National Institutes of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
U24 Resource-Related Research Projects – Cooperative Agreements
NOT-OD-23-012 Reminder: FORMS-H Grant Application Forms and Instructions Must be Used for Due Dates On or After January 25, 2023 - New Grant Application Instructions Now Available
NOT-OD-22-190 - Adjustments to NIH and AHRQ Grant Application Due Dates Between September 22 and September 30, 2022
This Funding Opportunity Announcement (FOA) 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 FOA 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 FOA will utilize a milestone-driven cooperative agreement mechanism of award and runs in parallel with a companion FOA PAR-22-192() that encourages applications 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 and diversity plans.
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.
30 days prior to the application due date
| Application Due Dates | Review and Award Cycles | ||||
|---|---|---|---|---|---|
| New | Renewal / Resubmission / Revision (as allowed) | AIDS | Scientific Merit Review | Advisory Council Review | Earliest Start Date |
| October 11, 2022 | November 10, 2022 | January 11, 2023 | March 2023 | May 2023 | July 2023 |
| February 10, 2023 | March 10, 2023 | May 11, 2023 | July 2023 | October 2023 | December 2023 |
| June 13, 2023 | July 11, 2023 | September 11, 2023 | November 2023 | January 2024 | April 2024 |
| October 11, 2023 | November 13, 2023 | January 11, 2024 | March 2024 | May 2024 | July 2024 |
| February 13, 2024 | March 11, 2024 | May 10, 2024 | July 2024 | October 2024 | December 2024 |
| June 11, 2024 | July 11, 2024 | September 11, 2024 | November 2024 | January 2025 | April 2025 |
| October 11, 2024 | November 12, 2024 | January 10, 2025 | March 2025 | May 2025 | July 2025 |
| February 11, 2025 | March 11, 2025 | May 12, 2025 | July 2025 | October 2025 | December 2025 |
| June 11, 2025 | July 11, 2025 | September 11, 2025 | November 2025 | January 2026 | April 2026 |
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.
Not Applicable
It is critical that applicants follow the instructions in 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 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.
There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.
- Use the NIH ASSIST system to prepare, submit and track your application online.
- Use an institutional system-to-system (S2S) solution to prepare and submit your application
to Grants.gov and eRA Commons to track your
application. Check with your institutional officials regarding availability.
- Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.
Research Objectives
This FOA supports applications to develop and implement a Data Coordinating Center (DCC) for investigator-initiated multi-site clinical trials submitted to the collaborating Clinical Coordinating Center FOA (PAR-22-192). Clinical trials supported by this FOA 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 FOA. This FOA 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 holds 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. Clinical trials require the recruitment of human participants, so it is of foremost importance that participant safety and inclusion of men, women, and individuals of all ages, including children and older adults from diverse backgrounds be considered. Recruitment should include populations affected by health disparities, which include Blacks/African Americans, Hispanics/Latinos, American Indians/Alaska Natives, Asian Americans, Native Hawaiians and other Pacific Islanders, socioeconomically disadvantaged populations, underserved rural populations, and sexual and gender minorities.
Proposed research may utilize a design anywhere along the continuum of efficacy, effectiveness, pragmatic and/or implementation research clinical trials. For this FOA, 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. Innovative trial designs such as adaptive designs will be considered. The trial design should be appropriate for the study question. Trials for which this FOA applies are expected to contribute to the evidence base for important health matters of relevance to the research mission of NHLBI, including approaches to increase diversity of participants in the research and reduce health inequities and disparities. 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 FOA is 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 subsequent approval of Data and Safety Monitoring Board; and Single Institutional Review Board (see NOT-OD-16-094) approvals of the trial protocol; and informed consent(s)/assent(s); manual of operations; data management systems and randomization procedures; and finalized integrated project management plans.
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 FOAs, 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.
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 Data Sharing Policy.
Note: This DCC FOA runs in parallel with a companion FOA (PAR-22-192) 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 FOA 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, and to provide information and guidance to potential applicants. Additionally, a staff consultation is required when direct costs (DCs) are $500,000 or higher (see NHLBI policy regarding direct costs of $500,000 or more).
Notice of NIH's Interest in Diversity
Every facet of the United States scientific research enterprise—from basic laboratory research to clinical and translational research to policy formation–requires superior intellect, creativity and a wide range of skill sets and viewpoints. NIH’s ability to help ensure that the nation remains a global leader in scientific discovery and innovation is dependent upon a pool of highly talented scientists from diverse backgrounds who will help to further NIH's mission. Research shows that diverse teams working together and capitalizing on innovative ideas and distinct perspectives outperform homogenous teams. Scientists and trainees from diverse backgrounds and life experiences bring different perspectives, creativity, and individual enterprise to address complex scientific problems. There are many benefits that flow from a diverse NIH-supported scientific workforce, including: fostering scientific innovation, enhancing global competitiveness, contributing to robust learning environments, improving the quality of the research, advancing the likelihood that underserved or health disparity populations participate in, and benefit from health research, and enhancing public trust. In spite of tremendous advancements in scientific research, information, educational and research opportunities are not equally available to all. NIH encourages institutions to diversify their student and faculty populations to enhance the participation of individuals from groups that are underrepresented in the biomedical, clinical, behavioral and social sciences. See NOT-OD-20-031 and Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019 for details.
See Section VIII. Other Information for award authorities and regulations.
Cooperative Agreement: A support 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 FOA.
Resubmission
Revision
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.
Required: Only accepting applications that propose clinical trial(s).
The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.
Application budgets are not limited but need to reflect the actual needs of the proposed project.
The combined budgets of the CCC and DCC will be used to determine whether the policy regarding direct costs of $500,000 or more in any year will be applied.
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 FOA.
1. Eligible Applicants
Higher Education Institutions
- Public/State Controlled Institutions of Higher Education
- Private Institutions of Higher Education
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
- Hispanic-serving Institutions
- Historically Black Colleges and Universities (HBCUs)
- Tribally Controlled Colleges and Universities (TCCUs)
- Alaska Native and Native Hawaiian Serving Institutions
- Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)
Nonprofits Other Than Institutions of Higher Education
- Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
- Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)
For-Profit Organizations
- Small Businesses
- For-Profit Organizations (Other than Small Businesses)
Local 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)
Federal Government
- 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)
Non-domestic (non-U.S.) Entities (Foreign Institutions) 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.
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.
- 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. SAM registrations prior to fall 2021 were updated to include a UEI. For applications due on or after January 25, 2022, the UEI must be provided on the application forms (e.g., FORMS-G); 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 full SAM and 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.
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. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019.
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.
Multiple PDs/PIs are allowed on any single application. Because the FOA already supports a team approach between groups of experts across sites and collaborating applications, the designation of multiple PDs/PIs on a single application may be less likely to apply. PD(s)/PI(s) from each linked application should not be designated as multiple PDs/PIs on each application of a collaborative set.
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 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, per 2.3.7.4 Submission of Resubmission Application. 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 2.3.9.4 Similar, Essentially Identical, or Identical Applications)
This FOA only accepts applications that are part of a collaborative pair of applications. The pair must include one DCC U24 application to this FOA plus one application to the companion CCC UG3/UH3 FOA.
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 FOA. 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 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.Letter of Intent
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
Email: [email protected]
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.
Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing (DMS) Plan will be attached in the Other Plan(s) attachment in FORMS-H and subsequent application forms packages. For due dates on or before January 24, 2023, the Data Sharing Plan and Genomic Data Sharing Plan GDS) will continue to be attached in the Resource Sharing Plan attachment in FORMS-G application forms packages.
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.
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. Each site should submit an identical listing.
If the direct costs of the combined CCC and DCC budgets equal or exceed $500,000 in any given year, a copy of the NHLBI approval letter must be attached.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
Facilities and Other Resources: 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 attachments listed below that are marked as "Required" must be provided or the application will not be peer reviewed.
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:
- Description of the project management team and levels of effort.
- Description of how the CCC and DCC project management teams will integrate with one another.
- A risk assessment plan
- A risk management plan that addresses contingencies in the event that there is inadequate progress toward achieving the U24 core milestones. The plan should identify a range of contingencies that could threaten study progress or feasibility, and propose solutions using study resources.
- Key methodology and standard operating procedures governing resource management, study deployment, operations/execution, and study closure.
- How the clinical trial management team, in collaboration with the CCC, will resolve fiscal and logistical issues in a timely manner including plans to pro-actively evaluate and prioritize study risks and issue corrective responses.
- Processes required for orderly project closure including how the study will comply with the NIH Data Sharing Policy, and biorepository plans if specimens will be stored after planned study testing and analyses are complete.
In summary, the trial management plan should provide sufficient detail 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:
- Name of Network
- Number of years and funding remaining to support the Network infrastructure and any information on the continuance of the Network
- Plans to replace sites that are under-performing or that are removed through the Network re-competition process. These plans should include contingencies for funding, data recovery, and the follow-up of enrolled trial participants.
- Infrastructure capacity and availability of patient populations considering current ongoing trials within the Network
- Plans to incorporate the current Network infrastructure into the proposed trial, including participant recruitment, trial implementation, and central coordination through the CCC and data management, data analysis, or statistical analysis through the DCC
- Plans to utilize master clinical trial agreements and a single IRB
- Describe the part of the Network that will be leveraged by the CCC and the DCC, respectively. If both the CCC and the DCC applications intend to leverage the infrastructure of an existing network, the CCC application must also include this information.
All instructions in the SF424 (R&R) Application Guide must be followed.
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
All instructions in the SF424 (R&R) Application Guide must be followed.
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.
Any cores (e.g., economics/quality of life) must be a subcontract to either the DCC or CCC. Separate itemized budgets must be prepared for each subcontract and/or for each collaborating center or core.
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.
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.
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 Plan(s):
Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H and subsequent application forms packages. For due dates on or before January 24, 2023, the Data Sharing Plan and Genomic Data Sharing Plan GDS) will continue to be attached in the Resource Sharing Plan attachment in FORMS-G application forms packages.
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.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
Introduction to Application: For Resubmission and Revision applications, an Introduction to Application is allowed. For Resubmission and Revision applications, an Introduction to Application is allowed. For Resubmission applications, the Introduction should be a summary response to the concerns expressed during the previous review. For Revision applications, provide sufficient information from the original grant application to allow evaluation of the proposed revision in relation to the goals of the original application.
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 communications 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 how the DCC will establish accessible and secure methods of communication. Explain how the DCC will help with the Plans for Enhancing Diverse Perspectives (PEDP) and Community Engagement Plans (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
- Complete finalized clinical protocol and informed consent
- DSMB review of final protocol, template consent(s) and/or assent(s), and data and safety monitoring plan
- IRB approval of final protocol and consent and/or assent
- Enrollment of the first participant during the UG3 period (of the CCC)
- 25% of sites activated
Core U24 Year 2 and Beyond Trial Milestones
- Enrollment of 25%, 50%, 75% and 100% of the projected recruitment for all study participants, including women, minorities and children (as appropriate)
- Study closure and completion plans
- Collection of data related to primary and secondary endpoints and database lock
- Submission of primary manuscript to peer-reviewed scientific journal(s), dissemination of results, and data sharing.
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.
The following modifications also apply:
- All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
- Awardees are expected to comply with the NHLBI Data Sharing Policy.
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 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:
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. 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. The Study Timelines need to address the relevant components of the PEDP. 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. Describe the process that will be utilized to identify unanticipated problems and describe procedures for intervention discontinuation and stopping guidelines.
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 gender, 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:
- Data management systems
- Methods of data entry and cleaning
- Event tracking and logistics
- Biospecimen tracking
- Case report forms
- Methods for quality assurance and quality control
- Methods for monitoring the quality and consistency of intervention(s)
- Test, validate and optimize data capture systems
- Policies and methods for ensuring blinding of study results
- Data confidentiality and subject privacy
- Plans for data and IT security at each site
- Disaster recovery plans
- Adjudication of events (as needed)
- Data analysis reports
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 SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
Foreign Institutions
Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.
3. Unique Entity Identifier and System for Award Management (SAM)
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. Each application of a collaborative set must be on-time. Considerations for late applications that are based on the institution or PD/PI apply only to his/her individual application.
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.
5. Intergovernmental Review (E.O. 12372)
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 How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. 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 fieldof the Senior/Key Person Profile form. 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 unique entity identifier (UEI) provided 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. Each application of a collaborative set must be complete and compliant.
Requests of $500,000 or more for direct costs in any year
Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact a Scientific/ Research Contact at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF424 (R&R) Application Guide.
Applicants 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.
1. Criteria
Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) as part of the Resource Sharing Plan will not be evaluated at time of review.
Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.
For this particular announcement, note the following:
Reviewers will consider the overall feasibility of the project and whether the clinical trial will answer a key scientific question and be completed on time and within the proposed budget.
A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.
Overall Impact
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).
Scored Review Criteria
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.
Significance
Does the proposed Data Coordinating Center address the needs of the collaborating Clinical Coordinating Center (PAR-22-192) that it will serve? Is the scope of activities proposed for the Data Coordinating Center appropriate to meet those needs? Will successful completion of the aims bring unique advantages or capabilities to the research Clinical Coordinating Center?
Specific to this FOA:
- How strong is the proposed DCC regarding ability to address the needs of the research program that it will support?
- How likely is it that the scope of activities proposed for the DCC will meet the needs of the research program?
- Will successful completion of the aims bring unique advantages or capabilities to the research program?
Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?
Investigator(s)
Are the PD(s)/PI(s) and other personnel well suited to their roles in the Data Coordinating Center? Do they have appropriate experience and training, and have they demonstrated experience and an ongoing record of accomplishments in managing multisite clinical trial research? Do the investigators demonstrate significant experience with coordinating collaborative clinical research? If the Center is multi-PD/PI, do the investigators have complementary and integrated expertise and skills; is their leadership approach appropriate for the Data Coordinating Center? Does the applicant have experience overseeing selection and management of subawards, if needed?
Specific to this FOA:
- How strong is the Clinical Trial Experience attachment in demonstrating the expertise of the personnel to conduct the proposed trial?
- How well-defined are the roles and responsibilities of the leadership?
- How adequate are the descriptions of roles/responsibilities of the Project Manager and other key personnel?
- How strong is the project management expertise represented among the key personnel?
- To what extend do the PDs/PIs and key personnel have the experience and capability in multidisciplinary 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 to successfully conduct the project to completion?
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?
Innovation
Does the application propose novel organizational concepts or management strategies in coordinating the research Clinical Coordinating Center that the Data Coordinating Center will serve? Are the concepts, strategies, or instrumentation novel to one type of research program or applicable in a broad sense? Is a refinement, improvement, or new application of organizational concepts or management strategies proposed?
Specific to this FOA
- Does the application propose innovative approaches to clinical trial design, management, or methods of data analysis?
- Where appropriate, does the proposed DCC utilize current best practices to improve the knowledge and/or skills of the multi-site clinical trial it will support?
Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?
Approach
Are the overall strategy, operational plan, and organizational structure well-reasoned and appropriate to accomplish the goals of the research Clinical Coordinating Center that the Data Coordinating Center will serve? Will the investigators promote strategies to ensure a robust and unbiased scientific approach across the multisite clinical trials, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the collaborating Clinical Coordinating Center is in the early stages of operation, does the proposed strategy adequately establish feasibility and manage the risks associated with the activities of the collaborating Clinical Coordinating Center? Are an appropriate plan for work-flow and a well-established timeline proposed? Have the investigators presented adequate plans to ensure consideration of relevant biological variables, such as sex, for studies of 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 individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?
Specific to this FOA:
- How strong are the plans to monitor accrual?
- If the clinical trial is Phase III, does the application include all relevant data to assess whether or not the trial should include adequate numbers of subgroups of participants to allow for valid and/or adequately powered analyses? If applicable, do the plans for adaptive designs include a pre-specified adaptation plan that allows for clear go/no-go decisions and pre-specified analysis boundaries?
- How strongly does the statistical approach justify the proposed sample size based on appropriate study assumptions; provide for plans for interim and final analyses; methods of bias control; and methods for handling missing data (as applicable)? How likely is the detail of the statistical methodology to allow replication of the analyses by an independent statistician?
- How strong is the plan for data management and validation, including data management systems, methods of data entry and cleaning, event tracking and logistics, case report forms, and methods for monitoring the quality and consistency of the intervention(s) and data collection; policies and methods for ensuring blinding of study results; data confidentiality and subject privacy; adjudication of events (as needed); and data reports?
- How strong is the approach of the DCC to collaborate with the CCC on supporting the Plan for Enhancing Diverse Perspectives (PEDP) and the Community Engagement Plan?
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?
Environment
Will the institutional environment in which the Data Coordinating Center will operate contribute to the probability of success in facilitating the research Clinical Coordinating Center it serves? Are the institutional support, equipment and other physical resources available to the investigators adequate for the Data Coordinating Center proposed? Will the Data Coordinating Center benefit from unique features of the institutional environment, infrastructure, or personnel? Are resources available within the scientific environment to support electronic information handling?
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
- How strong is the evidence that the facilities and resources available for the DCC infrastructure will support and enable the conduct of the research proposed in the multi-site clinical trial?
- If applicable, how strong are the stakeholders agreements to support the protocol?
- If applicable, does the trial leverage resources of a network appropriately?
Additional Review Consideration
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
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)?
Core Milestones
- Are the listed milestones appropriate for the DCC?
- To what extent are the milestones relevant, measurable, achievable, result-focused and time-bound?
- Is the study timeline appropriate to complete the goals, meet the milestones, and address the scientific question(s)?
Protections for Human Subjects
For research that involves human subjects but does not involve one of the 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 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.
Inclusion of Women, Minorities, and Individuals Across the Lifespan
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 individuals of all ages (including children and older adults) 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.
Vertebrate Animals
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.
Biohazards
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.
Resubmissions
For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.
Renewals
Not Applicable
Revisions
For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.
Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) as part of the Resource Sharing Plan will not be evaluated at time of review.
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.
Applications from Foreign Organizations
Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.
Select Agent Research
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).
Resource Sharing Plans
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).
Authentication of Key Biological and/or Chemical Resources:
For Clinical Coordinating Centers involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.
Budget and Period of Support
Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.
2. Review and Selection Process
Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NHLBI, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.
As part of the scientific peer review, all applications will receive a written critique.
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.
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 appropriate national Advisory Council or Board. 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.
3. Anticipated Announcement and Award Dates
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.
1. Award Notices
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 recipient's business official.
Recipients 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 and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm
Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient 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).
2. Administrative and National Policy Requirements
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, Recipients, and Activities, including of note, but not limited to:
- Federalwide Research Terms and Conditions
- Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
- Acknowledgment of Federal Funding
If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.
Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex (including gender identity , sexual orientation, and pregnancy). This includes ensuring programs are accessible to persons with limited English proficiency and persons with disabilities. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html
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.
- Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov.
- For information on an institution’s specific legal obligations for serving qualified individuals with disabilities, including reasonable accommodations and making services accessible to them, see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html.
- HHS funded health and education programs must be administered in an environment free of sexual harassment, see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.
- For guidance on administering programs in compliance with applicable federal conscience protection and associated anti-discrimination laws see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/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.
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 and 2 CFR Part 200.206 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.
The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS grant administration regulations at 45 CFR Part 75, 2 CFR Part 200, and other HHS, and NIH grant administration policies.
The administrative and funding instrument used for this program will be the cooperative agreement, an “assistance” mechanism (rather than an “acquisition” mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients’ activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.
The PD(s)/PI(s) will have primary responsibility for:
The awardee PD/PI will have primary and lead responsibilities for the project as a whole, including research design and protocol development, participant recruitment and follow-up, data collection, quality control, interim data and safety monitoring, final data analysis and interpretation, preparation of publications, as well as collaborations with other awardees.
Upon completion of the project, awardees are expected to put their data into the public domain and/or make them available to other investigators, according to the approved plan for making data and materials available to the scientific community (see section 3 below "Collaborative Responsibilities"). Third Party support of the proposed research activity (if proposed, accepted and approved) will be incorporated as a Special Award Condition in the NoA. Awardees will be responsible for ensuring third party compliance and if the 3rd party support is no longer available, and not replaceable in a timely fashion negotiated phase-out of the award may occur. Cost Share is not a requirement for this program; however, if cost share is proposed, peer reviewed and accepted by NHLBI it will become a Special Award Condition in the NoA.
Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.
NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
The NHLBI Project Scientist will assist with development of research protocols, monitor patient recruitment and study progress, ensure disclosure of conflicts of interest, and ensure adherence to NHLBI policies.
The NHLBI Project Scientist will serve on the Steering Committee and other study committees, when appropriate, as a non-voting member. The NHLBI Project Scientist may work with awardees on issues coming before the Steering Committee such as recruitment, protocol development, follow-up, quality control, adherence to protocol, possible changes to the protocol, interim data and safety monitoring, final data analysis and interpretation, preparation of publications, and development of solutions to major problems such as insufficient participant enrollment.
In addition to the Project Scientist, a separate NHLBI Program Official will be responsible for the normal program stewardship of the cooperative agreement, and will be in the Notice of Award. However, NHLBI may elect to have a dual-role approach where a single individual may act as both the NHLBI Project Scientist and Program Official. Final decision-making authority on matters of budgetary and funding actions, grants management actions, and management of intellectual property issues is assigned to NHLBI staff other than the Project Scientist. The responsibility for final decision making may reside with Senior Institute management, separate organizational components and/or oversight committees. Because it is anticipated that the Program Official will participate in activities that rise to a level of involvement (i.e., additional role as Project Scientist) that results in conflicts of interest, for example, co-publication, other staff members such as direct line supervisors and/or other Senior NHLBI Program management staff will serve as agency Program Officials and will be responsible for the normal scientific and programmatic stewardship of the award.
The NHLBI policy on authorship and manuscript review of NHLBI sponsored extramural research protects against conflicts of interest with the Program Officer.
An independent Data and Safety Monitoring Board (DSMB) will be established to oversee participant safety in the clinical trial and provide overall monitoring of interim data and safety issues. As part of the collaborative activities under this cooperative agreement, the NHLBI will collaborate with the awardees to appoint and/or agree upon a single DSMB for monitoring the clinical trial. The DSMB may be appointed by the NHLBI, or with the approval of NHLBI, the DSMB could be an institutional DSMB. At the first meeting in the UG3 phase of the collaborative CCC, the DSMB will review the awardee’s protocol and potentially recommend modifications. Subsequently, the DSMB will monitor and review recruitment, adverse events, data quality, outcome data, and overall awardee performance. The DSMB has the responsibility to review interim data and final data, and recommend whether the protocol should be modified, and, at each meeting, whether the study should be continued or should be terminated early. An NHLBI scientist other than the NHLBI Program Official or Project Scientist will serve as Executive Secretary to the Board. Because the DSMB serves as an independent group advisory to the NHLBI, study investigators shall not communicate with DSMB members regarding study issues, except as authorized by the Board's Executive Secretary.
The NHLBI reserves the right to phase-out or curtail the study (or an individual award) in the event of (a) failure to develop or implement a mutually agreeable protocol, (b) substantial shortfall in subject recruitment milestones, core milestones mutually agreed upon by the recipient organization and PD/PI and the NHLBI, consortium participation and collaboration with other awardees, (c) substantive changes in the agreed-upon methodologies and tools with which NIH cannot concur, (d) human subject ethical issues that may dictate a premature termination, or (e) results that substantially diminish the scientific value of study continuation.
Areas of Joint Responsibility include:
The Authorized Organizational Representative (AOR) is responsible for communicating progress on achievement of each milestone for the collaborative project to the NHLBI Grants and Program Officers listed on the Notice of Award. Award continuation, even during the period recommended for support, is conditional upon satisfactory progress. If, at any time, recruitment, as defined in the NHLBI Accrual of Human Subjects (Milestones) Policy, falls significantly below projections, or core milestones mutually agreed upon by the recipient organization and PD/PI and the NHLBI are not met, the NHLBI may consider ending support and negotiating an orderly phase-out of the award. NHLBI Grants Management and Program Officers will closely monitor progress at all trial stages including milestones, accrual, and safety.
Awardees will retain custody of and have primary rights to their data developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies. The Principal Investigator of this award will be required to participate in periodic meetings and telephone conference calls with other investigators performing large-scale genome wide association studies supported by the NHLBI. These meetings and calls will be arranged by NHLBI staff to promote sharing of information among investigators regarding state of science technologies, data management techniques, analytical strategies and tools, and data sharing. Support or other involvement of industry or any other third party in the study (e.g., participation by the third party; involvement of study resources or citing the name of the study or NHLBI support; or special access to study results, data, findings or resources) may be advantageous and appropriate. However, except for licensing of patents or copyrights, support or involvement of any third party will occur only following notification of and concurrence by NHLBI.
NHLBI will partner with the PD/PI to ensure that the dataset preparation is congruent with requirements for NHLBI data repository datasets and associated documentation for submission to the Biological Specimen and Data Repository Information Coordinating Center (BioLINCC) and the NHLBI Policy for Data Sharing from Clinical Trials and Epidemiological Studies, and is in accordance with the Guidelines for NHLBI Data Set Preparation.
Study investigators are strongly encouraged to publish and to release publicly and disseminate results, tools, resources and other products of the study, in accordance with the study protocols and governance. It is expected that all methods, analyses, software, and algorithms will be made available in a timely matter to the scientific community. A plan for dissemination of study results will be developed by the awardee PD/PI in collaboration with the NIH Project Scientist and incorporated as a Special Term and Condition in the NoA. Within 3 years of the end of the period of NHLBI support for the project, data not previously released and other study materials or products not previously distributed are expected to be made available to individuals who are not study investigators in accordance with the NHLBI Data Sharing Policy.
Dispute Resolution:
Any disagreement that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed will be convened. It will have three members: a designee selected by the Executive Committee (with the NHLBI member absent from the discussion) or by the individual awardee in the event of an individual disagreement, a second member selected by NIH, and the third designee with expertise in the relevant area selected by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution does not alter the awardees' right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations at 42 CFR part 50, subpart D and HHS regulation at 45 CFR part 16.
Multiple PD/PI Dispute Resolution
If a conflict develops between PD(s)/PI(s) in a multiple PD/PI application, the following procedures will apply:
The Departmental administrators representing the PD(s)/PI(s) shall meet and attempt in good faith to settle any dispute, claim or controversy arising out of or relating to the interpretation, performance or breach of this disagreement. However, if the Departmental administrators fail to reach resolution in 30 days then NIH may invoke dispute resolution procedures as described in the above paragraph.
Data Management and Sharing
Note: The NIH Policy for Data Management and Sharing is effective for due dates on or after January 25, 2023.
Consistent with the NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.
3. Reporting
When multiple years are involved, recipients 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. NIH FOAs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.
The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All recipients 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, application errors and warnings, documenting system problems that threaten submission by the due date, and 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)
General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-480-7075
Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]
Division of Blood Diseases and Resources
Nancy DiFronzo, PhD
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0065
Email: [email protected]
Division of Cardiovascular Sciences
Yves Rosenberg, MD, MPH
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-1292
Email: [email protected]
Division of Lung Diseases
Marishka K. Brown, PhD
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0199
Email: [email protected]
Center for Translational Research and Implementation Science
Cara C. Lewis, Ph.D.
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-594-9230
Email:[email protected]
Keary A. Cope, PhD
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-435-0287
Email: [email protected]
Tammi Simpson
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-827-8051
Email: [email protected]
Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 2 CFR Part 200, 42 CFR Part 52 and 45 CFR Part 75.
and Human Services (HHS)
