It is critical that applicants follow 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 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

Purpose

The objective of this FOA is to develop Phase 2 clinical trials to 1) Test strategies that will lead to increased use of cardiovascular rehabilitation (CR) and pulmonary rehabilitation (PR) in the U.S. population who are eligible based on clinical guidelines; 2) Test strategies that will lead to reduced disparities in the use of CR and PR based on age, gender, race/ethnicity, and socioeconomic status (SES); and 3) Test whether increased use of PR or CR, whether traditional center-based CR/PR or new models, is accompanied by improvements in relevant clinical and patient-centered outcomes, including exercise capacity, cardiovascular and pulmonary risk factors, and quality of life (QOL). This FOA addresses one of the compelling questions under Objective 4 of the NHLBI Strategic Vision: Which patients benefit from rehabilitation treatments (e.g., cardiac, vascular, and pulmonary), and how can the benefits of rehabilitation be sustained long-term".

Background and Objectives

Each year, nearly two million Americans have a coronary event or revascularization procedure, and millions more have a chronic cardiac condition for which CR is recommended (Class 1A). Cardiac rehabilitation is recommended after acute myocardial infarction, percutaneous coronary intervention, coronary artery bypass surgery, valvular heart surgery, chronic stable angina, and chronic stable heart failure. A substantial body of evidence demonstrates the benefits of CR, including a reduction in cardiovascular morbidity and mortality and improved quality of life (QOL) and functional status. Recent studies have shown that CR participation resulted in a 25-30% reduction in hospital readmissions and a similar decrease in cardiovascular deaths. However, less than 20% of eligible patients participate in CR.

Traditional CR for cardiac disease consists of an individualized treatment plan of 36 one-hour sessions of physician prescribed exercise, cardiovascular risk factor modification via education, counseling and behavioral intervention, and psychosocial assessment, typically delivered at a hospital-based outpatient facility over 12 weeks. Similar benefits for supervised exercise therapy (SET) in relieving symptoms of peripheral artery disease (PAD) have been demonstrated, leading to class IA recommendation in clinical guidelines and recent insurance coverage.

In 2010 there were 1.5 million emergency department (ED) visits and 700,000 hospitalizations in the U.S. for chronic obstructive pulmonary disease (COPD). Many of these patients qualify for pulmonary rehabilitation (PR), but only approximately 4% of those qualifying have used it. Pulmonary rehabilitation is a multi-disciplinary intervention for symptomatic patients with chronic respiratory diseases who often have decreased daily life activities and poor QOL; PR aims to reduce symptoms, decrease disability, increase participation in physical and social activities, and improve QOL for these patients. Although PR has not demonstrated a survival benefit to date, clinical trials of PR have shown a reduction in hospitalizations and emergency department or physician office visits as well as improvement in exercise capacity and QOL. Other data suggest that PR may shorten COPD exacerbations. Comprehensive PR programs generally have four major components: exercise training, education, a psychosocial/behavioral intervention, and an outcomes assessment using an individualized treatment plan. Medicare will normally pay for 36 sessions of PR per lifetime, but may pay up to 72 sessions if a clinician documents that extended PR services are medically necessary.

Despite these clear benefits on clinical and patient-centered outcomes, both CR and PR remain severely underutilized. Participation is especially low in the groups that are at highest risk for morbidity and mortality, including the elderly, sicker patients, women, minorities, and persons of lower socioeconomic status (SES). There are multiple contributors to low CR and PR participation rates. These include lack of referral or strong recommendation from a physician, inadequate follow-up or facilitation of enrollment after referral, limited or no health insurance coverage, conflicting work and home responsibilities, distance and transportation problems, lack of gender and racial diversity among CR/PR staff, language and cultural barriers, and lack of program availability and access. Newer delivery models for health care such as telemedicine and delivery of treatment in non-healthcare settings (e.g., home, community center) offer opportunities to address some of these patient and provider barriers and lower costs to facilitate participation in CR and PR.

Program Structure

This FOA is intended to support Phase 2 single site clinical trials to increase the use of CR or PR in traditional and community settings. The FOA will utilize a biphasic, milestone-driven R61/R33 mechanism consisting of an initial phase (R61) and a full enrollment and clinical trial execution phase (R33). Applicants are expected to address objectives for both an R61 and an R33 phase and are strongly encouraged to use project management principles as appropriate.

Selected Research Examples

NHLBI will support research aimed at increased use of CR and PR in the U.S. population. Examples of research include, but are not limited to the following:

• A Phase 2 randomized controlled trial (RCT) of PR or CR in the home or community center delivered by community health workers to older women patients, compared with a traditional hospital-based program, examining impact on adherence, physical fitness and risk factors.
  
  
• A similar RCT to that noted above, but with a focus in low SES minority patients, with attention to the patients native languages and culture (e.g., dietary preferences, beliefs about health, lifestyle, stress).
• A RCT evaluating the impact of CR or PR programs on rates of participation and adherence among other under-represented populations.
  
• A RCT comparing telemedicine-based home CR or PR to a traditional hospital-based program on adherence, measures of physical fitness, risk factors, and costs.
  
  
• A RCT comparing CR or PR participation and completion in a hybrid CR or PR program that combines home and hospital-based sessions with a traditional hospital-based program.
  
  
• A RCT evaluating a traditional versus novel approach for implementing SET for treatment of symptomatic PAD.
• A RCT to evaluate the effectiveness of shared decision-making between physicians and patients in increasing referral to and participation in CR and/or PR programs.
  
  
• A RCT testing electronic health record-based tools to facilitate patient referral to and participation in CR or PR programs.
  
  

Milestones

Delineation of milestones by the applicant for the R61 and R33 phases is a key characteristic of this FOA. A milestone is defined as a scheduled event in the project timeline that signifies the completion of a major project stage or activity. This FOA will support applications that propose a series of milestones, including expected enrollment goals in the R61 and R33 phases, and for accomplishing the completion of the clinical trial on-time and on-budget. Projects that incorporate contingency plans to proactively confront potential delays or disturbances in meeting the milestones are strongly encouraged. Satisfactory completion of R61 milestones will be assessed administratively by NHLBI to determine eligibility to transition to the R33 phase.

NHLBI policies regarding milestones and relevant clinical research/studies policies are described in NHLBI Accrual of Human Subjects (Milestones) Policy, NHLBI Policy for Inclusion of Women and Minorities in Clinical Research, and NHLBI Policy for Data and Safety Monitoring of Extramural Clinical Studies.

Clinical Trials Not Supported by this FOA

The following types of clinical trials are not responsive to this FOA and will not proceed to review:

• Phase I (first-in-human) trials
• Observational studies that do not meet the NIH definition of a clinical trial
• Multi-site trials
• Drug or device safety trials

Investigator Meetings

The Program Director/Principal Investigator(s) (PD/PIs) for each award will meet annually in the Bethesda, MD area to present updates on their research progress and discoveries, exchange scientific knowledge, and discuss potential collaborations. The agenda for the meetings will be determined by the Steering Committee composed of the PD/PIs and the NHLBI Program Directors. In addition to the annual meeting, investigators are expected to communicate with NHLBI Program staff through regularly scheduled teleconferences.

Specific Areas of Research Interest

Prior to submission of an application in response to this FOA, applicants are strongly encouraged to consult with the Scientific/Research contact(s). Early contact (at least 12 weeks prior to submission) is encouraged, as this provides an opportunity for NHLBI staff to provide information and guidance to a potential applicant.

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

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

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

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

Other

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

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

Buttons to access the online ASSIST system or to download application forms 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.

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

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

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

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

The letter of intent should be sent to:

Director, Office of Scientific Review
Division of Extramural Research Activities
National Heart, Lung, and Blood Institute
Telephone: 301-435-0270
Email: [email protected]

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

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

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

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

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

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

The application should propose a multidisciplinary team with the necessary expertise to design and implement the proposed clinical trial. Team members should include scientists, clinicians, and stakeholders whose members have demonstrated experience and expertise in CR and/or PR, and implementation science. Evidence of successful investigative collaborations or partnerships with the organizations and/or systems proposed in the application should be provided.

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

The R61 and R33 cannot be funded in the same fiscal year. For each budget year provide a justification indicating whether costs are for the R61 or R33 phase.

The application must provide detailed, annual budgets that will enable the trial to meet its milestones. If applicable, budgets should include all costs associated with DSMB activities, including preparing reports for the Data and Safety Monitoring Board (DSMB), meeting reimbursement for DSMB members, and support for at least one DSMB meeting per year. Applicants should assess the need for liability insurance for DSMB members and provide a plan commensurate with the risk of the trial. The budget should include provision for executing the plan proposed. Include a plan for assessing DSMB member conflict of interest, and put associated costs in the budget.

The budget should include provisions for the PD/PI of each award to meet annually in the Bethesda, MD area to present updates on their research progress and discoveries, exchange scientific knowledge, and discuss potential collaborations.

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:

Specific Aims: Describe and clearly demarcate the specific aims for both the R61 and the R33 phases. Describe how collaborators and stakeholders will be engaged in the program.

Research Strategy:

The following must be addressed in the research strategy:

Design a Phase 2 clinical trial to test novel strategies to increase participation and completion of PR or CR. The proposed clinical trial should address providers, patients, and health care delivery systems that serve populations that are eligible/candidates for CR or PR. The clinical trial should target key barriers at the provider, patient, and health care system level that impede utilization of cardiac or pulmonary rehabilitation in eligible patients. The proposed clinical trial should consider novel methodology such as telemedicine, internet-based interventions, or fitness tracking apps to facilitate participation in and completion of a cardiovascular or pulmonary rehabilitation program. Provide evidence that the clinical trial proposes strategies that include provider interaction with patients to improve adherence to cardiovascular or pulmonary rehabilitation. Innovative strategies such as electronic health record reminders to improve provider referral rates are strongly encouraged.

Describe how the clinical trial targets providers, patients, and health care delivery systems that serve medically underserved, racial/ethnic minority, low income, and/or rural populations. Indicate whether the research proposes to evaluate implementation outcomes such as fidelity, acceptability, sustainability, and adoption of the interventions. Provide evidence that the research team has the necessary support from health care systems to carry out the proposed implementation strategies.

Describe the process for engaging and involving stakeholders and collaborators within the context of the project. Provide evidence of successful collaborations and/or partnerships with health care delivery organizations or other organizations. Describe the infrastructure and support available to implement the clinical trial within the proposed setting(s) where research will be conducted. Describe how safety measures and risk management for in-home or community-based rehabilitation sessions will be addressed.

The R61 phase will support the formative phase of the study, including the following milestones:

• Finalization of the protocol and the informed consent/assent document;
• Development of the manual of operations, case report forms and other resources necessary to the performance of the protocol
• Further development of study partnerships
• Establishment of a Data and Safety Monitoring Board and review of the protocol
• Institutional Review Board approval of the trial
• All necessary regulatory approvals, as well as source(s) of the necessary drugs, devices or other resources as needed, should be obtained to allow for the successful launch of the proposed clinical trial in the R61 phase.
• Enrollment into the clinical trial must begin in the R61 phase to allow for an evaluation by the end of the R61 phase of early enrollment and the probability of successfully completing the trial on time and on budget.

The R33 phase is contingent on successfully meeting the milestones in the R61 phase. Milestones of particular interest during the R33 phase include but are not limited to:

• Meeting the projected recruitment for all study participants, including women and minorities
• Monitoring protocol implementation performance
• Collection of data related to primary and secondary endpoints and adverse events;
• Database lock and analysis
• Submission of primary manuscript(s) to peer-reviewed scientific journal(s) and dissemination of results
• Submission of study results to ClinicalTrials.gov within 12 months of primary completion date.

The application should include a series of milestones for completing the specific aims of the clinical trial (R33) phase and contingency plans. Milestones and timelines for the R33 phase may need to be revised and finalized at the time of the R61/R33 transition meeting.

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.

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

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

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

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

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

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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

For assistance with your electronic application or for more information on the electronic submission process, visit 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. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

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

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

See more tips for avoiding common errors.

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

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

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.

Does the project address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Specific to this FOA:
How well does the proposed trial address providers, patients, and health care delivery systems that serve populations that are eligible/candidates for CR or PR?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Specific to this FOA:
Does the project include multidisciplinary teams of scientists, clinicians, and stakeholders comprising expertise in CR or PR and implementation science? How well does the application describe the process for engaging and involving stakeholders and collaborators in this project? Does the application provide sufficient evidence that the PD/PI(s) and key personnel have the necessary expertise in designing and implementing the proposed study? Is there evidence of successful collaborations and/or partnerships with health care delivery organizations or other organizations proposed in the application?

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Specific to this FOA:

How likely is the proposed research to improve referral to and delivery of CR or PR for eligible patients? How well does the proposed study consider novel methodology such as telemedicine, internet-based interventions, or fitness tracking apps to facilitate participation in and completion of CR or PR programs?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

Specific to this FOA:

How well does the application clearly target key barriers at the provider, patient, and healthcare system level that impede utilization of CR or PR in eligible patients? How effectively does the study target providers, patients, and healthcare delivery systems that serve medically underserved, racial/ethnic minority, low income, and/or rural populations? Does the study propose strategies that include provider interaction with patients to improve adherence to CR or PR? Does the study propose innovative strategies such as electronic health record reminders to improve provider referral rates? Does the research propose to evaluate implementation outcomes such as fidelity, acceptability, sustainability, and adoption of the interventions? Is there ample evidence that the research team has the necessary support from health care systems to carry out the proposed implementation strategies?

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?

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Specific to this FOA:
How strong are the infrastructure, support, and expertise to implement the project within the proposed setting(s) where research will be conducted? How well does the application address safety measures and risk management for in-home or community-based rehabilitation sessions?

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 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.

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.

Not Applicable

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 (GDS).

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

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 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. 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.

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.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. 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. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

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

Cooperative Agreement Terms and Conditions of Award

Not Applicable

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

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

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

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons 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 Center Telephone: 800-518-4726
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

Division of Cardiovascular Sciences
Jerome Fleg, MD
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0420
Email: [email protected]

Lawton Cooper, MD, MPH
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0419
Email: [email protected]

Center for Translation Research and Implementation Science
Susan Shero, RN, MS
National Heart, Lung and Blood Institute (NHLBI)
Telephone: 301-496-1051
Email: [email protected]

Division of Lung Diseases
Antonello Punturieri, MD, PhD
National Heart, Lung and Blood Institute (NHLBI)
Telephone: 301- 827-7844
Email: [email protected]

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

Ann Marie Brasile Mejac
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0164
Email: [email protected]

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

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