Department of Health
and Human Services (HHS)
and Human Services (HHS)
EXPIRED
National Institutes of Health (NIH)
National Institute of Mental Health (NIMH)
See Notices of Special Interest associated with this funding opportunity
NIMH solicits clinical trial applications through a series of Funding Opportunity Announcements (FOAs) that cover the intervention development pipeline, from first-inhuman, early testing of new interventions, confirmatory efficacy trials, through to effectiveness trials. The purpose of this FOA is to encourage pilot research developing and testing innovative psychosocial intervention approaches in which the target and/or intervention strategy is novel. Consistent with NIMH’s experimental therapeutics approach, this FOA is intended to speed the translation of emergent research on mechanisms and processes underlying mental disorders into promising novel psychosocial preventative or therapeutic interventions. Targets may include, but are not limited to, potentially modifiable behavioral, cognitive, affective and/or interpersonal factors or processes, neural circuits or neural activity subserving specific behaviors or cognitive processes, and/or other neurobiological mechanisms. Novel psychosocial interventions may be standalone interventions or augmentations to efficacious interventions for which there is an empirical rationale by which the augmentation (and corresponding target) is expected to substantially enhance outcomes. Support will be provided for up to two years (R61 phase) for preliminary milestone-driven testing of a novel intervention's impact on a target process or mechanism associated mental disorder risk, causation, or maintenance (target engagement). Up to 3 years of additional support (R33 phase) will be provided for studies with findings that meet the "go/no-go" milestones embedded in the R61 phase. The R33 phase is intended to support the replication of target engagement and to test whether engaging the intervention target/mechanism mediates changes in clinical outcomes. Ultimately, trials must be designed so that results, whether positive or negative, will provide information of high scientific utility and will support "go/no-go" decisions about further development and/or testing of the intervention. Applicants pursuing other stages of the clinical trial pipeline should consider one of the companion FOAs listed above.
30 days prior to the application due date
Application Due Dates | Review and Award Cycles | ||||
|---|---|---|---|---|---|
| New | Renewal / Resubmission / Revision (as allowed) | AIDS | Scientific Merit Review | Advisory Council Review | Earliest Start Date |
| June 15, 2021 | June 15, 2021 | Not Applicable | October 2021 | January 2022 | March 2022 |
| October 15, 2021 | October 15, 2021 | Not Applicable | February 2022 | May 2022 | July 2022 |
| February 15, 2022 | February 15, 2022 | Not Applicable | June 2022 | October 2022 | December 2022 |
| June 15, 2022 | June 15, 2022 | Not Applicable | October 2022 | January 2023 | March 2023 |
| October 14, 2022 | October 14, 2022 | Not Applicable | February 2023 | May 2023 | July 2023 |
| February 15, 2023 | February 15, 2023 | Not Applicable | June 2023 | October 2023 | December 2023 |
| June 15, 2023 | June 15, 2023 | Not Applicable | October 2023 | January 2024 | March 2024 |
| October 17, 2023 | October 17, 2023 | Not Applicable | February 2024 | May 2024 | July 2024 |
| February 15, 2024 | February 15, 2024 | Not Applicable | June 2024 | October 2024 | December 2024 |
| June 15, 2024 | June 15, 2024 | Not Applicable | October 2024 | January 2025 | March 2025 |
| October 15, 2024 | October 15, 2024 | Not Applicable | February 2025 | May 2025 | July 2025 |
All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).
Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.
New Date October 16, 2024 per issuance of NOT-MH-24-155. (Original Expiration Date: February 16, 2024 )
Not Applicable
It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from NIH Guide for Grants and Contracts).
Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.
Applications that do not comply with these instructions may be delayed or not accepted for review.
There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.
Research Objectives
The mission of NIMH is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery and cure. The purpose of this Funding Opportunity Announcement (FOA) is to encourage Phased Innovation (R61/R33) grant applications that focus on psychosocial intervention development consistent with the NIMH emphasis on the experimental therapeutic approach for the treatment and prevention of mental disorders in adults and children. In this approach, clinical trials should be designed so that even negative results will provide information to guide further intervention development efforts. The focus of this FOA is on the early phases of intervention development, during which emergent research on mechanisms and processes underlying mental disorders is translated into clinical hypotheses and novel interventions are tested in a clinical population or population at-risk.
This FOA supports the development and testing of innovative psychosocial intervention approaches where the target and/or the intervention strategy is novel. Targets may include, but are not limited to, potentially modifiable behavioral, cognitive, affective and/or interpersonal factors or processes, neural circuits or neural activity subserving specific behaviors or cognitive processes, and/or other neurobiological mechanisms associated with risk for, causation of, or maintenance of a mental disorder. Eligible psychosocial intervention strategies might include in-person or technology-assisted delivery, provided the target and/or the intervention strategy is novel. This FOA supports the development and testing of novel psychosocial interventions, as defined above, as monotherapies or as augmentations to a standard treatment (which may be psychosocial, pharmacological, neuromodulation, biologic, or other somatic modality). Studies must include an examination of a defined intervention target/mechanism based on empirical evidence of disease processes or mechanisms that confer risk, causation, or maintenance of a disorder, and a clear hypothesis about how an intervention directed at changing the target/mechanism can lead to clinical benefit in persons with or at risk for mental disorders.
This FOA provides support for up to two years (R61 phase) for milestone-driven testing, refinement, replication, and/or validation of the intervention's impact on an empirically-supported, measurable intervention target/mechanism of disorder (i.e., the intervention's capacity for target engagement), and the possibility (contingent on meeting R61 "go/no-go" milestones) of up to 3 additional years of support (R33 phase) for studies to confirm target engagement in a larger sample, assess the relationship between target engagement and changes in measures of clinical benefit, and examine preliminary signal of efficacy. Results from the R33 phase should provide evidence to determine whether further development of the intervention is warranted, and if it is, to inform the design of a subsequent confirmatory efficacy trial. This FOA encourages highly innovative projects, with the recognition that such projects may entail a greater failure rate (e.g., failure to reach pre-specified milestones for continued development). NIMH values this early, efficient, and objective testing of an intervention's ability to alter a well-defined and objectively measured target/mechanism to help inform decisions about which interventions should be further developed. This FOA uses a phased innovation approach (R61/R33) to manage the risk of obtaining inconclusive or negative results in innovative therapeutic trials by requiring a demonstration of the intervention's effect on a target/mechanism that is associated with risk, causation, or maintenance of symptom expression or related impairment before moving into the R33 phase of the award.
Exploring potential synergies of combination therapies is of interest to the NIMH. For the purposes of this funding opportunity, a novel intervention should be paired with a previously established intervention. For drugs and devices, an established intervention is defined through FDA approval/clearance of the intervention for a specific disorder and for specific dosing. Applicants who are uncertain whether their intervention of interest has a sufficient evidence base to be considered an empirically-supported treatment should contact NIMH scientific program staff for discussion and clarification. For applications that test a combination of interventions in different modalities, applicants should apply to the relevant FOAon the basis of the novel intervention: an application to test a novel drug/device paired with an established psychosocial intervention should be submitted under the drug/device FOA while this funding opportunity announcement is appropriate for applications to test novel psychosocial interventions combined with established drug/device interventions. For all combination therapies, applicants should follow all other guidance/requirements of the FOA they are applying to including instructions for defining measures of target engagement and specifying how various doses/combinations will be tested. Applications must include clear and careful description of the combination of therapies and how the multitude of combination parameters will be assessed.
Information about the mission, strategic plan, and research interests of the NIMH can be found at the NIMH website. Applicants are also strongly encouraged to review the information on the NIMH clinical trials website.
This FOA is not intended to support research on novel (i.e., not established) pharmacological interventions or devices administering direct brain stimulation, alone or in combination with other treatment modalities. For a detailed description of the appropriate FOAs to support these areas of research, see a list of other NIMH clinical trials FOAs in related announcements and reference the Companion Funding Opportunities listed at the beginning of this FOA.
NIMH Priorities for Developing and Pilot-testing Interventions
NIMH requires applicants follow an experimental therapeutic approach to develop and test interventions. Clinical trials following this approach should explicitly address whether the intervention engages the target/mechanism presumed to underlie the intervention effects (target engagement).
Targets
The term "target" refers to a factor that an intervention intends to modify, based on a hypothesis that modification of that factor will result in improvement of symptoms, behavior, or functional outcomes, or lower risk for the onset of mental disorders. Targets/mechanisms can range from molecular, neural or neurophysiological systems to cognitive, behavioral, or emotional processes, to interpersonal/social group processes or contextual factors depending on the nature of the intervention and appropriate analyses. A target may be a disease mechanism, a factor related to a disease mechanism, or a factor that confers significant risk. An appropriate target is an intervening variable that has either been demonstrated to be associated with risk for a mental disorder, with a clinical symptom or functional deficit, or is hypothesized (based on empirical evidence) to impact the biological or psychological pathway through which a clinical or functional benefit would be expected to occur. Thus it is hypothesized that change in the target will mediate the intervention's clinical or functional impact. While exposure to broad, societal/environmental circumstances might be used to identify at-risk populations, NIMH will not accept applications that propose to directly target or intervene on broad, societal adverse exposures, such as strategies to reduce poverty or violence. "Target engagement" refers to verification that the intervention has had the predicted effect on the target/mechanism. In the experimental therapeutic approach, once target engagement is demonstrated, measures of target engagement are then related to clinical outcomes to begin to test the hypothesis that modification of the target/mechanism is sufficient to alter the clinical outcome under study.
Valid and reliable measures of change in the target/mechanism will provide useful information about the potential for further development of the intervention, whether or not target engagement is achieved. 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. NIMH encourages hypotheses and measures of potential mechanisms across molecular, biological, cognitive, psychological, social, affective, and/or behavioral domains of analysis that might account for change in the target and clinical outcome. The type of measure(s) will depend on the conceptual model, the nature of the target/mechanism, and the availability of valid, reliable measures of change in the target/mechanism. Measures might include self-reports, lab-based neurocognitive tasks, experimental psychopathological or other behavioral measures, psychophysiological measures, neuroimaging or other brain-based measures, sensor-based or other observational measures of interpersonal processes or contextual/environmental factors, or valid proxy measures as alternatives. Specifically encouraged are empirically validated measures of the construct that extend beyond self-report and other subjective measures, where possible.
Studies proposed under this FOA must include a novel target/mechanism or a novel intervention strategy to engage a known target/mechanism. Studies focused on novel strategies for assessing known targets or on using novel levels of assessment to measure engagement of a known target via an established intervention are not supported under this FOA. Applications adding a new level of analysis to assess or better understand known mechanisms of an established intervention should submit mechanistic clinical trial applications under the parent R01 announcement; (see Support for Clinical Trials for more information about NIMH’s use of parent announcements for mechanistic trials). Tests of multiple targets/mechanisms are allowed when appropriate. Each proposed novel target/mechanism must be supported by an empirically-supported rationale, a testable hypothesis, and valid and reliable measures of change. Applications to evaluate more than one target should define their go/no-go criteria clearly, define milestones accordingly, and justify the decision to make proceeding to the R33 phase contingent on the specified effect of the treatment on them. Applicants are strongly encouraged to review the information on the NIMH website focused on clinical trials.
The clinical endpoint or outcome will vary according to 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 psychological 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 rates of or delayed onset of the psychological disorder/condition (i.e., the clinical endpoint). Alternative conceptualizations might propose proximal targets/mechanisms that are intervening variables purported to be instrumental in reducing the risk state itself (i.e., with the clinical endpoint defined in terms of a reduction of risk).
Intervention Approaches
The primary purpose of this FOA is to support the development of novel intervention approaches that involve novel strategies and/or novel targets. Novel intervention approaches must be theoretically supported and hypothesis-driven with an emphasis on why the novel approach is expected to substantially improve outcomes via engagement of the target/mechanism. NIMH is particularly interested in the development of novel 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. For example, NIMH Research Domain Criteria (RDoC) constructs may inform mechanism-based hypotheses and the selection of interventions, outcome measures and clinical subjects. Intervention targets related to RDoC constructs are of interest for this FOA, but other, non-RDoC constructs may be suitable as well, especially if they maximize the probability that subjects share the same mechanism of disorder.
While the principal purpose of this FOA is to support the development of novel strategies, adaptations of efficacious interventions may be supported under specific conditions. Adaptations of existing interventions might be supported if they are based on empirical evidence suggesting that efficacy or specificity of the intervention could be substantially improved for a defined subpopulation of patients (e.g., non-responders) by engaging a different intervention target/mechanism or utilizing a different approach to the known target/mechanism. Adaptations of efficacious interventions may also be supported it they are based on evidence that the intervention may improve outcomes in a new subpopulation (e.g., children) or disorder by engaging a target that has not previously been known to be critical or considered feasible to address in that subpopulation or disorder.
It is important to note that while this FOA will support pilot testing of novel technology-assisted intervention approaches, it is not intended to support the translation of existing efficacious treatments into technology-based applications (e.g., mHealth). In addition, while exposure to broad, societal/environmental circumstances might be used to identify at-risk populations, NIMH will not accept applications that propose to directly target or intervene on broad, societal adverse exposures, such as strategies to reduce poverty or violence.
The R61 Phase
The R61 phase must include a test of whether an objective measure can be used to assess intervention effects on the target/mechanism (i.e., target engagement). Other specific activities and milestones appropriate for the R61 phase will depend on the type of intervention under study and its stage of development. Generally, R61 activities and milestones include: 1) operational definition and specification of objective measures of the target/mechanism, including establishing that the proposed measures are sensitive to intervention-induced change; 2) optimization of the intervention protocol to alter the target and standardize the intervention, 3) demonstration of target engagement with the proposed treatment parameters (such as intensity, duration, frequency, i.e., "dose"); 4) demonstration that the intervention, with the proposed treatment parameters, can be administered in the select human population with adequate safety, tolerability and acceptability; 5) initial manual or protocol development along with development of fidelity scales; and 6) demonstration of feasibility of recruitment and retention. These activities may or may not necessitate the inclusion of a control condition(s) or tests of a range of doses of the intervention. These methodological choices depend on the specific features of the research protocol such as the nature of the intervention and the target, participant characteristics, preliminary data, or other factors. Applicants should provide rigorous justification for their decision-making regarding the proposed experimental protocol.
Applications using only the R61 mechanism or only the R33 mechanism will not be accepted under this FOA. Applicants who already have sufficient preliminary data to progress to the R33 phase should apply directly to PAR-21-134 "Development of Psychosocial Therapeutic and Preventive Interventions for Mental Disorders (R33)".
The R33 Phase
Funding for the R33 phase is contingent on successfully meeting the milestones in the R61 phase (see Section VI. Award Administration Information, 1. Award Notices for further information).
The purpose of the R33 phase is to replicate target engagement demonstrated in the R61 study and to determine whether engaging the target affects clinical outcome(s) of interest. Studies in the R33 phase should not be powered as definitive tests of clinical efficacy, but rather should determine the magnitude of the relationship between changes in the targeted mechanism(s) and changes in clinical and/or functional outcomes in a clinical or at-risk population. In addition to the primary aim of linking target engagement and clinical benefit, secondary aims in the R33 phase may include: 1) intervention refinement and standardization (e.g., further manual or protocol development along with fidelity scales); 2) further testing of the feasibility, safety, and acceptability of the intervention; 3) preliminary testing of the association between a change in the target/mechanism and clinical benefit; 4) evaluating the feasibility of recruitment, randomization (if appropriate), retention, assessments, and reporting of adverse events; and 5) developing measures of functional target engagement and of clinical benefit feasible for use in larger efficacy and effectiveness trials. The specific activities appropriate for the R33 phase will depend on the type of intervention under study, and the stage of the study proposed. The dosage/delivery parameters (e.g., number, frequency, and duration of sessions) of the intervention in the R33 phase should be justified using outcomes from the R61 phase, other empirical data, and the conceptual model. The results of the R33 phase should inform a decision about whether the intervention shows the potential for improving clinical outcomes, including evidence of safety, acceptability and feasibility, and a preliminary signal of efficacy, and regarding the strength of the association between target engagement and clinical benefit. The study should also inform the design of a subsequent confirmatory efficacy trial, if indicated.
Examples of high priority studies under this FOA include those that:
Applications Not Responsive to this FOA
Studies that are not responsive to this FOA and will not be reviewed include the following:
Applicants are strongly encouraged to consult with NIMH staff when developing plans for an application (see Agency Contacts, Section VII). This early contact will provide an opportunity to clarify NIMH policies and guidelines and discuss whether the proposed project is consistent with NIMH program priorities.
Effective prevention and treatment of mental disorders 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. Accordingly, where feasible and appropriate, applicants are strongly encouraged to include assessment of suicidal behavior in clinical trials in response to this FOA using strategies that can facilitate integration and sharing of data (e.g., see NOT-MH-15-009 and https://www.phenxtoolkit.org/ for example constructs and corresponding assessment strategies).
The number of trial sites should be limited to minimize variability of the data.
PD(s)/PI(s)s submitting applications consistent with the experimental therapeutic approach, but whose scope does not fall within that of the current FOA are encouraged to contact Scientific/Research contacts or go to NIMH's Clinical Trials for Researchers page for further information.
Other Resources
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.
Applications with data collection plans that involve multiple respondent groups (e.g., clients/patients, therapists/providers, supervisors, administrators) should address provisions for human subject protections and consenting procedures for all participant groups, accordingly.
The NIMH is committed to enhancing the reliability of NIMH-supported research through rigorous study design and reporting (NOT-MH-14-004).
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 Protection of Human Subjects section and data and safety monitoring plans should reflect the policies and guidance in this notice. Plans for the protection of research subjects and data and safety monitoring will be reviewed by the NIMH for consistency with NIMH and NIH policies and federal regulations.
See Section VIII. Other Information for award authorities and regulations.
Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.
Resubmission from RFA-MH-18-704 and PAR-21-135
Revision RFA-MH-16-406, RFA-MH-17-604, RFA-MH-18-704, and PAR-21-135
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.
Required: Only accepting applications that propose clinical trial(s).
Need help determining whether you are doing a clinical trial?
NIMH intends to commit a total of $27 million for FY 2021 to fund this FOA and the companion FOAs listed in Part 1. Overview Information .
Application budgets are not limited but need to reflect the actual needs of the proposed project.
The scope of the proposed project should determine the project period. The maximum period of the combined R61 and R33 phases is 5 years, with up to 2 years for the R61 phase and up to 3 years for the R33 phase. Applications with a project period less than 5 years are encouraged where feasible.
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.
Higher Education Institutions
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
Nonprofits Other Than Institutions of Higher Education
For-Profit Organizations
Local Governments
Federal Governments
Other
Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.
Applicant organizations
Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.
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 his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
Number of Applications
Applicant organizations may submit more than one application, provided that each application is scientifically distinct.
The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:
The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.
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:
The letter of intent should be sent to:
Email: nimhpeerreview@mail.nih.gov
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.
Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing (DMS) Plan will be attached in the Other Plan(s) attachment in FORMS-H and subsequent application forms packages. For due dates on or before January 24, 2023, the Data Sharing Plan and Genomic Data Sharing Plan GDS) will continue to be attached in the Resource Sharing Plan attachment in FORMS-G application forms packages.
The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
R&R Budget
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
Other Plan(s):
Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H and subsequent application forms packages. For due dates on or before January 24, 2023, the Data Sharing Plan and Genomic Data Sharing Plan GDS) will continue to be attached in the Resource Sharing Plan attachment in FORMS-G application forms packages.
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.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
Specific Aims: A single Specific Aims page should be provided which includes headers titled "R61 Specific Aims" and "R33 Specific Aims" and includes a statement of the specific objectives of the research effort in the two phases of this project. Concisely describe the exploratory clinical trial(s) as well as how the proposed intervention could fill an important unmet need for those living with or at risk of developing mental illnesses.
Research Strategy: Applicants should include the following sections as part of the Research Strategy. Applications should not duplicate information provided in the attachment described in the PHS Human Subjects Clinical Trial Information form, but may reference it as needed.
Significance: In this section of the Research Strategy, the application should:
Innovation: In this section of the Research Strategy, the application should:
Approach: In this section of the Research Strategy, the application should describe the elements of the experimental therapeutics approach to be used in the investigation. The elements critical to this approach are described in the specific requirements below:
Milestones (Go/No-Go Criteria): Applications must provide this information in a section indicated by the heading "Milestones (Go/No-Go Criteria)".
Adequate functional target engagement must be a key criterion of a "go/no-go" decision to move from the R61 to R33 phase. This section should include a clear description of the R61 phase milestones that, if met, will justify taking the proposed intervention into the R33 pilot study. The milestones proposed in the application must be objective, quantifiable, and scientifically justified to allow program staff to assess progress in the R61 phase of an award. The milestones must specify the measures by which they will evaluate whether the intervention engages and alters the target/mechanism as hypothesized. If more than one target/mechanism is proposed, the milestones must be specific about whether target engagement is required of each to justify taking the proposed intervention into the R33 pilot study, and the applicant must justify the decision. Applicants must justify whether or not to make their go/no-go decision contingent on all the proposed targets or some combination of target measures. Milestones should not merely reflect progress in terms of accomplishing tasks or in terms of the study timeline (e.g., meeting target enrollment). Milestones must include a description of specific, quantitative threshold values for any measures proposed for go/no-go decision-making.
Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.
The following modifications also apply:
All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan
To advance the goal of advancing research through widespread data sharing among researchers, investigators funded under this FOA are expected to share those data via the National Data Archive (NDA; see NOT-MH-19-033). Established by the NIH, NDA is a secure informatics platform for scientific collaboration and data-sharing that enables the effective communication of detailed research data, tools, and supporting documentation. NDA links data across research projects through its Global Unique Identifier (GUID) and Data Dictionary technology. Investigators funded under this FOA are expected to use these technologies to submit data to NDA.
To accomplish this objective, it will be important to formulate a) an enrollment strategy that will obtain the information necessary to generate a GUID for each participant, and b) a budget strategy that will cover the costs of data submission. The NDA web site provides two tools to help investigators develop appropriate strategies: 1) the NDA Data Submission Cost Model which offers a customizable Excel worksheet that includes tasks and hours for the Program Director/Principal Investigator and Data Manager to budget for data sharing; and 2) plain language text to be considered in your informed consent available from the NDA's Data Contribution page. Investigators are expected to certify the quality of all data generated by grants funded under this FOA prior to submission to NDA and review their data for accuracy after submission. Submission of descriptive/raw data is expected semi-annually (every January 15 and July 15); submission of all other data is expected at the time of publication, or prior to the end of the grant, whichever occurs first (see NDA Sharing Regimen for more information); Investigators are expected to share results, positive and negative, specific to the cohorts and outcome measures studied. The NDA Data Sharing Plan is available for review on the NDA website. NDA staff will work with investigators to help them submit data types not yet defined in the NDA Data Dictionary.
When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:
If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.
Study Record: PHS Human Subjects and Clinical Trials Information
All instructions in the SF424 (R&R) Application Guide must be followed.
Delayed Onset Study
Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the SF424 (R&R) Application Guide must be followed.
Section 2 - Study Population Characteristics
2.5 Recruitment and Retention Plan
Applications must provide a clear description of:
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; (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
Applicants must upload the attachments for Intervention Manual/Materials as separate files, as applicable. Applicants must use the "Intervention Manual/Materials" to name these other attachments files. As appropriate, this may include screenshots of mobile interventions, technological specifications, training manuals or treatment algorithms.
All instructions in the SF424 (R&R) Application Guide must be followed.
Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.
See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov.
Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.
Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.
Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.
Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.
This initiative is not subject to intergovernmental review.
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.
Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.
Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.
For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.
Important reminders:
All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.
The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.
See more tips for avoiding common errors.
Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by 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.
NIMH encourages 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 (See NOT-MH-20-067: Notice Announcing the National Institute of Mental Health (NIMH) Expectations for Collection of Common Data Elements).
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.
Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.
Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) as part of the Resource Sharing Plan will not be evaluated at time of review.
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.
For this particular announcement, note the following:
The R61/R33 phased innovation grant supports investigation of novel scientific ideas or new interventions, model systems, tools, or technologies that have the potential for significant impact on biomedical or behavioral and social sciences research. An R61/R33 grant application need not have preliminary data and information or extensive background material; however, they may be included if available. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Accordingly, reviewers will focus their evaluation on the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Reviewers will assign a single impact score for the entire application, which includes both the R61 and R33 phases. Peer reviewers will address the strengths and weaknesses of each phase of the award in their review as both phases may not garner the same degree of enthusiasm.
A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.
Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).
Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.
Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?
Could the intervention fill an important unmet mental health need for those living with a mental disorder, or substantially (not incrementally) improve clinical care? Does the proposed project have the potential to test and potentially refute any hypotheses around the proposed mechanism(s) of action?
Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?
Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?
Does the evidence provided indicate that the researchers can function as a team? Does the research team have demonstrated clinical trials expertise and a track record in successfully conducting early clinical trials (e.g., subject recruitment and retention rates, reporting in clinicaltrials.gov, publications, etc.)? Does the investigative team have sufficient methodological and statistical expertise in the study and measurement of intervention change mechanisms (e.g., handling repeated measures designs, missing data, effect size)? Does the investigative team include sufficient expertise in the measurement methods proposed?
With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?
Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?
Does the application introduce a novel, well-specified target/mechanism and/or a novel approach to engaging an established target/mechanism? Is the proposed intervention derived from a recent basic, behavioral, cognitive, or neuroscientific finding or translating an established finding in a novel way (e.g., innovative methods or translation to a developmental framework)? Where applicable, if the proposed project concerns an adaptation or extension of an intervention with established efficacy, is the rationale based on empirical evidence that efficacy or specificity could be substantially improved for a defined subpopulation of patients with a different intervention target/mechanism or different approach to the known target/mechanism?
Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?
Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?
If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?
Does the application adequately address the following, if applicable
Study Design
Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?
Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?
Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?
Data Management and Statistical Analysis
Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?
Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?
Is there documented evidence that the PD(s)/PI(s) successfully carried out studies of similar structure and complexity as in the current application in the specified setting? If needed, is there a realistic timeline for establishing necessary agreements with all partners (e.g., single IRB)? Does the environment support timely subject recruitment and completion of each of the two phases (R61 and R33)?
If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?
Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?
If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?
If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?
As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.
Milestones
Are quantitative criteria pre-specified and rigorously defined to assess milestone achievement and operational feasibility required for advancing from the R61 to the R33 phase? Are success criteria defined in terms of outcomes achieved (e.g., specific measures of target engagement) rather than as tasks completed? Are R61 milestones feasible, justified, well developed and quantifiable with regard to the specific aims of each stage? Are quantitative threshold values specified for the proposed measures? If more than one target/mechanism is proposed, are the criteria specific regarding whether target engagement of both is necessary to advance to the R33? Specifically, will the investigators and NIMH Program Officials be able to determine if the project succeeded in (a) demonstrating that the intervention alters the target/mechanism (thus providing an initial proof of principle), and (b) providing preliminary evidence that the intervention can be applied in an at-risk or clinical population with adequate acceptability and tolerability?
Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate?
Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?
Protections for Human Subjects
For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.
For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.
Inclusion of Women, Minorities, and Individuals Across the Lifespan
When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.
Vertebrate Animals
Generally not applicable. Reviewers will bring any concerns to the attention of the Scientific Review Officer.
Biohazards
Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.
Resubmissions
For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.
Renewals
Not Applicable
Revisions
For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.
Note: Effective for due dates on or after January 25, 2023, the Data Sharing Plan and Genomic Data Sharing Plan (GDS) as part of the Resource Sharing Plan will not be evaluated at time of review.
As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.
Applications from Foreign Organizations
Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.
Select Agent Research
Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).
Resource Sharing Plans
Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).
Authentication of Key Biological and/or Chemical Resources:
For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.
Budget and Period of Support
Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.
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. 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:
Information regarding the disposition of applications is available in the NIH Grants Policy Statement.
If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.
A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the recipient's business official.
Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.
Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.
The NIMH has published policies and guidance for investigators regarding human research protection, data and safety monitoring, Independent Safety Monitors and Data and Safety Monitoring Boards, reportable events, and participant recruitment monitoring (NOT-MH-19-027). The application’s PHS Human Subjects and Clinical Trials Information should reflect the manner in which these policies will be implemented for each study record. These plans will be reviewed by the NIMH for consistency with NIMH and NIH policies and federal regulations. The NIMH will expect clinical trials to be conducted in accordance with these policies including, but not limited to: timely registration to ClinicalTrials.gov, submission of review determinations from the clinical trial’s data and safety monitoring entity (at least annually), timely submission of reportable events as prescribed, and establishment of recruitment milestones and progress reporting.
Individual awards are based on the application submitted to, and as approved by, the NIH and are subject to the IC-specific terms and conditions identified in the NoA.
ClinicalTrials.gov: If an award provides for one or more clinical trials. By law (Title VIII, Section 801 of Public Law 110-85), the "responsible party" must register and submit results information for certain applicable clinical trials on the ClinicalTrials.gov Protocol Registration and Results System Information Website (https://register.clinicaltrials.gov). NIH expects registration and results reporting of all trials whether required under the law or not. For more information, see https://grants.nih.gov/policy/clinical-trials/reporting/index.htm
Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.
Data and Safety Monitoring Requirements: The NIH policy for data and safety monitoring requires oversight and monitoring of all NIH-conducted or -supported human biomedical and behavioral intervention studies (clinical trials) to ensure the safety of participants and the validity and integrity of the data. Further information concerning these requirements is found at http://grants.nih.gov/grants/policy/hs/data_safety.htm and in the application instructions (SF424 (R&R) and PHS 398).
Investigational New Drug or Investigational Device Exemption Requirements: Consistent with federal regulations, clinical research projects involving the use of investigational therapeutics, vaccines, or other medical interventions (including licensed products and devices for a purpose other than that for which they were licensed) in humans under a research protocol must be performed under a Food and Drug Administration (FDA) investigational new drug (IND) or investigational device exemption (IDE).
All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities. More information is provided at Award Conditions and Information for NIH Grants.
Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex. This includes ensuring programs are accessible to persons with limited English proficiency. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html.
HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA.
Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.
In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.
Not Applicable
Data Management and Sharing
Note: The NIH Policy for Data Management and Sharing is effective for due dates on or after January 25, 2023.
Consistent with the 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.
A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.
The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.
In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) #160;about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.
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: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-480-7075
Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov
Alexander M. Talkovsky, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-827-7614
Email: alexander.talkovsky@nih.gov
Nick Gaiano, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-827-3420
Email: nick.gaiano@nih.gov
Tamara Kees
National Institute of Mental Health (NIMH)
Telephone: 301-443-8811
Email: tkees@mail.nih.gov
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 45 CFR Part 75.