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

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

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

Purpose

This Funding Opportunity Announcement (FOA) seeks to accelerate the pace and expand the breadth of scientific research on the clinical course, prevention and treatment of diseases within NHLBI's mission by leveraging ongoing clinical research studies through ancillary studies. This FOA invites research project applications to conduct ancillary studies to clinical research studies, including clinical trials, prospective observational studies, and or registries. Applications submitted to this FOA should propose to collect new information and/or biological samples from participants of the ongoing parent study, and should address new research questions that are beyond those specified in the approved protocol of the parent study and are within the scientific mission of the NHLBI. Applications submitted in response to this FOA should not be used to extend the duration of the parent study or to provide funds solely for parent study enrollment, capitation, or study performance.

Background and Objectives

Clinical studies represent a substantial research investment and are unique sources of well-characterized patient populations. They are not, however, usually structured to permit a detailed investigation of underlying mechanisms of a disease and its progression. For example, identifying surrogate markers is crucial for predicting which patients are at high risk, and for designing treatments that can be tailored and targeted to patients with specific characteristics. Such investigations often are best conducted as ancillary studies, and thus require supplementary funding. Overall, a relatively modest investment in time-sensitive ancillary studies can result in significant scientific gains in translational and clinical research without incurring the substantial cost of recruiting a new cohort, and can lead to improved diagnostic and prognostic assessments and patient care. This FOA will facilitate the use of existing patient cohorts for the study of disease processes and outcomes, genetics and proteomics, therapeutic response, quality of life, behavioral and lifestyle issues, treatment adherence, and health economics via a flexible, cost-effective, and administratively efficient mechanism. Experience has shown that the standard NIH grant process may take too long to initiate ancillary studies quickly enough to utilize existing large cohorts to full advantage.

This FOA will use an expedited peer review and modular funding to conduct time-sensitive ancillary studies related to heart, lung, and blood diseases and sleep disorders in conjunction with ongoing clinical research studies including clinical trials, prospective observational studies, and or registries. Applications to this FOA are expected to contribute to the evidence base for important health matters of relevance to the research mission of NHLBI. For additional information about the mission, strategic vision, and research priorities of the NHLBI, applicants are encouraged to consult the NHLBI website: http://www.nhlbi.nih.gov.

Specific research interests of the Institute are identified in the NHLBI Strategic Vision. Information about clinical trials currently supported by a variety of public and private entities can be obtained from http://www.clinicaltrials.gov. Applications submitted under this FOA must collect new information and/or biological samples from participants enrolled in the ongoing parent study or the application will not be supported. Ancillary studies which propose to use only previously collected data and/or biological samples may be submitted to the following NHLBI FOAs: Maximizing the Scientific Value of the NHLBI Biorepository (RFA-HL-17-022), Secondary Analysis of Existing Datasets in Heart, Lung, and Blood Diseases and Sleep Disorders (PAR-17-004), or other relevant NIH FOAs, including the NIH Parent R01.

This FOA will support applications that involve the entire parent cohort, selected subsets of the parent cohort, or participants from two or more parent cohorts, depending on the scientific questions posed and the required sample size. In general, this FOA will not support the recruitment of participants not currently enrolled in a parent cohort study or studies; however, recruitment of a comparator population for a specific measurement or a population that will substantially enhance the findings of the ancillary study is appropriate.

This FOA may not be used to extend the duration of the parent study. Thus, applications that request additional funds to extend the parent study are not appropriate for this FOA and will not be supported. Collection of data or biological samples for ancillary studies proposed under this FOA must be completed within the funding period of the parent study or a detailed plan, including associated costs, must be provided describing what components of the ancillary study will be performed after the parent study ends and how those activities will be accomplished.

Applications to this FOA must include a letter from the appropriate committee (e.g., Ancillary Study Committee) or person (e.g., Chair of the Steering Committee) representing the parent study indicating that the parent study is willing to provide the ancillary study investigators with access to participants, samples and data, and there is adequate time remaining in the parent study to complete the ancillary research project as scientifically and technically appropriate. The letter should indicate that the proposed ancillary study will not interfere with the parent study or unduly burden participants. All approved procedures and policies of the parent study must be followed. Applications that do not include letter(s) from the appropriate committees are incomplete for this FOA and will not be peer reviewed; please see Section IV.2.

To take advantage of a new clinical outcome and/or biological sample collection from the start of participant recruitment (baseline), ancillary study applications may be submitted to this FOA before a funded parent study has begun recruitment. Each ancillary study application must demonstrate the time-sensitive nature of the application and must explicitly address why an expedited review is essential to its feasibility. Applications in which the critical timelines for the parent study and ancillary study are incompatible or ambiguous are not appropriate for this FOA and will not be supported..

This program encourages basic scientists and clinical investigators from academia and industry to work together. In addition, this FOA encourages junior investigators to take a leading role in clinical research with the support and collaboration of senior investigators. In general, the program PD(s)/PI(s) of the ancillary study should not be a PD/PI of the parent study. However, partnerships between a senior investigator from the parent study and a junior PD/PI in the conduct of the ancillary study are appropriate.

Areas of Research Interest

Topics of study may include but are not limited to:

• Identify additional and/or unique/emerging risk factors for the disease(s) of interest to NHLBI
• Delineate pathogenic mechanisms of disease
• Identify mechanisms or factors that influence and/or predict response to treatment
• Discover or validate biomarkers of disease development and/or progression
• Identify or characterize co-morbid illnesses associated with the disease(s) of interest to NHLBI
• Describe the natural history and risk factors for an additional disease(s), i.e., different than the focus of the parent grant
• Determine the effects of the parent study intervention(s) on an additional outcome(s) or disease(s)
• Validate novel technologies and tools (including digital health tools) for disease prevention, diagnosis, treatment and management

A variety of approaches (including genetics, proteomics and metabolomics) may be used. Examples of relevant research include but are not limited to the following:

Cardiovascular: Mechanisms underlying cardiovascular diseases; cardiovascular disease risk factors; individual variations in the trajectory of disease progression and response to treatment; studies of cardiac energetics before and after control of metabolic abnormalities; imaging studies to elucidate disease progression or to clarify the mechanism of action of interventions; identification and validation of biomarkers of cardiovascular diseases; cardiovascular disease as a co-morbidity of other conditions, including HIV infection, chemotherapy, traumatic brain injury, spinal cord injury, and auto-immune diseases; identification of vascular pathologies associated with dementia; and adoption of the Accumulating Data to Optimally Predict Obesity Treatment (ADOPT) Core Measures from at least two of the four ADOPT domains to an adult weight loss or weight gain prevention trial.

Pulmonary: Mechanisms underlying pulmonary diseases, including immunological aspects of pathobiology; biomarkers and risk factors for acute and chronic pulmonary diseases, including genomics and other omics; factors contributing to individual variations in lung disease susceptibility, manifestations, or progression; characteristics associated with individual variations in responses to treatments; co-morbidities of pulmonary diseases; subgrouping of diseased populations based on clinical, imaging, and molecular measures; associations of pulmonary pathobiology with environmental factors such as historical measures of air pollution; interactions of pulmonary diseases with sleep disorders and circadian biology; associations between pulmonary diseases and cardiovascular abnormalities; and systems analyses of high dimensionality clinical/molecular datasets obtained in pulmonary cohorts.

Hematological: Mechanistic studies and biomarker research on non-malignant hematologic disorders, including hemoglobinopathies and disorders of thrombosis and hemostasis. Examples include mechanisms of action of therapeutic agents in sickle cell disease, identification of biomarkers of sickle cell crisis and other organ damage, and biomarkers to predict clinical events in disorders of thrombosis and hemostasis. Mechanistic studies and biomarker research on the outcomes and complications associated with cellular therapies and the transfusion of blood products. Examples include identifying the immune mechanism of cellular therapies, biomarkers to predict graft vs. host disease and immune and other effects of transfusion. Research to understand how female sex hormones affect development, proliferation and differentiation of hematopoietic stem cells and their associated blood disorders; and how high levels of female sex hormones and sex hormone therapies induce thrombo-embolism in adolescents, premenopausal and post-menopausal women.

Behavioral: Behavioral and psychosocial aspects of disease progression; lifestyle factors and their assessment or relationship to biomarkers; gene-environment interactions; adherence to treatment; quality of life indices; relationships with sleep; delivery of health services; and health economic factors.

Sleep: Delineate behavioral, physiological, and molecular signatures (i.e. biomarkers) to stratify individual susceptibility to sleep-disordered breathing (sleep apnea), insufficient sleep, sleepiness/fatigue, and circadian rhythm misalignment. Identify mechanisms by which sleep and/or circadian deficiency mediates cardiometabolic, pulmonary, and hematologic disease risk and pathophysiology. Investigate the interaction of sleep and circadian deficiency with social determinants resulting in racial/ethnic, gender, and socioeconomic status (SES) disparities in heart, lung, and blood pathobiology and outcomes. Determine the impact of co-morbid sleep/circadian deficiency on the effectiveness of existing treatments for heart, lung, and blood diseases.

Implementation research: Understand disparities in sleep phenotypes and the relationship to disparities in disease risk; determine the contribution of evidence-based interventions for sleep impairment to unexplained differences in cardiovascular risk and disease outcomes, by race/ethnicity, gender, socioeconomic position, and age; analyze the implementation of evidence-based, cost-effective stroke prevention (primary and secondary) programs for women in low- and middle-income countries; implement and evaluate evidence-based interventions to address obesity among adolescent females and adult women; enhance the diversity and foster career development of young female investigators involved in HLBS disparities science both domestically and abroad.

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

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from 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, 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
6701 Rockledge Drive, Room 7214
Bethesda, MD 20892-7924 (Express Mail Zip: 20817)
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.

Other Attachments: The attachments listed below must be completed and attached or the application will not be peer reviewed.

1. Parent Study Synopsis

A description of the parent study design and operation must be provided as an attachment using the filename "Parent Study Synopsis.pdf" and may not exceed 6 pages. Provide details for each bullet below:

• Sponsor
• Study name and website (when applicable)
• Lead investigator(s) and institutions
• Study design (including statistical analysis plan)
• Study objectives
• Primary outcomes/endpoints
• Secondary outcomes/endpoints
• Main inclusion criteria
• Main exclusion criteria
• Study duration
• Study site(s)
• Number of participants
• Present status of the study and timeline
• Visit schedule (including visits occurred and planned)
• Data and safety monitoring (when applicable)
• Funded ancillary studies (including relevant information that will help understand the impact of the ongoing ancillary studies on the proposed ancillary study)
• Other information that may impact the proposed ancillary study

2. Parent study informed consent form: A copy of the parent study IRB-approved informed consent form must be included as an attachment named "Parent Study Informed Consent.pdf".

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.

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

Research Strategy:

Applicants must specifically address the following:

• How the proposed ancillary research will contribute to the evidence base for important health matters of relevance to the research mission of NHLBI and/or align with the NHLBI's Strategic Vision
• How the parent study research design and cohort is able to provide appropriate infrastructure and resources for the proposed ancillary study
• Demonstrate the time-sensitive requirement of the ancillary study in relation to the parent study
• Provide the current status and relevance of the proposed research and the approach to data collection
• Provide a detailed plan for patient follow-up, data collection, and data coordination if the proposed ancillary study continues sample/data collection after the parent study is completed.
• Describe how the ancillary study will integrate with the organizational framework of the parent study. This should include, but is not limited to, the roles and responsibilities of the parent and ancillary study staff; a communication plan between the studies; plans for providing administrative, business, and operational support; and dispute resolution.

Note for Applications Proposing the involvement of Human Subjects and/or Clinical Trials: Use the Research Strategy section to discuss the overall strategy, methodology, and analyses of your proposed research, but do not duplicate information collected in the PHS Human Subjects and Clinical Trial Information Form. The PHS Human Subjects and Clinical Trial Information Form will capture detailed study information, including eligibility criteria; inclusion of women, minorities, and children; protection and monitoring plans; and statistical design and power.

Letters of Support:

Applications must include a letter from the appropriate committee or person (e.g., Ancillary Study Committee or Chair of the Steering Committee) indicating that the parent study is willing to provide the ancillary study investigators with access to participants, samples and data, and there is adequate time remaining in the parent study to complete the ancillary research project as scientifically and technically appropriate. The letter should indicate that the proposed ancillary study will not interfere with the parent study or unduly burden participants, and that all approved procedures and policies of the parent study will be followed. If the proposed ancillary study will extend beyond the project period of the parent study, the letter of support must include a commitment from the collaborating parent study PDs/PIs regarding continuity of the collaboration and available resources beyond the parent study period of support. The letter must also address the agreement between the parent and ancillary study regarding sample sharing, data harmonization and sharing, and communication between the investigators involved in the ancillary study and parent study. Applications that do not include letter(s) from the appropriate committee(s) or person(s) demonstrating the approval and cooperation of the parent study for the proposed ancillary research in response to this FOA will be considered incomplete and will not be peer reviewed.

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

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

Appendix:

Only limited Appendix materials are allowed. 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 (and when applicable, clinical trials research experience) 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 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

2.4 Inclusion of Women, Minorities, and Children has the following additional instructions:

Justify the anticipated or projected sample size for the overall cohort and for any relevant subgroups (i.e., demonstrate whether the sample size is sufficiently powered to address the study's aims).

2.5 Recruitment and Retention Plan has the following additional instructions:

Describe contingency plans to manage potential delays or barriers with participant recruitment in the overall cohort as well as in key subgroups

2.7 Study Timeline has the following additional instructions:

Applicants must include both a description and a table or graph of the overall study timeline and key milestones. Include the following milestones from receipt of award to the key milestone in the study timeline, as applicable:

• IRB approval(s) of final protocol and informed consent
• Study registration in ClinicalTrials.gov no later than 21 days following enrollment of the first study participant
• Finalized standard operating procedures (SOPs), operations manuals, data collection protocols, and informed consent/assent document(s)
• Anticipated start and end dates for participant recruitment and data collection(s)
• Study initiation
• Enrollment of the first participant
• Enrollment of 25%, 50%, 75% and 100% of the projected recruitment for all study participants, including women, minorities and children (as appropriate)
• Collection of data related to primary and secondary endpoints and database lock
• Submission of primary manuscript to peer-reviewed scientific journal(s) and dissemination of results
• Submission of study results to ClinicalTrials.gov within 12 months of the primary completion date

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 are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions 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?

Specific to this FOA:

How will the proposed ancillary study advance scientific knowledge in heart, lung, blood, or sleep disorders?

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?

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

Specific to this FOA:

In addition, for 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?

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, for 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?

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?

Specific to this FOA:

How well is the parent study research design and cohort able to provide appropriate infrastructure and resources for the proposed ancillary study? Does the proposed collect new information and/or biological samples from participants enrolled in the ongoing parent study or studies? How compelling is the time-sensitive requirement of the ancillary study demonstrated in relation to the parent study? Are the listed milestones and timeline appropriate for the goals of the project? To what extent are the milestones relevant, measurable, achievable, result-focused and time-bound? How strong are the proposed contingency plans in the event that there is inadequate progress towards achieving the milestones? Is the extension of the ancillary study beyond the parent study well justified, if applicable? If the ancillary study will continue after the parent study ends, is there sufficient resource(s) to support the ancillary study?

In addition, for 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 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?

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?

Specific to this FOA:

How well is the parent study research design and cohort able to provide appropriate infrastructure and resources for the proposed ancillary study? Does the proposed collect new information and/or biological samples from participants enrolled in the ongoing parent study or studies? How compelling is the time-sensitive requirement of the ancillary study demonstrated in relation to the parent study? Are the listed milestones and timeline appropriate for the goals of the project? To what extent are the milestones relevant, measurable, achievable, result-focused and time-bound? How strong are the proposed contingency plans in the event that there is inadequate progress towards achieving the milestones? Is the extension of the ancillary study beyond the parent study well justified, if applicable? If the ancillary study will continue after the parent study ends, is there sufficient resource(s) to support the ancillary study?

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?

In addition, for 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 this FOA:

Is there a clear commitment of the parent study to support the conduct of the ancillary study?

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

Study Timeline

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 potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

Burden

Has the burden of the proposed ancillary study on the parent study and its participants been adequately described?

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

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

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

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Not Applicable

Not Applicable

Not Applicable

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

Not Applicable

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

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

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

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

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by 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 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.

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: 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

Jue Chen, Ph.D.
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0550
Email: jue.chen@nih.gov

Division of Lung Diseases
Aaron Laposky, Ph.D.
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0199
Email: laposkya@nhlbi.nih.gov

Division of Blood Diseases and Resources

Sharon Smith, Ph.D.
National Heart, Lung, and Blood Institute
Telephone: 301-435-0065
Email: smithsh1@mail.nih.gov

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

Nina Hall, M.B.A.
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-2393
Email: nina.hall@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.