NIH's new Application Submission System & Interface for Submission Tracking (ASSIST) is available for the electronic preparation and submission of multi-project applications through Grants.gov to NIH. Applications to this FOA must be submitted electronically using ASSIST or an institutional system-to-system solution; paper applications will not be accepted. ASSIST replaces the Grants.gov downloadable forms currently used with most NIH opportunities and provides many features to enable electronic multi-project application submission and improve data quality, including: pre-population of organization and PD/PI data, pre-submission validation of many agency business rules and the generation of data summaries in the application image used for review.

It is critical that applicants follow the Multi-Project (M) 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) and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. 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 National Heart, Lung, and Blood Institute (NHLBI) Program Project Grant (P01) supports research related to fundamental processes and diseases of the heart, blood and lymphatic vessels, lungs, and blood, including transfusion medicine, blood resources, and sleep disorders and other programs including implementation science, health disparities, and translation research that address the mission of the Institute. This FOA requires a minimum of three interrelated research projects that investigate a complex biomedical theme or research question. The projects may be supported by core units, if justified, to facilitate economy of effort, space, and equipment. The NHLBI provides support for Program Project Grants (PPGs) in the belief that collaborative research efforts can accelerate the acquisition of knowledge more effectively than a simple aggregate of research projects that have no interaction or thematic integration.

NHLBI is particularly interested in encouraging new scientific directions in PPGs. Use of the P01 mechanism is viewed as an opportunity to attract and include scientists who traditionally have not been supported by the NHLBI. Further, the PPG environment presents an opportunity for emerging scientific leaders to gain insight into how to lead a successful scientific program, and applicants will have the opportunity to include a project led by an Early Stage Investigator (ESI). All projects in the Program must be interrelated and have objectives that address a central theme within the scientific mandate of the NHLBI.

Research Objectives

This Funding Opportunity Announcement (FOA), issued by the NHLBI, invites Program Project Grant (PPG) applications that address the mission of NHLBI as outlined in the Purpose section above. Investigators are encouraged to visit the NHLBI website for additional information about the research mission and high-priority research areas of the NHLBI (http://www.nhlbi.nih.gov/about/strategicplan/index.htm.)

The purpose of the Program Project is to support integrated, collaborative research programs that have a well-defined, central research focus or objective. Applications must include a minimum of three individual research projects that contribute to the Program objective. Since the NHLBI is interested in supporting new, innovative research through the Program Project, no more than half of the Projects included in a funded Program Project Grant application may include Projects that significantly overlap in time and objectives with currently funded individual research project grants, i.e., individual research project grants that would have to be relinquished if the Program Project application is funded. Each individual research Project should reflect a distinct, separate, scientifically meritorious research effort led by an independent investigator, the Project Leader. In addition, the individual Projects should be clearly interrelated and synergistic so that the research ideas, efforts, and outcomes of the Program as a whole will offer a distinct advantage over pursuing the individual projects separately. It is expected that, as part of this integration, the PD/PI (or each of the Multiple PD(s)/PI(s)) will also serve as the Project Leader of one of the Projects and each awarded Program Project will have a minimum of three distinct/individual Project Leaders.

In addition to individual research Projects, applicants may propose an Administrative Core and one or more shared Scientific Core(s) as necessary to facilitate the proposed research Projects. It is expected that each Scientific Core will be utilized by two or more Projects within the Program. Any proposed Scientific Core, if justified, is expected to be considered essential to conduct the Program and should not duplicate existing institutional resources. Responses to Frequently Asked Questions (FAQs) are available at: https://www.nhlbi.nih.gov/research/funding/faqs-nhlbi-program-project-applications. NOTE: Phase III Clinical Trials are not allowed for this FOA. Please refer to the FAQ page for additional guidance.

See Section VIII. Other Informationfor 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 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.

The PD(s)/PI(s) are expected to be a research scientist(s) of recognized stature in his/her scientific discipline with the demonstrated ability to ensure quality control, administrative oversight, and integration of all components of a Program. The PD(s)/PI(s), Project Leaders, and Core Leaders are expected to be fully established at their institution at the time of submission of the application. Additionally, Project Leaders are expected to have demonstrated the ability to lead an R01, or R01-equivalent, grant. The expectation of demonstrated ability to lead an R01, or R01 equivalent, grant does not apply to ESI Project Leaders.

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).

A button to access the online ASSIST system is available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

Most applicants will use NIH's ASSIST system to prepare and submit applications through Grants.gov to NIH. Applications prepared and submitted using applicant systems capable of submitting electronic multi-project applications to Grants.gov will also be accepted.

It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. 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:

Program Project Review Office
Director, Office of Scientific Review
National Heart, Lung, and Blood Institute
Email: [email protected]

Component Types Available in ASSIST	Research Strategy/Program Plan Page Limits
Overall Program	12
Admin Core (Use for Administrative Core)	12
Core (Use for Scientific Core)	6
Project (Use for Research Projects)	12
ESI Project (Use for ESI-Led Project)	12

Additional page limits 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 a multi-component application.

The application should consist of the following components:

• Overall Program: required
• Administrative Core: optional; maximum of 1
• Scientific Cores: optional
• Projects: minimum of 3 required
• ESI-Led Project: optional, maximum of 1

When preparing your application in ASSIST, use Component Type 'Overall'.

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

Complete entire form.

Note: Human Embryonic Stem Cell lines from other components should be repeated in cell line table in Overall component.

Follow standard instructions.

Enter primary site only.

A summary of Project/Performance Sites in the Overall section of the assembled application image in eRA Commons compiled from data collected in the other components will be generated upon submission.

Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this FOA) for the entire application. Applicants must provide strong justification for the use of a multi-leadership model for the Overall Program.

Note that multi-PD(s)/PI(s) are allowed for the Overall Program, however Multiple PDs/PIs for individual Projects or Cores are not permitted in response to this FOA.

A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.

The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover.

A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.

Introduction to Application: For Resubmission applications, an Introduction to Application is required in the Overall Program.

Specific Aims: Describe the specific aims for the Overall Program. List the goals of the research and summarize expected outcomes.

Research Strategy: Describe the significance, innovation, and approach of the overall application and highlight the Program's conceptual unity by describing the scientific problems to be addressed and laying out a broad research strategy to address them. The Program Project should be viewed as a group of interrelated research Projects, each of which is not only individually meritorious scientifically but also complementary to and interrelated with the other Projects in the research Program that contribute to the integrating theme. The theme of a proposed Program Project should be established in the first few sentences of this section. It should include a description of the major research objectives and strategic plan. Explain how the proposed Projects and shared Scientific Cores (if proposed and justified) will be coordinated and work together to address the overall goals and aims of the Program more effectively than if the Projects were conducted independently.

Describe any prior collaborative arrangements between investigators in the group to explain the genesis of the current application, to predict the anticipated unique advantages that would be gained by the research within the proposed Program Project, to describe how the Projects are interrelated, and to explain how the proposed Program Project would enable the stated objectives of the proposed research to be addressed more efficiently and effectively than a group of individual research project grants.

Summary Report of Progress: For renewal applications only, include a progress report that summarizes the aims and accomplishments of the Program during the prior funding period. See the SF424 instructions for details about what to include in the progress report. If a project from the prior funding period is being discontinued, explain in the overall progress report. A progress report is required for each research Project and Core(s) in the respective components of the application. The composite summary/progress report must include: a brief summary of major accomplishments that can be attributed to the Program Project and a brief explanation of how they relate to the stated objectives of the Program; a list of changes, if any, in the professional staffing since the last competitive review; a list of research Projects and Core(s), in tabular form, that have been discontinued, modified, or completed since the last competitive review, identified by number and title, with a brief explanation of the actions taken; and a list of research Projects and Cores in the current Program Project. Identify each as a "new" or "continuing" component.

In addition, if an Administrative Core is not proposed, applicants must provide the information outlined in the Administrative Core Research Strategy section.

Letters of Support: Attach letters of support relevant to the Program as a whole (e.g., letters of institutional support). Letters of support relevant to specific Projects or Cores should be attached in the relevant Project or Core Research Plan forms.

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.

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

If you answered "Yes" to the question "Are Human Subjects Involved?" on the R&R Other Project Information form, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

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

When preparing your application in ASSIST, use Component Type 'Admin Core.'

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

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant's Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the 'Are Human Subjects Involved?' and 'Is the Project Exempt from Federal regulations?' questions.

Vertebrate Animals: Answer only the 'Are Vertebrate Animals Used?' question.

Project Narrative: Do not complete.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of 'Other' with Category of 'Core Lead' and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• For this FOA, only one Core Lead may be designated for the Administrative Core. Multiple Core Leads are not permitted.

Budget forms appropriate for the specific component will be included in the application package.

While there is no minimum effort required, the Core Lead should dedicate appropriate time and effort commensurate with the complexity of the Core's function.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for each component.

Specific Aims: List in priority order, the broad, long-range objectives and goals of the proposed Administrative Core. In addition, state the Core's relationship to the proposed Program's goals and how it is related to the individual Research Projects and Core(s) in the application.

Research Strategy: If an Administrative Core is not proposed, the following must be addressed in the Research Strategy of the Overall Program section. The institution and the PD/PI are responsible for the application and collaborative research activities. Explain the plans for organizational and administrative management of the entire Program, and for coordination and communication within the Program. Explain the methods that will be used for monitoring progress in the Projects and effective use of the shared Scientific Cores. Explain the plans for internal quality control of on-going research, management of day-to-day program activities, management of contractual agreements (if applicable), and a plan for resolution of disputes. Describe how the Core Lead's administrative, management, and leadership capabilities adequately provide for: internal quality control of on-going research, management of day-to-day program activities, and management of contractual agreements. Describe communication and cooperation among program leaders and/or program investigators, plans for resolution of disputes, development of scientific meetings and allocation of funds as applicable.

Chain of Responsibility: Describe in detail, and by diagram, if appropriate, the chain of responsibility for decision making and administration, beginning with the PD/PI and including the leaders of the research Projects and Cores. Indicate where in the chain of responsibility advisory groups (internal and external consultants) would be used, and describe their function in ensuring quality control in the research efforts.

External and Internal Advisory Boards: Every Program Project should have plans for both an External Advisory Board and an Internal Advisory Board. For an External Advisory Board, describe the expertise and responsibilities of your potential Board members. If submitting a new application, do not contact, recruit, or name potential members of the External Advisory Board. New Program Project Grant applications should not constitute an External Advisory Board prior to or during the review of their application because individuals identified in an application cannot participate in its peer review.

Renewal applications should provide the names of current and former members. The External Advisory Board should consist of two or three named advisers committed to the evaluation of the Program by written documentation. Two or three additional advisers may be added once the progress of the Program and its needs are clearer. The Internal Advisory Board should consist of three to five members outside of the Program but within the applicant institution who are able to assist in frequent, ongoing oversight.

Specific Managerial Responsibilities: Indicate who would be responsible for assisting the PD/PI with day-to-day administrative details, Program coordination, planning, and evaluation of the Program.

Relation of the Program Project Grant to the Administration of the Applicant Institution: Describe the relationship between the proposed Program Project and other existing research, academic, and administrative units of the applicant institution such as schools, centers, institutions, departments, and central administration.

Designation of Replacement for PD/PI: Describe the procedure for selecting a proposed replacement for the PD/PI, should the need arise. The NHLBI must approve any request to replace the PD/PI.

Administrative Core Progress: A progress report must be provided for the Administrative Core in renewal applications. Provide the beginning and ending dates of the most recent award period. Summarize the specific aims of the Core during this period and the importance of the accomplished activities. Provide justifications for major changes in the Core.

Letters of Support: Attach letters of support relevant to the Administrative Core.

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.

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

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

Other Requested Information: All instructions in the SF424 (R&R) Application Guide must be followed.

Study Record: PHS Human Subjects and Clinical Trials Information: All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study: All instructions in the SF424 (R&R) Application Guide must be followed.

When preparing your application in ASSIST, use Component Type 'Core.'

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

SF424 (R&R) Cover (Scientific Core)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant's Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Scientific Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Scientific Core)

Human Subjects: Answer only the 'Are Human Subjects Involved?' and 'Is the Project Exempt from Federal regulations?' questions.

Vertebrate Animals: Answer only the 'Are Vertebrate Animals Used?' question.

Project Narrative: Do not complete.

Project /Performance Site Location(s) (Scientific Core)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Scientific Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of 'Other' with Category of 'Core Lead' and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• For this FOA, only one Core Lead may be designated on the application for a Scientific Core. Multiple Core Leads are not permitted.

Budget (Scientific Core)

Budget forms appropriate for the specific component will be included in the application package.

While there is no minimum effort required, the Core Lead should dedicate appropriate time and effort commensurate with the complexity of the Core's function.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Scientific Core)

Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for each component.

Specific Aims: List in priority order, the broad, long-range objectives and goals of the proposed Core. In addition, state the Core's relationship to the proposed Program's goals and how it is related to the individual Research Projects and Cores in the application.

Research Strategy: The application should list the Projects it will serve and services it will provide. Scientific Cores must accelerate the pace of discovery via essential support for the aims of proposed research Projects. Hypothesis-driven aims are not required for Scientific Cores. Research activities should only be conducted in the research projects.

Describe the function of the Scientific Core as a resource to the Program Project. Describe the facilities, techniques, and skills the Core will provide and the role of the Core Leader and each key participant. State the percentage of total dollars required to support each Project that will use each Scientific Core. Explain why the inclusion of this Scientific Core is essential to two or more of the individual research Projects and to the entire Program. Provide justification for the essential nature of this Scientific Core for the Program. Scientific Core activities should not duplicate existing institutional resources.

Letters of Support: Attach letters of support relevant to the Scientific Core. Any proposed Scientific Core must include an institutional letter from the Department Chair/Division Head/Dean documenting the need for this Scientific Core and including information regarding other related Core facilities that are currently provided at the Institution.

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. 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.

PHS Human Subjects and Clinical Trials Information (Scientific Core)

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

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

Study Record: PHS Human Subjects and Clinical Trials Information: All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study: All instructions in the SF424 (R&R) Application Guide must be followed.

Project

When preparing your application in ASSIST, use Component Type 'Project.'

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

If including an ESI-led Project, please follow the instructions in the ESI-Led Project Section for that project.

SF424 (R&R) Cover (Project)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant's Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Project)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Project)

Human Subjects: Answer only the 'Are Human Subjects Involved?' and 'Is the Project Exempt from Federal regulations?' questions.

Vertebrate Animals: Answer only the 'Are Vertebrate Animals Used?' question.

Project Narrative: Do not complete.

Project /Performance Site Location(s) (Project)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Project)

• In the Project Director/Principal Investigator section of the form, use Project Role of 'Other' with Category of 'Project Lead' and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• For this FOA, only one Project Lead may be designated on the application for a Project. Multiple Project Leads are not permitted.
• In general, each individual Project in a Program Project should have a different Project Leader. Although individual investigators are not precluded from leading more than one Project in a Program Project, strong justification must be provided for all such instances. In no case may one individual serve as Project Lead on more than two Projects. Each awarded Program Project must have a minimum of three distinct/individual Project Leads.
• All PD(s)/PI(s) must be the Project Leader of one of the component Projects.

Budget (Project)

Budget forms appropriate for the specific component will be included in the application package.

The Project Lead must devote a minimum of 2.40 person months (20% effort over 12 months) to the Project. If the Project Lead is also a PD/PI for the Overall Program, they must devote a minimum of 5% effort to one other component (e.g., another Project or a Core) for a total minimum of 3.0 person months (25% effort over 12 months).

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Project)

Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for each component.

Specific Aims: List the broad long-range objectives and goals of the proposed research Project. Concisely and realistically describe the hypothesis or hypotheses to be tested. In addition, state the individual project's relationship to the Program's goals and how it is synergistic to other projects and relevant cores.

Research Strategy: Use this section to describe the proposed research and how it will contribute to meeting the Program's goals and objectives and explain the rationale for selecting the methods to accomplish the specific aims. In addition to stating the biological significance of the research, indicate the project's relevance to the primary theme of the application. In addition to the standard scientific description, the interactions among Projects and Core(s) must be described within each Project. Describe how inclusion of this Project within the Overall Program offers distinct advantage or scientific gain over pursuing the Project independently.

Letters of Support: Attach letters of support relevant to the Project.

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. 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.

PHS Human Subjects and Clinical Trials Information (Project)

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

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

Study Record: PHS Human Subjects and Clinical Trials Information: All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study: All instructions in the SF424 (R&R) Application Guide must be followed.

ESI-Led Project (Optional)

When preparing your application in ASSIST, use Component Type 'ESI Led Project.'

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

SF424 (R&R) Cover (ESI Project)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant's Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (ESI Project)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (ESI Project)

Human Subjects: Answer only the 'Are Human Subjects Involved?' and 'Is the Project Exempt from Federal regulations?' questions.

Vertebrate Animals: Answer only the 'Are Vertebrate Animals Used?' question.

Project Narrative: Do not complete.

Project /Performance Site Location(s) (ESI Project)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (ESI Project)

• In the Project Director/Principal Investigator section of the form, use Project Role of 'Other' with Category of 'Project Lead' and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• For this FOA, only one Project Lead may be designated on the application for a Project. Multiple Project Leads are not permitted.
• In general, each individual Project in a Program Project should have a different Project Leader. Although individual investigators are not precluded from leading more than one Project in a Program Project, strong justification must be provided for all such instances. In no case may one individual serve as Project Lead on more than two Projects. Each awarded Program Project must have a minimum of three distinct/individual Project Leads.
• All PD(s)/PI(s) must be the Project Leader of one of the component Projects.
• The ESI Project Leader must have demonstrated independence. Evidence for independence may include:
• The candidate has a full-time faculty position.
• The candidate received a start-up package for support of his/her independent research.
• The candidate has research space dedicated to his/her own research.
• The candidate may attend faculty meetings, be the responsible supervisor for graduate students, and/or hire technical support or postdoctoral fellows.
• The candidate is eligible to apply for independent research funding as the PD/PI of an NIH research grant.

Budget (ESI Project)

Budget forms appropriate for the specific component will be included in the application package.

The Project Lead must devote a minimum of 2.40 person months (20% effort over 12 months) to the Project. If the ESI Project Lead is also a PD/PI for the Overall Program, they must devote a minimum of 5% effort to one other component (e.g., another Project or a Core) for a total minimum of 3.0 person months (25% effort over 12 months). It is important to note that inclusion of an ESI as PD/PI for the Overall Program will result in the loss of the investigator's ESI status. Inclusion of an ESI as Project Lead but not PD/PI for the Overall Program will not result in a loss of ESI status. The budget allocations to an ESI Project must be at least $250,000 in direct costs.

Note: The R&R Budget form included in many of the component types allow for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (ESI Project)

Introduction to Application: For Resubmission applications, an Introduction to Application is allowed for each component.

Specific Aims: List the broad long-range objectives and goals of the proposed research project. Concisely and realistically describe the hypothesis or hypotheses to be tested. In addition, state the individual project's relationship to the Program's goals and how it is synergistic to other Projects and relevant Core(s).

Research Strategy: Use this section to describe the proposed research and how it will contribute to meeting the Program's goals and objectives and explain the rationale for selecting the methods to accomplish the specific aims. In addition to stating the biological significance of the research, indicate the Project's relevance to the primary theme of the application. In addition to the standard scientific description, the interactions among projects and core facilities should be described within each Project. Describe how inclusion of this Project within the Overall Program offers distinct advantage or scientific gain over pursuing the Project independently.

Letters of Support:

• Attach letters of support relevant to the Project.
• The ESI-Led Project must include a statement from the Overall PD(s)/PI(s) describing how the participation in the Program provides a good leadership skills development environment and how the ESI Project Leader's scientific and professional career development will be enhanced through participation in the Program.
• The sponsoring institution must provide a statement of commitment to the candidate's development into a productive, outstanding investigator, provide assurance that the research facilities, resources, and training opportunities, including faculty capable of productive collaboration with the candidate, will be available for the candidate's planned career development and research programs, and include a statement that the candidate is eligible to apply as the PD/PI for an independent research grant.

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. 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.

PHS Human Subjects and Clinical Trials Information (ESI Project)

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

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

Other Requested Information: All instructions in the SF424 (R&R) Application Guide must be followed.

Study Record: PHS Human Subjects and Clinical Trials Information: All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study: 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) using ASSIST or other electronic submission systems. 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.

For information on how your application will be automatically assembled for review and funding consideration after submission go to: http://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.

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) and component Project Leads 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.

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 (SAM). 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 requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact a Scientific/ Research Contact at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF424 (R&R) Application Guide. Applicants to this FOA must also:

1. Discuss the proposed Program Project Grant application with NHLBI program, review, and grants management staff via an in-person meeting or a conference call (i.e., staff consultation). Potential applicants are strongly encouraged to begin informal discussions with NHLBI scientific staff as early as possible in the process of planning their proposed research application, but no less than 10 weeks prior to the submission deadline. The staff consultation: (1) ensures that the NHLBI receives applications that are scientifically aligned with the Institute's mission and strategic vision and (2) enables the Institute to consider the budgetary impact of supporting such a Program. NHLBI staff will not evaluate the technical and scientific merit of the proposed application/Program; technical and scientific merit will be determined during peer review using the review criteria indicated in this FOA.

2. Submit a letter of request to the NHLBI. After the staff consultation, the intended applicant(s) submit a letter of request (as a PDF attached to an email) to the Director of the NHLBI extramural Program Division whose research mission is most relevant to the proposed topic (Scientific/ Research Contact). This letter serves as the formal request seeking permission to submit an application with direct costs of $500,000 or more in any one year.

3. Obtain written agreement from NHLBI that the Institute will accept the application for consideration for award.

4. Applicants must include a cover letter with the application that identifies the NHLBI Program staff member(s) with whom they have been in contact regarding the application along with a copy of the written agreement letter from NHLBI. If the Subtotal Direct Cost on the cover page of the application exceeds the amount the NHLBI agreed to accept, the application may be withdrawn or not awarded.

The instructions in this section apply to all new, renewal, or resubmission applications, with the exception that renewal and resubmission applications do not need to obtain the staff consultation indicated in item 1.

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

Important Update: See NOT-OD-18-228 for updated review language for due dates on or after January 25, 2019.

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.

All Program Project Grant applications are reviewed through a two-step process by a Tailored Review Committee and by the Heart, Lung, and Blood Program Project Review Committee (HLBP) prior to review by the NHLBI Advisory Council.

The Tailored Review Committee is composed of scientific peers convened to review a Program Project Grant application in their area(s) of expertise. The Tailored Review Committee will:

• Provide an overall assessment of each Project based on its intrinsic and scientific merit within the field and provide a percentile descriptor ranking score of that Project broken down into seven categories (i.e., top 1% of projects within the field, 1%-10% of projects within the field, 10-20% of projects within the field, 20-30% of projects within the field, 30-40% of projects within the field, 40-50% of projects within the field, and 50% or less of projects within the field).
• Assign numerical scores to each scored criterion and provide written critiques of the strengths and weaknesses of the scored review criteria.
• Rate each Core as "Recommended" or "Not Recommended" based on whether it is essential and justified for the proposed research and has the capability to fulfill the proposed function (reviewers will evaluate the number of Projects serviced by the Core; the Core must service two or more Projects).
• Assess whether the proposed budget is appropriate.

The HLBP considers the review reports from the Tailored Review Committee, makes recommendations, and assigns an overall impact score to each application. It may not change an individual Project assessment assigned by the Tailored Review Committee, but it is asked to provide written comments to be included in the summary statement if it has any disagreement with a Project assessment.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the Overall Program 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 Overall Program proposed).

The Heart, Lung, and Blood Program Project Review Committee (HLBP) will consider each of the review criteria below in the determination of scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Is the Program as a whole scientifically compelling? Is there coordination and synergy of the individual research Projects and Cores towards the achievement of the central objectives of the Program? Will the integration of the individual Projects into a single Program be more beneficial than pursuing each Project independently? Do(es) the Program Director(s)/Principal Investigator(s) have the leadership and scientific ability to develop an integrated and focused research Program? Will the PD(s)/PI(s) devote adequate time and effort to the Program? Is there adequate evidence of sufficient institutional support for the PD(s)/PI(s)? For applications designating multiple PD(s)/PI(s), are there adequate and appropriate coordination and communication among the PD(s)/PI(s)? For renewal applications, have the Program's accomplishments made a major impact on the field or successfully achieved their original goals? Are the administrative and organizational structures sound?

As applicable for the Program 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.

Review Criteria for Individual Research Projects Within the Program

Reviewers will consider each of the review criteria below in the determination of scientific merit of each proposed research project, and give a separate numerical (1 to 9) score for each criterion, and provide a percentile descriptor ranking score of the overall Project broken down into seven categories (i.e., top 1% of projects within the field, 1%-10% of projects within the field, 10-20% of projects within the field, 20-30% of projects within the field, 30-40% of projects within the field, 40-50% of projects within the field, and 50% or less of projects within the field). A project 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.

Scored Review Criteria - Project

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

Significance

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 applications proposing clinical trials

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

Investigator(s)

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 applications proposing clinical trials

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

Specific to applications proposing an ESI-Led Project

Based on the investigator's prior research and training experience, track record, supporting letters, and the quality and originality of prior research and the current application, what is the investigator's potential to become a highly successful investigator who will contribute significantly to his/her research field? Will inclusion of the investigator in this Program enhance his/her career development scientifically and professionally? How capable does the applicant appear to be with respect to conducting independent research?

Innovation

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 applications proposing clinical trials

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

Approach

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?

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 of exclusion of children, justified in terms of the scientific goals and research strategy proposed?

Specific to applications proposing clinical trials

Does the application adequately address the following, if applicable:

Study Design

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

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

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable? Does the application adequately address Good Clinical Practices (GCP), Good Laboratory Practices (GLP), and Good Manufacturing Practices (GMP) compliance if applicable?

Data Management and Statistical Analysis

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

Environment

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 applications proposing clinical trials

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed? Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate? If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial? If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

Specific to applications proposing an ESI-Led Project

Does the Program and institution provide a high-quality environment appropriate for the investigator's scientific and professional development? Is there adequate evidence that the Program and institution are strongly committed to fostering the investigator's development scientifically and professionally?

Integration

How well-integrated is the Project within the Program? Does inclusion of this Project within a Program offer distinct advantage or scientific gain over pursuing the Project independently? Is the Project interrelated and synergistic within the overall Program? How well does the Project fit into the overall theme of the Program?

Review Criteria for Core Units Within the Program

Each Core will be evaluated as "Recommended" or "Not Recommended" based on whether it is essential for the proposed research and has the capability to fulfill the proposed function. Reviewers will evaluate the number of projects serviced by the Core (the Core must service two or more Projects); strengths and weaknesses of the proposed approaches, resources, and interactions; whether the investigators are qualified for their role(s) in the Core and have dedicated appropriate time and effort commensurate with the complexity of its functions; and whether the proposed budget for the Core is appropriate.

Administrative Core

Does the application clearly describe and justify the proposed Administrative Core operational plan and organizational structure? Is the proposed Administrative Core adequate to accomplish the objectives of the Overall Program? How well does it fit into the central focus of the Overall Program? Do the Administrative Core Leader's administrative, management, and leadership capabilities adequately provide for: internal quality control of on-going research, management of day-to-day program activities, management of contractual agreements, fair, effective communication and cooperation among Program leaders and/or Program investigators, resolution of disputes, development of scientific meetings and allocation of funds?

Scientific Core(s)

Is the Scientific Core sufficiently justified? Does it support at least two research projects? Is the Core adequately connected to the central focus of the Overall Program? Are the facilities or services provided by the Core (including procedures, techniques, and quality control) high quality? Will the services be used effectively? Is the Scientific Core leader and key personnel well qualified and is there an adequate commitment of time? Does the required institutional letter sufficiently justify the necessity of the Scientific Core for this Program or can the Core services be accomplished through other means?

As applicable for the application proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Study Timeline and Milestones

Specific to applications proposing clinical trials

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

Are appropriate, evaluative milestones clearly defined for the aims associated? Are the milestones feasible and quantifiable with regard to specific aims and timeline? Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

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.

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

For Renewals, the committee will consider the progress made in the last funding period.

Not Applicable

As applicable for the Program/Project/Core 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 .

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.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications . 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.

If the proposed clinical trial has elevated risks, NHLBI may require closer programmatic monitoring and it may be necessary to require the awardee to provide more frequent information and data as a term of the award (e.g., to clarify issues, address and evaluate concerns, provide documentation). All additional communications and information related to programmatic monitoring must be documented and incorporated into the official project file.

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

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

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that the application as well as all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

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

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

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 https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.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 https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/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 https://www.hhs.gov/ocr/about-us/contact-us/index.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
David Goff, M.D.
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0422
Email: [email protected]

Division of Lung Diseases
James Kiley, Ph.D.
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0233
Email: [email protected]

Division of Blood Diseases and Resources
W. Keith Hoots, M.D.
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0080
Email: [email protected]

Center for Translational Research and Implementation Science

George Mensah, M.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]

Ryan Lombardi
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.