The National Institutes of Health (NIH) invites applications for the NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Required). This opportunity provides support for early-stage, high-risk, and innovative research projects that require at least one clinical trial. Projects funded under this program aim to advance novel ideas, methodologies, or technologies with the potential to significantly impact biomedical, behavioral, or clinical research. The focus is on clinical trials that explore or understand biological, behavioral processes, disease pathophysiology, or mechanisms of action for interventions. Certain NIH Institutes and Centers participating in this program only accept mechanistic studies that meet the NIH’s definition of a clinical trial.

The R21 mechanism is intended for exploratory and developmental studies that are distinct from long-term projects typically funded through the R01 activity code. Proposed studies should address new areas of investigation, feasibility testing of novel methods, or exploratory research approaches that could lead to groundbreaking discoveries. Applications must align with the programmatic interests of one or more participating NIH Institutes and Centers, whose specific research priorities are outlined on the R21 Clinical Trial Required IC-Specific Scientific Interests and Contact website.

Eligible applicants include higher education institutions, nonprofits, for-profit organizations, small businesses, local and state governments, tribal entities, and foreign institutions. Non-domestic components of U.S. organizations are also eligible. All applicants must complete required registrations, including Dun and Bradstreet (DUNS), System for Award Management (SAM), eRA Commons, and Grants.gov, prior to submission. Applications must be submitted electronically through NIH ASSIST, Grants.gov Workspace, or an institutional system-to-system solution.

The total budget for the two-year project period cannot exceed $275,000 in direct costs, with no more than $200,000 requested in any single year. The project period is limited to a maximum of two years. Applications will be evaluated based on their significance, innovation, approach, and potential impact, with additional considerations for the study timeline, data management, and protections for human subjects. Reviewers will assess the feasibility and rigor of the proposed study design, including recruitment, retention, statistical analysis, and adherence to clinical trial requirements.

Applicants must propose clinical trials as defined by NIH, where human participants are prospectively assigned to interventions to evaluate biomedical or behavioral outcomes. Mechanistic studies exploring biological or behavioral processes are encouraged, particularly when aligned with IC-specific priorities. Applicants are strongly advised to contact NIH Scientific/Research staff to ensure the proposed study meets the requirements and aligns with the priorities of a participating Institute or Center.

Standard NIH due dates apply, with non-AIDS applications due by 5:00 PM local time on the designated dates. AIDS and AIDS-related applications have separate submission deadlines. Applicants are encouraged to submit early to resolve any errors during the submission process. Awards are contingent on the scientific merit of the proposed research, program priorities, and availability of funds. The expiration date for this funding opportunity is January 8, 2025.