PAR-25-179
Confirmatory Efficacy Clinical Trials of Non-Pharmacological and Pharmacological Interventions for Mental Disorders (R01 Clinical Trial Required)
Summary
PAR-25-179: Confirmatory Efficacy Clinical Trials for Mental Disorders
Research Focus
This funding opportunity supports confirmatory efficacy clinical trials testing non-pharmacological and selected pharmacological interventions for mental disorders in adults and children. NIMH seeks trials designed around an experimental therapeutics approach: interventions must engage and alter a hypothesized mechanism of action (target), demonstrate preliminary efficacy, and address an unmet therapeutic need. Eligible interventions include behavioral, cognitive, interpersonal, device-based (invasive/surgically implanted or noninvasive/transcranial), and technology-assisted psychosocial approaches, or combinations thereof. Trials may examine monotherapy, combination treatments, or stepped approaches. Proposed targets or mediators span psychological processes (e.g., attention bias, cognitive control, stress regulation), interpersonal processes, and neurobiological processes including brain circuits and neural oscillatory patterns. The trial must measure the hypothesized mechanism of action and demonstrate the relationship between target engagement and clinical or functional outcomes, ultimately providing high scientific utility to support go/no-go decisions about further development or dissemination.
At a Glance
- Who can apply: Not stated (see full FOA for institution eligibility)
- Funding & project length: Not stated in excerpt
- Award mechanism: R01 Clinical Trial Required
- Key dates: Applications due February 14, 2025 (earliest cycle); subsequent cycles through October 15, 2027; earliest start date December 2025 (varies by cycle)
- Best fit for: Clinical researchers testing behavioral, cognitive, device-based, or combination interventions for mental health disorders with validated target engagement measures and preliminary efficacy data
Key Facts
Deadline
Fri, October 15, 2027
Posted
Tue, November 26, 2024
Keywords
Research Areas
Gotchas (6)
This NOFO explicitly requires that pharmacological interventions must be either FDA-approved drugs (for any indication) or off-patent medications being developed for a new mental health indication. In
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Source Text
“Pharmacological interventions to be studied under this grant mechanism are expected to primarily focus on drugs approved for marketing by the FDA (for any indication). These will include medications off-patent which are undergoing development for a new mental health indication... the presence of an industry sponsor will not preclude support of pharmacotherapy confirmatory efficacy clinical trials that are designed to address important scientific questions of public health significance during dru”
The NOFO requires measurement of the hypothesized mechanism of action and explicit examination of the relationship between change in the target mechanism and change in clinical/functional outcomes. Th
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Source Text
“Support will be provided for a trial of the intervention's efficacy that includes measurement of the hypothesized mechanism of action and the relationship between change in the target mechanism and change in functional or clinical effects.”
Interventions must be based on: (1) compelling scientific rationale, (2) previous demonstration of target engagement and mechanism of action alteration, and (3) preliminary efficacy signal. These are
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Source Text
“Interventions appropriate for efficacy testing must be based on a compelling scientific rationale, previous demonstration that the intervention engages and alters the hypothesized mechanism of action (target), a preliminary efficacy signal, and must address an unmet therapeutic need...interventions appropriate for confirmatory efficacy testing must be based on a compelling scientific rationale, previous demonstration that the intervention engages and alters the hypothesized mechanism of action, ”
The NOFO explicitly states it is NOT intended to support translation of existing treatments into technology-based applications (e.g., mHealth), which could disqualify applications proposing to adapt e
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Source Text
“While this NOFO will support efficacy testing of novel technology-assisted intervention approaches, it is not intended to support the translation of existing treatments into technology-based applications (e.g., mHealth).”
NIMH encourages direct and objective measures of target engagement beyond self-report where feasible, and multi-level assessment measures. The data analysis plan for examining target changes must be d
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Source Text
“NIMH encourages the use of measures that are as direct and objective as is feasible in the clinical research setting. Specifically encouraged are empirically validated measures of the construct that extend beyond self-reports and other subjective measures, where possible, and inclusion of measures that span more than one level of assessment if possible and appropriate. The detailed data analysis plan for examining changes in targets and related changes in outcomes should be included in the Resea”
The NOFO was updated March 31, 2025 to align with agency priorities. Applicants are instructed to 'carefully reread the full funding opportunity' and make needed adjustments. The nature of these updat
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Source Text
“This funding opportunity was updated to align with agency priorities. Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission.”