Effectiveness Trials to Test Mental Health System Interventions (R61/R33 Clinical Trial Required)

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Description

This opportunity from the National Institute of Mental Health (NIMH) supports a two-phase (R61/R33) clinical trial mechanism to rigorously test the effectiveness of system-level interventions designed to improve the organization, delivery, coordination, and outcomes of mental health care. The R61 phase funds feasibility and infrastructure development, while the R33 phase supports a fully powered effectiveness trial contingent on successful completion of R61 milestones.

System interventions may address structural, policy, organizational, or multi-level factors within or across care settings (e.g., health systems, community clinics, schools, child welfare, or justice systems). The focus is on interventions that can improve access, equity, engagement, value, management, or quality and safety of mental health services, with the ultimate goal of better clinical and functional outcomes for priority populations.

Projects must use a clinical trial design and explicitly test how, why, for whom, and in which settings the system intervention is effective. The program encourages research that addresses disparities and incorporates deployment-focused, practice-relevant questions, with stakeholder engagement and data sharing as key components.

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Due Dates

• Next deadlines:

  • June 17, 2025 (New, Renewal, Resubmission, Revision)
  • October 15, 2025
  • February 13, 2026
  • June 15, 2026
  • October 15, 2026
  • February 17, 2027
  • June 15, 2027
  • October 15, 2027

• Letter of Intent:

  • January 14, 2025 (for first cycle; not required but encouraged)

• Expiration:

  • October 16, 2027

All applications are due by 5:00 PM local time of the applicant organization.

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Funding Amount

• Total NIMH Commitment: $27 million in FY26 (shared across this and companion NOFOs; future years depend on appropriations)
• Award Budget: No specific budget cap; budgets must reflect actual project needs.
• Project Period: Up to 5 years total (R61 phase: up to 2 years; R33 phase: up to 4 years)
• Mechanism: R61/R33 Exploratory/Developmental Phased Award

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Eligibility

• Eligible Applicants:

  • Higher education institutions (public, private, domestic, and foreign)
  • Nonprofits (with or without 501(c)(3) status)
  • For-profit organizations (including small businesses)
  • State, county, city, township, and special district governments
  • Independent school districts
  • Public housing authorities/Indian housing authorities
  • Native American tribal governments and organizations (federally recognized and other)
  • Faith-based and community-based organizations
  • Regional organizations
  • U.S. territories and possessions
  • Non-domestic (non-U.S.) entities and foreign components

• Individuals:

  • Any individual(s) with the skills, knowledge, and resources to carry out the proposed research as PD/PI.

• Multiple applications:

  • Allowed if each is scientifically distinct.

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Application Process

• Submission:

  • Applications must be submitted electronically via ASSIST, Grants.gov Workspace, or an institutional system-to-system solution.
  • All required registrations (SAM, eRA Commons, Grants.gov) must be completed prior to submission.

• Required Application Components:

  • Timeline & Milestone Plan (2 pages max)
  • Stakeholder Engagement Plan (2 pages max)
  • Specific Aims (with separate R61 and R33 aims)
  • Research Strategy (including conceptual model, analytic plan, and justification for system-level focus)
  • Data Management and Sharing Plan (per NIH policy)
  • Human Subjects and Clinical Trials Information (including recruitment/retention, timeline, and safety monitoring)
  • Budget and Budget Justification

• Review Criteria:

  • Importance (significance, innovation, public health impact)
  • Rigor and Feasibility (design, analytic plan, milestones, scalability)
  • Expertise and Resources (investigator qualifications, environment)
  • Additional: Human subjects protections, data sharing, budget justification

• Transition from R61 to R33:

  • Progress on R61 milestones is administratively reviewed by NIMH; transition to R33 is not guaranteed.

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Additional Information

• Scope:

  • Only clinical trials of system-level interventions are eligible. Projects focused solely on individual-level interventions (e.g., provider training, patient engagement) are not responsive.
  • Interventions must be tested in real-world (not academic-only) settings.
  • Projects must include a plan for data sharing via the NIMH Data Archive (NDA).
  • Applications must address how, why, for whom, and in which settings the intervention is effective, using appropriate analytic methods (e.g., mediation, moderation, dismantling designs).

• Not Responsive:

  • Projects not using a clinical trial design
  • Interventions tested only in academic/research settings
  • Solely individual-level implementation strategies
  • Health literacy interventions without service impact assessment

• Companion Opportunities:

  • See related NIMH clinical trial NOFOs for other stages of intervention development and testing.

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External Links

• NIH Funder Home Page
• Full Funding Opportunity Announcement (PAR-25-285)
• Grants.gov Opportunity Listing
• NIMH Clinical Trials FOAs
• NIH Application Guide (Forms-H)
• NIMH Data Archive (NDA)

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Contact Information

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