Department of Health
and Human Services (HHS)
and Human Services (HHS)
EXPIRED
National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
U01 Research Project Cooperative Agreements
New
RFA-HL-21-016 - HeartShare: Next Generation Phenomics to Define Heart Failure Subtypes and Treatment Targets Data Translation Center (U54) Clinical Trial Not Allowed)
93.837
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 Clinical Centers (CCs) that will recruit and retain heart failure patients, comparators, and controls. CCs will participate in all aspects of planning and conducting a deep phenotyping protocol for HFpEF patients, as well as interpretation and translation of results. A companion FOA (RFA-HL-21-016) will support a Data Translation Center for overall coordination of the HeartShare program.
30 days prior to the application due date
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.
Not Applicable
March 2021
May 2021
July 2021
New Date January 9, 2021 per issuance of NOT-HL-20-822 . (Original Expiration Date: December 8, 2020 )
Not Applicable
It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide,except where instructed to do otherwise (in this FOA or in a Notice from 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.
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 are 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 have 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.
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 new prospective cohort of HFpEF patients will undergo a comprehensive deep phenotyping protocol at four Clinical Centers (CCs). 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 (https://www.nhlbiwgs.org/) for bioprofiling, and BioData Catalyst (https://biodatacatalyst.nhlbi.nih.gov/) 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; https://datascience.nih.gov/strategicplan).
Clinical Center Objectives
CC investigators will participate in developing and conducting a common deep phenotyping protocol, data standardization, planning and interpreting analyses, and interpreting and disseminating study findings. CCs will screen and enroll HF patients and controls. They will conduct clinical examinations, collect biospecimens for biomarker and multi-omics signaling pathway analyses, and provide information, images, and biospecimens to the DTC or designated core labs.
CCs will partner with the DTC for development and maintenance of a patient-facing interface of the Data Portal with the goal of facilitating and increasing patient interactions with the research process. Recruited participants will be able to consent for studies remotely, provide information from home monitoring of symptoms, provide mobile health and wearable data summaries, and review aggregate data and results through this portal. 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.
CCs will also partner with the DTC to create a new paradigm for clinical research in which baseline data on participants is obtained from the EHR and combined with research testing, patient-provided data, and biospecimen testing. CCs should have informatics expertise and experience in using the EHR data for research, and they will collaborate with the DTC on data standardization and harmonization. EHR data will be curated locally before transfer to the DTC, and plans will be made for baseline and longitudinal data sharing.
CCs are strongly encouraged to form multidisciplinary teams consisting of one HF investigator and one investigator from a complementary area of expertise, including but not limited to geriatrics, metabolic disease, and/or genomics. Teams are expected to include clinical/health informatics expertise. A CC must demonstrate a very strong track record of successful enrollment of HF participants, the ability to collect and analyze data, work cooperatively as a member of a large group, adhere to a common protocol and have capacity to mentor junior investigators. CCs are encouraged to partner with professional societies, industry or patient groups to leverage research resources. CCs will screen and enroll HF patients and controls for a target enrollment of approximately 1,000 subjects among 4 CCs over the study period. CCs are encouraged to include more than one site if necessary to accomplish recruitment goals.
Applicants are requested to propose a common deep phenotyping protocol that could be performed at all sites. Suitable cores, including but not limited to an imaging core, biomarker and omics core, and others, should be proposed. The final deep phenotyping protocol, cores, and skills training activities will be determined by the HeartShare Steering Committee (SC) once the program is funded. Applicants should highlight their specific areas of strength and their unique contributions to the HeartShare program, including their interest and ability to function as a core facility.
HeartShare Organization and Governance
The HeartShare 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 investigators representing the retrospective portion of the study. The SC will meet shortly after funding to begin planning for development and implementation of a comprehensive deep phenotyping protocol; establish scientific cores; and develop governance details.
The DTC will operate four cores to support the research envisioned in HeartShare:
The four CCs will serve as the performance sites for the deep phenotyping protocol. CCs 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. CCs 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 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.
See Section VIII. Other Information for award authorities and regulations.
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.
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.
Need help determining whether you are doing a clinical trial?
The NHLBI intends to commit up to $1,232,000 for up to 4 new awards in FY2021.
Application budgets may request up to $200,000 in direct costs per year (excluding consortium F&A) in FY2021 through FY2025 and need to reflect the actual needs of the proposed project.
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.
Higher Education Institutions
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
Nonprofits Other Than Institutions of Higher Education
For-Profit Organizations
Local Governments
Federal Governments
Other
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.
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.
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.
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.
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
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:
The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.
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:
The letter of intent should be sent to:
Director, Office of Scientific Review
National Heart, Lung, and Blood Institute
Telephone: 301-435-0270
Email: [email protected]
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.
The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
Facilities and Other Resources: Institution descriptions should include information about the clinics and medical facilities in which HF patients (HFrEF, HFmEF, and HFpEF) and sex/age-matched controls are cared for, including a description of the numbers of patients that would be expected to be eligible for participating in HeartShare.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
R&R or Modular Budget
All instructions in the SF424 (R&R) Application Guide must be followed with the following additional instructions.
1. Operational Budget
CC applicants must submit a detailed budget for costs related to the study site operation (including investigator/research coordinator salaries). This budget should include travel costs to attend Steering Committee (SC) meetings as well as other travel related to HeartShare operations. These costs must not exceed $200,000 direct costs per year for 5 years. This budget is expected to support a research coordinator and a percentage of time for co-investigators.
Suggested Year 1 travel commitments for planning purposes:
Suggested Years 2-5 travel commitments for planning purposes:
2. Deep Phenotyping Protocol
As discussed in the Research Strategy section below, CCs should describe their vision of a deep phenotyping protocol that will be standardized across all sites by the SC after funding. CCs will propose a preliminary baseline clinical examination protocol and budget. Protocol funds to perform the deep 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 per year for years 1-2 and $1,345,000 direct costs per year for years 3-5 will be available for the study-wide phenotyping protocol(s). This will be finalized and agreed upon by the SC across HeartShare after funding. As the intent is to use existing NHLBI resources, such as TOPMed for omics, the cost of omics should not be included in budget totals.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
Research Strategy
Participant selection, enrollment, and biospecimen collection and handling should be described. Applicants will propose details of deep phenotyping for all participants and a plan for integrating the data obtained from the EHR, patient-provided data, and research testing. Sub-groups of participants will undergo deeper phenotyping for specific metabolic, renal, peripheral or other abnormalities and a general plan for this should be discussed. Consideration for how to transition from mechanistic evaluations and target identification to proof-of-concept clinical trials should be included. Applicants should define potential skill development activities for junior investigators that will be coordinated by the DTC across the entire HeartShare program.
In lieu of a traditional research strategy, with the usual headings, applicants should use the following content guidelines in preparing their applications:
CC Organization and Recruitment Plan (recommend 6 pages)
Phenotyping Proposal (recommend 6 pages):
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.
The following modifications also apply:
When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the 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 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.
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.
All instructions in the SF424 (R&R) Application Guide must be followed.
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
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). 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.
This initiative is not subject to intergovernmental review.
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.
Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.
Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.
For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.
Important reminders:
All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile 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. See Section III of this FOA for information on registration requirements.
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. 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.
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.
Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.
Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).
Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.
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:
If successful, will this CC make a significant contribution to the overall goals and objectives of the HeartShare Program? If successful, will the data and knowledge generated by this CC 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:
How well does the experience of the PD(s)/PI(s) qualify him/her to lead a large deep phenotyping study and its related activities (e.g., recruitment, data, image, and biospecimen collection; overseeing multiple components of data acquisition)? To what extent is the research team multidisciplinary, in terms of integrating expertise from the geriatrics research community to leverage knowledge of aging-related disease mechanisms and/or the metabolic diseases/obesity research or other communities to leverage appropriate expertise? What is the research team’s track record of leadership and investigations relevant to the goals of the HeartShare Program such as elucidation of HFpEF subtypes, understanding the influence of co-morbidities, aging and/or cognitive decline, and identification of underlying mechanisms of disease?
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 proposed deep phenotyping protocol address the research need to define HF subtypes and discover treatment targets? How well does the research team leverage mobile technology, remote monitoring, and wearables as part of research protocols?
Approach
Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the 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:
Does the team have adequate health informatics expertise to conduct the EHR data processes necessary to achieve the goals of the HeartShare program? How rigorous are the applicant's plans for patient recruitment and retention?
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:
To what extent, will the described facilities and other resources be able to effectively support the proposed collection of the data, image, and biospecimen collection of study participants?
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.
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
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.
Specific to this FOA:
Reviewers will comment on the likelihood of success of skills development for early career investigators at the CC, and how well sites are likely to achieve cross-disciplinary learning and application of data science principles in clinical research.
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 (GDS).
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.
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 will receive a written critique.
Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
Applications will be assigned on the basis of established PHS referral guidelines 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 NHLBI Advisory Council or Board. The following will be considered in making funding decisions:
Information regarding the disposition of applications is available 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.
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.
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:
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:
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:
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, video conference, or in-person.
The appointed voting Steering Committee members will be required to attend all Steering Committee meetings and tele/video conferences, or to appoint a substitute that will be fully briefed on the issues at hand. Additional non-voting members to serve in an advisory capacity may be added to the Steering Committee as needed by a decision of the existing voting committee members. The Steering Committee may also form an Executive Committee (EC) and/or subcommittees as needed. The NHLBI Project Scientist(s) may serve on the EC and on subcommittees as deemed appropriate. The Chair of the Steering Committee will be selected from the SC voting members.
The Steering Committee will have primary responsibility for:
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)) in accordance with the NIH Genomic Data Sharing Policy available at 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.
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.
We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.
eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)
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: [email protected] (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: [email protected]
Vandana Sachdev, MD
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-496-3015
Email: [email protected]
Director, Office of Scientific Review
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0270
Email: [email protected]
Annette Singletary
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-827-8052
Email: [email protected]
Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.