Full-Scale Hybrid Effectiveness-Implementation Trials for Mental Health Interventions (R01 - Clinical Trial Required)

Full-Scale Hybrid Effectiveness-Implementation Trials for Mental Health Interventions (R01 - Clinical Trial Required) is sponsored by National Institutes of Health. Supports clinical trials to test the effectiveness of optimized therapeutic and preventive interventions for use in community and practice settings, and to evaluate the effectiveness of patient-, provider-, organizational-, or systems-level services interventions to improve access, continuity, quality, equity, and/or value of mental health services.

PAR-25-178: Pilot Hybrid Effectiveness-Implementation Trials for Mental Health Interventions (R01 Clinical Trial Required) 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. Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) Components of Participating Organizations National Institute of Mental Health ( NIMH ) Funding Opportunity Title Pilot Hybrid Effectiveness-Implementation Trials for Mental Health Interventions (R01 – Clinical Trial Required) R01 Research Project Grant March 31, 2025 - 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. December 02, 2024 - Notice of the Effectiveness and Services Trials Pre-Application Webinar for PAR-25-177, PAR-25-187, and PAR-25-285. See Notice NOT-MH-25-105 .

April 4, 2024 - Overview of Grant Application and Review Changes for Due Dates on or after January 25, 2025. See Notice NOT-OD-24-084 . August 31, 2022 - Implementation Changes for Genomic Data Sharing Plans Included with Applications Due on or after January 25, 2023.

See Notice NOT-OD-22-198 . August 5, 2022 - Implementation Details for the NIH Data Management and Sharing Policy. See Notice NOT-OD-22-189 .

Funding Opportunity Number (FON) Companion Funding Opportunity Research Project (Cooperative Agreements) Exploratory/Developmental Grants Phase II Phase 1 Exploratory/Developmental Grant/ Exploratory/Developmental Grants Phase II Exploratory/Developmental Grants Phase II Phase 1 Exploratory/Developmental Grant/ Exploratory/Developmental Grants Phase II Phase 1 Exploratory/Developmental Grant/ Exploratory/Developmental Grants Phase II See Section III.

3. Additional Information on Eligibility .

Assistance Listing Number(s) Funding Opportunity Purpose This NOFO seeks pilot hybrid effectiveness implementation research consistent with NIMH's priorities for: 1) refining and optimizing preventive and therapeutic interventions with previously demonstrated efficacy for use with broader target populations or for delivery routine care, school, community, or online settings, and 2) research on implementation strategies that support the delivery and sustainability of evidence supported interventions in accessible settings.

This NOFO supports pilot research designed to generate the preliminary data needed as a prerequisite to a well powered clinical trial. This includes research designed to assess the feasibility, acceptability, safety, and fit of approach, and explore the impact of the approach on both the outcomes of interest and at least one hypothesized mechanism of action.

Support for well powered hybrid effectiveness implementation studies is provided through separate NOFOs that are described on the NIMH Support for Clinical Trials web page. Funding Opportunity Goal(s) The mission of the National Institute of Mental Health (NIMH) is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery, and cure.

Open Date (Earliest Submission Date) Renewal / Resubmission / Revision (as allowed) AIDS - New/Renewal/Resubmission/Revision, as allowed All applications are due by 5:00 PM local time of applicant organization. Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

Required Application Instructions It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide , except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts ). Conformance to all requirements (both in the Application Guide and the NOFO) is required and strictly enforced.

Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

There are several options available to submit your application through Grants. gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

Use the NIH ASSIST system to prepare, submit and track your application online. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants. gov and eRA Commons to track your application.

Check with your institutional officials regarding availability. Workspace to prepare and submit your application and eRA Commons to track your application. Part 1.

Overview Information Part 2. Full Text of Announcement Section I. Notice of Funding Opportunity Description Section II.

Award Information Section III. Eligibility Information Section IV. Application and Submission Information Section V.

Application Review Information Section VI. Award Administration Information Section VII. Agency Contacts Section VIII.

Other Information Part 2. Full Text of Announcement Section I. Notice of Funding Opportunity Description Key Definitions for this NOFO: Scalability: Scalability refers to features of the approach that support implementation fidelity.

Strategies to enhance scalability include but are not limited to consumer-facing technology for intervention delivery and provider-facing technology for implementation support, training, or consultation.

Implementation strategies: Implementation strategies seek to improve (1) intervention acceptability, satisfaction, and perceived fit, (2) intervention access and engagement, (3) intervention quality and fidelity, and/or (4) intervention uptake and scalability. Hybrid effectiveness implementation trials (hybrid trials): Hybrid trials include methods for evaluating intervention effectiveness and implementation factors.

In hybrid trials participants are randomized to conditions at the level of the intervention, the level of the implementation strategy, or at both levels. In intervention settings where randomization is not feasible, a rigorous alternative may be appropriate. Hybrid type 1 trials emphasize evaluating intervention effectiveness while also assessing consumer-, provider- and setting-level implementation factors.

Hybrid type 2 trials place equal emphasis on evaluating intervention effectiveness and the effectiveness of an implementation strategy related to the intervention. Hybrid type 3 trials emphasize evaluating implementation strategy effectiveness while also gathering patient or consumer outcome data to confirm intervention effectiveness.

Deployment-focused: Deployment-focused design and testing systematically assesses and incorporates the perspectives of community and practice partners (e.g., consumers, providers, administrators, payers) and setting characteristics (e.g., workforce capacity; clinical workflows).

This approach helps to ensure that the resultant interventions are feasible, scalable, can be disseminated into practice, given typically available resources (e.g., trained, skilled providers), typical service and financing structures, and typical service use patterns, and that the study results have utility for end-users.

Mechanism of action: A mechanism of action, or target mechanism, is a factor that an intervention intends to modify based on a hypothesis suggesting that modification will result in improved mental disorder risk, symptoms, or functional outcomes or enhanced implementation outcomes.

NIMH seeks applications for pilot research to optimize and test the effectiveness of therapeutic or preventative mental health interventions and related implementation strategies in routine care, community, school, or online settings where individuals can readily access mental health services.

This NOFO supports intervention development work when there is a compelling empirical justification for the proposed augmentation, optimization, personalization, or sequencing approach.

This justification may be based on evidence that the unmodified intervention or strategy is associated with suboptimal clinical response, engagement, or adherence, is a poor cultural fit for specific populations, or is likely to encounter implementation challenges in routine care, school, community, or online settings (see recommendation 2. 4.

1, page 19 regarding the empirical justification for intervention adaptations in the NAMHC Workgroup Report, From Discovery to Cure: Accelerating the Development of New and Personalized Interventions for Mental Illnesses) .

Online-only interventions may be appropriate for pilot development and testing when an existing sustainable infrastructure is available to continually connect consumers with the intervention and support ongoing maintenance and delivery outside the research enterprise.

Studies that incorporate technology into the intervention design should align with NOT-MH-18-031 : NIMH High-Priority Areas for Research on Digital Health Technology to Advance Assessment, Detection, Prevention, Treatment, and Delivery of Services for Mental Health Conditions.

Scale and Scope of Research NIMH supports pilot research to optimize, personalize, or sequence preventative or therapeutic interventions and related implementation strategies in accessible settings where individuals can feasibly be connected to mental health interventions. With appropriate justification, this NOFO may support effectiveness research in the absence of extensive efficacy data.

This includes, but is not limited to, studies of interventions comprised of research-informed strategies that have not previously been tested in combination or with the proposed target population, or interventions with strong pilot efficacy data that can be used to justify deployment-focused research as a logical next step to expedite the translation of research into practice.

Proposed pilot research must include plans to assess the feasibility and acceptability of the modified approach in the intervention setting, conduct a preliminary evaluation of the intervention or implementation strategy’s impact on the outcomes of interest, and explore the intervention’s impact on at least one hypothesized mechanism of action.

NIMH encourages pilot research that also seeks to establish the feasibility and acceptability of research methods that may be applied in a future well powered clinical trial. Given sample size limitations, applications are not required to include effect size estimates or plans for well-powered mediation or outcome analyses.

Proposed pilot research may include plans for deployment-focused development and testing that span a series of three steps. Step 1: systematically evaluate of the characteristics of typical intervention consumers, providers, and the intended delivery setting and obtain feedback from community and practice partners.

Step 2: operationalize and develop the experimental intervention or implementation strategy and iteratively refine the approach within the context of a case series or similar methodology (e.g., to establish dosing, refine intervention manuals and training materials). S tep 3: conduct a pilot hybrid trial to generate preliminary outcome and implementation data as a prerequisite to a fully powered hybrid trial.

Applications submitted in response to this announcement must include Step 3 at a minimum and may also include any of Steps 1 – 2 as appropriate.

Applications must include a hybrid trial design that proposes to simultaneously evaluate (1) the clinical impact of the intervention on symptoms, functional outcomes, or risk factors associated with a mental disorder, (2) implementation factors or strategies that impact intervention access, engagement, or sustainability, and (3) at least one hypothesized mechanism of action.

The proposed pilot development work must incorporate the perspectives of community and practice partners and address characteristics of the implementation setting. NIMH encourages pilot hybrid trials that maximize efficiencies by utilizing existing infrastructure to facilitate data collection, enhance the sustainability of the approach, and improve the feasibility of participant recruitment.

Examples of existing infrastructure include practice-based research networks, electronic medical records, administrative databases, patient registries, and routinely collected school data.

Consistent with NIMH’s commitment to supporting research that reduces mental health disparities and advances health equity , this NOFO strongly encourages applicants to include plans to address drivers of disparities in mental health outcomes and include strategies to optimize interventions in under-resourced settings and across racial and ethnic, geographical, and socioeconomic groups.

Consistent with the NIMH experimental therapeutics approach , this NOFO requires trial designs that include a preliminary evaluation of a hypothesized mechanism of action.

Applications must specify (1) at least one hypothesized mechanism of action for the intervention and/or implementation strategy, (2) measurement plans designed to feasibly assess the mechanism of action and primary outcomes in the intended intervention setting, and (3) an analytic plan designed to evaluate both changes in the mechanism of action and the association between changes in the mechanism of action and the primary outcome(s).

The nature of the proposed mechanism will vary depending on the characteristics of the experimental intervention or implementation strategy. For preventive and therapeutic interventions, mechanisms include factors that have been empirically associated with mental disorder risk, etiology, maintenance, or severity. These might involve specific psychological, behavioral, or interpersonal processes or neurobiological entities.

For implementation strategies, mechanisms may include mutable consumer- or provider- behaviors or intervention delivery approaches that are intervened upon to improve intervention access, engagement, quality, fidelity, or scalability. Proposed measures of mechanisms and primary outcomes should be validated, accepted by the field, and considered in context of NIMH's expectations for the use of common data elements .

At times a validated measure may not be available for a proposed mechanism of action or a proposed study population. In these instances, applications should provide a justification for the selected unvalidated measure and propose plans to further validate the measure as part of the pilot research methods.

NIMH encourages the use of measures that are as direct and objective as is feasible in the intended intervention setting and/or span more than one level of assessment when appropriate. Examples include behavioral observation data, computer-based tasks, electronic health records, or other administrative sources.

As appropriate, study designs may include Research Domain Criteria (RDoC) or RDoC-like constructs when defining the participant inclusion, mechanisms of action, and outcomes.

Areas of interest include, but are not limited to: Multi-modal or integrated intervention approaches, such as combination treatments or sequenced pharmacological, psychosocial, and/or neuromodulation interventions, to evaluate if combination or sequencing results synergistic effects on outcomes.

Effectiveness and implementation of best practices for youth mental health in school, juvenile justice, foster care, pediatric medicine, and other settings serving youth. Effectiveness and implementation of best practices for older adults served through accessible settings and providers.

Innovative interventions and implementation strategies that seek to reduce mental health disparities in intervention access, quality, and outcomes for racial and ethnic minority groups, individuals limited by language or cultural barriers, individuals living in rural areas, groups that have been economically/socially marginalized, and other underserved groups.

Personalized, modular or stepped-care approaches for matching treatment components of varying intensity to patient preferences or areas of greatest need. Augmentation strategies for treatment-refractory groups that are designed to address factors empirically linked with suboptimal response.

Approaches that incorporate risk information to stratify and assign participants to preventive interventions in routine care, school, or community settings. Patient- and provider-level interventions designed to promote service access, use, engagement, and retention or improve quality or outcomes of care.

Provider-level interventions, such as training and supervision approaches, to increase the uptake, fidelity, and sustained use of evidence-supported interventions.

Task sharing models that propose and test clear roles for non-specialty providers, staff, peers, or lay persons and incorporate scalable and sustainable approaches to training and supervision, safety monitoring, and credentialing to complement and extend the mental health workforce.

Applications Not Responsive to this NOFO Studies that are not responsive to this NOFO and will not be reviewed include the following: Applications that do not propose a hybrid effectiveness implementation trial design.

Applications that propose to test interventions or implementation strategies in research settings rather than routine care, community, school, or online settings and/or propose the use of research therapists or include other features specific to research or academic contexts.

Applications that do not propose an evaluation of the mechanism(s) of action and its impact on the primary outcomes, including the following components section of the application: (1) specified mechanism(s) of action; (2) measurement plans designed to assess the mechanism(s) of action and clinical outcomes in the intervention setting; and (3) a description of the analytic plan for evaluating whether intervention-induced mechanism(s) of action are associated with outcomes.

Applications that propose adaptations of existing interventions without a compelling empirical justification. Applications that use patented medications that lack superior efficacy or safety relative to currently available off-patent medications. Applications that propose to test health literacy interventions without explicitly examining the impact on service access, engagement, quality and/or outcomes of care.

Applications that propose to evaluate service level interventions that incorporate multiple implementation strategies to increase access, use, reach, adoption, and implementation of mental health services. Full scale hybrid implementation effectiveness trial applications: Support for well powered hybrid implementation effectiveness trials is provided through PAR-25-177. .

Mental health services applications: Support for clinical trials evaluating service level interventions that target system-level factors or incorporate multiple implementation strategies to increase access, use, reach, adoption, and implementation of mental health services is provided through PAR-25-285 : Effectiveness Trials to Test Mental Health System Interventions (R61/R33 Clinical Trial Required).

Support for mental health services research not using a clinical trial design is provided through PAR-25-284 : Innovative Pilot Mental Health Services Research Not Involving Clinical Trials (R34 Clinical Trial Not Allowed) and PAR-25-283 : Innovative Mental Health Services Research Not Involving Clinical Trials (R01 Clinical Trials Not Allowed).

Suicide-Related Outcomes: Effective prevention and treatment of mental illness have the potential to reduce morbidity and mortality associated with suicide attempts and deaths (see www. suicide-research-agenda. org).

Lack of attention to the assessment of these outcomes has limited our understanding of the degree to which effective mental health interventions might offer prophylaxis. Accordingly, NIMH encourages research that includes assessment of suicidal behavior in clinical trials using strategies that facilitate data sharing and harmonization (see NOT-MH-23-100 and https://www. phenxtoolkit.

org/ ). Data and Safety Monitoring : The NIMH has published updated policies and guidance for investigators regarding human research protection and clinical research data and safety monitoring ( NOT-MH-19-027 ) and Conducting Research with Participants at Elevated Risk for Suicide: Considerations for Researchers) .

The application's PHS Human Subjects and Clinical Trials Information, including the Data and Safety Monitoring Plan, should reflect the policies and guidance in this notice. Applications with data collection plans that involve multiple respondent groups should include human subject protections, consenting procedures, and planned enrollment tables for each participant group.

Plans for the protection of research subjects and data and safety monitoring will be reviewed by the NIMH for consistency with NIMH and NIH policies and federal regulations. NIMH intends to hold a web-based pre-application webinar for applicants to PAR-25-178 Information on how to attend the optional webinar will be published through a Guide Notice.

Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs. See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information Grant: A financial assistance mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity. Application Types Allowed The OER Glossary and the How to Apply Application Guide provide details on these application types.

Only those application types listed here are allowed for this NOFO. Required: Only accepting applications that propose clinical trial(s). Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards NIMH intends to commit a total of $27,000,000 for FY 2026 to fund this NOFO and the companion NOFOs listed in Part 1. Overview Information. Future year amounts will depend on annual appropriations.

Direct costs are limited to $750,000 over the R01 project period, with no more than $250,000 in direct costs allowed in any single year. The total project period for an application submitted in response to this funding opportunity may not exceed three years. NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this NOFO.

Section III.

Eligibility Information Higher Education Institutions Public/State Controlled Institutions of Higher Education Private Institutions of Higher Education Nonprofits Other Than Institutions of Higher Education Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education) Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education) For-Profit Organizations (Other than Small Businesses) City or Township Governments Special District Governments Indian/Native American Tribal Governments (Federally Recognized) Indian/Native American Tribal Governments (Other than Federally Recognized).

Eligible Agencies of the Federal Government U.S. Territory or Possession Independent School Districts Public Housing Authorities/Indian Housing Authorities Native American Tribal Organizations (other than Federally recognized tribal governments) Faith-based or Community-based Organizations Non-domestic (non-U.S.) Entities (Foreign Organizations) Non-domestic (non-U.S.) Entities (Foreign Organizations) are eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply. Foreign components, as defined in the NIH Grants Policy Statement , are allowed. Applicant organizations must complete and maintain the following registrations as described in the How to Apply- Application Guide to be eligible to apply for or receive an award.

All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference the NIH Grants Policy Statement Section 2.

3. 9. 2 Electronically Submitted Applications for additional information.

System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually . The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.

NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM. Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM. gov registration process.

The same UEI must be used for all registrations, as well as on the grant application. eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants. gov registrations; all registrations must be in place by time of submission.

eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application. Grants. gov – Applicants must have an active SAM registration in order to complete the Grants.

gov registration. Program Directors/Principal Investigators (PD(s)/PI(s)) All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons.

If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Eligible Individuals (Program Director/Principal Investigator) Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the How to Apply-Application Guide. This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1. 2 Definition of Terms .

3. Additional Information on Eligibility Applicant organizations may submit more than one application, provided that each application is scientifically distinct. The NIH will not accept duplicate or highly overlapping applications under review at the same time, per NIH Grants Policy Statement Section 2.

3. 7. 4 Submission of Resubmission Application .

This means that the NIH will not accept: A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application. A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.

An application that has substantial overlap with another application pending appeal of initial peer review (see NIH Grants Policy Statement 2. 3. 9.

4 Similar, Essentially Identical, or Identical Applications ). Section IV. Application and Submission Information 1.

Requesting an Application Package The application forms package specific to this opportunity must be accessed through ASSIST, Grants. gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.

gov Workspace are available in Part 1 of this NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution. 2.

Content and Form of Application Submission It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced.

Applications that are out of compliance with these instructions may be delayed or not accepted for review. All page limitations described in the How to Apply- Application Guide and the Table of Page Limits must be followed. Instructions for Application Submission The following section supplements the instructions found in the How to Apply- Application Guide and should be used for preparing an application to this NOFO.

All instructions in the How to Apply - Application Guide must be followed. SF424(R&R) Project/Performance Site Locations All instructions in the How to Apply- Application Guide must be followed. SF424(R&R) Other Project Information All instructions in the How to Apply- Application Guide must be followed.

Facilities and Other Resources: The description of the resources and environment should address how the study utilizes existing infrastructure (e.g., CTSAs, practice-based research networks, electronic medical records, administrative databases, patient registries) or utilizes other available resources to increase the efficiency of participant recruitment and data collection or provide a justification in the event that such efficiencies cannot be incorporated.

SF424(R&R) Senior/Key Person Profile All instructions in the How to Apply- Application Guide must be followed. In the biosketch, describe Senior/Key Personnel experience and expertise at collaborating with community practice partners/providers, consumers, and relevant policy makers to conduct effectiveness studies, as appropriate All instructions in the How to Apply- Application Guide must be followed.

All instructions in the How to Apply-Application Guide must be followed. PHS 398 Cover Page Supplement All instructions in the How to Apply- Application Guide must be followed. All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions: Research Strategy: The Research Strategy must include the following information.

Applications should not duplicate information provided in the attachment described in PHS Human Subjects Clinical Trial Information form, but may reference it to provide context as needed Factor 1.

Importance of the Research Justify the practical effect on public health of the intervention or service approach in terms of the magnitude and clinical meaningfulness of the anticipated effects on the key outcomes (e.g., clinical benefit, safety/tolerability, value and efficiency, or scalability), compared to existing approaches.

Address the degree to which the proposed intervention or implementation strategy is scalable and could be disseminated into practice, given typically available resources (e.g., trained, skilled providers), typical service and financing structures, and typical service use patterns.

Detail how the proposed research will generate data that will lead to a firm conclusion about the feasibility of a regular research project grant or full-scale clinical trial and provide information about the anticipated scope and goals of intended future work. As appropriate, address the degree to which the proposed intervention addresses disparities in access, ongoing engagement, and/or clinical or functional outcomes.

Highlight how innovative research strategies and design/analytic elements (e.g., adaptive sequential randomization, equipoise stratification, technology-based assessments) are incorporated, as appropriate, in order to enhance the study's potential for yielding practice-relevant information.

As relevant, describe how applications of technology or other innovative approaches are leveraged to facilitate the conduct of the research project (e.g., participant identification, data collection) and/or to increase the reach, efficiency, or effectiveness of the intervention or service delivery strategy that is being evaluated. Factor 2.

Rigor and Feasibility Detail the plan to explicitly address whether the intervention engages the one or more mechanisms of action.

Include the following: A conceptual framework that clearly identifies the mechanism of actions and the empirical evidence linking the mechanisms to the primary outcomes of interest (i.e., clinical symptoms, functional deficits, or patient-, provider- or system-level behaviors/processes that the intervention seeks to improve).

The plans for assessing preliminary engagement of the mechanism(s) and outcome(s), the assessment schedule, and evidence regarding the validity and feasibility of the proposed measures in the effectiveness context. A statistical analysis plan for exploring whether intervention-induced changes in the mechanism(s) are associated with changes in the outcomes.

The Research Strategy section of the application must include a description of this planned analytic approach, whereas the full details of the proposed statistical methods should be included in the PHS Human Subjects and Clinical Trials Information Form.

In the case of multicomponent interventions, specify the conceptual basis, assessment plan, and analytic strategy, as detailed above, for the mechanisms corresponding to each intervention component, as appropriate in the effectiveness context. Articulate the process for determining the intervention's initial degree of "fit" and the iterative process that will be used to adapt/refine the intervention or implementation strategy.

Describe provisions for the assessment and monitoring of the fidelity of intervention delivery via procedures that are feasible and valid for use in the community setting.

Describe design features that will be incorporated to help ensure that the approach is feasible, scalable, and robust against implementation drift in the community setting (e.g., using technology as scaffolding or expert consultation via existing resources/ other sustainable means to support delivery).

Describe plans for deployment-focused design and testing that systematically assesses the perspective of community and practice partners (e.g., consumers, providers, administrators, payers) and setting characteristics (e.g., workforce capacity; clinical workflows) to help ensure that the resultant approach is feasible and scalable, and to ensure the results are compelling to and have utility for end-users.

Consistent with hybrid effectiveness implementation methods, describe plans for using standardized measures to assess and examine consumer-, provider- and setting- level factors that might be associated with uptake, implementation fidelity, and sustained use of the approach.

Incorporate outcome measures that are validated and feasible in the effectiveness context, including stakeholder-relevant outcomes (e.g., functioning, health services use).

For studies proposing adaptations of existing interventions, provide the empirical justification for the proposed adaptation based on data describing characteristics of client subgroups, settings, care providers or other relevant variables that are associated with non-response, partial response, relapse, or poor uptake (see page 19 of NAMHC Workgroup Report " From Discovery to Cure: Accelerating the Development of New and Personalized Interventions for Mental Illnesses.

").

Justify the adaptation in terms of (a) theoretical and empirical support for the adaptation target (e.g., a prognostic variable such as a neurocognitive functioning variable, that has been associated with non-response, partial response, patient non-engagement, or relapse); (b) a theoretical/empirical explanation of how the prognostic variable interferes with the response to the un-adapted intervention (i.e., a clear hypothesis regarding the mechanism by which