Single-Site Investigator-Initiated Clinical Trials (R61/R33 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, has released a forecast for a funding opportunity titled “Single-Site Investigator-Initiated Clinical Trials (R61/R33 Clinical Trial Required)” (Opportunity Number: FON-HL-25-028). The forecast signals the NIH’s intent to issue a formal Notice of Funding Opportunity (NOFO) to support clinical trials aligned with the NHLBI’s mission in heart, lung, blood, and sleep disorders research. This funding opportunity is designed to support investigator-initiated, single-site clinical trials including those focused on efficacy, comparative effectiveness, pragmatic, and implementation research. The NHLBI encourages applications utilizing innovative trial designs such as platform trials, adaptive methodologies, and Bayesian approaches. Acceptable trials may test various therapeutic, behavioral, or preventive strategies. The primary goal is to ensure the trials are consistent with the NHLBI’s research mission and meet NIH’s definition of a clinical trial. The NOFO will utilize the R61/R33 activity code, which supports exploratory/developmental research with a clear transition from feasibility to full-scale studies. This mechanism allows for initial assessment and development (R61 phase) followed by full implementation and effectiveness testing (R33 phase). The NHLBI emphasizes that applications are not currently being accepted, and this forecast serves to provide potential applicants with adequate time to build relevant collaborations and develop responsive project proposals. Eligibility for this opportunity includes a wide range of entities: nonprofits with 501(c)(3) status, public and private institutions of higher education, for-profit organizations excluding small businesses, small businesses, county governments, independent school districts, public housing authorities, Native American tribal organizations and governments. The opportunity does not require cost sharing or matching contributions. Estimated timelines include a post date of July 11, 2025, an application due date of October 13, 2025, award notification by May 1, 2026, and project commencement by July 1, 2026. Interested parties should prepare for this schedule and consider initiating pre-application activities such as partnership development and research planning now. For further details or inquiries, potential applicants may contact Dr. Yves Rosenberg, MD, MPH, at the NHLBI's Division of Cardiovascular Sciences via email at rosenbey@nhlbi.nih.gov or phone at 301-435-1292.