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: Next Generation Phenomics to Define Heart Failure Subtypes and Treatment Targets – Data Translation Center (U54 Clinical Trial Not Allowed)

Activity Code

U54 Specialized Center- Cooperative Agreements

Announcement Type

New

Related Notices

October 22, 2020 - NOT-HL-20-822 -Notice of Change of Receipt Date for RFA-HL-21-016.

October 09, 2020 - Notice of Technical Assistance Webinar and Frequently Asked Questions (FAQs) for NHLBI HeartShare RFA-HL-21-015 "Clinical Centers (U01)" and RFA-HL-21-016 "Data Translation Center (U54)". See Notice NOT-HL-20-819.

NOT-OD-19-022 - Fast Healthcare Interoperability Resources (FHIR®) Standard.

Funding Opportunity Announcement (FOA) Number

RFA-HL-21-016

Companion Funding Opportunity

RFA-HL-21-015 - HeartShare: Next-Generation Phenomics to Define Heart Failure Subtypes (U01 Clinical Trial Not Allowed), U01 Research Project – Cooperative Agreements

Catalog of Federal Domestic Assistance (CFDA) Number(s)

93.837  

Funding Opportunity Purpose

This funding opportunity announcement (FOA) invites applicants to participate in a new NHLBI phenomics program, HeartShare: Next Generation Phenomics to Define Heart Failure Subtypes and Treatment Targets (hereafter referred to as “HeartShare”). The goal of this program is to conduct large-scale analysis of phenotypic data, images, and omics from patients with heart failure with preserved ejection fraction (HFpEF) in order to characterize mechanisms of disease and identify therapeutic targets.

This FOA solicits applications for a Data Translation Center (DTC) that will be responsible for overall project coordination, support development of a new cohort of HFpEF patients, and curate and analyze existing data from NIH cohorts and trials. A companion FOA (RFA-HL-21-015) will support the Clinical Centers.

Key Dates

 

Posted Date

September 14, 2020

Open Date (Earliest Submission Date)

New Date December 8, 2020

Letter of Intent Due Date(s)

30 days prior to the application due date

Application Due Date(s)

New Date January 8, 2021

All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).

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.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

April 2021

Advisory Council Review

May 2021

Earliest Start Date

July 2021

Expiration Date

New Date January 9, 2021 per issuance of NOT-HL-20-822 . (Original Expiration Date: December 8, 2020 )

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) 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. Table of Contents

    Part 1. Overview Information
    Part 2. Full Text of the Announcement

    Section I. 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. Funding Opportunity Description

    Background

    Heart failure (HF) research has significant public health importance due to the staggering human and economic costs of this disorder. Clinical diagnosis and management of HF are currently linked to ejection fraction, with HF with preserved ejection fraction (HFpEF) now considered a distinct disease from HF with reduced ejection fraction (HFrEF). Although the morbidity and mortality rates of HFpEF and HFrEF are comparable, therapeutic options for HFpEF patients remain elusive. HFpEF was initially thought to be due to diastolic dysfunction but is now recognized as a complex interplay of impairments in cardiac reserve, as well as altered pulmonary, renal, skeletal muscle and vascular function. There is increasing interest in the association of HFpEF with extra-cardiac features, including disorders of peripheral skeletal muscle, adipocytes, and metabolic regulation. The co-existence of HFpEF with cognitive impairment and its resulting higher morbidity is an understudied area that is likely to be another manifestation of these extra-cardiac contributors.

    Recent work suggests that applying machine learning approaches to phenotypic data from HFpEF patients allows the detection of more precise endophenotypes of disease with different outcomes. The addition of bioprofiling (e.g., genomics, proteomics, metabolomics) to this approach will allow improved characterization of the underlying pathophysiology and mechanisms of HFpEF.

    Standard approaches to data-gathering, however, are increasingly expensive, burdensome to investigators and patients, and limited in scope. Furthermore, the traditional research or clinical visit does not capture sufficient information regarding a patient’s condition and functional limitations outside of the medical encounter. For robust, multilayered deep phenotyping to achieve its maximum potential, creative approaches are needed that optimally match data-gathering and data analysis requirements with available resources. Partnering with patients to achieve this goal is imperative to both inform study design and facilitate collection and analysis of relevant data from surveys, sensors, and other non-traditional data sources.

    Research Approach

    Aggregation and harmonization of demographic, clinical, laboratory, and imaging data from large numbers of HFpEF patients combined with bioprofiling has the potential to improve the categorization of HFpEF subtypes and help uncover novel targets for mechanism-based therapies. This initiative will support a systematic and comprehensive assessment across the HFpEF spectrum, including prevalent HFpEF, incident HFpEF (risk factors leading up to disease), and the longitudinal course of disease. Although the focus will be on HFpEF, comparators with HF with mid-range ejection fraction (HFmEF), HFrEF, and age/sex-matched controls will also be studied. Finally, the complex interactions of comorbid conditions, aging and cognitive decline with HFpEF and how they contribute to its progression will also be studied.

    A new prospective cohort of HFpEF patients will undergo a comprehensive deep phenotyping protocol at four Clinical Centers (CCs).  Existing patient data and images will be acquired from NIH cohorts and completed trials, and biospecimens will be identified for performance of new omics analyses. A Data Translation Center (DTC) will support the activities of both the retrospective and prospective components of HeartShare. Collection of demographic, clinical, laboratory, and imaging data from HFpEF patients will be combined with further bioprofiling (e.g., genomics, proteomics, metabolomics) to allow discovery and validation of new biologic targets. Existing NHLBI programs, such as TOPMed for bioprofiling, and BioData Catalyst for advanced analytics, are expected to be leveraged for the HeartShare program.

    A central data platform, designed and supported by the DTC, will allow longitudinal collection of basic demographic, clinical, and laboratory data on HFpEF patients from the electronic health record (EHR) using the FHIR (Fast Healthcare Interoperability Resources) standard. Baseline and longitudinal data collected through the EHR on a larger denominator of patients will be used to then identify a subset of ~1,000 subjects for more detailed deep phenotyping. Patient-centered digital tools will be incorporated into data collection methods for electronic consents, survey completion, and acquisition of data from mobile sensors. Results from standard clinical and research testing not included in the EHR will also be collected. Outcome data may be brought in from the Centers for Medicare & Medicaid Services (CMS) Blue Button Application Programming Interface (API). Integration of various data types will be necessary to form a common data resource.

    To supplement these data, subgroups of HFpEF patients will undergo additional prospective research testing for deep phenotyping through tests such as cardiopulmonary stress testing, and cardiac magnetic resonance imaging (MRI). Remote testing for this group may include ambulatory blood pressure monitoring, activity monitoring, home sleep monitoring, and additional health surveys. Novel testing including proteomics, metabolomics, microRNAs, and molecular characterization at a single cell level from biopsy tissue may be incorporated to further characterize specific subsets of HFpEF patients.

    Sharing of resources and effective communication of findings to collaborators and broader research communities are high priorities for the HeartShare program and are strongly encouraged for applications submitted in response to this FOA. To address new challenges, NIH has articulated specific priorities and encourages rapid and open sharing of scientific efforts in development and dissemination of innovative data analytics approaches (see Goal 3 of the NIH Strategic Plan For Data Science).

    Data Translation Center Objectives

    The primary role of the DTC will be to provide overall management and oversight for the HeartShare program, including coordination and communication across all subsections and cores of the program. While the retrospective and prospective components of HeartShare will begin and run in parallel, the majority of the work in the retrospective component is expected to be completed within 2 years. The prospective component of the study will continue for up to 5 years. The DTC will provide oversight for timely completion of HeartShare’s retrospective component such that it will inform planning and future directions for the prospective component.

    DTC staff must possess strong scientific qualifications related to bioinformatics, clinical/health informatics, biostatistics, machine learning, data science, and omics. The DTC must have experience in the supervision of complex, multi-center clinical studies, as well as experience in the statistical analysis of high volume demographic, clinical, laboratory, and imaging data. The activities of the DTC will require effective communication with the clinical communities to achieve HeartShare goals, therefore, they must have personnel capable of serving as liaisons and translators among clinical researchers, clinicians, and bioinformaticians. DTC personnel should also have experience with phenotype ontology and harmonization, as well as experience in coordinating biospecimens and linking to a biospecimen repository(ies).

    The DTC’s responsibilities will cover four broad areas:

    (1) the Administrative and Outreach Core will oversee study operations, research skills development, support a call center to follow patient outcomes, and oversee capitation to the CCs for deep phenotyping costs;

    (2) the Data Portal Core will serve as the primary access for all HeartShare data;

    (3) the Data Management Core will oversee data quality, integration of various data types, performance of advanced analytics, and coordination of biospecimen and imaging biorepositories; and

    (4) the Cohort Core will aggregate data on HF patients from existing epidemiology cohorts and ongoing/completed trials and combine this information with further bioprofiling of existing samples to allow discovery and validation of new biologic targets.

    For both the retrospective and prospective components of HeartShare, the selected awardee will provide a web-based interface, or Data Portal, to enable access to aggregated HeartShare project datasets and images. Rapid and broad data-sharing of clinical and molecular data is intended to be a hallmark of the HeartShare program to enable the detection of markers of disease, progression, subtypes, and novel therapeutic targets. The Data Portal will be closely linked to NHLBI’s BioData Catalyst and will support data curation, data storage, and advanced analytics. It will link various data types and support timely and open sharing of a common data and image repository focused on HFpEF. The Data Portal will also provide links to relevant partners to promote interoperability and data sharing. The Steering Committee (SC), in collaboration with NHLBI, will oversee timeliness, policies, and standards for data sharing in the “open science” concept supported by this Data Portal.

    For the retrospective component, the DTC will be expected to work closely with cohorts and trials that have data on adjudicated HFpEF patients, with the goal of bringing individual patient data and images into a pooled HeartShare dataset. Eligible cohorts must be established and have assessed a broad array of factors (e.g., diet, exercise, therapies, environmental, behavioral, and biological variables) underlying HF development and/or progression. Cohorts may include NHLBI-supported large cohort studies, NHLBI-sponsored ongoing clinical trials, and completed clinical trials, programs primarily supported by other NIH Institutes, and other federal and non-federal programs. The cohorts and trials do not have to be currently funded by the NHLBI, but must be aligned with the NHLBI’s Strategic Vision. This FOA is intended to support research in the following cohort types:

    • Epidemiological cohorts predominantly focused on U.S. populations and based on participants with HF in defined population groups (e.g., racial or ethnic minorities, geographic area)
    • Cohorts established through either solicited or unsolicited awards, or through independent funding sources (e.g., industry, foundations).

    The DTC will work with TOPMed and other repositories, as necessary, to facilitate access to large-scale phenotypic and omics datasets. Existing biospecimens from cohorts and trials will be identified and new omics analyses will be performed in collaboration with TOPMed. HeartShare intends to prioritize the generation and collection of data from cohorts that are approved for broad data sharing and use, but recognizes that cohort data may involve a variety of data use limitations.

    The DTC will be expected to develop procedures for data harmonization and standardization for omics analyses. The DTC will distribute funds for collection of cohort and trial data in accordance with protocol budgets as determined by NHLBI and the SC.

    For the prospective component of HeartShare, the Data Portal will provide a patient-facing interface to support remote consent, completion of forms, and collection of mobile health data. Personal data will be made available to participants, according to their individual preferences. Applications are expected to use and integrate the existing platforms, tools, and workspaces of BioData Catalyst. It is anticipated that a HeartShare Data Portal will be developed through an iterative process based on user feedback and will have the capability to grow and expand with the HeartShare program. A long-term feature of the Data Portal will be the capability to facilitate proof-of-concept clinical trials. The Data Portal will support an up-to-date electronic “registry” of HFpEF patients that may be recruited for future HFpEF trials.

    The DTC will plan and provide oversight to conduct a state-of-the art deep phenotyping protocol at clinical sites.  The DTC will coordinate and implement EHR data acquisition from each clinical site to collect baseline and longitudinal information on enrolled patients. It will provide oversight for research testing; acquisition of patient-provided home monitoring data; acquisition of biospecimens; oversight for omics analyses in collaboration with TOPMed and other resources as necessary; integration of various data types to form a common data resource; and advanced analysis and interpretation of results. In addition to the funds awarded directly to the DTC for conducting DTC responsibilities, funds to conduct the phenotyping protocol will be part of the DTC’s grant award and will be distributed by the DTC as capitation to the clinical sites in accordance with protocol budgets (see RFA-HL-21-015) as determined by NHLBI and the SC. The DTC will establish core laboratories as determined by the needs of the common protocol with input from NHLBI and the SC.

    HeartShare Organization and Governance

    The HeartShare Steering Committee (SC) will provide oversight and direction for the entire program and will consist of Principal Investigators from the DTC and from each clinical site, NHLBI Project Scientists and Program Officials, and academic researchers. The SC will meet shortly after funding to begin planning for development and implementation of the comprehensive deep phenotyping protocol; establish scientific cores; and develop governance details.

    The four clinicals centers, described in RFA-HL-21-015, will serve as performance sites for the deep phenotyping protocol. Clinical sites are responsible for recruiting participants, assuring good clinical practice, supporting remote monitoring, and participating in a cooperative and interactive manner with one another, the DTC, and NHLBI. Clinical sites will be responsible for the planning and collection of high-quality data, images, and biospecimens for omics analyses and their transfer to the DTC or appropriate core labs for curation and analysis.

    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 awardees as partners, consistent with the Cooperative Agreement mechanism. The NHLBI will appoint an independent Observational Safety and Monitoring Board (OSMB) to provide ongoing review of HeartShare activities. An independent External Advisory Committee (EAC) will be appointed by NHLBI to provide periodic reviews of HeartShare operations and scientific directions. NHLBI will appoint an external study chair or co-chairs to oversee all study activities and scientific activities.

    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 or computer science or statistics) to foster cross-disciplinary learning and 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 and from the DTC. Both the DTC 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.

    In particular, DTC applications lacking an Overall component, an Administrative and Outreach Core, a Data Portal Core, a Data Management Core, and/or a Cohort Core will be considered nonresponsive and will not be reviewed.

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

    Section II. Award Information
    Funding Instrument

    Cooperative Agreement: A support 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 FOA.

    Application Types Allowed

    New

    The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.

    Clinical Trial?

    Not Allowed: Only accepting applications that do not propose clinical trials

    Need help determining whether you are doing a clinical trial?

    Funds Available and Anticipated Number of Awards

    The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

    NHLBI intends to commit total costs of up to $3,765,000 in FY2021 to fund 1 new award.

    Award Budget

    Application budgets may request up to $2,445,000 in direct costs per year (excluding consortium F&A) in FY2021 through FY2025 and need to reflect the actual needs of the proposed project.

    Award Project Period

    The maximum project period is five 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 FOA.

    Section III. Eligibility Information
    1. Eligible Applicants
    Eligible Organizations

    Higher Education Institutions

    • Public/State Controlled Institutions of Higher Education
    • Private Institutions of Higher Education

    The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

    o   Hispanic-serving Institutions

    o   Historically Black Colleges and Universities (HBCUs)

    o   Tribally Controlled Colleges and Universities (TCCUs)

    o   Alaska Native and Native Hawaiian Serving Institutions

    o   Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

    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)

    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)
    • 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 Institutions

    Non-domestic (non-U.S.) Entities (Foreign Institutions) 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.

    Required Registrations

    Applicant Organizations

    Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) 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. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

    • Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
    • 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.
    • o   NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM. 
    • eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but 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 DUNS number and 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.

    Eligible Individuals (Program Director/Principal Investigator)

    Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH 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 SF424 (R&R) Application Guide.

    2. Cost Sharing

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

    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.  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 NOT-OD-11-101).
    Section IV. Application and Submission Information
    1. Requesting an Application Package

    The application forms package specific to this opportunity must be accessed through ASSIST or an institutional system-to-system solution. A button to apply using ASSIST is available in Part 1 of this FOA. 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 Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. 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.

    Letter of Intent

    Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

    By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

    • Descriptive title of proposed activity
    • Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
    • Names of other key personnel
    • Participating institution(s)
    • Number and title of this funding opportunity

    The letter of intent should be sent to:

    Director, Office of Scientific Review

    National Heart, Lung, and Blood Institute
    Telephone: 301-435-0270
    Fax: 301-435-0270
    Email: NHLBIChiefReviewBranch@nhlbi.nih.gov

    Page Limitations

    Available Component Types

    Research Strategy/Program Plan Page Limits

    Overall

    6

    Administrative and Outreach Core

    6

    Data Portal Core

    6

    Data Management Core

    6

    Cohort Core

    6

    Additional page limits described in the SF424 Application Guide and the Table of Page Limits must be followed.

    Instructions for the Submission of Multi-Component Applications

    The following section supplements the instructions found in the SF424 (R&R) Application Guide, and should be used for preparing a multi-component application.

    The application should consist of the following components:

    • Overall: required
    • Administrative and Outreach Core: one required
    • Data Portal Core: one required
    • Data Management Core: one required
    • Cohort Core: one required
    Overall Component

    When preparing your application, use Component Type ‘Overall’.

    All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

    SF424 (R&R) Cover (Overall)

    Complete entire form.

    PHS 398 Cover Page Supplement (Overall)

    Note: Human Embryonic Stem Cell lines from other components should be repeated in cell line table in Overall component.

    Research & Related Other Project Information (Overall)

    Follow standard instructions.

    Project/Performance Site Location(s) (Overall)

    Enter primary site only.

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

    Research & Related Senior/Key Person Profile (Overall)

    Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this FOA) for the entire application.

    A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.

    Budget   (Overall)

    The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover. 

    A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.

    PHS 398 Research Plan (Overall)

    Specific Aims: Concisely address the overall goals of the DTC and how its work supports the overall objectives of the HeartShare program.

    Research Strategy:

    • Provide a general overview including considerations that will lead to successful development and coordination of the proposed DTC.
    • Describe the overall design and structure of the DTC including its management structure, integration of 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 plans for coordination and integration between the DTC cores and the overall goals of HeartShare to achieve a cohesive resource for the research community.
    • Coordinate activities of a Steering Committee (SC), an Observational Study Monitoring Board (OSMB), an External Advisory Committee (EAC), and a Research Skills Committee (RSC).
    • Describe plans to maximize the impact of the HeartShare resource by creating an ‘open science’ framework with rapid data curation and sharing.

    Letters of Support: An Institutional Letter of Support should be provided stating the institutional support for the proposed center.

    Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

    Applicants should state their general support of collaborative research and their willingness to participate in a collaborative and interactive manner with the CCs, DTC, SC, and NHLBI in all aspects of the HeartShare program.

    The DTC will be responsible for coordinating the dissemination of HeartShare research findings and relevant protocol materials. Applicants to this FOA for HeartShare CCs should indicate here their willingness to collaborate with the DTC and other SC members in dissemination efforts.

    It is expected that HeartShare research resources, such as the Manual of Operations, case report forms, and phenotype ascertainment instruments will be made available to all study members immediately after approval by the HeartShare SC and implementation into the study. The DTC applications are expected to include a plan for sharing these resources.

    All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

    Appendix:

    Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.   

    PHS Human Subjects and Clinical Trials Information (Overall)

    When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

    If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.

    Study Record: PHS Human Subjects and Clinical Trials Information

    All instructions in the SF424 (R&R) 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 SF424 (R&R) Application Guide must be followed

    PHS Assignment Request Form (Overall)

    All instructions in the SF424 (R&R) Application Guide must be followed. 

    Administrative and Outreach Core

    When preparing your application, use Component Type ‘Admin and Outreach Core.’

    All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

    SF424 (R&R) Cover (Admin and Outreach Core)

    Complete only the following fields:

    • Applicant Information
    • Type of Applicant (optional)
    • Descriptive Title of Applicant’s Project
    • Proposed Project Start/Ending Dates
    PHS 398 Cover Page Supplement (Admin and Outreach Core)

    Enter Human Embryonic Stem Cells in each relevant component.

    Research & Related Other Project Information (Admin and Outreach Core)

    Human Subjects: Answer only the ‘Are Human Subjects Involved?’ and 'Is the Project Exempt from Federal regulations?’ questions.

    Vertebrate Animals: Answer only the ‘Are Vertebrate Animals Used?’ question.

    Project Narrative:  Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

    Project /Performance Site Location(s) (Admin and Outreach Core)

    List all performance sites that apply to the specific component.

    Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

    Research & Related Senior/Key Person Profile (Admin and Outreach Core)
    • In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Project Lead’ and provide a valid eRA Commons ID in the Credential field.
    • In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
    • Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
    • If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

     Specific to this FOA:

    • Describe the previous experience, if any, of the Administrative and Outreach Core Lead in managing or participating in large-scale collaborative programs involving coordination of data generation across multiple projects.
    • An investigator should be identified as the skills development coordinator, and their experience in skills development documented in the Biosketch.
    • Sub-contract to study chair/co-chairs for oversight of all HeartShare activities.
    Budget (Admin and Outreach Core)

    Budget forms appropriate for the specific component will be included in the application package.

    Specific to this FOA:

    The suggested budget for the Admin and Outreach Core is $1,245,000 direct costs per year for years 1-2 and $1,945,000 direct costs per year for years 3-5 to cover the following:

    • Study operations and support for the patient call center: $300,000 direct costs per year for 5 years. The operational budget should include plans for conducting regular meetings for the SC, EAC, and OSMB. Reasonable costs for consultants serving on the EAC and OSMB should be proposed. The DTC will be responsible for reimbursing the Chair (or Co-Chairs) and consultants for the EAC and OSMB. An approximate consultant budget of $50,000 should be included and restricted for this use.
    • The study Chair (or Co-Chairs) will be selected from outside the study personnel. The DTC will be responsible for reimbursing the Chair (or Co-Chairs). An approximate consultant budget of 1.8 person months (15% full-time professional effort) should be included and restricted for this use.
    • Deep phenotyping: approximately $645,000 direct costs per year for years 1-2, and $1,345,000 direct costs per year for years 3-5. Existing NHLBI resources (BioData Catalyst, TOPMed, etc.) should be leveraged in budget planning. Performance of omics will be coordinated through the Steering Committee (SC) and NHLBI Project Scientists.
    • Research Skills Program across four Clinical Sites: $300,000 direct costs per year for 5 years.

    Suggested Year 1 travel commitment for planning purposes:

    • PD/PI (or PDs/PIs if a multi-PD/PI plan is used) and core leaders attending two (2) SC meetings to be held in Bethesda, MD, or another convenient/central location(s). Additional meetings may be held virtually.
    • Suggested Years 2-5 travel commitments for planning purposes:
    • PD/PI (or PDs/PIs if a multi-PD/PI plan is used) and core leaders attending one (1) SC meeting to be held in Bethesda, MD, or another convenient/central location(s). Additional meetings may be held virtually.

    CCs will propose preliminary baseline clinical examination protocols and budget. Protocol funds to perform the study-wide phenotyping protocol will be awarded to the DTC and be distributed by the DTC to the CCs on a capitation basis in accordance with budgets approved by the SC and NHLBI. For planning purposes, it is estimated that $645,000 direct costs for years 1-2 and $1,345,000 direct costs for years 3-5 will be available for the study-wide phenotyping protocol(s) to be finalized across HeartShare after funding.

    Allowable costs for the Research Skills Program include salary support for senior investigators and staff participating in mentoring activities; salary support and travel costs for early career investigators; supplies and equipment to support developmental activities; and costs for courses, seminars, workshops, and other activities directly related to the HeartShare program. All costs requested should be justified with respect to developmental activities and may not be used to supplement the costs of research proposed in the rest of the DTC application. Both the DTC 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.

    Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

    PHS 398 Research Plan (Admin and Outreach Core)

    Specific Aims: Describe how the specific aims for the Admin and Outreach Core will be accomplished.

    Research Strategy: Discuss how the activities listed below will be accomplished, staffed, and managed in support of the DTC. Describe how the proposed plans will leverage the experience described in the Biographical Sketch(es). Propose and justify any other coordination activities that would be useful to the HeartShare Project but are not listed explicitly elsewhere in this FOA.

    Describe plans for administrative and outreach activities, including but not limited to:

    • Designing, implementing, and integrating program components.
    • Monitoring and reporting metrics for patient enrollment, engagement, and retention.
    • Supporting a call center that facilitates acquisition of mobile health data, outside records, and longitudinal contact with patients.
    • Coordinating with clinical centers for all required agreements related to EHR connectivity and acquisition of longitudinal research data.
    • Ensuring consistency and standardization across clinical sites for all aspects of the program.
    • Working directly with BioData Catalyst to coordinate data storage and access.
    • Monitoring program resources and planning publications.
    • Describing plans for development of a Research Skills Program, formation of a Research Skills Committee, required and optional activities for the participants, selection of mentors and supervision, and their integration into HeartShare activities.
    • Designing a strategy for recruitment of high-quality candidates for the Research Skills Program. Explain how differing backgrounds of candidates (fellows vs. computer science post-docs) can be leveraged to enhance collaborations.
    • Coordinating yearly face-to-face meetings for the Steering Committee and investigators.
    • Hosting an annual External Advisory Committee (EAC) meeting to evaluate the progress of the program and to provide advice to the NIH and the Steering Committee about scientific direction; EAC membership will be determined by NIH.
    • Documenting discussions, decisions and actions discussed during meetings and conference calls, and following up with relevant stakeholders when necessary.
    • Compiling formal progress reports, or other reports as directed by the Project Scientists.
    • Promoting and facilitating all communications between and among all aspects of the program.
    • Establishing and maintaining of a registry of investigators participating in HeartShare program activities.
    • Establishing Core laboratories as needed to support the common phenotyping protocol.
    • Providing oversight to meet performance metrics for enrollment, retention and data quality.
    • Reimbursing Clinical Centers funds for each participant enrolled as agreed to by the protocol.

    Letters of Support: Only letters of support specific to ‘Admin and Outreach Core’ should be attached to this section.

    Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

    All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

    Appendix:

    Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.   

    PHS Human Subjects and Clinical Trials Information (Admin and Outreach Core)

    When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

    If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

    Study Record: PHS Human Subjects and Clinical Trials Information

    All instructions in the SF424 (R&R) 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 SF424 (R&R) Application Guide must be followed

    Data Portal Core

    When preparing your application, use Component Type ‘Data Portal Core.’

    All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

    SF424 (R&R) Cover (Data Portal Core)

    Complete only the following fields:

    • Applicant Information
    • Type of Applicant (optional)
    • Descriptive Title of Applicant’s Project
    • Proposed Project Start/Ending Dates
    PHS 398 Cover Page Supplement (Data Portal Core)

    Enter Human Embryonic Stem Cells in each relevant component.

    Research & Related Other Project Information (Data Portal Core)

    Human Subjects: Answer only the ‘Are Human Subjects Involved?’ and 'Is the Project Exempt from Federal regulations?’ questions.

    Vertebrate Animals: Answer only the ‘Are Vertebrate Animals Used?’ question.

    Project Narrative:  Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

    Project /Performance Site Location(s) (Data Portal Core)

    List all performance sites that apply to the specific component.

    Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

    Research & Related Senior/Key Person Profile (Data Portal Core)

    ASSIST will default to “Project Lead”. If you would like to use a different category, then replace “Project Lead” below with a different Category (e.g., Core Lead).

    • In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Project Lead’ and provide a valid eRA Commons ID in the Credential field.
    • In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
    • Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.

    If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

    Specific to this FOA:

    • Describe the previous experience, if any, of the Data Portal Core Lead in developing a web-based interface to support data curation, data storage, advanced analytics, and linkage to relevant partners for interoperability and data sharing.   
    Budget (Data Portal Core)

    Budget forms appropriate for the specific component will be included in the application package.

    Specific to this FOA:

    The Data Portal Core and Data Management Core combined budget is expected to be approximately $1,000,000 direct costs per year for years 1-2 and $500,000 direct costs per year for years 3-5.

    Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

    PHS 398 Research Plan (Data Portal Core)

    Specific Aims: Briefly describe how the specific goals of the Data Portal Core will be addressed.

    Research Strategy: Describe how existing infrastructure in BioData Catalyst will be utilized to fulfill the web-based data portal requirement of the HeartShare DTC. Provide a detailed timeline of activities with a particular focus on early design and launch milestones to measure progress. Specify metrics to evaluate usage and usability of the data through the Data Portal.

    The plans to utilize or develop a Data Portal must include, but are not limited to:

    • Data Portal Interface: Describe plans for the design and implementation of a web-based data portal to make HeartShare data accessible to the research community. Propose methods for leveraging BioData Catalyst resources for data access and storage and data analysis; provide online tools for phenotype and omics data visualization.
    • Include a description of how the proposed Data Portal will catalog, display, make searchable, enable summary statistics and basic analyses of all HeartShare data and facilitate access to associated individual level -omics data which may be stored and/or distributed through other mechanisms or data resources, such as dbGaP.  Propose solutions for linking to controlled access data per NIH policies, to be finalized in discussions with NIH. The environment should have the ability to become interoperable with the NIH Data Ecosystem in the future.
    • Data Storage: Describe plans for hosting data, including summary data, in the portal to facilitate search capability and access to datasets that may reside in other data resources. Outline proposed actions for establishing partnerships with other data resources, per the guidance of HeartShare staff, to build avenues of data exchange, where appropriate. 
    • Integration of diverse datasets: Describe plans for facilitating access to and integration of diverse datasets to form a common data resource. These datasets include, but are not limited to, cohort data, trial data, multi-omics data, EHR data, research testing, imaging, biomarkers, and others.
    • Data Analysis: Describe plans for leveraging BioData Catalyst and other resources for viewing and manipulating all data types and performing advanced analytics.
    • Data Display: Describe plans to develop or adapt existing open source or commercially available software utilities to provide online tools for phenotype and -omics data visualization. Outline plans for providing intuitive and easy-to-understand display of data and query results.
    • Patient Engagement: Create an interface for patient participants that allows remote consenting and completion of forms and that facilitates communication with participants; support development of mobile tools for these activities.
    • Collect data from home devices, sensors, and mobile apps from individual patients and seamlessly integrate with other data sources.
    • Engage patients enrolled in all phenotyping protocols and provide access to their individual data and aggregate research findings in an easily understandable and verifiable format.
    • Record patient preferences for method/time of contact, self-reported data, and other program activities.
    • Facilitate collection of outcome data that can be collected through interfaces with the Centers for Medicare & Medicaid Services (CMS, Blue Button), insurers, and other agencies.
    • Explain plans for devising and maintaining a system for collecting metrics on portal usage and functionality, including a user login/registration system, to inform future decisions about changes and modifications needed for website improvements.
    • Develop a program website.
    • EHR Connectivity: Facilitate flow of data from EHR’s to core dataset using FHIR standard (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-19-122.html).
    • Ensure data resources created by the data portal follow FAIR principles (to make data findable, accessible, interoperable, and reusable) consistent with the NIH strategic plan for data science.

    Letters of Support: Only letters of support specific to ‘Data Portal Core’ should be attached to this section.

    Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

    All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

    Appendix:

    Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.   

    PHS Human Subjects and Clinical Trials Information (Data Portal Core)

    When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

    If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

    Study Record: PHS Human Subjects and Clinical Trials Information

    All instructions in the SF424 (R&R) 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 SF424 (R&R) Application Guide must be followed.

    Data Management Core

    When preparing your application, use Component Type ‘Data Management Core.’

    All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

    SF424 (R&R) Cover (Data Management Core)

    Complete only the following fields:

    • Applicant Information
    • Type of Applicant (optional)
    • Descriptive Title of Applicant’s Project
    • Proposed Project Start/Ending Dates
    PHS 398 Cover Page Supplement
    (Data Management Core)
     

    Enter Human Embryonic Stem Cells in each relevant component.

    Research & Related Other Project Information
    (Data Management Core)

    Human Subjects: Answer only the ‘Are Human Subjects Involved?’ and 'Is the Project Exempt from Federal regulations?’ questions.

    Vertebrate Animals: Answer only the ‘Are Vertebrate Animals Used?’ question.

    Project Narrative:  Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

    Project /Performance Site Location(s)
    (Data Management Core)

    List all performance sites that apply to the specific component.

    Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

    Research & Related Senior/Key Person Profile (Data Management Core)

    ASSIST will default to “Project Lead”. If you would like to use a different category, then replace “Project Lead” below with a different Category (e.g., Core Lead).

    • In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Project Lead’ and provide a valid eRA Commons ID in the Credential field.
    • In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
    • Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.

    If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

    Specific to this FOA:

    • Describe the previous experience, if any, of the Data Management Core Lead in participating in large-scale collaborative programs involving coordination of data generation across multiple projects.   
    Budget (Data Management Core)

    Budget forms appropriate for the specific component will be included in the application package.

    Specific to this FOA:

    The Data Portal Core and Data Management Core combined budget is expected to be approximately $1,000,000 direct costs per year for years 1-2 and $500,000 direct costs per year for years 3-5.

    Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

    PHS 398 Research Plan (Data Management Core)

    Specific Aims: State the specific aims for the Data Management Core and how they will be accomplished.  

    Research Strategy:

    Applicants are expected to:

    • Develop procedures and standards for data pooling, cleaning, and harmonization of all data from cohorts and trials.
    • Provide expertise in bioinformatics, statistical support, machine learning/artificial intelligence, and systems biology.
    • Develop and implement best approaches for data standardization.
    • Coordinate de-identification, data linkages, and other privacy methods as appropriate.
    • Ensure efficient visualization, reporting, and communication of findings.
    • Develop strategies to integrate self-reported data, home monitoring data from mobile technologies, environmental data, EHR data, research testing data, and outcome data to form a core data resource.
    • Support implementation of Natural Language Processing technologies for unstructured clinical data.
    • Provide expertise in planning and facilitating all omics analyses.
    • Describe activities to support an integrated biorepository resource or a network of biospecimen repositories relevant to HFpEF research, housing samples such as DNA/RNA, plasma/serum, cell lines, urine, and various types of tissues. Explain how linkages and coordination to one or more of these resources will be leveraged to provide an integrated resource to the investigator community.
    • Coordinate biobank activities including processes for acquisition of specimens, storage, analysis plans; coordinate with TOPMed for omics analyses on existing and new specimens.
    • Describe activities to support an integrated imaging repository for HFpEF research; facilitate automated analyses with deep learning approaches for echocardiograms, electrocardiograms, and other types of images.
    • Work with BioData Catalyst to transition publicly available data into NHLBI cloud storage, implement governance within BioData Catalyst, and to make tools/workflows cloud compatible.
    • Apply advanced analytics and machine learning to detect subgroups of patients and identify mechanistic abnormalities in each subgroup using tissue, omics analyses, and other novel approaches.

    Letters of Support: Only letters of support specific to ‘Data Management Core’ should be attached to this section.

    Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

    All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

    Appendix:

    Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.   

    PHS Human Subjects and Clinical Trials Information (Data Management Core)

    When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

    If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

    Study Record: PHS Human Subjects and Clinical Trials Information

    All instructions in the SF424 (R&R) 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 SF424 (R&R) Application Guide must be followed

    Cohort Core

    When preparing your application, use Component Type ‘Cohort Core.’

    All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

    SF424 (R&R) Cover (Cohort Core)

    Complete only the following fields:

    • Applicant Information
    • Type of Applicant (optional)
    • Descriptive Title of Applicant’s Project
    • Proposed Project Start/Ending Dates
    PHS 398 Cover Page Supplement (Cohort Core)

    Enter Human Embryonic Stem Cells in each relevant component.

    Research & Related Other Project Information (Cohort Core)

    Human Subjects: Answer only the ‘Are Human Subjects Involved?’ and 'Is the Project Exempt from Federal regulations?’ questions.

    Vertebrate Animals: Answer only the ‘Are Vertebrate Animals Used?’ question.

    Project Narrative:  Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

    Project /Performance Site Location(s) (Cohort Core)

    List all performance sites that apply to the specific component.

    Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

    Facilities and Other Resources: As appropriate, describe available resources such as clinical and laboratory facilities, geographic distribution of space and personnel, and resources relevant to the effective data collection and biospecimen inventory of existing prospective epidemiology cohort and clinical trial participants.

    Research & Related Senior/Key Person Profile (Cohort Core)

    ASSIST will default to “Project Lead”. If you would like to use a different category, then replace “Project Lead” below with a different Category (e.g., Core Lead).

    • In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Project Lead’ and provide a valid eRA Commons ID in the Credential field.
    • In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
    • Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.

    If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

    Specific to this FOA:

    • Describe the previous experience, if any, of the Cohort Core Lead in organizing and managing epidemiological cohort studies and/or clinical trials.   
    Budget (Cohort Core)

    Budget forms appropriate for the specific component will be included in the application package.

    Specific to this FOA:

    The expected budget for collection of data and images through the Cohort Core is approximately $200,000 direct costs per year for years 1-2.

    Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

    PHS 398 Research Plan (Cohort Core)

    Specific Aims: Briefly describe how the specific goals of the Cohort Core will be addressed.

    Research Strategy: Describe how the following functions will be conducted by the Cohort Core in support of the HeartShare program.

    • Describe how collection of cohort/trial data can facilitate a broad HF research agenda. Describe the research questions being investigated and major findings and relevance to HF, as well as the alignment with NHLBI’s Strategic Vision (https://www.nhlbi.nih.gov/sites/default/files/2017-11/NHLBI-Strategic-Vision-2016_FF.pdf).
    • Describe plans for quality management, including how data collection activities will be managed and quality control measures.
    • Propose methods for data management, internal and external data sharing strategies as appropriate and consistent with achieving the goals of the program. Where applicable, applicants are expected to describe plans for data harmonization, metadata generation, and adoption/use of data standards or common data elements.
    • Describe data aggregation plans, including the proposed elements of the basic data collection, such as any clinical, laboratory, physiological, or behavioral assessments.
    • Describe how available study biospecimens were collected, managed, analyzed, and stored. Describe how biospecimens on identified HFpEF patients, comparators, and controls will be identified, prepared and shared with the DTC for omics assessment.
    • Describe previous experience with omics evaluations in HFpEF patients and any previous collaborations with TOPMed.
    • Describe biospecimen storage facilities and plans for maintenance and organization of existing biospecimens. Describe plans for adherence to Good Laboratory Practices (GLP). Opportunities to leverage institutional resources should be detailed, if applicable.

    Letters of Support: Only letters of support specific to ‘Cohort Core’ should be attached to this section.

    • A statement of commitment from each participating institution or organization must be provided. If parts of the study are to be provided by sources other than the NHLBI, provide Letter(s) of Support signed by an authorized representative. If an application is received without Letter(s) of Support, it will be returned without review.

    Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

    All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

    Appendix:

    Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.   

    PHS Human Subjects and Clinical Trials Information (Cohort Core)

    When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

    If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

    Study Record: PHS Human Subjects and Clinical Trials Information

    All instructions in the SF424 (R&R) 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 SF424 (R&R) Application Guide must be followed

    3. Unique Entity Identifier and System for Award Management (SAM)

    See Part 1. 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. Overview Information 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) using ASSIST or other electronic submission systems. 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 Policy on Late Application Submission.

    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 SF424 (R&R) 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.

    7. Other Submission Requirements and Information

    Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide.  Paper applications will not be accepted.

    For information on how your application will be automatically assembled for review and funding consideration after submission go to: http://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.

    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) and component Project Leads must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. 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.

    The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management (SAM). Additional information may be found in the SF424 (R&R) 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.

    Use of Common Data Elements in NIH-funded Research

    Many NIH ICs encourage the use of common data elements (CDEs) in basic, clinical, and applied research, patient registries, and other human subject research to facilitate broader and more effective use of data and advance research across studies. CDEs are data elements that have been identified and defined for use in multiple data sets across different studies. Use of CDEs can facilitate data sharing and standardization to improve data quality and enable data integration from multiple studies and sources, including electronic health records. NIH ICs have identified CDEs for many clinical domains (e.g., neurological disease), types of studies (e.g. genome-wide association studies (GWAS)), types of outcomes (e.g., patient-reported outcomes), and patient registries (e.g., the Global Rare Diseases Patient Registry and Data Repository). NIH has established a "Common Data Element (CDE) Resource Portal" (http://cde.nih.gov/ (http://cde.nih.gov/)) to assist investigators in identifying NIH-supported CDEs when developing protocols, case report forms, and other instruments for data collection. The Portal provides guidance about and access to NIH-supported CDE initiatives and other tools and resources for the appropriate use of CDEs and data standards in NIH-funded research. Investigators are encouraged to consult the Portal and describe in their applications any use they will make of NIH-supported CDEs in their projects.

    Post Submission Materials

    Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

    Section V. Application Review Information
    1. Criteria

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

    Overall Impact

    Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

    Scored Review Criteria

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

    Significance

    Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous?  If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

    Specific to this FOA:

    Will the DTC make a significant contribution to the overall goals and objectives of the HeartShare Program? Will the data and knowledge generated by this DTC lead to a better understanding of HF phenotypes and treatment targets?

    Investigator(s)

    Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

    Specific to this FOA:

    Does the PD(s)/PI(s) have the appropriate experience in managing complex, multi-site projects involving teams of scientists? Do the PD(s)/PI(s) and research team have a strong track-record of generating, integrating and analyzing high-quality data as part of a consortium? Does the research team have a strong expertise across all areas of the data generation pipeline and a clear leadership plan for integrating their expertise to meet the specific aims of the HeartShare program? 

    Innovation

    Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed? 

    Specific to this FOA:

    How well does the DTC address the research need to define HF subtypes and treatment targets? Does the DTC propose innovative approaches to data management/standards, data collection, and/or active/passive participant follow-up/surveillance?

    Approach

    Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed?  Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

    If the project involves human subjects and/or NIH-defined clinical research, are the plans to address:

     1) the protection of human subjects from research risks, and

     2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed? 

    Specific to this FOA:

    How feasible are the data collection, curation, and integration goals? How rigorous are the applicant's plans for managing study data? How achievable are the study’s timeline and milestones? Does the plan provide ample opportunity for collaboration, integration, and interaction within the DTC, with the rest of the HeartShare Program, and the wider research community?  

    Environment

    Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

    Specific to this FOA:

    Are the resources, equipment and infrastructure available and in place (or readily obtainable) to achieve the required output from the screening and analysis pipeline? Are the computational resources in place (or readily obtainable) and adequate to support the project? Are safeguards in place to protect personally identifiable information? Will the available facilities and other resources enable the applicant(s) to effectively aggregate data from participants and operate a large consortium efficiently?   

    Additional Review Criteria - Overall

    As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

    • Is the leadership plan, including how decisions will be made across the Project and Resource Cores, appropriate?
    • Are the plans for communicating and collaborating with the HeartShare Program and NIH staff appropriate and likely to facilitate overall program objectives?
    • Are the plans for submitting data, protocols, and making resources available to the HeartShare Program acceptable?
    • Will there be coordination, communication, cohesiveness and synergy among the components of the DTC as they relate to achieving the overall objectives of HeartShare?
    • Are mechanisms proposed for regular communication and coordination among investigators in HeartShare?
    Admin and Outreach Core

    As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

    • Are the staffing, equipment, and other resources that are available to the Admin and Outreach Core sufficient and relevant to meeting the goals?
    • Are plans for patient outcome ascertainment, including the Call Center, sufficient and likely to facilitate research efforts for longitudinal follow-up?
    • Are plans for the Research Skills Program likely to provide high-quality mentoring and synergy for new clinical investigators and data scientists?
    Data Portal Core

    As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

    • Are the staffing, equipment, and other resources that are available to the Data Portal Core sufficient and relevant to meeting the goals?
    Data Management Core

    As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

    • Are plans for an imaging repository likely to contribute to the understanding of HFpEF subtypes? Will the imaging resource facilitate projects involving deep learning and automated approaches for imaging analysis?
    • Are resources described for the biorepository sufficient for meeting its objectives and for facilitating mechanistic studies with multi-omics and newer technologies?
    Cohort Core

    As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

    • How well will the established cohort(s) and/or clinical trial(s) be able to address a research agenda to define HF subtypes?
    • How feasible are the data integration goals? How rigorous are the applicant's plans for managing study data? How achievable are the study’s timeline and milestones?
    • How will the facilities and other resources available to the applicant(s) enable the effective data aggregation of cohort participants and, if applicable, the efficient operation of a multi-site study?
    Protections for Human Subjects

    For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

    For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

    Inclusion of Women, Minorities, and Individuals Across the Lifespan  

    When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed.  For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

    Vertebrate Animals

    The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

    Biohazards

    Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

    Resubmissions

    Not Applicable

    Renewals

    Not Applicable

    Revisions

    Not Applicable

    Additional Review Considerations - Overall

    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.

    Applications from Foreign Organizations

    Not Applicable

    Select Agent Research

    Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

    Resource Sharing Plans

    Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genomic Data Sharing Plan.


    Authentication of Key Biological and/or Chemical Resources

    For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

    Budget and Period of Support

    Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

    2. Review and Selection Process

    Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s), convened by the National Heart, Lung, and Blood Institute, in accordance with NIH peer review policy and procedures, 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:

    • 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.
    • Will receive a written critique.

    Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

    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 FOA. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. 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. 
    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 VI. Award Administration Information
    1. Award Notices

    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.

    A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

    Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

    Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website.  This includes any recent legislation and policy applicable to awards that is highlighted on this website.

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

    Prior Approval of Pilot Projects

    Awardee-selected projects that involve {clinical trials or studies involving greater than minimal risk to human subjects} require prior approval by NIH prior to initiation. 

    2. Administrative and National Policy Requirements

    All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. 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, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

    Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex.  This includes ensuring programs are accessible to persons with limited English proficiency.  The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS.  Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html.

    HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.  For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA.

    Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.   

    In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements.  FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award.  An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS.  The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 “Federal awarding agency review of risk posed by applicants.”  This provision will apply to all NIH grants and cooperative agreements except fellowships.

    Cooperative Agreement Terms and Conditions of Award

    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 (DHHS) grant administration regulations at 45 CFR Part 75, 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 awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the 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 awardee 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 U54 award
    • Developing collaborations with and making data accessible to external investigators
    • Ensuring submission of reports to the OSMB, if applicable

    The awardee 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. Awardees 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.

    Awardees 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 (http://biospecimens.cancer.gov/bestpractices). Awardees will be required to explore, with NHLBI staff, the feasibility of data harmonization and pooling with other cohorts and studies. Awardees 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.

    Awardees 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).

    Awardees are expected to make their data widely available to other investigators per NIH and NHLBI data sharing policies (https://www.nlm.nih.gov/NIHbmic/nih_data_sharing_policies.html, https://www.nhlbi.nih.gov/grants-andtraining/policies-and-guidelines/nhlbi-policy-for-data-sharing-from-clinical-trials-and-epidemiological-studies). 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 awardees and other NHLBI-sponsored programs, investigators, or organizations that may contribute to the study's goals
    • Assisting in the interaction between the awardees 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 awardees as appropriate
    • Ensuring disclosure of conflicts of interest and adherence to NHLBI policies

    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 deep phenotyping protocol in a timely manner
    • Data portal is poorly functional and/or insufficient for proposed activities
    • Data curation is not robust or data sharing activities are inadequate
    • 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 FOA 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 Coordinating Center PI(s) (if applicable), and the biorepository 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, videoconference, or in-person.

    The appointed voting Steering Committee members will be required to attend all Steering Committee meetings and tele/videoconferences, 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 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 awardee 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 Policy for Data Sharing from Clinical Trials and Epidemiological Studies (https://www.nhlbi.nih.gov/grants-and-training/policies-andguidelines/nhlbi-policy-for-data-sharing-from-clinical-trials-and-epidemiological-studies), and the Guidelines for Preparing Clinical Study NHLBI Data Sets for Submission to the NHLBI Data Repository (https://www.nhlbi.nih.gov/grants-and-training/policies-and-guidelines/guidelines-for-preparing-clinical-studydata-sets-for-submission-to-the-nhlbi-data-repository). Large-scale genomic data generated by the awardee are to be deposited along with associated phenotype data into the database of Genomic and Phenotype Data (dbGaP, accessed at http://www.ncbi.nlm.nih.gov/gap (http://www.ncbi.nlm.nih.gov/gap)) in accordance with the NIH Genomic Data Sharing Policy available at https://osp.od.nih.gov/wpcontent/uploads/NIH_GDS_Policy.pdf (https://osp.od.nih.gov/wp-content/uploads/NIH_GDS_Policy.pdf).

    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 awardee. This special dispute resolution procedure does not alter the awardee'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.

    3. Reporting

    When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

    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.

    The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later.  All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000.  See the NIH Grants Policy Statement for additional information on this reporting requirement. 

    In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period.  The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS).  This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313).  As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available.  Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 – Award Term and Conditions for Recipient Integrity and Performance Matters.

    Section VII. Agency Contacts

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

    Application Submission Contacts

    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)

    Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
    Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

    General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
    Email: GrantsInfo@nih.gov (preferred method of contact)
    Telephone: 301-945-7573

    Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
    Contact Center Telephone: 800-518-4726
    Email: support@grants.gov

    Scientific/Research Contact(s)

    Vandana Sachdev, MD
    National Heart, Lung, and Blood Institute (NHLBI)
    Email:
    sachdevv@nhlbi.nih.gov  

    Peer Review Contact(s)

    Director, Office of Scientific Review
    National Heart, Lung, and Blood Institute (NHLBI)
    Telephone: 301-435-0270
    Email: NHLBIChiefReviewBranch@nhlbi.nih.gov

    Financial/Grants Management Contact(s)

    Annette Singletary
    National Heart, Lung, and Blood Institute (NHLBI)
    Telephone: 301-827-8052
    Email: annette.singletary@nih.gov

    Section VIII. Other Information

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

    Authority and Regulations

    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 45 CFR Part 75.    

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