Precision Mental Health: Develop Tools to Inform Treatment Selection in Depression (UG3/UH3 Clinical Trial Optional) | RFA MH 25 190

Opportunity Information: Apply for RFA MH 25 190

The Precision Mental Health: Develop Tools to Inform Treatment Selection in Depression (UG3/UH3 Clinical Trial Optional) funding opportunity (RFA-MH-25-190) is a milestone-driven NIH cooperative agreement designed to speed up the creation and early validation of practical prediction tools and biomarkers that can help clinicians choose between two or more already-established depression treatments for an individual patient. The central idea is to move beyond one-size-fits-all care by supporting projects that can forecast which patients are more likely to respond better to one proven therapeutic option versus another, using measurable signals such as clinical features, behavioral or digital measures, neurophysiological readouts, imaging-derived metrics, laboratory biomarkers, or other feasible decision-support tools.

The program is structured as a two-phase pipeline (UG3 followed by UH3) meant to reduce risk and concentrate resources on approaches that show early promise. In the UG3 planning and development phase, applicants are expected to identify and refine candidate predictive tools or biomarker(s) that could plausibly differentiate treatment response across established depression interventions. This first phase can be accomplished in several ways: by running secondary analyses of existing datasets from completed clinical trials, by leveraging real-world clinical data sources, or by conducting small, efficient pilot and feasibility studies to test whether a new or emerging measure is practical to collect and has enough signal to predict individual-level response for a specific depression treatment. The UG3 phase is where teams are expected to do the hard work of evaluating candidate predictors, defining the intended clinical use case, establishing analytic plans, and demonstrating feasibility and early performance against clear milestones.

Projects that meet the predefined UG3 milestones can transition to the UH3 phase, which focuses on independent, prospective clinical trials intended to provide initial validation that the tool or biomarker can actually guide differential treatment selection in real patients. The UH3 work is meant to show that the predictive approach is not only statistically promising in retrospective or pilot work, but also useful when tested prospectively in a clinical-trial setting. While the NOFO notes that a clinical trial is optional overall, the second phase is explicitly oriented toward prospective validation, meaning applicants should be prepared to design and run a study that can credibly test whether the tool meaningfully predicts who does better on Treatment A versus Treatment B among well-established depression therapeutics.

A defining feature of this opportunity is that it is designed to actively down-select. The program is not just trying to generate interesting signals; it is intentionally set up to stop development of tools that fail to meet performance thresholds or feasibility requirements before they consume larger resources. In practice, this means applicants should expect strong emphasis on quantitative milestones, go/no-go criteria, and disciplined evaluation of whether a proposed tool is accurate enough, reliable enough, and practical enough to justify continued investment. At the same time, the NOFO highlights the value of multidisciplinary support and expects teams to address not only scientific and clinical questions, but also technical development needs and the real-world constraints that often prevent promising biomarkers from becoming usable products. That includes attention to regulatory pathways, implementation considerations, and commercialization requirements where relevant, reflecting the program goal of producing tools that could ultimately influence routine clinical decision-making rather than staying confined to research settings.

The funding mechanism is a cooperative agreement, which generally signals substantial involvement from the funding agency beyond a standard grant, often including milestone oversight and coordinated program support. The activity category is health (CFDA 93.242), and the opportunity was created on 2024-04-03 with an original closing date of 2024-10-18. While an award ceiling and expected number of awards are not specified in the provided listing, applicants should interpret the milestone-based UG3/UH3 structure as indicating that continued funding into the UH3 phase is contingent on meeting the UG3 phase requirements.

Eligibility is broad and includes many types of U.S. and non-U.S. organizations. Eligible applicants listed include state, county, and local governments; special districts; independent school districts; public and 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 (other than institutions of higher education); for-profit organizations (other than small businesses) as well as small businesses; and other entities. The NOFO also explicitly calls out additional eligible applicant categories such as Alaska Native and Native Hawaiian Serving Institutions, AANAPISISs, Hispanic-serving Institutions, Historically Black Colleges and Universities, Tribally Controlled Colleges and Universities, faith-based or community-based organizations, U.S. territories or possessions, regional organizations, eligible federal agencies, and non-domestic (foreign) entities. This breadth is consistent with the program’s translational intent and the need for diverse clinical settings, data sources, and development capabilities to produce tools that generalize and can be deployed in practice.

Overall, this opportunity is aimed at building a practical, evidence-based route from promising predictor ideas to early clinical validation for depression treatment selection, with explicit emphasis on comparative prediction across existing treatments, prospective testing, and a realistic pathway toward clinical utility. The end state the NOFO is trying to enable is a set of early-validated decision-support tools or biomarkers that could later be studied further and, if successful, used to improve patient outcomes by matching individuals to the depression treatment most likely to work for them.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "Precision Mental Health: Develop Tools to Inform Treatment Selection in Depression (UG3/UH3 Clinical Trial Optional)" 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 2024-04-03.
• Applicants must submit their applications by 2024-10-18. (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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