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

The National Institutes of Health (NIH), operating under the U.S. Department of Health and Human Services, issues the Exploratory/Developmental Research Project Grant (Parent R21 Clinical Trial Required) to support early-stage, high-risk research with the potential for significant scientific advancement. This program reflects NIH’s mission to enhance health, reduce illness, and expand scientific understanding through innovative biomedical, behavioral, and clinical research. Managed across multiple Institutes and Centers (ICs) — including the National Eye Institute, National Cancer Institute, National Institute on Aging, and others — the Parent R21 mechanism enables cross-disciplinary discovery and the testing of new hypotheses that might not yet have sufficient preliminary data for larger-scale R01 funding. The R21 mechanism specifically funds projects at the conceptual or developmental stage that may explore novel ideas, methods, model systems, or technologies. NIH emphasizes innovation and potential impact, even where feasibility is uncertain. Applications must include at least one NIH-defined clinical trial, either mechanistic or exploratory, designed to understand biological or behavioral processes, disease pathophysiology, or intervention mechanisms. These trials can include human subjects, biomarker analyses, or physiological studies that do not necessarily evaluate treatment safety or efficacy. NIH encourages mechanistic trials that contribute to the scientific foundation of future interventions. The combined direct cost limit for the R21 is $275,000 over a two-year period, with no more than $200,000 allowable in any single year. The total project period cannot exceed two years. Funding levels and the number of awards depend on annual NIH appropriations and the number of meritorious applications received. This mechanism does not require cost-sharing or matching funds. Standard NIH policies on pre-award costs, human subjects protections, vertebrate animal use, data sharing, and clinical trial registration apply. Awards are issued as grants, not cooperative agreements, and follow NIH Grants Policy Statement terms. Applications may be submitted by a wide range of U.S. and foreign institutions, including higher education institutions (both public and private), nonprofit organizations, for-profit entities (including small businesses), local and state governments, tribal governments, and eligible foreign organizations. Faith-based, community-based, and regional organizations may also apply. Eligible individuals with the necessary skills, knowledge, and institutional support are encouraged to apply. Applicants must maintain active registrations in SAM.gov, eRA Commons, and Grants.gov. Each PD/PI must hold an active eRA Commons ID linked to the applicant institution. Applications are accepted on NIH’s standard due dates: February 16, June 16, and October 16 annually for new applications, with corresponding resubmission and AIDS-related deadlines in the following months. Applications are due by 5:00 p.m. local time of the applicant organization and must be submitted electronically via ASSIST, Grants.gov Workspace, or institutional S2S systems. Review occurs three times annually, with earliest start dates approximately six months after submission. This opportunity will remain active through January 8, 2028, unless reissued. The funding opportunity is recurring annually, allowing applicants to plan future submissions on the same schedule. Proposals are reviewed by NIH’s Scientific Review Groups using three core evaluation factors: importance of research (significance and innovation), rigor and feasibility (approach), and expertise and environment (investigators and institutional support). Additional considerations include protections for human subjects, vertebrate animal welfare, and biohazard safety. Applications must clearly justify their scientific merit, the novelty of their approach, and their feasibility within the limited R21 scope. Applicants are encouraged to contact the relevant Institute’s Scientific/Research Contact prior to submission to confirm programmatic fit. Award notifications are issued by NIH Grants Management Officers via a Notice of Award (NoA). Recipients must comply with all applicable federal statutes, data management and sharing policies, and cybersecurity standards for health information systems. For assistance, applicants may contact NIH’s eRA Service Desk, GrantsInfo email, or Grants.gov Customer Support. Updated participation by Institutes and policy notices are published on the NIH Guide for Grants and Contracts website.