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:

• o Hispanic-serving Institutions
• o Historically Black Colleges and Universities (HBCUs)
• o Tribally Controlled Colleges and Universities (TCCUs)
• o Alaska Native and Native Hawaiian Serving Institutions
• o 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.
• o 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
National Heart, Lung, and Blood Institute
Telephone: 301-435-0270
Email: NHLBIChiefReviewBranch@nhlbi.nih.gov

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.

Facilities and Other Resources: As appropriate, describe available resources such as clinical and laboratory facilities, geographic distribution of space and personnel, and resources relevant to the effective implementation of the basic content exam/data collection cycle and the maintenance and follow-up of existing prospective epidemiology cohort participants.

Other Attachments: The attachments listed below must be completed and attached or the application will not be peer reviewed, with the exception of the "Biospecimen Plan", which must only be provided if applicable.

1. Cohort History

A description of the cohort's history and research program must be provided as an attachment using the filename "Cohort History.pdf" and may not exceed 4 pages. Provide details for each bullet below:

• Established name of the existing cohort
• Brief description of the main research questions investigated and the major findings
• Summary of previous examination or data collection cycles including a brief description of the data collection instruments and number and types (e.g., biospecimens, questionnaire, imaging, physiological testing, etc.) of ancillary content supported by the existing cohort infrastructure.
• Outcomes of interest and current vital status of participants
• Available phenotypic/genomic data and biospecimens

2. Biospecimen Plan (Optional)

If applicable, a Biospecimen Plan should be provided as an attachment using the filename "Biospecimen Plan.pdf" and may not exceed 5 pages. The Biospecimen Plan must describe how study biospecimens will be collected, managed, analyzed, and stored. Applicants must describe biospecimen storage facilities, and plans for maintenance and organization of existing and future biospecimens. Describe plans for adherence to Good Laboratory Practices (GLP). Opportunities to leverage institutional resources should be detailed, if applicable.

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

Biographical Sketch: The experience with epidemiological cohort studies for proposed PD(s)/PI(s) must be described, specifically documenting their respective abilities to organize and manage a cohort study and related activities.

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:

Specific Aims: Provide Specific Aims for the enhancement and/or maintenance of the cohort infrastructure as well as research proposed in the application.

Research Strategy:

The Research Strategy must discuss the overall approach to coordinate and administer the cohort. Plans for study management, oversight of regulatory responsibilities, and maintenance of data should be described. Applicants must specifically address:

Coordination and Administration of the Cohort

• Regulatory oversight: Describe how oversight of participants will be implemented, including IRB approvals and the consent/assent process. Applicants are encouraged to review NIH guidance on consent for future research use in the informed consent process. Include plans for compliance with the NIH single IRB policy as permitted by local regulations, as applicable.
• Quality management: Describe how data collection activities will be managed, including quality control measures.
• Training/monitoring: Describe how training/monitoring of sites and staff will be managed.
• Participant follow-up: Describe how continued follow-up of cohort participants will be conducted; specifically, describe any active follow-up involving participant contact and/or plans for the ascertainment/adjudication of events of clinical significance.
• Data management: Describe internal and external data sharing strategies as appropriate and consistent with achieving the goals of the program. Where applicable, applicants are expected to describe plans for data harmonization, metadata generation, and adoption/use of data standards or common data elements.
• Innovative approaches: Describe any innovative approaches to data management/standards, data collection, or participant follow-up.
• Basic content examination/data collection cycle: Briefly describe the proposed elements of the basic content exam/data collection cycle including any clinical, laboratory, physiological, or behavioral assessments. Justification must be provided as to how the proposed assessments can be leveraged for potential ancillary content.
• Management of ancillary research: Describe plans for the mangement of additonal, independently peer-reviewed ancillary research content including the process by which ancillary content will be approved by the study, administration of ancillary proposals, and integration of ancillary content into the examination/data collection cycle and study databases.

Cohort Design and Relevance to the NHLBI

• Cohort design: Describe how the cohort design can facilitate a broad research agenda in the short, medium, and long-term time frames.
• Relevance to the NHLBI: Describe the research questions being investigated and major findings and relevance to heart, lung, blood, or sleep disorders. Clearly indicate the need for and timeliness of the cohort study with emphasis on how the maintenance and follow-up of the proposed cohort will advance our knowledge, methods, or prevention strategies in heart, lung, blood, or sleep disorders. The application should describe the scientific rationale underpinning the need for the cohort.

Letters of Support: A statement of commitment from each participating institution or organization must be provided. If parts of the study are to be provided by sources other than the NHLBI, provide Letter(s) of Support signed by an authorized representative. If an application is received without Letter(s) of Support, it will be returned without review.

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:

Data collected under this FOA, along with previously collected data, are expected to be widely shared through the NHLBI data repository and/or other NIH-designated repository. Metadata, protocols, manuals of procedures, algorithms for calculated data elements, and other documentation necessary to describe the study and resultant data to investigators not affiliated with the study are also expected to be widely available. Applications should detail how data generated from studies ancillary to the parent cohort will be shared.

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.

Study Record: PHS Human Subjects and Clinical Trials Information

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

Section 2 - Study Population Characteristics

Recruitment and Retention Plan

Specific to this FOA: Include a description of participant retention at the most recent examination or data collection cycle.

Study Timeline

Specific to this FOA: A study timeline is required. Provide a summary of the milestones of the overall study. If funding support for the next renewal is not secured prior to the end of the project period, a description of close-out activities is required. The study timeline must include key milestones, a description of the key milestone, and the elapsed time from receipt of award to the key milestone.

Milestones may include, but are not limited to, the following: IRB approval(s), finalized protocols and informed consent/assent document(s), operations manuals, basic content exam/data collection participant recruitment targets, integration of ancillary content, and database cleaning/lock for analysis.

Section 3 - Protection and Monitoring Plans

Overall Structure of the Study Team

Specific to this FOA: The Overall Structure of the Study Team attachment is required. Applicants must provide, but are not limited to, the following:

• A description of the applicant's role in the cohort in the overview of organizational structure,
• A description of key committee structures needed to manage the cohort
• If applicable, a description of the oversight and coordination of any sites proposed
• If applicable, a description of the role of any subcontractors
• How the committees/structures/sites proposed will be integrated with the organizational framework
• A plan to promote collaborations among investigators affiliated with the cohort
• A description of outreach efforts and prior success collaborating with investigators not affiliated with the cohort
• a description of the coordination between the various components of the organizational framework, including NHLBI

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.

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 requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact a Scientific/ Research Contact at least 20 weeks to schedule a consultation 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.

The NHLBI anticipates that all applications submitted in response to this Funding Opportunity Announcement (FOA) will be subject to the NIH policy that requires investigator-initiated applications requesting $500,000 or more in direct costs in any one year to obtain documented approval from the NHLBI. Applicants are strongly encouraged to review the NHLBI's policy regarding applications with direct costs of $500,000 or more in any one year (https://www.nhlbi.nih.gov/research/funding/500k-costs) to learn more about the pre-submission review process, including required content in the Letter of Request. Following the consultation, formal Letters of Request are required no later than 14 weeks prior to the deadline for application submission.

Granting permission to submit the application for review does NOT guarantee that the NHLBI will fund the application or that it will fund the application at the requested levels, regardless of the outcome of peer review.

Many NIH ICs encourage the use of common data elements (CDEs) in basic, clinical, and applied research, patient registries, and other human subject research to facilitate broader and more effective use of data and advance research across studies. CDEs are data elements that have been identified and defined for use in multiple data sets across different studies. Use of CDEs can facilitate data sharing and standardization to improve data quality and enable data integration from multiple studies and sources, including electronic health records. NIH ICs have identified CDEs for many clinical domains (e.g., neurological disease), types of studies (e.g. genome-wide association studies (GWAS)), types of outcomes (e.g., patient-reported outcomes), and patient registries (e.g., the Global Rare Diseases Patient Registry and Data Repository). NIH has established a "Common Data Element (CDE) Resource Portal" (http://cde.nih.gov/) to assist investigators in identifying NIH-supported CDEs when developing protocols, case report forms, and other instruments for data collection. The Portal provides guidance about and access to NIH-supported CDE initiatives and other tools and resources for the appropriate use of CDEs and data standards in NIH-funded research. Investigators are encouraged to consult the Portal and describe in their applications any use they will make of NIH-supported CDEs in their projects

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.

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?

In addition, specific to this FOA:

How will maintenance and follow-up of the proposed cohort advance scientific knowledge, methods, or prevention strategies in heart, lung, blood, or sleep disorders? How will continuation of the cohort address a broad research agenda? How will maintenance and follow-up of the cohort address current research needs in heart, lung, blood, or sleep disorders?

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

In addition, specific to this FOA:

What are the strengths in the research team's accomplishments in managing the epidemiological cohort study? How will the applicant's plan to promote collaboration and outreach efforts with the proposed team and/or with other investigators enhance the productivity of the study?

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?

In addition, specific to this FOA:

What are the strengths and potential weaknesses of the innovative approaches to the facilitation of data collection or data management of the cohort?

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

In addition, specific to this FOA:

What are the strengths and potential weaknesses in the research strategy for addressing the needs of the research program and cohort that it will support? How appropriate are the proposed outcomes for the cohort? How will the cohort management and organization plan ensure the rigorous oversight and coordination of cohort activities and sites? How will the follow-up rates and/or prior cycles of examination/data collection response rates facilitate meeting the research agenda of the cohort? What are the strengths and weaknesses of the proposed basic examination/data collection cycle as a platform for ancillary content? How effective are plans for continued longitudinal follow-up of cohort participants? How will meeting the study milestones and timeline ensure achieving the research aims? If applicable, have the investigators proposed reasonable plans for the acquisition, storage, and maintenance of biospecimens for the cohort?

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?

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.

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.

Not Applicable

Not Applicable

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

Not Applicable

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

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

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

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

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

As part of the scientific peer review, all applications:

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

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.

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

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 primary responsibility for:

The PD(s)/PI(s) assume(s) 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 in accordance with these terms and conditions of the award. As such, the awardee PD(s)/PI(s) will be responsible for all aspects of the study and cohort, as well as any modification(s), unless otherwise provided for in these terms or by action of the Steering Committee.

Specific responsibilities include:

• Defining objectives and approaches of the research
• Defining the research plan and goals
• Project design and protocol development
• Obtaining all requisite study and protocol approvals
• Participant retention and follow-up
• Data collection and quality control
• Safety and data monitoring
• Oversight of study activities, such as data analysis and interpretation, manuscript preparation, and dissemination of study results
• Overseeing/performing other scientific activities of the research plan
• Monitoring the completion of the supported activities and taking corrective actions if needed
• Participating in the activities of the cohort Steering Committee
• Accepting and implementing the policies approved by the cohort Steering Committee to the extent consistent with applicable grant regulations
• Cooperating with NHLBI programmatic, technical, and administrative staff
• Administratively managing the U01 award
• Developing collaborations with external investigators
• Making study data accessible to investigators affiliated with study (e.g. ancillary study investigators), as well as those not affiliated with the study

The awardee will provide analytical data files (illustrative examples include: derived/calculated data variables; finalized questionnaire data; data from procedures, such as spirometry, echocardiography, ECG, exercise testing, polysomnography, etc.; participant follow-up data; clinical event outcomes data) to the NHLBI PO periodically based upon a mutually agreed schedule and format and at the end of the period of this award, along with documentation necessary for their use and including ancillary study data that have been incorporated into the main database.

Awardees will be expected to evaluate and document compliance with NCI's Best Practices for Biospecimen Resources for collection, processing, and storage of future previously collected biospecimens http://biospecimens.cancer.gov/bestpractices. Awardees will be required to explore, with NHLBI staff, the feasibility of data harmonization and pooling with other cohorts and studies. Awardees are encouraged to register the cohort through ClinicalTrials.gov (http://clinicaltrials.gov). Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.

Awardees agree to the governance of the study through a Steering Committee and to accept and implement decisions approved by the Steering Committee (see "Joint Responsibilities" section below).

Awardees are expected to make their data widely available to other investigators, per NIH/NHLBI data sharing policies [https://www.nlm.nih.gov/NIHbmic/nih_data_sharing_policies.html] [https://www.nhlbi.nih.gov/research/funding/human-subjects/data-sharing].

Study investigators are strongly encouraged to publish and disseminate results, tools, resources, and other products of the study, in accordance with the study protocols and governance. It is expected that all methods, analyses, software, and algorithms will be made available in a timely manner to the scientific community.

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

The PD(s)/PI(s) are required to commit to a minimum effort of 1.2 calendar months per year, equivalent to 10% effort.

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

A designated NHLBI Project Scientist(s) will have the following responsibilities:

• Participating in the activities of the cohort's Steering Committee, as well as any relevant subcommittees as appropriate, and helping to address issues that come before these committees
• Facilitating collaborations between the awardees and other NHLBI-sponsored programs, investigators, or organizations that may contribute to the study's goals
• Assisting in the interaction between the awardees and investigators at other institutions, as appropriate for the cohort
• Promoting collaborative research efforts that involve interactions with other NIH-supported projects, programs, and centers and helping with the coordination of such efforts
• Facilitating harmonization of data and biospecimen resource optimization
• Participating in study meetings
• Providing technical assistance and advice to the awardees as appropriate
• Organizing and conducting regular meetings to share progress either by teleconference, videoconference, or face-to-face, as needed between the study investigators and centers
• Assisting with the development of research protocols
• Monitoring participant retention and study progress
• Ensuring disclosure of conflicts of interest and adherence to NHLBI policies

At the discretion of the NHLBI, an independent Observational Study Monitoring Board (OSMB) may be appointed by the Director, NHLBI, to provide overall monitoring of data and safety issues in accordance with NHLBI DSMB/OSMB policy [https://www.nhlbi.nih.gov/research/funding/human-subjects/data-safety-monitoring-policy]. Meetings of the OSMB will ordinarily be held in Bethesda, MD. An NHLBI scientist other than the NHLBI Program Official or Project Scientist will serve as Executive Secretary to the Board. Because the OSMB serves as an independent group advisory to the NHLBI, study investigators shall not communicate with OSMB members regarding study issues, except as authorized by the Board's Executive Secretary.

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

The NHLBI policy on authorship and manuscript review of NHLBI-sponsored extramural research protects against conflicts of interest with the Program Officer.

The NHLBI reserves the right to withhold funding or curtail the study in the event that any of the following occur:

• Substantial shortfall in participant recruitment, follow-up, data reporting, or quality control
• Major breach of the protocol or substantive changes in the agreed-upon protocol, methodologies, and/or tools with which the NHLBI cannot concur
• Failure to develop or implement a mutually agreeable protocol
• Human participant ethical issues that may dictate a premature end of the award
• Results that substantially diminish the scientific value of study continuation

Areas of Joint Responsibility:

NHLBI will publish a guide notice announcing the date of the exam and the suggested timing to submit applications for ancillary study components (research projects that rely on study infrastructure and basic content exam/data collection cycle). The PD(s)/PI(s) will be expected to work collaboratively with investigators proposing ancillary study components.

Funding support for the basic content examination/data collection cycle is conditional upon obtaining support for at least one research project that relies on the study infrastructure and basical content examination/data collection cycle. The funding support for the research project must be obtained through a process that involves independent peer review.

Each cohort funded under this FOA shall have a Steering Committee (SC) that serves as the main governing board. The SC voting membership shall be determined jointly by the PDs/PIs and the NHLBI, but shall minimally consist of the study center PIs, the NHLBI Project Scientist(s), the DCC PI (if applicable), and the biorepository PI (if applicable).

The appointed voting Steering Committee members will be required to attend all Steering Committee meetings and teleconferences, or to appoint a substitute that will be fully briefed on the issues at hand. Additional non-voting members to serve in an advisory capacity may be added to the Steering Committee as needed by a decision of the existing voting committee members. The Steering Committee may also form subcommittees as needed. The NHLBI Project Scientist(s) may serve on such subcommittees as deemed appropriate. The Chair of the Steering Committee will be selected from the SC voting members.

The Steering Committee will have primary responsibility for:

• Overseeing the overall organization of the study's core functions
• Providing guidance on scientific and infrastructural issues pertinent to the funded cohorts
• Providing guidance, oversight, and coordination of the activities of the cohort investigators towards cross-cohort data harmonization, if requested by the NHLBI
• Contributing to the development of policies and processes pertinent to the cohort infrastructure and for approving ancillary components to the cohort

All investigators/staff within the study will be required to accept and implement the policies approved by the Steering Committee to the extent consistent with applicable grant regulations.

Where applicable, the awardee will work with the NHLBI on efforts to harmonize data across NHLBI cohorts and studies, and explore the feasibility of using common data standards and elements.

NHLBI will partner with the PD(s)/PI(s) to ensure dataset and documentation preparation is congruent for submission to the Biological Specimen and Data Repository Information Coordinating Center (BioLINCC) (https://biolincc.nhlbi.nih.gov/submit_datasets/) as described in the NHLBI Policy for Data Sharing from Clinical Trials and Epidemiological Studies (https://www.nhlbi.nih.gov/research/funding/human-subjects/data-sharing), and the Guidelines for NHLBI Data Set Preparation (https://www.nhlbi.nih.gov/research/funding/human-subjects/set-preparation-guidelines). Large-scale genomic data generated via ancillary studies are to be deposited along with associated phenotype data into the database of Genomic and Phenotype Data (dbGaP, accessed at http://www.ncbi.nlm.nih.gov/gap) in accordance with the NIH Genomic Data Sharing Policy available at https://gds.nih.gov/03policy2.html.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

Multiple PD/PI Dispute Resolution:

If a conflict develops between the PD(s)/PI(s) in a multiple PD/PI application, the following procedures will apply: The Departmental administrators representing the PD(s)/PI(s) shall meet and attempt in good faith to settle any dispute, claim, or controversy arising out of or relating to the interpretation, performance, or breach of this disagreement. However, if the Departmental administrators fail to reach a resolution in 30 days then the NHLBI may invoke dispute resolution procedures as described in the above paragraph.

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: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573

Division of Cardiovascular Sciences

Sean Coady, MS
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-1289
Email: coadys@mail.nih.gov

Division of Lung Diseases

Lisa Postow, PhD
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-827-7843
Email: postowl@mail.nih.gov

Division of Blood Diseases and Resources

Ellen Werner, PhD
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-827-8298
Email: wernere@mail.nih.gov

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

Benjamin Sakovich
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-827-8049
Email: sakovichbj@mail.nih.gov

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

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