Part 1. Overview Information

Key Dates

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.

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.

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.



Table of Contents
Part 1. Overview Information
Key Dates
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

Purpose

The purpose of this notice of funding opportunity (NOFO) is to support confirmatory efficacy testing of non-pharmacological and, under certain conditions, pharmacological, therapeutic and preventive interventions for mental disorders in adults and children that address unmet therapeutic needs, and are consistent with the NIMH emphasis on the experimental therapeutics approach. In this approach, clinical trials should be designed to increase knowledge of the relationship between underlying disease processes and the targets/mechanisms of action through which any intervention produces therapeutic change.

Therefore, interventions appropriate for confirmatory efficacy testing must be based on a compelling scientific rationale, previous demonstration that the intervention engages and alters the hypothesized mechanism of action, and a preliminary efficacy signal (for further information, see the NIMH webpage on Clinical Trials). The proposed trial must include plans to replicate these target engagement and validation findings in a fully powered, confirmatory efficacy study that is likely to show superiority of the intervention over an appropriately justified comparison condition.

Interventions appropriate to this NOFO may include in-person or technology-assisted psychosocial intervention approaches, device-based approaches (both invasive and non-invasive), or combinations of these approaches as monotherapies, stepped approaches, or as augmentations to standard interventions. While this NOFO will support efficacy testing of novel technology-assisted intervention approaches, it is not intended to support the translation of existing treatments into technology-based applications (e.g., mHealth). FDA-indicated drugs may be included as part of a combination treatment when the intent is to test the efficacy of the other (novel) non-pharmacological treatment component or the novel combination. However, applications to establish the efficacy of pharmacological interventions will be considered responsive to this NOFO primarily for drugs lacking a commercial sponsor and otherwise meeting the criteria for confirmatory efficacy testing as described in this announcement. While in the usual case of drug development leading to regulatory approval for marketing, confirmatory efficacy and subsequent effectiveness clinical trials would be supported by the industry sponsor, the presence of an industry sponsor will not preclude support of pharmacotherapy confirmatory efficacy clinical trials that are designed to address important scientific questions of public health significance during drug development; such applications should indicate whether the sponsor is supplying the drug without costs. 

Scale and Scope of Research

Under the required experimental therapeutics approach (see "An Experimental Therapeutic Approach to Psychosocial Interventions"), intervention targets, or mediators, might include, but are not limited to, potentially modifiable specific psychological, behavioral, or interpersonal processes (e.g., cognitive-affective processes such as attention bias, cognitive control, stress regulation) or neurobiological processes or entities (e.g., brain circuits). Circuit-based targets can include networks of brain regions defined anatomically as well as temporal dynamics of network function defined physiologically as neural oscillatory patterns. The intended target(s)/mechanism(s) and clinical endpoints will vary with the type of intervention. In the case of preventive interventions, the proximal target might involve a risk factor that has been associated with the etiology or onset of a mental health disorder. Accordingly, the intervention's efficacy might be evaluated in terms of whether or not the intervention, mediated by changes in the target, resulted in decreased onset of the mental health disorder/condition (i.e., the clinical endpoint). More than one target/mechanism may be proposed if each target/mechanism is supported by an empirical rationale, there are testable hypotheses proposed for each, and there are valid and reliable measures of change available for each.

In the assessment of target engagement, NIMH encourages the use of measures that are as direct and objective as is feasible in the clinical research setting. Specifically encouraged are empirically validated measures of the construct that extend beyond self-reports and other subjective measures, where possible, and inclusion of measures that span more than one level of assessment if possible and appropriate. The detailed data analysis plan for examining changes in targets and related changes in outcomes should be included in the Research Strategy of the application.

This NOFO supports confirmatory efficacy trials of non-pharmacological and pharmacological therapeutic and preventive interventions that are powered to provide a definitive answer regarding the study intervention's efficacy.

PD(s)/PI(s)s submitting applications consistent with the NIMH experimental therapeutic approach but whose application does not fall within the scope of this NOFO are encouraged to contact Scientific/Research staff or view the NIMH Clinical Trial web page and Frequently Asked Questions section: http://www.nimh.nih.gov/funding/clinical-trials-for-researchers/index.shtml.

This NOFO is focused on trials that establish the efficacy of interventions. Applications that involve adding a new level of analysis to assess or better understand mechanisms of an established intervention (e.g., a study that adds brain-based assessments such as neuroimaging or psychophysiological measures to evaluate neurobiological underpinnings/correlates that are associated with changes in cognitive/affective processes commonly targeted by CBT) are encouraged to consult NIMH Program Staff and consider NOFOs that NIMH uses to support mechanistic trials (see Support for Clinical Trials at NIMH).

Applicants interested in initial intervention development and pilot testing of novel non-pharmacological interventions are directed to PAR-25-182Development of Psychosocial Therapeutic and Preventive Interventions for Mental Disorders (R61/R33)" and PAR-25-181 "Development of Psychosocial Therapeutic and Preventive Interventions for Mental Disorders (R33)" for psychosocial interventions and to PAR-25-184, "Early Stage Testing of Pharmacologic or Device-based Interventions for the Treatment of Mental Disorders (R61/R33)" and PAR-25-183 "Early Stage Testing of Pharmacologic or Device-based Interventions for the Treatment of Mental Disorders (R33)" for pharmacological and device-based intervention development and pilot testing. 

Investigators interested in conducting fully-powered effectiveness trials in community-practice settings are referred to PAR-25-177"Full-Scale Hybrid Effectiveness-Implementation Trials for Mental Health Interventions (R01 Clinical Trial Required). A review of the NIMH role in several aspects of medication development can be found in the report of the 2020 NAMHC Workgroup on Drug Development.

Potential applicants are strongly encouraged to contact the Scientific/Research contacts far in advance as possible to discuss the potential clinical practice/public health impact of the proposed confirmatory efficacy investigation, as well as concordance with current NIMH priorities.

NIMH Priorities for Confirmatory Efficacy Trials

NIMH is interested in pivotal studies to enable device-based interventions to receive FDA approval. Studied interventions should be compared against established treatments in superiority or non-inferiority trials, based on the clinical context. It is advised that research groups consider utilizing a project manager with industry experience in managing clinical trials to oversee their pivotal study. Contract Research Organizations (CROs) or institutions with Clinical and Translational Science Awards (CTSAs) may be appropriate to conduct device trials. FDA involvement may not be necessary for those trials where device-based measures are employed as a component of an intervention that is centered on a psychosocial or software-based treatment that is the focus of establishing confirmatory efficacy.

This NOFO supports confirmatory efficacy trials of interventions for which preliminary evidence of target engagement has already been demonstrated and there is a signal suggesting clinical efficacy that serves as a basis for anticipating at least a moderate clinically meaningful effect size (d = 0.5) in the fully-powered confirmatory efficacy trial. The earlier stages of intervention development, which include optimization of intervention delivery parameters, preliminary tests of target engagement, and target validation, are not appropriate for this NOFO and are supported by NIMH through companion NOFOs (NIMH Clinical Trials NOFO page). It is expected that the design of the trial would inform the next stage of intervention development, whether that be an effectiveness trial, further investigation in dissemination and/or implementation research, or actual dissemination into practice.

NIMH is particularly interested in the development of therapeutic and preventive interventions that focus on operationally defined, empirically supported functional domains or symptom(s) of mental disorders as opposed to broad diagnostic categories in which not all subjects may share the same underlying disease process. NIMH Research Domain Criteria (RDoC) principles and constructs should, as appropriate, inform subject eligibility or stratification, identification of intervention targets, and/or selection of outcome measures, and in many cases can serve to complement traditional DSM diagnostic categories. 

Studies that incorporate a deployment-focused approach are encouraged. Deployment-focused research 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, and are likely to be feasible and scalable.

 Applications Not Responsive to this NOFO

Studies that are not responsive to this NOFO and will not be reviewed include the following:

• Applications that test efficacy of a new intervention that is undergoing initial development with the ultimate aim of seeking FDA approval that fail to meet NIMH Clinical Trial experimental therapeutics requirements.
• Applications that are not focused on a functional domain, symptoms, or mental health disorder.
• Applications that focus on efficacy without having already established compelling evidence of target engagement and at least initial evidence for target validation, in addition to an initial efficacy signal.
• Applications that do not propose an experimental therapeutics approach (i.e., do not test a mechanism of action), including the following components of the application: (1) specified target(s)/mechanism(s) of action; (2) measurement plans designed to assess the target(s)/mechanism(s) of action and clinical outcomes; and (3) a description of the analytic plan for evaluating whether intervention-induced target(s)/mechanism(s) of action are associated with outcomes. 
• Applications that involve adding a new level of analysis to assess or better understand mechanisms of an established intervention (e.g., a study that adds brain-based assessments such as neuroimaging or psychophysiological measures to evaluate neurobiological underpinnings/correlates that are associated with changes in cognitive/affective processes commonly targeted by CBT (see Support for Clinical Trials at NIMH).
• Adaptation of an efficacious intervention in the absence of a compelling justification for such a need, and in the absence of a clear experimental therapeutics approach (in 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.)
• Studies involving vertebrate animals.

Other Considerations

For applications that plan to test the efficacy of devices that require federal regulatory approval processes, NIMH expects FDA guidance meetings to be performed prior to submission of the application, so that information from the guidance meeting is incorporated into the protocol design. Documentation of discussions and meetings with FDA staff should be included in the application.

While digital mental health interventions that meet the above criteria are acceptable for confirmatory efficacy testing, given the inherent necessity of scalability and implementation in the community for such approaches, most mobile-application-based treatment studies are supported using an Effectiveness Clinical Trial mechanism (PAR-25-177; PAR-25-178) or the Laboratories to Optimize Digital Health mechanism (PAR-25-136). 

Applicants are encouraged to leverage existing resources and infrastructure such as those provided by institutions with Clinical and Translational Science Awards (CTSAs) and/or other existing consortia/networks to promote efficient cross-disciplinary collaborations. Applicants are also expected to use common data collection instruments (see: NOT-MH-20-067).

Consistent with NIH efforts to promote a diverse scientific workforce, NIMH strongly encourages applications from members of underrepresented/minoritized groups at every career level. 

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 and the NIMH webpage on clinical research.

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

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

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

1. Eligible Applicants

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 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

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.

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. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019 and Notice of NIH's Interest in Diversity, NOT-OD-20-031.

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.

2. Cost Sharing

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

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, 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.

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 protected]

Page Limitations

All page limitations described in the How to Apply- Application Guide and the Table of Page Limits must be followed.

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.

SF424(R&R) Cover

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: Provide the description of the resources available which include an overview of the institutional environment and expected commitment, as reflected in physical resources, staffing – including any expertise contributed by individuals not listed as “key personnel” – governance, and organizational structure as appropriate to conduct the study as proposed and within efficacy clinical trial principles and specified timelines. Address how the proposed study utilizes relevant existing infrastructure (e.g., electronic medical records, administrative databases, patient registries) or utilizes other available resources to increase the efficiency of participant recruitment and data collection. Discuss ways that the proposed confirmatory efficacy clinical trial will benefit from unique features of the scientific environment or from unique subject populations. If multiple performance sites are planned, describe intended collaborative arrangements and the resources available at each site. 

SF424(R&R) Senior/Key Person Profile

All instructions in the How to Apply- Application Guide must be followed.

As appropriate, biographical sketches and the Research Strategy section are required to detail the expertise and track record of the Senior/Key Personnel in clinical trials of similar structure and complexity, including: recent subject recruitment and retention rates of trial subjects; reporting in ClinicalTrials.gov; publications; methodological and statistical expertise (e.g., handling repeated measures designs, missing data; assessing effect size; and measurement of intervention change mechanisms). Also include recent collaborative clinical research efforts among members of the proposed team, if any.

R&R or Modular Budget

All instructions in the How to Apply- Application Guide must be followed.

R&R Subaward Budget

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.

PHS 398 Research Plan

All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions:

Research Strategy: Applicants must include the following information as part of the Research Strategy. Applications should not duplicate information provided in the Other Attachment included on the PHS Human Subjects and Clinical Trial Information form, but can refer to it as needed in order to provide context.

Applications must address the transportability/scalability of the proposed intervention and should detail how the treatment manual, therapist training procedures, and fidelity assessment and enhancement methods could be adapted and refined to be applicable to clinical practice. Justify the potential impact of the intervention compared to existing approaches and should address the degree to which the proposed intervention could potentially be brought to scale in an effectiveness study or be disseminated into practice.

Factor 1. Importance of the Research

Significance:  

• Describe the unmet therapeutic need that will be addressed by the intervention.
• Describe the intervention's potential to significantly reduce the burden of serious mental disorders.
• Describe how the proposed project will advance knowledge of pathophysiologic and/or psychopathologic mechanisms relevant to the functional domain, symptom(s) or diagnosis of interest, or mechanisms that underlie intervention response, whether the trial results are positive or negative.
• Describe the rationale for the anticipated effect size and explain how it is clinically meaningful.
• Describe the scientific advances to be gained in the research study.

Innovation:  

• Describe how technology or other innovative approaches will be leveraged, as appropriate, to facilitate the delivery, efficacy, and future scalability of the approach that is being evaluated.

Factor 2. Rigor and Feasibility

Approach: In this section of the Research Strategy:

• Provide a compelling scientific rationale for the approach chosen, including: 1) theory-driven, scientifically grounded, and refutable hypotheses about the mechanisms involved in triggering or maintaining the disorder and the mechanisms/mediators of the intervention's effect; 2) a description of how the approach will ensure that the underlying hypothesized target(s)/mechanism(s) will be tested; and 3) a detailed data analysis plan for examining changes in target(s)/mechanism(s) and related changes in outcomes. For multi-component interventions, hypothesized targets/mechanisms are expected for each intervention component.   
• If testing an adaptation or extension of an intervention with established efficacy, describe how the study will focus on providing clear evidence of target engagement and how the design will be able to provide an empirically supported basis for (a) identifying prognostic indicators (subgroups) that predict differential benefit from target engagement (e.g., in comparison to the existing, unadapted intervention), and/or (b) paring the intervention down to its essential elements based on clear evidence of target engagement.
• Describe the existing evidence of the intervention's potential, including 1) evidence of the intervention's target/mechanism engagement (e.g., a significant difference in target/mechanism change between the experimental and control groups); 2) preliminary evidence of target/mechanism validation (e.g., a signal that changes in the presumed target/mechanism are associated with changes in the clinical outcome in the hypothesized direction); and 3) an initial efficacy signal that serves as a basis for anticipating at least a moderate clinically meaningful effect size (d=0.5) in the fully-powered confirmatory efficacy trial.
• Describe the empirical foundation for the intervention dosage and delivery parameters. For psychosocial interventions, these parameters may include duration, frequency, and number of sessions. For computer-administered interventions, parameters may include the stimulus characteristics, number of trials, difficulty level and intervals between trials. For pharmacological interventions, these parameters  include dose, formulation, mode and frequency of administration, and duration of treatment course. For neuromodulatory interventions, these parameters include all aspects of the administered electric field or alternative form of energy, including the spatial distribution (including specification of the electric field distribution in the brain as quantified via realistic head modeling), the temporal characteristics (including all aspects of pulse shape, pulse directionality, frequency, inter-train interval, burst paradigms, etc.), and the contextual aspects of when and how the dose is administered (e.g., time-locking to underlying neural oscillations, brain state at time of administration, engagement in on-line or off-line cognitive/behavioral therapies, concomitant pharmacological intervention, etc.).
• Describe preliminary evidence of feasibility, including the availability of intervention manuals and fidelity measures.
• Provide the scientific rationale for the measures used to assess the link between the hypothesized target(s)/mechanism(s) and clinical/functional outcomes, including measurement reliability and validity, and measurement schedules suitable for detecting relevant changes in target(s)/mechanism(s). 
• Explain how the delivery of the intervention will be operationalized, monitored, and quantified, including any modifications to existing treatment manuals and fidelity measures. For neuromodulatory interventions, this should include information on device operator performance and accuracy in site identification and dosage individualization.
• Describe features that will be incorporated to help ensure that the approach can be feasibly implemented in practice, and that it is scalable, including: 
  • Plans to involve collaborations and/or input from community practice partners/providers, consumers, and relevant policymakers in a manner that informs the research (e.g., to ensure the interventions/service delivery approaches are acceptable, feasible, and scalable) and to ensure the results will have utility;
  • Treatment manuals, therapist training procedures, and protocols for monitoring and enhancing fidelity that anticipate use in community practice; 
  • The intervention's compatability with typically available resources and reimbursement practices; 
  • Technology or other design features to promote sustained fidelity (e.g., using technology as scaffolding or expert consultation via existing resources/other sustainable means to support fidelity); and 
  • Plans to develop surrogate endpoints that would be feasible to use in everyday clinical settings.
• Describe the clinical trial methodology and how sufficient data will be collected to inform a "go/no-go" decision about the therapeutic target for further clinical development or effectiveness testing. Describe the selection of the control condition and how it is likely to address the research question. Subject inclusion/exclusion criteria should be well-justified and the selection should be made on the basis of a measurable disruption in the mechanism under study.
• Describe the approach feasibility in terms of having in place all the necessary elements to carry out data acquisition and analysis in a timely manner.
• Where feasible and appropriate, applicants are strongly encouraged to include assessment of suicidal behavior in clinical trials in response to this NOFO 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). 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.
• Provide a statistical analysis plan and corresponding power analysis for examining whether intervention-induced changes in the mechanism(s) are associated with changes in the outcomes (i.e., mediation). The Research Strategy section of the application must include a description of this planned analytic approach and power analysis, whereas the full details of the proposed statistical methods must be included in the PHS Human Subjects and Clinical Trials form.   

Letters of Support: For applications proposing use of an FDA-regulated device, letters of support from an industry partner for the device should be documented as well as plans for a collaborative research agreement (CRA) must be included.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply- Application Guide.

Other Plan(s): 

All instructions in the How to Apply-Application Guide must be followed, with the following additional instructions:

• All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.

To advance the goal of advancing research through widespread data sharing among researchers, investigators funded by NIMH under this NOFO are expected to share those data via the National Institute of Mental Health Data Archive (NDA; see NOT-MH-23-100). 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 NOFO 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 website 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 NOFO 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.For more guidance on submitting data to NDA, refer to the NDA Data Management and Sharing Plan 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 How to Apply- Application Guide.

• No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

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 How to Apply- 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 How to Apply- 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

 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 intervention 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 3 - Protection And Monitoring Plans

3.5 Overall Structure of Study Team

Applicants must provide a detailed description of their study team, including details on program management structure and oversight. For device-based studies, a program manager should be included in the team structure. Information including what contract research organization (CRO) or CTSA will be used. If a CRO or a CTSA is not proposed, the applicant should provide justification for why the study team has required expertise (e.g., GCP trials, regulatory expertise, and project management) to successfully conduct the trial in a reasonable and time-efficient manner, and to collect registration quality data.

Section 4 - Protocol Synopsis

4.5 Will the study use an FDA-regulated intervention?

4.5.a. If yes, describe the availability of Investigational Product (IP) and Investigational New Drug (IND)/Investigational Device Exemption (IDE) status:

(Required for all device-based studies)

Applications that propose a device-based study that lacks this attachment will be considered incomplete and will not be reviewed. 

For studies of devices, a regulatory strategy must be clearly documented. In the case of devices not yet marketed, tThis should discuss the FDA pathway (PMA, 510(k), de novo) that the device will be submitted for. Information regarding the coverage/coding/reimbursement plan should be included. Centers for Medicare & Medicaid Services (CMS) coverage for clinical and/or device costs of Investigational Device Exemption (IDE)-approved studies should be sought, and documentation provided to demonstrate outreach. 

The regulatory strategy for device approval/clearance must be outlined, as described below, and interactions with the FDA documenting the study as a pivotal study should be incorporated. Likewise, the coverage/coding/reimbursement plan for the device must be described. For studies of devices, at the time of the application's submission, there must be an open IDE in place, or a documented FDA-submitted application/request for an IDE for a pivotal device study [feedback on the pivotal nature of the study is required]. The grant application must describe the status of any such pending regulatory submissions. If an FDA IDE application/request has not yet been submitted by the time of the grant application submission due date, the grant application should describe the plan and schedule for submitting the request for and obtaining the IDE. All major study design considerations in the IDE must be addressed and approved prior to the start of the clinical trial. CMS and private payers should be invited to pre-submission meetings via the parallel path review (FDA/CMS) and an invitation to private payers should be extended. An expedited access pathway should be sought, or if not possible, documentation that the study is ineligible. Registration in an appropriate trial registry should be completed prior to trial onset. 

All necessary agreements for use of the device in the study, including clinical research agreements (CRAs) and licensing agreements, must be executed prior to grant award. There must be documentation of sufficient devices and matching placebo/sham stimulation devices available for testing at the time of award. Documentation should be provided from the 3rd party supplying the device. A description should be included in the attachment showing activities with 3rd parties, such as: 1) execution of necessary agreements, 2) availability of devices, and 3) permission to reference an open IDE (as applicable).

Device-based trials must use the NIH and FDA clinical trial protocol as detailed in https://grants.nih.gov/grants/guide/notice-files/NOT-OD-17-064.html. 

Section 5 - Other Clinical Trial-Related Attachments

5.1 Other Clinical Trial-related Attachments:

Applications may include materials related to intervention delivery or training of providers in this section. As appropriate, this may include screenshots of mobile interventions, technological specifications, training manuals or treatment algorithms. Videos are not allowable. Applicants must upload the attachments for Intervention Manual/Materials as a separate file, as applicable. Combine these into one file and must use the "Intervention Manual/Materials" to name this other attachments file. 

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 How to Apply- Application Guide must be followed.

PHS Assignment Request Form

All instructions in the How to Apply- Application Guide must be followed.

Foreign Organizations

Foreign (non-U.S.) organizations must follow policies described in the NIH Grants Policy Statement, and procedures for foreign organizations described throughout the How to Apply- Application Guide.

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

See Part 2. 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. 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 Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

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 How to Apply-Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

Use of Common Data Elements in NIH-funded Research

Many NIH ICs encourage the use of common data elements (CDEs) in basic, clinical, and applied research, patient registries, and other human subject research to facilitate broader and more effective use of data and advance research across studies. CDEs are data elements that have been identified and defined for use in multiple data sets across different studies. Use of CDEs can facilitate data sharing and standardization to improve data quality and enable data integration from multiple studies and sources, including electronic health records. NIH ICs have identified CDEs for many clinical domains (e.g., neurological disease), types of studies (e.g. genome-wide association studies (GWAS)), types of outcomes (e.g., patient-reported outcomes), and patient registries (e.g., the Global Rare Diseases Patient Registry and Data Repository). NIH has established a “Common Data Element (CDE) Resource Portal" (http://cde.nih.gov/) to assist investigators in identifying NIH-supported CDEs when developing protocols, case report forms, and other instruments for data collection. The Portal provides guidance about and access to NIH-supported CDE initiatives and other tools and resources for the appropriate use of CDEs and data standards in NIH-funded research. Investigators are encouraged to consult the Portal and describe in their applications any use they will make of NIH-supported CDEs in their projects.

NIMH expects investigators for this funding announcement to collect Common Data Elements (CDEs) for mental health human subjects research. Unless NIMH stipulates otherwise during the negotiation of the terms and conditions of a grant award, this Notice applies to all grant applications involving human research participants. The necessary funds for collecting and submitting these CDE data from all research participants to the NIMH Data Archive (NDA) should be included in the requested budget. A cost estimator (https://nda.nih.gov/ndarpublicweb/Documents/NDA_Data_Submission_Costs.xlsx) is available to facilitate the calculation of these costs. NIMH may seek further information regarding CDEs prior to award. Additional information about CDEs can be found at the NIMH webpage on Data Management and Sharing for Applicants and Awardees. 

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 Section 7.9.1 Selected Items of Cost.

Applications must be submitted electronically following the instructions described in the How to Apply 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 form. 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 NOFO for information on registration requirements.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the How to Apply 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 NIMH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Applicants Requesting $500,000 or more for direct costs (less consortium F&A) in any year

Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) do not need to contact a Scientific/Research Contact to follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF424 (R&R) Application Guide.

Recipients or subrecipients must submit any information related to violations of federal criminal law involving fraud, bribery, or gratuity violations potentially affecting the federal award. See Mandatory Disclosures, 2 CFR 200.113 and NIH Grants Policy Statement Section 4.1.35.

Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to the HHS Office of Inspector Grant Self Disclosure Program at [email protected].

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in the policy

Videos are not allowed as post-submission material.

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 Confirmatory Efficacy 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, for example, effectiveness trials under typical clinical conditions.

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 scored review criteria and additional review criteria (as applicable for the project proposed). An application does not need to be strong in all categories to be judged likely to have a major scientific impact.

Reviewers will consider Factors 1, 2 and 3 in the determination of scientific merit, and in providing an overall impact score. In addition, Factors 1 and 2 will each receive a separate factor score. 

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

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.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the 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 NOFO. 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.

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 Section 2.5.1. Just-in-Time Procedures. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding.

Prior to making an award, NIH reviews an applicant’s federal award history in SAM.gov to ensure sound business practices. An applicant can review and comment on any information in the Responsibility/Qualification records available in SAM.gov. NIH will consider any comments by the applicant in the Responsibility/Qualification records in SAM.gov to ascertain the applicant’s integrity, business ethics, and performance record of managing Federal awards per 2 CFR Part 200.206 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.

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 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

A Notice of Award (NoA) is the official authorizing document notifying the applicant that an award has been made and that funds may be requested from the designated HHS payment system or office. The NoA is signed by the Grants Management Officer and emailed to the recipient’s business official.

In accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Any pre-award costs incurred before receipt of the NoA are at the applicant's own risk.  For more information on the Notice of Award, please refer to the NIH Grants Policy Statement Section 5. The Notice of Award and NIH Grants & Funding website, see Award Process.

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 recipient 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

The following Federal wide and HHS-specific policy requirements apply to awards funded through NIH:

• The rules listed at 2 CFR Part 200, Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards.
• All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the terms and conditions in the Notice of Award (NoA). The NoA includes the requirements of this NOFO. 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.
• If a recipient receives an award, the recipient must follow all applicable nondiscrimination laws. The recipient agrees to this when registering in SAM.gov. The recipient must also submit an Assurance of Compliance (HHS-690). To learn more, see the Laws and Regulations Enforced by the HHS Office for Civil Rights website.
  • HHS recognizes that NIH 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 NOFO.

All federal statutes and regulations relevant to federal financial assistance, including those highlighted in NIH Grants Policy Statement Section 4 Public Policy Requirements, Objectives and Other Appropriation Mandates.

Recipients are responsible for ensuring that their activities comply with all applicable federal regulations.  NIH may terminate awards under certain circumstances.  See 2 CFR Part 200.340 Termination and NIH Grants Policy Statement Section 8.5.2 Remedies for Noncompliance or Enforcement Actions: Suspension, Termination, and Withholding of Support. 

Successful recipients under this NOFO agree that:

Where the award funding involves implementing, acquiring, or upgrading health IT for activities by any funded entity, recipients and subrecipient(s) are required to: Use health IT that meets standards and implementation specifications adopted in 45 CFR part 170, Subpart B, if such standards and implementation specifications can support the activity.  Visit https://www.ecfr.gov/current/title-45/subtitle-A/subchapter-D/part-170/subpart-B to learn more.

Where the award funding involves implementing, acquiring, or upgrading health IT for activities by eligible clinicians in ambulatory settings, or hospitals, eligible under Sections 4101, 4102, and 4201 of the HITECH Act, use health IT certified under the ONC Health IT Certification Program if certified technology can support the activity. Visit https://www.healthit.gov/topic/certification-ehrs/certification-health-it to learn more.

Pursuant to the Cybersecurity Act of 2015, Div. N, § 405, Pub. Law 114-113, 6 USC § 1533(d), the HHS Secretary has established a common set of voluntary, consensus-based, and industry-led guidelines, best practices, methodologies, procedures, and processes.

Successful recipients under this NOFO agree that:

When recipients, subrecipients, or third-party entities have:

1. ongoing and consistent access to HHS owned or operated information or operational technology systems; and 
2. receive, maintain, transmit, store, access, exchange, process, or utilize personal identifiable information (PII) or personal health information (PHI) obtained from the awarding HHS agency for the purposes of executing the award.

Recipients shall develop plans and procedures, modeled after the NIST Cybersecurity framework, to protect HHS systems and data. Please refer to NIH Post-Award Monitoring and Reporting for additional information. 

Not Applicable

Consistent with the 2023 NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

4. Reporting

When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement Section 8.4.1 Reporting. To learn more about post-award monitoring and reporting, see the NIH Grants & Funding website, see Post-Award Monitoring and Reporting.

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 Section 8.6 Closeout. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 2 CFR Part 200.301.

Section VII. Agency Contacts

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

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: https://www.era.nih.gov/need-help (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: [email protected] (preferred method of contact)
Telephone: 301-480-7075

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

Adam Haim, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-435-3593
Email: [email protected]

Matthew Rudorfer, M.D.
National Institute of Mental Health (NIMH)
Telephone: 301-443-1111
Email: [email protected]

Nicholas Gaiano, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-827-3420
Email: [email protected]

Tamara Kees
National Institute of Mental Health (NIMH)
Telephone: 301-443-8811
Email: [email protected]

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.

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 2 CFR Part 200.