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

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

What is this funding opportunity?

This is an NIH milestone-driven cooperative agreement opportunity focused on speeding the development and early validation of practical prediction tools and biomarkers that help clinicians choose between two or more already-established depression treatments for an individual patient.

What problem is the program trying to solve?

The program aims to move beyond one-size-fits-all depression care by supporting tools that can forecast which patients are more likely to respond better to one proven treatment versus another, using measurable signals that can realistically support clinical decision-making.

What kinds of tools or biomarkers does the opportunity support?

The opportunity supports practical decision-support tools and biomarkers that could inform treatment selection in depression, including approaches based on clinical features, behavioral measures, digital measures, neurophysiological readouts, imaging-derived metrics, laboratory biomarkers, and other feasible measures that could be used in a real-world setting.

Does the program focus on new experimental treatments for depression?

No. The emphasis is on predicting differential response across already-established depression treatments (for example, choosing between Treatment A versus Treatment B that are both proven options), rather than developing entirely new treatments.

What does "treatment selection" mean in this context?

Treatment selection here means using a predictor (tool/biomarker) to help decide which of two or more established depression treatments is more likely to work better for a specific patient, based on measurable patient signals.

What is the UG3/UH3 structure?

This opportunity uses a two-phase pipeline. The UG3 phase is a planning and development stage focused on identifying/refining candidate predictors and demonstrating feasibility and early performance against milestones. Projects that meet the UG3 milestones can transition to the UH3 phase, which focuses on prospective clinical-trial work for initial validation in real patients.

What happens during the UG3 phase?

During UG3, teams are expected to identify and refine candidate predictive tools or biomarker(s), define the intended clinical use case, establish analytic plans, and demonstrate feasibility and early performance. UG3 work can include secondary analyses of existing completed-trial datasets, leveraging real-world clinical data, and/or running small pilot and feasibility studies to assess practicality of collection and predictive signal.

What data sources are acceptable for the UG3 phase?

Based on the description, UG3 efforts can be supported through secondary analyses of existing datasets from completed clinical trials, use of real-world clinical data sources, or small and efficient pilot/feasibility studies.

What is the purpose of the UH3 phase?

The UH3 phase supports independent, prospective clinical trials intended to provide initial validation that the tool or biomarker can guide differential treatment selection in real patients. The goal is to test whether the predictive approach is useful prospectively, not just statistically promising in retrospective or pilot work.

Is a clinical trial required to apply?

The NOFO indicates that a clinical trial is optional overall. However, the second (UH3) phase is explicitly oriented toward prospective validation in a clinical-trial setting, so applicants should be prepared to design and run a study that can credibly test treatment-differential prediction among established depression treatments.

What does "milestone-driven" mean for applicants?

It means the program strongly emphasizes quantitative milestones, clear go/no-go criteria, and disciplined evaluation of feasibility, reliability, and performance. Continued support into the UH3 phase is contingent on meeting the predefined UG3 requirements and milestones.

What does it mean that the program is designed to "down-select" projects?

The program is intentionally structured to stop development of tools that do not meet performance thresholds or feasibility requirements before larger resources are invested. Applicants should expect early-stage evaluation and the possibility that projects will not transition if go/no-go criteria are not met.

What is the cooperative agreement mechanism and why does it matter?

A cooperative agreement generally indicates substantial involvement from the funding agency compared to a standard grant, including milestone oversight and coordinated program support. This aligns with the program's emphasis on milestone tracking and down-selection.

What kinds of outcomes is NIH looking for by the end of this program?

The intended end state is early-validated decision-support tools or biomarkers that can help match individuals to the depression treatment most likely to work for them. These tools are expected to have a realistic path toward clinical utility and could be studied further after early validation.

Is the program only interested in statistically interesting findings?

No. The opportunity is framed around producing tools that are accurate, reliable, and practical enough to justify continued investment and, ultimately, to influence routine clinical decision-making rather than remaining confined to research settings.

What implementation or real-world considerations are expected?

Teams are expected to address real-world constraints that can prevent biomarkers from becoming usable products. The description specifically highlights attention to regulatory pathways, implementation considerations, and commercialization requirements where relevant.

Who is eligible to apply?

Eligibility is broad and includes many U.S. and non-U.S. organizations. Eligible applicants include state, county, and local governments; special districts; independent school districts; public and private institutions of higher education; federally recognized tribal governments; non-federally recognized tribal organizations; public housing authorities and Indian housing authorities; nonprofits with or without 501(c)(3) status (other than institutions of higher education); for-profit organizations (including small businesses and other than small businesses); and other entities.

Are specific institution types explicitly included as eligible?

Yes. The opportunity explicitly calls out eligibility for 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.

What is the activity area and assistance listing identifier?

The activity category is health, and the CFDA/Assistance Listing is 93.242.

What is the opportunity number?

The funding opportunity is RFA-MH-25-190.

When was the opportunity created and what was the original closing date?

The listing indicates it was created on 2024-04-03, and the original closing date was 2024-10-18.

Is the award ceiling or expected number of awards provided?

Not in the information provided. The listing notes that an award ceiling and the expected number of awards are not specified in the provided materials.

How should applicants think about funding continuity between phases?

The UG3/UH3 structure indicates that continued funding into UH3 is contingent on successfully meeting UG3 milestones and requirements, consistent with the program's emphasis on go/no-go decision points.

What kind of validation is expected in the UH3 phase?

The UH3 phase is aimed at initial validation through independent, prospective clinical trials that can test whether the tool meaningfully predicts who does better on Treatment A versus Treatment B among well-established depression therapies.

Can an application rely only on retrospective analyses?

Retrospective analyses and existing datasets are described as appropriate for UG3 development and early evaluation. However, the program is structured so that projects that progress to UH3 are expected to pursue prospective validation in a clinical-trial setting.

What is meant by "intended clinical use case" in UG3?

It refers to clearly defining how the predictor would be used to guide treatment selection between established depression interventions, including what decision it supports and how it would fit into clinical workflows, as part of meeting UG3 milestones.

What disciplines or capabilities are implied to be important for teams?

The description emphasizes multidisciplinary support and expects teams to address scientific and clinical questions alongside technical development needs, plus practical considerations like implementation and regulatory/commercialization pathways when relevant.