based CDS tools into clinical workflows to enable novel personalized medicine strategies that address significant health challenges.

The purpose of this NOFO is to solicit applications for the creation of a Validation Center to serve as a dedicated hub for the comprehensive evaluation and characterization of AI-enabled, image-based, multimodal CDS tools developed by the PRIMED-AI Consortium, to ensure these tools are reliable, reproducible, and generalizable.

The Validation Center will focus on verification, validation, interoperability, and uncertainty quantification to comprehensively characterize performance of the CDS tools developed by the program.

The core functions of the Validation Center will involve the systematic validation of PRIMED-AI Consortium deliverables, including those emerging from award recipients under the Playbook, Data-to-Model Academic-Industrial Partnerships, and Model-to-Clinic NOFOs.

Funding Opportunity Goal(s) The Office of Strategic Coordination ( Common Fund ) supports research and other projects that will accelerate fundamental biomedical discovery and translation of that knowledge into effective prevention strategies and new treatments.

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 Multi-Project (M) Instructions in the How to Apply - Application Guide , except where instructed to do otherwise (in this NOFO or in a Notice from the NIH Guide for Grants and Contracts ). Conformance to all requirements (both in the How to Apply - Application Guide and the NOFO) is required and strictly enforced.

Applicants must read and follow all application instructions in the How to Apply - Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the How to Apply - 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. 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 Validation Center (VC) will serve as a dedicated hub for the comprehensive evaluation and characterization of AI-enabled , image-based, multimodal Clinical Decision Support (CDS) tools developed by the PRIMED-AI Consortium, to ensure these tools are reliable, reproducible and generalizable.

Clinical imaging plays a pivotal role in diagnosis, treatment, and assessment of health outcomes; however, it is often utilized in isolation from other types of data during the development of artificial intelligence (AI)-based clinical decision support (CDS) tools. Current AI applications typically leverage a single imaging modality from radiological or ophthalmological sources.

Because health is shaped by a variety of interconnected factors–clinical, biological, genetic, environmental and social–the Precision Medicine with AI: Integrating Imaging with Multimodal Data (PRIMED-AI) Program seeks to integrate clinical imaging with relevant, complementary multimodal data (MMD).

The overarching goal of the PRIMED-AI Program is to catalyze the development and adoption of innovative AI-based CDS tools into clinical workflows. The PRIMED-AI Program initiatives collectively aim to tackle complex clinical challenges by fostering cross-disciplinary collaboration to create innovative, reliable, cost-effective, and sustainable AI solutions that enable precision medicine strategies.

Prior to applying, applicants are encouraged to check the PRIMED-AI Program website for updates to relevant FAQs and informational webinars, and are also encouraged to read all companion NOFOs to ensure they are aware of the goals and responsibilities of all PRIMED-AI award recipients, including methods PRIMED-AI intends to utilize to address error mitigation and technical management.

Familiarity with the companion NOFOs may better inform proposed Validation Center interconnections with other aspects of the PRIMED-AI Program . Detailed definitions for key terms used in the PRIMED-AI program can be found on the PRIMED-AI website mentioned above.

Key Requirements of the Validation Center The organizational structure of the Validation Center must include three main Cores, 1) a Validation Core; 2) Translation Core to establish sustainable tool(s) in support of AI model clinical translation; and 3) Fast-track Core, addressing identified unmet needs. Validation Core - Independent validation of PRIMED-AI CDS tools.

The Validation Center will function as a hub for independent, rigorous AI tool validation - focused on the overall reproducibility of AI models developed by the PRIMED-AI Program, including those developed under the companion NOFOs. The Validation Center supports PRIMED-AI generated tools in relation to the patient care continuum.

The Validation Center will focus on verification, validation, interoperability, and uncertainty quantification to comprehensively characterize performance of the CDS tools developed by the PRIMED-AI Consortium. These validated resources and evaluation findings will be made available through a publicly accessible, centralized PRIMED-AI web portal managed by the Logistics Cente r in consultation with the model developers.

Translation Core - Sustainable tools for regulatory clinical translation support. Through the development of a validation pipeline, the Validation Center will also be expected to develop a tool (or tools) that will allow users to benchmark and evaluate models in various clinical environments ( e. g .

accuracy, monitor drift). Ideally, the tool(s) should promote sustainability after the end of the Program and have the ability to be utilized by the broader research community. This could take the form of, but not limited to, an Independent Test Assessment Program ( https://www.

nibib. nih. gov/programs/radx-innovation-funnel ), modular performance assessment tools and/or metrics/protocols.

While not required, the applicants should also work towards having these tools be MDDT–eligible (Medical Device Development Tools - https://www. fda. gov/medical-devices/medical-device-development-tools-mddt ).

This could also include integration with other AI-enabled science efforts, including the Genesis Mission. Fast-track Core – funding support for unmet clinical and data science needs. The Validation Center will develop a fast-track process that addresses unmet clinical needs in PRIMED-AI relevant areas.

The fast-track process requirements include network ideation activities, development of solicitations, and evaluation of proposals in consultation with the Steering Committee and NIH PRIMED-AI Program staff. The Fast-track Core will support modular software tool development sub-projects and/or other identified needs.

This will create opportunities to expand the PRIMED-AI community, bring in new collaborations, and address existing relevant gaps. It is anticipated that the Validation Center would manage no more than ten (10) sub-projects per year. The first round of sub-project awards is to be made in Year Two of the grant project period.

MPI and Validation Center staff requirements - A multi-PD/PI application is required - one PD/PI is expected to commit at least 2 person months annually and the other(s) should devote at least 1 person month each. The PRIMED-AI Program will have regular conference calls and meetings. Applicants should request funds for 2-6 group members to attend annual meetings, Consortium-led tutorials, and open innovation meetings, as appropriate.

The Validation Center should budget at least 6 person months for a dedicated project manager/director (PM/PD) for the project with the appropriate scientific expertise and project management responsibilities, who would support the PI(s) with project management. The PM/PD will be the primary liaison with the PRIMED-AI Program and Steering Committee.

Specifically, the Validation Center will perform the following cross-cutting tasks: Develop a coordination plan consistent with achieving the goals of this Program incorporating all PRIMED-AI Consortium award recipients. Continuously sequester and annotate multimodal data for validation and benchmarking purposes, independent of data utilized by PRIMED-AI award recipients to train models.

Benchmark data sets will be made public through the PRIMED-AI web portal in collaboration with the Logistic Center . Develop a coordinated plan for interaction with other governmental AI-infrastructure efforts as appropriate (e.g. Genesis Mission). Implement and execute standardized, rigorous protocols for the benchmarking, evaluation and risk assessment of CDS tools developed by PRIMED-AI award recipients.

Develop technical validation guidelines for the PRIMED-AI Consortium proposed interaction with regulatory bodies (e.g. FDA, ONC) to facilitate that validation plans are consistent with relevant regulations. Develop best practices on how the Validation Center 's processes will remain transparent , reproducible , and sustainable. See Section VIII.

Other Information for award authorities and regulations. Section II. Award Information Cooperative Agreement: A financial assistance mechanism used when there will be substantial Federal scientific or programmatic involvement.

Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI. 2 for additional information about the substantial involvement for this NOFO.

Application Types Allowed The OER Glossary and the How to Apply - Application Guide provides 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 NIH Common Fund intends to commit approximately $2,700,000 in FY2027. One award is anticipated, contingent upon availability of funds and receipt of a sufficient number of meritorious applications.

Application budgets are limited to $2,000,000 direct costs for the first year and up to $3,200,000 direct costs for the remaining four years of the project. Requested budgets 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. 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 - Includes all types 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 Foreign Organizations/International Collaborations Non-domestic (non-U.S.) Entities (Foreign Organization) 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 not 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 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.

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

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

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

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

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

The personal profile associated with the PD(s)/PI(s) eRA Commons account must be linked to a valid ORCID ID. For more information on linking an ORCID ID to an eRA Commons personal profile see the ORCID topic in our eRA Commons online help.

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 his/her 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 . Effective management will require a significant commitment by the Program Director(s)/Principal Investigator(s).

A multi-PD/PI application is required - one PD/PI is expected to commit at least 2 person months annually and the other(s) should devote at least 1 person month each. This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1. 2- Definitions 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 or an institutional system-to-system solution. A button to apply using ASSIST is available in Part 1 of this NOFO. See the administrative office for instructions if planning to use an institutional system-to-system solution.

2. Content and Form of Application Submission It is critical that applicants follow the Multi-Project (M) Instructions in the How to Apply - Application Guide , except where instructed in this notice of funding opportunity to do otherwise (in this NOFO, in a policy notice , or other notice from NIH Guide for Grants and Contracts ) and where instructions in the How to Apply - Application Guide are directly related to the Grants.

gov downloadable forms currently used with most NIH opportunities. Conformance to the requirements in the How to Apply - 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. Component Type for Submission Instructions for the Submission of Multi-Component Applications The following section supplements the instructions found in How to Apply- Application Guide and should be used for preparing a multi-component application. When preparing the application, use Component Type 'Overall'.

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions, as noted. SF424(R&R) Cover (Overall) PHS 398 Cover Page Supplement (Overall) Follow standard instructions. Research & Related Other Project Information (Overall) Follow standard instructions.

Project/Performance Site Locations (Overall) A summary of Project/Performance Sites in the Overall section of the assembled application image in eRA Commons compiled from data collected in the other components will be generated upon submission.

Research and Related Senior/Key Person Profile (Overall) Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this NOFO) for the entire application. A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.

The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover. A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.

PHS 398 Research Plan (Overall) Introduction to Application: For Resubmission and Revision applications, an Introduction to Application is required in the Overall component. As part of the research strategy, applicants are required to structure the Validation Center to include three main Cores as described in the Part 2, Section 1: 1) a Validation Core; 2) Translation Core; and 3) Fast-track Core.

The Validation Center should address the following cross-cutting plans: Coordination Plan with PRIMED-AI Consortium Award Recipients – The Validation Center will develop a coordination plan for interactions with (1) the Logistics Center , to include plans for ensuring timely validation of resources for inclusion in the PRIMED-AI Web Portal, and jointly develop a sustainability plan beyond the PRIMED-AI Program support period; (2) the Playbook award recipients, to ensure that frameworks developed by the Playbook award recipients are incorporated into the validation process, (3) Data-to-Model AIP , and Model-to-Clinic award recipients, to implement and execute standardized, rigorous protocols for the initial and ongoing evaluation of CDS tools.

Milestones and Progress – Applicants must define semi-annual milestones with metrics that will document progress towards the achievement of the ultimate goals of the PRIMED-AI Program. The milestone and progress section should address the three main cores of the Validation Center , in an easily identifiable and attributable way ( e. g .

Gantt chart). Applicants should include plans for critically evaluating and revising these milestones on a regular basis, in consultation with NIH program staff.

Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply - Application Guide, with the following additional instructions: All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions: A Data Management and Sharing Plan (DMS Plan) is required for any NIH-funded or conducted research that will generate scientific data.

Applicants must submit the DMS Plan at the time of application using the NIH DMS Plan Format Page . The DMS Plan must address the elements in the structured format. Where the DMS Plan Format Page requires a "Yes or No" response, no additional narrative is allowed.

The Data Management and Sharing (DMS) Plan must be provided in the Overall component. Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in How to Apply- Application Guide ; any instructions provided here are in addition to the How to Apply - Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Overall) When involving human subjects research, clinical research, and/or NIH-defined clinical trials 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, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components.

To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components. 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 (Overall) All instructions in the How to Apply- Application Guide must be followed.

When preparing your application, use Component Type 'Core.' All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover (Validation Core) Complete only the following fields: Type of Applicant (optional) Descriptive Title of Applicant's Project Proposed Project Start/Ending Dates Research & Related Other Project Information (Validation Core) Human Subjects: Answer only the 'Are Human Subjects Involved?' and 'Is the Project Exempt from Federal regulations?' questions.

Vertebrate Animals: Answer only the 'Are Vertebrate Animals Used?' question. Project Narrative: Do not complete.

Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components. Project /Performance Site Location(s) (Validation Core) List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries. Research & Related Senior/Key Person Profile (Validation Core) In the Project Director/Principal Investigator section of the form, use Project Role of 'Other' with Category of 'Project Lead' and provide a valid eRA Commons ID in the Credential field.

In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component. Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.

If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used. Budget forms appropriate for the specific component will be included in the application package. Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries.

All other SF424 (R&R) instructions apply. PHS 398 Research Plan (Validation Core) Specific Aims: State concisely the goals of the Validation Core. Include a succinct summary of the core and its relevant experience to the stated objectives of this solicitation.

Research Strategy: This section should provide a clear description of the plan, timeline, and milestones to implement the proposed Validation Core activities, including but not limited to: Independent validation of PRIMED-AI CDS tools, developed by other PRIMED-AI Program participants, including those developed under companion NOFOs Establish and implement independent, rigorous AI tool validation, with reproducibility in mind, including access to multimodal data, and tools for privacy preserving interoperability, Deploy algorithm verification, validation and uncertainty quantification to comprehensively characterize performance of CDS tools Make the validated resources and evaluation findings available through the centralized PRIMED-AI web portal managed by the Logistics Center , in consultation with the original model developers [SK2] 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 , with the following modification: All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions: Do not include a Data Management and Sharing (DMS) Plan within this Component.

If a DMS Plan is required for this NOFO, it must be included within the Overall Component. Data Sequestration and Interoperability Plan – The Validation Center is responsible for independently evaluating performance and accuracy of CDS tools developed by D2M-AIP and M2C teams in real world clinical environments. The Center will be required to continuously sequester and annotate multimodal data for validation and benchmarking purposes.

A separate dataset must be maintained independent of data utilized by other PRIMED-AI award recipients for model training and be representative of the variety of real-world clinical data in cooperation with D2M-AIP and M2C teams. Interoperability efforts shall focus on standardizing metadata, data elements, dictionaries, evaluation metrics, methodologies, and reporting requirements.

The above, the applicant must include the following in a data sequestration and interoperability plan: Potential sources and types of data that will be utilized for validation; A description of how the Validation Center will oversee the appropriate collection, curation, linkage, privacy, and interoperability of data utilized for benchmarking and validation of PRIMED-AI tools.

A detailed plan for ensuring the integrity and confidentiality of sequestered data. Evaluation and Validation Plan - The Center must implement and execute standardized, rigorous protocols for the initial and ongoing evaluation of CDS tools developed by PRIMED-AI award recipients ( D2M-AIP and M2C ).

This requires establishing and maintaining high-quality, representative benchmark datasets to assess validity, generalizability, fit-for-purpose, and performance stability over time or across deployment contexts. This plan must include a proposed "model card" protocol or similar.

Components of model cards may include, but are not limited to, context of model use including provenance, uncertainty quantification, datasets used for model training, relevant patient populations, limits of predictive accuracy, code documentation, etc. The applicants must include in the plan an explanation of how the validation pathway will remain transparent, reproducible, and sustainable.

Error Mitigation and Technical Management Plan - Applicants must submit a required Error Mitigation and Technical Management Plan as a separate attachment (up to three pages in length,excluded from the 12-page Research Strategy page limit) that addresses all components listed in the guidance. The filename "Error Mitigation and Technical Management Plan. pdf" should be used for this attachment.

The Error Mitigation and Technical Management Plan may be revised during the award period in accordance with Consortium policies and updated NIH guidance. Only limited items are allowed in the Appendix. Follow all instructions for the How to Apply- Application Guide ; any instructions provided here are in addition to those in the How to Apply- Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Validation Core) When involving human subjects research, clinical research, and/or NIH-defined clinical trials 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 a 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. When preparing your application, use Component Type 'Core.'

All