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, reissued as PAR-25-028 by the National Institutes of Health (NIH), is administered through the National Heart, Lung, and Blood Institute (NHLBI). It supports applications for the development and implementation of investigator-initiated single-site clinical trials. These trials may include efficacy, comparative effectiveness, pragmatic, and/or implementation research clinical trials that align with NHLBI’s mission. Innovative designs such as adaptive or Bayesian trials are encouraged. The NOFO mandates that all trials adhere to the NIH definition of a clinical trial and be relevant to NHLBI's research priorities. This grant utilizes a bi-phasic R61/R33 mechanism. The R61 phase, lasting up to one year, covers protocol finalization and preparatory activities, including IRB approvals and Data and Safety Monitoring Board (DSMB) setup. The R33 phase can last up to four years and is dedicated to full trial implementation. Core milestones must be met to transition from the R61 to the R33 phase, including early participant enrollment. A milestone-driven approach emphasizes on-time, on-budget project completion and efficient trial management practices. Eligibility spans a broad range of U.S.-based and foreign entities, including higher education institutions, non-profits, for-profits, governments at all levels, tribal organizations, and public housing authorities. Foreign organizations and components of U.S. organizations are eligible. Applicants must complete several registrations, including SAM, eRA Commons, and Grants.gov, prior to submission. Principal Investigators must have eRA Commons accounts. While new, resubmission, and revision applications are accepted, only single-site trials are supported. Phase I, observational, and multi-site trials are excluded. Applications require several mandatory attachments: a Single-site Justification Plan, Trial Management Plan, Clinical Trials Research Experience table, and a Community Engagement Plan. Additionally, detailed project management, data monitoring, milestone plans, and adherence to the NIH Data Sharing Policy are critical. Applications must be submitted via ASSIST, Grants.gov, or institutional systems. Applications must comply with NIH formatting and submission guidelines. Deadlines for 2025 include February 11, June 11, and October 10 for new applications. Advisory council reviews and potential start dates follow a scheduled cycle, with final submission dates extending to January 12, 2026. Awards depend on NHLBI funding availability, scientific merit, and alignment with program priorities. Key contacts include scientific and peer review representatives from NHLBI, with specific contacts listed for different divisions. Pre-application consultations are strongly encouraged, especially when requesting $500,000 or more in direct costs annually. Awards are subject to all applicable NIH, HHS, and federal funding policies and oversight protocols.