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 SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from NIH Guide for Grants and Contracts).

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

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

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Background and Objectives

Congenital cardiac malformations affect about 1% of live births and are the primary cause of death under age 1 due to a birth defect. Due to improved surgical and management techniques, survival has increased significantly in recent decades, and the number of adults living with congenital heart disease is now approximately twice the number of affected children. Acquired heart disease affects thousands of additional children each year.

The objective of the Pediatric Heart Network (PHN) is to provide an infrastructure for equitable multi-center collaborative clinical research in children and adults with congenital heart disease (CHD) and pediatric acquired heart disease. The infrastructure will support evaluation of medical, interventional, and surgical therapies; development of novel treatment techniques and methodologies; identification of and attempts to address equity gaps in care and outcomes; and to serve as a clinical research training ground for fellows, junior faculty and research nurses.

In the PHN, multiple clinical trials and studies are active at all times. In addition to conducting observational studies and clinical trials, the PHN supports nursing, health services, and quality improvement research, and oversees a robust program of clinical research mentoring. Details about current and previous studies and other activities can be found at https://www.pediatricheartnetwork.org/.

In this funding cycle, the PHN's emphasis will continue to be on research addressing the most important problems facing affected children and adults with CHD and children with acquired heart disease, building on the existing sense of community and established structure. However, this renewal will emphasize two specific pillars to support transformational impact:

• Addressing existing unequal clinical outcomes; and
• Big data/data science

Addressing existing unequal clinical outcomes: The many gains that have been made in outcomes for individuals born with congenital heart defects have not been distributed equally across racial and ethnic groups. A major goal of the next evolution of the PHN is to attempt to address such inequity. A Research Protocol Concept is requested (see Section 2, Research Strategy) to describe a study that will address unequal clinical outcomes in congenital heart disease. In addition, PHN sites, with assistance from the Data Coordinating Center (DCC), will be expected to develop a patient/family community that is more representative of the US population demographics, and engaged as partners in the research process. Sites will be expected to propose a plan to earn the trust of their local community to increase to increase racial and ethnic diversity in PHN studies.

Big data/Data Science: There are many groups collecting data on individuals with congenital heart disease across the lifespan and across specific conditions (e.g., single ventricle, heart failure). Another major goal of the next evolution of the PHN is to identify ways, using sophisticated data science tools, to harness the clinical data that sites send to various registries and data repositories and combine that data with omics data, social determinants of health, and environmental health data to answer important clinical questions. Data science research in the PHN might enable identification of clinical sub-phenotypes that could serve as the basis for studies of precision medicine approaches to treatment.

The PHN will retain its infrastructure consisting of a DCC and up to nine Clinical Research Centers (CRCs). The PHN FOAs (this FOA and its companion, RFA-HL-24-002 Limited Competition: Pediatric Heart Network for the Data Coordinating Center (U24 Clinical Trial Not Allowed) (U24 Resource-Related Research Project (Cooperative Agreements)) will support this infrastructure for seven years. PHN site budgets will support investigator and study coordinator effort. Funding for a small number of trials and other studies will be included in the DCC budget, but PHN investigators will also be encouraged to seek funding for additional trials and studies through investigator-initiated grants, industry participation, and foundation grants.

Protocol topic areas will be decided cooperatively by the PHN Steering and Executive Committees, which includes representation from the DCC and each participating PHN site. CRCs selected to join the PHN should be prepared to contribute to the development of and participate in all ongoing protocols.

The objective of this FOA is to identify CRCs with the experience, expertise, and infrastructure to collaboratively design and execute studies, enroll participants efficiently and safely in PHN protocols, and participate actively in all other PHN activities.

In particular, this FOA seeks applications from CRCs with expertise in pediatric and adult congenital and pediatric acquired heart disease that can demonstrate their ability to:

• Work cooperatively to provide scientific supervision of study development, study conduct, and results dissemination and implementation.
• Identify, enroll and retain a diverse array of participants in multi-center cardiovascular clinical studies such that the trial will provide information about differences by sex/gender, race and/or ethnicity (Public Health Service Act sec. 492B, 42 U.S.C. sec. 289a-2).
• Interface with the local community to enhance engagement, recruitment, and retention
• Effectively and efficiently manage all CRC administrative activities.
• Interface with a variety of other cardiovascular databases and registries.
• Assemble the resources necessary for optimal conduct and support for PHN activities and studies.
• Encourage participation and training of fellows, junior faculty, nurses, and study coordinators in multicenter clinical research by engaging them as active members of the site’s PHN team.

Organization and Governance

The PHN is a cooperative Network of CRCs, a DCC, NHLBI Project Scientists, an independent Protocol Review Committee and a Data and Safety Monitoring Board (DSMB).The DCC is supported by a separate award, described in detail in RFA-HL-24-002.

CRCs are responsible for proposing, developing, and refining protocols; identifying, recruiting and retaining a diverse array of study participants such that the trial will provide information about differences by sex/gender, race and/or ethnicity; entering data promptly and accurately into the electronic data capture system; contributing to manuscripts and otherwise disseminating research findings; and contributing to PHN governance through committee participation. The CRCs are expected to participate in a cooperative and interactive manner with the NHLBI and the DCC.

The Executive Committee is the main governing body of the PHN and is composed of the Principal Investigators (PIs) of the core CRCs and the DCC, the chairs of select PHN Committees, a Study Coordinator, and the NHLBI Project Scientists. Each member has one vote; the NHLBI staff has one collective vote.

The Steering Committee consists of PHN investigators from all participating sites (the 9 main CRCs funded through this FOA and auxiliary sites funded through subcontracts with the DCC to support recruitment in specific studies) the DCC, and NHLBI staff. PHN investigators, study coordinators, DCC statisticians and staff, and NHLBI staff meet in person an average of twice a year, and by teleconference on a monthly basis, as needed.

The DCC supports protocol development; provides sample size calculations, sophisticated statistical advice, and data analysis; supports manuscript preparation; and provides overall study coordination, and quality assurance, including coordination of the activities of the DSMB and other standing committees. Funds to support the patient care costs associated with the protocols will be part of the DCC grant award and will be distributed to the CRCs by the DCC on a per-patient basis and according to the approved protocol budgets.

The PHN's scientific and administrative work is assisted by a variety of committees whose membership is drawn from the CRCs, the DCC, and the NHLBI. Committees may include protocol development, publications, finance, core lab, ancillary studies, nursing research, biospecimens, health service research, and other committees as needed to support PHN activities. CRC investigators are expected to participate in committee activities.

NHLBI is responsible for strategic direction and support for the PHN. 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.

The PHN’s NHLBI-appointed DSMB monitors patient safety and reviews performance of each study. As a part of its monitoring responsibility, the DSMB submits recommendations to the NHLBI regarding the conduct and continuation of each protocol.

Participation in Trials and Other Studies

Multiple trials and other clinical studies will be conducted during the project period. Once the CRCs are convened in the new funding cycle, the PHN Executive and Steering Committees will consider proposed protocols and prioritize them. It is expected that each protocol will be implemented in all of the core CRCs. As specific protocols are developed, support will depend on the availability of funds, and sites will be reimbursed on a capitated basis. The PHN DCC will manage approval of clinical protocols by the PHN’s single IRB.

The number of protocols supported in the program will depend on the nature and extent of the investigations proposed and on available funds. Both short-and-long term projects will be considered.

Applications Not Responsive to this FOA
Examples of projects that are not responsive to this FOA include, but are not limited to the following and will not be reviewed:

• Applications that do not propose a research protocol concept in pediatric and adult congenital and pediatric acquired heart disease
• Applications that propose basic science
• Applications that do not describe the site’s clinical research capabilities in multi-center collaborative research
• Applications that do not include a description of the site’s data science and integration capabilities

Notice of NIH's Interest in Diversity

Every facet of the United States scientific research enterprise from basic laboratory research to clinical and translational research to policy formation requires superior intellect, creativity and a wide range of skill sets and viewpoints. NIH’s ability to help ensure that the nation remains a global leader in scientific discovery and innovation is dependent upon a pool of highly talented scientists from diverse backgrounds who will help to further NIH's mission. Research shows that diverse teams working together and capitalizing on innovative ideas and distinct perspectives outperform homogenous teams. Scientists and trainees from diverse backgrounds and life experiences bring different perspectives, creativity, and individual enterprise to address complex scientific problems. There are many benefits that flow from a diverse NIH-supported scientific workforce, including: fostering scientific innovation, enhancing global competitiveness, contributing to robust learning environments, improving the quality of the research, advancing the likelihood that underserved or health disparity populations participate in, and benefit from health research, and enhancing public trust. In spite of tremendous advancements in scientific research, information, educational and research opportunities are not equally available to all. NIH encourages institutions to diversify their student and faculty populations to enhance the participation of individuals from groups that are underrepresented in the biomedical, clinical, behavioral and social sciences. See, NOT-OD-20-031 and Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities NOT-OD-22-019 for details.

To support the best science, the PHN encourages inclusivity in research. Examples of structures that promote diverse perspectives include but are not limited to:

• Transdisciplinary research projects and collaborations among neuroscientists and researchers from fields such as computational biology, physics, engineering, mathematics, computer and data sciences, as well as bioethics.
• Engagement from different types of institutions and organizations (e.g., research-intensive, undergraduate-focused, minority-serving, community-based).
• Individual applications and partnerships that enhance geographic and regional heterogeneity.
• Investigators and teams composed of researchers at different career stages.
• Participation of individuals from diverse backgrounds, including groups traditionally underrepresented in the biomedical, behavioral, and clinical research workforce (see NOT-OD-20-031), such as underrepresented racial and ethnic groups, those with disabilities, those from disadvantaged backgrounds, and women.
• Project-based opportunities to enhance the research environment to benefit early- and mid-career investigators.

Plan for Enhancing Diverse Perspectives (PEDP)

This FOA requires a Plan for Enhancing Diverse Perspectives (PEDP) as part of the application (see further below). Applicants are strongly encouraged to read the FOA instructions carefully and view the available PEDP guidance material. Applications must include a Plan for Enhancing Diverse Perspectives (PEDP) submitted as Other Project Information as an attachment (see Section IV). The PEDP will be assessed as part of the scientific and technical peer review evaluation, as well as considered among programmatic matters with respect to funding decisions.

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

Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs.

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 FOA.

Section III. Eligibility Information

1. Eligible Applicants

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)

Local 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)

Federal Government

• 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 restricted to Canadian sites only

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• 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 registration; 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 his/her organization to develop an application for support. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019.

A multi-PI plan is encouraged. For institutions/organizations proposing multiple PD/PIs, visit the Multiple Program Director/Principle Investigator Policy and submission details in the senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide. For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see 2.3.9.4 Similar, Essentially Identical, or Identical Applications)

Section IV. Application and Submission Information

1. Requesting an Application Package

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

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) 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.

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

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages.

All instructions in the SF424 (R&R) Application Guide must be followed with the following additional instructions:

Descriptive Title of Applicant's Project: Applications must use the naming convention Pediatric Heart Network [insert Site Name]" replacing the words in italics with the name of the applicant's site.

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

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

All instructions in the SF424 (R&R) Application Guide must be followed with the following additional instructions:

Facilities and Other Resources: Include the following information:

Applications from institutions that have a Clinical and Translational Science Award (CTSA) funded by NIH should identify the resources that could be available to support the proposed CRC, commenting particularly on aspects that will enhance the ability to conduct clinical research efficiently, including data science resources. In such a case, a description of the CTSA and how the applicant proposes interacting with it should be included. Given the fiscal limitations and costs of clinical research, applications with additional research support for clinical studies are of special interest.

Other Attachments: The application must include the following documents, uploaded as separate pdf files with the names indicated below.

1. Research Protocol Concept

The filename Research Protocol Concept.pdf should be used and will be reflected in the final image bookmarking for easy access for reviewers.

• Propose a concept for a research protocol that focuses on improving the health and quality of life for children and adults with congenital heart disease or pediatric heart disease through multi-center collaborative clinical research. At a minimum, one of the study aims should address equity in outcomes. Data science/precision medicine/environmental health researchapproaches are encouraged as part of the study design will be considered a strength.
• A full protocol is not expected. A concept for a research protocol can be up to 6 pages, and should propose a multi-center study that could benefit from the PHN’s structure. The concept should include a description of the research question and rationale for choosing it, a summary of the population to be included, an estimate of the number of participants required, and a description of how the study proposed would improve in congenital heart disease and pediatric heart disease outcomes.

Note that not all study proposals will be conducted by the PHN. The purpose of the research protocol concept is to stimulate thinking about the important problem of congenital heart disease and pediatric heart disease outcomes while addressing existing unequal clinical outcomes to all studies, and to provide a portfolio of studies that could be prioritized quickly and implemented at the start of the new grant cycle.

2. Population Available for Clinical Studies

The filename "Population Clinical Studies.pdf" should be used and will be reflected in the final image bookmarking for easy access for reviewers.

Provide details for each bullet below about eligible populations for PHN studies. For applicants proposing consortia with more than one site, please include each site's information separately.

• Number of fetal patients seen per year; % of abnormal fetal echocardiograms per year
• Number of surgeries (specify neonatal, infant, childhood, and adult congenital surgeries as week as bypass versus non-bypass cases) per year for the past 5 years
• Number of interventional cardiac catheterizations per year for the past 5 years
• Number of single ventricle patients followed in each of the following age ranges: 0 to 11 years old, 12 to <18 years old, and 18+ years of age
• The racial and ethnic composition of the site’s congenital heart disease population across the lifespan based on standard NIH inclusion categories
• Number of patients seen annually in the site's general outpatient pediatric cardiology clinics
• Number of patients with adult congenital heart disease (ACHD) seen in the site's program. Specify how the ACHD program is integrated into the pediatric cardiology practice
• Number of patients seen annually in the site's outpatient heart failure clinics

3. Clinical Research Capabilities Table

The filename "Capabilities Table.pdf" should be used and will be reflected in the final image bookmarking for easy access for reviewers.

Describe the resources available to conduct clinical trials and studies, and provide a table that demonstrates the site's prior experience with multi-center collaborative clinical research in adult and pediatric congenital heart disease and pediatric acquired heart disease. List all trials and studies conducted at the site over the past 3 years. The table columns should include:

• Column A: name of the study/trial
• Column B: a brief description of the study/trial
• Column C: funding source(s) (NIH, industry, foundation, other)
• Column D: gender, race, and ethnicity of participants enrolled using standard NIH inclusion categories
• Column E: planned total enrollment for the site
• Column F: actual total enrollment at the site

4. Plan for Enhancing Diverse Perspectives (PEDP)

The filename "Plan for Enhancing Diverse Perspectives.pdf" should be used and will be reflected in the final image bookmarking for easy access for reviewers.

All applicants must include a summary of strategies to advance the scientific and technical merit of the proposed project through expanded inclusivity. The PEDP should provide a holistic and integrated view of how enhancing diverse perspectives is viewed and supported throughout the application and can incorporate elements with relevance to any review criteria (significance, investigator(s), innovation, approach, and environment) as appropriate. Where possible, applicant(s) should align their description with these required elements within the research strategy section. The PEDP will vary depending on the scientific aims, expertise required, the environment and performance site(s), as well as how the project aims are structured. The PEDP may be no more than 1-page in length and should include a timeline and milestones for relevant components that will be considered as part of the review. Examples of items that advance inclusivity in research and may be part of the PEDP can include, but are not limited to:

• Discussion of engagement with different types of institutions and organizations (e.g., research-intensive, undergraduate-focused, minority-serving, community-based).
• Description of any planned partnerships that may enhance geographic and regional diversity.
• Plan to enhance recruiting of women and individuals from groups traditionally under-represented in the biomedical, behavioral, and clinical research workforce.
• Proposed monitoring activities to identify and measure PEDP progress benchmarks.
• Plan to utilize the project infrastructure (i.e., research and structure) to support career-enhancing research opportunities for diverse junior, early- and mid-career researchers.
• Description of any training and/or mentoring opportunities available to encourage participation of students, postdoctoral researchers and co-investigators from diverse backgrounds.
• Plan to develop transdisciplinary collaboration(s) that require unique expertise and/or solicit diverse perspectives to address research question(s).
• Publication plan that enumerates planned manuscripts and proposed lead authorship.
• Outreach and planned engagement activities to enhance recruitment of individuals from diverse groups as research participants including those from under-represented backgrounds.

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

Multiple PDs/PIs are encouraged for this application. The PDs/PIs should have expertise leading clinical research in adult and pediatric congenital heart disease and pediatric acquired heart disease.

A team of key personnel should be assembled that, collectively, demonstrates skills in clinical research in this population, data science and data integration across multiple sources, participation in collaborative research efforts, and community engagement.

A full-time clinical research Nurse or Study Coordinator must be designated, with a biographical sketch included as part of the application.

R&R Budget

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

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

Clinical Center awards will be for core infrastructure costs only (see section II: Award Information)

• PD/PI: at least 1.2 person-months (10 percent) effort
• Multiple PD/PI or additional PD/PI support: at least 1.2 person-months (10 percent) effort
• Research or Nurse Coordinator: 12 person-months (100 percent) effort
• Additional Research or Nurse Coordinator or Research Assistant: at least 6 person-months (50 percent) effort
• Travel: In-person Steering Committee meetings are held twice each year. Meetings will take place in Bethesda, MD and Boston, MA and other locations based on geographical distribution of the CRCs. The PD/PI or designee and full-time Research or Nurse Coordinator are required to attend the meetings.

• PEDP implementation costs: Applicants may include allowable costs associated with PEDP implementation (as outlined in the Grants Policy Statement section 7:https://grants.nih.gov/grants/policy/nihgps/html5/section_7/7.1_general.htm).

R&R Subaward Budget

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

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

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

Research Strategy: Applicants must provide a proposal for a research protocol suitable for the PHN, and a description of the center's capabilities in multi-center collaborative research. These should demonstrate detailed knowledge of the conduct of multi-center clinical studies in the field of pediatric and adult congenital heart disease and pediatric acquired heart disease.

NOTE: All applications in response to this specific PHN FOA will use the Delayed Onset record designation as described in the section PHS Human Subjects and Clinical Trials Information, Delayed Onset Study. Applicants must check the Delayed Onset box on the application form. This is inherent in the PHN as sites will be submitting research concepts, but these concepts, if approved by the PHN, will be delayed and also since they are concepts only, they may not be fully defined.

All applicants should address how they plan to be a contributing member of the PHN beyond enrolling participants in studies.

Clinical Research Capabilities

• Using studies in the "Capabilities Table.pdf" (requested above in "Other Attachments") or other recent studies, describe how recruitment and retention challenges have been handled, as described below.
• Describe plans to include both genders, and racial and ethnic minorities as appropriate for the scientific goals of the research within the PHN.
• Provide examples of prior success with engaging a study team having a diverse background and experience.
• Discuss recruitment strategies used for different populations in previous studies, such as use of social media, and collaborations with foundations and patient advocacy groups. Applicants should also describe capabilities for recruiting study participants at night and on weekends.
• Describe how dedicated coordinator staff and other research personnel such as research echo technicians with experience in pediatric and adult cardiovascular studies will be provided.
• Describe experience with FDA-regulated clinical trials.
• If more than one clinical site is proposed, evidence of collaboration among sites on recent trials must be provided. Management plans including supervision, training, in-service, certification, data handling, quality assurance, cost-effective management, and communication are also required for centers with more than one clinical site.
• Describe how complete, accurate and timely transmission of data to the PHN DCC will be accomplished. Describe processes for responses to data entry edits and audits, including suggested timelines for responses.

Clinical Capabilities

• Describe the clinical attributes of the program, including clinical services provided, availability of applicable subspecialists, non-invasive imaging capabilities, exercise laboratory, and neurodevelopmental assessment capabilities.
• Document the availability and capacity of an institutional pharmacy capable of supporting clinical research.

Data Science and Integration Capabilities

• Describe the site's involvement with various cardiovascular databases and registries, and describe their data pipeline infrastructure. Demonstrate how interactions with these databases and registries may be leveraged to facilitate clinical research through the PHN.
• Describe participation in and performance in one or more pediatric cardiovascular or adult congenital heart disease (ACHD) registries/databases or national quality improvement activities. Specify which system and provide a detailed description of variables collected, timeliness of data entry, quality control, and management of the data system.
• Describe efforts at the applicant institution to integrate and standardize data across multiple data sources to create resources for research. Data integration efforts may be intra-institutional and/or inter-institutional.
• Provide a plan to develop and maintain extraction, transformation and loading (ETL) procedures to link various and/or disparate clinical data sources into a common location (server, institutional cloud, etc.).
• Describe how the site maintains data quality, including approaches to investigating and aiding in remediation of data abnormalities; processes for fixing issues with ETL procedures; and investigating causes of failed investigative data checks. Provide the plan for resolving investigative check errors that are not caused by source data constraints.
• Describe the institutional technical and personnel capabilities exist at the site to support data integration efforts.
• Describe site compliance with applicable laws, regulations, and legal requirements, including but not limited to those governing privacy, security, data, research, and human subjects.

Special Strengths

• Applicants are encouraged to describe special or unique strengths that may be relevant to PHN research. This can include state-of-the art scientific or technical capabilities, or unique personnel resources that could be brought to bear to develop the scientific productivity of the PHN.

Consortium/Contractual Arrangements: Applicants can propose consortia of two or more sites. For sites with more than one CRC, collaboration and interaction among institutions should be clearly documented in the application, including the investigator responsible at the collaborating site(s). Management plans including supervision, training, certification, data handling, quality assurance, cost effective management, and communication are required for centers with more than one clinical site. Consortia should also describe the combined racial and ethnic demographics of patients who may be eligible for research studies at each site and collectively.

Letters of Support: Letters of institutional and departmental support for participation in the PHN are requested, which should include assurances that in the case of studies competing for the same patient population, NHLBI-funded studies will take priority. Applicants should confirm their willingness to accept fee-for-service (capitated) reimbursement from the DCC for patient care costs as approved by the Executive Committee and NHLBI for each protocol.

Applications from institutions that have a CTSA funded by NIH should include a letter of support from either the CTSA Program Director or PD/PI.

The following modifications also apply:

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

Other Plan(s):

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages.

• 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.

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

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

Foreign Institutions

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

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

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

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

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

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

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

5. Intergovernmental Review (E.O. 12372)

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.

• Awards issued under this FOA will be incrementally funded for up to 7 years. These will not be Multi-Year Funded.
• Awards issued under this FOA will be excluded from automatic carryover. All carryover actions will require NHLBI prior approval.
• Awards issued under this FOA will not be provided the authority to automatically extend the final budget period. All extensions, including the first, will require NHLBI prior approval.
• Awards issued under this FOA will be excluded from SNAP.

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

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

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

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential fieldof 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 FOA 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 SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

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

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.

Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) will not be evaluated at time of review.

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

Overall Impact

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

Scored Review Criteria

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

Significance

Edit to read as follows Does the proposed Clinical Research Center (CRC) address the needs of the research network that it will serve? Is the scope of the activities proposed for the Clinical Research Center (CRC) appropriate to meet those needs? Will successful completion of the aims bring unique advantages or capabilities to the research network?

In addition, for applications involving clinical trials

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

Specific to this FOA

How strongly does the application demonstrate that the CRC will be able to contribute successfully to the research conducted by the PHN? Does the research protocol concept, if conducted, have the potential to contribute to improved outcomes, advance equity, and change clinical practice?

To what extent do the efforts described in the Plan for Enhancing Diverse Perspectives further the significance of the project?

Investigator(s)

Are the PD(s)/PI(s) and other personnel well suited to their roles in the CRC? Do they have appropriate experience and training, and have they demonstrated experience and an ongoing record of accomplishments in managing multicenter collaborative clinical research? Do the investigators demonstrate significant experience with coordinating collaborative clinical research? If the Center is multi-PD/PI, do the investigators have complementary and integrated expertise and skills; is their organizational structure appropriate for the CRC? Does the applicant have experience overseeing selection and management of subawards, if needed?

In addition, for applications involving clinical trials

With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

Specific to this FOA

What experience do the PDs/PIs have in multi-center research that makes the site likely to succeed in the PHN? How well does the application demonstrate that the CRC has the expertise to recruit and retain a population that permits evaluation of differences by sex/gender, race and/or ethnicity (Public Health Service Act sec. 492B, 42 U.S.C. sec. 289a-2) for the heart diseases under study? How strong is the applicant's prior experience with multi-center collaborative clinical research in adult and pediatric acquired heart disease? Does the application demonstrate that the CRC and its research team will be able to achieve the goals of the PHN, including having a research team with diverse backgrounds and experiences, data science, environmental health, and data integration goals? To what extent does the application demonstrate an adequate track record of conducting multi-center clinical research and in managing multi-disciplinary research teams? How likely is it that the proposed research team will be disposed to work as part of the PHN, with the DCC and with the NHLBI Project Scientists? Does the applicant describe adequate involvement of a full-time Research or Nurse Coordinator?

To what extent will the efforts described in the Plan for Enhancing Diverse Perspectives strengthen and enhance the expertise required for the project?

Innovation

Does the application propose novel organizational concepts, management strategies, or instrumentation in coordinating the research network the CRC will serve? Are the concepts, strategies, or instrumentation novel to one type of research program or applicable in a broad sense? Is a refinement, improvement, or new application of organizational concepts, management strategies or instrumentation proposed?

In addition, for applications involving clinical trials

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

Specific to this FOA

To what extent does the proposed Research Protocol Concept have the potential to be an innovative approach to addressing inequity in congenital heart disease outcomes?

How strong is the evidence that the proposed strategies in the application offer state-of-the art scientific capabilities that could develop and expand the scientific productivity and impact of the PHN? How likely is it that the proposed strategies will be novel enough to challenge and shift current research or clinical practice paradigms by using novel concepts, approaches or methodologies, or interventions?

To what extent will the efforts described in the Plan for Enhancing Diverse Perspectives meaningfully contribute to innovation?

Approach

Are the overall strategy, operational plan, and organizational structure well-reasoned and appropriate to accomplish the goals of the research network the CRC will serve? Will the investigators promote strategies to ensure a robust and unbiased scientific approach across the network, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the network is in the early stages of operation, does the proposed strategy adequately establish feasibility and manage the risks associated with the activities of the network? Are an appropriate plan for work-flow and a well-established timeline proposed? Have the investigators presented adequate plans to ensure consideration of relevant biological variables, such as sex, for studies of vertebrate animals or human subjects?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

In addition, for applications involving clinical trials

Does the application adequately address the following, if applicable

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

Specific to this FOA

Recognizing that the Research Protocol Concept is not a full protocol, does the approach outlined include an aim to address inequity in congenital heart disease outcomes?

How strongly does the application demonstrate that the CRC has the appropriate processes in place to recruit and retain a diverse population for PHN studies? Are plans described to include eligible populations for both genders, minorities, and their subgroups across the lifespan, appropriate for the goals of the PHN? How adequate are the described plans for recruitment and retention of participants?

How thoroughly does the applicant discuss previous successes and challenges in recruiting the patient population? Does the CRC have data systems that would allow it to integrate data across multiple data sources for research purposes? How well-suited are the applicant's approaches to data integration?

Are the outreach activities and project prioritization plan likely to ensure a highly qualified and diverse user pool? Are the timeline and milestones associated with the Plan for Enhancing Diverse Perspectives well-developed and feasible?

Environment

Will the institutional environment in which the CRC will operate contribute to the probability of success in facilitating the research network it serves? Are the institutional support, equipment and other physical resources available to the investigators adequate for the CRC proposed? Will the CRC benefit from unique features of the institutional environment, infrastructure, or personnel? Are resources available within the scientific environment to support electronic information handling?

In addition, for applications involving clinical trials

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

Specific to this FOA

Does the application demonstrate adequate institutional resources and multi-disciplinary expertise to successfully carry out PHN research protocols? How well does the application demonstrate adequate institutional resources and multi-disciplinary expertise to successfully carry out PHN research protocols? Does the CRC demonstrate that it has the administrative and clinical resources necessary to meet those needs? Which attributes demonstrate that the CRC has an adequate research pharmacy? How likely is it that the CRC (or consortium) will be able to recruit the targeted heart disease patient population such that evaluation of differences by sex/gender, race and/or ethnicity can be achieved? Does the application demonstrate adequate institutional resources and expertise to facilitate data integration across multiple registries and other databases?

To what extent will features of the environment described in the Plan for Enhancing Diverse Perspectives (e.g., collaborative arrangements, geographic diversity, institutional support) contribute to the success of the project?

Additional Review Criteria

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.

Study Timeline

Specific to applications involving clinical trials

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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

Vertebrate Animals

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

Biohazards

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

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

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

Applications from Foreign Organizations

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

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

Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) will not be evaluated at time of review.

Reviewers will comment on whether the Resource Sharing Plan(s) (i.e., Sharing Model Organisms) or the rationale for not sharing the resources, is reasonable.

Authentication of Key Biological and/or Chemical Resources:

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

Budget and Period of Support

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

2. Review and Selection Process

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

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Heart, Lung and Blood 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.

3. Anticipated Announcement and Award Dates

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

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

Section VI. Award Administration Information

1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

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

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

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

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain applicable clinical trials on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that all 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.

Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:

• Federalwide Research Terms and Conditions
• Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
• Acknowledgment of Federal Funding

If a recipient is successful and receives a Notice of Award, 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.

Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS will be required to complete an HHS Assurance of Compliance form (HHS 690) in which the recipient agrees, as a term and condition of receiving the grant, to administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, age, sex and disability, and agreeing to comply with federal conscience laws, where applicable. This includes ensuring that entities take meaningful steps to provide meaningful access to persons with limited English proficiency; and ensuring effective communication with persons with disabilities. Where applicable, Title XI and Section 1557 prohibit discrimination on the basis of sexual orientation, and gender identity. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html

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

• Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov.

• For information on an institution’s specific legal obligations for serving qualified individuals with disabilities, including providing program access, reasonable modifications, and to provide effective communication, see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html.

• HHS funded health and education programs must be administered in an environment free of sexual harassment, see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.

• For guidance on administering programs in compliance with applicable federal religious nondiscrimination laws and applicable federal conscience protection and associated anti-discrimination laws see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.

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

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

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS grant administration regulations at 45 CFR Part 75 and other HHS, PHS, and NIH grant administration policies.

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

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

Participation in and oversight of all aspects of PHN studies, including proposing protocols, participating in their overall development, preparing protocol budgets in collaboration with the DCC, modifying proposals if indicated, recruiting study participants, conducting the research, assuring the quality of study participant care and protocol adherence, assuring the accurate and timely transmission of data collected in conjunction with the DCC, analyzing and interpreting data, preparing publications, and working with the DCC and NHLBI to disseminate research findings.

Ensuring that study results are disseminated in accordance with PHN policies.

Providing input into PHN activities including the PHN’s programs for early-stage investigators and other PHN committees.

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

NIH Project Scientists will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below.

The NHLBI Project Scientists will assist with development of research protocols, monitor patient recruitment and study progress, ensure disclosure of conflicts of interest, and ensure adherence to NHLBI policies. NHLBI is responsible for appointments to the PHN’s standing DSMB.

The NHLBI Project Scientists will serve on the Executive and Steering Committee and other study committees, when appropriate, and will have one collective vote. The NHLBI Project Scientists will work with awardees on issues coming before the Steering Committee such as recruitment, protocol development, follow-up, quality control, adherence to protocol, possible changes to the protocol, interim data and safety monitoring, final data analysis and interpretation, preparation of publications, and development of solutions to major problems.

In addition to the Project Scientist, a separate NHLBI Program Official will be responsible for the normal program stewardship of the cooperative agreement, and will be named in the Notice of Award. 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.

The NHLBI reserves the right to phase-out or curtail the study (or an individual award) in the event of (a) failure to develop or implement mutually agreeable collaborative protocols; (b) substantial shortfall in participant recruitment, follow-up, data reporting, or quality control; (c) major breach of the protocols or substantive changes in the agreed-upon protocols with which NHLBI cannot concur; (d) attaining of a major study endpoint before schedule with persuasive statistical significance; or (e) human subject ethical issues that may dictate a premature termination.

Areas of Joint Responsibility include:

Governance of the PHN through the Executive Committee. This Committee has primary responsibility for identification of priority areas for research, management of the PHN’s policies and procedures, oversight of the PHN budget, and general PHN operations. Executive Committee membership consists of all Principal Investigators, the chairs of select PHN Committees, a Study Coordinator, and the NHLBI Project Scientists. Each member has one vote; the NHLBI staff has one collective vote.

Negotiation of mutually agreed upon performance and accrual milestones during the development of each clinical research protocol.

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 regulations 42 CFR Part 50, Subpart D and HHS regulations 45 CFR Part 16.

3. Data Management and Sharing

Note: The NIH Policy for Data Management and Sharing is effective for due dates on or after January 25, 2023.

Consistent with the 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.

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. NIH FOAs 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 45 CFR Part 75.301 and 2 CFR Part 200.301.

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

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

Section VII. Agency Contacts

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

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: GrantsInfo@nih.gov (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: support@grants.gov

D'Andrea Egerson, RN, MSN
National Heart, Blood, and Lung Institute (NHLBI)
Telephone: 301-443-7045
Email: dandrea.egerson@nih.gov

Gail Pearson, MD, ScD
National Heart, Blood, and Lung Institute (NHLBI)
Telephone: 301-435-0477
gail.pearson@nih.gov

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

Kristen Williams
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-827-5513
Email: kristen.williams@nih.gov

Section VIII. Other Information

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

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.