Development of Psychosocial Therapeutic and Preventive Interventions for Mental Disorders (R61/R33 Clinical Trial Required) | PAR 21 135

Opportunity Information: Apply for PAR 21 135

The National Institute of Mental Health (NIMH), under the National Institutes of Health (NIH), is soliciting applications for a phased grant opportunity titled Development of Psychosocial Therapeutic and Preventive Interventions for Mental Disorders (R61/R33 Clinical Trial Required), funding opportunity number PAR-21-135. This announcement is a reissue of an earlier NIMH request (RFA-MH-18-704) and sits within NIMH's broader clinical trials pipeline. The overall goal is to accelerate the creation and early testing of new psychosocial interventions, or new intervention targets, that could prevent mental disorders or improve treatment outcomes. The emphasis is not simply on showing that an intervention "works," but on building interventions in a way that clearly tests mechanisms of change, consistent with NIMH's experimental therapeutics approach.

A central feature of this opportunity is its focus on translating advances from basic and applied science into real-world preventive or therapeutic strategies. The FOA encourages investigators to draw from developments in behavioral science, cognitive science, affective science, and neuropsychological research to identify promising targets (for example, a specific cognitive bias, emotion regulation process, social learning mechanism, or other modifiable process linked to symptoms or functioning). Applicants are expected to design psychosocial interventions that can engage those targets in measurable ways, and then connect that target engagement to clinically meaningful improvement. In practical terms, the work is meant to move beyond broad intervention packages and toward interventions that can demonstrate, with data, that they are affecting the intended mechanism and that this mechanistic change is tied to changes in clinical outcomes.

The grant uses a two-phase R61/R33 structure. The R61 phase supports early, milestone-driven work for up to two years. This first phase is intended for piloting, refining, and parameter-setting, with a strong focus on evaluating whether the intervention actually engages the proposed target and on establishing key intervention parameters (such as dose, intensity, delivery format, feasibility benchmarks, fidelity procedures, and measures sensitive to change). If the project meets its prespecified milestones, it can transition into the R33 phase, which can provide up to three additional years. The R33 phase is designed to replicate target engagement findings from earlier work and to more directly test whether target engagement is associated with improvement in one or more clinical outcomes. Across both phases, clinical trials are required, meaning the project must involve prospective assignment to an intervention condition and evaluation of outcomes in a way that meets NIH's definition of a clinical trial.

The opportunity is categorized as a discretionary grant within the health funding activity area, associated with CFDA number 93.242. While the notice does not specify an award ceiling or expected number of awards in the provided excerpt, it does indicate an original closing date of October 15, 2024, and a creation date of March 2, 2021. Because the mechanism is milestone-driven, applicants should expect that clear, objective go/no-go criteria and rigorous measurement plans will be important to competitiveness, particularly around how target engagement will be assessed and how links between mechanistic change and clinical endpoints will be evaluated.

Eligibility is broad and includes many types of domestic applicants such as state, county, and local governments; special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; and federally recognized Native American tribal governments. Eligible organizational applicants also include public housing authorities and Indian housing authorities; Native American tribal organizations that are not federally recognized tribal governments; nonprofit organizations with or without 501(c)(3) status (excluding institutions of higher education when specified in the eligibility listing); for-profit organizations other than small businesses; and small businesses. In addition, the FOA explicitly highlights other eligible applicants such as Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISIs), Hispanic-serving Institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), faith-based or community-based organizations, eligible federal government agencies, regional organizations, U.S. territories or possessions, and even non-U.S. entities (foreign organizations). This wide eligibility scope signals NIMH's interest in supporting diverse research teams and settings, including community-linked organizations that may be well positioned to develop and test interventions in populations with unmet needs.

In summary, PAR-21-135 is aimed at early-stage, mechanism-focused development of psychosocial preventive and therapeutic interventions for mental disorders, using a structured R61/R33 pathway to move from initial target engagement testing and intervention optimization to replication of target engagement and evaluation of how mechanistic change relates to clinical improvement. The defining expectation is a rigorous experimental therapeutics framework: identify a plausible, measurable target; show that the intervention engages it; and demonstrate that engaging it matters for clinical outcomes.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Development of Psychosocial Therapeutic and Preventive Interventions for Mental Disorders (R61/R33 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 2021-03-02.
• Applicants must submit their applications by 2024-10-15. (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 PAR 21 135

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