Part 1. Overview Information

Key Dates

All applications are due by 5:00 PM local time of applicant organization. 

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

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

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

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

There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

1. Use the NIH ASSIST system to prepare, submit and track your application online.
2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.
   
   
3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.



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

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Background

The B2B Program was launched by the NHLBI in 2009 as a novel approach to break through the major barriers of translational research, identify the causes of human congenital heart disease (CHD), and ultimately improve outcomes for individuals with CHD. It included two consortia designed to inform each other’s work: the Pediatric Cardiac Genomics Consortium (PCGC) and the Cardiac Developmental Data Research Center (CDDRC). The initial focus of B2B was data generation describing the developmental biology and genetic basis of CHD. Through the CHD GENES study, the PCGC enrolled and conducted genomic sequencing on over 13,000 participants with CHD and 18,000 family members. CHD GENES data is a valuable resource of human genetic data shared through the NHLBI BioData Catalyst platform; developmental biology data is shared through the CDDRC (https://cddrc.org/).

The PCGC’s CHD GENES cohort is one of the largest CHD cohorts to date with genomic and clinical data. Using this robust cohort, the PCGC has changed the landscape of CHD genetics through discoveries that now account for an estimated 25% of previously unexplained CHD. In the final project cycle of the PCGC, ending in 2025, the B2B has expanded its focus beyond studying genetic etiology to investigate clinical outcomes through phenotyping of this cohort. This necessitated consortium members working with the current Coordinating Center (CC) to develop processes to capture clinical data through electronic medical records. Although CHD GENES was not originally designed as a longitudinal cohort, the NHLBI recognizes the opportunity provided by this unique cohort to couple genomics data with deep longitudinal phenotyping. Through this solicitation, NHLBI directs the CC to coordinate deep phenotyping of a subset of CHD GENES participants and make the data available to the scientific community as the B2B CHANGE Cohort.   

Research Objectives and Scope

The B2B PCGC will evolve into the B2B CHANGE Cohort to conduct ongoing clinical follow-up and deep phenotyping on cohort participants. The overall objectives of the B2B CHANGE Cohort are:

1. To sustain and expand a large, unique cohort of individuals with CHD across the lifespan, leveraging the genetic analyses and phenotyping already completed by the PCGC
2. To advance the understanding of the genetic architecture of CHD to improve clinical outcomes for children and adults living with CHD

The B2B CHANGE Cohort will include longitudinal follow-up and deep phenotyping on an estimated 6,000 individuals in the current PCGC cohort. The B2B CHANGE Cohort should be racially and ethnically diverse to adequately represent the CHD population; this diversity should be achieved through community engagement to retain the current cohort and limited continued enrollment at the clinical research sites to increase representation. Consistent with existing NIH practices and applicable law, NIH does not use the race, ethnicity, or sex of prospective participants, participants, or faculty in the application review process or funding decisions. 

The B2B CHANGE Cohort will provide a platform for independently funded, investigator-initiated, ancillary studies to answer important clinical and mechanistic questions. The role of the CC will be to lead, advance, and coordinate critical outreach, data and resource management, and administrative activities of the B2B CHANGE Cohort. The CC will issue subawards to clinical research sites that have previously enrolled participants into CHD GENES to engage cohort participants and deepen clinical phenotyping (e.g., using registry and electronic health record extraction) under a B2B CHANGE protocol. The CC will support the clinical research sites to perform a one-time in-person assessment, which will include a questionnaire, vital signs and anthropomorphic measurements, blood specimen collection, ancillary study testing and other testing as determined by the CC and investigators. 

CC functions, which may be supported by subawards or provided in-house, include but are not limited to:

1. Operations:

• Provide logistical and administrative assistance in arranging meetings of the B2B CHANGE Cohort Steering Committee and any subcommittees to advance the scientific agenda for the cohort follow-up (e.g., scheduling meetings, as well as preparing, distributing and maintaining minutes of meetings).
• Provide logistical and administrative assistance in arranging semiannual meetings of an External Oversight Committee (EOC) and an Observational Study Monitoring Board (OSMB).
• Produce, maintain, and disseminate all documents, including a Manual of Operations and procedures manuals.
• Work with NHLBI Project Scientists to develop a process for the review of proposals and applications that are submitted to the Steering Committee for ancillary studies.
• Facilitate collaboration with the Pediatric Heart Network (PHN) to sequence biospecimens of participants in PHN studies.
• Collaborate with PHN to allow biospecimen and clinical study data to be shared across the PHN and B2B CHANGE Cohort.
• Update and maintain a public-facing website to publicize the B2B, to announce the availability of B2B-supported resources, and to provide information to investigators.
• Update website to include participant-tailored information for those involved in the cohort. 
• Facilitate scientific discussions and collaborations for future grant applications utilizing the cohort data or previously collected PCGC data.
• Maintain an infrastructure for internal communications including a web portal for document sharing, scheduling, announcements, and other activities as needed.
• Provide logistical and administrative assistance in organizing fellowship project awards. The fellowship projects will be expected to conduct research projects using data from the cohort accessed through NHLBI BioData Catalyst and the data repository. The program should be open nationwide to early-career researchers and to

  2. Cohort Engagement and Follow up:

  • Organize cohort recontact efforts at the individual sites and nationally.
  • Use community engagement strategies to re-engage the cohort and CHD community, ensuring a diverse and representative cohort is re-engaged.
  • Coordinate baseline exams with the clinical research sites.
  • Organize limited, continued enrollment of CHD participants into the cohort to further enhance cohort diversity in regard to race, ethnicity, geography, and those from disadvantaged backgrounds.
  • Engage with existing pediatric and CHD registries to gather data on the cohort.

  3.  Protocol Development and Implementation:

  • Support the development, coordination, implementation and conduct of B2B collaborative research protocols (in conjunction with the Clinical Research Sites and Steering Committee), including determination of key phenotyping measures to be collected via follow up questionnaires, electronic health record extraction, and linking to existing registries.
  • Develop study materials (e.g., case report forms, questionnaires, recruitment tables).
  • Monitor protocol adherence, data collection, and submission, and report violations to the NHLBI, the PCGC Steering Committee, and the OSMB.
  • Provide advice and consultation to investigators in study design and protocol development of studies that plan to use B2B data. 

  4. Core Facilities and Data Management:

  • Continue to maintain and improve a query-able data repository.
  • Enable streamlined access to data repository in a secure manner for CHD investigators.
  • Work with data repositories to make data rapidly publicly available, as determined by NHLBI and B2B data sharing policies.
  • Maintain a B2B specimen biorepository subcontract (with existing or new biorepository) to allow continued access to existing biospecimens and incorporation of additional biospecimens. Clinical research sites will collect biospecimens from study participants for storage and distribution to biorepository.
  • Monitor subaward site activities, deliverables, and use of funds.
  • Report at least quarterly to the NHLBI subaward funds spent, pending, and remaining for the budget year. Support development and implementation of standard procedures and instruction manuals for data collection at subaward clinical research sites.  

  5.  Establish a governance process

  • Assemble a Steering Committee (SC) composed of representatives from the subaward clinical research sites, the CC, and NHLBI Program Scientists. The SC will be the main governing body of the B2B CHANGE Cohort and have primary responsibility for overseeing cohort data collection activities, assessment of feasibility of ancillary studies, and expeditious reporting of study results. The SC will determine if subawards to additional clinical research sites are indicated in order to achieve adequate representation of the CHD population. All major scientific and administrative decisions are determined by majority vote of the SC with one vote for each site and one each for the CC and NHLBI. The SC will meet monthly by videoconference and will have an annual SC meeting to be held via videoconference or in-person. The SC may authorize working groups of investigators to facilitate opportunities to share data and discuss and implement collaborative projects. Working groups should be composed of investigators using the cohort data across the CHD research community and include early-career investigators.
  • The NHLBI is responsible for organizing and providing overall support for the B2B CHANGE Cohort. The NHLBI Program Office and Office of Grants Management are responsible for the overall management of the B2B CHANGE Cohort. In addition to regular grant stewardship, NHLBI Project Scientists will be involved substantially with the awardees as a scientific partner, consistent with the Cooperative Agreement mechanism.
  • An independent External Oversight Committee (EOC), appointed by the NIH and funded through the CC, reviews the progress of the program annually and as needed to provide advice to the NHLBI about scientific direction. Members of the EOC and ad hoc external experts may be involved in reviewing applications for ancillary studies when requested by the CC or NHLBI Project Scientists.
  • An Observational Safety and Monitoring Board (OSMB), also appointed by the NIH and funded through the CC, monitors patient safety and data integrity and reviews the performance of each study involving human subjects. The OSMB will also review proposed ancillary studies for issues of participant burden and successful achievement of milestones. As a part of its monitoring responsibility, the OSMB submits recommendations to the NIH regarding the conduct and continuation of each protocol.
  • An Ancillary Studies Platform will be maintained by the CC and the SC as a process to review ancillary study proposals. The ancillary studies themselves will not be funded by this NOFO, but rather by successful investigator-initiated grant applications or other sources of funding. The B2B CHANGE Cohort CC will support coordination of approved and funded ancillary studies, including tracking biospecimen inventory and making relevant data and biospecimens available to ancillary study investigators. This NOFO includes the general processes and inventory tracking for ancillary studies but does not cover additional costs related to a specific ancillary study (e.g., aliquoting, shipping) that are expected to be funded by the ancillary study.

  Specific Areas of Research Interest

  To enhance the scientific value of the B2B CHANGE Cohort, it is anticipated that investigators will apply for grants or other funding mechanisms to conduct ancillary studies. The CC will provide advice and consultation to investigators in ancillary study design and protocol development process. Approved ancillary studies will allow for additional testing or data collection either during an in-person baseline assessment or through longitudinal data extraction efforts. The CC will coordinate with the ancillary study PIs and the subaward sites to facilitate this process.

  Examples of Research Questions for Future Ancillary Studies include, but are not limited to:

  • Can genomic and phenotypic information be combined to predict those most at risk for neurodevelopment and executive function delays or mental health issues, all known to be more prevalent in individuals with CHD?
  • Can biomarkers or gene expression networks be identified as potential mechanisms of neurodevelopmental delay?
  • What risk factors place a patient with complex CHD at highest risk for heart failure or other co-morbidities (e.g., liver and kidney disease)?
  • How do damaging variants in CHD genes result in ventricular dysfunction later in life? 
  • What mechanisms and potential druggable targets underlie the increased risk of cancer in CHD?
  • Can genomics be used to predict with better accuracy which patients with tetralogy of Fallot are most likely to have life-threatening arrhythmias and benefit most from an implantable cardioverter-defibrillator (ICD)? 
  • Does genomic signature and/or other phenotypic factors affect valvular and ventricular dysfunction in single ventricle heart disease? 

  Data Sharing

  A critical mission of the B2B program is to expand resources to the broader scientific community to advance research. Data generated by the B2B CHANGE Cohort are expected to be made available to the broader research community through open, shared databases such as dbGaP or NHLBI BioData Catalyst. Appropriate controls will be implemented to ensure patient privacy and regulatory compliance. 

  This is a non-competitive funding opportunity intended to fund a single award. NHLBI is announcing its intent to issue a single source cooperative agreement to Cincinnati Children’s Hospital Medical Center for the transition of the Bench-to-Bassinet (B2B) Program Administrative Coordinating Center into a B2B CHANGE (Congenital Heart disease Advancing New understanding in GEnomics) Cohort Data Coordinating Center (CC). This award is single-source in order to continue and maintain long-term infrastructure investments. The award will enable the current PCGC Administrative Coordinating Center to build on its existing infrastructure, including its robust datahub, to support the goals of the B2B CHANGE Cohort.

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

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

Only the following applicant is eligible to apply for this single source funding: Cincinnati Children's Hospital Medical Center. Please refer to Section I. Notice of Funding Opportunity Information for more details. 

Non-domestic (non-U.S.) Entities (Foreign Organizations) 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 How to Apply- Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information.

• System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • 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.
  • Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registrations; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov – Applicants must have an active SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

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

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

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the How to Apply-Application Guide.

Only the PI(s)/PD(s) associated with award issued under RFA-HL-21-002 to the Cincinnati Children's Hospital Medical Center are eligible to apply for this single source funding. Please refer to Section I. Notice of Funding Opportunity Information for more details.

2. Cost Sharing

This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1.2 Definition of Terms.

3. Additional Information on Eligibility

Number of Applications

Special Requirements

Only a single award will be issued to the Cincinnati Children's Hospital Medical Center under this single source funding opportunity. Please refer to Section I. Notice of Funding Opportunity Information for more details.

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Letter of Intent

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

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

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

The letter of intent should be sent to:

Director, Office of Scientific Review
Division of Extramural Research Activities
National Heart, Lung, and Blood Institute
Email: [email protected]

Page Limitations

All page limitations described in the How to Apply- Application Guide and the Table of Page Limits must be followed.

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

SF424(R&R) Cover

All instructions in the How to Apply - Application Guide must be followed.

SF424(R&R) Project/Performance Site Locations

All instructions in the How to Apply- Application Guide must be followed.

SF424(R&R) Other Project Information

All instructions in the How to Apply- Application Guide must be followed.

Facilities and Other Resources: Describe special or unique strengths that are relevant to B2B infrastructure and research. An example could include the availability of state-of-the art biomedical or research informatics systems (e.g., innovative tools, methods and algorithms), which may be shared or may be available to develop and expand scientific productivity of the B2B.

SF424(R&R) Senior/Key Person Profile

All instructions in the How to Apply- Application Guide must be followed.

Without duplicating information from the individual biosketches, investigators are encouraged to describe special or unique strengths that may be relevant to B2B infrastructure and research. Examples could include significant previous experience coordinating genomics research programs or prior participation in research funded by NIH cooperative agreements. Describe previous experience in organizing, supporting, and conducting annual in-person, monthly teleconference, and video conference meetings, and preparation of minutes and other related reports. Demonstrate experience in providing logistical services for multi-center translational or clinical research.

R&R or Modular Budget

All instructions in the How to Apply- Application Guide must be followed.

In addition, the budget should designate a minimum of 2.4 person months effort for the PD/PI, or a minimum of 2.4 person months combined effort for all PDs/PIs if the application includes multiple PDs/PIs.  

R&R Subaward Budget

All instructions in the How to Apply-Application Guide must be followed.

PHS 398 Cover Page Supplement

All instructions in the How to Apply- Application Guide must be followed.

PHS 398 Research Plan

All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions:

The main focus of the application should be to propose a plan to meet the research coordination activities to support the B2B CHANGE Cohort objectives. The Research Strategy must consist of the following subsections:

A. Management Strategy

Provide a description of the leadership approach, governance, and organizational structure including an organized, feasible strategy for the coordination of the clinical research sites through subawards. Include detailed timelines for the initiation and completion of key activities (operations, core facilities and data management).

Include a statement indicating willingness to engage in collaborative activities across the B2B, in partnership with NHLBI staff, to support the goals of the B2B CHANGE Cohort and to accelerate translation of study findings to the scientific community and clinical practice.

B. Operations

Expertise and Experience in Logistical and other Support Services: The CC will provide arrangements for logistical support associated with meetings and conference calls for the SC, working groups, the EOC, the OSMB, and other meetings as required. Describe plans for organizing, supporting, and conducting monthly videoconference meetings, and preparation of minutes and other related reports. Describe plans for providing logistical services for multi-center translational or clinical research.

Describe a plan to review applications submitted to the SC, including ancillary study applications.

Electronic Information and Data Systems: Describe plans to produce, maintain, and disseminate all documents including a Manual of Operations and procedures manuals. Dissemination is expected to include an interactive website to publicize the B2B CHANGE Cohort to investigators and cohort participants, to announce the availability of B2B-supported resources, and to receive input from CHD investigators; and provide a mechanism for rapid and routine exchange of materials (e.g., manuscripts, reports, etc.) among the B2B investigators, the NHLBI Project Scientists, and other NHLBI staff. Internal communications infrastructure is to include a web portal for document sharing, scheduling, announcements, and other activities as needed.

Provide details of prior experience with electronic information and data systems activities, including innovative systems for management and archiving of email traffic and electronic reports, development of standard operating procedures, and ensuring data safety and confidentiality.

Describe plans for development and implementation of a program to enable CHD researchers to readily access the B2B CHANGE Cohort data in a secure manner. Describe plans to facilitate trainees and early-career investigators interested in working with the data for their research. Describe plans for periodic updates.

Cohort Outreach: The CC will work with the subaward sites to actively re-engage and communicate with previously enrolled B2B participants. Describe plans for outreach efforts to the cohort either on a national or site level, and plans on how to incentivize participation in the cohort. A subaward may be considered to enhance outreach efforts.

C. Protocol Development

Describe a plan to support the development, coordination, implementation, and conduct of B2B collaborative research protocols to include but not limited to:

• Monitoring protocol adherence and data collection and submission; and reporting violations to the NHLBI, the SC and the OSMB
• Uniform investigative protocols for data and specimen collection and tracking
• Development and maintenance of a computerized data system for data management and statistical analysis
• Providing support services for the production of data forms and reports, graphics, and other materials
• Providing advice and consultation to investigators in ancillary study design and protocol development for B2B CHANGE Cohort ancillary studies

D. Subaward Sites and Data Management

Applicants must describe plans for:

• Support of a biorepository of DNA and tissue specimens
• Support of a data repository or repositories with role-based permission levels (e.g., to all B2B investigators, subsets of investigators, or approved external investigators)
• Coordination with the data repositories to make data publicly available, as determined by NHLBI and B2B data sharing policies
• Monitoring of subaward sites activities, deliverables, and use of funds
• Reporting at least quarterly to the Project Scientists the amount of subaward funds spent, pending, and remaining for the budget year
• Assuring data quality
• Management and disbursement of funds for consortia subaward sites and protocols

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply- Application Guide.

Other Plan(s): 

All instructions in the How to Apply-Application Guide must be followed, with the following additional instructions:

• All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan

Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the How to Apply- Application Guide.

• No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

PHS Human Subjects and Clinical Trials Information

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the How to Apply- Application Guide, with the following additional instructions:

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

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the How to Apply- Application Guide must be followed.

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the How to Apply- Application Guide must be followed.

PHS Assignment Request Form

All instructions in the How to Apply- Application Guide must be followed.

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

See Part 2. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

4. Submission Dates and Times

Part I. contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time.  If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the How to Apply-Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement Section 7.9.1 Selected Items of Cost.

Applications must be submitted electronically following the instructions described in the How to Apply - Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile form. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this NOFO for information on registration requirements.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the How to Apply - Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Recipients or subrecipients must submit any information related to violations of federal criminal law involving fraud, bribery, or gratuity violations potentially affecting the federal award. See Mandatory Disclosures, 2 CFR 200.113 and NIH Grants Policy Statement Section 4.1.35.

Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to the HHS Office of Inspector Grant Self Disclosure Program at [email protected].

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in the policy

Section V. Application Review Information

1. Criteria

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

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following scored review criteria and additional review criteria (as applicable for the project proposed).  An application does not need to be strong in all categories to be judged likely to have a major scientific impact.

Reviewers will consider Factors 1, 2 and 3 in the determination of scientific merit, and in providing an overall impact score. In addition, Factors 1 and 2 will each receive a separate factor score. 

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

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the 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 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.

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

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 NOFO. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions, consistent with applicable law.

• 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.

Please note that reviewers will not consider race, ethnicity, age, or gender of a researcher, award participant, or trainee, even in part, in providing critiques, scores, or funding recommendations. NIH will not consider such factors in making its funding decisions.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement Section 2.5.1. Just-in-Time Procedures. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding.

Prior to making an award, NIH reviews an applicant’s federal award history in SAM.gov to ensure sound business practices. An applicant can review and comment on any information in the Responsibility/Qualification records available in SAM.gov. NIH will consider any comments by the applicant in the Responsibility/Qualification records in SAM.gov to ascertain the applicant’s integrity, business ethics, and performance record of managing Federal awards per 2 CFR Part 200.206 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement Section 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

A Notice of Award (NoA) is the official authorizing document notifying the applicant that an award has been made and that funds may be requested from the designated HHS payment system or office. The NoA is signed by the Grants Management Officer and emailed to the recipient’s business official.

In accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Any pre-award costs incurred before receipt of the NoA are at the applicant's own risk.  For more information on the Notice of Award, please refer to the NIH Grants Policy Statement Section 5. The Notice of Award and NIH Grants & Funding website, see Award Process.

Institutional Review Board or Independent Ethics Committee Approval: Recipient 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 recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

2. Administrative and National Policy Requirements

The following Federal wide and HHS-specific policy requirements apply to awards funded through NIH:

• The rules listed at 2 CFR Part 200, Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards.
• All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the terms and conditions in the Notice of Award (NoA). The NoA includes the requirements of this NOFO. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities.
• If a recipient receives an award, the recipient must follow all applicable nondiscrimination laws. The recipient agrees to this when registering in SAM.gov. The recipient must also submit an Assurance of Compliance (HHS-690). To learn more, see the Laws and Regulations Enforced by the HHS Office for Civil Rights website.
  • HHS recognizes that NIH 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 NOFO.

All federal statutes and regulations relevant to federal financial assistance, including those highlighted in NIH Grants Policy Statement Section 4 Public Policy Requirements, Objectives and Other Appropriation Mandates.

Recipients are responsible for ensuring that their activities comply with all applicable federal regulations.  NIH may terminate awards under certain circumstances.  See 2 CFR Part 200.340 Termination and NIH Grants Policy Statement Section 8.5.2 Remedies for Noncompliance or Enforcement Actions: Suspension, Termination, and Withholding of Support. 

Successful recipients under this NOFO agree that:

Where the award funding involves implementing, acquiring, or upgrading health IT for activities by any funded entity, recipients and subrecipient(s) are required to: Use health IT that meets standards and implementation specifications adopted in 45 CFR part 170, Subpart B, if such standards and implementation specifications can support the activity.  Visit https://www.ecfr.gov/current/title-45/subtitle-A/subchapter-D/part-170/subpart-B to learn more.

Where the award funding involves implementing, acquiring, or upgrading health IT for activities by eligible clinicians in ambulatory settings, or hospitals, eligible under Sections 4101, 4102, and 4201 of the HITECH Act, use health IT certified under the ONC Health IT Certification Program if certified technology can support the activity. Visit https://www.healthit.gov/topic/certification-ehrs/certification-health-it to learn more.

Pursuant to the Cybersecurity Act of 2015, Div. N, § 405, Pub. Law 114-113, 6 USC § 1533(d), the HHS Secretary has established a common set of voluntary, consensus-based, and industry-led guidelines, best practices, methodologies, procedures, and processes.

Successful recipients under this NOFO agree that:

When recipients, subrecipients, or third-party entities have:

1. ongoing and consistent access to HHS owned or operated information or operational technology systems; and 
2. receive, maintain, transmit, store, access, exchange, process, or utilize personal identifiable information (PII) or personal health information (PHI) obtained from the awarding HHS agency for the purposes of executing the award.

Recipients shall develop plans and procedures, modeled after the NIST Cybersecurity framework, to protect HHS systems and data. Please refer to NIH Post-Award Monitoring and Reporting for additional information. 

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (HHS) grant administration regulations at 2 CFR Part 200, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the recipients is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and NIH as defined below.

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

• The CC PD(s)/PI(s) will have the primary responsibility for the overall function of the CC. This includes the (1) coordination of the activities of the of the Steering Committee and other working groups, External Oversight Committee, and Observational Study Monitoring Board; (2) allocation of subaward sites’ funds and monitoring of subaward site deliverables and use of funds; (3) designing and maintaining an internal website for document sharing; (4) designing and maintaining a public website to publicize the B2B Program and facilitate data sharing; (5) writing and maintaining governance documents such as a Manual of Operations; and (6) coordination of all aspects of the B2B CHANGE Cohort activities, including any modification of study protocol, 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.
• Recipient agrees to provide quarterly financial reports to the Project Scientists of subaward funds paid out, pending invoices, and funds remaining for the budget year.
• The recipient will assure that all members of the CC team are aware of B2B policies and procedures and kept informed of B2B activities, meetings, and results.
• The recipient agrees to publicly release data and other products of the study in a timely manner and publish results in peer-reviewed journals, in accordance with B2B policies and governance. Genomic and clinical data will be shared through dbGaP or NHBLI BioData Catalyst consistent with the NIH data sharing policies. The goal for the program will be to share data as promptly after quality assessment as feasible.
• Recipients agree to follow best practice in clinical research and to follow procedures to protect and ensure the privacy of medical and genetic data and records of individuals.
• Engaging with NIH staff, at least bimonthly, to discuss scientific and/or administrative progress (e.g., including NIH staff in CC meetings with PD(s)/PI(s) and key personnel).
• Complying with resource, data, and biospecimen sharing.
• Publishing of CC project results in peer-reviewed journals, presentation of CC project outcomes at professional meetings, and annual meetings.
• Recipients will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies. 
•  

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 B2B CHANGE Cohort. 
• The NHLBI Project Scientists will serve on the Steering Committee; he/she or other NIH scientists may serve on other study working groups, when appropriate. The NHLBI Project Scientist (and other NIH scientists) may work with the recipient on issues coming before the Steering Committee and, as appropriate, other committees, e.g., recruitment, follow-up, quality control, adherence to protocol, assessment of problems affecting the study and possible changes in protocol, interim data and safety monitoring, final data analysis and interpretation, preparation of publications, and development of solutions to major problems such as insufficient participant enrollment or engagement.
• The NHLBI Project Scientists, on behalf of the NIH, will have the same access, privileges and responsibilities regarding the collaborative data as the other members of the Steering Committee.
• The NHLBI reserves the right to withhold funding or curtail the study (or an individual subaward) in the event of (a) failure to develop or implement a mutually agreeable collaborative protocol; (b) substantial shortfall in participant recruitment, follow-up, data reporting, or quality control; (c) major breach of the protocol, substantive changes in the agreed-upon protocol, or B2B policies with which NHLBI cannot concur; or (d) human subject ethical issues that may dictate a premature end of the award.
• The NHLBI will appoint members of the External Oversight Committee (EOC).
• 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 NIH 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 NIH.
• 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.
• Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

• Coordinating the overall objectives and progress at the annual meeting to facilitate the achievement of CC goals.
• Reviewing and assisting in developing operating guidelines consistent policies for dealing with situations that require coordinated action.
• The SC has primary responsibility for overseeing a protocol for cohort data collection and a baseline in-person assessment. The SC will also evaluate the feasibility of proposed ancillary studies. All major decisions brought to the SC will be determined by a majority vote.
• The SC voting membership shall consist of the Research Center principal investigators (i.e. PD/PI), the NHLBI Project Scientists, and the CC PD/PI(s). Meetings of the Steering Committee will ordinarily be held by telephone conference call or in person. Additional members may be added by majority vote of the Steering Committee.
• An independent OSMB will be appointed by the Director, NHLBI, to provide overall monitoring of cohort study data and safety issues. An NHLBI scientist, other than the NHLBI Program Scientist, will serve as Executive Secretary to the OSMB.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between recipients and NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened: 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 recipient. This special dispute resolution procedure does not alter the recipient's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and HHS regulation 45 CFR Part 16.

Consistent with the 2023 NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

4. Reporting

When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement Section 8.4.1 Reporting. To learn more about post-award monitoring and reporting, see the NIH Grants & Funding website, see Post-Award Monitoring and Reporting.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement Section 8.6 Closeout. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 2 CFR Part 200.301.

Section VII. Agency Contacts

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: https://www.era.nih.gov/need-help (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: 301-480-7075

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

Bryanna Schwartz, MD, MPH
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-594-8868
Email: [email protected]   

Charlene Schramm, PhD
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)
Email: [email protected]

E-Bijan Cox 
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-480-8628
Email: [email protected]

Section VIII. Other Information

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

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 2 CFR Part 200.