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

Background

New cases of HIV-related infections have significantly decreased in the U.S., but among many populations (e.g., urban, African American), the infection rates remain disproportionately high and represent a significant health disparity. Furthermore, innovation in creation and utilization of various treatment regimens, e.g., highly active antiretroviral therapy (ART), and recent World Health Organization guideline recommendations (2013) suggest that there will be significant increases in the life expectancy of people living with HIV. Increased life expectancy has resulted in an increase of heart, lung, blood and sleep (HLBS) comorbid diseases and disorders among populations with HIV. Proven effective interventions and guidelines exist for HLBS diseases and disorders for people living with HIV (PLWHIV). However, these interventions have not been fully implemented for PLWHIV in the U.S, and significant gaps remain in their implementation.

PLWHIV have a twofold higher risk of myocardial infarction compared to those without HIV. Cross-sectional data indicate that PLWHIV have a higher prevalence rate of hypertension (i.e., 43%), yet many of these patients do not meet treatment goals for control of their hypertension (i.e., of 75% treated, only 57% were at goal). Recent research studies found that few patients in need received acetylsalicylic acid (ASA or aspirin) for primary cardiovascular (CVD) prevention. A large percentage of the at-risk HIV+ population eligible for pharmacologic treatment for CVD are not receiving recommended interventions and are not reaching recommended treatment goals. Thus, there is an established need for the rapid scale-up of proven effective interventions for CVD comorbidities and other HLBS comorbid diseases and conditions in the U.S. HIV-infected population.

It is currently estimated that over half of the people living with HIV in the US are over 50 years of age and are thereby at increased risk of age-related HLBS comorbid disorders. To further complicate health ramifications for PLWHIV, some HLBS complications may be caused by effects of HIV, while others may be caused by effects of chronic use of ART. Together, aspects of HIV disease, ART, and other risk factors could be associated with increasing HLBS comorbidities for the aging population of PLWHIV. The scientific literature has identified that the aging HIV+ population within the U.S. will require long-term care to address the projected increases in non-communicable diseases (NCDs), particularly hypertension, CVD, and COPD. Since information is still emerging, research is necessary to understand the extent of the problem and the best and most effective ways to intervene. With effective late-stage T4 translation of research evidence into practice at the population level, the risks of HLBS comorbid conditions in PLWHIV may be reduced. A significant opportunity exists to positively impact the health of people living with HIV and chronic HLBS diseases and disorders using proven evidence-based practices.

There is a unique opportunity to link implementation science research with clinical research by utilizing the knowledge gained from significant investments in the clinical arena. Additionally, treatment is suboptimal in many localities in the U.S. This FOA is intended to support multidisciplinary collaborative research teams to conduct late-stage T4 translation research that addresses complex HLBS comorbidities in PLWHIV. T4 translation research is defined as research to identify implementation strategies to enhance sustainable uptake of proven-effective interventions into routine clinical practice and community-based settings to maximize population health impact. T4 translation research evaluates the salient implementation research outcomes for evidence-based interventions including acceptability, affordability, and appropriateness of interventions, feasibility, fidelity, penetration, and sustainability of the intervention in specific contexts.

Specific Areas of Research Interest

It is anticipated that PRECluDE research applications will consist of the key elements of implementation research such as:

• Utilization of an evidence-based implementation science research program using appropriate theoretical or conceptual frameworks for implementation science (e.g. CFIR, RE-AIM, PRECEDE-PROCEED, K2A, etc.); implementation research outcomes as primary outcome measures (e.g. acceptability, adoption, appropriateness, affordability, etc. (e.g. Proctor et al., 2011); implementation science study designs (e.g. experimental, quasi-experimental, observational, modeling, cluster randomization, hybrid designs, etc.) and a justification of how the implementation framework, research study design, and outcomes assessed will address multilevel and multidimensional implementation barriers that impede scale-up of the evidence-based interventions at the patient, local, community, and systems levels.

Potential research examples include but are not limited to those listed below:

• Pharmacologic interventions: Identification of deficiencies in the delivery of proven-effective pharmacologic treatment interventions for comorbid HLBS disorders in PLWHIV.
• Implementation Barriers to Successful Adoption: Research that utilizes a T4 implementation research framework to address the barriers that impede scale-up of preventive care of CVD by addressing multilevel barriers at the community, provider, and patient levels to facilitate better preventive care for PLWHIV. Research that explores the adoption of significant evidence-based practice and guidelines for patients infected with HIV to receive preventive care of CVD.
• Hematological and vascular complications due to HIV: Uptake of interventions with fidelity for hematologic dysfunctions including anemia, chronic thrombocytopenia, endothelial dysfunction, and thrombophilia using guidelines currently available for treating PLWHIV.
• Sleep Disturbances: Management of sleep disturbances for PLWHIV, including insomnia and obstructive sleep apnea using evidenced-based approaches and T4 translational research.
• Implementation strategies for at-risk populations: T4 translation research to improve implementation strategies associated with HIV at-risk populations including prison release populations, marginalized individuals, and LGBT and transgender populations, homeless populations and other defined at-risk populations are strongly encouraged. Racial/ethnic minority, rural and other underserved populations are of particular interest for the development of effective T4 translation research models.
• Adopting and Adapting Chronic Care Models (CCM) for COPD: Adaptation of evidenced-based CCM for COPD and/or other lung diseases among PLWHIV to improve outcomes, including marginalized groups with significant risk factors and health disparities. Late-stage T4 translational research using CCM that address HIV-positive veterans suffering from COPD and emphysema is an area of high interest (http://www.hiv.va.gov/provider/manual-primary-care/copd.asp).
• Multi-level implementation strategies: Tools that incorporate education and decision support into routine care, promote a team approach, and encourage an active but efficient interaction with PLWHIV using innovative technologies.

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

Applicant Organizations

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

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

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

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

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

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

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

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

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

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

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 (NHLBI)
Telephone: 301-435-0279
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.

Provide appropriate evidence that the PD(s)/PIs and key personnel have the necessary expertise in design and implementation of the proposed study. Provide evidence of successful investigative collaborations or partnerships with the organizations and/or systems proposed in the application.

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, with the following additional instructions:

Research Strategy:

Implementation Strategy

• Describe conceptual framework and model of the implementation strategy. A validated implementation framework that is feasible for the project is preferred.
• Identify strategies that take a systems approach by including healthcare systems or organizations and community resources to enable providers to improve care, that help providers to efficiently navigate the healthcare systems in which they work, and that include provider interaction with patients to improve adherence to care.
• Identify key barriers at the provider, healthcare system, and patient levels that impede current implementation efforts, and identify potential methods to facilitate the improved wide-scale adoption of practice guidelines in Federally Qualified Health Centers (FQHCs), community clinics, and other relevant and community based settings.
• Describe plans for investigators to partner closely with the health care systems and community based settings in which they work to develop the necessary support to carry out the implementation strategy. Describe how the proposed implementation strategy incorporates multi-level methods to facilitate the effective and efficient adoption of evidenced-based care and guidelines.
• Provide a compelling justification for the evidence-based practice and/or guidelines that are targeted, and describe how the proposed research is likely to improve delivery of HLBS evidence-based care among PLWHIV. Evidence-based care must be relevant to comorbid heart, lung, and blood diseases, and sleep disorders for PLWHIV. It is strongly encouraged to include plans to extend the reach of the intervention(s) to communities with different cultural values, if applicable.

Significance. Describe how the proposed project addresses comorbid HLBS disorders and HIV sequelae for populations at risk, including PLWHIV. Indicate if the proven evidence-based interventions are ready for scale-up to address significant HLBS diseases and disorders among PLWHIV.

Target Population. Clearly describe the study population. Implementation strategies to be developed and tested must target providers and health care delivery systems that serve PLWHIV, including specifically those who are medically underserved, racial/ethnic minorities, low income, and/or rural dwelling patients in either primary care or specialty care. Demonstrate access to and ability to recruit from a sufficient pool of eligible participants.

Study Design. Describe the proposed study design. Applications must utilize the most rigorous study design possible for the strategies to be tested. This may include randomized controlled trials, including cluster-randomized trials. Other design approaches may also be appropriate, including systems and population-based approaches, quasi-experimental strategies, mixed-methods designs, and the use of adaptive treatments. Describe plans to document and evaluate the fidelity, quality, and delivery of the implementation strategy.

Environment. Describe the infrastructure available to implement the study within the proposed setting and population. Indicate if there are sufficient numbers of eligible stakeholders available for collaborations in the proposed study.

Outcomes. Clearly describe primary outcomes. Appropriate outcomes include process-focused measures such as provider acceptability, uptake and adoption of guidelines, affordability analysis, and provider assessments of suitability and feasibility of the evidence-based HLBS care among PLWHIV. Clinical outcomes are desirable. Identify key factors at the provider, healthcare system, and patient levels that determine successful implementation of specific guideline-based practices for HLBS among PLWHIV.

Research Teams. Without repeating information from individual biosketches, describe plans for the multi-disciplinary teams of scientists, clinicians and stakeholders to work together to develop and test models of implementation that are feasible and applicable across diverse community and practice settings and populations of patients. Identify the collaborative process for engagement and involvement of stakeholders. Describe how the expertise and resources of stakeholders will be leveraged. Describe how the expertise and resources of stakeholders will be leveraged.

Letters of Support:

To be considered complete, applications must include letter(s) of support from relevant community based partners, healthcare provider(s), and other organization(s) related to the proposed project indicating their relevant expertise and commitment to participate.

If partial funding is to be provided by sources other than NHLBI, provide Letter(s) of Support signed by an authorized representative.

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. Applications should address plans to make available within one year of the end of the NHLBI period of support for the project, data not previously released and other study materials or products not previously distributed to individuals who are not study investigators in accordance with the NHLBI Data Sharing Policy available at http: http://www.nhlbi.nih.gov/funding/datasharing.htm.

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, NIH. Applications that are incomplete or non-compliant 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:

Does this project adequately address comorbid HLBS disorders and HIV sequelae for populations at risk, including PLWHIV? Are the proven evidence-based interventions ready for scale-up to address significant HLBS diseases and disorders among PLWHIV?

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?

Specific to this FOA:

Does the project include multi-disciplinary teams of scientists, clinicians and stakeholders, including HLBS and HIV? Does the application identify the collaborative process for engagement and involvement of stakeholders? Does the application provide appropriate evidence that the PD(s)/PIs and key personnel have the necessary expertise in design and implementation of the proposed study? Is there evidence or a track record for successful investigative collaborations or partnerships with the organizations and/or systems proposed in the application? Is the research team closely partnered with the relevant systems and organizations to develop the necessary support to carry out the implementation strategy or strategies?

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:

Does the proposed implementation strategy incorporate multi-level methods to facilitate the effective and efficient adoption of evidenced-based care and guidelines? Is the proposed research likely to improve delivery of HLBS evidence-based care among PLWHIV?

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:

Does the application clearly identify key barriers at the provider, system, and patient levels that impede current implementation efforts, as well as methods to facilitate improvements in wide-scale adoption of evidence-based interventions and practice guidelines? Does the application provide a compelling justification for the evidence-base targeted and the need for improvements in delivery of care for PLWHIV and relevant heart, lung, and blood diseases, and sleep disorders? How strong are the plans to document and evaluate the fidelity, quality, and delivery of the implementation strategy?

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?

Specific to this FOA:

Does the project consider successful strategies for PLWHIV as appropriate?

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:

Is there sufficient infrastructure to implement the proposed study within the proposed setting and population? Are sufficient numbers of potentially eligible stakeholders available for collaborations in the study?

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.

Evidence of collaboration required for the project proposed through letter(s) and as explained in the research proposal.

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 Committee (NHLBAC). The following will be considered in making funding decisions:

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

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

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR 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 PD(s)/PI(s) will have primary authority and responsibility to define objectives and approaches, and to plan, conduct, analyze, and publish results, interpretations, and conclusions of studies conducted under this program. The PD(s)/PI(s) assume responsibility and accountability to the applicant organization officials and to the NHLBI for the performance and proper conduct of the research supported by the U01 award.

• The PD(s)/PI(s) will create procedures for late-stage T4 translation research including needs assessment for both disease control and infrastructure, and creation of comprehensive, actionable, and context specific research plan.
• The PD(s)/PI(s) will be actively engaged in skills development for T4 translational research by collaborating with organizations to develop the necessary domain expertise. Furthermore, the PI will also provide outreach activities targeting research partners to develop skills and training for T4 translational research and implementation as necessary. These partners may include but will not be limited to health centers, public health agencies, community organizations and other regional collaborators without the necessary implementation skill sets.
• The PD(s)/PI(s) or their delegates will participate in all annual meetings, workshops, and working groups. The PD(s)/PI(s) will agree to accept close coordination, cooperation, and participation of NIH staff in those aspects of scientific and technical management of the project as described under the NIH Program Staff: Program Official (PO) and Project Scientist (PS) Roles.
• The PD(s)/PI(s) will agree to the governance of the program through the Steering Committee(SC).
• The PD(s)/PI(s) will be expected to work closely and deposit publications, findings and other documents into a NHLBI funded archive or repository or central location to facilitate data sharing and knowledge dissemination activities. The awardee will retain custody of and have primary rights to the documents, publications and other items developed under the award, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.

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

• The NIH Project Scientist will coordinate and facilitate interactions and collaborations among the awardees of the PRECluDE and provide technical assistance and advice to the awardees as appropriate. The NIH Project Scientist will serve as the liaison between individual projects and NHLBI.
• The NIH Project Officer will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.
• The assigned NIH Project Officer may not also serve as an NIH Project Scientist. The NIH Project Officer will periodically report progress about PRECluDE to NHLBI leadership including the Director of the NHLBI; PD(s)/PI(s) will provide timely assistance in providing relevant updates, documents, and other materials for the annual progress reports to the NHLBI.

The NHLBI reserves the right to withhold funding or curtail the pilot study or needs assessment for an individual award in the event of a substantive changing in, or failure to make sufficient progress toward, the agreed-upon work scope with which the NIH cannot concur or when there are ethical issues that may dictate a premature close-out.

Areas of Joint Responsibility include:

• The awardee will retain custody of and have primary rights to data development under this award, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.
• The PD(s)/PI(s) of this award will be required to participate in periodic meetings and telephone conference calls with the NHLBI Project Officer and Scientist.
• The PD(s)/PI(s) are expected to publish and release publicly and disseminate results, tools, protocols, resources and other products, in accordance with established protocols and governance of the SC. It is expected that all methods, analyses, and data (e.g., software, and algorithms) will be made available in a timely manner to the scientific community.

Steering Committee (SC):

A Steering Committee (SC) will serve as the main governing board and monitor progress; facilitate coordination and synergy across the entire program; and develop recommendations for uniform procedures and policies.

• The Steering Committee membership will include the NIH Project Scientist(s) and the PD/PI of each award. The Steering Committee Chair will not be an NIH staff member but will be appointed by NIH staff. Additional members may be added by action of the Steering Committee. Other government staff may attend the Steering Committee meetings, if their expertise is required for specific discussions. As necessary, NIH staff will create appropriate subcommittees to handle interests that may be specific to a set of awardees funded by this FOA.

SC Responsibilities:

• SC will discuss progress in meeting the goals of various PRECluDE projects; facilitate coordination and synergy across the entire PRECluDE program; and develop recommendations for uniform procedures and policies necessary to meet the goals of the PRECluDE. For example, SC will determine research collaborations such as methodology, data, and core measures and assessment available.
• SC will lead organizational management including the schedule and concise summaries of the Steering Committee meetings. The SC will meet at least once a year in person and hold regular conference call meetings. The SC will seek to operate by consensus, but in the event that a vote is needed, the PD/PI of each award, the NIH Project Scientist and Project Officer will each have one vote. In the case of multiple PD/PI awards, the awardee will identify one PD/PI who will vote on behalf of the awardee's team.
• 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. The three members will be: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

When multiple years are involved, awardees will be required to submit the 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.

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

Cheryl Anne Boyce, Ph.D.
National Heart, Lung, and Blood Institute (NHLBI))
Telephone: 301-496-1051
Email: [email protected]

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

Erin Davis
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0166
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.