NIH Exploratory/Developmental Research Project Grant (Parent R21 Clinical Trial Required)

The National Institutes of Health (NIH), an agency within the U.S. Department of Health and Human Services, is offering the NIH Exploratory/Developmental Research Project Grant (Parent R21 Clinical Trial Required) under announcement number PA-25-306. This program involves multiple participating NIH Institutes and Centers (ICs), including the National Eye Institute, National Human Genome Research Institute, National Institute on Aging, and others. Not all NIH ICs participate, and applicants are advised to confirm interest from relevant ICs before applying. This reissue of PA-20-194 supports innovative research ideas in biomedical, behavioral, and clinical sciences at their early conceptual stages, requiring at least one proposed clinical trial. Some ICs only accept mechanistic clinical trials under this announcement. The primary purpose of this funding opportunity is to support early-stage exploratory and developmental research that has the potential to significantly advance the understanding, prevention, diagnosis, or treatment of human diseases and disorders. Projects are encouraged to take innovative approaches, test new hypotheses, or apply existing methods in novel ways. The research should be distinct from R01 projects and should not be long-term or focused solely on expanding knowledge in well-established areas. The NIH emphasizes fostering discoveries that could lead to breakthroughs or the development of novel methodologies, tools, and models. The funding instrument is a grant, with a combined direct cost limit of $275,000 for the two-year project period, and no more than $200,000 in any single year. The total project period cannot exceed two years. NIH grants policies apply, and the number of awards depends on appropriations and the quality of applications. The program does not require cost sharing, and foreign organizations and components are eligible to apply. The program accepts new, resubmission, and revision applications, and all proposals must involve a clinical trial as defined by NIH. Applications must follow the NIH application instructions and be submitted electronically through ASSIST, Grants.gov Workspace, or institutional system-to-system solutions. Key application dates follow NIH’s standard due dates, with the earliest submission date being January 16, 2025. Applications are accepted on February 16, June 16, and October 16 each year through January 8, 2028. All applications are due by 5:00 PM local time of the applicant organization. The program is recurring with multiple application cycles annually until the expiration date. The review process will consider three main factors: the importance of the research (significance and innovation), rigor and feasibility (approach), and expertise and resources (investigator(s) and environment). Reviewers will also assess protections for human subjects, care of vertebrate animals, handling of biohazards, and other relevant considerations. Awards will be made based on scientific merit, program priorities, and availability of funds. Applicants may be from a broad range of eligible entities, including higher education institutions, nonprofits, for-profit organizations, local and state governments, tribal entities, and foreign organizations. Registrations in SAM.gov, Grants.gov, eRA Commons, and related systems are required prior to submission. For application and submission support, NIH provides contact points for eRA Commons, Grants.gov, and general grant inquiries, as well as IC-specific scientific, peer review, and financial management contacts. The program is governed under the authority of the Public Health Service Act and applicable federal regulations.