The Department of Health and Human Services, through the National Institutes of Health (NIH) and specifically the National Institute of Dental and Craniofacial Research (NIDCR), offers the Clinical Trial Planning and Implementation Cooperative Agreement (UG3/UH3) to support investigator-initiated clinical trials focused on dental, oral, and craniofacial conditions. This funding opportunity, reissued as PAR-25-057, is a phased award that begins with a one-year planning phase (UG3) and potentially progresses to a five-year implementation phase (UH3) for approved projects. The UG3 phase emphasizes detailed planning, while the UH3 phase covers trial execution. Projects supported under this FOA are required to be milestone-driven, with progression contingent upon achieving specific goals, alignment with NIDCR priorities, and availability of funds.

The primary purpose of this FOA is to advance clinical trials that test FDA-regulated drugs, biologics, devices, or procedures, aiming to improve outcomes in dental, oral, or craniofacial diseases. Eligible trials may include diagnostics, preventive measures, or treatments for conditions such as periodontal disease, tissue regeneration, oral infections in immunocompromised patients, and pain management related to temporomandibular disorders. Notably, the FOA excludes studies testing behavior change interventions or those exploring mechanisms of behavior change. This structure reflects NIDCR's commitment to clinical studies with significant potential for impact on dental and craniofacial health.

The scope of funding includes a cap of $400,000 in direct costs for the UG3 planning phase, with no specified cap for the UH3 implementation phase, though budgets must be justified. Funds may support a single clinical trial, and the UG3 phase may cover protocol finalization, development of a Manual of Procedures, statistical analysis planning, and feasibility assessments. Transition to UH3 requires successful completion of UG3 milestones, such as finalizing the study protocol and setting up fidelity monitoring. NIH will engage substantively with awardees throughout both phases, providing guidance on scientific and operational aspects.

Eligible applicants encompass a broad range of U.S.-based institutions, including higher education institutions, nonprofits, for-profit organizations, and government entities at various levels. Foreign institutions and non-U.S. components of domestic entities are not eligible to apply. All applicants must complete essential registrations in DUNS, SAM, eRA Commons, and Grants.gov, and comply with NIH's human subjects and clinical trial policies. Submission must be through NIH’s ASSIST or compatible systems, with application deadlines staggered across multiple review cycles.

Applications are evaluated on criteria such as significance, investigator qualifications, innovation, methodological approach, and potential to address unmet needs. Specific UG3 criteria focus on the adequacy of planning activities, feasibility of recruiting participants, and anticipated challenges, while the UH3 criteria center on trial execution and data analysis plans. Both phases require detailed milestones, quality management, and data handling protocols. Applications must also include a clear data and safety monitoring plan to ensure fidelity to study protocols across sites.

Key dates for submission start from June 2021, with standard NIH cycles applied. Each cycle includes submission dates for new, resubmission, and AIDS-related applications, followed by scientific merit review, advisory council review, and start date windows. Applicants must submit letters of intent 30 days before the due date and are encouraged to submit early to allow time for corrections. The FOA is set to expire on January 9, 2025, offering multiple submission opportunities across its active period.