Single-Site Investigator-Initiated Clinical Trials (R61/R33 Clinical Trial Required)

The Single-Site Investigator-Initiated Clinical Trials (R61/R33 Clinical Trial Required) funding opportunity is issued by the National Institutes of Health under the U.S. Department of Health and Human Services, specifically aligned with the mission of the National Heart, Lung, and Blood Institute. This federal funding opportunity supports scientific research in health-related fields, particularly those addressing cardiovascular, lung, blood, and sleep disorders. The program is designed to advance clinical research by funding investigator-initiated trials that are conducted at a single site and that demonstrate strong scientific rationale and operational feasibility. The purpose of this funding opportunity is to support the development and execution of clinical trials that evaluate therapeutic, behavioral, prevention, and implementation strategies. The program encourages a wide range of trial types, including efficacy trials, comparative effectiveness studies, pragmatic trials, and dissemination and implementation research. Innovative trial designs such as adaptive, Bayesian, and platform trials are explicitly encouraged, reflecting the agency’s interest in advancing methodological approaches in clinical research. Applicants are expected to align their proposed work with the strategic priorities of the National Heart, Lung, and Blood Institute and demonstrate how their research will improve health outcomes and reduce disparities within the United States. Funding is provided through a bi-phasic R61/R33 mechanism, which is milestone-driven. The R61 phase supports initial development and feasibility, while transition to the R33 phase depends on successful completion of predefined milestones. Applicants must present a comprehensive plan that includes scientific rationale, operational design, project management structure, participant recruitment and retention strategies, and dissemination of results. While specific funding amounts are not provided in the available summary, the structure indicates support for complex, multi-stage clinical research efforts. Eligibility for this opportunity is broad and includes a wide range of organizational types such as public and private institutions of higher education, nonprofit organizations with or without 501(c)(3) status, small businesses, for-profit entities, state and local governments, tribal governments, and independent school districts. Both domestic and international organizations are eligible to apply; however, restrictions apply to foreign subawards. Applications involving foreign subawards or subcontracts are not allowed under this opportunity, although foreign components and collaborations without direct funding are permitted. The application process requires submission through standard NIH channels and must include detailed components such as scientific and operational plans, milestone definitions, and strategies for community engagement. Applicants are encouraged to include multiple principal investigators, particularly those with expertise in biostatistics and clinical trial design. The evaluation process emphasizes scientific merit, feasibility, and alignment with NIH priorities, including efforts to improve health equity and broaden community engagement throughout the research lifecycle. The opportunity was posted on March 18, 2026, and remains open for applications until November 2, 2028. There are no stated pre-application requirements such as letters of intent. The program does not require cost sharing or matching funds. While specific award timelines and performance periods are not detailed in the summary, applicants should expect a structured review process consistent with NIH standards. For additional information or assistance, applicants may contact the Division of Cardiovascular Sciences via the provided program email address. This funding opportunity is not explicitly described as recurring, but its long open window suggests multiple submission cycles within the stated timeframe.

Applicants should clearly articulate core milestones and contingency plans to secure continuation to the R33 phase. Community engagement and inclusive recruitment metrics are heavily emphasized. Poor milestone performance may result in early termination.