This Notice of Funding Opportunity (NOFO) from the National Institute of Dental and Craniofacial Research (NIDCR) invites applications for the continuation or competitive revision of ongoing clinical trials under the UH3 Cooperative Agreement mechanism. The NOFO supports clinical trials focusing on diagnostic, prevention, management, or treatment interventions for dental, oral, or craniofacial diseases and conditions. Applications may propose the extension of trials requiring additional time to achieve objectives or to collect long-term outcome data. Competitive revisions may be considered for modifying the scope of an existing trial, provided there is a strong justification and fully powered hypotheses for the proposed changes. Applicants are strongly encouraged to consult with NIDCR Scientific/Research contacts at least 12 weeks before submission to ensure alignment with NIDCR’s research priorities.

The primary purpose of this NOFO is to advance the understanding and treatment of dental, oral, and craniofacial diseases through well-designed clinical trials. Eligible projects include interventions testing drugs, biologics, devices, procedures, or behavioral/social approaches aimed at improving health outcomes. The NIDCR emphasizes hypothesis-driven trials with clinically meaningful endpoints that are significant to patients and healthcare providers. Multi-site trials are encouraged, and applicants must adhere to NIH policies regarding trial design, safety monitoring, and data management. Applications must include robust statistical designs, fidelity monitoring plans, and well-defined milestones to track progress annually.

Funding under this NOFO is dependent on NIH appropriations and the merit of submitted applications. While no budget ceiling is explicitly stated, budgets must reflect the actual needs of the project. Projects requiring $500,000 or more in direct costs per year must seek NIDCR approval six weeks before submission. The maximum project period is five years. Applications proposing investigational drugs, biologics, or devices must demonstrate compliance with relevant FDA regulations and ensure the proposed intervention aligns with Good Manufacturing Practice (GMP) standards.

Eligible applicants include public and private higher education institutions, nonprofits, for-profit organizations, small businesses, and government entities. Foreign organizations are not eligible to apply, although foreign components of U.S. organizations may participate. Applicants must have active registrations in SAM.gov, eRA Commons, and Grants.gov, and the Program Director/Principal Investigator (PD/PI) must have an active eRA Commons account. Multi-Principal Investigator (MPI) applications are permitted, provided they include a leadership plan.

The application process requires adherence to NIH submission guidelines, including the use of ASSIST, Grants.gov Workspace, or institutional system-to-system solutions. Applications must include a detailed Research Strategy, Data Management and Sharing Plan, Study Timeline, and Milestone Plan. Specific elements such as recruitment and retention plans, quality management plans, and a Schedule of Events must also be addressed. Milestones must be objective, measurable, and achievable, with annual reviews to determine continued funding eligibility.

Applications will undergo NIH’s standard peer review process, with evaluations based on significance, innovation, rigor, feasibility, investigator expertise, and institutional environment. For renewals, reviewers will assess progress from the previous funding period, the rationale for continued funding, and the necessity of proposed changes. For revisions, reviewers will evaluate the justification for modifications and the feasibility of achieving new study aims. Applications deemed meritorious will proceed to the National Advisory Dental & Craniofacial Research Council for final funding decisions.

The first application due date is March 7, 2025, with subsequent cycles in July, November, and March annually until the final deadline on January 6, 2028. Letters of intent are encouraged 30 days before application deadlines. Applicants are advised to contact NIDCR program officials early in the planning stages to ensure compliance with program priorities and application requirements.