Full-Scale Hybrid Effectiveness-Implementation Trials for Mental Health Interventions (R01 - Clinical Trial Required) | PAR 25 177

Opportunity Information: Apply for PAR 25 177

The National Institute of Mental Health (NIMH), part of the National Institutes of Health (NIH), is offering a discretionary grant opportunity titled "Full-Scale Hybrid Effectiveness-Implementation Trials for Mental Health Interventions (R01 - Clinical Trial Required)" under funding opportunity number PAR 25-177 (CFDA 93.242). The program supports full-scale clinical trials using the R01 mechanism and is positioned as a major component of NIMH's broader set of funding announcements that cover the full pipeline of intervention development and testing. Applications are accepted through an original closing date of 2027-10-15.

The core purpose of this opportunity is to fund rigorous, adequately powered effectiveness trials that can directly inform real-world mental health practice. NIMH is looking for studies that tackle significant mental health problems where the results have clear potential to change or improve how interventions are delivered in community and routine care settings. The announcement emphasizes that supported trials should be designed to definitively answer primary research questions, rather than serving as exploratory pilots. Proposals are expected to be grounded in well-justified hypotheses supported by pilot or preliminary data, and they should be structured to examine not only whether an intervention works, but also how and for whom it works through planned analyses of mediators and moderators.

The NOFO supports two broad categories of clinical trials. First, it funds trials that test the effectiveness of optimized therapeutic and preventive interventions when delivered in community or practice settings, meaning interventions that are sufficiently developed and ready for real-world evaluation beyond tightly controlled efficacy contexts. Second, it funds trials that evaluate the effectiveness of mental health services interventions at multiple levels, including patient-level strategies, provider-level strategies, organizational changes, or broader system-level approaches. These services interventions should be aimed at improving key dimensions of care such as access to services, continuity of care, quality, equity, and/or value, with an emphasis on outcomes that matter for real-world service delivery.

A defining feature of this announcement is its alignment with NIMH's experimental therapeutics approach. In practical terms, NIMH expects effectiveness trials to explicitly test whether the intervention engages the proposed target(s) or mechanism(s) that are presumed to drive improvement. Depending on the type of intervention, those mechanisms could involve changes in clinical or functional outcomes for patients, changes in provider behavior, or measurable improvements in service access, engagement, retention, or continuity. The intent is to move beyond simple outcome comparisons and ensure that the trial design includes measurement and analytic plans that can evaluate whether the intervention is influencing the hypothesized mechanism and whether that mechanism is linked to meaningful improvements.

The grant uses the R01 clinical trial required framework, and it also references a collaborative R01 option to support multisite trials when multiple sites are needed to successfully complete the study. Multisite collaboration is encouraged when it is necessary to reach adequate sample size, speed recruitment, or increase participant diversity and representation, which can strengthen both the internal validity of the trial and the generalizability of the findings to varied real-world settings.

Eligibility is broad and includes many types of domestic and non-domestic organizations. Eligible applicants include state, county, city or township governments; special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; federally recognized tribal governments; tribal organizations that are not federally recognized; public housing authorities and Indian housing authorities; nonprofits with or without 501(c)(3) status (excluding institutions of higher education in those nonprofit categories); for-profit organizations (other than small businesses); and small businesses. The announcement also highlights additional eligible applicant categories such as Historically Black Colleges and Universities (HBCUs), Hispanic-serving Institutions, Tribally Controlled Colleges and Universities (TCCUs), Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISISs), faith-based or community-based organizations, eligible federal government agencies, regional organizations, U.S. territories or possessions, and non-U.S. entities (foreign organizations).

Overall, this opportunity is geared toward teams prepared to run full-scale, practice-relevant mental health clinical trials that combine strong real-world effectiveness questions with explicit testing of mechanisms, and that are built to deliver clear, actionable conclusions for clinical care and mental health service systems.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Full-Scale Hybrid Effectiveness-Implementation Trials for Mental Health Interventions (R01 - Clinical Trial Required)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.242.
• This funding opportunity was created on 2024-11-26.
• Applicants must submit their applications by 2027-10-15.
• 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 PAR 25 177

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