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.

No late applications will be accepted for this Notice of Funding Opportunity (NOFO).

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

Background

Long considered a disorder of childhood, until relatively recently, treatments for Attention-Deficit Hyperactivity Disorder (ADHD) were exclusively focused on young people. More recently, it has been recognized that what diminishes with age in many cases is not the entire disorder, but its most visible manifestation, for example, the motor hyperactivity that disrupts the classroom. Difficulty with sustained attention, a tendency to lose things, challenges with organization, and other symptoms of the disorder can persist into adulthood, impairing relationships, higher education, and work functioning. Four percent of adults – more than 15 million in the U.S., according to the CDC – are estimated to live with ADHD, compared with 11% in those younger than age 18.

Different rates of diagnosis by sex has been observed in young people, with fewer girls, whose disorder is more likely to be the easily-overlooked inattentive subtype, receiving an ADHD diagnosis than boys, with more obvious motor hyperactivity; this disparity in diagnosis is expected to result in fewer women carrying an ADHD diagnosis into adulthood.

Since the development of amphetamines in the 1930s, stimulants have been the mainstay of ADHD treatment across the lifespan, exhibiting one of the highest effect sizes in mental health and, indeed, in all medicine. With some 30 formulations available in the U.S. market, today, most young people with ADHD receive a member of the methylphenidate drug family as their main pharmacotherapy, whereas most adult ADHD is initially treated with an amphetamine. Given the risk of dependency and abuse, stimulants are classified as tightly controlled Drug Enforcement Administration Schedule II drugs.  Since late 2022, intermittent shortages of stimulant medications, especially mixed amphetamine salts, have been reported in the U.S. and globally. Attributed to manufacturing issues and increased prescribing during 2020-2023, these shortages have affected approximately 10% of individuals taking those compounds, encouraging consideration of nonstimulant alternative treatments for ADHD.

Efforts at replicating the basic mechanism of action of the stimulants – increased availability of the catecholamine neurotransmitters, dopamine and norepinephrine, associated with activation of prefrontal brain areas of cognitive control – has led to the development and adaptation of several non-stimulant medications without abuse potential as alternatives to the stimulants in the treatment of ADHD. The first such compound, the selective norepinephrine reuptake inhibitor, atomoxetine, was approved by the FDA in 2002 for treatment of ADHD, initially in children and adolescents, and later in adults. The centrally-acting alpha-2 adrenergic agonists, clonidine and guanfacine, have FDA approval as ADHD monotherapy or as an adjuctive to stimulants, but only in pediatric patients. The newest non-stimulant to receive FDA approval for the treatment of ADHD is viloxazine, like atomoxetine, a selective norepinephrine reuptake inhibitor, which is indicated for adults as well as children and teens. Lacking FDA approval but bearing some support in the literature, other medications are used off-label for adult ADHD, such as the dopamine and norepinephrine reuptake inhibitor, bupropion. Fewer than 10% of prescriptions for ADHD medications today are for nonstimulants.   

Beyond medications, trigeminal nerve stimulation is a device-based intervention that has received FDA approval for overnight use in the treatment of childhood ADHD.  Psychosocial interventions, most notably the adaptation of cognitive-behavioral therapy (CBT) in individual and group formats, have shown promise in college-aged patients and older adults.

Research Scope and Objectives

This notice of funding opportunity (NOFO) seeks applications for clinical research to adapt, optimize and test empirically-supported non-stimulant pharmacological, device-based, and/or psychosocial interventions to augment or replace stimulant medication in the treatment of ADHD in adults when stimulant monotherapy has proven clinically insufficient, undesirable (e.g., due to adverse effects or concern about tolerance or dependence), or unavailable. Proposed clinical trials may include multiple treatments used in combination or sequentially in a stepped-care design. Any non-stimulant intervention(s) – pharmacological, psychosocial, or device-based, as monotherapy or combined approaches – with evidence from the literature or pilot data, of efficacy in the treatment of adult ADHD, may be incorporated in the proposed treatment plan.

Consistent with the NIMH experimental therapeutics approach, this NOFO supports studies that not only test the intervention effects on outcomes of interest in real world settings, but also inform understanding of the intervention’s mechanisms of action. As such, applications must include an assessment of target engagement that includes (1) specified target mechanisms associated with the intervention, (2) measurement plans designed to assess the target mechanisms and mental health outcomes, and (3) analytic plans designed to evaluate both the intervention-induced changes in the target mechanisms and the associations between changes in the target mechanisms and the intervention outcomes.  Any identified putative target should be evidence-based. Although formal pilot testing is not required, ideally, all steps in submitted applications would have been successfully undertaken by applicants with similar patients in a similar context, ranging from clinical assessment to treatment delivery to outcome measures, and appropriate control groups, conditions, and interventions must be defined. Valid and reliable instruments should be used to assess outcome measures, including changes in symptoms and functioning.

In line with current clinical practice, participants in clinical trials designed in response to this NOFO must meet full DSM-5-TR criteria for ADHD, either inattentive or combined subtype. Participants must be age 18 years and older. There is no upper age limit and younger participants may be included as a control group if scientifically justified. Exploration of age as a potential moderator of response should be considered. Appropriate confirmation of symptom onset prior to age 12 should be part of the screening process. Efforts at refining diagnosis, for example with experimental aims studying putative biomarkers or Research Domain Criteria (RDoC) parameters, are welcome as adjuncts, but not replacements for DSM-5-TR criteria. Especially in older adults, adequate differential diagnosis should rule out the presence of dementia, medication effects, or other disinhibition syndromes that might overlap with adult ADHD. The presence of comorbid conditions, including other mental health or substance use disorders, is acceptable. Consistent with effectiveness clinical trial principles, comorbid mental or physical health or substance use disorders may be present, provided that they are not the main focus of clinical attention, and are not mimicking the symptoms of true ADHD, and are expected not to interfere with the response of ADHD symptoms to treatment.

Applications submitted in response to this NOFO should consider individual, social, and/or environmental challenges associated with ADHD in adults, and their impact on diagnosis, functioning, and treatment, including their role as possible moderators of treatment response. Consistent with NIMH’s commitment to supporting research that reduces mental health disparities and advances health, this NOFO strongly encourages applicants to include plans to address and/or evaluate factors related to disparities or differences in outcomes and co-existing disorders and include strategies to optimize interventions in under-resourced settings and among populations that experience health disparities.  NIMH also encourages approaches that include input from key stakeholders in the research process in a manner that helps to ensure that study results will have utility for end users. 

Proposed clinical trials research should fit an effectiveness model designed to test the therapeutic value of interventions for which there is already evidence of efficacy either in adults or children/adolescents with ADHD, for use in community and practice settings. Consistent with an effectiveness approach, NIMH encourages research studies that take place in generalizable community practice settings (i.e., outside academic laboratories or research clinics), including mental health specialty care (e.g., community mental health clinics), primary care, college mental health clinics, and other community settings where individuals receive care.  Proposed effectiveness clinical trials should employ a deployment-focused design that systematically assesses and incorporates the perspectives of community and practice partners (e.g., consumers, providers, administrators, payers) and setting characteristics (e.g., workforce capacity; clinical workflows). This approach helps ensure that the resultant interventions are feasible and scalable and that the research study results have utility for end-users.

Representative research studies that would be responsive to this announcement include:

• A clinical trial to test the effectiveness of augmenting a partially effective stimulant medication with the addition of a nonstimulant medication, a psychosocial intervention, or a device-based treatment.
• A clinical trial to test the effectiveness of beginning treatment with a nonstimulant approach, e.g., in situations where the use of a stimulant is deemed undesirable.
• A clinical trial aimed at personalizing treatment of adults with ADHD plus substance use disorders or other specific comorbidities.

Potential Exploratory Research Goals:

• Assessment of potential moderators of treatment response, including age and other demographic and clinical characteristics. 
• Optimal approaches to sustaining short-term clinical response during maintenance treatment.

Contacting a Program Officer: Potential applicants are strongly encouraged to contact the Scientific/Research contacts in advance to discuss the potential clinical practice/public health impact of the proposed pilot investigation, as well as concordance with current NIMH priorities.

Additional Considerations

Statistical analysis. A statistical analysis plan and corresponding power analysis for examining whether intervention-induced changes in the presumed mechanism(s) of action are associated with changes in the outcomes (i.e., mediation) is required as central to the experimental therapeutics approach. 

Suicide-Related Outcomes: 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). 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 to reduce injury associated with suicide attempts and deaths. Accordingly, where feasible and appropriate, NIMH encourages effectiveness research that includes 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-23-100 and PhenX Toolkit | National Institutes of Health, for example constructs and corresponding assessment strategies).

NIMH Strategic Plan: 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.

Applications Not Responsive to this NOFO.

The following types of studies are not responsive to this NOFO. Applications proposing such studies will be considered non-responsive and will not be reviewed or considered for funding.

• Applications that propose an examination of intervention effectiveness without also including an assessment of target engagement that includes the following components: (1) description of specified target mechanisms, (2) measurement plans designed to assess the target mechanisms and clinical outcomes, and (3) analytic plans designed to evaluate both the intervention-induced changes in the target mechanisms and the associations between changes in the target mechanisms and the intervention outcomes.
• Applications that include participants younger than age 18.  
• Applications that fail to meet full DSM-5-TR criteria for ADHD.
• Applications that do not assess for the presence of comorbid conditions and account for their presence in the planned treatment protocol.
• 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).

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). 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.

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 - Includes all types

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

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• 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)

Foreign Organizations/ International Collaborations

NIH will no longer issue awards (new, renewal, or non-competing continuation) to domestic or foreign entities that involve foreign subawards/subcontracts. All NIH-funded research involving foreign subawards/subcontracts must be submitted in response to a NOFO that is specifically designated for funded international collaborations. This new requirement was effective, May 1, 2025.

Applications involving foreign subawards/subcontracts submitted in response to this NOFO will be deemed noncompliant and will not be considered for funding. This policy applies to all monetary international collaborations resulting in foreign subawards/subcontracts, however, it does not preclude unfunded international collaborations or foreign components, funding for foreign consultants, or procurement of unique equipment or supplies from foreign vendors.

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 not 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.

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.

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.

SF424(R&R) Senior/Key Person Profile

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

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

Factor 1. Importance of the Research 

Significance:

• Justify the practical benefit of the intervention approach in terms of the estimated hypothesized effect size (in terms of key outcomes, such as clinical benefit, safety/tolerability, value, and efficiency, or scalability), compared with already available approaches. Address the potential benefit 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 delivery approach is scalable and could be disseminated into practice (if the proposed research is successful), given typically available resources (e.g., trained, skilled providers), typical service and financing structures, and typical service use patterns.
• As appropriate, address the degree to which the proposed intervention addresses health disparities in access, ongoing engagement, and/or clinical or functional outcomes.  

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 research study’s potential for yielding practice-relevant information.
• As relevant, describe how applications of technology or other innovative approaches are leveraged to facilitate the conduct of the research project (e.g., participant identification, data collection) and/or to increase the reach, efficiency, or effectiveness of the intervention strategy that is being evaluated.
• Discuss the creativity and completeness of the research plan in terms of treatment sequencing or combination. Address the likelihood that post-acute treatments will be necessary to maintain improvement and/or prevent relapse.

Factor 2. Rigor and Feasibility 

Approach: 

• Proposed clinical trials may include multiple treatments used in combination or sequentially in a stepped-care design. Any non-stimulant intervention(s) – pharmacological, psychosocial, or device-based, as monotherapy or combined approaches – with evidence from the literature or pilot data, of efficacy in the treatment of adult ADHD, may be incorporated in the proposed treatment plan.
• Describe and justify in detail the selection of medications, including dose and delivery method, whether alone or in combination with other drugs or psychosocial interventions with particular attention to prevention or minimization of serious adverse effects where medication use in adults is off-label and lacks existing adequate safety data in this population. For stepped-care approaches, include specific decision-point criteria for proceeding through multiple treatment phases. Use of blinded raters and standardized rating scales to assess clinical outcomes and functioning, as well as adverse effects, including suicidal thoughts and behaviors, is expected. Justify technology-assisted measurements, using, for example, actigraphy or wearable devices, is acceptable if employed. Where appropriate, include analysis of moderators (including comorbidities and ADHD subtypes) of treatment effect that can inform personalized treatment. 
• Detail the plan to address whether the intervention engages one or more mechanisms of action. Include the following: (1) a conceptual framework that clearly identifies the mechanism(s) of action and the empirical evidence linking the mechanisms to the primary outcomes of interest (i.e., clinical symptoms, functional deficits, or patient- or provider-level behaviors that the intervention seeks to improve; (2) plans for assessing engagement of the mechanism(s), including the specific measures, the assessment schedule, and evidence regarding the validity and feasibility of the proposed measures in the effectiveness context; and (3) a statistical analysis plan and corresponding power calculations for data analyses that will be used to examine whether intervention-induced changes in the mechanism(s) are associated with changes in the outcomes (i.e., mediation). In the case of multi-component interventions, specify the conceptual basis, assessment plan, and analytic strategy, as detailed above, for the mechanisms corresponding to each intervention component, as appropriate in the effectiveness context.
• The Research Strategy section of the application must include a description of this planned analytic approach and power analysis. Full details of the proposed statistical methods must be included in the PHS Human Subjects and Clinical Trials form.   
• When appropriate, 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 for use in community practice settings.
• Describe design features that will be incorporated to help ensure that the approach is feasible, scalable, and robust against implementation drift in the practice setting (e.g., using technology as scaffolding or expert consultation via existing resources/ other sustainable means to support delivery).
• Describe plans for deployment-focused testing that systematically assesses and incorporates the perspective of community and practice partners (e.g., consumers, providers, administrators, payers) and setting characteristics (e.g., workforce capacity; clinical workflows) to help ensure that the resultant approach is feasible and scalable, and that the research results have utility for end-users.
• Incorporate outcome measures that are validated and are feasible in the effectiveness context, including stakeholder-relevant outcomes (e.g., functioning, health services use).
• Detail plans to assess functional and/or clinical outcomes, using valid and reliable rating scales; use of blinded raters is recommended.
• Describe plans to examine the reduction of health disparities in access to or ongoing engagement in treatment, if relevant.
• Examine the role of age and comorbid conditions among planned participants as examples of potential moderators of clinical response to treatment. 
• As relevant, address how the trial contributes to advancing the personalization of mental health care and describe the collection of variables 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.
• For studies that involve the assessment of patient-level outcomes, describe 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) for constructs and corresponding assessment strategies; see NIMH's expectations for common data elements: NIMH Data Archive - NDA Home Page (nih.gov), as appropriate, or provide a strong rationale for excluding such measures if they are not included. Accordingly, 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. 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, e.g., due to unique issues related to participant burden or safety/monitoring concerns, the application should provide an appropriate justification for excluding these assessments.
• Where appropriate, for example, in the case of device-based interventions, it is expected that applicants will consult with FDA staff ahead of grant application submission, including details and recommendations of the FDA consultation in the application. Where safety-related issues in the off-label use of specific medications in adults, e.g., guanfacine, have been raised, consultation with FDA or other drug safety experts is recommended to ensure optimization of the benefit-risk ratio in all proposed clinical trials. Intervention features specifically designed to prevent threats to implementation fidelity, enhance scalability, and promote sustained implementation within the target setting are also encouraged (e.g., self-administered content, provider training, fidelity supports, telehealth consultation). Online-only interventions may be appropriate when existing infrastructure is available to support ongoing intervention maintenance and delivery outside the research enterprise.  Align studies that incorporate technology into the intervention design with NOT-MH-18-031: NIMH High-Priority Areas for Research on Digital Health Technology to Advance Assessment, Detection, Prevention, Treatment, and Delivery of Services for Mental Health Conditions.
• For applications proposing the study of pharmacologic or device-based interventions to be used in the absence of FDA-approved labeling for an indication of ADHD in adults, i.e., “off-label”, include a detailed Data and Safety Monitoring Plan (DSMP), with careful attention to dosing and observation for adverse effects, aimed at maximizing participant safety. 

Factor 3. Expertise and Resources 

Environment: 

• Detail the proposed treatment settings and facilities, including community-based mental health specialty care, and their sufficiency to evaluate and treat complex cases of adult ADHD with co-occurring mental/physical health and/or substance use disorders, including complications arising during clinical trials (e.g., requiring emergency intervention or hospitalization). 

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. 

• 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 broad, 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 intervention manual and assessment protocols, including fidelity measures/procedures, where applicable; (3) enrollment benchmarks (cumulative target enrollment figures during the life of funded applications, forming the basis of the NIMH Recruitment Milestone Reporting system, will be requested for well-scoring proposals following review); (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 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 applicable. If more than one set of Intervention Manual/Materials are used, they should be combined in this attachment. Applicants must use “Intervention Manual/Materials” to name these other attachments files. 

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 and NOT-MH-25-055.

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, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

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

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.

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 Center for Scientific Review, in accordance with NIH peer review policies and practices, 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.

Appeals of initial peer review will not be accepted for applications submitted in response to this NOFO.

Applications will be assigned 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 National Advisory Mental Health Council. 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.

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. 

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]

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

Center for Scientific Review (CSR)
Email: [email protected]

Christine Clarkson
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.