Clinical Coordinating Center for Multi-Site Investigator-Initiated Clinical Trials (Collaborative UG3/UH3 Clinical Trial Required)

The National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health (NIH) under the Department of Health and Human Services (HHS), has reissued a funding opportunity aimed at supporting the development and implementation of Clinical Coordinating Centers (CCCs) for multi-site, investigator-initiated clinical trials. This bi-phasic cooperative agreement, designated under the activity code UG3/UH3, is designed for clinical trials that address health issues relevant to the NHLBI mission, with an emphasis on improving trial efficiency, increasing community engagement, and addressing health disparities. This funding opportunity, known as PAR-25-029, is applicable only to clinical trials that meet the NIH definition of a clinical trial, including Phase II and above, multi-site trials with a requirement to enroll participants from at least two locations. Supported trials can span various trial designs such as efficacy, effectiveness, pragmatic, implementation research, and innovative formats like adaptive or Bayesian trials. The initiative aligns with strategic NHLBI goals and encourages trials that contribute significantly to the evidence base on important health concerns. The NOFO mandates the concurrent submission of a companion application for a Data Coordinating Center (DCC) under a separate opportunity (PAR-22-193), reinforcing a collaborative structure for trial execution. The UG3 phase, up to one year in duration, supports protocol development and trial readiness, while the UH3 phase (up to 4 years, or 6 with justification) supports trial implementation. Transition to UH3 funding depends on satisfactory milestone achievement during UG3. These milestones encompass protocol finalization, IRB and DSMB approvals, site activation, recruitment initiation, and adherence to diversity inclusion targets. Eligibility is broad and includes institutions of higher education, nonprofits, for-profits, government entities, and foreign organizations, provided all required registrations (SAM, eRA Commons, Grants.gov, etc.) are complete. Applications must be submitted electronically and conform to detailed application and submission guidelines, including the provision of specific required documents such as a Trial Management Plan, Clinical Trial Research Experience, and Community Engagement Plan. The CCC and DCC must coordinate on milestones, study timelines, and dissemination strategies. Applications are accepted on three annual cycles, with the next due dates being June 11, 2025, October 10, 2025, and continuing until the program expires on January 12, 2026. Letters of intent are encouraged 30 days before the application deadline. A comprehensive review process evaluates applications based on significance, innovation, approach, investigator expertise, and environmental support. Strong emphasis is placed on trial feasibility, milestone planning, and community engagement. For application-related questions, designated NHLBI contacts are available across scientific, peer review, and grants management domains. Prospective applicants are advised to contact these individuals, especially if requesting over $500,000 in direct costs annually, to ensure compliance with NHLBI policies and increase the likelihood of funding success.