Required Application Instructions

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

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

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

The purpose of this FOA is to invite applications to participate as a Clinical Research Center in the Pediatric Heart Network (PHN), whose mission it is to improve the health of children and adults with structural congenital heart defects, as well as children with acquired heart disease through multi-center clinical research.

Congenital cardiac malformations affect about 1% of live births and are the primary cause of death due to a birth defect under age 1. 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.

NHLBI established the PHN as a research enterprise in 2001, and it now anchors the clinical end of the Bench to Bassinet program's translational spectrum. The PHN has established best practices for multi-center research in pediatric cardiology and has completed 14 studies with 4 ongoing and an additional 3 nearing launch. There are multiple clinical trials and studies active at all times. In addition to performing observational studies and clinical trials, the PHN has supported nursing, health services, and quality improvement research and oversees a robust program of clinical research mentoring. Ongoing and previous study details can be found at www.PediatricHeartNetwork.org

The PHN's emphasis will continue to be on research that is based on the most important problems facing affected children and adults. During this funding cycle, the PHN will be transitioned from a classic research network model into a flexible platform upon which studies funded by a variety of sources can be conducted. In the new paradigm, the PHN will retain its infrastructure consisting of a Data Coordinating Center (DCC) and up to nine Clinical Research Centers. The PHN FOAs will support this infrastructure for seven years, as well as up to three PHN-initiated trials or studies. Additional studies and trials will be funded through investigator-initiated R01s, industry, and/or foundation grants. Protocol topic areas will be decided cooperatively by the PHN Steering and Executive Committees. Clinical Research Centers selected to join the PHN should be prepared to participate in ongoing protocols. New protocols will be decided cooperatively by the PHN Executive and Steering Committees. A Data Safety and Monitoring Board reviews all protocols before initiation and also advises NHLBI on research design issues, data quality and analysis, and ethical and human subject protection matters.

The objective of this FOA is to identify Clinical Research Centers that, through rigorous patient evaluation using common protocols, can enroll and study the required numbers of patients and provide answers more rapidly than individual centers acting alone, with the goal of providing evidence that guides clinical practice in congenital heart disease and pediatric acquired heart disease.

In particular, this FOA seeks applications from Clinical Research Centers 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.
• Identify, enroll and retain participants in multi-center cardiovascular clinical studies.
• Have sufficient numbers of patients available for potential study enrollment.
• Effectively and efficiently manage all Clinical Center 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.

The PHN is a cooperative Network of up to nine Clinical Research Centers, a DCC, and the NHLBI. The DCC is supported by a separate award, described in detail in RFA-HL-17-005. Clinical Research Centers are responsible for proposing, developing, and refining protocols; identifying, recruiting and retaining study subjects; entering data promptly and accurately into the web-based data collection system; contributing to manuscripts and otherwise disseminating research findings; and contributing to PHN governance through committee participation. All individual Clinical Research Centers should be prepared to participate in a cooperative and interactive manner with one another, the NHLBI, and the DCC.

The Executive Committee is the main governing body of the PHN and will be composed of the PDs/PIs of the Clinical Research Centers and the DCC, the PHN Network Chair, and the NHLBI Project Scientists.

The Steering Committee consists of all PHN investigators from the Clinical Research Centers and the DCC, NHLBI staff, and the PHN Network Chair. The Network Chair is named by NHLBI to oversee and guide Executive and Steering Committee activities. 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.

The DCC supports protocol development; provides sample size calculations, statistical advice, and data analysis; supports manuscript preparation; and provides overall study coordination, and quality assurance, including coordination of the activities of the Data and Safety Monitoring Board (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 Clinical Research Centers 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 Clinical Research Centers, the DCC, and the NHLBI. Committees may include protocol development committees, a publications committee, a finance committee, a core lab committee, an ancillary studies committee, and other committees that may be needed to support PHN activities.

NHLBI is responsible for organizing and providing overall 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 partner, consistent with the Cooperative Agreement mechanism.

A Data Safety and Monitoring Board (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.

As per the intent of the NHLBI in supporting the PHN, multiple trials will be conducted during the project period. Once the Clinical Research Centers are convened in the new funding cycle, the PHN Executive and Steering Committees will consider proposed protocols and prioritize them along with other research ideas. It is anticipated that each protocol will be implemented in all of the Clinical Research Centers. As specific protocols are developed, support will depend on the availability of funds, and per-patient funding made available. All the Clinical Research Centers must be willing to pursue this funding arrangement for each new protocol conducted. Clinical protocols must be approved by local IRBs, and Clinical Research Centers will be supported in this effort by the PHN DCC. The exact 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 for prioritization and implementation.

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

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

Non-domestic (non-U.S.) Entities but only if based in Canada

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply but only if they are based in Canada.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply except for Canadian components.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

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

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

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

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

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

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

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

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

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

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

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

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

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

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

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

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 should include sources of research support through Clinical and Translational Science Awards (CTSAs), departments, institutions, etc. Applications from institutions that have a CTSA funded by NIH should identify the resources that could be available to support the proposed Clinical Center, commenting particularly on those aspects that will enhance their programmatic and scientific efficiency. 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, applicants with additional research support for clinical studies or projects are of special interest.

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

1. 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.

Please provide details for each bullet below about eligible populations for PHN studies. Large eligible populations with low trial enrollment numbers are considered less desirable than smaller populations with higher enrollment rates. For applicants proposing consortia with more than one site, please include each site's information separately.

• # of fetal patients seen per year; % of abnormal fetal echos per year;
• # of surgeries (specify neonatal versus adult congenital surgeries and bypass versus non-bypass cases) per year for the past 5 years;
• # 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.
• 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;
• Number of patients seen annually in the site's outpatient pediatric preventive cardiology clinics;

2. Clinical Research Capabilities

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

Applicants should 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 by listing 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 and/or foundation/other)
• Column D: time from initiation to completion of contracting process
• Column E: time from protocol receipt by the trial PD/PI (or time protocol finalized if local trial) to IRB approval
• Column F: time from IRB approval to first patient enrolled
• Column G: planned monthly enrollment for the site
• Column H: actual monthly enrollment at the site.

All instructions in the SF424 (R&R) Application Guide must be followed. Multiple PDs/PIs are encouraged for this application. The PDs/PIs may be individuals with expertise in adult and pediatric congenital heart disease and pediatric acquired heart disease and should describe their clinical, research, administrative and academic commitments in the Biosketches.

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

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 and may not exceed $220,000 in direct costs per year.

• 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: Up to 8 trips per Network team, as appropriate. In-person Steering Committee meetings are held twice each year. Meetings will take place in Bethesda, MD and other locations based on geographical distribution of the Clinical Research Centers. The PD/PI or designee and full-time Research or Nurse Coordinator are required to attend the meetings in their entirety.

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 description of the center's capabilities in multi-center collaborative research. This 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.

Applicants that are not currently a PHN Clinical Center also should address how they plan to be a contributing member of the PHN.

Clinical Research Capabilities

• Using studies in the "Clinical Research Capabilities.pdf" (requested above in "Other Attachments") or other recent studies, applicants should describe how they handled up to five trials/studies that struggled with recruitment and/or retention of subjects and up to five that succeeded and discuss key challenges, successes, and lessons learned.
• Applicants should describe plans to include both genders, and racial and ethnic minorities as appropriate for the scientific goals of the research within the PHN.
• Applicants should discuss how they will go about recruiting various types of populations into trials/studies, i.e. use of social media, patient engagement, collaboration with foundations and patient advocacy groups.
• Applicants should demonstrate that the site can provide dedicated coordinator staff and other research personnel such as research echo technicians with experience in pediatric and adult cardiovascular trials.
• Applicants should describe their site's ability to de-identify echocardiograms and other non-invasive imaging studies locally prior to sending them to a core lab.
• Centers with more than one clinical site must provide evidence of collaboration among sites on recent trials. 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.
• Capabilities for patient recruitment on nights and weekends must be described in the application.
• Applicants should describe their site's ability to engage in a central IRB model.
• Applications must provide complete, accurate and timely transmission of data to the PHN DCC. Applicants should describe their processes for responses to data entry edits and audits, including suggested timelines for responses.

Clinical Capabilities

• Applicants should provide a detailed description of the clinical attributes of the program, including clinical services provided, availability of applicable subspecialists, non-invasive imaging capabilities, exercise laboratory, and neurodevelopmental assessment capabilities.
• The availability and capacity of an institutional pharmacy capable of supporting clinical research must be also documented.

Data Integration Capabilities

• The applicant should describe the site's involvement with various cardiovascular databases and registries. Applicants should demonstrate how their interactions with these databases and registries may be leveraged to facilitate clinical research through the PHN.
• Applicants should describe their participation in one or more pediatric cardiovascular or ACHD registries/databases or national quality improvement activities - specify which system and provide a detailed description of variables collected, quality control, and management of the data system.
• Applicants should describe efforts at their institution to integrate data across multiple data sources to create resources for research. Data integration efforts may be intra-institutional and/or inter-institutional.
• Applicants should describe what institutional technical and personnel capabilities exist at their site to support data integration efforts.
• Applicants should provide an illustrative use case for how an integrated data resource can support a clinical research study.

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 capabilities that may be shared or may be available and that may develop and expand the scientific productivity of the PHN.
• Special administrative strengths or experience and participation in administrative aspects of clinical research (e.g., IRBs, data and safety monitoring committees, advisory board for clinical research, clinical research committees) should be highlighted.

Consortium/Contractual Arrangements: Applicants can propose consortia of two or more sites. For sites with more than one Clinical Research Center, 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.

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 discuss their willingness, and that of their institutions involved, to accept fee for service 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 agreement from either the CTSA Program Director or PD/PI .

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

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

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide. All applicants should describe their plan to provide a link to the Pediatric Heart Network and the Children and Clinical Studies websites at their respective institutions.

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

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

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.

See Part I. Section III.1 for information regarding the requirements for obtaining a Dun and Bradstreet Universal Numbering System (DUNS) Number and for completing and maintaining an active System for Award Management (SAM) registration. Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission.

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

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

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

This initiative is not subject to intergovernmental review.

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

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

Specific to this FOA:

• Awards issues 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 Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

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

See more tips for avoiding common errors.

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

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

Important Update: See NOT-OD-16-006 and NOT-OD-16-011 for updated review language for applications for due dates on or after January 25, 2016.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

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

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

How strongly does the application demonstrate that the Clinical Research Center will be able to promote the field of pediatric congenital heart disease and pediatric acquired heart disease?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project? What experience do the PDs/PIs have in multi-center research that makes the site likely to succeed in the Network? How well does the application demonstrate that the Clinical Research Center has the expertise to recruit and retain the population 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 Clinical Research Center and its research team will be able to achieve the goals of the PHN? Do the PDs/PIs demonstrate an adequate track record of conducting multi-center clinical research and in managing multi-disciplinary research teams? Does the research team express willingness 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?

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed? Does the application include state-of-the art scientific capabilities that may develop and expand the scientific productivity of the PHN?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? How strongly does the application demonstrate that the Clinical Research Center has the appropriate processes in place to recruit and retain the population under study? How thoroughly does the applicant discuss previous successes and challenges in recruiting the patient population? Has the applicant proposed adequate plans to participate in a central IRB model? Does the application describe the site's ability to de-identify imaging studies locally prior to submission to a core? Does the Clinical Research Center have data systems that would allow it to integrate data across multiple data sources for research purposes? What is the quality of the applicant's approaches to data integration?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed? Are plans described to include eligible populations for both genders, minorities and their subgroups, and children appropriate for the goals of the PHN? Have plans for recruitment and retention of subjects been adequately described?

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements? Does the Clinical Research Center have the research capabilities to fully participate in the activities of the PHN? Does the application demonstrate adequate institutional resources and multi-disciplinary expertise to successfully carry out the research protocols? Does the Clinical Research Center demonstrate that it has the administrative and clinical resources necessary to meet those needs? Does the applicant describe adequate clinical attributes of the center and availability of a research pharmacy? Does the applicant demonstrate that adequate patient populations exist at the clinical center for PHN studies? Does the application demonstrate adequate institutional resources and expertise to facilitate data integration across multiple registries and other databases?

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.

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

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

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

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

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.

Not Applicable

Not Applicable

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.

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.

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).

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

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

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the NHLBI, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
• Will receive a written critique.

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

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications 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.

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons.

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

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

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

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

Any application awarded in response to this FOA will be subject to 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.

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable 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:

The Clinical Center PD(s)/PI(s)will have the primary responsibility in 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. Clinical Center PDs/PIs will also be responsible for working with the DCC to develop common definitions and standardization across protocols wherever appropriate. Awardees must agree to the governance of the study through a Steering Committee. Investigators will be required to project patient enrollment for a specific protocol during a specified time frame; continuation and level of funding will be based on actual recruitment.

Support or other involvement of industry or any other third party in the study,--e.g. participation by the third party; involvement of study resources or citing the name of the study or NHLBI support, or special access to study results, data, findings or resources may be advantageous and appropriate. However, except for licensing of patents or copyrights, support or involvement of any third party will occur only following notification of and concurrence by NHLBI.

Study PDs/PIs are encouraged to publish and disseminate results and other products of the study in accordance with study protocols and governance. For applicable studies, data not previously released and other study materials or products not previously distributed are to be made available to individuals who are not study investigators, within three years of the end of the period of NHLBI support, provided such release is consistent with the study protocol and governance. Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.

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 will appoint the Protocol Chair and the Data and Safety Monitoring Board (DSMB). The Protocol Chair will be responsible for ensuring that there are well-documented policies, procedures, and bylaws to guide all aspects of Network activities and operations.

The NHLBI Project Scientists will serve on the Steering Committee and other study committees, when appropriate, and will have one vote. The NHLBI Project Scientists may 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 such as insufficient participant enrollment.

In addition to the Project Scientist, a separate NHLBI Program Official will be responsible for the normal program stewardship of the cooperative agreement, and will be in the Notice of Award. However, NHLBI may elect to have a dual-role approach where a single individual may act as the NHLBI Project Scientist and Project Officer. Final decision-making authority on matters of budgetary and funding actions, grants management actions, and management of intellectual property issues is assigned to NHLBI staff other than the Project Scientist. The responsibility for final decision making may reside with Senior Institute management, separate organizational components and/or oversight committees. Because it is anticipated that the Project Scientist/Program Official will participate in activities that rise to a level of involvement that results in conflicts of interest, for example, co-publication, other staff members such as direct line supervisors and/or other Senior NHLBI Program management staff will serve as agency Program Officials and will be responsible for the normal scientific and programmatic stewardship of the award.

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:
Awardee(s) agree to the governance of the study through a Steering Committee. The Steering Committee will have primary responsibility for identification of priority areas for research, the conduct of protocols, data analysis and the preparation of publications and dissemination products. Steering Committee voting membership shall consist of all Principal Investigators (i.e., cooperative agreement awardees), one NHLBI Project Scientist, and the Protocol Chair. Each full member will have one vote. Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.

Awardee(s) agree to collaboratively develop achievable/feasible agreed-upon metrics to evaluate the overall success of the PHN on an annual basis. Metrics should include stakeholder feedback and modifications to enhance the efficiency and scientific rigor of the program.

Awardee(s) agree to negotiate mutually agreed upon milestones during the development of each clinical research protocol and may include such things as time to IRB approval, time to subcontract finalization, first patient screened, first patient enrolled, etc.

A DSMB will be appointed by the Director, NHLBI to provide overall monitoring of interim data and safety issues. An NHLBI scientist, other than the NHLBI Project Scientist, shall serve as Executive Secretary to the Boards. Because the Boards serve as independent groups advisory to the NHLBI, study investigators will not communicate with Board members regarding study issues, except as authorized by the Board’s Executive Secretary.

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.

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

A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

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

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

eRA Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

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

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-710-0267

Victoria Pemberton, RNC, MS, CCRC
National Heart, Blood, and Lung Institute (NHLBI)
Telephone: 301-435-0510
Email: Pembertonv@mail.nih.gov

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

Lauren Ruane
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0166
Email: lauren.ruane@nih.gov

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.