NIH Directors Transformative Research Awards (R01 Clinical Trial Optional) | RFA RM 25 003

Opportunity Information: Apply for RFA RM 25 003

The NIH Directors Transformative Research Awards (R01 Clinical Trial Optional), announced under Funding Opportunity Number RFA-RM-25-003 (CFDA 93.310), is a National Institutes of Health grant program designed for research that is intentionally high-risk and high-reward. It targets projects that are bold, unconventional, and exceptionally innovative, with the clear potential to change the way a field thinks or operates. NIH is looking for work that could create entirely new scientific paradigms, lead to fundamentally improved clinical approaches, or produce transformative technologies rather than incremental advances. The program sits within the NIH Common Fund High-Risk, High-Reward Research (HRHR) portfolio, which is specifically meant to encourage daring ideas that might struggle in more traditional funding mechanisms.

A central theme of this opportunity is that applicants do not need preliminary data. Instead, NIH expects applicants to make a compelling, logically grounded case that the proposed idea could have major impact if it succeeds. In practice, that means reviewers will be weighing the strength and originality of the concept, the soundness of the reasoning, and the plausibility that the work could shift a broad area of NIH-relevant science or health. The scope is intentionally wide: proposals can fall anywhere across the NIH mission, including behavioral, social, biomedical, applied, and formal sciences, and can span basic, translational, and clinical research. As the title indicates, clinical trials are optional, meaning the mechanism can support projects with or without a clinical trial component, as long as they fit the program goals and NIH requirements.

NIH also emphasizes broad participation and encourages applications from scientists of diverse backgrounds, including individuals from underrepresented groups, and from a wide range of eligible institutions across all geographic regions. Eligibility covers a broad set of organization types, including state, county, and local governments; special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; federally recognized Native American tribal governments; other Native American tribal organizations; public housing authorities/Indian housing authorities; nonprofits (both 501(c)(3) and non-501(c)(3)); for-profit organizations (other than small businesses); and small businesses. Additional eligible applicants mentioned include eligible federal government agencies, faith-based or community-based organizations, Indian/Native American tribal governments that are not federally recognized, regional organizations, and U.S. territories or possessions.

There are important restrictions related to international involvement. Non-domestic (non-U.S.) entities (foreign organizations) are not eligible to apply, and non-domestic components of U.S. organizations are not eligible to apply. However, foreign components are allowed when they meet the NIH Grants Policy Statement definition, which typically means a discrete part of the project can be conducted outside the U.S. when it is well-justified and adds unique scientific value.

A notable feature of this specific funding opportunity is its peer review approach. NIH, through the Office of Strategic Coordination and the Center for Scientific Review, is piloting an anonymized initial review process in which the identities of investigators and institutions are withheld until the final phase of review. The intent is to focus evaluation as much as possible on the idea and proposed approach rather than reputation, institution, or other identifying factors. Applicants must follow the specific instructions in the funding announcement for anonymizing parts of the application, because this is a compliance requirement tied directly to how the application will be reviewed.

Key administrative details included in the listing are that the opportunity category is discretionary, the funding instrument is a grant, and the activity category is health. The original closing date is listed as 2025-09-03, and the posting creation date is 2025-06-16. The award ceiling and expected number of awards are not specified in the provided source data, so applicants would need to consult the full Notice of Funding Opportunity for budget structure, project period expectations, and the most current program-specific limits and submission requirements.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "NIH Directors Transformative Research Awards (R01 Clinical Trial Optional)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.310.
• This funding opportunity was created on 2025-06-16.
• Applicants must submit their applications by 2025-09-03. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

Apply for RFA RM 25 003

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