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.

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 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.

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

This is a Notice of Funding Opportunity (NOFO) for a Single Source that will invite an application from an eligible organization to apply. Please see Section III. Eligibility for additional information. In accordance with NIH standard peer-review processes, the application will be peer-reviewed, and only a meritorious application will be considered for funding.

Purpose

This Notice of Funding Opportunity (NOFO) invites a single cooperative agreement application for the Resource Center for the Cardiovascular Repository for Type 1 Diabetes (CaRe-T1D).  The purpose of CaRe-T1D is to support innovative, discovery and mechanistic research through the study of human cardiovascular (CV) tissue. This research seeks to better understand cardiovascular disease (CVD) in type 1 diabetes, compare differences with type 2 diabetes, and ultimately guide the development of therapies to treat this major cause of morbidity and mortality for individuals with T1D. To achieve these goals, the Resource Center will expand the CaRe-T1D biorepository of human CV tissue, further develop the data commons for data sharing and for artificial intelligence (AI) tools, coordinate the research activities of the investigative teams in the CaRe-T1D consortium, and make CaRe-T1D resources accessible to the broader research community.  

Background

Premature atherosclerosis is the leading cause of death for people living with type 1 diabetes.  Treatments directed at established CV risk factors such as hyperglycemia, hypertension and hyperlipidemia have improved outcomes, but type 1 diabetes still confers a 2- to 4-fold higher risk of CV events and mortality compared to the general population.  A major knowledge gap is the limited understanding of the differences in the pathophysiology of CVD in people with type 1 diabetes compared to those with type 2 diabetes and without diabetes. These differences have major implications for treatment and prevention of CVD in type 1 diabetes.

A significant limitation to advancing research to more fully understand the development of CVD in type 1 diabetes has been the lack of availability of well-characterized human tissue and research networks for synergistic projects.  Human tissue is optimal for studying disease pathogenesis in that it takes a human-first approach to identify genetic, molecular and cellular disease markers that can be further validated mechanistically in animal, cellular and computational models.  CVD in individuals with type 1 diabetes develops over many years to decades and involves numerous biologic pathways.  Addressing these challenges requires a broad range of perspectives, expertise and approaches working together to dissect the similarities and differences in atherosclerosis and cardiomyopathy between type 1 and type 2 diabetes.

NIDDK, in partnership with NHLBI, created the CaRe-T1D program in 2022 through RFA-DK-21-010 to address these knowledge and research gaps. CaRe-T1D established a biorepository from organ donors with type 1 diabetes, type 2 diabetes or no diabetes that includes heart, kidney and arterial tissue, as well as careful clinical characterization.  All tissues undergo rigorous quality control procedures and analysis, including imaging for vascular calcification and microscopic evaluations.  Beyond CaRe-T1D, there are no comparable national-scale biorepositories focused on the study of T1D CVD with standardized tissue processing and operating protocols. In 2024, six investigative teams were added to the consortium through RFA-DK-23-021 to perform hypothesis-driven research on CVD disease mechanisms with CaRe-T1D resources.

Research Goals and Objectives

The objective of this funding opportunity is to continue and expand the current effective infrastructure of the CaRe-T1D Resource Center and advance research on CVD disease mechanisms through the following research activities, with the goal of driving groundbreaking discoveries that foster the development of novel, targeted therapies for CV and renal diseases for people with type 1 and type 2 diabetes.

This funding opportunity will support continuation of the basic infrastructure of CaRe-T1D, with the Resource Center serving three critical functions: Biorepository, Data Commons, and Coordinating Center. Investigative teams funded through RFA-DK-27-108 have the charge to perform pioneering, innovative and hypothesis-driven research as separate and collaborative projects on the pathogenesis of CVD in type 1 diabetes and its distinctions from type 2 diabetes.

Biorepository – The Resource Center will continue to obtain hearts (including coronary arteries, myocardium and epicardial fat), arteries (carotid and aorta), kidneys and blood from U.S. Organ Procurement Organizations through the generosity of organ donors and their families.  In addition, the Resource Center, upon advice from its scientific advisory board or requests from investigators, will explore the ability to collect other tissue types relevant to an improved understanding of complications pathogenesis in type 1 diabetes. All tissue must meet the CaRe-T1D selection criteria for quality. Donors with type 2 diabetes and no diabetes will be matched to type 1 diabetes donors, with approximately equal numbers of cases across the three groups and a total of about 30 cases collected per year.  An extensive medical history will be obtained for each donor together with a careful characterization of the type of diabetes that will include autoantibody evaluation, genetic testing, and pancreatic tissue analysis.  A comprehensive case summary will be annotated to each case and available to investigators in the Data Commons.

The Resource Center will continue its extensive quality control testing and tissue characterization, including histopathologic examinations, electron microscopic evaluation, and RNA quality assessments.  Whole hearts will undergo microCT imaging to detect and quantify vascular calcification.  Tissue will be stored in a variety of modalities to support a wide range of modern techniques.  Additional testing will be conducted through the biorepository when appropriate to benefit individual and collaborative projects within the consortium.  All results will be incorporated into the case records and made accessible to investigators through the Data Commons.  The Resource Center will also manage the distribution of biosamples to investigators who have been approved through the CaRe-T1D Ancillary Study process, with shipping costs covered by the recipient.

When feasible, the Resource Center will adapt its collection protocols in response to new scientific opportunities being explored by the consortium.  This may include obtaining tissue from surgical specimens, targeting a population subgroup, or modifying tissue collection procedures to support emerging research needs.

Data Commons- CaRe-T1D will continue to expand its Data Commons, which currently includes all clinical data and the results of analysis performed by the Resource Center and investigative teams, and is accessible with different levels of clearance via the CaRe-T1D website.  The Data Commons will also continue its collaboration with the NHLBI BioData Catalyst cloud-based ecosystem for secure, long-term data storage.

Funding through this NOFO will support three interconnected objectives for the Data Commons as follows:

1) Shared Data Resources – The results and descriptions of specific assays, donor-specific data, and available biospecimens will be made accessible to investigators for downloading and for tissue requests.  The Data Commons will collaborate with investigators to integrate results from diverse approaches, including single cell and –omics analyses and tissue imaging;

2) Artificial Intelligence (AI) Recommender System – This system will allow investigators to submit study questions inputted in plain language and receive recommended biospecimens and datasets, accompanied by an explanation of the rationale for those selections;

3) AI-Assisted High-Level Analysis System – The well-curated CaRe-T1D Data Commons will be optimized for large-scale, multimodal data analysis using the most advanced and ever-improving AI tools.

For all aspects of the Data Commons, best practices will be followed to ensure data privacy, established policy guardrails for prohibited uses, detect and mitigate bias, and provide robust model validation and explainability.

Coordinating Center - The Resource Center will coordinate CaRe-T1D activities for the Biorepository, Data Commons and investigative teams to leverage the consortium infrastructure and build synergies across all the parts of CaRe-T1D with the goal of providing insights in CVD mechanisms to illuminate the path to new therapies.  The coordinating center will:

• Coordinate regular steering committee meetings of investigators for operational and scientific discussions.
• Organize annual in-person meetings at the NIH to foster collaboration across the investigative teams and identify new research opportunities.
• Convene semi-annual meetings (either in-person or virtual) of a Scientific Advisory Board to receive feedback from experts in the larger research community.
• Promote the careers of early-stage investigators by providing opportunities to present at CaRe-T1D meetings and by offering travel funds to the annual meeting.
• Launch a Pilot and Feasibility program for investigators to obtain funding and CaRe-T1D biosamples and/or data for pilot projects that will include an application and review process.  The program could be directed to early-stage investigators and/or a specific scientific area.
• Support collaborative projects within the consortium that can test novel associations discovered through computational data mining.
• Continue the CaRe-T1D Ancillary Study program that supports the distribution of CV tissues and data to investigators outside the consortium.
• Lead consortium governance activities such as the development of data sharing and publication policies.
• Promote CaRe-T1D through presentations, publications, and other outreach activities.
• Provide consultative services to external groups developing new therapies or planning clinical trials for diabetic CVD.

NIH Gold Standard Science – The tenets of Gold Standard Science will be embedded CaRe-T1D Resource Center activities.  CaRe-T1D is a collaborative, interdisciplinary group of investigators, each contributing unique expertise to this research endeavor.  The Resource Center will facilitate meetings that encourage critical evaluation of findings, including those that may refute a hypothesis. A core purpose of the Data Commons is to transparently share results, enabling other investigators to reproduce study findings.  Priority will be given to Ancillary Study requests that seek biosamples for reproducibility studies. 

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

Only the following applicant is eligible to apply for this single source funding: University of Florida. Please refer to Section I. Notice of Funding Opportunity Information for more details. 

Foreign Organizations/Foreign 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 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.

Only the current CaRe-T1D Resource Center funded under RFA-DK-21-010 is eligible to apply.

2. Cost Sharing

This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement 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 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.

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 Budget

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

The budget should include travel to the CaRe-T1D annual meeting in Bethesda, MD.

R&R Subaward Budget

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

The budget should include funds for small subawards to domestic investigators for pilot and feasibility projects through a Special Opportunity funding program.  

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:

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.

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.

Study title: Possible Collection of Surgical Tissue Specimens for CaRe-T1D

Clinical trial: No

Justification for the possible collection of surgical tissue specimens and participants' medical histories to supplement tissue collection from organ donors. 

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.

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the How to Apply - Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

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

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 review criteria and additional review criteria (as applicable for the project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

None

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.

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

The application submitted in response to this NOFO will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Following initial peer review, recommended applications will receive a second level of review by the National Diabetes and Digestive and Kidney Diseases Advisory Council  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 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 award 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 the NIH as defined below.

The Cardiovascular Repository for Type 1 Diabetes (CaRe-T1D) consists of a Resource Center and investigative teams that use the CaRe-T1D resources.  The Resource Center collects, analyzes, stores and distributes human cardiovascular tissue that is obtained from organ donors.  The investigative teams perform mechanistic research on bio-specimens from the repository and share the results in the Data Commons managed by the Resource Center.

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

• Defining the objectives and approaches, planning, conduct, analysis, and publication of results, interpretations, and conclusions of studies conducted under the terms and conditions of the cooperative agreement award.
• Assuming responsibility and accountability to the applicant organization officials and to the NIH for the performance and proper conduct of the research supported under this Notice of Funding Opportunity Announcement (NOFO) in accordance with the terms and conditions of award, as well as all pertinent laws, regulations and policies. Recipients must agree to comply with the processes and goals as delineated within the NOFO.
• Sharing data, materials, models, methods, information and unique research resources that are generated by the projects in concordance with Consortium policies in order to facilitate progress. When appropriate, and in accordance with NIH and NIDDK policies, collaborate; share novel reagents, biomaterials, methods and models and resources; and share both positive and negative results that would help guide the research activities of other members.
• Maintaining confidentiality of the information as developed by the consortium, including, without limitation, study protocols, data analysis, conclusions, etc. per policies approved by the Steering Committee (SC) as well as any confidential information received by third party collaborators.
• Analyzing, publishing and/or publicly releasing and disseminating results, data and other products of the study in a timely manner, concordant with the approved plan for making quality-assured data and materials available to the scientific community and the NIH, consistent with NIH policies and achieving the goals of the NOFO.
• Data Management and Sharing Plan: In accordance with the NIH Policy for Data Management and Sharing (NIH NOT-OD-21-013), the NIDDK approved plan will become a term and condition of award, be routinely monitored during the award period, and compliance may factor into future funding decisions. By the end of the funding or proprietary period, a recipient or study group may not continue to use or share study generated resources until those resources are available to the public via a NIDDK approved repository per the NIDDK approved plan.
• Recipient(s) will be required to participate in a cooperative and interactive manner with members of the consortium including designated NIH staff (e.g., Program Official, Project Scientist, Project Coordinator).
• Recipient(s) agree to establish agreements among themselves that address the following issues: (1) procedures for data sharing among consortium members and data sharing with industry partners; (2) procedures for safeguarding confidential information, including without limitation, any data generated by the consortium as well as information and/or data received from external collaborators; (3) procedures for addressing ownership of intellectual property that result from aggregate multi-party data; (4) procedures for sharing bio-specimens under an overarching Material Transfer Agreement (MTA) among consortium members that operationalizes material transfer in an efficient and expeditious manner; (5) procedures for reviewing publications, determining authorship, and industry access to publications.
• Any third-party collaboration (including but not limited to interactions with organizations from industry, academia, and nonprofit institutions) should be governed by a research collaboration agreement (e.g., Clinical Trial Agreement, Research Collaborative Agreement, etc.) or any third-party contract mechanism(s) with terms that ensure the collaboration is conducted in accordance with the Cooperative Agreement, applicable NIH/NIDDK policies and procedures, applicable consortium policies, and with written approval from NIDDK Program staff. Any relevant proposed third-party agreements related to the consortium studies between grantee and third-party will be provided to the NIDDK Program staff and NIDDK Technology Advancement Office for review, comment, and approval to assure compliance with NIH/NIDDK policies and consortium policies. Further, at the request of the NIDDK Program staff, any other consortium-relevant third-party agreements must be shared with NIDDK. Failure to comply with this term may prompt action in accordance with NIH Grants Policy Statement, Section 8.5 titled: "Special Award Conditions and Remedies for Noncompliance (Special Award Conditions and Enforcement Actions)", and Section 8.5.2, titled: "Remedies for Noncompliance or Enforcement Actions: Suspension, Termination, and Withholding Support", noncompliance with the terms and conditions of award will be considered by the funding IC for future funding and support decisions and may result in termination of the award."
• Any involvement of a third-party (including but not limited to industry, academia, and nonprofit institutions) in the study and consortium activities that includes access to any consortium generated resources (i.e., data and biosamples), or study results that are not publicly available, or using the name of the consortium or study or the name of the NIH or NIDDK, is permitted only after written permission by the NIDDK Program staff who will consult with others at NIH and NIDDK Technology Advancement Office.
• Recipient(s) will retain custody of and have primary rights to the data and software developed under these awards, subject to Government policies regarding rights of access consistent with current HHS, PHS, and NIH policies.
• Recipient(s) agree to the governance of the study through a Steering Committee and will accept and implement the goals, priorities, procedures, protocols, and policies agreed upon by the Steering Committee and subcommittees. Recipient will attend all meetings of the Steering Committee and serve on Subcommittees as needed.
• Recipients may be asked to scientifically review applications for special opportunity pool funds, as it is deemed appropriate.

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

The NIDDK and other involved NIH ICs will designate program staff, including a Program Official and a Grants Management Specialist to provide normal program stewardship and administrative oversight of the cooperative agreement. The Program Official and Grants Management Specialist will be named in the Notice of Grant Award (NOA).

An NIH IC Project Scientist will be substantially involved in this project above and beyond the normal stewardship of an NIH IC Program Official as follows:

1. Serve as the contact point for all facets of the scientific interaction with the recipient(s). As required for the coordination of activities and to expedite progress, NIDDK may designate additional NIDDK staff to provide advice to the recipient on specific scientific and/or analytic issues.

2. For multi-center studies, participate in the Steering Committee that oversees study conduct. The NIDDK Project Scientist will be a full participant and voting member of the Steering Committee and, if applicable, subcommittees.

3. Serve as a resource to study investigators with respect to other ongoing NIDDK activities that may be relevant to the study to facilitate compatibility with the NIDDK missions and avoid unnecessary duplication of effort.

4. Have substantial involvement assisting in the design and coordination of research activities for Recipients as elaborated below:

a. Assisting by providing advice in the management and technical performance of the investigations.

b. The NIDDK Project Scientist may coordinate activities among recipients by assisting in the design, development, and coordination of a common research protocol and statistical evaluations of data; and in the publication of results. 

 c. Reviewing procedures for assessing data quality and study performance monitoring.

d. The NIDDK Project Scientist may be co-authors on study publications. In general, to warrant co-authorship, NIDDK staff must have contributed to the following areas: (a) design of the concepts or experiments being tested; (b) performance of significant portions of the activity; (c) participation in analysis and interpretation of study results and (d) preparation and authorship of pertinent manuscripts.

The NIDDK Program Official identified in the Notice of Award will:

1. Interact with the PI(s) on a regular basis to monitor study progress. Monitoring may include regular communications with the PI and staff, periodic site visits, observation of field data collection and management techniques, quality control, fiscal review, and other relevant matters; as well as attendance at Steering Committee, Scientific Advisory Board, and related meetings. The NIDDK retains, as an option, periodic review of progress by researchers not involved with the study.
2. Review and approve protocols prior to implementation to ensure they are within the scope of peer review for safety considerations, as required by federal regulations. .
3. The NIDDK Program Official will monitor protocol progress, and may request that a protocol study be closed to accrual for reasons including: (a) accrual rate insufficient to complete study in a timely fashion; (b) accrual goals met early; (c) poor protocol performance; (d) participant safety and regulatory concerns; (e) study results that are already conclusive; (f) low likelihood of showing a benefit of the intervention (futility); and (g) emergence of new information that diminishes the scientific importance of the study question. The NIDDK will not permit further expenditure of NIDDK funds for a study after requesting closure except as specifically approved by the NIDDK.
4. Make recommendations for continued funding based on: a) overall study progress, including sufficient donor case and/or data accrual; b) cooperation in carrying out the research (e.g., attendance at Steering Committee meetings, implementation of group decisions, compliance with the terms of award and reporting requirements); and/or c) maintenance of a high quality of research, which will allow pooling of data and comparisons across multiple cooperative agreement awards for common data elements.
5. Appoint an independent Data and Safety Monitoring Board (DSMB) as appropriate for Phase III clinical trials or other high-risk studies, or an Observational Study Monitoring Board (OSMB) for observational/epidemiologic studies; these Boards will review study progress, safety data, and interim results, as appropriate, and provide guidance to the NIDDK. The NIDDK Program Official or their Project Coordinator will serve as the Executive Secretary and/or NIDDK program representative on the DSMB/OSMB.
6. The NIDDK [and participating IC(s)] may invite External Consultants with relevant scientific expertise for the sole purpose of consultative advice on scientific developments and opportunities that may enhance the achievement of the study goals.
7. The NIDDK Project Scientist(s) and Program Official will review and approve applications for the Special Opportunity Funds to ensure that they are within the scope of consortium research as described in the NOFO and NIH guidelines.

Areas of Joint Responsibility include:

Through the Recipient, Steering Committee and NIH staff, the study members will cooperatively develop and implement processes to submit information and data to the Resource Center, determine criteria and processes for quality control of information and data to be posted for the research community, refine scientific objectives, and implement research advances to facilitate the goals of the study, consistent with NIH policies and achieving the goals of the program as described in the NOFO.

Executive Committee (EC)

• The EC will consist of: the Principal Investigator and co-Investigators of the Resource Center, the NIH Project Scientist(s), and two Principal Investigators of U01 grants serving one-year terms on a rotating basis among the U01 Principal Investigators; the EC is not a governing body and does not cast votes.
• The EC will review the progress of all projects that use CaRe-T1D resources, whether funded independently or through the Special Opportunity funding program of CaRe-T1D.  Annual reports will be prepared for each project to coincide with the annual CaRe-T1D SC meetings.
• The EC will be responsible for organizing the annual scientific meeting.
• The EC will have meetings that will be organized by the PI of the Resource Center. Any EC member may place items on the agenda. The designated NIDDK Program Official(s) of the CaRe-T1D consortium may be asked to participate in order to provide additional information and to summarize actions that are taken.

Steering Committee (SC)

A Steering Committee organized by the study investigator(s) will be the main governing body of the study.

The Steering Committee has primary responsibility to design research activities, establish priorities, develop common protocols and manuals, data recording forms, establish and maintain quality control among recipients, review progress, coordinate and standardize data management, and cooperate on the publication of results. Major scientific decisions regarding the core data will be determined by the Steering Committee. The Steering Committee will document progress in written reports to the NIDDK Program Official and will provide periodic supplementary reports upon request.

The Steering Committee will be composed of all Principal Investigators and the NIDDK Project Scientist. Each full member will have one vote. The final structure of the Steering Committee, including membership of co-investigators, and voting procedures will be established at the first meeting.  The NIDDK Project Scientist will have voting membership on the Steering Committee, and as appropriate, its subcommittees. The NIDDK Project Scientist's vote will represent NIH, as all NIH staff members will share one vote in support of the project. The frequency of Steering Committee meetings will be dictated by a vote of the members of the Steering Committee. The NIDDK Program Official may serve as a non-voting member on the Steering Committee. Subcommittees will report progress at Steering Committee Meetings and/or lead discussions at the Annual Investigator's Retreat.

A Chairperson of the Steering Committee will be selected and voted on by the Steering Committee members.  The Chairperson provides leadership to the Committee by conducting the Steering Committee meetings and by interacting closely with the recipients during protocol development and implementation.  The NIDDK Project Scientist may not serve as Chairperson.  The NIDDK Program Official will review the Committee's selection for potential bias, conflicts of interest, or lack of required expertise. If the Program Official has concerns regarding selection of the Chairperson which are not satisfactorily resolved, the Program Official may withhold concurrence if approved by the Director of NIDDK Division of Extramural Activities based on written justification.  In cases where Program Official concurrence is withheld, the Steering Committee will be required to make another selection.

External Consultants

An independent panel of External Consultants may be established by the Steering Committee.  The External Consultants may periodically review interim progress of the project(s) and provide reports to the Steering Committee. Members of the panel of External Consultants may be asked, on an ad hoc basis, to participate in the peer review of applications for new research initiatives that utilize special "opportunity pool" funds. The NIDDK Program Official will review the Committee's selections for potential bias, conflicts of interest, or lack of required expertise. If the NIDDK Program Official has concerns regarding selection of one or more External Consultants which are not satisfactorily resolved, the NIDDK Program Official may withhold concurrence if approved by the Director of NIDDK Division of Extramural Activities based on written justification.  In cases where NIDDK Program Official concurrence is withheld, the Steering Committee will be required to make another selection.

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 Steering Committee chosen without NIH staff voting, one NIH designee, and  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 individual recipient. This special dispute resolution procedure does not alter the Recipient's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and HHS regulation 45 CFR Part 16.

3. Data Management and Sharing

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. 

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.

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).

Division of Diabetes, Endocrinology and Metabolic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Email: NIDDK_DEM@nih.gov 

Division of Cardiovascular Sciences
National Heart, Lung, and Blood Institute (NHLBI)
Email: CARE-T1D@nhlbi.nih.gov
Subject: RFA-DK-27-109

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

Grants Management Contact:
Email: NIDDKGMBManagementTeam@niddk.nih.gov 

Office of Grants Management
National Heart, Lung, and Blood Institute (NHLBI)
Email: NHLBIOGMInbox@nhlbi.nih.gov
Subject: RFA-DK-27-109

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.

This NOFO is supported under the authority of P.L. 118-22, Further Continuing Appropriations and Other Extensions Act, 2024; Section 202. "Extension of Special Diabetes Programs