The National Institutes of Health (NIH) invites applications for the Research Project Grant (Parent R01 Clinical Trial Required). This funding opportunity supports discrete, specific, and circumscribed projects in scientific areas aligned with the missions of the participating NIH Institutes and Centers (ICs). Applicants must propose at least one clinical trial in their projects, defined as studies prospectively assigning human subjects to interventions to evaluate their effects on biomedical or behavioral outcomes. Mechanistic studies—designed to understand biological or behavioral processes, disease pathophysiology, or mechanisms of action of interventions—are eligible under this announcement, though some participating ICs only accept such trials. Applicants are encouraged to identify ICs with relevant research interests and consult program staff before submission.

The purpose of this opportunity is to advance health-related research through clinical trials that address scientific knowledge, technical capability, and clinical practice. Trials may include safety, efficacy, exploratory mechanistic studies, biomarker investigations, and behavioral interventions, contributing to understanding diseases, prevention, and potential treatments. Projects should address significant health-related problems, and applications are evaluated on their scientific merit, innovation, and feasibility.

Eligible applicants include higher education institutions (public, private, and minority-serving), nonprofits, for-profit organizations (including small businesses), local, state, and federal governments, tribal entities, independent school districts, and foreign institutions. Individuals with the requisite skills, knowledge, and resources may serve as Program Directors/Principal Investigators (PD/PI), including those from underrepresented racial and ethnic groups and individuals with disabilities. All applicants must complete necessary registrations, including DUNS, SAM, eRA Commons, and Grants.gov, prior to submission.

There are no budget limits for this opportunity, but budgets must align with the project’s needs. The maximum project period is five years. Applicants requesting $500,000 or more in direct costs in any year must contact relevant IC staff at least six weeks prior to submission to ensure alignment with policies. Multiple applications from the same organization are allowed, provided each is scientifically distinct. Applications must adhere to the NIH’s strict submission guidelines outlined in the SF424 (R&R) Application Guide.

Applications will undergo peer review based on key criteria: significance, investigator qualifications, innovation, approach, environment, and overall impact. Reviewers will assess the justification for the proposed trial, its scientific premise, study design, statistical analyses, and inclusion of women, minorities, and individuals across the lifespan. The advisory council will conduct a second level of review, considering the scientific merit, funding availability, and program priorities. Special considerations apply for foreign institutions, vertebrate animal research, and research involving select agents.

Standard NIH submission deadlines apply. Non-AIDS applications are due June 5, October 5, and February 5 annually, while AIDS-related applications are due September 7, January 7, and May 7 annually. Applications must be submitted by 5:00 PM local time of the applicant’s organization. The earliest start dates follow standard NIH timelines after the completion of peer and council reviews.

For submission, applicants must use NIH ASSIST, Grants.gov Workspace, or an institutional system-to-system solution. Data Management and Sharing Plans are required for applications submitted after January 25, 2023. Awardees must comply with NIH’s policies on human subjects research, data safety monitoring, ClinicalTrials.gov registration, and FDA requirements for investigational products, where applicable.

Questions regarding scientific or financial aspects of this funding opportunity should be directed to IC-specific staff listed on the R01 Clinical Trial Required IC-Specific Scientific Interests and Contact website. Full details, including submission requirements, application instructions, and evaluation criteria, can be found in the SF424 (R&R) Application Guide and the official NIH Grants Policy Statement. This opportunity remains open until its expiration on January 8, 2025.