NIH Exploratory/Developmental Research Project Grant (Parent R21 Clinical Trial Not Allowed)

The National Institutes of Health (NIH), an agency within the U.S. Department of Health and Human Services, has reissued the NIH Exploratory/Developmental Research Project Grant (Parent R21 Clinical Trial Not Allowed), under funding opportunity number PA-25-304. This program is designed to support innovative and high-risk exploratory and developmental research projects at their early and conceptual stages. The grant is intended to foster creative discoveries, encourage new lines of inquiry, and advance novel methodologies, techniques, and models that could significantly impact biomedical, behavioral, or clinical research. Unlike the NIH R01 program, which supports longer-term and more established research areas, this opportunity is explicitly targeted at new and exploratory projects that are distinct, novel, and potentially transformative. Applications may be submitted to any of the NIH Institutes and Centers (ICs) that participate in this announcement, each of which supports specific mission areas such as aging, genetics, mental health, nursing, child development, cancer, and others. Applications are assigned to ICs based on NIH receipt and referral guidelines. Applicants are strongly encouraged to review the R21 IC-Specific Scientific Interests and Contact website and consult program officers from relevant ICs to verify alignment with the specific mission priorities of each Institute or Center. Not all NIH ICs participate, so applicants must carefully verify which ICs are eligible to fund their research. Certain NIH Offices, including the Office of Data Science Strategy, may also co-fund applications aligned with their priorities. The funding instrument is a grant, with the award ceiling set at a maximum of $275,000 in direct costs for the combined two-year project period. No more than $200,000 may be requested in any single year. Awards are subject to NIH appropriations, and the number of funded applications will depend on the availability of funds and the quality of submissions. Project periods may not exceed two years. NIH grant policies and cost principles, as outlined in the NIH Grants Policy Statement, apply to all awards. This funding opportunity does not require cost sharing, and there is no matching requirement. Foreign and domestic entities are eligible, including higher education institutions, nonprofits, small and large businesses, governments at all levels, independent school districts, faith-based and community organizations, tribal governments, and regional organizations. Applications must be submitted electronically through Grants.gov using NIH ASSIST, Grants.gov Workspace, or an institutional system-to-system solution, with tracking managed in eRA Commons. All applicant organizations must have active registrations in System for Award Management (SAM), eRA Commons, and Grants.gov, and must have a valid Unique Entity Identifier (UEI). Program Directors/Principal Investigators (PDs/PIs) must hold an eRA Commons ID. Applications must comply strictly with the instructions in the NIH Application Guide. Late or incomplete submissions will not be accepted. While Letters of Intent are not required, applicants must ensure complete compliance with all submission and registration requirements. Applications will undergo NIH’s rigorous peer review process, which evaluates significance, innovation, approach, rigor, feasibility, investigator qualifications, and institutional resources. Reviewers will emphasize the conceptual framework and the potential for transformative discoveries, while recognizing that preliminary data are not required. Proposals involving human subjects or vertebrate animals must include detailed protections and justifications, while projects using biohazards must outline adequate safety measures. Applications are further evaluated for alignment with NIH priorities, availability of funds, and programmatic relevance. Highly meritorious projects will receive an overall impact score and may proceed to a second-level review by the appropriate NIH Advisory Council or Board. The opportunity was posted on December 18, 2024, with the earliest submission date beginning January 16, 2025. Applications follow NIH’s standard due dates of February 16, June 16, and October 16, with parallel deadlines for renewals and AIDS-related projects. Applications are accepted until January 8, 2028, when the program expires. Each submission cycle follows NIH’s standard review and award process, beginning with scientific merit review, followed by Advisory Council review, and earliest possible award start dates set approximately four to six months after submission. This funding opportunity is recurring, with annual cycles expected until expiration. Applicants with questions may contact the eRA Service Desk at 301-402-7469 or 866-504-9552, GrantsInfo@nih.gov for general NIH grants information, or Grants.gov support at 800-518-4726 for registration and technical issues. For scientific inquiries, program-specific contacts are available through the IC-Specific R21 website. Financial and grants management contacts are also available at each participating Institute or Center. This Notice of Funding Opportunity operates under the authority of Sections 301 and 405 of the Public Health Service Act and applicable federal regulations. All awards are subject to NIH and HHS grant policies and regulations, including those concerning human subjects protections, nondiscrimination, and financial accountability.