Required Application Instructions

It is critical that applicants follow the 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.

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

Congenital heart disease (CHD) results from genetic, biomechanical, and environmental influences acting on the developmental processes that give rise to the heart. Studies of cardiovascular development in animal models have provided tremendous insight into the molecular mechanisms that direct morphogenesis of the heart. However, there is still only a piecemeal picture of the sequence of nuclear regulatory mechanisms, cellular molecular pathways, cell functions and behaviors, and tissue interactions that make up the multi-scale network that directs cardiovascular development. Even less is known as to which components and levels within this network, when disrupted, manifest as CHD in humans. The major barriers preventing researchers from identifying the mechanisms of human disease include knowledge gaps within the regulatory network that controls cardiovascular development in animal models, the complexity of analyses of the vast amounts of data needed to fill those gaps, difficulties relating information from animal models to human disease, and limited means for clinical researchers to spotlight those gaps in basic research that are of most relevance to human disease.

The Bench-to-Bassinet Program (B2B) was launched by the NHLBI in 2009 as a novel approach to break through these barriers, identify the causes of human congenital heart disease, and ultimately improve outcomes for individuals with congenital heart disease. The B2B strategy is to accelerate the translation of scientific discovery into clinical practice through collaborations of basic, translational, and clinical researchers. Recognizing that many research institutions excel in one or two of these areas, but not necessarily all three, the B2B is structured into three consortia. The CvDC comprises basic scientists; the Pediatric Cardiac Genomics Consortium (PCGC) human genetics and genomics researchers; and the Pediatric Heart Network (PHN) clinical and observational study experts. Although each component is free-standing, the B2B Program overall is designed to enable the findings of one consortium to be readily communicated to and acted upon by the others, thereby driving the science forward in a more comprehensive, translational manner. An Administrative Coordinating Center (ACC) subcontracts core facilities to support the scientific work of the CvDC and PCGC, supports the PCGC’s clinical protocols, and performs administrative tasks for the CvDC and PCGC. See the companion announcement for the PCGC (RFA-HL-15-012). The NHLBI also intends to publish an FOA for an ACC at a later date.

The NHLBI recognizes that a vast amount of the research progress achieved to date toward understanding mechanisms of heart development has come out of individual laboratories and will continue to do so. What is missing is a framework for communication between basic and clinical researchers and within the cardiovascular development field. It is the objective of the B2B to build that framework, with the expectation that the communication lines established between the consortia will become self-sustaining and eventually stretch beyond the consortia. During the first funding cycle of the B2B, the CvDC focused on developing lines of communication within the CvDC and with the PCGC. Specifically, the consortium has been active in generating and sharing genome-level datasets, developing tools to enable and standardize complex analyses, harmonizing phenotype ontologies and genomic analyses across species, and providing animal model-based functional assays of candidate genes identified by the PCGC as potentially causing CHD. The public website of the B2B program serves as a portal for interested investigators to access links to datasets, query selected datasets, and view standardized protocols.

The primary goal of the CvDC remains to produce a body of basic knowledge that can be applied toward a mechanistic understanding of human CHD. The CvDC approach continues to be grounded in hypothesis-driven research, but the CvDC will also leverage its established infrastructure to serve as a vanguard of robust data-sharing practices. A secondary goal is to use real-time data sharing to further accelerate progress by the greater scientific community toward a complete understanding of the mechanisms of cardiovascular development. Data output will be standardized and released to the community immediately following appropriate quality control. Data and data links will be made available through a public portal. The CvDC will also introduce the basic science community to fully collaborative research by piloting a strategy of common research protocols that has proven successful for its sister consortia, the PHN and PCGC.

Another important secondary goal of the CvDC is to prepare junior scientists and junior faculty to succeed in an evolving research environment where intensely collaborative science is becoming more common. Central to accomplishing this mission is equipping future leaders with the experience and skills to direct studies that integrate well with multidisciplinary programs, coordinate large datasets across multiple centers, and make effective use of shared resources. Also important is preparing them for a future research environment where rapid data-sharing becomes the norm.

The purpose of this FOA is to select Centers capable of leading the CvDC through this transition toward deeper intra-consortium collaboration and greater transparency with the external research community. The second phase of the CvDC will support (1) up to four centers focused on separate but interrelated research projects; (2) at least one cross-consortium collaborative research project; and (3) collaborations with the PCGC to reveal the underlying biology of observed cases of genetically-caused CHD in humans.

Specific areas of research interest

Investigators should propose hypothesis-driven research that addresses critical knowledge gaps in cardiovascular developmental biology and mechanisms of CHD. Leading questions include, but are not limited to:

• What are the mechanisms by which perturbations of developmental networks result in cardiovascular anatomical abnormalities in animal models?
• What are the effects of human genetic variants on these networks?
• What can be learned of developmental networks by cross-species meta-analysis?
• What are the spatial and temporal domains of human genetic variants during embryogenesis?

Priority will be given to applications that exploit and expand the collaborative potential of the CvDC. The main research project will draw predominantly on the research team and local resources of the individual Research Center, while the collaborative project(s) will draw on the expertise across the CvDC. The CvDC Steering Committee (see below) will evaluate the proposed collaborative projects. Projects selected will be those that best complement the Centers' main research projects. Collaborative projects will be developed collectively by study committees comprising members from all Research Centers, junior scientists, the ACC, and the NHLBI. The exact number of collaborative projects supported will depend on the nature and extent of the investigations prioritized by the CvDC leadership and the availability of funds. Collaborative projects may be selected from the studies proposed by the successful applicants to this FOA, but a decision to fund a particular Research Center will not commit the CvDC to develop that applicant’s proposed collaborative project. All Research Centers are expected to participate in all collaborative projects.

Examples of research topics

Some examples of research topic areas appropriate for this FOA include, but are not limited to, those listed below:

• Computational modeling of cardiovascular development networks.
• Proteomics of cardiovascular development.
• Temporal and spatial regulation of developmental networks by cis-regulatory elements.
• Medium- or high-throughput characterization of the mechanistic consequences of genetic variants discovered by the PCGC, such as their effects on downstream mediators.
• Lineage studies to identify target cell populations affected by human genetic variants.
• High-throughput testing of network components using differentiated cells derived from pluripotent cell cultures.
• Multi-species approaches to identify optimal models of molecular mechanisms of specific human cardiovascular malformations.

The following topics would NOT be responsive to this FOA:

• Projects that are self-contained and lack a collaborative aspect.
• Studies focused on characterizing progenitor cells in the context of regenerative medicine.
• Applications for mechanistic studies of a particular candidate gene reported by the B2B.
• Discovery studies using publicly-available PCGC or CvDC data.
• Studies that investigate gene function outside the context of network or genome-level analysis. For example, characterization of cardiovascular malformations resulting from mutation of a single gene would not be responsive.

Applicants proposing the above are encouraged to submit an R01 application to the parent program announcement, PA-13-302.

Studies that propose genome-wide analysis of CHD exclusively in human subjects are more appropriate for RFA-HL-15-012, which solicits PCGC Research Centers.

The CvDC is a consortium of cooperative Research Centers, an ACC, and NHLBI Project Scientists.

Research Centers are responsible for proposing, developing, and conducting studies; entering data into a web-based CvDC data repository; training junior investigators; and disseminating research findings. All individual Research Centers are expected to participate in a cooperative and interactive manner with one another, the PCGC Research Centers, and the ACC.

The Administrative Coordinating Center (ACC) performs administrative tasks for the entire B2B program, issues subcontracts to core facilities that support the scientific work of the consortium, organizes meetings, and coordinates activities of the External Advisory Committee.

The Steering Committee is the main governing body of the CvDC. The Steering Committee is composed of the PDs/PIs of each Research Center and the ACC, NHLBI Program Scientists, and Core Directors. The Steering Committee has primary responsibility for the general organization of the CvDC, allocation of core resources, and expeditious reporting of study results. All major scientific and administrative decisions are determined by majority vote of the Steering Committee, which meets at least monthly by teleconference.

Subcommittees are established as necessary, and membership includes appropriate representation from the Research Centers, the ACC, and the NHLBI.

Cores are necessary to support the science and to provide resources and services to multiple Research Centers. For example, during the initial funding cycle of the CvDC, cores included (1) a centralized data hub to provide a platform to share data within the B2B Program and with outside investigators; (2) a Bioinformatics Core to standardize data format and analyses across the CvDC and to develop tools as needed; (3) other core facilities used in an ad hoc fashion, as driven by the science, to perform sequencing, functional testing of candidate disease genes, and other scientific tasks. Once the CvDC is convened, requirements for Cores across the Consortium will be evaluated. The ACC will determine the Core configuration with input from the Steering Committee, External Advisory Committee (see below), and NHLBI Project Scientists. Cores can be located at Research Centers or at institutions outside of the CvDC, depending upon expertise, performance, and cost. The ACC and NHLBI will oversee the process of Core selection, and the ACC will administer the budget for the Cores. Cores may be phased in and out based on scientific need during the course of the funding cycle.

The NHLBI is responsible for organizing and providing overall support for the CvDC. The NHLBI Program Office and Office of Grants Management are responsible for the overall management. In addition to regular grant stewardship, the NHLBI Project Scientists will be involved substantially with the awardees as a scientific partner, consistent with the Cooperative Agreement mechanism.

An independent External Advisory Committee (EAC), appointed by the NHLBI and funded through the ACC, reviews the progress of the program every 6 months and provides advice to the NHLBI Project Scientists about scientific direction. Members of the EAC and ad hoc external experts review all applications for potential cores and provide advice to the Project Scientists about core selection.

Interaction with the PCGC

An important aspect of the program is the interaction of scientists along the translational spectrum. Therefore, CvDC investigators will meet regularly with investigators from the PCGC, through teleconferences and in-person meetings, to share data and discuss and implement collaborative projects.

Data sharing

A critical mission of the program is to expand resources to the broader scientific community. The CvDC strives to meet or exceed expectations in NIH data sharing policies. A goal of the CvDC will be to achieve real-time data sharing with the broader scientific community through the CvDC data repository and the B2B program's public website.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

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:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• 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

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are 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.

• 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) (formerly CCR) 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.
• 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 and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. 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.

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:

• 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).

In addition, the NIH will not accept a resubmission (A1) application that is submitted later than 37 months after submission of the new (A0) application that it follows. The NIH will accept submission:

• To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;
• Of an investigator-initiated application that was originally submitted to an RFA but not paid; or
• Of an application with a changed grant activity code.

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise. 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.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

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
Division of Extramural Research Activities
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 7214
Bethesda, MD 20892-7924
Bethesda, MD 20817 (express/courier service)
Telephone: (301) 435-0270
FAX: (301) 480-0730
Email: [email protected]

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed, with the following exceptions or additional requirements.

The Research Strategy should consist of the following subsections with the indicated page limits:

A. Overview: one required; 6 pages
B. Main Research Project: one required; 12 pages
C. Collaborative Project(s): one required; 6 pages
D. Cores (optional): one optional; 6 pages

The forms package associated with this FOA includes all applicable components, required and optional. Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate optional components.

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.

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. The budget should:

• Designate a minimum of 2.4 calendar months effort for the PD/PI, or a minimum of 2.4 calendar months combined effort for all PDs/PIs if the application includes multiple PDs/PIs.
• Identify and provide sufficient effort level for a representative to the B2B and CvDC Informatics Committees.
• Include the level of personnel effort to be made available for collaborative projects.
• Include travel costs for 2 Steering Committee meetings per year in Bethesda, MD, for 2-3 members of the Research Center, including at least one PD/PI and the Informatics Committee representative.

Enter the estimated costs for two protocols as line items in Section F. Other Direct Costs:

• Line 8 should be identified as Main Research Project and the corresponding project costs should be entered under Funds Requested ($) in this line.
• Line 9 should be identified as Collaborative Projects and the corresponding protocol costs should be entered under Funds Requested ($) in this line.

As part of the budget justification, applicants will support the Collaborative Project budget by estimating the direct costs necessary for the successful completion of the study, such as:

• any special personnel who are not already listed in Sections A and B of the SF424 R&R Budget form;
• materials and supplies;
• other costs such as animal care costs.

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:

Specific Aims: Applicants should list the overall Specific Aims.

Research Strategy: The Research Strategy must consist of the following subsections uploaded as a single attachment:

A. Overview

The Overview subsection should address the following areas:

Research Center goals

This narrative subsection should discuss the Research Center's overall research goals and the strategic plan to achieve those goals. The research goals should be put into the context of the current state of knowledge of cardiovascular development and current technologic capabilities.

Qualifications and experience

Research Centers must have an established research program in the scientific areas of interest, appropriate expertise, and a track record of data and resource sharing as appropriate.

Application to participate in the CvDC should not be undertaken lightly, as it entails a significant commitment in terms of time, organizational skills, and administrative ability. Applicants should indicate their willingness to attend (1) all Steering Committee meetings, which may include teleconference calls at least monthly and in-person meetings at least twice a year, (2) all joint teleconference calls and meetings with the PCGC, and (3) other committee meetings, as necessary, to develop collaborative projects, coordinate standardized bioinformatics pipelines, and oversee cores.

Collaboration

All applications should provide examples of prior dynamic and productive collaborations. For renewal applications, applicants should describe their collaborative activities and interactions with other CvDC Research Centers, the NHLBI, the ACC, and the PCGC. Collaborative history will include activities associated with B2B cross-consortium committees and cores, collaborative services provided to fellow Research Centers, and services to the external scientific community on the behalf of the CvDC.

Applicants should provide a clear and concise description of the interrelationships among the members of their team, and the contribution of each member to fulfill the objectives of this FOA. In addition, the applicant should provide a plan to ensure the maintenance of close cooperation and effective communication among members of the applicant’s team and evidence of the capability of the applicant’s organization to participate and interact effectively in cooperative multi-center research.

The applicant should address how the Research Center will benefit the greater scientific community.

• Provide examples of anticipated datasets that would be of value to non-consortium investigators.
• Describe the data types expected to be made public. Include any data standards that will be applied to enable ready use of the datasets by non-consortium investigators.
• Elucidate a strategy for real-time sharing of data which incorporates the B2B public website and CvDC data repository.
• Provide examples of other anticipated resources to be developed (software, reagents, etc.).

Training

Applications should describe how the Research Center will integrate junior investigators into B2B activities, such as interactions with fellow B2B members from the sister Research Centers, attendance at annual meetings, and data presentations. Current CvDC centers should describe the degree of B2B involvement by junior scientists during the initial funding cycle. Applications for new centers may describe training in collaborative science through other efforts and programs.

Statement of assurance that the applicant will (1) accept the Cooperative Agreement Terms and Conditions of Award in Section VI. 2. A. (2) comply with all CvDC policies and procedures, including those specified in the Resource Sharing Plan instructions below; (3) provide timely responses to all communications from the CvDC Steering Committee Chair, ACC, and NHLBI Project Scientists; and (4) be proactive to involve external investigators in CvDC collaborative projects.

B. Main Research Project: The Main Research Project subsection should discuss a project or group of related projects, consistent with the objectives of the FOA that can be completed in 5 years by the Research Center within the context of the Consortium. Describe the project rationale, study design and timetable; provide preliminary data sufficient to support the rationale; and address potential collaborations within the consortium that could arise out of the Main Research Project.

C. Collaborative Project(s)

The applicant must propose at least one collaborative project. If more than one project is proposed, the descriptions must still comply with the page limit indicated above for this subsection. Preliminary data are not required. Describe the project rationale, research aims, study design and timetable. Describe core services to be provided through the ACC. Provide a management plan as to how the collaborative activities will be coordinated across the CvDC or B2B Program.

D. Cores (Optional): Applicants may propose cores that would support the collaborative aspects of the primary and collaborative projects. Describe the scope of services to be provided by the core and required areas of expertise. Multiple cores may be proposed, but descriptions for all cores must be contained within the 6 page total limit for this single section.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide, with the following modifications:

• The Resource Sharing Plan is expected to include assurances that the applicant will appropriately (1) comply with the CvDC requirement for real-time data sharing by releasing data immediately following completion of data quality assessment; and (2) will provide descriptive summaries of all datasets to the ACC for posting on a public website concurrent with or prior to public release of the data, consistent with achieving the goals of the program.
• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

Part I. Overview Information contains information about Key Dates. 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.

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. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

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 Applying Electronically.

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 by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research 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? 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 for this FOA:

Does the applicant propose to develop data or resources of potentially high value to the scientific community?

Main Research Project: Does the Main Research Project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved?

Collaborative Project: Does the Collaborative Project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? Does the nature or depth of the collaboration exceed the level typical of collaborations within the scientific community?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or 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? Does the research team have expertise capable of making a significant contribution to the scope and impact of collaborative projects? Do the PDs/PIs have a strong history of intensive collaborative science? Do the PDs/PIs have a strong history of freely sharing high quality datasets and other resources? Have the PDs/PIs dedicated adequate levels of effort to participate fully in consortium activities? Are the plans for training new investigators comprehensive and likely to enhance junior scientists' skills in collaborative science?

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? Does the nature or depth of the collaborations exceed the level typical of collaborations within the scientific community?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? 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?

Specific for this FOA:

Main Research Project: Are the strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the Main Research Project? 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?

Collaborative Project: Are the strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the Collaborative Project? Does the approach demonstrate a commitment to collaborative research? 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?

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 children, justified in terms of the scientific goals and research strategy proposed?

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?

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.

Resource Sharing

Does the Overview propose a feasible means of real-time sharing of data, consistent with achieving the goals of the program? Will the data be appropriately shared in a format or level of analysis that can be readily used by other labs? Does the project propose to develop resources that can be readily adopted by other labs?

Training Potential

Does the project provide junior scientists with experience in collaborative science that is likely to be beneficial to their future careers?

Protections for Human Subjects

For research that involves human subjects but does not involve one of the six 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 six 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 Children

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 children 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 five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. 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

For Renewals, the committee will consider the progress made in the last funding period.

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.

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) Genome Wide Association Studies (GWAS)

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 NHLBI, 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 . Following initial peer review, recommended applications will receive a second level of review by the NHLBI Advisory Council. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.
• Compliance with resource sharing policies as appropriate.

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.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

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 the DUNS, SAM Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

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.

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 Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), 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 the primary responsibility for:

• All aspects of the study, including any modification of study design, conduct of the study, quality control, data analysis and interpretation, preparation of publications, and collaboration with other investigators, unless otherwise provided for in these terms or by action of the Steering Committee.
  
  
• Assuring that all members of the research team are aware of CvDC policies and procedures and kept informed of CvDC activities, meetings, and results.
  
  
• Serving as a member of a joint leadership committee with the PCGC PDs/PIs, and joint committees with the PHN members, as necessary.
  
  
• Serving as Chair of the Steering Committee for one year, if selected by the NHLBI Project Scientist.
  
  
• Awardee(s) agree to the governance of the study through a Steering Committee and to accept and implement policies approved by the Steering Committee. The Steering Committee voting member for the Awardee will be the PD/PI. For Centers with multiple PDs/PIs, the contact PD/PI will serve as the voting member.
  
  
• Awardee(s) agree to public release of data and other products of the study in a timely manner and to publish results in peer-reviewed journals, in accordance with CvDC policies and governance. Genomic data is expected to be shared consistent with the anticipated NIH Genomic Data Sharing Policy and CvDC policy. Data release to the public is expected immediately following quality control.
  
  
• 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 DHHS, PHS, and NIH policies.

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

• The NHLBI is responsible for organizing and providing overall support for the CvDC. The NHLBI Program Office and Office of Grants Management are responsible for the overall management.
  
  
• The NHLBI Project Scientist will serve on the Steering Committee. He/she or other NHLBI scientists may serve on additional B2B committees, when appropriate. The NHLBI Project Scientist (and other NHLBI scientists) may work with awardees on issues coming before the committees, e.g., requests to use core services, preparation of core monthly progress reports, and improvements to data sharing procedures.
  
  
• The NHLBI Project Scientist, on behalf of the NHLBI, will have the same access, privileges and responsibilities regarding the collaborative data as the other members of the Steering Committee.
  
  
• The NHLBI will appoint members of the External Advisory Committee.
  
  
• The NHLBI reserves the right to withhold funding or curtail studies (or an individual award) in the event of failure to develop or implement a mutually agreeable collaborative project.
  
  
• Support or other involvement of industry or any other third party in the study - e.g., participation by the third party; involvement of study resources or citing the name of the study or NHLBI support; or special access to study results, data, findings or resources - may be advantageous and appropriate. However, except for licensing of patents or copyrights, support or involvement of any third party will occur only following notification of and concurrence by NHLBI.
  
  
• 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.

In addition to the above responsibilities, the NHLBI Project Scientists will also serve as Program Official, and be responsible to normal program stewardship, consistent with the provisions of the Cooperative Agreement mechanism.

Areas of Joint Responsibility include:

• The Steering Committee will be responsible for the general organization of the CvDC, allocation of core resources, monitoring progress of the cores, development and conduct of collaborative projects, and expeditious reporting of study results.
  
  
• The Steering Committee voting membership shall consist of the Research Center principal investigators (i.e., PD/PI), the NHLBI Project Scientist, and the ACC PD/PI. Additional members may be added by majority vote of the Steering Committee. Meetings of the Steering Committee will be held at least monthly by telephone conference call and at least annually in-person at sites selected by the Steering Committee. The Steering Committee Chair will be appointed by the NHLBI from the Steering Committee membership or other experts and will be supported through the ACC. All major scientific and administrative decisions will be determined by majority vote

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.

When multiple years are involved, awardees will be required to submit the annual Non-Competing Progress Report (PHS 2590 or RPPR) and financial statements as required in the NIH Grants Policy Statement.

A final progress report, 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.

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

eRA Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
Finding Help Online: http://grants.nih.gov/support/index.html
TTY: 301-451-5939
Email: [email protected]

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact CenterTelephone: 800-518-4726
Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone: 301-710-0267
TTY 301-451-5936
Email: [email protected]

Charlene Schramm, Ph.D.
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0510
Email: [email protected]

Office of Scientific Review
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0270
Email: [email protected]

John Diggs
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-402-4267
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 Parts 74 and 92.