Development of Psychosocial Therapeutic and Preventive Interventions for Mental Disorders (R61/R33- Clinical Trial Required) | RFA MH 18 704

Opportunity Information: Apply for RFA MH 18 704

The National Institutes of Health (NIH) funding opportunity titled "Development of Psychosocial Therapeutic and Preventive Interventions for Mental Disorders (R61/R33 - Clinical Trial Required)" is designed to accelerate the early-stage development of new psychosocial treatments and prevention approaches for mental disorders across the lifespan, including both adults and children. The central goal is to fund efficient, milestone-driven clinical trials that test whether a novel intervention meaningfully affects a clearly defined target that is believed to play a role in the risk for, cause of, or maintenance of a mental disorder. The announcement uses an "experimental therapeutics" framework, meaning the study is not just about whether symptoms improve, but whether the intervention engages a specific mechanism or process in a measurable way. A key expectation is that the trial will produce results that remain scientifically valuable even if the intervention does not work as hoped, because the findings should still help the field decide whether the intervention should move forward, be revised, or be discontinued.

This FOA focuses on innovation in either (1) the intervention target or (2) the intervention strategy. Targets can include modifiable behavioral, cognitive, affective, or interpersonal processes, as well as neural circuits, patterns of neural activity tied to specific behaviors or cognitive functions, or other neurobiological mechanisms linked to mental disorders. In other words, applicants are expected to ground their intervention in contemporary basic science about how mental disorders emerge and persist, then translate that science into an intervention that can be tested in a structured way. The intervention itself can be delivered in person, through technology (such as digital tools or telehealth-enabled approaches), or via other formats, as long as what is being tested is genuinely novel in its target and/or strategy. The FOA also allows these psychosocial interventions to be tested either as stand-alone treatments (monotherapies) or as additions that augment standard care, as long as the study design can isolate and evaluate the proposed mechanism and its relationship to outcomes.

The award mechanism is a phased R61/R33 grant, which is meant to support fast, evidence-based decisions about whether further investment is justified. The first phase (R61) provides up to two years of support for preliminary, milestone-driven testing, with an emphasis on demonstrating target engagement. Target engagement here means showing that the intervention measurably changes the proposed mechanism or process it is designed to affect, not simply that participants report feeling better. This early phase is built around explicit "go/no-go" milestones, so the project should be structured with clear decision points and measurable criteria that determine whether it is ready to advance. If the project meets those milestones, the second phase (R33) can provide up to three additional years of funding. In the R33 phase, the work typically expands to replicate the target engagement finding and, critically, to test whether changes in the target/mechanism are linked to meaningful clinical benefit, such as symptom reduction, improved functioning, or reduced risk of developing a disorder for prevention-focused projects.

A defining feature of this opportunity is its insistence on high-utility results. Applicants are expected to design trials so that, regardless of whether the intervention produces the desired clinical outcomes, the study still provides strong evidence about whether the hypothesized mechanism was engaged and whether engaging it appears to matter for clinical change. This emphasis helps avoid ambiguous trials that only measure symptom shifts without clarifying why they occurred, and it supports faster scientific learning by making it easier to decide what to refine, what to scale, and what to abandon. Overall, the program is intended to shorten the path from basic mechanistic discoveries (for example, findings about specific cognitive biases, interpersonal dynamics, affect regulation processes, or neurobiological pathways) to interventions that can restore functioning, reduce symptoms, or prevent the onset of mental disorders among people at risk.

From an eligibility and administrative standpoint, this is a discretionary NIH grant in the health funding category (CFDA 93.242), listed under Funding Opportunity Number RFA-MH-18-704. A wide range of applicants can apply, including state, county, and local governments; public and private institutions of higher education; independent school districts; special district governments; federally recognized Native American tribal governments; tribal organizations that are not federally recognized; public housing authorities and Indian housing authorities; nonprofit organizations (with or without 501(c)(3) status); for-profit organizations (other than small businesses); and small businesses. The FOA also explicitly highlights additional eligible applicant types 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 (AANAPISI), faith-based or community-based organizations, regional organizations, U.S. territories or possessions, and even non-U.S. entities (foreign organizations), reflecting an intent to broaden participation and encourage diverse research settings and partnerships.

Finally, this opportunity is explicitly a clinical trial required announcement, meaning applicants must be proposing a clinical trial that tests the psychosocial intervention in human participants. The original posting indicates a creation date of November 13, 2017, with an original closing date of February 18, 2021. Even though those dates describe that specific listing, the core structure and intent of the FOA are clear: fund early, rigorous, mechanism-focused psychosocial intervention studies with built-in decision rules, and use that disciplined approach to speed the development of next-generation treatments and prevention strategies for mental disorders.

• 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 2017-11-13.
• Applicants must submit their applications by 2021-02-18. (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.

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