The National Institutes of Health (NIH) funding opportunity titled "Transformative Research to Address Health Disparities and Advance Health Equity (U01 Clinical Trial Optional)" (RFA-NR-25-003) aims to support exceptionally innovative intervention research that addresses social determinants of health (SDOH) to prevent, reduce, or eliminate health disparities and advance health equity. This funding initiative targets transformative projects with the potential for a significant and lasting impact on health outcomes through intervention, dissemination, or policy evaluation approaches. Proposals must focus on SDOH, which NIH defines as the structural factors and conditions of daily life shaping health outcomes. Interventions solely targeting individual- or family-level social and economic circumstances without addressing upstream SDOH factors will not be considered responsive.

The program seeks projects that address one or more NIH-designated health disparity populations, including racial and ethnic minorities, low socioeconomic status groups, underserved rural populations, sexual and gender minorities, people with disabilities, and intersecting subpopulations. Projects must incorporate meaningful community partnerships throughout the research process to ensure the feasibility, relevance, and sustainability of interventions. Partnerships across sectors such as education, housing, transportation, and social services are strongly encouraged. Applications must also include a Plan for Enhancing Diverse Perspectives (PEDP) outlining actionable strategies to enhance inclusivity and diverse representation in the project team, participants, and research outcomes.

Funding will be provided through cooperative agreements (U01) with substantial programmatic involvement from NIH staff. NINR intends to allocate approximately $3 million in Fiscal Year 2025 to fund 4–6 awards. Each award will be limited to less than $500,000 in direct costs per year, with a maximum project period of five years. Applications should present a timeline with deliverables that demonstrate potential for transformative impact by the end of the funding period. Preliminary data are not required but can be included if available.

Eligible applicants include higher education institutions (public and private), non-profits, small businesses, state and local governments, tribal organizations, and other qualifying entities within the United States. Foreign institutions are not eligible to apply, though foreign components of U.S.-based institutions are permitted. Applicant organizations must register with SAM, eRA Commons, and Grants.gov. Individuals designated as Program Directors/Principal Investigators (PDs/PIs) must have an active eRA Commons account.

Applications must follow the How to Apply – Application Guide and include sections addressing specific aims, research strategy, community partnerships, and plans for meaningful engagement with populations experiencing health disparities. NIH will use its standard merit review process, focusing on significance, innovation, rigor, feasibility, and alignment with the funding opportunity's goals. Specific evaluation criteria include the novelty and transformative potential of the intervention, robustness of the methodological approach, strength of community partnerships, and the inclusion of diverse perspectives as outlined in the PEDP.

The application due date is February 28, 2025, with the earliest anticipated award start date in September 2025. A letter of intent is encouraged by January 29, 2025. Applications must be submitted via ASSIST, an institutional system-to-system solution, or Grants.gov Workspace. Compliance with NIH data management and sharing policies is required. For further details and clarification, applicants are encouraged to contact the relevant NIH program officers, including Dr. Julia Seay (NINR), Dr. Deidra Roach (NIAAA), Dr. Ashlinn Quinn (NIEHS), and others listed in the funding announcement.