Part 1. Overview Information

Key Dates

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.

No late applications will be accepted for this Notice of Funding Opportunity (NOFO).

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.

1. Use the NIH ASSIST system to prepare, submit and track your application online.
2. 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.
3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Purpose

To promote the success of clinically relevant, multimodal AI tools in real-world environments, the PRIMED-AI Program will develop of standardized processes to organize and support the emerging multimodal-AI field.  This initiative will fund discrete, two-year projects for development and initial testing of frameworks, which are actionable guidelines, standardized protocols, and/or standardized operating procedures for development and deployment of multimodal clinical decision support tools. These frameworks will be compiled into a "playbook."  The frameworks in this playbook will address PRIMED-AI Program objectives while remaining flexible enough for broader use by the community. The Playbook award recipients will work closely with each other and with PRIMED-AI members overall.  Awards made under this funding opportunity that will allow for the creation of responsible multimodal AI tools that will improve patient care. 

Background

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 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 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 will 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 to read all companion NOFOs , including methods PRIMED-AI intends to utilize to address error mitigation and technical management. Familiarity with the companion NOFOs may better inform proposed Playbook project 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

All frameworks developed under this NOFO and the resulting playbook are expected to be shared and adopted by the broader research community and must be designed in such a way as to ensure that this is achievable.

Organizations/academic institutions/industry can accelerate their CDS model solutions by understanding how different types of frameworks can inform their approach to addressing inherent issues in their design and implementation.  Frameworks should be practical, adapt to the rapidly evolving multimodal health AI landscape, address specific obstacles associated with imaging data (in addition to other types of data), and be operational to varying degrees. When applying frameworks, applicants must understand the dependencies between different types of frameworks and the particular healthcare problem they wish to address, customizing the use of the framework accordingly.  Applicants must also identify what classes of data and/or models the developed frameworks would apply to and who the target audience is intended to be for the proposed frameworks.  The context and use cases for frameworks as well as any limitations must be clear, and this must be included in the final output of the recipient project. 

Each applicant is required to propose two or more distinct frameworks for development – the frameworks should be on two separate framework topics, rather than two methods of addressing the same framework topic.

Applicants may submit frameworks on the following topics, either individually or combined, and not limited to:

• AI-enabled scientific discovery frameworks for using multimodal clinical data to generate hypotheses around patient health and care, not just prediction models.
• World-class dataset generation frameworks to encourage the creation of curated, interoperable, AI-ready datasets that could serve as a shared resource across clinical AI projects. This could include proposals to support the Genesis program and other Administration AI Action Plan priorities.
• Training frameworks for the development of training modules or curricula for clinicians to support AI literacy and promote AI adoption into clinical practice.
• Data quality frameworks to guide the collection and preparation of AI-ready data while working to minimize the introduction of errors when training the model;
• Frameworks that address data leakage, where data used to train an algorithm has the information which the model is trying to predict, resulting in unreliable and bad prediction;
• Data lifecycle management frameworks to help to ensure the availability and disposition of production data as well as reduce drift and minimize the possible reintroduction of errors;
• Frameworks to quantify uncertainty, deriving typically from either the data used to train the model or the model itself; 
• Harmonization frameworks that define guidelines for ensuring that multimodal data and/or models can be utilized together;
• Generalizability frameworks that utilize benchmarks to interrogate model generalizability at differing clinical environments, and what must be specific for certain clinical environments;
• Transparency/explainability frameworks to increase user trust in multimodal AI tools by enabling stakeholders to understand AI decision-making processes;
• Model card and data card formatting frameworks to provide guidelines and requirements for proper model card and data card development;
• Standards-based (e.g., OMOP, FHIR) frameworks to support interoperable, data linkage and that highlights useful data features, improve AI-readiness, and mitigates risk while maintaining security;
• Privacy Enhancing Technologies frameworks for model sharing to prevent the unintended disclosure of sensitive and/or secure data used for model training;
• Navigating regulatory hurdles frameworks for identifying and providing guidance on steps to address moving multimodal AI tools from development to the clinic.

Framework Overlap - It is expected that frameworks evolve and mature to meet multiple user needs. Thus, many frameworks overlap or are complementary to each other. Because interdisciplinary teams with differing backgrounds and objectives must come to a consensus, overlaps between frameworks provide groups with the flexibility to utilize relevant aspects of multiple frameworks when developing their specific AI models.  After award receipt, it is anticipated that Playbook award recipients will collaborate to synergize frameworks. Upon award, all Playbook award recipients are required to establish a working group that will enable the recipients to coordinate development of the final playbook product and ensure minimal overlap between each of the recipients.  This working group will be required to meet at least monthly to streamline playbook development.

Applications proposing frameworks or methods that are duplicative to existing frameworks or are incremental advancements to existing frameworks will be considered of low programmatic relevance, which will decrease likelihood of funding.

The following will be considered non-responsive and will not be reviewed:

• Projects that do not propose two or more distinct frameworks for development.

See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information

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

1. Eligible Applicants

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

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Local Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized).

Federal Governments

• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• 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
• Regional Organizations

Applications Involving the NIH Intramural Research Program

The requests by NIH intramural scientists will be limited to the incremental costs required for participation.   As such, these requests will not include any salary and related fringe benefits for career, career conditional or other Federal employees (civilian or uniformed service) with permanent appointments under existing position ceilings or any costs related to administrative or facilities support (equivalent to Facilities and Administrative or F&A costs).  These costs may include salary for staff to be specifically hired under a temporary appointment for the project, consultant costs, equipment, supplies, travel, and other items typically listed under Other Expenses.  Applicants should indicate the number of person-months devoted to the project, even if no funds are requested for salary and fringe benefits.

If selected, appropriate funding will be provided by the NIH Intramural Program. Intellectual property will be managed in accord with established policy of NIH in compliance with Executive Order 10096, as amended, 45 CFR Part 7; patent rights for inventions developed in NIH facilities are NIH property unless NIH waives its rights.

Should an extramural application include collaboration with intramural scientists, no funds for the support of the intramural scientists may be requested in the application.  The intramural scientist may submit a separate request for intramural funding as described above.

Foreign Organizations/International Collaborations

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 not allowed.

Applicant Organizations

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. 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 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.

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.

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.

2. Cost Sharing

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

Number of Applications

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 (in this NOFO, in a policy notice, or other notice from NIH Guide for Grants and Contracts). 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.

Page Limitations

All page limitations described in the How to Apply- Application Guide and the Table of Page Limits must be followed.

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.

SF424(R&R) Cover

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.

R&R or Modular Budget

All instructions in the How to Apply- Application Guide must be followed.

If the application is submitted by or includes collaboration with an NIH Intramural Research program, the budget request for this NOFO must distinguish between extramural costs, and the NIH intramural investigator costs. Extramural costs are associated with the extramural investigator and the applicant organization. NIH intramural investigator costs are those required by the intramural investigator for carrying out the proposed work and which are specifically identified with the project.

NIH Intramural Costs (only include if applicable)

Each NIH Institute and Center maintains individual policies with respect to the scope of resources available for intramural collaboration. The requests by NIH intramural scientists will be limited to the incremental costs required for participation. As such, these requests will not include any salary and related fringe benefits for career, career conditional or other Federal employees (civilian or uniformed service) with permanent appointments under existing position ceilings or any costs related to administrative or facilities support (equivalent to Facilities and Administrative or F&A costs). These costs may include salary for staff to be specifically hired under a temporary appointment for the project, consultant costs, equipment, supplies, travel, and other items typically listed under Other Expenses. Applicants should indicate the number of person-months devoted to the project, even if no funds are requested for salary and fringe benefits. Resources required need to be determined before the research protocol can be approved by the respective NIH Institute/Center. Prospective applicants are strongly encouraged to contact staff at the participating NIH Institute/Center to discuss intramural investigator costs, because individual Institutes/Centers may have different policies regarding support for the intramural portion of the project. 

Once the intramural investigator costs are known, the extramural applicant will enter this amount as a "subaward" budget in the application, and attach appropriate justification and documentation. 

Intellectual property will be managed in accord with established policy of NIH in compliance with Executive Order 10096, as amended, 45 CFR Part 7; patent rights for inventions developed in NIH facilities are NIH property unless NIH waives its rights.  

Extramural Award Recipient Costs (all applicants)

Extramural costs may include such items as salary support for the extramural PD/PI and staff at the applicant organization, supplies, laboratory animals, data analysis, and other allowable costs for work performed at the (extramural) applicant organization, as well as travel costs for the extramural investigator(s).

• The PD/PI and up to two other key personnel with complementary expertise are required to attend an annual in person Consortium meeting in Bethesda, MD, as well as virtual Consortium-led tutorials and open innovation meetings, as appropriate. Funds to attend these in person meetings should be budgeted in the application.
• Extramural costs should also include travel costs for participation in an in-person frameworks showcase event at the end of year 2 of award and should include funds for 2-3 members, including the PD/PI, to attend this showcase.

R&R Subaward Budget

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.

PHS 398 Research Plan

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

Research Strategy

Required Components

Each applicant is required to propose two or more distinct frameworks for development – the frameworks should be on two separate framework topics, rather than two methods of addressing the same framework topic. All frameworks developed under this NOFO and the resulting playbook are expected to be shared and adopted by the broader research community and must be designed in such a way as to ensure that this is achievable. Frameworks must be practical, adapt to the rapidly evolving multimodal health AI landscape, and address specific obstacles associated with imaging data, in addition to other types of data.

As part of the research strategy, applicants must describe clear plans for developing two or more frameworks, to include the following:

• Summary of proposed frameworks, to include the area of need, why the frameworks are needed, and how the proposed frameworks would address PRIMED-AI objectives and needs, while also remaining flexible enough for use with multimodal biomedical AI inside and outside the PRIMED-AI Program;
• Description of comprehensive team for development of proposed frameworks, to include relevant stakeholders (e.g. patients, clinicians, software developers, data scientists, regulators, others) to ensure that frameworks are usable throughout their lifecycles by the relevant parties and in appropriate environments;
• Description of classes of data, to include imaging data, and/or models the developed frameworks would apply to and who the target audience is for the developed framework;
• Summary of any potential dependencies between different types of frameworks and the particular healthcare problem they wish to address;
• Description of a plan to promote clinical AI adoption and innovation through obtaining user feedback on framework usability and applicability, to include iterative rounds of framework updates based on this feedback.

The application must include a detailed draft of the expected final framework layout to provide a starting point for iteration during the project and during discussions with the other Playbook award recipients.  The proposal must include an early SOP, relevant definitions, and framework management plans.

Recipients will work with the PRIMED-AI Steering Committee and, the Logistics Center to post a final framework on the PRIMED-AI web portal as a 12-month milestone.

The following additional items must also be addressed in the application:

• Relevant Expertise. Describe the investigators' expertise in developing AI frameworks. Demonstrate the capacity for flexibility within the proposed framework development strategy to account for varying multimodal data, tool type and clinical environments.
• Management Plan. Describe how the PD(s)/PI(s) will manage the proposed project, who will oversee the day-to-day activities (e.g., a Project Manager if not a PD/PI), and how the management structure will support achievement of the proposed goals and milestones. Describe the organization of the proposed project, its management structure, key personnel, and how it will interface with the other Playbook award recipients and Validation Center, as well as with the PRIMED-AI Steering Committee.
• Consortium Collaboration Plan. All Playbook award recipients will collaborate effectively and participate in the PRIMED-AI consortium to maximize the chances of overall success of the Program. Briefly describe plans to work with other Playbook award recipients, the Logistics Center for dissemination and web portal inclusion, and the Validation Center to harmonize processes for appropriate development and validation of multimodal AI tools.
• Milestone Plan. Define clear goals and a timeline for the development of proposed frameworks, and metrics that will document progress towards the goals for the PRIMED-AI Program. This plan must include a Gantt chart of proposed timelines and milestones, as well as a detailed list of all milestones with associated details. Examples include, but are not limited to, milestones that track software development, validation timelines for frameworks, or deployment of frameworks for use by the Validation Center. Include plans for critically evaluating and revising milestones . The number and duration of milestones will depend on the project.Include these items for each year, as appropriate. Milestones may be revised at the time of the award and/or periodically as described in the terms and conditions of a Cooperative Agreement in section VI.2.
• Performance Reporting. Describe a plan for collection and reporting of quantitative performance metrics to demonstrate progress. Such metrics can be used to monitor the progress and impact of the Program, and will be shared with the Logistics Center, which will be responsible for coordinating evaluations across the Consortium. Plans will include a mechanism for critical evaluation and timely revision of these metrics on a regular basis.

NIH Intramural Program Applicants:

Letters of Support: Applications from the NIH Intramural Program, either as primary applicants or as collaborators, submitted in response to this NOFO must include a current (i.e. within 2 months of application due date) letter from the Scientific Director of their Division indicating that the intramural scientist will be able to collaborate on the project.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply - Application Guide.

Applicants should indicate their willingness to abide by all data deposition, quality control metrics, standardization, metadata requirements, data and software release, and public copyright license policies developed by the PRIMED-AI Consortium and approved by NIH staff. Prior to funding, NIH Program Staff may negotiate modifications to the Sharing Plan with the applicant.

 Other Plan(s): 

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. 

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.

Delayed Onset Study

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.

6. Funding Restrictions

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.

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.

Important reminders:

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 grantdisclosures@oig.hhs.gov.

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

1. Criteria

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

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

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

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.

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s), convened by CSR, in accordance with NIH peer review policies and practices, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications will receive a written critique.

Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.

Requests for reconsideration of initial peer review will not be accepted for applications submitted in response to this NOFO. 

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this NOFO. Following initial peer review, recommended applications will receive a second level of review by the National Center for Advancing Translational Sciences Advisory Council. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement Section 2.5.1. Just-in-Time Procedures. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding.

Prior to making an award, NIH reviews an applicant's federal award history in SAM.gov to ensure sound business practices. An applicant can review and comment on any information in the Responsibility/Qualification records available in SAM.gov. NIH will consider any comments by the applicant in the Responsibility/Qualification records in SAM.gov to ascertain the applicant's integrity, business ethics, and performance record of managing Federal awards per 2 CFR Part 200.206 "Federal awarding agency review of risk posed by applicants." This provision will apply to all NIH grants and cooperative agreements except fellowships.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement Section 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

A Notice of Award (NoA) is the official authorizing document notifying the applicant that an award has been made and that funds may be requested from the designated HHS payment system or office. The NoA is signed by the Grants Management Officer and emailed to the recipient's business official.

In accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Any pre-award costs incurred before receipt of the NoA are at the applicant's own risk.  For more information on the Notice of Award, please refer to the NIH Grants Policy Statement Section 5. The Notice of Award and NIH Grants & Funding website, see Award Process.

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

2. Administrative and National Policy Requirements

The following Federal wide and HHS-specific policy requirements apply to awards funded through NIH:

• The rules listed at 2 CFR Part 200, Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards.
• All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the terms and conditions in the Notice of Award (NoA). The NoA includes the requirements of this NOFO. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities.

All federal statutes and regulations relevant to federal financial assistance, including those highlighted in NIH Grants Policy Statement Section 4 Public Policy Requirements, Objectives and Other Appropriation Mandates.

By applying for or accepting federal funds from HHS, recipients certify compliance with all federal antidiscrimination laws and these requirements and that complying with those laws is a material condition of receiving federal funding streams. Recipients are responsible for ensuring subrecipients, contractors, and partners also comply.

Applicants and recipients are strongly encouraged to refer to the NIH Director's Statement of Priorities, entitled "Advancing NIH's Mission Through a Unified Strategy." 

Recipients are responsible for ensuring that their activities comply with all applicable federal regulations. Pursuant to 2 CFR 200.340, by accepting an NIH award, the recipient agrees that continued funding for the award is contingent upon the availability of appropriated funds, recipient satisfactory performance, compliance with the Terms and Conditions of the award, and may also otherwise be terminated, to the extent authorized by law, if the agency determines that the award no longer effectuates the program goals or agency priorities, in line with 2 CFR 200.340(a)(4).

Pursuant to the Cybersecurity Act of 2015, Div. N, § 405, Pub. Law 114-113, 6 USC § 1533(d), the HHS Secretary has established a common set of voluntary, consensus-based, and industry-led guidelines, best practices, methodologies, procedures, and processes.

Successful recipients under this NOFO agree that:

When recipients, subrecipients, or third-party entities have:

• ongoing and consistent access to HHS owned or operated information or operational technology systems; and
• receive, maintain, transmit, store, access, exchange, process, or utilize personal identifiable information (PII) or personal health information (PHI) obtained from the awarding HHS agency for the purposes of executing the award.

Cybersecurity plans and procedures must at minimum include the following:

• Develop cybersecurity plans and procedures, modeled after the NIST Cybersecurity framework, to protect HHS systems and data:
  • Identify:
    • Develop an inventory of all assets and accounts with access to HHS owned and operated information or operational technology systems or which obtain PII or PHI for the purposes of the award.
  • Protect:
    • Limit access to HHS owned and operated systems to only those in need of access to complete reward activities.
    • Require all staff to complete annual cybersecurity and privacy awareness training. Visit 405(d): Knowledge on Demand (hhs.gov) to obtain free trainings, if needed.
    • Enable multifactor authentication for all employees, subrecipients, and third-party entities to access HHS owned and operated information or operational technology systems.
    • Regularly backup sensitive data and test backups.
  • Detect:
    • Install anti-virus or anti-malware software on all devices, servers, and accounts used to connect to HHS owned and operated systems.
  • Respond:
    • Develop an incident response plan. See Incident-Response-Plan-Basics_508c.pdf (cisa.gov) to learn about developing incident response plans.
    • Have cybersecurity incident reporting procedures that ensure the relevant HHS awarding agencies are notified of a cybersecurity incident within 48 hours of discovery. A cybersecurity incident is defined as an unplanned interruption to a technology service or reduction in the quality of a technology service, or an occurrence that actually or potentially jeopardizes the confidentiality, integrity, or availability of an information system or the information the system processes, stores, or transmits.
  • Recover:
    • Investigate incidents and plug any security gaps identified. 

All activities proposed in your application and budget narrative must align with applicable law, including but not limited to statutes, executive orders, federal regulations and applicable judicial holdings.  Accordingly, discretionary awards shall not be used to fund, promote, encourage, subsidize, or facilitate; racial preferences or other forms of racial discrimination by the recipient, including activities where race or intentional proxies for race will be used as a selection criterion for employment or program participation; denial by the recipient of the sex binary in humans, or the belief that sex is a chosen or mutable characteristic; illegal immigration; or any other initiatives that compromise public safety.  If an application does not align, the application will not receive funding to the extent permitted by law and applicable court orders.

For applications involving substance abuse, the application must not support harm reduction. Please see Updated Funding Guidance for Recipients on Supplies and Services.

For applications involving funding Medication-Assisted Treatment (MAT) or medications for opioid use disorder (MOUD), this funding should be used to provide comprehensive treatment and recovery support services rather than medication-only models for opioid use disorder. Services should include medications, where clinically indicated, in conjunction with psychosocial and other treatment and recovery support services. Funding can also be used to support individualized tapering and discontinuation of medications when clinically indicated. Please see Updated Funding Guidance for Recipients on  MAT/MOUD.

As of October 1, 2025, HHS has adopted 2 CFR Part 200, with some modifications included in 2 CFR Part 300. These regulations replace those in 45 CFR Part 75. However, for NIH, under the Consolidated Appropriations Act for FY 2026, (P.L. 119-75, Division B, Title II, Sec. 224), the provisions relating to indirect costs in 45 CFR 75 continue to apply to NIH awards. Consistent with the statute, NIH will not apply updated thresholds outlined within 2 CFR Part 200, at this time.

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (HHS) grant administration regulations at 2 CFR Part 200, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this Program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the recipients is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and NIH as defined below.

Roles and Responsibilities:

Playbook Working Group: Consists of PIs and relevant key personnel from Playbook projects. This group will primarily be responsible for coordinating the development of the final playbook product and ensuring minimal overlap between each of the recipients.

NIH PRIMED-AI Working Group (WG): Consists of NIH programmatic staff from multiple Institutes and Centers of the NIH. This group will be primarily responsible for the stewardship of the PRIMED-AI Program and will participate as non-voting members in the committees.   

External Program Consultants (EPCs):  External Program Consultants provide critical scientific and managerial insights and recommendations to NIH staff. These recommendations might be relayed to the awardees at the discretion of the NIH.  EPC are invited to attend annual meetings and other key events to have awareness of progress and provide feedback to NIH staff in their consulting capacity.

PRIMED-AI Steering Committee (SC):  The SC includes funded contact PIs and NIH PRIMED-AI Program staff to jointly provide scientific input and coordination for the PRIMED-AI Program. It is expected that most of the decisions on the activities of the SC will be reached by consensus. If a vote is needed, each project PD/PI (or Contact PI in the case of multi-PI projects) will have one vote. NIH staff will be non-voting members of the SC . When a vote is required, at least 60% of the votes must be affirmative for approval. To address particular issues, the SC may establish working groups as needed, which will include representatives from the PRIMED-AI Consortium, the NIH, and possibly other experts.

PRIMED-AI Consortium: The PRIMED-AI Consortium will be made up of all PRIMED-AI award recipients. The organizational structure is meant to enable the overall goals of the PRIMED-AI Program.

The PD(s)/PI(s) will have the primary responsibility for:

• Leading the project as a whole, and agree to accept close assistance, advice, coordination, and collaborate with the NIH PRIMED-AI Program Staff and other award recipients.
• Planning, direction, and execution of the proposed project will be solely that of the PD(s)/PI(s). They will determine experimental approaches, design protocols, set project milestones and conduct experiments.
• Participating in group activities, including the Playbook working group, and the SC to share design and analysis techniques and promote comparability across studies wherever possible.
• Ensuring active participation of partner sites and collaborators in group activities, if applicable.
• Implementing consensus SC recommendations for designing, implementing, evaluating, and disseminating PRIMED-AI Consortium modeling research projects, as appropriate and feasible.
• Agreeing to abide by any policies -- including those regarding intellectual property, data and software release, publication of PRIMED-AI Consortium papers, quality control metrics, standardization, metadata requirements, and public copyright licensing -- that are recommended and consented to by the PRIMED-AI SC and approved by the NIH PRIMED-AI WG, as well as applicable NIH policies, laws, and regulations.
• Providing information to the NIH Program Official and Project Scientist concerning progress and activities on a regular basis in an agreed upon format, no less than monthly.
• Attending and participating in SC meetings and accepting and implementing the consensus guidelines and procedures, as appropriate.

Recipients will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.

NIH Staff has substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

The Program Official (PO) is an NIH staff member who will provide programmatic oversight and stewardship of the projects, including review of pre-award and award documents/requirements, review of progress reports and budgets, and any other programmatic issues that may arise. The PO will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the Notice of Award. The PO will make the final determination on the negotiated milestones and will also make the final determination on whether the milestones are met. The PO has the option to recommend, following consultation with the NIH PRIMED-AI Program staff, the withholding or reduction of support from any project that substantially fails to achieve its goals according to the milestones agreed to at the time of the award.

The Project Scientist (PS) is a NIH staff member who will have substantial scientific and programmatic involvement during the conduct of this activity through technical assistance, advice, and coordination. However, the role of NIH staff will be to facilitate and not to direct the activities. It is anticipated that decisions in all activities will be reached by consensus of the PRIMED-AI Consortium and that NIH staff will be given the opportunity to offer input to this process, as a non-voting member. 

The NIH PS will have the following substantial involvement:

• Participating with the other SC members in the group process of setting research priorities, deciding optimal research approaches and protocol designs, and contributing to the adjustment of research protocols or approaches as warranted. The PS may facilitate the group process and not direct it.
• Serving as a liaison, helping to coordinate activities among and for the award recipients, including acting as a liaison to the NIH, and as an information resource for the award recipients about other research activities. The PS will coordinate the efforts of the Program with other groups conducting similar studies.
• Attending all SC meetings as a non-voting member and assisting in developing operating guidelines, quality control procedures, and consistent policies for dealing with situations that require coordinated action. The PS will be responsible for working with the PD/PIs in facilitating logistical aspects of the Program.
• Reporting periodically on the progress of the Program to the NIH PRIMED-AI Program staff and leadership.
• Serving as a liaison between the SC and the external advisory groups.
• Providing oversight and advice in the management and technical performance of the award projects.
• Facilitation of sharing and dissemination of the data and related resources developed in the course of the PRIMED-AI Program to the scientific community at large.

The NIH may enlist additional scientific experts as necessary from within the NIH, or other government agencies, whose function will be to advise the PD(s)/PI(s) in carrying out the goals and aims of the approved studies.

The NIH reserves the right to curtail or phase out the award in the event of (1) a substantial shortfall in accomplishing the management goals and responsibilities as stated in the reviewed application, (2) failure to meet procedures and milestones, and/or (3) substantive changes in the management of award(s) that are not in keeping with the objectives of the NOFO.

Areas of Joint Responsibilities:

Consistent with achieving the goals of the PRIMED-AI Program, the NIH requires all award recipients to collaborate effectively with each other to maximize the chances of overall success of the entire Program. Close interaction among the participating investigators will be required, as well as significant involvement from the NIH. The award recipients and designated NIH Staff will participate in the annual PRIMED-AI Consortium meeting and scheduled conference calls and share information on data resources, methodologies, analytical tools, as well as preliminary developments. PDs/PIs, key personnel and pre- and post-doctoral trainees are eligible to attend these meetings. EPCs will attend the annual meetings, as well as other relevant NIH staff.

PRIMED-AI Program Evaluation:

Award recipients must work collaboratively with all members of the PRIMED-AI Consortium to develop and provide usage statistics and quantitative metrics for data and resources for the purposes of programmatic evaluation and continuous improvement. In carrying out stewardship of this NOFO, the NIH or its Institutes and Centers may request information essential to an assessment/evaluation of the effectiveness of the PRIMED-AI Program from the award recipients. Award recipients may be contacted for periodic updates on information helpful in evaluating the impact of the program.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the SC chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the recipients. This special dispute resolution procedure does not alter the recipients' right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.  

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. 

Incumbent upon being a Common Fund award recipient, engagement with the Common Fund Data Ecosystem (CFDE) is required for dissemination of PRIMED-AI assets and resources. This may include the sharing of software, CDS tools, AI models, and other related resources with managers of the CFDE infrastructure for the purpose of increasing distribution and integrating with other Common Fund data resources.

Sharing scientific data accelerates biomedical research discovery, in part, by enabling validation and ensuring reproducibility of research results, providing accessibility to high-value datasets, and promoting data reuse for future research studies. PRIMED-AI applicants must provide a Data Management and Sharing Plan. Applicants are encouraged to review the following resources supporting the Data Management and Sharing Plan:

• Artificial Intelligence in Research: Policy Considerations and Guidance: https://osp.od.nih.gov/policies/artificial-intelligence/

• NOT-OD-25-081: Protecting Human Genomic Data when Developing Generative Artificial Intelligence Tools and Applications
• Checklist to evaluate the suitability of data for record linkage: https://github.com/NIH-NICHD-Ecosystem/E2_Record-Linkage-Implementation-Checklist/tree/main

Intellectual Property (IP) Rights

The successful development of multi-modal AI models and the integration of imaging and multimodal data sets on the PRIMED-AI AIP projects are anticipated to require either substantial investment and support by private sector industries, and/or may involve collaborations with other organizations such as academic, other government agencies, and/or non-profit research institutions not directly involved in the PRIMED-AI program. NIH recognizes that intellectual property rights are likely to play an important role in achieving the goals of this program.

To this end, all award recipients shall understand and acknowledge the following:

• The award recipient is solely responsible for the timely acquisition of all appropriate proprietary rights, including intellectual property rights, and all materials needed for the award recipient to perform the project.
• Before, during, and subsequent to the award, the U.S. Government is not required to obtain for the recipient any proprietary rights, including intellectual property rights, or any materials needed by the recipient to perform the project.
• The award recipient is required to report to the U.S. Government all inventions made in the performance of the project, as specified by 35 U.S.C. Sect. 202 (Bayh-Dole Act).
• The award recipient acknowledges the applicability of 35 U.S.C. 200 et. seq. (Bayh-Dole Act) and the resulting US Government rights that apply to any agreements resulting from this NOFO.
• Recipients will have primary rights to the data and resources developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH regulations and policies, including 2 CFR § 200.315.
• The Recipient will declare any relevant Intellectual Property, pre-existing or otherwise, that was not made with the NIH funds, during the application process.

4. Reporting

When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement Section 8.4.1 Reporting. To learn more about post-award monitoring and reporting, see the NIH Grants & Funding website, see Post-Award Monitoring and Reporting.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement Section 8.6 Closeout. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 2 CFR Part 200.301.

Award recipients must work collaboratively with all members of the PRIMED-AI Consortium to develop and provide usage statistics and quantitative metrics for data and resources for the purposes of programmatic evaluation and continuous improvement. In carrying out stewardship of this NOFO, the NIH or its Institutes and Centers may request information essential to an assessment/evaluation of the effectiveness of the PRIMED-AI Program from the award recipients. Award recipients may be contacted for periodic updates on information helpful in evaluating the impact of the program.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

eRA Service Desk - Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues.

Grants.gov Support Center - Questions regarding Grants.gov registration and services (e.g., Workspace, subscriptions).

Common Fund PRIMED-AI Program
Email: ODPRIMED-AI@od.nih.gov

Center for Scientific Review (CSR)
Email: NOFOReviewContact@csr.nih.gov

Email: ncatsgmbnofo@mail.nih.gov

Section VIII. Other Information

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 2 CFR Part 200.