Part 1. Overview Information

Key Dates

All applications are due by 5:00 PM local time of applicant organization. 

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

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

Conformance to all requirements (both in the Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

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

1. Use the NIH ASSIST system to prepare, submit and track your application online.
2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.
   
   
3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.



Table of Contents
Part 1. Overview Information
Key Dates
Part 2. Full Text of Announcement
Section I. Notice of Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Purpose

The goal of this initiative is to identify neurophysiological measures as potential assays for treatment development research. The Notice of Funding Opportunity (NOFO) will support efforts to optimize and evaluate pharmacodynamic (PD) measures of neurophysiological processes that are disrupted within or across mental disorders in both healthy humans and in another species relevant to the therapeutic development pipeline.The initiative will support initial proof of concept studies aimed at identifying measures for potential development as preclinical assays for evaluating potential new drug and device therapies and their targets. Data may also reveal assay measures where performance is dissimilar between preclinical animal species and humans, thus establishing a firm basis for limiting speculative extrapolations of preclinical animal findings to humans. The ultimate practical goal of this NOFO is to improve the efficiency of the therapeutic development process by identifying congruent measures as well as inconsistencies between the preclinical screening pipeline and clinical evaluation of new treatment candidates.

The objectives of the NOFO will be accomplished by supporting partnerships among basic and translational neuroscientists who are committed to advancing the discovery of in vivo physiological measures as tools for target validation and therapeutic development. Groups will be tasked with developing and optimizing in vivo assays of brain processes in both animals and in healthy humans. Groups will evaluate assay performance across both species in response to specific pharmacologic manipulations. In this way, projects will reveal the potential of specific assays to translate from animals to humans, suggesting assays for further development as tools in the treatment development pipeline.

Background

The NIMH Strategic Plan for Research outlines research priorities for transforming the understanding and treatment of mental illnesses. The plan includes two cross-cutting themes which are directly relevant to the goals of this Funding Opportunity – Transforming Diagnostics and Accelerating Therapeutics. A core component of the Transforming Diagnostics theme is the Research Domains Criteria (RDoC) project. RDoC has grown into a significant effort for the NIMH that frees investigators from the current symptom-based diagnostic categories (i.e., Diagnostic and Statistical Manual, DSM) and encourages clinical researchers to study dimensions of observable behavior and neurobiological measures that may span multiple disorders. As outlined in NOT-MH-19-053, basic neuroscientists are encouraged to address molecular and neural mechanisms underlying specific domains of mental function, rather than creating animal models of diseases. Relevant to the Accelerating Therapeutics theme, NIMH has shifted its clinical trials portfolio toward studies with defined targets and milestones. The Institute’s experimental medicine approach seeks trials that will address the clinical assessment of the mechanism of action of the therapeutic treatment, providing a foundation for building specific treatment strategies. 

Implementation of experimental medicine designs in early phase trials of novel treatments for mental disorders requires a demonstration that the proposed intervention engages the target sufficiently to evaluate target-mediated effects on brain processes and clinical outcomes. In this context, ‘target’ refers to the brain signaling system, circuit, or physiological process the therapeutic strategy aims to correct as a means of improving function across mental disorders. The RDoC effort has the potential to identify measures that can be incorporated in experimental medicine trial designs to evaluate links between targets, circuits, and key functional domains in relation to clinical improvements. However, the potential success of the emerging clinical efforts is diluted by the lack of reciprocal efforts to develop assays of neural processes in the preclinical species. This lack of continuity of functional measures of target engagement between the preclinical species selected for use in treatment development and evaluation of effects in humans contributes uncertainty to an already risky pipeline of treatment development for mental disorders. For example, it is not surprising that commonly used preclinical behavioral assays whose original value was based on their ability to detect certain classes of compounds (e.g., the Porsolt swim test to identify serotonin uptake inhibitors as antidepressants), are poor predictors of the potential clinical efficacy of compounds that engage novel molecular targets.

Research Objectives

The purpose of this NOFO is to address the translational divide between preclinical and clinical measures implemented in the treatment development pipeline for mental disorders by supporting the construction of a suite of in vivo functional brain assays that evaluate measures for translational predictive value. Towards this goal, the NOFO will support the identification, development, optimization, and evaluation of in vivo CNS assays that measure brain functions that are evolutionarily conserved between the selected animal species and humans. The NOFO will additionally support assessment of the performance (test-retest reliability, sensitivity) of brain-based assays in both the preclinical species and in healthy humans in response to carefully selected pharmacologic-based dose response pharmacokinetic (PK)/PD assessment. Assays will aim to identify quantitative, robust, and reliable measures that tap into specific neurophysiological systems that are potentially impacted in mental disorders such as neural plasticity, cognitive or affective regulatory processes, or impulsivity. The manipulations will provide a critical first evaluation of how the measure performs in the context of the therapeutic development pipeline spanning from the preclinical species to humans.

Proposed assay measures are expected to have a reasonable likelihood of shared conservation of physiology and brain circuitry across healthy human controls and preclinical species. While there is a risk that measures of some brain processes may be difficult to optimize for cross-species evaluation or may not show coherence between species, this risk is managed by the UG3/UH3 mechanism, a two-stage phased innovation cooperative agreement award. The UG3 phase supports the planning and preliminary studies needed to conduct an evaluation of the performance of assays in both species in the UH3 phase. Projects will be milestone driven with an administrative review by internal NIMH staff to identify UG3 projects attaining milestones and demonstrating feasibility of assays in both species for advancement to the assay testing (UH3) phase. The cooperative agreement mechanism allows for greater involvement of NIMH staff in these projects, including suggesting external advisors and providing opportunities for multiple NOFO awardee groups to interact and share data. Should multiple UG3/UH3 awards be issued, it is expected that the groups will meet annually as a consortium to share updates on progress, to troubleshoot, and to outline strategies for disseminating data.

While it is understood that many protocols and the data generated will be at an early proof-of-concept stage, a central goal of this NOFO is to contribute to building a more robust, experimentally based therapeutic development pipeline for mental disorders. Regardless of study outcomes, it is expected that experimental protocols and data generated through both the UG3 and UH3 phases of this NOFO will be made available to the research community as a valuable source of information regarding relationships between animal assay results and human data no later than within one year of completion of the studies.  

The initiative will support partnerships among basic and translational neuroscientists who are committed to the discovery of translational physiological measures that may be used across preclinical development and that have the highest potential to be advanced into healthy human trials as tools for use in phase 1 or phase 2 therapeutics development.

Potential applicants are strongly encouraged to read the Frequently Asked Questions (FAQs) for this NOFO and to contact NIMH Scientific/Research Contact(s) prior to preparing an application.

Research Scope

This NOFO will support the phased development of in vivo assays to address translational gaps in treatment development for mental disorders. Support will be provided for assay development efforts that propose quantitative measures to assess alterations in neurophysiology/circuit activity that contribute to or reflect clinically relevant domains of function (e.g., cognitive function, impulsivity, motivation, etc.).

Proposed projects may include:

• Development and testing of in vivo measures that tap into fundamental processes that are disrupted within or across mental disorders such as aspects of vigilance, neural plasticity, reward processing, or attentional mechanisms contributing to cognition and/or affect regulation, that can be objectively measured in both live animals and humans using brain imaging or neurophysiological measures such as spectral EEG or MEG to assess brain rhythms with different frequencies. Innovative measures are encouraged.
• Development and testing of highly tractable behavioral paradigms as assays that may serve as proxies of neural circuit activity linked to a specific functional domain in both humans and animals. For example, the CNTRICS program identified constructs across six cognitive systems relevant to schizophrenia and selected tasks from cognitive neuroscience that measure the constructs and the CNTRACS initiative extended those measures (goal maintenance, relational encoding, gain control, visual integration). Such studies should combine behavioral and physiological measures (for example, tracking changes in forebrain oscillations during performance). Since the goal is to build innovation and address translational gaps, the inclusion of behavioral paradigms that are already commonly used cross species (e.g., fear conditioning) must incorporate novel measures of underlying neuronal processes.

See the NIH/NIMH Therapeutics Discovery web page for links to other NIMH drug discovery NOFOs: Drug Discovery for Nervous System Disorders PAR-19-147 (R01) and PAR-19-146 (R21), National Cooperative Drug Discovery/Development Groups (NCDDG) for the Treatment of Mental Disorders, Substance Use Disorders, or Alcohol Disorder PAR-22-144 (U19) and PAR-22-143 (U01). Note the related NOFOs titled Understanding and Modifying Temporal Dynamics of Coordinated Neural Activity, PAR-21-175 (R01) and PAR-21-176 (R21).

The UG3/UH3 is a two-phased mechanism. Each phase is milestone driven and only those projects attaining the UG3 milestones have the potential to progress to the UH3 phase. The UG3 phase supports feasibility testing and optimization of measures in animals and humans. The UH3 phase supports parallel testing of the measures in both animals and humans in response to pharmacologic dose ranging PK/PD studies to evaluate the performance, sensitivity, and coherence of measures across species.

1. The UG3 Preparatory Testing and Prioritization Phase (Stage 1) for this NOFO supports milestone-driven optimization of testing and prioritization of measures that tap into mental health relevant brain processes (e.g., neural plasticity, cognitive or affect regulatory processes, impulsivity) and neural circuit activity as assays in both animals and humans. For example, some assay measures that are already developed in the animal species selected will need to be adapted for humans while other assays may need to be back-translated from humans to the preclinical species. Other measures in this phase may need to be optimized in both species. Studies are expected to be performed in live animals and humans and not in cell culture, post mortem, or in vitro preparations. The only exception would be the allowance of a small number of limited studies in the UG3 phase aimed at identifying pharmacologic dose levels of the manipulations to be used in the UH3 phase for equivalent target engagement across species. 

UG3 projects are milestone driven and include go-no-go criteria for each assay that will be used to determine whether assays are sufficiently optimized and methodologically equated across species. UG3 assays that meet the scientific milestones and feasibility requirements may be eligible for transition to the UH3 stage pending NIH administrative review, availability of funds, and programmatic balance.

2. The UH3 Measure Evaluation Phase (Stage 2) will support milestone-driven evaluation of measures optimized in the UG3 phase by examining the effects of FDA-approved pharmacologic drugs selected based on demonstrated action on the circuit/brain process, in both humans and the preclinical species in parallel. By employing a dose ranging PK/PD study design, where dosing is chosen for comparable potency across species, data collected in this phase will assess the degree of cross species coherence of performance of the measures as assays.

Expected outcomes include the identification of promising measures for further development as tools for assessing the biological effects of novel therapeutic candidates across preclinical and healthy human studies. Data will also identify measures that differ in performance between preclinical species and humans, thus establishing a firm basis for limiting speculations about the potential clinical significance of preclinical assay data. Although only preclinical and healthy human studies would be supported by this NOFO, the emphasis is on developing (PK/PD) measures that will ultimately be useful for the evaluation of novel therapeutic mechanisms in phase 1 or 2 studies in patients with mental disorders.

The overall goal is to transform experimental protocols in both animals and humans into assays for use in the therapeutic development pipeline. Ideally, the most promising in vivo assays have the potential to be standardized and adapted for broader use across laboratories. This effort will build towards a critical understanding of the predictive value of assays as applied across preclinical species and humans. The effort will also begin to build critical measures of analytical performance (sensitivity, specificity, precision, stability, and reproducibility) that may be used to set standards for replication and verification of assay findings and to advance promising biomarkers and targets to clinical applications in subsequent projects.

Experimental Rigor: Translating discoveries into evidence-based treatments is predicated on the existence of strong, well-powered, adequately controlled, and replicated preclinical and clinical data. In addition, the value of such research is greatly enhanced when detailed information is made available about study design, execution, analysis, and interpretation. Examples of critical elements are outlined in section IV.2 and detailed in NOT-OD-15-103 as well as NIMH guidelines. As per NOT-OD-15-102, it is expected that animal and human studies will include both males and females.

Milestones

Because novel translational assay development and evaluation in the UG3 phase are likely to be high risk, it is anticipated that there will be attrition of some projects after the assay optimization phase (UG3). Objective milestones of success and go/no-go rules for assay progression will be required and both should have quantitative criteria associated with them (see Section IV.2 for details).

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.

Applications Not Responsive to this NOFO

The following will be considered not responsive and will not be reviewed:

• Development or inclusion of animal models "of" mental disorders. Projects should adhere to recommendations in NOT-MH-19-053, NIMH’s Considerations Regarding the Use of Animal Neurobehavioral Approaches in Basic and Pre-clinical Studies, as well as the Recommendations of the NAMHC Workgroup on Genomics.
• Behavioral assays without the inclusion of measures of associated brain processes and/or neural circuits.
• Broad batteries of behavioral tests or clinical battery testing.
• Invasive manipulations that cannot feasibly be performed in healthy humans.
• Cell culture, post-mortem, or in vitro assay measures in either species.
• Mechanistic studies of brain systems testing hypotheses about their role underlying functional domains, pathophysiology of disease, or treatment response.
• Studies aimed at clinical testing of novel therapeutics or therapeutics discovery.

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

Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs.

Section II. Award Information

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this NOFO.

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Local Governments

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

Federal Governments

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

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations
• Non-domestic (non-U.S.) Entities (Foreign Organizations)

Non-domestic (non-U.S.) Entities (Foreign Organizations) are eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the How to Apply- Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information.

• System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
  • Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registrations; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov – Applicants must have an active SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account.  PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019 and Notice of NIH's Interest in Diversity, NOT-OD-20-031.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the How to Apply-Application Guide.

2. Cost Sharing

This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1.2 Definition of Terms.

3. Additional Information on Eligibility

Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per NIH Grants Policy Statement Section 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NIH Grants Policy Statement 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Letter of Intent 

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

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

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

The letter of intent should be sent to:

Email: [email protected]

Page Limitations

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

For this specific NOFO, the Research Strategy is limited to 15 pages.

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.

The biosketches should clearly describe the role of all key personnel along with a description of the specific expertise each contributes towards the assay development and testing across species.

R&R Budget

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

Budget Justification: For each budget year, indicate if the requested budget is for the UG3 phase or the UH3 phase. The UG3 and UH3 cannot be funded in the same fiscal year.

The UG3/UH3 budget may include travel costs for one or two trips per year to attend meetings of the cooperative group.

It is expected that the PD/PI or each PD/PI on a multiple PD/PI application will dedicate at least 15% level of effort (1.8 calendar months) to managing the project.

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:

Specific Aims: Provide the overall goals for the entire application. The Specific Aims section should include distinct Aims for the UG3 and UH3 phases. All applications are required to include both UG3 and UH3 phases.

Research Strategy: Organize the Research Strategy in the subsections identified below, addressing all specific points below.

Applicants should describe both the UG3 phase and the UH3 phase within these subsections as described, including milestones.

Factor 1. Importance of the Research

Significance:

• Discuss how the proposed measures of neurophysiological processes address a translational gap.
• Provide justification as to why the proposed measures are clinically relevant.
• Describe how the study findings will advance the field regardless of outcome.

Innovation:

• Explain how the project offers a novel approach to evaluating potential new treatments for mental disorders.
• If similar measures are common practice in either a preclinical treatment development pathway, clinical neuroscience research, or clinical trials, explain how the proposed approach provides important new information or a benefit over existing measures.

Factor 2. Rigor and Feasibility

Approach: This section should cover the application as a whole as well as the UG3 and UH3 phases with the appropriate headers within the text.

Overall Approach:

• Justify the choice of measures, including a brief description of evidence that the measures have potential to either directly or indirectly assess activity or function within the same targeted circuits or physiological processes in both the preclinical species and humans.
• Include discussion of evidence indicating how the planned measures and pharmacologic drugs are relevant to key neural circuits/processes that are disrupted in mental disorders.
• Provide evidence of feasibility to perform the measurements and manipulations in both preclinical species and humans.
• Explain the rationale behind the choice of preclinical species.
• If assays will require optimization, explain what aspects require optimization, why, and how potential roadblocks as well as strategies for addressing the barriers that may arise in the course of optimization in one or both species.
• Provide the rationale for the selection of manipulations that will be used to perturb the measures and thus evaluate the performance, reliability, and sensitivity of the measures in both species. Include the rationale for the dosing ranges planned for the UH3 phase in both species along with evidence of similar potency, if known (e.g., selection of drug doses with similar receptor occupancy across species, for example).
• Include a detailed Results and Interpretation section for both the UG3 and UH3 phases that outlines how results will be quantitatively evaluated.
• For each assay proposed, provide quantitative criteria and operational definitions of results that would indicate coherence between species. Explain how results will be communicated with the research community regardless of outcome.

Preparatory Testing and Prioritization Stage (UG3): All supported projects will begin with a UG3-funded preparatory phase to identify measures and manipulations to be evaluated in the testing phase (UH3).

• Describe the research team's approach toward selecting, planning and prioritizing assays for optimization and evaluation in both humans and a preclinical species.
• Provide the goals and rationale for all requisite preliminary studies planned for this phase.
• Provide sufficient detail regarding how preliminary data presented in the application were collected and how planned studies are required to extend these data, to prioritize measures, optimize parameters or level of perturbations, and evaluate the feasibility of the assays.
• Clearly describe studies to be performed in this phase and how results will contribute towards the selection of assays for cross-species evaluation in the UH3 phase. It is recommended that, to the extent feasible, multiple measures be included for optimization in the UG3 phase to maximize the potential for advancement of some assays to the UH3 evaluation phase.
• Describe the explicit go and no-go criteria for each measure that will be used to determine if it will be advanced to full evaluation in both species in the UH3 stage.  If there is more than one type of measurement included in an assay, such as behavior and physiology, outline a strategy for determining the degree to which the measures must co-vary for the task to progress. Indicate how assay stability and precision will be assessed. It is not sufficient to indicate that the best match across tasks would go forward to full evaluation in the UH3 phase.
• If applicable, provide details of UG3 phase studies aimed at optimizing the pharmacologic challenge for cross species comparisons in the UH3. The pharmacologic testing and measures should be either the same in both species or, if there are necessary procedural differences across species, evidence should be provided to justify direct comparisons based on comparable physiological effects.
• Describe explicit go and no-go criteria for inclusion of manipulations in the UH3 phase where optimization is required in the UG3 phase.

Describe plans for annual in person (travel permitting) Steering Committee meetings among key personnel, NIH project scientists. The initial meeting should prioritize two-three measure/manipulation sets for cross species evaluation and to identify and plan preliminary studies within the timeframe of the UG3. The second meeting should review new data, summarize the UG3 activities, and prepare a refined UH3 plan for conducting the comparative studies. At least monthly teleconferences are expected during the intervening months of UG3 support. The Steering Committee should include outside expert advisors.

For the Measure Evaluation Phase (UH3): Based on the successful conduct of the UG3 and approval by the  NIMH, the awardee will be provided with additional years of support through the UH3. The award of the UH3 phase will depend on the strength of the evidence, rationale, and plan for evaluating primary and back up measures in animals and humans including: a) evidence that the measures are robust and reliable, b) preliminary evidence that the assays are sensitive to pharmacologic testing, and c) demonstration of equivalent intensity or dose effect in animals and humans of the drug levels proposed.

The UH3 period will support the performance of the experiments outlined in the original application and refined during the UG3 phase. Support for each year will be milestone driven with the expectation that at least one measure evaluation can be completed in both species in each year of support.

• Describe explicit criteria for prioritizing assays, how they could be used in therapeutics development, and manipulations to be selected for progression from the UG3 phase to the UH3 phase in both species.   
• Detail the experimental approach to evaluate the measures in both humans and the preclinical species in parallel. Outline where experimental details will rely on completion of UG3 studies.
• Provide the rationale for the choice of drug(s), dose ranges to be tested to modify activity of the neural circuits or behavioral readouts in both species. Outline strategies and/or evidence to assure comparable degrees of effects of the pharmacologic challenge across species.
• Describe plans for data analysis and interpretation including an operational, objective definition of coherence of measures between species as go and no-go criteria for further measure development or implementation in a therapeutic discovery pipeline. Include plans for analyzing PK/PD relationships for each species.
• Outline plans for at least one in person (travel permitting) Steering Committee meeting and five or more interim meeting update teleconferences each year.
• Describe procedures that will be included for evaluating assay reliability. Include plans for evaluating test-retest stability either in the funded project period or in future studies.

Milestones:

The clarity and completeness of the UG3/UH3 application with regard to specific goals and feasibility milestones are critical. Separate milestones should be proposed for the UG3 and UH3 phases. The milestones should be unambiguous, quantifiable, and scientifically justified to allow NIMH staff to assess progress. The UG3 phase milestones should include a timeline for completion of all preliminary studies needed to move the measure evaluation to the UH3 phase, as well as plans for publication or sharing of assay results regardless of outcome.  UH3 milestones should include plans for evaluating a minimum of one assay measure in both species per year. These milestones are distinct from the go/no-go criteria for measures, manipulations, and assays.

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.

While it is understood that many protocols and the data generated will be at an early proof-of-concept stage, a central goal of this NOFO is to contribute to building a more robust, experimentally based therapeutic development pipeline for mental disorders. Regardless of study outcomes or publication status, the experimental protocols and data generated through this NOFO will be valuable to the research community by indicating assays with variable levels of potential predictive value in cross species comparisons.

Accordingly, applicants are expected to include a detailed Data and Experimental Protocol sharing plan that specifies how data will be shared and who will be responsible for managing sharing of all protocols and data, consistent with achieving the goals of this program. At a minimum, plans should include annual submission of raw and summary data on their website, through PubChem or some other venue. Human data from the UH3 phase are expected to be submitted to the appropriate NIMH Data Archive database and detailed in NOT-MH-23-100.

Data sharing plans must include items from the list below:

• The expected schedule for data sharing
• The format of the dataset
• The documentation to be provided with the dataset
• Whether any analytic tools also will be provided
• Whether a data-sharing agreement will be required. If so, consider including:
  • A brief description of such an agreement
  • Criteria for deciding who can receive the data
  • Whether or not any conditions will be placed on their use
  • The mode of data sharing (e.g., the PI could handle data sharing by mailing a disk or posting data on their institutional or personal website, or the data sharing could be handled through a data archive or enclave).
    • Investigators choosing to handle their own data sharing may wish to enter into a data-sharing agreement.

Applicants must include the following key elements:

• Description of how protocols and data will be shared as well as schedule/timeline for sharing data. At a minimum, plans are expected to include annual submission of raw and summary data.
• Description of project management of protocol and data sharing.

To advance the goal of advancing research through widespread data sharing among researchers, investigators funded under this NOFO are expected to share those data via the National Institute of Mental Health Data Archive (NDA; see NOT-MH-123-100). 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 web site provides two tools to help investigators develop appropriate strategies: 1) the NDA Data Submission Cost Model which offers a customizable Excel worksheet that includes tasks and hours for the Program Director/Principal Investigator and Data Manager to budget for data sharing; and 2) plain language text to be considered in your informed consent available from the NDA's Data Contribution page. Investigators are expected to certify the quality of all data generated by grants funded under this FOA prior to submission to NDA and review their data for accuracy after submission. Submission of descriptive/raw data is expected semi-annually (every January 15 and July 15); submission of all other data is expected at the time of publication, or prior to the end of the grant, whichever occurs first (see NDA Sharing Regimen for more information); Investigators are expected to share results, positive and negative, specific to the cohorts and outcome measures studied. The NDA Data Sharing Plan is available for review on the NDA website. NDA staff will work with investigators to help them submit data types not yet defined in the NDA Data Dictionary.

Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the How to Apply- Application Guide.

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

PHS Human Subjects and Clinical Trials Information

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

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 Sharing for Applicants and Awardees.

6. Funding Restrictions

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

Pre-award costs are allowable only as described in the NIH Grants Policy Statement Section 7.9.1 Selected Items of Cost.

Applications must be submitted electronically following the instructions described in the How to Apply Application Guide. Paper applications will not be accepted.

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

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

Important reminders:

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

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the How to Apply Application Guide.

See more tips for avoiding common errors.

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

Requests of $500,000 or more for direct costs in any year

Applicants requesting $500,000 or more in direct costs in any year (excluding consortium F&A) must contact a Scientific/ Research Contact at least 6 weeks before submitting the application and follow the Policy on the Acceptance for Review of Unsolicited Applications that Request $500,000 or More in Direct Costs as described in the SF424 (R&R) Application Guide.

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

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

Post Submission Materials

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

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.

For this particular announcement, note the following:

• Evaluation of the approach should emphasize the biological rationale and, the degree to which the planned experiments contribute towards building innovative and useful preclinical assays and approaches in a therapeutic development pipeline through evaluation of the coherence of measures between the preclinical species and healthy humans.
• Very few, if any, measures currently have sufficient evidence of shared physiology between preclinical species and humans. As such, it is expected that groups will have limited preliminary data.
• Risk is expected; it is anticipated that this inherent risk will be managed through the use of the two phase mechanism. Projects should be evaluated relative to expectations for their proposed entry stage, when assessing risk.
• The goal of this NOFO is practical, to evaluate the coherence of physiological measures between humans and a preclinical species. The expected outcome from this NOFO is the identification of 1) in vivo measures with some potential to serve as preclinical assays in therapeutic development based on coherence of measures between animals and humans, and 2) in vivo measures demonstrating a lack of coherence between animals and humans which should indicate the need for caution in interpreting preclinical results using similar assays. Thus, both positive and negative outcomes of well controlled, rigorous studies will be valuable.
• The purpose of the pharmacologic dose ranging study in the UH3 phase is solely to evaluate the performance of the assays, not to address mechanistic hypotheses or test novel therapeutic targets.

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 evaluate 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 criterion 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 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 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.
• Compliance with data management and sharing policies.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement Section 2.5.1. Just-in-Time Procedures. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding.

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

3. Anticipated Announcement and Award Dates

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

Information regarding the disposition of applications is available in the NIH Grants Policy Statement Section 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

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

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

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

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

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

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

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

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

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

2. Administrative and National Policy Requirements

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

• The rules listed at 2 CFR Part 200, Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards.
• All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the terms and conditions in the Notice of Award (NoA). The NoA includes the requirements of this NOFO. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities.
• If a recipient receives an award, the recipient must follow all applicable nondiscrimination laws. The recipient agrees to this when registering in SAM.gov. The recipient must also submit an Assurance of Compliance (HHS-690). To learn more, see the Laws and Regulations Enforced by the HHS Office for Civil Rights website.
  • HHS recognizes that NIH research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this NOFO.

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

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

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (HHS) grant administration regulations at 2 CFR Part 200, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the recipients is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

The PD(s)/PI(s) will have primary authority and responsibility to define objectives and approaches and to plan and conduct the proposed research. She/he will assume responsibility and accountability to the applicant organization and to the NIMH for performance and proper conduct of all research supported in the cooperative agreement, including any NIH intramural component, if applicable, in accordance with the Terms and Conditions of Award. The PD(s)/PI(s) will be a member of the Steering Committee (SC). Intramural research scientists participating as collaborators have the same rights and responsibilities as other members of the SC (see below for Participation of NIH Intramural Scientists).

The Recipient Institution and/or PD(s)/PI(s) Institution will retain primary custody of and have primary rights to data as specified under the data and research resource sharing plans (described above). The Government, via the NIMH Project Scientist(s), will have access to data generated under this cooperative agreement and may periodically review the data consistent with current DHHS, PHS, and NIH policies. Timely publication of major findings by the PD/PI and grant investigators is encouraged. Publication or oral presentation of work done under this agreement will require appropriate acknowledgment of NIMH support, including the assigned cooperative agreement award number. The PD(s)/PI(s) may invite external scientist(s) to serve as advisors on the SC post grant submission and review, as needed, and in consultation with the NIH Program Official and NIH Project Scientist(s).

Each annual progress report will describe progress toward achieving milestones submitted prior to award.

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

The Project Scientist(s) interacts scientifically with the PD/PIs and other SC members and may provide appropriate assistance, including assisting in research planning, suggesting studies within the scope of the research team's objectives and research activities, presenting experimental findings to the SC from published sources or from relevant contract projects, participating in the design of experiments agreed to by the SC, participating in the analysis of results, suggesting external experts as consultants, and advising in management and technical performance. The Project Scientist(s) will be a member(s) of the Steering Committee. However, the total membership by NIH staff will not exceed one-third (1/3) of the membership of the Steering Committee. In all cases, the role of NIMH will be to assist and facilitate and not to direct activities. For matters requiring a vote, NIH staff will have one vote.

The NIH Project Scientist retains the option to consult with non-NIH experts in the field in evaluating progress in achieving milestones.

Additionally, an NIMH Program Official will be responsible for the normal scientific and programmatic stewardship of the award, including monitoring implementation of data and research resource sharing plans and will be named in the award notice.

Areas of Joint Responsibility include:

Should more than one UG3/UH3 be funded, the Groups will be federated through a Consortium Committee composed of the PD(s)/PI(s) and additional project leader from each Group, NIMH Project Scientist(s), and NIMH Program Official (as a non-voting member). The Consortium Committee members will meet annually in person or by teleconference to review progress and identify emerging opportunities for strategic partnerships. The Consortium Committee will select, by majority vote, a Chair from among the PD(s)/PI(s) for a one-year term. The Consortium Committee Chair, who will be responsible for organizing the meeting and preparing concise proceedings or minutes (two to four pages) which will be delivered to the members of the Group within 2 weeks of the meeting.

Steering Committee:

A governing Steering Committee composed of the PD(s)/PI(s) and all other key personnel, NIH Project Scientist(s), and NIH Program Official (as a non-voting member) will be established in each cooperative agreement to assist in monitoring and developing the scientific content and direction of the program.

The Steering Committee members will meet periodically to review and monitor progress, plan and design research activities, and establish priorities. Meetings will occur as monthly teleconferences with one in person meeting over the course of the UG3 phase and include at least one in-person (if travel is permitted) and 5 teleconferences each year over the course of the UH3 phase. The PI(s)/PD(s) will be responsible for scheduling the time and place (in person or by video or audio teleconference) and for preparing concise proceedings or minutes (two or three pages) which will be delivered to the members of the SC within 2 weeks of the meeting.

The principal end products of SC activities for NIMH are expected to include: 1) the identification and prioritization of measures and manipulations to be evaluated in humans and a preclinical species, 2) planning and evaluation of data required to support full evaluation of measures and manipulations, and 3) analyses and dissemination of study results.

It is expected that novel assays, experimental protocols, and data generated through both the UG3 and UH3 phases of this FOA will be made widely available to the research community as a valuable source of information.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between recipients and NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual recipient. This special dispute resolution procedure does not alter the recipient's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and HHS regulation 45 CFR Part 16.

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]

Sofiya Hupalo, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-827-3752
Email: [email protected] 

Jamie Driscoll
National Institute of Mental Health (NIMH)
Telephone: 301-443-5288
Email: [email protected]

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

Heather Weiss
National Institute of Mental Health (NIMH)
Telephone: 301-443-4415
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.