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 Effectiveness Trials for Post-Acute Interventions and Services to Optimize Longer-term Outcomes (R34 Clinical Trial Required)
Activity Code

R34 Planning Grant

Announcement Type
Reissue of PAR-18-431
Related Notices

None

Funding Opportunity Announcement (FOA) Number
PAR-21-211
Companion Funding Opportunity
PAR-21-210 , R01 Research Project
Assistance Listing Number(s)
93.242
Funding Opportunity Purpose

NIMH seeks applications for pilot projects to evaluate the preliminary effectiveness of therapeutic and service delivery interventions for the post-acute management of mental health conditions that are matched to the stage of illness in terms of both their focus (e.g., consolidating and maintaining gains from initial treatment, managing residual symptoms/impairment, preventing relapse, promoting adherence and appropriate service use) and intensity/burden. In this pilot phase of effectiveness research, the trial should be designed to evaluate the feasibility, tolerability, acceptability, safety, and potential effectiveness of the approach; to address whether the intervention engages the target(s)/mechanisms(s) that is/are presumed to underlie the intervention effects; and to obtain preliminary data needed as a pre-requisite to a larger-scale effectiveness trial (e.g., comparative effectiveness study, practical trial) designed to definitely test the effectiveness of interventions to improve post-acute outcomes.

This FOA supports pilot research to evaluate the feasibility, tolerability, acceptability, safety and preliminary indications of effectiveness of post-acute phase intervention approaches and inform the design of definitive effectiveness trials. Support for fully-powered, definitive effectiveness studies focused on post-acute phase interventions is provided via the R01, PAR-21-210.

Key Dates

Posted Date
April 01, 2021
Open Date (Earliest Submission Date)
May 16, 2021
Letter of Intent Due Date(s)

30 days prior to the application due date

The following table includes NIH standard due dates marked with an asterisk.
Application Due Dates Review and Award Cycles
New Renewal / Resubmission / Revision (as allowed) AIDS Scientific Merit Review Advisory Council Review Earliest Start Date
June 16, 2021 * July 16, 2021 * Not Applicable November 2021 January 2022 April 2022
October 16, 2021 * November 16, 2021 * Not Applicable March 2022 May 2022 July 2022
February 16, 2022 * March 16, 2022 * Not Applicable July 2022 October 2022 December 2022
June 16, 2022 * July 16, 2022 * Not Applicable November 2022 January 2023 April 2023
October 16, 2022 * November 16, 2022 * Not Applicable March 2023 May 2023 July 2023
February 16, 2023 * March 16, 2023 * Not Applicable July 2023 October 2023 December 2023
June 16, 2023 * July 16, 2023 * Not Applicable November 2023 January 2024 April 2024
October 16, 2023 * November 16, 2023 * Not Applicable March 2024 May 2024 July 2024
February 16, 2024 * March 16, 2024 * Not Applicable July 2024 October 2024 December 2024

All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).

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.

Expiration Date
March 17, 2024
Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide,except where instructed to do otherwise (in this FOA or in a Notice from NIH Guide for Grants and Contracts ).

Conformance to all requirements (both in the Application Guide and the FOA) 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.

  1. Use the NIH ASSIST system to prepare, submit and track your application online.
  2. 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.

  3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.


  4. Table of Contents

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Rationale

While there has been progress at developing therapeutic and services interventions for the acute management of many mental health disorders, far less attention has been paid to developing and testing mental health interventions and services to improve longer-term outcomes and recovery of function. More research on post-acute phase interventions and services is warranted given that mental health conditions are often chronic or relapsing (e.g., anxiety disorders, mood disorders, ADHD, psychotic disorders) and are often better conceptualized and managed as chronic conditions. The clinical response to currently available pharmacological, device-based and psychosocial interventions is often incomplete. Therapeutic gains can dissipate with time, and residual symptoms and impairment pose risk for relapse and ongoing dysfunction. Even when acute treatment is successful, the risk for associated downstream comorbidities (e.g., substance abuse disorders) remains high. Management of many mental disorders requires not only ongoing treatment to prevent symptom recurrence, but interventions to promote long-term adherence to treatment plans and engagement with providers and health systems.

Research Scope and Objectives

The purpose of this Funding Opportunity Announcement (FOA) is to encourage pilot trials to assess the preliminary effectiveness of therapeutic and services interventions for the post-acute phase management of mental health conditions affecting youth and adults, including older adults. In this pilot phase of effectiveness research, the trial should be designed to evaluate the feasibility, tolerability, acceptability, safety, and potential effectiveness of the approach; to address whether the intervention engages the target(s)/mechanisms(s) that is/are presumed to underlie the intervention effects; and to obtain preliminary data needed as a pre-requisite to a larger-scale effectiveness trial (e.g., comparative effectiveness study, practical trial) designed to definitely test the effectiveness of interventions to improve post-acute outcomes.

For purposes of this FOA, acute treatment refers to the management of an episode, crisis, or worsening of mental illness that requires intense treatment in order to contain symptoms, prevent harm, and stabilize functioning, in either outpatient or hospital settings. While the goal of acute treatment is typically symptomatic improvement, management of immediate risks for harm, and behavioral stabilization, continuation and maintenance treatment aims to achieve symptom recovery and return the patient to an optimal baseline of functioning, while preventing relapse and recurrence. Likewise, following acute-phase treatment, additional interventions and/or services might be necessary to facilitate care transitions (e.g., from inpatient services to outpatient care) or promote appropriate adherence and continuity of services.

Across conditions, post-acute phase interventions/service strategies are needed that are matched to the stage of illness in terms of both their focus (e.g., consolidating and maintaining gains from initial treatment, managing residual symptoms/impairment, preventing relapse, promoting adherence and appropriate service use) and intensity/burden, in order to ensure that the interventions are not only relevant and effective, but also acceptable and sustainable for promoting optimal longer-term outcomes. Technology-assisted approaches might be especially useful for facilitating post-acute phase monitoring, for delivering interventions (e.g., maintenance therapy, relapse prevention), and for promoting treatment engagement/adherence and appropriate service use.

NIMH is committed to supporting research that reduces disparities and advances equity in mental health interventions, services, and outcomes. Accordingly, this FOA encourages pilot phase research that addresses disparities in post-acute care outcomes for racial and ethnic minority groups, individuals limited by language or cultural barriers, sexual and gender minorities, individuals living in rural areas, socioeconomically disadvantaged persons and other underserved groups.

Examples of relevant research topics include but are not limited to:

  • Continuation treatments (psychosocial, pharmacological, and/or neuromodulation strategies) that strengthen and extend gains achieved during initial treatment, or specifically target residual symptoms/impairments associated with relapse/ongoing dysfunction;
  • Strategies for negotiating transitions from an initial intensive treatment to a less intensive follow-up care;
  • Maintenance therapies that promote ongoing monitoring and continued use of pharmacological, neuromodulation, and/or psychosocial approaches tailored to the stage of illness;
  • Targeted strategies to optimize longer-term pharmacotherapy/neuromodulation, prevent long-term adverse effects of treatment (e.g., metabolic syndrome with antipsychotics, memory loss with electroconvulsive therapy), and reduce unnecessary polypharmacy;
  • Strategies for initiating preventive interventions among youth treated for “gateway conditions” (e.g., ADHD, anxiety, first episode psychosis) in order to reduce risk for common downstream comorbidities (e.g., substance use disorders, suicidality);
  • Novel adherence interventions that combine monitoring with engagement strategies to promote mental health hygiene habits, adherence and appropriate service use (e.g., minimize ED visits and re-hospitalization);
  • Technology-assisted self-monitoring or passive monitoring to detect clinical deteriorations or problematic adherence combined with prompts for self-management strategies or more intense services (e.g., via a patient-clinician interface or portal);
  • Empirically informed transition planning strategies to facilitate community reintegration, promote continuity of care, and prevent re-hospitalization following inpatient or residential treatment;
  • Population-level strategies that use routinely collected data within healthcare networks/EHRs for surveilling, monitoring, prompting engagement (e.g., care manager check-ins) and promoting appropriate service use.
  • Innovative approaches for reducing disparities in post-acute care outcomes for racial and ethnic minority groups, individuals limited by language or cultural barriers, sexual and gender minorities, individuals living in rural areas, socioeconomically disadvantaged persons, and other underserved groups.

Consistent with the NIMH experimental therapeutics approach, this FOA is intended to support effectiveness trials that not only test the intervention effects on outcomes of interest, but also explicitly inform understanding regarding whether the intervention engages associated change mechanisms that were previously identified under more controlled, efficacy conditions, thereby reconfirming the intervention targets and testing whether previously identified change mechanisms are operative in the effectiveness context (see NIMH web page on Clinical Trials). In this manner, the results of the effectiveness trial will advance knowledge regarding therapeutic change mechanisms and have utility regardless of trial outcomes (e.g., in the event of negative results, information about whether the intervention was successful at engaging its targets can facilitate interpretation)


Depending on the nature of the intervention, the "targets" or mechanism of action might involve specific psychological or behavioral processes (e.g., attention bias, cognitive control, stress regulation) or neurobiological entities (e.g., brain circuits).For studies that involve preventive or therapeutic interventions, NIMH encourages research that takes into account RDoC or RDoC-like constructs when defining the subject eligibility (inclusion), intervention targets or mechanisms, and outcomes, as appropriate and feasible in the effectiveness setting (see the RDoC webpage for more details). In the case of services interventions, targets/mechanisms might involve mutable consumer- or provider-behaviors, or organizational-/system-level factors that are intervened upon in order to improve access, continuity, quality, equity, and/or value of services.

Valid and reliable measures of change in the hypothesized target(s)/mechanism(s) will provide useful information about key change mechanisms that account for intervention effects. In the assessment of target engagement, NIMH encourages the use of measures that are as direct and objective as is feasible in the effectiveness 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.

NIMH encourages a deployment-focused model of intervention and services design and testing that considers the perspective of key stakeholders (e.g., service users, providers, administrators, payers) and the characteristics of the settings (e.g., resources, including workforce capacity; existing clinical workflows) where optimized mental health interventions and services are intended to be implemented. This attention to end-user perspectives and characteristics of intended clinical and/or community practice settings is intended to ensure that the resultant interventions and service delivery strategies are feasible and scalable, and to ensure that the research results will have utility for end users.

NIMH encourages projects testing the effectiveness of preventive, therapeutic, or services interventions that are designed as hybrid effectiveness-implementation trials, as appropriate, depending on the level of pre-existing effectiveness evidence and implementation readiness. Thus, in addition to testing the effectiveness of a preventive or therapeutic intervention, NIMH encourages effectiveness trials that are designed to assess and examine consumer-, provider- and setting- level factors that might be associated with implementation fidelity (i.e., as Hybrid Type-I trials) or to simultaneously test strategies to promote successful implementation (i.e., as Hybrid Type II trials). Likewise, studies that are primarily aimed at testing an implementation or dissemination strategy should be designed to also assess the outcomes and effectiveness of the intervention/approach that is being implemented, as appropriate and feasible (i.e., as Hybrid Type III trials).

NIMH encourages effectiveness research on potentially scalable preventive, therapeutic, and services interventions that focuses on practice-relevant questions. Accordingly, collaborations between academic researchers and clinical or community practice partners or networks are encouraged. When possible, studies should capitalize on existing infrastructure (e.g., practice-based research networks such as the NIMH-sponsored Mental Health Research Network (MHRN) and the Early Psychosis Intervention Network (EPINET), electronic medical records, administrative data bases, patient registries, institutions with Clinical and Translational Science Awards) to increase the efficiency of participant recruitment (i.e., more rapid identification and enrollment) and to facilitate the collection of moderator data (e.g., clinical characteristics, biomarkers), longer-term follow-up data, and broader, stakeholder-relevant outcomes (e.g., mental health and general health care utilization, value and efficiency of intervention approaches).

NIMH encourages studies that test intervention and service delivery strategies that incorporate features that are specifically designed to prevent threats to implementation fidelity, as appropriate. Strategies that might be used to enhance scalability and sustained implementation include but are not limited to: consumer-facing technology (e.g., self-administered content) and provider-facing technology (e.g., technology to support provider training and sustained implementation fidelity); expert consultation via existing resources or other sustainable means (e.g., telehealth, collaborative care approaches); or other robust design features that promote provider competence and sustained implementation fidelity.

Effective prevention and treatment of mental illness have the potential to reduce morbidity and mortality associated with intentional injury (i.e., suicide attempts and deaths, see: www.suicide-research-agenda.org). Lack of attention to the assessment of these outcomes has limited our understanding regarding the degree to which effective mental health interventions might offer prophylaxis. Where feasible and appropriate, NIMH encourages intervention research that includes assessment of suicidal behavior in order to advance understanding of how effective prevention and treatment of mental disorders might impact suicide relevant outcomes.

Information about the mission, strategic plan, and research interests of the NIMH can be found on the NIMH website. Applicants are also strongly encouraged to review the information on Support for Clinical Trials at NIMH.

Potential applicants are also strongly encouraged to consult with NIH staff as early as possible when developing plans for an application (see Scientific/Research Contacts, Section VII). This early contact will provide an opportunity to clarify NIH policies and guidelines and help to identify whether the proposed project is consistent with NIMH program priorities and the goals of this FOA.

Applications Not Responsive to this FOA

The following will be considered nonresponsive to this FOA and will not be reviewed:

  • Studies examining the effectiveness of acute phase interventions.
  • Studies that do not involve trials with prospective data collection in which patients are assigned to specific intervention conditions. While random allocation to intervention conditions is expected in most cases, depending on the study question, practical constraints, and ethical considerations, quasi-experimental designs with non-randomized comparison groups might be appropriate, with strong justification
  • Applications whose scope of work involves examining intervention effectiveness without studying whether the intervention engages the target(s) presumed to underlie benefits and without examining whether intervention-induced changes in targets are associated with clinical benefit.
  • Adaptations of existing interventions in the absence of a compelling justification and in the absence of a clear experimental therapeutics approach to examining how the intervention engages the adaptation target (see the NAMHC Workgroup Report, "From Discovery to Cure: Accelerating the Development of New and Personalized Interventions for Mental Illnesses", see Recommendation 2.4.1, page 19, for additional guidance regarding the empirical justification for intervention adaptations and augmentations.)
  • Applications focused on the development and initial efficacy testing of novel intervention strategies and/or novel intervention targets for the post-acute phase or on interventions for the acute phase of treatment will not be supported under this FOA.
  • Studies conducted in academic research laboratories as opposed to effectiveness studies in community practice clinics/settings (e.g., studies in research clinics that involve research therapists or other features that are not representative of typical practice settings and substantially impact generalizability).
  • Trials using patented medications that lack superior efficacy or safety relative to currently available off-patent medications.
  • Studies of stigma or health literacy interventions that do not explicitly study the impact on mental health service access, engagement, quality and/or outcomes of care.
  • Studies that address questions regarding the impact of interventions using only archival or observational/naturalistically collected data

Scale and Scope of Studies Covered Under this Announcement

This FOA supports pilot research to evaluate the feasibility, tolerability, acceptability, safety and preliminary indications of effectiveness of post-acute phase intervention approaches; to examine whether the intervention engages the target/mechanism that is presumed to underlie the intervention effects; and to obtain preliminary data needed as a pre-requisite to a larger-scale effectiveness trial (e.g., comparative effectiveness study, practical trial) designed to definitely test the effectiveness of interventions to improve post-acute outcomes. Support for fully-powered, definitive effectiveness studies focused on post-acute phase interventions is provided via PAR-21-210 (Effectiveness Trials for Post-Acute Interventions and Services to Optimize Longer-term Outcomes (R01)).

This FOA is intended to support pilot research focused on the effectiveness of therapeutic and service-delivery interventions: (1) that are intended specifically for the post-acute management of mental health conditions, and (2) that principally involve the use of research-supported strategies (e.g., in sequence or in combination), matched to the stage of illness. Applicants are encouraged to visit the NIMH Clinical Trials webpage for a list of alternative FOAs, including FOAs that are intended to support the translation of emerging basic science findings of mechanisms and processes underlying mental disorders into novel psychosocial interventions ("Development of Psychosocial Therapeutic and Preventive Interventions for Mental Disorders," (PAR-21-135 (R61/R33) and PAR-21-134 (R33)) and novel pharmacological or device-based interventions (“Early Stage Testing of Pharmacologic or Device-based Interventions for the Treatment of Mental Disorders," (PAR-21-137 (R61/R33) and PAR-21-136 (R33)). Effectiveness research for acute-phase interventions is supported through additional FOAs, including "Pilot Effectiveness Trials for Treatment, Prevention and Services Interventions" (PAR-21-131 (R34)) and "Clinical Trials to Test the Effectiveness of Treatment, Preventive, and Services Interventions" (PAR-21-130 (R01) and PAR-21-129 (Collaborative R01)).

All PD(s)/PI(s)s submitting clinical trials applications consistent with NIMH priorities are encouraged to visit the NIMH Clinical Trials webpage and consult with Scientific/Research Staff regarding FOAs that are appropriately matched to the study scope and stage of intervention development and testing.

Applications with data collection plans that involve multiple respondent groups (e.g., clients/patients, therapists/providers, supervisors, administrators) should address provisions for human subject protections and consenting procedures for all participant groups, accordingly.

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. Plans for the protection of research participants and data and safety monitoring will be reviewed by the NIMH for consistency with NIMH and NIH policies and federal regulations.

See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information

Funding Instrument

Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.

Application Types Allowed
New
Resubmission
Revision

Resubmission from PAR-18-431 and PAR-21-211

Revision from PAR-17-271, PAR-18-431, and PAR-21-211

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.

Clinical Trial?

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

The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

Award Budget

Direct costs are limited to $450,000 over the R34 project period, with no more than $225,000 in direct costs allowed in any single year.

Award Project Period

The total project period 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 FOA.

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions

  • Public/State Controlled Institutions of Higher Education
  • Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

  • Hispanic-serving Institutions
  • Historically Black Colleges and Universities (HBCUs)
  • Tribally Controlled Colleges and Universities (TCCUs)
  • Alaska Native and Native Hawaiian Serving Institutions
  • Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

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

  • Small Businesses
  • For-Profit Organizations (Other than Small Businesses)

Local Governments

  • State Governments
  • County Governments
  • City or Township Governments
  • Special District Governments
  • Indian/Native American Tribal Governments (Federally Recognized)
  • Indian/Native American Tribal Governments (Other than Federally Recognized)

Federal Governments

  • Eligible Agencies of the Federal Government
  • U.S. Territory or Possession

Other

  • 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
  • Regional Organizations
  • Non-domestic (non-U.S.) Entities (Foreign Institutions)
Foreign Institutions

Non-domestic (non-U.S.) Entities (Foreign Institutions) 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. 

Required Registrations

Applicant organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) 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. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

  • Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
  • 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.
  • eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but 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 DUNS number and 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 his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH 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 SF424 (R&R) Application Guide.

2. Cost Sharing

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

3. Additional Information on Eligibility

Number of Applications

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.  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 NOT-OD-11-101)

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 FOA. 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 SF424 (R&R) Application Guide except where instructed in this funding opportunity announcement 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.

Letter of Intent

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

  • Descriptive title of proposed activity
  • Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
  • Names of other key personnel
  • Participating institution(s)
  • Number and title of this funding opportunity

The letter of intent should be sent to:
Email: nimhpeerreview@mail.nih.gov

Page Limitations

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

Instructions for Application Submission

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

SF424(R&R) Cover

All instructions in the SF424 (R&R) Application Guide must be followed.

SF424(R&R) Project/Performance Site Locations

All instructions in the SF424 (R&R) Application Guide must be followed.

SF424(R&R) Other Project Information

All instructions in the SF424 (R&R) 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 SF424 (R&R) Application Guide must be followed.

R&R or Modular Budget

All instructions in the SF424 (R&R) Application Guide must be followed.

R&R Subaward Budget

All instructions in the SF424 (R&R) Application Guide must be followed.

PHS 398 Cover Page Supplement

All instructions in the SF424 (R&R) Application Guide must be followed.

PHS 398 Research Plan

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.

The following modifications also apply:

All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan

To foster the goal of advancing research through widespread data sharing among researchers, investigators funded under this FOA are expected to share those data via the National Data Archive (NDA; see NOT-MH-19-033). Established by the NIH, NDA is a secure informatics platform for scientific collaboration and data-sharing that enables the effective communication of detailed research data, tools, and supporting documentation. NDA links data across research projects through its Global Unique Identifier (GUID) and Data Dictionary technology. Investigators funded under this FOA are expected to use these technologies to submit data to NDA.

To accomplish this objective, it will be important to formulate a) an enrollment strategy that will obtain the information necessary to generate a GUID for each participant, and b) a budget strategy that will cover the costs of data submission. The NDA web site provides two tools to help investigators develop appropriate strategies: 1) the NDA Data Submission Cost Model which offers a customizable Excel worksheet that includes tasks and hours for the Program Director/Principal Investigator and Data Manager to budget for data sharing; and 2) plain language text to be considered in your informed consent available from the NDA's Data Contribution page. Investigators are expected to certify the quality of all data generated by grants funded under this FOA prior to submission to NDA and review their data for accuracy after submission. Submission of descriptive/raw data is expected semi-annually (every January 15 and July 15); submission of all other data is expected at the time of publication, or prior to the end of the grant, whichever occurs first (see NDA Sharing Regimen for more information); Investigators are expected to share results, positive and negative, specific to the cohorts and outcome measures studied. The NDA Data Sharing Plan is available for review on the NDA website. NDA staff will work with investigators to help them submit data types not yet defined in the NDA Data Dictionary.

Appendix:
Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

Research Strategy: Applicants should include the following sections as part of the Research Strategy. Applications should not duplicate information provided in the attachment described in the PHS Human Subjects Clinical Trial Information form, but may reference it to provide context as needed.

Significance

  • Justify the practical effect of the intervention or service approach in terms of the estimated hypothesized effect size (e.g., in terms of remediation of residual symptoms or functional impairment, reduced likelihood of relapse or re-hospitalization, improved adherence), compared with already available approaches. Address the potential impact of the intervention/service delivery approach in terms of both (1) the empirical basis for the anticipated effect size (e.g., citing data regarding the magnitude of the association between the target and the clinical endpoint of interest and/or effect sizes obtained in prior efficacy studies), and (2) the clinical meaningfulness of the anticipated increment in effects compared to existing approaches.
  • Address the degree to which the proposed intervention/service delivery approach is scalable and could be disseminated into practice, given typically available resources (e.g., trained, skilled providers), typical service structures (including MH financing), 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.

Innovation

  • Highlight how innovative research strategies and design/analytic elements (e.g., adaptive sequential randomization, equipoise stratification) are incorporated, as appropriate, in order to enhance the study's potential for yielding practice-relevant information.
  • As relevant, highlight how applications of information technology are leveraged to increase the reach, efficiency, or effectiveness of interventions to improve the post-acute outcomes

Approach

  • Detail the rationale and empirical basis for the intervention approach in terms of: the intended target population (e.g., their prior acute-phase intervention exposure and current status (e.g., individuals who have achieved pre-determined response criteria, individuals with a pre-defined level of residual symptomatic/functional impairment, individuals at risk for relapse)); the stage of illness that is targeted (e.g., continuation therapy, maintenance therapy, illness management, transition to outpatient care); the corresponding goals and focus of the intervention (e.g., remediating residual symptoms or functional impairment; preventing relapse or re-hospitalization; promoting adherence, appropriate service use, and/or health-maintaining behaviors); the proximal intervention targets/ presumed mechanisms; the match between the stage of illness/goals and the intensity of the intervention (e.g., in terms of patient/consumer burden, provider/system demands, and cost); and the key window or timeframe over which the post-acute phase intervention or service strategy should be administered.
  • Consistent with NIMH's experimental therapeutics approach, detail plans to explicitly address whether the preventive, therapeutic, or services interventions engage the mechanism(s) presumed to underlie the intervention effects (the mechanism(s) that accounts for changes in clinical/ functional outcomes, changes in patient or provider behavior, etc.). Include the following: (1) a conceptual framework that clearly identifies the target(s)/mechanism(s) and the empirical evidence linking the target(s)/mechanism(s) to the clinical symptoms, functional deficits, or patient-, provider- or system-level behaviors/processes that the intervention seeks to improve; (2) plans for assessing engagement of the target(s)/mechanism(s) using valid measures that are as direct and objective as is feasible in the effectiveness context, including the specific measures, the assessment schedule, and the justification for the assessment strategy (e.g., evidence regarding the validity and feasibility of the proposed measures in the effectiveness context); and (3) analytic strategies that will be used to examine whether the intervention engages the target(s) and to examine whether intervention-induced changes in the target(s) are associated with clinical benefit (i.e., mediation). In the case of multi-component approaches, the application should specify the conceptual basis, assessment plan, and analytic strategy, as detailed above, for the target(s)/mechanism(s) corresponding to each intervention component, as appropriate in the effectiveness context.
  • Provide a clear justification for the type of experimental design chosen; the goal of this phase of research is to propose the most rigorous means of collecting data (in light of ethical or other limitations) that will inform a larger, more definitive test of the intervention. Provide a clear rationale for the choice of methods proposed (e.g., address the rationale for the decision regarding whether or not to include a control group at this stage of pilot research; justify plans to interpret observed outcomes, including feasibility, given the sample size and limitations) and describe how the results will inform the next stages of research.
  • When appropriate, for studies that involve preventive or therapeutic interventions, detail how the study takes into account RDoC or RDoC-like constructs when defining the subject eligibility (inclusion), intervention targets or mechanisms, and outcomes, as feasible in the effectiveness setting.
  • Describe provisions for the assessment and monitoring of the fidelity of intervention delivery via procedures that are feasible and valid.
  • As appropriate, describe plans to involve collaborations and/or input from community practice partners/providers, consumers, and relevant policy makers in a manner that informs the research (e.g., to help ensure the interventions/service delivery approaches are acceptable, feasible, and scalable) and helps to ensure the results will have utility.
  • As appropriate, detail plans to assess and examine consumer-, provider- and setting- level factors that might be associated with uptake, implementation fidelity, and sustained use of the approach that is being developed and tested. Describe the consumer-, provider- and setting- level characteristics that will be assessed and the measures that will be used (e.g., standardized measures of provider attitudes/experience, clinic-/organizational characteristics).

  • As appropriate, describe design features that will be incorporated to help ensure that the approach can be feasibly implemented in practice, that it is scalable, and that it is robust against implementation drift (e.g., using technology as scaffolding or expert consultation via existing resources/ other sustainable means to support delivery).

  • As relevant, address how the trial contributes to advancing the personalization of mental health care and describe the collection of clinical and biological variables (e.g., blood for genetic analysis, other potential biomarkers) that might be used to examine moderators or inform/test algorithms for more prescriptive approaches. Address statistical power to test for moderators and/or the potential to contribute information regarding potential moderators to larger databases for future use.

  • Incorporate outcome measures that are validated and generally accepted by the field, including stakeholder-relevant outcomes (e.g., functioning, health services use), as appropriate.

  • For studies that involve the assessment of patient-level outcomes, describe plans for the assessment of suicidal behavior and related outcomes using strategies that can facilitate integration and sharing of data (e.g., see NOT-MH-15-009 and https://www.phenxtoolkit.org/ for constructs and corresponding assessment strategies), as appropriate, or provide a rationale for excluding such measures if they are not included. Accordingly, the application should provide the rationale for the selection of suicide-related constructs and corresponding assessment instruments (e.g., measures of ideation, attempts), the time periods assessed (e.g., lifetime history, current), and the assessment schedule for administration (e.g., baseline, during intervention, post-intervention, follow up), taking into account the nature of the target population, participant burden, etc. The application should also address provisions for clinical management when suicidal behavior is reported. In situations where it is not appropriate or feasible to include assessment of suicide outcomes due to the nature of the intervention (e.g., services interventions that target provider behavior or systems-level factors), the target population (e.g., very young children), or unique issues related to participant burden or safety/monitoring concerns, the application should provide an appropriate justification for excluding these assessments.
PHS Human Subjects and Clinical Trials Information

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed.

Section 2 - Study Population Characteristics

2.5 Recruitment and Retention Plan

Applications must provide a clear description of:

1. Recruitment and Referral sources, including detailed descriptions of the census/rate of new cases and anticipated yield of eligible participants from each source;

2. Procedures that will be used to monitor enrollment and track/retain participants for follow-up assessments;

3. Strategies that will be used to ensure a diverse, representative sample;

4. Potential recruitment/enrollment challenges and strategies that can be implemented in the event of enrollment shortfalls (e.g., additional outreach procedures, alternate/back-up referral sources);

5. Evidence to support the feasibility of enrollment, including descriptions of prior experiences and yield from research efforts employing similar referral sources and/or strategies.

2.7 Study Timeline

Applications must provide a timeline for reaching important study benchmarks such as: (1) finalizing the study procedures and training participating clinical site staff; (2) finalizing the service tool manual and assessment protocols, including fidelity measures/procedures, where applicable; (3) enrollment benchmarks; (4) completing all subject assessments and data collection activities, including data quality checks; (5) analyzing and interpreting results; and (6) preparing de-identified data and relevant documentation to facilitate data sharing, as appropriate.

Section 4 - Protocol Synopsis

4.2 Outcome Measures

Incorporate outcome measures that are validated and generally accepted by the field, including stakeholder-relevant outcomes (e.g., functioning, health services use), as appropriate.

4.3 Statistical Design and Power

Address statistical power to test for moderators and/or the potential to contribute information regarding potential moderators to larger databases for future use.

Section 5 - Other Clinical Trial-related Attachments

5.1 Other Clinical Trial-related Attachments

Applicants must upload the attachments for Intervention Manual/Materials, as applicable. If more than one set of Intervention Manual/Materials are used, they should be combined in this attachment. Applicants must use the “Intervention Manual/Materials” to name this other attachments file. As appropriate, this may include screenshots of mobile interventions, technological specifications, training manuals or treatment algorithms.

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.

PHS Assignment Request Form

All instructions in the SF424 (R&R) Application Guide must be followed.

Foreign Institutions

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

3. Unique Entity Identifier and System for Award Management (SAM)

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

4. Submission Dates and Times

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time.  If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide.  Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process.  Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

Overall Impact

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Scored Review Criteria

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance

Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

How well does the application adequately justify the practical effect of the intervention or service approach in terms of the estimated hypothesized effect size (e.g., in terms of remediation of residual symptoms or functional impairment, reduced likelihood of relapse or re-hospitalization, improved adherence), compared with already available approaches? How well does the application address both (1) the empirical basis for the anticipated effect size (e.g., citing data regarding the magnitude of the association between the target and the clinical endpoint of interest and/or effect sizes obtained in prior efficacy studies), and (2) the clinical meaningfulness of the anticipated increment in effects compared to existing approaches?

If the approach is successful, what are the potential scalability and potential for dissemination into practice given typically available resources (e.g., trained, skilled providers), typical service structures (including health care financing), and typical service use patterns?

How likely is it that 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?

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

As relevant and appropriate, how well does the application leverage innovative applications of information technology to increase the reach, efficiency, or effectiveness of interventions to improve the post-acute outcomes?

Examples of innovative elements could include adaptive sequential randomization, equipoise stratification, or technology assisted assessment and others.

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Evaluate the degree to which the application provides a clear rationale and compelling empirical basis for the intervention approach in terms of: the intended target population (e.g., prior acute-phase intervention exposure and current status (e.g., individuals who have achieved pre-determined response criteria, individuals with a pre-defined level of residual symptomatic/functional impairment, individuals at risk for relapse)); the stage of illness that is targeted (e.g., continuation therapy, maintenance therapy, illness management, transition to outpatient care); the corresponding goals and focus of the intervention (e.g., remediating residual symptoms or functional impairment; preventing relapse or re-hospitalization; promoting adherence, appropriate service use, and/or health-maintaining behaviors); the proximal intervention targets/ presumed mechanisms; the timing of the intervention (timeframe over which the post-acute phase intervention or service strategy should be administered); and the match between the stage of illness/goals and the intensity of the intervention (e.g., in terms of patient/consumer burden, provider/system demands, and costs); and the key window or timeframe over which the post-acute phase intervention or service strategy should be administered.

How well does the study design address whether the intervention engages the mechanism that is presumed to underlie the intervention effects (the mechanism that accounts for changes in clinical/ functional outcomes, changes in patient or provider behavior, etc.)? To what extent does the application include:

  • A well-supported conceptual framework that clearly identifies the target(s)/mechanism(s) and the empirical evidence linking the target(s)/mechanism(s) to the clinical symptoms, functional deficits, or patient-, provider- or system-level behaviors/processes that the intervention seeks to improve;
  • Well-justified plans for assessing engagement of the target(s)/mechanism(s), including the specific measures, the assessment schedule, and the justification for the assessment strategy (e.g., evidence regarding the validity and feasibility of the proposed measures in the effectiveness context); and
  • Appropriate analytic strategies that will be used to examine whether the intervention engages the target(s) and to conduct a preliminary examination of whether intervention-induced changes in the target(s) are associated with clinical benefit, as appropriate in the pilot trial? In the case of multi-component interventions, does the application specify the conceptual basis, assessment plan, and analytic strategy, as detailed above, for the target(s)/mechanism(s) corresponding to each intervention component, as appropriate in the effectiveness context?

When appropriate, for studies that involve preventive or therapeutic interventions, does the study take into account RDoC or RDoC-like constructs when defining the subject eligibility (inclusion), intervention targets or mechanisms, and outcomes, as feasible in the effectiveness setting?

Evaluate the justification for the experimental design chosen and the plan for collecting data that will inform a larger, more definitive test of the intervention. How strong is the rationale for the choice of methods proposed (e.g., the rationale for the decision regarding whether or not to include a control group at this stage of pilot research; the plans for interpreting observed outcomes, including feasibility, given the sample size and limitations)? To what extent will the results inform the next stages of research?

Evaluate the provisions for the assessment and monitoring of the fidelity of intervention delivery via procedures that are practical and valid.

Are proposed outcome measures validated and generally accepted by the field; are stakeholder-relevant outcomes included, as appropriate (e.g., functioning, health services use)?

Does the application include plans to involve collaborations and/or input from community practice partners/providers, consumers, and relevant policy makers in a manner that informs the research (e.g., to help ensure the interventions/service delivery approaches are acceptable, feasible, and scalable) and helps to ensure the results will have utility?

To what extent does the application include plans to assess and examine consumer-, provider- and setting- level factors that might be associated with uptake, implementation fidelity, and sustained use of the approach that is being developed and tested? How well does the application describe the consumer-, provider- and setting- level characteristics that will be assessed and the measures that will be used (e.g., standardized measures of provider attitudes/experience, clinic-/organizational characteristics)?

As appropriate, to what extent does the approach incorporate design features that will help ensure that the intervention can be feasibly implemented in practice, that it is scalable, and that it is robust against implementation drift (e.g., using technology as scaffolding or expert consultation via existing resources/ other sustainable means to support delivery)?

How likely is it that the trial will contribute to advancing the personalization of mental health care? Does it include collection of clinical and biological variables (e.g., blood for genetic analysis, other potential biomarkers), as appropriate, that might be used to examine moderators or inform/test algorithms for more prescriptive approaches?

Does the application adequately address the following, if applicable

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

To what extent does the study utilize 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?

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

Additional Review Criteria

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Study Timeline


Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

Protections for Human Subjects

For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Individuals Across the Lifespan

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

Renewals

Not Applicable

Revisions

For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

Additional Review Considerations

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Applications from Foreign Organizations

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3)  Genomic Data Sharing Plan (GDS).

Authentication of Key Biological and/or Chemical Resources:

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Budget and Period of Support

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by NIMH, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications will receive a written critique.

Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:
  • Scientific and technical merit of the proposed project as determined by scientific peer review.
  • Availability of funds.
  • Relevance of the proposed project to program priorities.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

Section VI. Award Administration Information

1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the recipient's business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website.  This includes any recent legislation and policy applicable to awards that is highlighted on this website.

The NIMH has published policies and guidance for investigators regarding human research protection, data and safety monitoring, Independent Safety Monitors and Data and Safety Monitoring Boards, reportable events, and participant recruitment monitoring (NOT-MH-19-027). The application’s PHS Human Subjects and Clinical Trials Information should reflect the manner in which these policies will be implemented for each study record. These plans will be reviewed by the NIMH for consistency with NIMH and NIH policies and federal regulations. The NIMH will expect clinical trials to be conducted in accordance with these policies including, but not limited to: timely registration to ClinicalTrials.gov, submission of review determinations from the clinical trial’s data and safety monitoring entity (at least annually), timely submission of reportable events as prescribed, and establishment of recruitment milestones and progress reporting.

Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.

ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain “applicable clinical trials” on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).

Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex. This includes ensuring programs are accessible to persons with limited English proficiency. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html.

HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA.

Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

Not Applicable

3. Reporting

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later.  All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000.  See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period.  The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS).  This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313).  As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available.  Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 – Award Term and Conditions for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

Application Submission Contacts

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

Scientific/Research Contact(s)

Adam Haim, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-435-3593
Email: haima@mail.nih.gov

Peer Review Contact(s)

Nick Gaiano, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-827-3420
Email: nick.gaiano@nih.gov

Financial/Grants Management Contact(s)

Tamara Kees
National Institute of Mental Health (NIMH)
Telephone: 301-443-8811
Email: tkees@mail.nih.gov

Section VIII. Other Information

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Authority and Regulations

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.


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