National Cooperative Drug/Device Discovery/Development Groups (NCDDG) for the Treatment of Mental Disorders (U01 Clinical Trial Optional)

National Cooperative Drug/Device Discovery/Development Groups (NCDDG) for the Treatment of Mental Disorders (U01 Clinical Trial Optional) is sponsored by National Institutes of Health (NIH). Funds groups dedicated to drug/device discovery and development for mental disorders.

PAR-25-352: National Cooperative Drug/Device Discovery/Development Groups (NCDDG) for the Treatment of Mental Disorders (U01 Clinical Trial Optional) This funding opportunity was updated to align with agency priorities. Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission. Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) Components of Participating Organizations National Institute of Mental Health ( NIMH ) Funding Opportunity Title National Cooperative Drug/Device Discovery/Development Groups (NCDDG) for the Treatment of Mental Disorders (U01 Clinical Trial Optional) U01 Research Project – Cooperative Agreements March 31, 2025 - This funding opportunity was updated to align with agency priorities.

Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission. April 4, 2024 - Overview of Grant Application and Review Changes for Due Dates on or after January 25, 2025. See Notice NOT-OD-24-084 .

August 31, 2022 - Implementation Changes for Genomic Data Sharing Plans Included with Applications Due on or after January 25, 2023. See Notice NOT-OD-22-198 . August 5, 2022 - Implementation Details for the NIH Data Management and Sharing Policy.

See Notice NOT-OD-22-189 . Funding Opportunity Number (FON) Companion Funding Opportunity Research Program (Cooperative Agreement) See Section III. 3.

Additional Information on Eligibility . Assistance Listing Number(s) Funding Opportunity Purpose The purpose of this notice of funding opportunity (NOFO) is to accelerate innovative drug and device therapies translation from discovery to early human studies.

Studies appropriate for this NOFO will develop pharmacologic and neuromodulatory tools for basic and clinical research on mental health disorders; develop and validate tools (pharmacologic or neurostimulation) in support of experimental therapeutic studies of innovative candidates for mental disorders; and support early-stage human studies to rapidly assess the safety, tolerability, and pharmacodynamics of promising drug candidates/devices and new indications for novel Investigational New Drug (IND)-ready agents or Investigational Device Exemption (IDE)-ready devices for the treatment of mental disorders.

This NOFO encourages applications to advance the discovery, preclinical development, and proof of concept (PoC) testing of new, rationally based candidate agents and neurostimulation approaches to treat mental disorders, and to develop novel ligands and circuit-engagement devices as tools to further characterize existing or to validate new drug/device targets. Partnerships between academia and industry are strongly encouraged.

This NOFO will also support applications proposing preclinical discovery of biotechnology products and biologics with potential as candidate therapeutics including, but not limited to, large biologic macromolecules, (e.g., proteins, antibodies, and peptides), gene-based therapies (i.e., oligonucleotide- and viral vector-based), cell therapies, and novel emerging therapies (e.g., microbial and microbiome therapies).

This NOFO supports a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies.

Projects seeking support for a research program of multiple projects directed toward a specific major objective, basic theme, or program goal, requiring a broadly based, multidisciplinary, and often long-term approach should consider the companion NOFO PAR-25-353 Funding Opportunity Goal(s) The mission of the National Institute of Mental Health (NIMH) is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery, and cure.

Open Date (Earliest Submission Date) Renewal / Resubmission / Revision (as allowed) AIDS - New/Renewal/Resubmission/Revision, as allowed 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.

Required Application Instructions 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.

Use the NIH ASSIST system to prepare, submit and track your application online. 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. Workspace to prepare and submit your application and eRA Commons to track your application. Part 1.

Overview Information 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 The intent of this NOFO is to encourage applications from academic, biotechnology, biomedical device industry, or pharmaceutical industry investigators interested in participating with the National Institute of Mental Health (NIMH) in a National Cooperative Drug/Device Discovery/Development Group (NCDDG) program.

The objectives of this program are: to advance the discovery, preclinical development, early-stage human studies, and/or proof of concept testing of new, rationally based candidate agents or devices to treat mental disorders, and to develop novel ligands and novel brain circuit-modulatory technologies as tools to advance biological research on the function of genes, cells, biochemical pathways, distributed neural circuits, and neural oscillatory patterns implicated in the etiology and pathophysiology of mental disorders, and as potential new therapeutics.

Partnerships between academia and industry are strongly encouraged. This program strongly encourages in-kind resource contributions of the partners within the NCDDG (e.g., biotechnology, pharmaceutical, or disease foundations). Each NCDDG program should consist of a multidisciplinary team of scientists with appropriate expertise to further the development and evaluation of novel candidate agents or proposed biomedical devices.

Scientists from both academia and pharmaceutical industry are encouraged to participate within an NCDDG; scientists from foreign institutions and NIH Intramural laboratories may participate in some aspects.

It is anticipated that the interaction of academic and non-profit research institutions with industry and NIH via the NCDDG model will: 1) accelerate the discovery and development of new therapeutics for mental disorders; 2) increase the availability of pharmacologic and device-based research tools (including Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) imaging agents) for basic and clinical research; 3) facilitate the development and validation of neurophysiological, pharmacokinetic (PK), and pharmacodynamic (PD) measures to evaluate novel therapeutics for mental disorders; 4) increase the availability of new compounds, agents, and devices suitable for testing in humans; 5) facilitate the development and validation of new clinical measures or biomarkers suitable for use in human Proof of Concept (PoC) trials of novel therapeutics for mental disorders; and/or 6) develop and validate novel neurostimulation technologies and protocols for mental disorders.

The goal of the NCDDG program is not to duplicate or compete with the private sector but to complement and accelerate the development of research tools for new molecular and circuit targets implicated in mental disorders, and effective compounds, agents, and devices for the prevention and treatment of psychiatric and addictive disorders, as well as core features of these illnesses, especially in areas of unmet medical need.

Background and Research Objectives Significant advances in neuroscience, genetics, genomics, and related omics, behavioral neuroscience, together with technological developments (structural biology, in silico and high throughput screening, in vivo imaging methods), have provided a rich knowledge base for understanding pathophysiology, identifying new molecular targets for drug discovery, new circuit/oscillatory targets for device development, and developing rational pharmacotherapies and neuromodulation interventions for the treatment of psychiatric disorders.

With the wealth of potential new drug/device targets, the opportunity exists to accelerate the process of target validation and medication discovery to make great strides toward novel and effective treatments for mental disorders. A U01 application can include no more than a single Research Project.

Applications proposing two or more Research Projects along with Scientific and/or Administrative Core components should respond to the companion NOFO utilizing the U19 mechanism ( PAR-25-353 ) NIMH's Objectives and Interests for the NCDDG Program NIMH’s objective for the NCDDG program is to support innovative, high impact research focused on the discovery of pharmacological agents selective for novel molecular targets and new neuromodulation devices targeting novel neural circuit and neural oscillatory targets with potential to prevent or reverse pathophysiological processes underlying mood and anxiety disorders, schizophrenia, eating disorders, obsessive-compulsive disorder, fragile x, autism, and other mental illnesses.

Public-Private partnerships are particularly encouraged. NIMH-relevant NCDDG research projects should focus on novel interventions, using either pharmacological agents or neuromodulation devices that interrogate a molecular, circuit or clinical target that is linked to a biological mechanism or pathophysiology of the proposed mental disorder. The NIMH strongly encourages an experimental medicine approach to therapeutic development.

This NOFO will support up through First-in-Human (FIH) for devices or Phase Ia or Ib trials for pharmacological agents. For these trials, studies are expected to assess the agent/device for 1) safety and tolerability, 2) target engagement, and 3) pharmacodynamic effects on relevant circuits or systems.

Data resulting from Phase I trials in healthy controls and in the target patient population are expected to determine optimal clinical dosing and to establish feasibility for further testing in PoC and efficacy trials. Agents/devices should be sufficiently potent and selective for critical evaluation of target engagement and brain exposure.

The agent/indication (if successful) should have a major, not merely incremental, impact on unmet medical need in psychiatric disorders. In support of this effort, NIMH recognizes the need for the timely development of new PET tracers for targets that are of interest for assessing target engagement/dose selection for clinical trials of novel therapeutics and for studies of the pathophysiology of psychiatric disorders.

Consistent with NIMH’s Research Domain Criteria (RDoC) initiative, research projects directed towards ameliorating pathophysiology that is potentially more proximal to specific functional deficits (domains) than Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnostic entities are encouraged. Additional information about the RDoC approach can be found on the RDoC website .

The testing of functional domains not included specifically in RDoC may also be considered, if well justified. NIMH encourages applications ranging from ligand discovery and testing in preclinical assays through human Phase I studies of novel agents.

Examples include, but are not limited to: An application that integrates machine learning (ML) tools, including human-in-the-loop ML (an ML model that requires researcher interaction), into the drug discovery process at any of its stages, from hit/lead identification to lead optimization.

Use of generative ML models in de-novo design of drug chemical structures with desired properties Ligand-based virtual screening and computational hit expansion following high-throughput screening (HTS) campaigns Use of ML in the design of new molecules employing phenotypic and high-content screening data and assessing their potency, selectivity, and binding affinity Use of ML models for predicting bioactivity and ADMET parameters of compounds Ligand discovery for therapeutics development or as clinical research tools (e.g., imaging probes) for novel molecular targets implicated in mental illnesses.

Biotechnology products and biologics including, but not limited to, large biologic macromolecules, (e.g., proteins, antibodies, and peptides), gene-based therapies (i.e., oligonucleotide- and viral-based), cell therapies, and novel emerging therapies (e.g., microbial and microbiome therapies). The inclusion of measures to assess the functional pharmacological activity of the agent is encouraged in dose-finding studies.

Phase Ib studies in the proposed disease population to confirm target engagement, establish optimal dosing, pharmacokinetic/pharmacodynamic (PK/PD), CNS exposure, functional pharmacological or neurophysiological activity, and tolerability of the novel agent, compound, or device.

Novel tool and biomarker development to enable studies to assess target engagement, brain PD, and PK for innovative drug targets; for example, PET or SPECT tracers for evaluating receptor occupancy and interrogating dose-response relationships.

Phase I studies (FIH pharmacology experiments) that include (PD/PK biomarkers to assess target engagement, functional pharmacological activity or neurophysiological effect, safety, and tolerability of new drugs. Initial Good Laboratory Practice (GLP) toxicology, safety pharmacology, and pharmacokinetics to support an Investigational New Drug (IND) application to the Food and Drug Administration (FDA) to begin human clinical testing.

Development and application of novel assays for evaluating brain PD/PK relationships in preclinical and early-phase human studies. NIMH also encourages applications ranging from early-stage, pre-clinical, device development to FIH clinical trials.

Examples include, but are not limited to: Regulatory activities, including pre-submission meetings with FDA, Investigational Device Exemption (IDE) submission, risk determinations, or other FDA regulatory submissions.

Modeling technologies capable of precisely characterizing delivered dose of neuromodulation technologies (e.g., electric field modeling) and to accurately measure the impact of the delivered dosage on neural functioning (e.g., simultaneous TMS-EEG, TMS-fMRI or other technologies to demonstrate engagement of the targeted distributed network or neural oscillatory target).

Linkage of behavior with brain recordings via high-density recordings of both. FIH, proof of concept studies that may assess initial measures of safety and efficacy and lead to further refinement of the device. Development of packaging, connectors, and other accessories necessary for the translation of this technology.

Activities to bring the development process under Design and Quality Systems Control. Activities to become current Good Manufacturing Practice (GMP) compliant. GLP compliant large animal model safety and/or testing of an implanted device.

Bench-top and/or animal testing to demonstrate compliance with FDA Recognized Standards. Non-GLP animal studies to develop techniques relevant to the device, optimize relevant therapeutic parameters, and refine device design as necessary for subsequent GLP testing or additional clinical studies for regulatory approval. Device, software, and firmware design verification and validation activities.

In summary, the NCDDG Program will support broad, innovative, multidisciplinary approaches to the discovery of new, rationally based treatments and research tools for mental disorders. Since the creative talents in the required scientific disciplines are rarely available in a single institution, a multi-institutional, group approach involving academic, nonprofit, commercial, and/or industrial institutions is envisioned.

Academic, pharmaceutical, and biomedical technology scientists are strongly encouraged to form partnerships that take full advantage of their combined intellectual and material resources for drug discovery, lead optimization, model development, and clinical testing.

Further, the interaction of academic and non-profit research institutions with the pharmaceutical and biomedical device industry and NIH is expected to facilitate subsequent development and marketing of new pharmacologic and device treatments, although these latter activities are not within the scope of this NOFO.

Molecular targets for drug/device discovery, and the sources and types of chemical/circuit entities to be investigated will be selected by the applying group. Both novel mechanisms of action and disease-oriented approaches are of interest.

The objective of this NOFO is to establish NCDDG Groups to conduct innovative, high-impact research focused on the discovery and testing of small molecules or biotechnology products and biologics with potential as candidate therapeutics including, but not limited to, large biologic macromolecules, (e.g., proteins, antibodies, and peptides), gene-based therapies (i.e., oligonucleotide- and viral vector-based), cell therapies, and novel emerging therapies (e.g., microbial and microbiome therapies) for novel molecular targets, as well as novel devices for novel circuit/neural dynamic targets implicated in the pathophysiology of mental disorders.

The NCDDG serves as a vehicle for pharmaceutical, biomedical devices, and academic scientists to pool intellectual and material resources for the translation of basic science findings into the conceptualization, discovery, and evaluation of new chemical entities and devices.

Groups are encouraged to select molecular targets for drug discovery and circuit targets for device discovery based on recent findings in basic and clinical neuroscience, genetics, and proteomics relevant to the understanding of mental disorders. The identification of lead compounds/candidate agents/devices and refining them for target validation and medication development are important goals of this initiative.

It is anticipated that the interaction of academic and non-profit research institutions with NIH and pharmaceutical industry will facilitate timely evaluation and development of preclinical and clinical research tools, models, and novel therapeutics.

Applicants seeking additional sources of support for preclinical development activities such as toxicology and safety pharmacology assessment, bulk synthesis, GMP synthesis, and formulation development should consider the NIH Blueprint Neurotherapeutics Network program ( http://neuroscienceblueprint. nih. gov/bpdrugs/index.

htm or https://neuroscienceblueprint. nih. gov/neurotherapeutics/bpn-biologics ) and/or the NIH Bridging Interventional Development Gaps (BrIDGs) Program .

Prior to submission of an application, applicants are strongly encouraged to contact the relevant Scientific/Research Contact listed in Section VII of this NOFO to determine if the proposed Research Project would be considered a priority for NIMH.

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

The NIMH has published updated policies and guidance for investigators regarding human research protection and clinical research data and safety monitoring ( NOT-MH-19-027 ). The application’s PHS Human Subjects and Clinical Trials Information, including the Data and Safety Monitoring Plan, should reflect the policies and guidance in this notice.

Plans for the protection of research participants and data and safety monitoring will be reviewed by the NIMH for consistency with NIMH and NIH policies and federal regulations. Investigators proposing NIH-defined clinical trials may refer to the Research Methods Resources website for information about developing statistical methods and study designs. See Section VIII.

Other Information for award authorities and regulations. Section II. Award Information Cooperative Agreement: A financial assistance mechanism used when there will be substantial Federal scientific or programmatic involvement.

Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI. 2 for additional information about the substantial involvement for this NOFO.

Application Types Allowed The OER Glossary and the How to Apply Application Guide provide details on these application types. Only those application types listed here are allowed for this NOFO. Optional: Accepting applications that either propose or do not propose clinical trial(s).

Need help determining whether you are doing a clinical trial? Funds Available and Anticipated Number of Awards The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications. Application budgets are not limited but need to reflect the actual needs of the proposed project.

The total project period may not exceed five years. 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 Higher Education Institutions Public/State Controlled Institutions of Higher Education Private Institutions of Higher Education Nonprofits Other Than Institutions of Higher Education Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education) Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education) For-Profit Organizations (Other than Small Businesses) City or Township Governments Special District Governments Indian/Native American Tribal Governments (Federally Recognized) Indian/Native American Tribal Governments (Other than Federally Recognized).

Eligible Agencies of the Federal Government U.S. Territory or Possession 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 Non-domestic (non-U.S.) Entities (Foreign Organizations) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply. Foreign components, as defined in the NIH Grants Policy Statement , are allowed. 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.

Eligible Individuals (Program Director/Principal Investigator) Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the How to Apply-Application Guide. An NIH intramural scientist may not serve as the PD/PI of an NCDDG but may participate as a research collaborator or consultant (see Section IV. 7 for more information).

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 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 ). The PD/PI will be expected to devote at least 1.

8 person months of effort to the NCDDG program. If an MPI application, each MPI is expected to devote at least 1. 8 person months of effort to the NCDDG program.

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

Instructions for Application Submission 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. 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. Include in the biosketch information about the PD/PI demonstrated leadership in the development, implementation, and management of comprehensive research programs.

If biotechnology or pharmaceutical partners are used, identify the key personnel who have authority within the company to allocate resources to ensure the successful completion of the proposed discovery and development efforts. All instructions in the How to Apply- Application Guide must be followed. 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.

All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions: Research Strategy: The Research Strategy must provide the following details: Describe to what extent the proposed plan for the discovery, and testing of novel treatments, research tools, or clinical studies supports the needs of the targeted disease.

Include evidence of the novelty of the proposed biological targets, mechanisms, or measures. For applications involving device stimulation or biomarker development, include evidence that the target circuit or neural dynamic signal is novel and there is evidence provided to suggest the strategy is likely to succeed.

For applications involving clinical trials, describe the design/research plan includes innovative elements, as appropriate, that enhance its sensitivity, potential for information, or potential to advance scientific knowledge or clinical practice. Provide scientific evidence of the relevance of the targets, screens, and preclinical to therapeutic discovery for mental disorders.

Provide scientific evidence of the pharmacogenetic or other biomarkers as patient selection strategies are appropriate to the proposed clinical studies of mental disorders. For applications involving device development, provide scientific evidence that the proposed device capabilities and neural targets are novel and appropriate for the proposed clinical studies of mental disorders.

For applications involving radiotracer development: Provide adequate evidence of feasibility that the target can be detected in the brain region(s) and brain circuits of interest. Clearly describe the desired properties of the radiotracer and are reasonable for the proposed target.

Provide scientific evidence that the proposed pharmaceutical or device partnerships will facilitate the development and evaluation of candidate drugs or therapeutics, tools for clinical research, and model validation for testing therapeutics.

For applications proposing multi-sites/centers, provide 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.

For applications including a chemical series developed by a biotechnology or pharmaceutical industry, provide adequate evidence of involvement of industry chemists as collaborators or advisors in the project and how their expertise will contribute to advancing the project. Letters of Support: Include letters of commitment to the collaboration by private sector partners or collaborators.

If the application involves collaboration with an NIH intramural scientist, the intramural scientist must obtain written approval of his/her NIH Institute Scientific Director for the amount of resources that may be allocated to the project; this amount must be specified in the letter, and cannot exceed $200,000 in direct costs of intramural resources.

The approval must also specify that the conduct of the project will comply with the DHHS regulations for research involving human subjects (if applicable) and with the PHS policy on vertebrate animal research. 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.

All instructions in the How to Apply-Application Guide must be followed, with the following additional instructions: All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan.

All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan. To advance the goal of advancing research through widespread data sharing among researchers, investigators funded by NIMH under this NOFO are expected to share those data via the National Institute of Mental Health Data Archive (NDA; see NOT-MH-23-100 ).

Established by the NIH, NDA is a secure informatics platform for scientific collaboration and data-sharing that enables the effective communication of detailed research data, tools, and supporting documentation. NDA links data across research projects through its Global Unique Identifier (GUID) and Data Dictionary technology. Investigators funded under this NOFO are expected to use these technologies to submit data to NDA.

To accomplish this objective, it will be important to formulate a) an enrollment strategy that will obtain the information necessary to generate a GUID for each participant, and b) a budget strategy that will cover the costs of data submission. The NDA website provides two tools to