The NIH Exploratory/Developmental Research Project Grant (Parent R21 Clinical Trial Required), issued by the National Institutes of Health (NIH), supports early and conceptual stages of research projects that include at least one clinical trial. The program is designed to encourage novel ideas, innovative methodologies, and exploratory research that has the potential to substantially advance biomedical, behavioral, and clinical research. Projects may involve significant risk but are expected to lead to breakthroughs, the development of new tools, or applications that can transform a field.

The purpose of the grant is to support research that explores new avenues, assesses the feasibility of innovative concepts, and applies existing methods to novel areas. Unlike traditional R01 grants, R21 projects are shorter in duration and require a defined scope. Applications must propose research that meets the NIH definition of a clinical trial, including mechanistic studies that aim to understand biological or behavioral processes, disease pathophysiology, or intervention mechanisms. Studies must align with the scientific missions of participating NIH Institutes and Centers (ICs), which may have unique programmatic interests.

Eligible applicants include higher education institutions, nonprofit organizations, for-profit organizations, government entities, and foreign organizations. Non-domestic components of U.S. organizations are also eligible. Applicants must ensure all required registrations, including SAM.gov, eRA Commons, and Grants.gov, are completed before submission. The total project period is limited to two years, with a combined budget for direct costs not exceeding $275,000, and no more than $200,000 may be requested in a single year.

Applications will be reviewed based on significance, innovation, rigor, feasibility, investigator expertise, and institutional resources. Specific criteria include the novelty of the research, its potential impact, and the scientific quality of the proposed approach. Applications must also address protections for human subjects, data management and sharing plans, and the validity of key resources. NIH emphasizes that R21 applications need not include extensive preliminary data but must justify the conceptual framework and methodology.

Key deadlines follow NIH’s standard schedule, with applications due three times per year starting February 16, 2025. Submissions must be completed electronically through Grants.gov and tracked in eRA Commons. Applicants are encouraged to submit early to address any system errors before the deadline. Award decisions will be based on scientific merit, availability of funds, and programmatic priorities. Successful applicants will receive a Notice of Award outlining specific terms and conditions.

This funding opportunity requires that all proposed projects include clinical trials. Applicants should consult the R21 IC-Specific Scientific Interests and Contact website to confirm IC participation and alignment with their programmatic goals. NIH staff are available to provide guidance on application requirements and program fit. Final awards are contingent on compliance with NIH policies, scientific review outcomes, and funding availability.