RFA-HL-27-008-Revised-Full-Announcement.html

Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Heart, Lung, and Blood Institute (NHLBI)

Funding Opportunity Title

HeartShare 2.0: Refining Heart Failure Subtypes and Treatment Targets for Personalized Clinical Trials - Clinical Trial Center and Clinical Centers (U01 Clinical Trial Optional)

Activity Code

U01 Research Project – Cooperative Agreements

Announcement Type

Reissue of

RFA-HL-21-015

Related Notices

Check for any recent Notices of NIH Policy Changes that may impact application requirements.

Funding Opportunity Number (FON)

RFA-HL-27-008

Companion Funding Opportunity

RFA-HL-27-009

, U54 Specialized Center (Cooperative Agreements)

Number of Applications

See Part 2, Section III. 3. Additional Information on Eligibility.

Assistance Listing Number(s)

93.837

Funding Opportunity Purpose

The purpose of this Notice of Funding Opportunity (NOFO) is to solicit applications for a new Clinical Trial Center (CTC) and up to seven Clinical Centers (CCs) for the HeartShare 2.0 program. The CTC will coordinate precision clinical trial activities focused on heart failure with preserved ejection fraction (HFpEF), including master protocol development, project management, recruitment oversight, performance milestones, and scientific conduct of trials. The CCs will recruit and retain heart failure patients and controls. The CCs will participate in all aspects of conducting a deep phenotyping protocol and longitudinal follow-up of HFpEF patients; obtaining tissue biopsies; and recruiting patients for future clinical trials.

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

Companion NOFO for RFA-HL-27-009 will support a Data Translation Center (DTC) for overall coordination of the HeartShare program.

Funding Opportunity Goal(s)

The Division of Cardiovascular Sciences fosters heart and vascular research in the basic, translational, clinical, and population sciences, and to foster training to build talented young investigators in these areas, funded through competitive research training grants.

Key Dates

Posted Date

May 19, 2026

Open Date (Earliest Submission Date)

June 09, 2026

July 09, 2026

July 09, 2026

Not Applicable

April 2027

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.

Due Dates for E.O. 12372

Not Applicable

Expiration Date

July 10, 2026

Required Application Instructions

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts).

Conformance to all requirements (both in the Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

Table of Contents

Part 1. Overview Information Key Dates Part 2. Full Text of Announcement Section I. Notice of Funding Opportunity Description Section II. Award Information Section III. Eligibility Information Section IV. Application and Submission Information Section V. Application Review Information Section VI. Award Administration Information Section VII. Agency Contacts Section VIII. Other Information

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

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:

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

Funding Instrument

Cooperative Agreement: A financial assistance mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this NOFO.

Application Types Allowed

New

Renewal

All CTC applicants should submit new applications.

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

The OER Glossary and the How to Apply Application Guide provide details on these application types. Only those application types listed here are allowed for this NOFO.

Clinical Trial?

Optional: Accepting applications that either propose or do not propose clinical trial(s).

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

The NHLBI intends to commit up to $770,000 in total costs to fund up to one (1) new CTC award and up to $2,695,000 in total costs to fund up to seven (7) new CC awards in FY2027.

Award Budget

The amount of funding that applicants can request depends on if an application is to be the CTC or a CC. After determining which type of application is being submitted (as described in Section IV. Application and Submission Information, 2. Content and Form of Application Submission, R&R Budget), applicants may request the following amounts:

CTC application budgets may request up to $500,000 in total direct costs (excluding consortium F&A) in FY2027; up to $800,000 in total direct costs in FY2028; and up to $1,000,000 in total direct costs per year in FY2029 through FY2032; and should reflect the actual needs of the proposed project.

CC application budgets may request up to $250,000 in total direct costs per year (excluding consortium F&A) in FY2027 through FY2032 and should reflect the actuals needs of the proposed project.

Award Project Period

The maximum project period is six (6) years. The scope of the proposed project should determine the project period.

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

Eligible Organizations

Nonprofits Other Than Institutions of Higher Education

For-Profit Organizations

Local Governments

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.

Required Registrations

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.

Program Directors/Principal Investigators (PD(s)/PI(s)) All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

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

Eligible Individuals (Program Director/Principal Investigator)

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with 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.

Instructions for Application Submission

The following section supplements the instructions found in the How to Apply- Application Guide and should be used for preparing an application to this NOFO.

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

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

R&R or Modular Budget

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):

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

R&R Subaward Budget

PHS 398 Cover Page Supplement

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):

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

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):

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

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 should not exceed two (2) pages. Where the DMS Plan Format Page requires a “Yes or No” response, no additional narrative is allowed.

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

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

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.

Mandatory Disclosure

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…