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 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

Background

The prevalence of heart failure with preserved ejection fraction (HFpEF) is rising due to an aging population and contributing comorbidities, such as obesity and diabetes. Epidemiologic studies have shown an increase in the proportion of HFpEF patients, and this trajectory continues to rise. Hospitalized HFpEF patients have a poor 5-year outcome with a 50% mortality rate, and emerging data suggest that HFpEF may be the dominant HF subtype in the future, affecting approximately 1 in 10 adults during their lifetime.

In addition to its increasing prevalence, HFpEF is a heterogeneous syndrome with multiple pathophysiological processes and varied clinical presentations. Phenomapping studies have identified between two and six HFpEF clusters or phenogroups with shared features. Of these, three overlapping phenotypes repeatedly arise: an ‘older, vascular aging’ phenotype, a ‘metabolic, obese’ phenotype, and a ‘relatively younger, natriuretic peptide (NP) deficiency’ phenotype. Further refinement of these HFpEF subtypes is ongoing in HeartShare 1.0 with a focus on evaluating the underlying biologic and molecular mechanisms of disease. Defining clinically actionable phenotypes or clusters and their associated biomarkers will form the basis for designing precision clinical trials for HFpEF patients.

Research Approach

HeartShare represents a new paradigm in longitudinal observational cardiovascular studies. The first HeartShare iteration (HeartShare 1.0; September 2021 – August 2026) uses deep phenotyping, imaging, multi-omics, and advanced analytics to deconstruct the HFpEF syndrome.

HeartShare 1.0 has two components: 1) a retrospective portion responsible for aggregating, harmonizing, and analyzing extant datasets from NHLBI trials and cohorts along with multi-omics on available biospecimens using NHLBI’s Trans-Omics for Precision Medicine (TOPMed) program; and 2) a prospective, observational, longitudinal cohort. Data from both components will become available through the NHLBI BioData Catalyst (BDC) cloud-based platform.

The prospective component consists of three parts: 1) electronic health record (EHR) data from HF patients at the HeartShare Clinical Centers is collected from the previous 7 years and followed prospectively; 2) a virtual registry of patients (HF individuals and age- and sex-matched comparators), who complete surveys longitudinally and agree to be consented for future trials; and 3) a deep phenotyping cohort, which aims to enroll up to 1,000 participants (75% with HFpEF and 25% age- and sex-matched individuals without HFpEF). The goal of the deep phenotyping study is to identify clinical and omics biomarkers of distinct HFpEF subtypes. A rich BDC repository of clinical data [e.g., demographic, social determinants of health (SDOH), physiological, laboratory], images, and multi-omics (blood and tissue samples) will serve as a resource for all investigators and ultimately, the research community.

In September 2022, the Foundation for NIH (FNIH) Accelerating Medicines Partnership in Heart Failure (AMP HF) was launched to form a 5-year pre-competitive partnership with HeartShare, industry partners, non-profit organizations, NHLBI, and the FDA. HeartShare 1.0/AMP HF consists of a Data Translation Center (DTC) and 7 Clinical Centers (CCs). Projected outcomes from the HeartShare 1.0/AMP HF program include a large, deeply phenotyped cohort of HFpEF patients; a virtual registry of participants who have agreed to be contacted for recruitment into precision HFpEF trials; identification of subtypes of HFpEF patients; and exploration of new subtype-specific biomarkers and pathways for therapeutic development. The identified subtypes and potential biomarkers will be used for stratification of HFpEF patients into precision clinical trials in HeartShare 2.0.

HeartShare’s competitive continuation (HeartShare 2.0) is critical to realizing HeartShare 1.0/AMP HF goals. A Data Translation Center (DTC) will continue to support overall HeartShare 2.0 activities, including oversight of deep phenotyping, follow-up, tissue biopsies (myocardial, skeletal, adipose), and data management/analysis. A new Clinical Trial Center (CTC) will coordinate HFpEF trial activities, including master protocol development, project management, recruitment oversight, performance milestones, and scientific conduct of trials. Up to seven CCs will be selected to serve as the performance sites for the deep phenotyping protocol, biopsy (myocardial, skeletal, adipose) collection, and future clinical trials.

The overall objectives of HeartShare 2.0 are described here along with their associated components:

1. Expand and complete HeartShare 1.0's enrollment, phenotyping, and longitudinal follow-up of a participant cohort that reflects the population for results that are generalizable to the U.S. population  (CCs, DTC)
2. Continue to collect and analyze myocardial, skeletal muscle, adipose tissue through molecular tissue profiling (CCs, DTC)
3. Pursue experimental validation and translation of mechanistic signals (DTC)
4. Create a framework and conduct precision clinical trials (CTC, CCs, DTC)

This NOFO describes the objectives of the CTC and CCs separately below, while the DTC objectives are described in the companion NOFO (RFA-HL-27-009).

Clinical Trial Center Objectives

The new Clinical Trial Center (CTC) will coordinate all trial activities during HeartShare 2.0. The initial phase of this award will include integration of input from various partners about the optimal design for a clinical trial network and design of a master protocol for Phase II precision trials for HFpEF subtypes. Partners will include HeartShare academic; industry; non-profit members of AMP HF; FDA; and others. Design considerations for the network will include feasibility of identifying and recruiting subtypes of interest, financial sustainability through industry partnership, and ability to collaborate with academic investigators through the submission process for trial applications. Early CTC efforts (years 1-2) may include investigator workshops and outreach to partners interested in planning HFpEF clinical trials over the next 2-3 years. The CTC will work with the NHLBI, FNIH, DTC, and CCs to develop the HeartShare trial infrastructure (e.g., establish subcontracts, obtain regulatory approvals). The HeartShare trial network will facilitate shared information and infrastructure; efficiency in trial execution (e.g., reduced start-up time, increased likelihood of successful enrollment, and potential cost savings); standardization of data elements; and the ability to test multiple strategies concurrently.

The CTC will be tasked with screening and prioritizing trial requests from AMP HF partners and non-partners through an NHLBI-appointed  Protocol Review Committee (PRC), and collaborating with trial applicants interested in leveraging the HeartShare trial infrastructure. Trial applicants will be expected to provide their own funding support through CTC-supported investigator-initiated NHLBI clinical trial grant applications (e.g., PAR-22-193, PAR-25-029, and their reissues) and/or industry funding to contribute to infrastructure and trial costs. The PRC may include participants from NIH, FNIH, DTC, CTC, and CCs. The CTC will partner with the DTC to build capabilities to conduct precision trials and facilitate EHR/virtual registry connectivity for trial investigators to identify participants from the registry and deep phenotyping cohort for enrollment of specific HFpEF subtypes. During trial implementation, the CTC is expected to support Clinical Coordinating Center activities (site selection and management, quality control, sample coordination, etc.) and the DTC is expected to support Data Coordinating Center activities (statistical design, sample size calculation, data analysis plan, etc.). 

The CTC will collaborate with the CCs, which will serve as potential sites for all trials. Additionally, the CTC will identify additional ancillary trial sites based on specific needs and will coordinate meetings of the Data and Safety Monitoring Board (DSMB) with the DTC. CTC responsibilities will also include project management, recruitment oversight, performance milestones, and scientific conduct of trials. Robust management, oversight and monitoring of trials is integral to NHLBI's stewardship of clinical trials (see Optimizing NHLBI's Clinical Trials Enterprise). Towards these goals, HeartShare trials will follow NHLBI's use of performance milestones to monitor and oversee trial conduct and results dissemination. The CTC will work with trial investigators to meet NHLBI's expectations for performance-based, milestone-driven study designs with metrics for overall recruitment/enrollment and retention goals, including demographic accrual goals to ensure results are generalizable to the U.S. population.

CTC applicants should have a strong track record of conducting multi-center HF clinical trials, including success in meeting milestones and timelines. Appropriate personnel [e.g., clinical trialist, clinician, project manager, study coordinator(s), etc.] should be included to facilitate the implementation of all aspects of clinical trials, including recruitment of participants; community and patient engagement; design/implementation of the trial protocol; and coordination of roles/responsibilities of the CTC leadership.  

As the CTC is a new component in HeartShare 2.0, all CTC applicants should submit new applications.

Clinical Center Objectives

CCs are responsible for recruiting participants, assuring good clinical practice, supporting remote monitoring, and participating in a cooperative and interactive manner with other CCs, the DTC, the CTC, NHLBI, FNIH, and other AMP HF partners.

In years 1-2 of HeartShare 2.0, CC investigators will screen and enroll HF patients and controls into a common deep phenotyping protocol. They will conduct clinical examinations and collect skeletal muscle, adipose tissue, and biospecimens for biomarker and multi-omics analyses. CCs will be expected to participate in a myocardial biopsy protocol in which HFpEF patients referred for right heart catheterization undergo a research right heart biopsy for tissue molecular profiling and analysis of mechanistic pathways. CCs will be responsible for collection of high-quality clinical information, images, biospecimens, and tissue samples and their transfer to the DTC or designated core labs. Each CC is expected to enroll approximately 35-40 HF patients and controls per year (~3-4 participants per month) to reach the current 1,000-participant target. Longitudinal follow-up of participants will be planned with return visits expected at the 1-year timepoint, as well as additional visits as determined by the HeartShare/AMP HF leadership team.

CCs will also recruit HF patients into a virtual registry for future HFpEF trials. Recruited participants will be able to consent for studies remotely, provide information from home monitoring of symptoms, and review aggregate data and results through the Eureka app. CCs will partner with the DTC to facilitate patient engagement with the deep phenotyping study and to collect and validate data on clinical outcomes. CCs will also collaborate with the DTC to collect and analyze data from the EHR on HF patients at their sites. Baseline data on participants from the EHR will be combined with research testing, patient-provided data, longitudinal follow-up, and biospecimen testing. CCs should have health informatics expertise and experience in using EHR data for research, and they will collaborate with the DTC on data standardization and harmonization. EHR data will be curated locally before transfer to the DTC, and plans will be made for sharing all baseline and longitudinal data.

In years 1-2, CCs will also collaborate with the CTC in development of a clinical trial network and master protocol. Once the trial network has been established, CCs will collaborate with the CTC and any future trial ancillary sites to recruit patients into HFpEF clinical trials. CCs must demonstrate a strong track record of successful enrollment of HF participants into trials, the ability to collect and analyze data, work cooperatively as a member of a large group, adhere to a common protocol, and have capacity to mentor junior investigators. CCs are encouraged to partner with professional societies, industry or patient groups to leverage research resources for recruitment purposes. CCs are also encouraged to include more than one site, if necessary, as subawards to accomplish recruitment goals.  

Information is publicly available for the HeartShare deep phenotyping protocol, core labs, and the research skills program for fellows to gain clinical research skills in data science. CC applicants should highlight their specific areas of strength and unique contributions to the HeartShare program [e.g., capabilities to perform the deep phenotyping protocol, operate in a core lab capacity, recruit HFpEF participants, collect tissue biopsies (myocardial, skeletal, adipose), etc.]. CC applicants should also detail their capabilities in clinical trial recruitment, retention and protocol compliance including follow-up.

Current CC recipients should submit renewal applications and all other CC applicants should submit new applications.

HeartShare Organization and Governance

HeartShare's Steering Committee (SC), consisting of all academic investigators, meets monthly and provides oversight and direction for the entire program. The AMP HF SC, consisting of all private partners, meets monthly as well. A leadership team (NHLBI, FNIH, HeartShare/AMP HF study co-chairs, DTC) connects both SCs. The new CTC investigator will join the HeartShare SC and the leadership team and will be invited to attend the AMP HF SC meeting. New and renewed CC investigators will continue to participate in the HeartShare SC.

NHLBI will provide overall support for HeartShare. The NHLBI Program Office and Office of Grants Management are responsible for the federal stewardship of the award (management, financial, and administrative oversight). In addition to regular award oversight, the NHLBI Project Scientists will be involved substantially with the recipients as partners, consistent with the Cooperative Agreement mechanism. The NHLBI has appointed an independent Observational Safety and Monitoring Board (OSMB) to provide ongoing review of HeartShare activities. The CTC will be expected to manage the NHLBI Protocol Review Committee (PRC) and the Data and Safety Monitoring Board (DSMB) when clinical trials begin. NHLBI has appointed external study co-chairs to oversee all study activities. An independent External Advisory Committee (EAC) may be appointed by NHLBI to provide periodic reviews of HeartShare operations and scientific directions.

HeartShare will support a Research Skills component that will bring together early career clinical researchers (fellows and junior investigators) and early career data science experts (in masters or PhD programs for data science, computer science, or statistics) to foster cross-disciplinary application of data science principles in clinical research. The DTC will coordinate the skills development activities across HeartShare by forming a Research Skills Committee (RSC), composed of an identified senior investigator from each CC, DTC, and CTC. The DTC, CTC, and CCs will share responsibilities for development and implementation of the Research Skills component. Skills development activities will be finalized and agreed upon across HeartShare after funding.

Application Scope

This NOFO invites applications for a CTC to coordinate HFpEF precision clinical trial activities and/or a CC to screen, enroll and perform patient activities [e.g., recruit, phenotype, biopsy, follow-up and clinical trial intervention(s)].

Eligible applicants may submit separate proposals for either the CTC or CC, but must have different PIs. Each application must include CTC or CC as part of their project title.

Applicants are encouraged to carefully review the unique NOFO requirements on specific application components, budget, and review criteria for CTC and CC proposals.
 

Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs.

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

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 eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

NIH will no longer issue awards (i.e., new, renewal, or non-competing continuation) to domestic or foreign entities that involve foreign subawards/subcontracts. All NIH-funded research involving foreign subawards/subcontracts must be submitted in response to a NOFO that is specifically designated for funded international collaborations. See NIH Grants Policy Statement 16.8 Collaborative International Research Awards.

Applications involving foreign subawards/subcontracts submitted in response to this NOFO will be deemed noncompliant and will not be considered for funding. This policy applies to all monetary international collaborations resulting in foreign subawards/subcontracts, however, it does not preclude unfunded international collaborations or foreign components, funding for foreign consultants, or procurement of unique equipment or supplies from foreign vendors.

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.

Each application must include CTC or CC as part of their project title.

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.

Other Attachments:

Clinical Experience (Required): Provide the following information as a single PDF attachment entitled “(PD/PI name) Clinical Experience.pdf.” The attachment may not exceed 5 pages and must be completed and attached or the application will not be peer reviewed.

• Table documenting participation in observational studies and/or clinical trials (highlight studies and/or trials with HF patients) from the last 5 years by the PD(s)/PI(s): study title, intervention or observational objectives, dates, numbers of patients enrolled and percent completion of agreed to targets.

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.

Award Budget

Determination of Allowable Budget Request Amount

U01 applications submitted in response to this NOFO must identify whether they are to be considered for the CTC award or a CC award. Each application must identify as either a CTC application or a CC application as part of their project title. For description of activities associated with the CTC award and CC awards, see Section I. Funding Opportunity Description. Data Management and Sharing costs should be included separately in the budget; if not applicable or funds are not being requested, note that in the budget justification.

Clinical Trial Center (CTC) Operational Budget (specific to this NOFO):

• CTC applicants must submit a detailed budget for costs related to the center operation (including personnel salaries). This budget should include travel costs to attend Steering Committee (SC) meetings as well as other travel related to HeartShare operations. These costs must not exceed $500,000 in direct costs (excluding consortium F&A) in FY2027; $800,000 in direct costs in FY2028; and $1,000,000 in direct costs per year in FY2029 through FY2032.
• Suggested years 1-6 travel commitments for planning purposes: PD/PI (or PDs/PIs if a multi-PD/PI plan is used) and a research coordinator attending one (1) SC meeting to be held in Bethesda, MD, or another convenient/central location(s). Additional meetings may be held virtually.

Clinical Center (CC) Operational Budget (specific to this NOFO):

• CC applicants must submit a detailed budget for costs related to the study site operation (including investigator/research coordinator salaries). This budget should include travel costs to attend Steering Committee (SC) meetings as well as other travel related to HeartShare operations. These costs must not exceed $250,000 direct costs per year for six (6) years. This budget is expected to support a research coordinator and a percentage of time for co-investigators.
• These costs should include portions of each Co-PD/PI FTE(s), study coordinator FTE(s), and appropriate administrative support.
• CCs using geographically or organizationally linked satellites should consider how best to apportion FTEs to facilitate patient recruitment and enrollment at the constituent sites.
• Although regulatory monitoring of satellites will be performed by the DTC, CCs are expected to provide scientific and clinical leadership of their own clinical site and any satellite sites.
• Suggested years 1-6 travel commitments for planning purposes: PD/PI (or PDs/PIs if a multi-PD/PI plan is used) and a research coordinator attending one (1) SC meeting to be held in Bethesda, MD, or another convenient/central location(s). Additional meetings may be held virtually.

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:

Clinical Trial Center (CTC) Research Strategy:

Applicants should propose a design for a clinical trial network for precision HF clinical trials. The network design should leverage current infrastructure of the HeartShare/AMP HF program, including the CC's and deeply phenotyped participants (data obtained from the EHR, patient-provided data, and research testing) and the DTC's data management and analysis capabilities. Considerations for the transition from the current deep phenotyping, HFpEF subtype characterization, mechanistic evaluations, and target identification to proof-of-concept clinical trials should be included. Applicants should offer examples of trials that could be initiated in this network.

In lieu of a traditional research strategy, with the usual headings, applicants should use the following content guidelines in preparing their applications:

CTC Organization (recommend 4 pages):

• Describe the overall design and structure of the CTC including its project management structure, integration of any components, and any possible subcontracts. Include an organizational chart of the associated tasks and milestones. Identify the types of staff associated with each task and describe their respective roles and responsibilities.
• Describe previous participation in large-scale research networks involving coordination of data across multiple projects and experience in heart failure clinical trials.
• Describe institutional informatics expertise and technical staff to utilize the EHR and other relevant approaches to identify potential patents.

CTC Master Protocol Development and Trial Management Plan (recommend 4-8 pages):

• Describe a detailed process and timeline to develop a clinical trial network design and needed infrastructure to be able to test multiple strategies in personalized trials.
• Indicate the key elements for establishing a master protocol or other appropriate protocol design (e.g., partner buy-in and project planning) and how these factors will be achieved.
• Demonstrate knowledge of current opportunities and challenges for precision medicine for heart failure and describe strategic vision of implementing advanced technologies and clinical methods to translate promising discoveries to therapeutics.
• Demonstrate clear commitment and approach to collaborate with the CCs, DTC, and other partners to design, implement, and use a study-wide common clinical trial platform and master protocol or other mutually agreed upon design.
• Describe the strategy and milestones that will be used throughout the project to ensure that management activities of clinical trials are performed successfully, including directly supporting the needs of scientific study leadership to identify barriers, make timely responses, and optimize the allocation of limited resources to meet pre-defined study objectives.
• Discuss the challenges and solutions for the identification of appropriate HFpEF patients, as well as HFrEF, HFmEF, and age/sex-matched controls (as needed). The application should describe plans to recruit patients from multiple, pertinent departments, and/or clinics, and/or satellite sites, if necessary.
• Describe plans for increasing participant engagement through all phases of the HeartShare program, including patient outreach, enrollment, retention for longitudinal follow-up, and sharing of results.
• Detail a risk assessment and management plan that addresses contingencies in the event that there is inadequate progress toward achieving clinical trial core milestones. The plan should identify a range of contingencies that could threaten study progress or feasibility and propose solutions using study resources.
• Key methodology and standard operating procedures governing resource management, study deployment, operations/execution, and study closure.

Clinical Center (CC) Research Strategy:

Participant selection, enrollment, retention, and biospecimen collection and handling should be described. Applicants will propose details of a plan for integrating the data obtained from the EHR, patient-provided data, and research testing. Sub-groups of participants will undergo deeper phenotyping for specific metabolic, renal, peripheral or other abnormalities and a general plan for this should be discussed. Consideration for how to transition from mechanistic evaluations and target identification to proof-of-concept clinical trials should be included. Applicants should define potential skill development activities for junior investigators that will be coordinated by the DTC across the entire HeartShare program.

In lieu of a traditional research strategy, with the usual headings, applicants should use the following content guidelines in preparing their applications:

CC Organization (recommend 4 pages):

• Describe key personnel and their interactions to accomplish recruitment and retention in the study-wide HeartShare deep phenotyping protocol; previous collaborations and interactions should be described.
• Demonstrate experience and success in conducting longitudinal research including a track record depicting high rates of enrollment and retention over the short- and long-term.
• Describe experience with standardization and sharing of data from EHRs and other types of unstructured participant information. Describe institutional informatics expertise and technical staff to facilitate data preparation and integration across multiple data sources.
• Demonstrate clear commitment to collaborate with other CCs, the CTC, and the DTC to design and implement a clinical trial network design and master protocol.
• Define the potential opportunities for skills development for early career investigators at the CC to achieve cross-disciplinary learning and application of data science principles in clinical research.

CC Capabilities for HeartShare Activities and Recruitment Plan (recommend 4-8 pages):

• Describe site experience and capabilities to execute the HeartShare baseline/longitudinal clinical examination, deep phenotyping protocol (see Table 2 on pages 13-15), and biopsy (myocardial, skeletal, adipose) collection.
• Describe a myocardial biopsy procurement plan, including a description of sample collection; processing; and quality control methods, metrics, and analysis.
• Describe prior and ongoing research using myocardial tissue relevant to HFpEF and description of how tissue analysis contributes to understanding of HFpEF pathogenesis. Indicate the yearly number of biopsies performed at your institution.
• Discuss the challenges and solutions for identification of appropriate HFrEF, HFmEF, and HFpEF patients, as well as age/sex-matched controls. The application should describe plans to recruit patients from multiple, pertinent departments and/or clinics and/or satellite sites.
• Describe the ability to enroll at least 35-40 participants into the deep phenotyping protocol over the first two (2) years of the study following demographic accrual goals to ensure results are generalizable to the U.S. population.
• Describe experience in recruiting participants into clinical trials, registries, or other large-scale observational studies; clinical catchment capacity and staffing may be part of this narrative.
• Describe plans for increasing participant engagement through all phases of the HeartShare program, including patient outreach, enrollment, retention for longitudinal follow-up, recruitment for future clinical trials, and sharing of results.
• Describe any special expertise or unique strengths the applicant can offer to the collaborative effort (e.g., innovative study design, omics, bioinformatics, team leadership and training, patient recruitment strategies, dissemination activities, access to already characterized cohorts of patients, HFpEF clinical trials).
• Propose ideas for Phase II precision clinical trials in HFpEF that may be supported by the HeartShare network.

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.

• Rapid and broad data-sharing of clinical and molecular data is intended to be a hallmark of the HeartShare program.
• Applicants should state their general support of collaborative research and their willingness to participate in a collaborative and interactive manner with the CCs, CTC, DTC, Steering Committee, AMP HF partners, and the NHLBI in all aspects of the HeartShare program.

 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 should not exceed two (2) pages. 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

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 the Center for Scientific Review, 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 Heart, Lung, and Blood 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.

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain “applicable clinical trials” on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that all 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.

Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

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.

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.

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

The PD(s)/PI(s) assume(s) responsibility and accountability to the applicant organization officials and to the NHLBI for the performance and proper conduct of the research supported by the U01 award in accordance with these terms and conditions of the award. As such, the recipient PD(s)/PI(s) will be responsible for all aspects of the study and cohort, as well as any modification(s), unless otherwise provided for in these terms or by action of the cohort Steering Committee.

Specific responsibilities include:

• Defining objectives and approaches of the research
• Defining the research plan and goals
• Project design and protocol development
• Obtaining all requisite study and protocol approvals
• Data collection and quality control
• Data monitoring
• Oversight of study activities, such as data analysis and interpretation, manuscript preparation, and dissemination of study results
• Overseeing/performing other scientific activities of the research plan
• Monitoring the completion of the supported activities and taking corrective actions if needed
• Participating in the activities of the cohort Steering Committee
• Accepting and implementing the decisions approved by the cohort Steering Committee to the extent consistent with applicable grant regulations
• Cooperating with NHLBI programmatic, technical, and administrative staff
• Administratively managing the U01 award
• Developing collaborations with and making data accessible to external investigators
• Ensuring submission of reports to the OSMB, if applicable

The recipient will be required to provide updated descriptive and meta-data to the NHLBI upon request, including cohort characteristics, study protocols, basic counts of study participants, enrollment progress, biospecimen availability, and study variable definitions. Recipients must also provide analytical data files (illustrative examples include: derived/calculated data variables; finalized questionnaire data; data from procedures, such as spirometry, echocardiography, ECG, exercise testing, polysomnography, etc.; participant follow-up data; clinical event outcomes data) to the NHLBI periodically based upon a mutually agreed schedule and format and at the end of the period of this award, along with documentation necessary for their use.

Recipients will be expected to evaluate and document compliance with NCI's Best Practices for Biospecimen Resources for collection, processing, and storage of previously collected biospecimens (https://biospecimens.cancer.gov/bestpractices/). Recipients will be required to explore, with NHLBI staff, the feasibility of data harmonization and pooling with other cohorts and studies. 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.

Recipients agree to the governance of the study through a Steering Committee and to accept and implement decisions approved by the Steering Committee (see "Joint Responsibilities" section below).

Recipients are expected to make their data widely available to other investigators per NIH and NHLBI data sharing policies (https://sharing.nih.gov/data-management-and-sharing-policy, https://www.nhlbi.nih.gov/grants-and-training/policies-and-guidelines/nhlbi-policy-for-data-sharing). Study investigators are strongly encouraged to publish and disseminate results, tools, resources, and other products of the study, in accordance with the study protocols and governance. It is expected that all methods, analyses, software, and algorithms will be made available in a timely manner to the scientific community.

Support or other involvement of industry or any other third party in the study may be advantageous and appropriate. Participation by the third party; involvement of study resources; citing the name of the study or NHLBI support; or special access to study results, data, findings, or resources requires notification of and concurrence by NHLBI. Except for licensing of patents or copyrights, support or involvement of any third party will occur only following notification to and concurrence by NHLBI.

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

A designated NHLBI Project Scientist(s) will have the following responsibilities:

• Participating in the activities of the cohort's Steering Committee, as well as any subcommittees as appropriate, and helping to address issues that come before these committees
• Facilitating collaborations between the recipients and other NHLBI-sponsored programs, investigators, or organizations that may contribute to the study's goals
• Assisting in the interaction between the recipients and investigators at other institutions, as appropriate for the cohort
• Promoting collaborative research efforts that involve interactions with other NIH-supported projects, programs, and centers and helping with the coordination of such efforts
• Facilitating harmonization of data and biospecimen resource optimization
• Participating in study meetings
• Providing technical assistance and advice to the recipients as appropriate

In addition to the Project Scientist, a separate NHLBI Program Official will be responsible for the normal program stewardship of the cooperative agreement and will be in the Notice of Award. However, the NHLBI may elect to have a dual-role approach where a single individual may act as both the NHLBI Project Scientist and Program Official. Final decision-making authority on matters of budgetary and funding actions, grants management actions, and management of intellectual property issues is assigned to NHLBI staff other than the Project Scientist. The responsibility for final decision making may reside with Senior Institute management, separate organizational components, and/or oversight committees. Because it is anticipated that the Program Official will participate in activities that rise to a level of involvement (i.e., additional role as Project Scientist) that results in conflicts of interest (e.g., co-publication), other staff members such as direct line supervisor and/or other Senior NHLBI Program management staff may serve as agency Program Officials and will be responsible for the normal scientific and programmatic stewardship of the award. Additional NHLBI staff members may be designated to have substantial involvement in the study.

The NHLBI policy on authorship and manuscript review of NHLBI-sponsored extramural research protects against conflicts of interest with the Program Officer.

The NHLBI reserves the right to withhold funding or curtail the study in the event that any of the following occur:

• Substantial shortfall in participant data reporting or quality control
• Major breach of the protocol or substantive changes in the agreed-upon protocol, methodologies, and/or tools with which the NHLBI cannot concur
• Failure to develop or implement a mutually agreeable protocol
• Human participant ethical issues that may dictate a premature end of the award
• Results that substantially diminish the scientific value of study continuation

Areas of Joint Responsibility:

Each cohort established under this NOFO shall have a Steering Committee (SC) that serves as its main governing board. The SC voting membership shall be determined jointly by the PDs/PIs and the NHLBI, but shall minimally consist of the study center(s) PI(s), the NHLBI Project Scientist(s), the Data Translation Center PI(s) (if applicable), and the Clinical Trial Center PI(s) (if applicable). Additional members may be added by majority vote of the SC. Meetings of the SC will ordinarily be held by teleconference, video conference, or in-person. All NIH staff members will share one combined vote in support of the project. 

The appointed voting Steering Committee members will be required to attend all Steering Committee meetings and tele/video conferences, or to appoint a substitute that will be fully briefed on the issues at hand. Additional non-voting members to serve in an advisory capacity may be added to the Steering Committee as needed by a decision of the existing voting committee members. The Steering Committee may also form an Executive Committee (EC) and/or subcommittees as needed. The NHLBI Project Scientist(s) may serve on the EC and on subcommittees as deemed appropriate. The Chair(s) of the Steering Committee will be selected from the SC voting members.

The Steering Committee will have primary responsibility for:

• Overseeing the overall organization of the study's core functions
• Providing guidance on scientific and infrastructural issues pertinent to the funded cohort study
• Providing guidance, oversight, and coordination of the activities of the cohort investigators towards cross-cohort data harmonization, if requested by the NHLBI
• Contributing to the development of policies and processes pertinent to the cohort infrastructure

All investigators/staff within the study will be required to accept and implement the policies approved by the Steering Committee to the extent consistent with applicable grant regulations.

Where applicable, the recipients will work with the NHLBI on efforts to harmonize data across NHLBI cohorts and studies and explore the feasibility of using common data standards and elements.

NHLBI will partner with the PD(s)/PI(s) to ensure dataset and documentation preparation is congruent for submission to the Biological Specimen and Data Repository Information Coordinating Center (BioLINCC (https://biolincc.nhlbi.nih.gov/submit_datasets/)) as described in the NHLBI Supplement to the NIH Policy for Data Management and Sharing (https://www.nhlbi.nih.gov/grants-and-training/policies-and-guidelines/nhlbi-policy-for-data-sharing). Large-scale genomic data generated by the recipients are to be deposited along with associated phenotype data into the database of Genomic and Phenotype Data (dbGaP, accessed at (https://www.ncbi.nlm.nih.gov/gap/)) in accordance with the NIH Genomic Data Sharing Policy available at https://sharing.nih.gov/genomic-data-sharing-policy.

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 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 individual recipients. 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 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 should not exceed two (2) pages. 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 Cardiovascular Sciences, HeartShare Team
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: N/A
Email: nhlbiheartshare@mail.nih.gov 

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

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

Office of Grants Management
National Heart, Lung, and Blood Institute (NHLBI)
Email: NHLBIOGMInbox@nhlbi.nih.gov
Subject: RFA-HL-27-008

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.