The National Heart, Lung, and Blood Institute (NHLBI) has announced funding opportunity PAR-25-029, titled Clinical Coordinating Center for Multi-Site Investigator-Initiated Clinical Trials. This notice of funding opportunity (NOFO) supports investigator-initiated multi-site clinical trials that focus on efficacy, effectiveness, pragmatic, or implementation research relevant to NHLBI’s mission. It encourages innovative designs such as platform, adaptive, or Bayesian approaches. The NOFO requires strong emphasis on community engagement, inclusion of diverse populations, and addressing health inequities. Applications must propose trials that meet the NIH definition of a clinical trial and contribute to the evidence base for improved health outcomes.

The funding mechanism consists of two phases under a UG3/UH3 cooperative agreement. The UG3 phase provides up to one year of funding for start-up activities, including protocol development, securing regulatory approvals such as IND or IDE if applicable, activating clinical sites, and initiating recruitment. Successful completion of predefined milestones in the UG3 phase is required for progression to the UH3 phase. The UH3 phase supports full trial implementation, including recruitment, data collection, and dissemination of results. The UH3 phase typically lasts four years but may extend to six years with strong justification. Progress is evaluated against core milestones, including site activation, participant enrollment targets, data collection, and database lock.

This NOFO requires submission of two linked applications: one for the Clinical Coordinating Center (CCC) under this announcement and one for the Data Coordinating Center (DCC) under the companion NOFO PAR-22-193. Both applications must be submitted on the same date for review. The CCC oversees trial protocol development, participant recruitment, trial management, and site coordination, while the DCC focuses on data management, statistical analyses, and supporting oversight committees such as the Data and Safety Monitoring Board (DSMB). Each application must clearly describe the respective responsibilities and how the two centers will collaborate.

Key requirements include a Trial Management Plan, Community Engagement Plan, and a Plan for Enhancing Diverse Perspectives (PEDP). The Trial Management Plan must describe the processes for project oversight, risk management, and contingency planning to ensure milestones are met. The Community Engagement Plan outlines strategies to collaborate with communities and stakeholders to enhance recruitment, retention, and inclusion of underrepresented populations. The PEDP details actionable steps to promote inclusivity in the project team, research sites, and participant populations. Failure to include the PEDP will result in the application being administratively withdrawn before review.

Applications must address the trial’s significance, innovation, and feasibility. This includes demonstrating scientific equipoise, justifying the trial design, and providing plans for recruitment, retention, and risk mitigation. Budget requests must reflect the actual needs of the project and include travel costs for annual Steering Committee meetings in Washington, D.C., as well as costs for PEDP implementation, dissemination of results, and data sharing. Applications with combined CCC and DCC budgets exceeding $500,000 in direct costs per year require NHLBI approval at least six weeks before submission.

Eligible applicants include higher education institutions, nonprofits, for-profit organizations, local and state governments, and foreign organizations. Applicants must complete all required registrations, including SAM.gov, eRA Commons, and Grants.gov, prior to submission. Multiple applications from a single institution are allowed if each is scientifically distinct. Letters of intent are encouraged and must be submitted at least 30 days before the application deadline. Applications are due February 11 and June 11, 2025, and will undergo peer review based on factors including significance, approach, feasibility, community engagement, and the PEDP.

NHLBI will closely monitor trial progress to ensure adherence to milestones and timely completion. Awardees are required to comply with NIH’s Data Management and Sharing Policy, disseminate results through publications, and deposit data in NHLBI-approved repositories. If progress is insufficient or milestones are not met, NHLBI reserves the right to phase out or terminate funding. Awardees will also collaborate with NHLBI and the DSMB to ensure participant safety, data quality, and overall trial integrity. This funding opportunity supports rigorous, innovative multi-site trials aimed at advancing clinical research and addressing health disparities across diverse populations.