The Department of Health and Human Services, through the National Institutes of Health (NIH), is offering a funding opportunity under the HEAL Initiative to support action-oriented research that accelerates the translation of evidence-based and promising treatments into practice to address the overdose crisis. This funding opportunity, titled *HEAL Initiative: Translating Research to Practice to End the Overdose Crisis* (R33 Clinical Trial Optional), focuses on tackling barriers and identifying facilitators to reducing overdose deaths at individual, provider, organizational, community, or system levels. The program encourages projects that align with the HEAL Initiative’s goals, focusing on equitable, scalable, and sustainable solutions for the treatment of opioid use disorder, stimulant use disorder, and recovery support.

The HEAL Initiative aims to advance the development of stigma-free, patient-centered systems of care that help individuals experiencing addiction achieve and sustain recovery. This particular Notice of Funding Opportunity (NOFO), RFA-DA-25-077, is specifically for research projects that have preliminary data available and are ready for large-scale studies. A companion NOFO, RFA-DA-25-078, targets projects that do not yet have feasibility data and require preparatory work.

Eligible projects must go beyond descriptive studies, focusing instead on the development and testing of systematic strategies that improve the quality of addiction-related care. Research methods such as implementation science and hybrid implementation/effectiveness trials are highly encouraged. Applicants must demonstrate meaningful engagement with stakeholders, including patients, families, providers, and payers, and address issues of health disparities, scalability, and sustainability. Studies may be conducted in various settings such as healthcare systems, criminal justice, workplaces, pharmacies, and community-based locations, including nontraditional delivery settings that increase access to underserved populations.

Projects funded under this initiative should address critical gaps, such as improving service delivery, testing novel care models, enhancing dissemination and implementation of evidence-based practices, and eliminating ineffective or low-value interventions. Applications that propose studies solely focused on primary prevention or opioid prescribing are not eligible. NIDA and other participating NIH Institutes emphasize the importance of engaging diverse perspectives through a required *Plan for Enhancing Diverse Perspectives* (PEDP), which must include actionable strategies for inclusivity and will be part of the review criteria.

Applicants may request funding without a budget cap but are strongly advised to limit requests to no more than $750,000 in direct costs per year unless adequately justified. The maximum project period is five years, though applicants are encouraged to streamline projects for completion within four years. NIH expects to commit up to $10 million in fiscal year 2026 to fund approximately 12 awards across this NOFO and its companion, RFA-DA-25-078.

Eligible applicants include higher education institutions, nonprofit organizations, for-profit organizations, local and state governments, tribal entities, and other eligible U.S.-based entities. Foreign institutions are not eligible, though foreign components of U.S. institutions may participate. Applications must include required registrations, a letter of intent submitted 30 days before the due date, and a completed PEDP. NIH also requires a data management and sharing plan that adheres to the HEAL Data Sharing Policy.

Applications are due by March 20, 2025, with scientific merit review expected in July 2025, advisory council review in October 2025, and project start dates as early as December 2025. NIH anticipates holding annual scientific meetings for awardees, and applicants are encouraged to include travel costs for relevant personnel in their budgets.

For further details, prospective applicants are encouraged to consult with NIH program staff during the early application preparation process to ensure alignment with HEAL Initiative goals. More information can be obtained from the NIH HEAL Initiative website or by contacting the program officials listed in the NOFO