PAR-27-013-Full-Announcement.html

Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Heart, Lung, and Blood Institute (NHLBI)

Funding Opportunity Title

Data Coordinating Center for Multi-Site Investigator-Initiated Clinical Trials (Collaborative U24 Clinical Trial Required)

Activity Code

U24 Resource-Related Research Projects – Cooperative Agreements

Announcement Type

Reissue of

PAR-22-193

Related Notices

Check for any recent Notices of NIH Policy Changes that may impact application requirements.

Funding Opportunity Number (FON)

PAR-27-013

Companion Funding Opportunity

PAR-27-012

UG3/

UH3

Phase 1 Exploratory/Developmental Cooperative Agreement/Exploratory/Developmental Cooperative Agreement Phase II

Number of Applications

See Section III. 3. Additional Information on Eligibility.

Assistance Listing Number(s)

93.837, 93.840, 93.233, 93.838, 93.839

Funding Opportunity Purpose

This Notice of Funding Opportunity (NOFO) supports applications for a collaborating Data Coordinating Center (DCC) for investigator-initiated multi-site clinical trials including efficacy, comparative effectiveness, pragmatic and/or implementation research clinical trials. Trials using innovative designs such as platform trials, adaptive, and Bayesian designs are encouraged. These trials may include ones that test different therapeutic, behavioral, and/or prevention strategies. Trials for which this NOFO applies must be relevant to the research mission of the NHLBI and meet the NIH definition of a clinical trial (see NOT-OD-15-015). For additional information about the mission, strategic vision, and research priorities of the NHLBI, applicants are encouraged to consult the NHLBI website.

This NOFO will utilize a milestone-driven cooperative agreement mechanism of award and runs in parallel with a companion NOFO (PAR-27-012) for a collaborating Clinical Coordinating Center (CCC). The objective of the DCC application is to present a comprehensive plan to provide overall project coordination, administration, data management, and biostatistical support for the clinical trial proposed in the collaborating CCC application. The application should also describe its approaches to collaborate with the CCC on implementation of the clinical trial community engagement plan.

Both a DCC application and a collaborating CCC application must be submitted on the same application due date for consideration by NHLBI. Applicants are strongly encouraged to contact the appropriate Scientific/Research contact prior to submitting an application.

Funding Opportunity Goal(s)

The Division of Cardiovascular Sciences supports research and training to foster heart and vascular research in the basic, translational, clinical and population sciences, and to foster training to build talented young investigators in these areas, funded through competitive research training grants.

The Division of Lung Diseases supports research and research training on the causes, diagnosis, prevention, and treatment of lung diseases and sleep disorders.

The Division of Blood Diseases and Resources supports and research and training to foster research and research training on the pathophysiology, diagnosis, treatment, and prevention of non-neoplastic blood diseases, including anemias, sickle cell disease, thalassemia; biology of red blood cells, white blood cells, and platelets, hematopoietic stem cells and the bone marrow niche, hemophilia and other abnormalities of hemostasis and thrombosis.

The Center for Translation Research and Implementation Science (CTRIS) plans, fosters, and supports late-stage research to identify promising approaches for ensuring successful integration of evidence and evidence-based interventions within clinical and public health settings, such as health centers, worksites, schools, and communities in the United States and abroad.

The National Center on Sleep Disorders Research (NCSDR) supports research and research training related to sleep disordered breathing, and the fundamental functions of sleep and circadian rhythms.

Key Dates

Posted Date

March 18, 2026

Open Date (Earliest Submission Date)

May 02, 2026

June 02, 2026

July 02, 2026

Not Applicable

April 2027

October 02, 2026

November 02, 2026

Not Applicable

July 2027

February 01, 2027

March 01, 2027

Not Applicable

December 2027

June 02, 2027

July 02, 2027

Not Applicable

April 2028

October 01, 2027

November 01, 2027

Not Applicable

July 2028

February 01, 2028

March 01, 2028

Not Applicable

December 2028

June 01, 2028

June 30, 2028

Not Applicable

April 2029

October 02, 2028

November 02, 2028

Not Applicable

July 2029

All applications are due by 5:00 PM local time of applicant organization.

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

Expiration Date

November 03, 2028

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts).

Conformance to all requirements (both in the How to Apply - Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the How to Apply - Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the How to Apply - Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

Table of Contents

Part 1. Overview Information Key Dates Part 2. Full Text of Announcement Section I. Notice of 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

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

NOFO Research Objectives This NOFO supports applications to develop and conduct a Data Coordinating Center (DCC) for investigator-initiated multi-site clinical trials submitted to the collaborating Clinical Coordinating Center NOFO (PAR-27-012). Clinical trials supported by this NOFO include Phase II and above clinical trials that will enroll participants from two or more recruitment sites. Applications that propose to leverage resources and infrastructure of active clinical trial networks are also supported by this NOFO. This NOFO will utilize a cooperative agreement mechanism (U24) and will be milestone-driven and performance-based to achieve completion of the clinical trial on time and on budget. The DCC is integral to the proficient operation of a clinical trial. The DCC contributes critically to the study design, ensures appropriate adverse event monitoring and reporting, manages data, conducts statistical analyses, and helps with the dissemination of results. The data are often randomized and blinded and the DCC statistician(s) hold the key to the codes. Thus, an independent DCC is a necessary component of any multi-site clinical trial in order to ensure data integrity.

Proposed research may utilize a design anywhere along the continuum of efficacy, effectiveness, pragmatic and/or implementation research clinical trials. For this NOFO, pragmatic trials are considered those that test an intervention under the usual clinical conditions in which it will be applied, while efficacy trials do so under more idealized circumstances. Implementation trials test strategies to adopt and integrate evidence-based health interventions and change practice patterns within specific settings. These implementation trials can include hybrid implementation/effectiveness studies. Innovative trial designs such as adaptive designs will be considered. The trial design should be appropriate for the study question. Trials for which this NOFO applies are expected to contribute to the evidence base for important health matters of relevance to the research mission of NHLBI, close gaps in health outcomes within the US population and increase health for all. For additional information about the mission, strategic vision, and research priorities of the NHLBI, applicants are encouraged to consult the NHLBI website.

A key characteristic of this NOFO is the completion of core milestones. A core milestone is defined as a scheduled event in the project timeline that signifies the completion of a major project stage or activity. Milestones must be performance-based to achieve completion of the trial on time and on budget, and must be established to align with the bi-phasic mechanism of the CCC award. Milestones must be established for both the first year (coinciding with the UG3 phase of the CCC award) and subsequent years (coinciding with the UH3 phase of the CCC award) of the project. These clinical trials are expected to be conducted with a high degree of efficiency, with streamlined administrative procedures wherever possible. Applicants are strongly encouraged to employ project management principles as appropriate. Applications that address contingency plans to proactively confront potential delays or disturbances in meeting the milestones are strongly encouraged.

Phases of Award The first year of the DCC will correspond to the UG3 phase of the collaborative CCC application and is intended to support the development of case report forms and other resources necessary to the performance of the clinical trial; further development of study partnerships; finalization of the protocol and approval by a Data and Safety Monitoring Board (DSMB); Single Institutional Review Board (see NOT-OD-16-094) approvals of the trial protocol; informed consent(s)/assent(s); development of the manual of operations; data management systems and randomization procedures; finalized integrated project management plans; training and activation of clinical sites; and initiation of enrollment of trial participants by the end of the first year.

The second year of the DCC award is contingent on the successful completion of the UG3 phase of the collaborative CCC application, and corresponds to the first year of the UH3 phase of the CCC. The decision to proceed beyond the first year of the DCC award will be made after administrative reviews of the progress made by both the DCC and the CCC are conducted approximately 9 months into award (i.e., progress report will be due), with particular attention paid to the extent to which agreed-upon milestones have been met and are subject to the availability of funds. Due to the collaborative and parallel nature of these NOFOs, NHLBI will enter into negotiation with the DCC to achieve early phase-out of the award if CCC or DCC progress is deemed inadequate upon administrative review.

For trials using an FDA regulated product and requiring an IND or IDE application to administer the product to humans, investigators must (1) secure IND authorization or IDE approval and (2) provide documentation of this authorization or approval to NHLBI before a funding decision will be made. Necessary drugs, devices, or other resources must be obtained by the end of the first year of the award to allow for the full execution of the proposed clinical trial. In addition, proposed clinical trials are expected to be able to begin enrollment by the end of the first year of the DCC award.

U24 milestones must address timing of overall recruitment/enrollment and retention goals, including accrual goals for women, minorities, and individuals of all ages including children and older adults. It is expected that, if funded, both the CCC and DCC will be responsible for milestone completion but that only one party, the CCC or the DCC, will be responsible for recording the completion of both CCC and DCC milestones through eConnect, an NHLBI platform that facilitates transfer of electronic information to NHLBI.

NHLBI policies regarding milestones and relevant clinical research/studies policies are described in the following: NHLBI Accrual of Human Subjects (Milestones) Policy, NHLBI Policy for Inclusion of Women and Minorities in Clinical Research, NHLBI Policy for Data and Safety Monitoring of Extramural Clinical Studies, NIH Single IRB Policy and NHLBI Supplement to the NIH Policy for Data Management and Sharing Note: This DCC NOFO runs in parallel with a companion NOFO (PAR-27-012) for a collaborating Clinical Coordinating Center (CCC). Both a DCC application and a collaborating CCC application must be submitted on the same due date for consideration by NHLBI. DCC applications submitted without a collaborative CCC (UG3/UH3) application will be deemed incomplete and will not proceed to review. Applicants are encouraged to use the Compendium of Best Practices for Data Coordinating Centers as a reference tool.

Prior to Submission Applicants are strongly encouraged to consult with the Scientific/Research contacts for the area of science for which they are planning to develop an application prior to submission to confirm the NHLBI-specific clinical trial NOFO to which the application should be submitted. Early contact (at least 12 weeks prior to submission) is encouraged. This period of time provides an opportunity for NHLBI staff to discuss the scope and goals of the applications, and to provide information and guidance to potential applicants.

Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs.

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

Section II. Award Information

Funding Instrument

Cooperative Agreement: A financial assistance mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this NOFO.

Application Types Allowed

New

Resubmission

Revision

The OER Glossary and the How to Apply - Application Guide provide details on these application types. Only those application types listed here are allowed for this NOFO.

Clinical Trial?

Required: Only accepting applications that propose clinical trial(s).

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

Award Budget

Application budgets are not limited but need to reflect the actual needs of the proposed project.

Award Project Period

The scope of the proposed project should determine the requested project award period.

The period of award is expected to be 5 years. Up to 7 years may be requested if strongly justified.

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

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Nonprofits Other Than Institutions of Higher Education

For-Profit Organizations

Local Governments

Federal Governments

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 Organizations)

Foreign Organizations/Foreign Collaborations

Non-domestic (non-U.S.) Entities (Foreign Organizations) are 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.

NIH will no longer issue awards (i.e., new, renewal, or non-competing continuation) to domestic or foreign entities that involve foreign subawards/subcontracts. All NIH-funded research involving foreign subawards/subcontracts must be submitted in response to a NOFO that is specifically designated for funded international collaborations. This new requirement was effective, May 1, 2025.

Applications involving foreign subawards/subcontracts submitted in response to this NOFO will be deemed noncompliant and will not be considered for funding. This policy applies to all monetary international collaborations resulting in foreign subawards/subcontracts, however, it does not preclude unfunded international collaborations or foreign components, funding for foreign consultants, or procurement of unique equipment or supplies from foreign vendors.

Required Registrations

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the How to Apply - 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. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information

System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.

NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.

Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.

eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registrations; all registrations must be in place by time of submission. 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 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.

Eligible Individuals (Program Director/Principal Investigator)

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 their organization to develop an application for 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 How to Apply - Application Guide.

Because the NOFO already supports a team approach between groups of experts across sites and collaborating applications Multiple PDs/PIs (MPIs) are encouraged. The CCC application and DCC application should refrain from having overlapping key personnel on both applications.

ESI applicants can be the PI/PD of an application providing they can show support of investigators with appropriate clinical trial data coordinating experience (as part of a multiple PI team). ESIs are encouraged to be part of the study team and they should be budgeted for support at a level appropriate for the role on the project.

2. Cost Sharing This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement NIH Grants Policy Statement Section 1.2 Definition of Terms.

3. Additional Information on Eligibility Number of Applications

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, per NIH Grants Policy Statement Section 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:

This NOFO only accepts applications that are part of a collaborative pair of applications. The pair must include one DCC U24 application to this NOFO (PAR-27-013) plus one application to the companion CCC UG3/UH3 NOFO (PAR-27-012).

Section IV. Application and Submission Information

1. Requesting an Application Package The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise (in this NOFO, in a policy notice, or other notice from NIH Guide for Grants and Contracts). Conformance to the requirements in the How to Apply - Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Page Limitations All page limitations described in the How to Apply – Application Guide and the Table of Page Limits must be followed.

Instructions for Application Submission

The following section supplements the instructions found in the How to Apply – Application Guide and should be used for preparing an application to this NOFO.

SF424(R&R) Cover All instructions in the How to Apply - Application Guide must be followed.

Descriptive Title of Applicant's Project: To allow NIH to identify a related set of collaborative applications, the title of each application in the set must have the following format: a “1/N” indicator + Identical Title (e.g., “1/3”, where the 1/3 means this is site 1 of 3 sites in the set. The other sites will be labeled 2/3, etc.) Titles may not exceed 200 characters in length, including the tag, e.g., 1/3, at the beginning of the title.

Cover Letter Attachment: The Cover Letter is one PDF file only. The following collaborative information is required in the Cover Letter: a listing of all the applications that are a part of the set of collaborative applications being submitted, including for each: 1) the PD/PI(s) name(s), 2) the Title (including the tag, e.g., “1/3”), and 3) the Applicant Institution.

SF424(R&R) Project/Performance Site Locations

SF424(R&R) Other Project Information

Facilities and Other Resources: Describe the facilities and resources available for the coordination of a multi-site clinical trial, including project management tools that will be used. Describe how the infrastructure at the DCC and performance sites will facilitate the efficient operation of the proposed multi-site clinical trial. If applicable, discuss any community participatory agreements and/or stakeholder agreements to support the protocol.

Other Attachments: The following attachments marked as "Required", must be provided, or the application will not proceed to peer-review:

1. Trial Management Plan (Required): A description of how the proposed trial will be managed must be provided as an attachment using the filename "Trial Management Plan.pdf" and may not exceed 5 pages. Describe the strategy that will be used throughout the project to ensure that management activities of the clinical trial are performed including directly supporting the needs of scientific study leadership to identify barriers, make timely responses, and optimize the allocation of limited resources to meet pre-defined study objectives. This description should include:

In summary, the trial management plan should provide sufficient details to demonstrate the ability to achieve the goals of the clinical trial on-budget and on-time and to successfully manage and mitigate risks.

2. Clinical Trial Research Experience (CTE) (Required):

Applicants must provide a table listing the characteristics of trials that demonstrate experience from key personnel in trial coordination in the last 5 years. The table must be provided as an attachment called "Clinical Trial Research Experience.pdf" and may not exceed 3 pages.

The table columns should include:

Column A: clinical study title Column B: applicant's role in the study Column C: a brief description of the study design Column D: planned enrollment Column E: actual enrollment Column F: number of sites Column G: whether the studies were completed on schedule or not Column H: publication reference(s)

3. Network Description (Optional):

A Network Description Plan is optional and should only be provided as an attachment using the filename "Network Description.pdf" if the proposed clinical trial is to be conducted using the infrastructure of an existing Network. This attachment may not exceed 6 pages and should include the following description:

SF424(R&R) Senior/Key Person Profile

The PD/PI (or Multi-PDs/PIs) of the DCC must be experienced in the coordination and management of multi-center clinical trials, including success in meeting milestones and timelines. The experience of each PD/PI and all Key Personnel must be carefully documented and roles and responsibilities must be well-defined. DCCs require a multidisciplinary team and the application should reflect the team's hands-on involvement in DCC functions, including coordination, tracking, logistics and administration, communications, data management (including quality control), data security and IT infrastructure (including development of public and secure study websites), regulatory support, and biostatistical/analytical support. Applicants must include personnel and corresponding biographical sketches for the DCC only. All Key Personnel who are major scientific contributors to the study must provide an NIH Biosketch whether or not they are budgeted. The PD/PI (or Multi-PDs/PIs) for the DCC cannot be Key Personnel on the CCC application.

R&R Budget

The application must include only its own budget, including any subcontract budgets associated with it. Separate itemized budgets must be prepared for each subcontract. The application must provide detailed annual budgets that will enable the DCC to meet its milestones.

All costs requested and all changes in budgets after the first year should be clearly identified and justified. The DCC budget must be synchronized with the CCC budget. Include costs associated with community engagement activities (e.g., community advisory board(s), infrastructure needs), as applicable.

If parts of the costs of the trial are to be provided by sources other than NHLBI, these contributions must be presented in detail in the budget justification. Third Party support of the proposed research activity (if approved) will be incorporated as a Special Award Condition. Applicants are reminded that although Cost Share is not required, if these types of costs are included in the research application and peer reviewed, it is expected that these costs will not be covered by NHLBI.

An NHLBI-appointed DSMB will be required per NHLBI policy. The DCC should include in their budget all costs associated with DSMB activities. This includes the costs for preparing reports for the DSMB and meeting reimbursement for the DSMB members. The DCC should assess the need for liability insurance for DSMB members and provide a plan commensurate with the risk of the trial. The budget should include provision for executing the plan proposed. The DCC should also include a plan for assessing DSMB member conflict of interest, and put associated costs in the budget. Additionally, if the DSMB is convened by NHLBI, the DCC should include in their budget coordination of support for at least one DSMB meeting per year in Bethesda, MD and coordinate regular DSMB calls as needed (by teleconference or videoconference).

Include budget support for steering committee meetings whether in person or as a hybrid video conference. Include budget support for publication, dissemination of results, and data sharing.

The DCC budget should request only the costs that will be required for the activities to be performed in a given year.

R&R Subaward Budget

PHS 398 Cover Page Supplement

PHS 398 Research Plan All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

Research Strategy: The Research Strategy must present a discussion of the ways in which the DCC plans to provide expert assistance in protocol design and analysis plans, and feasibility assessments.

The following criteria must be addressed:

Significance: Explain why the chosen study design is optimal to answer the scientific questions posed for the trial described in the CCC application.

Innovation: Describe plans to employ unique or novel methodologies that will enhance the clinical trial design, management, or methods of data analysis. Describe how the DCC plans to utilize current best practices to improve the knowledge and/or skills of the multi-site clinical trial it will support.

Approach: Describe how the multi-site clinical trial will be coordinated including plans for providing administrative, operational support and data management and tracking support. Explain the communication strategy including how the DCC will interact with the CCC and individual sites, how data will be transmitted in an accurate and timely fashion and securely stored and shared, and how the DCC will establish accessible and secure methods of communication. Explain how the DCC will support enrollment of participants and help with the Community Engagement Plan (CEP) described in the CCC application. Provide plans to assess recruitment feasibility using available data on the target population from registries and prior studies to the extent possible.

Core Milestones Propose and justify milestones that will be subject to peer-review. A milestone is defined as a scheduled event in the project timeline that signifies the completion of a major project stage or activity. Milestones should be relevant, measurable, results-focused and time-bound, and should address timing of overall recruitment/enrollment and retention goals. The milestones must address accrual goals for women, minorities and individuals of all ages, including children and older adults, and any other identified requirements for completion of the approved research.

Describe the milestones that will be met to address the specific aims and ensure the successful completion of the clinical trial and dissemination of its results. The U24 core milestones should include but are not limited to:

Core U24 Year 1 Trial Milestones

Core U24 Year 2 and Beyond Trial Milestones

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply - Application Guide.

Other Plan(s):

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.

Additionally, applicants should consult and incorporate the NHLBI Supplement to the NIH Policy for Data Management and Sharing into their DMSP as applicable. This includes, but is not limited to, plans to share scientific data through existing NIH-supported Scientific Data Repositories, Ancillary Studies, and the Data Freeze Approach.

Data Repositories NHLBI-supported researchers are expected to share scientific data through existing NIH-supported Scientific Data Repositories or other repositories that have the desired characteristics described in the Supplemental Information to the NIH Policy for Data Management and Sharing: Selecting a Repository for Data Resulting from NIH-Supported Research. NHLBI encourages submission of data into NHLBI BioData Catalyst (BDC), especially for data from studies that must comply with NHLBI’s Accrual of Human Subjects (Milestones) Policy and for those projects supported by funding opportunity announcements that encourage data deposition into BDC. NHLBI also encourages the submission of data into BDC for NHLBI projects and ancillary studies to NHLBI parent studies subject to the NIH GDS Policy. For data submitted to repositories other than BDC, an appropriate globally-unique, persistent identifier with sufficient metadata should be shared with NHLBI to promote FAIR principles and populate a master index for data generated from all NHLBI-supported research.

NHLBI discourages the deposition of data in multiple places, which may incur issues of version control and excess storage costs. If researchers need to deposit data generated from NHLBI support into more than one repository, the rationale for this need should be provided within the Data Preservation, Access, and Associated Timelines element in DMS Plans. When approved for deposition in multiple repositories by appropriate NHLBI staff, for data deposited in repositories other than BDC, an appropriate globally-unique, persistent identifier for each repository, with sufficient metadata, should be provided to the NHLBI to promote FAIR principles.

Ancillary Studies NHLBI defines ancillary studies as studies that collect new data or derive data for purposes that are separate from the main “parent” study. The goal of ancillary studies is to extend scientific knowledge beyond the parent study’s original scope. NHLBI ancillary studies are primarily supported by NIH funds but may also be funded, in part or whole, by other sources such as non-profit and private sector organizations. Studies approved as ancillary, regardless of funding sources, to an NHLBI-funded parent observational study or clinical trial (including studies co-funded by multiple institutes, centers, and offices or to which NHLBI provides administrative oversight) are required to adhere to the parent study’s data sharing policies as a condition of approval. The requirements of data sharing agreements between NHLBI-funded parents and their ancillary studies should be consistent with the principles of the NIH DMS Policy.

Data sharing requirements are outlined in the agreement between the parent and respective ancillary study, and it is the responsibility of the ancillary study principal investigator to state in writing to the parent study steering committee any special circumstances that would preclude or limit data sharing. As specified in contract terms or award terms, designees from the parent studies shall submit updated and new ancillary data to an NHLBI-approved data repository on the same data submission timeline as the parent data (for example, core exam data, annual event surveillance, etc.). Ancillary study principal investigators should get advance approval from the parent study steering committee for any plans to share data with other repositories which have characteristics consistent with those described in the Supplemental Information to the NIH Policy for Data Management and Sharing: Selecting a Repository for Data Resulting from NIH-Supported Research.

Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the How to Apply - Application Guide.

No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

PHS Human Subjects and Clinical Trials Information When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the How to Apply - 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

Only the following fields are required:

1.1 Study Title

1.2 Is this Study Exempt from Federal Regulations?

1.3 Exemption Number (if applicable)

1.4 Clinical Trials Questionnaire

2.1 Conditions or Focus of Study

2.4 Inclusion of Women and Minorities

2.7 Study Timeline

3.1 Protection of Human Subjects

3.2 Is this a multi-site study what will use the same protocol to conduct non-exempt human subjects research at more than one domestic site?

3.3 Data and Safety Monitoring Plan

4.1.a Detailed Description

4.3 Statistical Design and Power

4.7 Dissemination Plan

5.1 Other Clinical Trial-related Attachments

Section 2 - Study Population Characteristics

2.1 Conditions or Focus of Study

The information provided for Conditions or Focus of Study must be the same as that provided in the collaborating CCC application.

2.3.a Inclusion of Individuals Across the Lifespan The information provided for Inclusion of Individuals Across the Lifespan must be the same as that provided in the collaborating CCC application.

2.4 Inclusion of Women and Minorities

The information provided for Inclusion of Women and Minorities must be the same as that provided in the collaborating CCC application.

2.7 Study Timeline

Include a table or graph of the overall study timeline. This is expected to be a visual representation (such as a Gantt Chart) of core milestones and key project management activities, including but not limited to study start-up including regulatory approvals, enrollment, intervention phase, follow-up phase, data analysis and dissemination of results. A narrative is not expected in this section.

The CCC and DCC are expected to provide the same 2 study timelines in their respective application. Each application should include a timeline for the first year of the trial (UG3 phase) and a separate timeline for subsequent years (UH3 phase). The study timelines should include core milestones that need to be met throughout the lifecycle of the clinical trial. It is expected that the timelines will clearly indicate which subtasks are needed to reach the core milestones; and which subtasks will be performed by the CCC and which ones will be performed by the DCC. The period of time for the study duration is expected to be displayed in months and must include, but is not limited to, the following:

(a) the study opens to enrollment

(b) core milestones are met

(c) subtasks needed to reach the core milestones

(d) when final transfer of the data to the DCC will occur

(e) database lock and analysis of the study data

(f) submission of the primary study manuscript for publication Section 3 - Protection and Monitoring Plans

3.3 Data and Safety Monitoring Plan

The information provided for the Data and Safety Monitoring Plan must be the same as that provided in the collaborating CCC application.

Section 4 - Protocol Synopsis 4.1.a Detailed Description Describe the proposed experimental design including a discussion of the clinical trial design and the rationale for the particular design chosen (pragmatic, explanatory, cluster-randomized, adaptive, etc.). Provide details of the randomization scheme, if applicable.

4.3 Statistical Design and Power

Provide content requested with respect to each outcome measure listed in Question 4.3 "Outcome Measures" of the collaborating CCC application. Justify the proposed sample size based on appropriate study assumptions, event rates, and power calculations. Justify the event rate and provide contingency plans should the event rate or effect size be underestimated. The calculations must be linked to the study endpoints and to the hypothesis(es) being tested. Explain how the outcome(s) will address the hypothesis(es) being tested. Provide details of the randomization scheme, if applicable. Describe plans for interim and final analyses; methods of bias control; and methods for handling missing data (as applicable). The description should be detailed enough to allow replication of the analysis by an independent statistician.

Adaptive designs should include a pre-specified adaptation plan that allows for clear go/no-go decisions and pre-specified analysis boundaries.

For all clinical trials (unless appropriately justified as not needed), the statistical analysis plans should include a description of an interim monitoring plan including stopping guidelines for safety as well as efficacy and futility.

For Phase III clinical trials, include plans for evaluation of the primary outcome(s) by race/ethnicity and sex, and include all relevant data to assess whether or not the trial includes adequate numbers for valid analyses of subgroups. In addition, justify adequacy of power to analyze subgroups of participants. Adaptive designs should include a pre-specified adaptation plan that allows for clear go/no-go decisions and pre-specified analysis boundaries.

The approach to data management must include, but is not limited to, a description of:

4.7 Dissemination Plan

The information provided for Dissemination Plan must be the same as that provided in the collaborating CCC application.

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the How to Apply - Application Guide must be followed.

PHS Assignment Request Form

Foreign Organizations Foreign (non-U.S.) organizations must follow policies described in the NIH Grants Policy Statement, and procedures for foreign organizations described throughout the How to Apply Application Guide.

3. Unique Entity Identifier and System for Award Management (SAM) See Part 2. 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

4. Submission Dates and Times Part I. 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.