It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. 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

The intent of this Funding Opportunity Announcement (FOA) 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), the National Institute on Drug Abuse (NIDA), or the National Institute on Alcohol Abuse and Alcoholism (NIAAA) 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, substance use disorders (SUDs), or alcohol use disorder (AUD); 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, SUDs or AUD, and as potential new therapeutics. Partnerships between academia and industry are strongly encouraged.

Each NCDDG program should consist of a multi-disciplinary team of scientists with appropriate expertise to further the development and evaluation of novel compounds 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, SUDs or AUD; 2) increase the availability of pharmacologic and device-based research tools (including imaging agents) for basic and clinical research; 3) facilitate the development and validation of neurophysiological and pharmacokinetic (PK) and pharmacodynamic (PD) measures to evaluate novel therapeutics for mental disorders, SUDs, or AUD; 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 PoC trials of novel therapeutics for mental disorders, SUDs or AUD; 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, SUDs, or AUD, 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 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, SUDs, or AUD. 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, SUDs, or AUD.

An application to this FOA can include two to three scientific projects along with Scientific and/or Administrative Cores. Applications proposing only a single research project and no cores should respond to the companion FOA utilizing the U01 mechanism (see PAR-20-118).

The intent of this FOA 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), the National Institute on Drug Abuse (NIDA), or the National Institute on Alcohol Abuse and Alcoholism (NIAAA) 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, substance use disorders (SUDs), or AUD; and to develop novel ligands and novel brain circuit-modulatory technologies as tools to advance biological and clinical 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, SUDs, or AUD, and as potential new therapeutics. Partnerships between academia and industry are strongly encouraged.

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 FOA 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 DSM diagnostic entities are encouraged. Additional information about the RDoC approach can be found at 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:

• Ligand discovery for therapeutics development or as clinical research tools (e.g., imaging probes) for novel molecular targets implicated in mental illnesses;
• Development and application of novel assays for evaluating brain pharmacodynamic (PD)/pharmacokinetic (PK) relationships in preclinical and early phase human studies;
• 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;
• Phase I studies (FIH pharmacology experiments) that include PD/PK biomarkers to assess target engagement, functional pharmacological activity or physiological effect, safety, and tolerability of new drugs;
• Novel tool and biomarker development to enable studies to assess target engagement, brain PD and PK for innovative drug targets; for example, PET tracers for evaluating receptor occupancy and interrogating dose-response relationships;
• Phase Ib studies in the proposed disease population to confirm target engagement, establish optimal dosing, PK/PD, CNS exposure, functional pharmacological or neurophysiological activity, and tolerability of the novel compound, agent, or device.
• The inclusion of PD measures to assess functional pharmacological activity of the agent is encouraged in dose-finding studies.
• The Phase IIa PoC study should provide sufficient objective data on CNS pharmacological activity and associations with functional measures for projects to be "de-risked" to attract public or private funding for further clinical and commercial development;

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, IDE submission, risk determinations, or other FDA regulatory submissions.
• Device, software, and firmware design verification and validation activities.
• 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.
• Bench-top and/or animal testing to demonstrate compliance with FDA Recognized Standards.
• GLP compliant large animal model safety and/or testing of an implanted device.
• Activities to become current Good Manufacturing Practice (GMP) compliant.
• Activities to bring the development process under Design and Quality Systems Control.
• Development of packaging, connectors, and other accessories necessary for the translation of this technology.
• FIH, proof of concept studies that may assess initial measures of safety and efficacy and lead to further refinement of the device.
• Linkage of behavior with brain recordings via high density recordings of both.
• 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).

For PoC studies, priority will be given to novel agents that are IND-ready or IDE-ready with pre-clinical profiles suggesting the possibility of therapeutic effect in mental disorders. Testing of novel indications for already approved agents/devices will be considered, based on feasibility, strong theoretical rationale, and unmet clinical or medical need.

NIAAA's interests pertaining to the NCDDG program are in the discovery of novel ligands and development of medications for the treatment of AUD as well as novel ligands to be used as tools to research biological processes contributing to excessive drinking as well as to other important AUD clinical features (e.g., hyperkatifeia, sensory and emotional pain, stress responsivity, and impaired sleep function). The focus of proposed research projects should follow that described above by NIMH but should be relevant to the mission of NIAAA. Applicants are strongly encouraged to discuss applications involving toxicity, safety and pharmacokinetics as well as PoC studies of novel compounds with NIAAA staff listed in Section VII. Agency Contact(s). Scientific/Research Contacts.

Pharmaceutical strategies currently of interest to NIAAA for treating AUD include agents that: a) reduce craving or the urge to drink, b) reduce the signs and symptoms of protracted alcohol withdrawal including sleep disturbances and negative affect, and c) reduce psychological distress which contributes to elevated alcohol consumption. Alcohol's multiple biological effects and the spectrum physical and behavioral alterations that occur following chronic excessive alcohol drinking offer opportunities for developing additional pharmacotherapies.

NCDDG is an opportunity to identify and develop compounds towards both existing and new molecular targets having the potential to treat alcohol use disorders, or to facilitate and enhance basic and clinical research on identifying the neurobiological and behavioral processes that contribute to the transition from voluntary to compulsive drinking. Alcohol-seeking and excessive alcohol drinking are modulated through the actions of neurotransmitter receptors and transporters, ion channels, neuromodulators, hormones, and intracellular signaling networks. Thus, there are many potential target sites for which new pharmaceutical agents may be developed, such as effectors of neurotransmitter systems, neuroimmune pathways, and signal transduction pathways.

Cell and tissue platforms may be developed and validated as initial screening tools to evaluate candidate compounds. We further expect that compounds of high interest will be tested and evaluated in validated animal models of AUD clinical features. Because no single compound is expected to address all behavioral aspects and consequences of AUD, projects that propose integrating multiple testing paradigms are sought.

Identifying and developing agents towards novel targets previously unrecognized or understudied for the treatment of alcohol abuse disorders is especially encouraged. Functional alcohol antagonists, targets aimed at blocking the rewarding effects of alcohol, therapies eliciting noxious states in response to drinking, and narrow variants of clinically validated AUD medications (e.g., naltrexone, ondansetron) are deemed low priority by NIAAA. Applications that essentially propose to further extend the testing of established or well-studied compounds and strategies are not appropriate for this FOA.

The National Institute on Drug Abuse (NIDA) is interested in applications focused on research projects that are looking into elucidation of constellations and patterns of addictions noninvasive peripheral biomarkers, neurocircuitry, neurophysiological patterns, gene expression changes and other human objective measures in their composite combinations, aiming at discovery of SUDs biosignatures and biotypes of addictions. This research will allow for patients stratification in future clinical studies, define therapeutic efficacy, help to predict disease outcomes (e.g., time to relapse), predict a response to a therapeutic and/or behavioral intervention and provide insight into target discovery based on the defined context of use. Delineation of biotypes will lead to more precise diagnosis in highly heterogenous populations of drug users that can transcend current diagnostic boundaries, as well as provide a range of novel targets for addictions drug development. We encourage applications that use big data analytics and/or utilize computational approaches analyzing large, complex datasets acquired from existing drug addiction research.

Summary

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, SUDs or AUD. 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 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 FOA. 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 mechanism of action and disease-oriented approaches are of interest.

Research Scope

The objective of this FOA is to establish NCDDG Groups to conduct innovative, high impact research focused on the discovery and testing of chemical entities for novel molecular targets, as well as novel devices for novel circuit/neural dynamic targets modulation implicated in the pathophysiology of mental disorders, or SUDs, or AUD. The NCDDG serves as a vehicle for pharmaceutical, biomedical device 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, SUDs, or AUD.

The identification of lead compounds/devices and refining them for target validation and medication development are important goals of this initiative.

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) and/or the NIH Bridging Interventional Development Gaps (BrIDGs) Program (https://ncats.nih.gov/bridgs/about).

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

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 Protection of Human Subjects section and data and safety monitoring plans should reflect the policies and guidance in this notice. Plans for the protection of research subjects and data and safety monitoring will be reviewed by the NIMH for consistency with NIMH and NIH policies and federal regulations.

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

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

Higher Education Institutions

• 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)

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)
• 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 Institutions) 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

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• 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.
• eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but 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 DUNS number and 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 his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

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

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

• 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 NOT-OD-11-101).

The application forms package specific to this opportunity must be accessed through ASSIST or an institutional system-to-system solution. A button to apply using ASSIST is available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. 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:

Email: [email protected]

Available Component Types	Research Strategy/Program Plan Page Limits
Overall	12 pages
Admin Core (use for Administrative Core)	6 pages
Core (use for Scientific Cores)	6 pages per Core
Project (use for Research Projects)	12 pages per Project

Additional page limits described in the SF424 Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the SF424 (R&R) Application Guide, and should be used for preparing a multi-component application.

Revision applications must include an Overall component and the components that are affected by the revision. Therefore, the component requirements listed below may not apply to the revision application.

The application should consist of the following components:

• Overall: required
• Administrative Core: required; maximum of 1
• Scientific Cores: optional; maximum of 2
• Research Projects: required, minimum of 2; maximum of 3

When preparing your application, use Component Type Overall .

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

Complete entire form.

Note: Human Embryonic Stem Cell lines from other components should be repeated in cell line table in Overall component.

Follow standard instructions.

Enter primary site only.

A summary of Project/Performance Sites in the Overall section of the assembled application image in eRA Commons compiled from data collected in the other components will be generated upon submission.

Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this FOA) for the entire application.

It is anticipated that the NCDDG will include multi-disciplinary teams of scientists with appropriate expertise for the NCDDG project. Scientists from both academia and biotechnology or pharmaceutical industry are encouraged to participate in the project and may serve as the only PD/PI or one of multiple PD/PI.

A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.

The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover.

A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.

Introduction to Application: For Resubmission and Revision applications, an Introduction to Application is required in the Overall component and should include how, or if, specific aims have changed from the earlier application.

Specific Aims: Provide a concise description of overall NCDDG aims. Outline how the Projects and Core(s) will contribute to attaining objectives. The renewal should state how, or if, specific aims have changed from the previous funding period.

Research Strategy: The following information should be included:

• The NCDDG Program objectives and goals should be relevant to and compatible with the NIMH, NIDA, or NIAAA priorities in Section I - Funding Opportunity Description.
• Applicants should describe plans to accommodate the stated NCDDG requirements, criteria, and NIMH, NIDA, or NIAAA involvement. The development of analogs of established or well-studied agents for the treatment of mental disorders, SUDs or alcohol abuse is not appropriate for this FOA.
• An overview of the proposed NCDDG Group, its central theme and goals; this overview should describe the general objectives, and explain the proposed contribution of each of the individual Research Project(s) and Scientific and Administrative Cores (if any) towards achieving the objectives of the Group.
• A clear description of how each Research Project is required for the attainment of the NCDDG Program's objectives, including available professional and technical personnel to permit efficient and successful conduct of the proposed research, and description of the contribution of each to fulfillment of group objectives.

Letters of Support: Include letters of commitment to the collaboration and communication plan (described in the Research Strategy) by all Research Project Leaders.

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 are allocated to the project; this amount must be specified in the letter. 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 SF424 (R&R) Application Guide, with the following modification:

NIMH Data Sharing Notice NOT-MH-19-033, with the following modification:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
• Data from the NCDDG program should be made available to the research community through publications, or public website, consistent with achieving the goals of the Program.
• Positive or negative data from NIH supported clinical trials should be made available to the research community through ClinicalTrials.gov, publications, or public website, consistent with achieving the goals of the Program.
• The applicant should address a plan and timeline for sharing chemical synthesis, preclinical and clinical trials data, and research tools generated by the NCDDG.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Overall)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).

All instructions in the SF424 (R&R) Application Guide must be followed

All instructions in the SF424 (R&R) Application Guide must be followed.

When preparing your application, use Component Type Admin Core.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• It is anticipated that the NCDDG will include multi-disciplinary teams of scientists with appropriate expertise for the NCDDG project. Scientists from both academia and biotechnology or pharmaceutical industry are encouraged to participate in the project.
• Biotechnology or pharmaceutical partners should include key personnel who have authority within the company to allocate resources to ensure successful completion of the proposed discovery and development efforts.
• The inclusion of a Project Manager in the Administrative Core appropriate to the complexity of the group is strongly encouraged.

Budget forms appropriate for the specific component will be included in the application package.

The Admin Core Lead will be expected to devote at least 1.8 person months of effort per year to the NCDDG program.

This program strongly encourages in-kind resource contributions of the partners within the NCDDG (e.g., biotechnology, pharmaceutical, or disease foundations).

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Introduction to Application: For Resubmission and Revision applications, an Introduction to Application is allowed for each component.

Specific Aims: Provide a concise description of the Administrative Core aims.

Research Strategy: Describe how the Administrative Core will contribute to the goals of the overall NCDDG as well as any novel features of the Administrative Core that enhance the collaborative effort, including optimizing communication, decision-making and sharing between the Project and/or Scientific Core teams. Describe how each Project or Scientific Core (as applicable) will draw upon the Administrative Core and how it in turn will respond to Project or Scientific Core needs. The description of the Core should clearly indicate the facilities, resources, services and professional skills that the Core will provide. Moreover, information must be provided about how the collective operation of the Core will be effected in a coherent manner. Include plans for scheduling group meetings, notifying group members (including NIMH, NIDA, or NIAAA), and documenting and disseminating group meeting proceedings.

Applicants should summarize proposed plans for further development of promising compounds or clinical candidates that are generated and/or tested by the NCDDG program.

A plan should be described for decision-making regarding identification and evaluation of promising drug candidates for development.

A plan to assure the maintenance of close collaboration and effective communication among members of the group.

Letters of Support: Include letters of commitment to the collaboration by private sector partners or collaborators. 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 SF424 (R&R) Application Guide, with the following modifications:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
• Data from the NCDDG program should be made available to the research community through publications, or public website, consistent with achieving the goals of the Program.
• Positive or negative data from NIH supported clinical trials should be made available to the research community through ClinicalTrials.gov, publications, or public website, consistent with achieving the goals of the Program.
• The applicant should address a plan and timeline for sharing chemical synthesis, preclinical and clinical trials data, and research tools generated by the NCDDG.

Appendix:

Only limited items are allowed in the Appendix.Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

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

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the SF424 (R&R) Application Guide must be followed.

When preparing your application in ASSIST, use Component Type Scientific Core.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover (Scientific Core)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Scientific Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Scientific Core)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Scientific Core)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Scientific Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• It is anticipated that the NCDDG will include multi-disciplinary teams of scientists with appropriate expertise for the NCDDG project. Scientists from both academia and biotechnology or pharmaceutical industry are encouraged to participate in the project.
• Biotechnology or pharmaceutical partners should include key personnel who have authority within the company to allocate resources to ensure successful completion of the proposed discovery and development efforts.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget (Scientific Core)

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Scientific Core)

Introduction to Application: For Resubmission and Revision applications, an Introduction to Application is allowed for each component.

Specific Aims: Provide a concise description of Core aims.

Research Strategy: Describe how the Core will contribute to the goals of the overall NCDDG as well as how each individual Research Project will draw upon the Core. The description of the Core should clearly indicate the facilities, resources, services and professional skills that the facility will provide. Moreover, information must be provided about how the collective operation of the Cores will be effected in a coherent manner. Identify measurable milestones and a time line of the research activities for the core over the life of 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. 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 SF424 (R&R) Application Guide, and NIMH Data Sharing Notice NOT-MH-19-033, with the following modifications:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
• Data from the NCDDG program should be made available to the research community through publications, or public website, consistent with achieving the goals of the Program.
• Positive or negative data from NIH supported clinical trials should be made available to the research community through ClinicalTrials.gov, publications, or public website, consistent with achieving the goals of the Program.
• The applicant should address a plan and timeline for sharing chemical synthesis, preclinical and clinical trials data, and research tools generated by the NCDDG.

Appendix: Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

PHS Human Subjects and Clinical Trials Information (Scientific Core)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

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

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). AAll instructions in the SF424 (R&R) Application Guide must be followed.

When preparing your application in ASSIST, use Component Type Project.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover (Research Project)

• Complete only the following fields:
• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Research Project)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Research Project)

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

Project /Performance Site Location(s) (Research Project)

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

Research & Related Senior/Key Person Profile (Research Project)

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• Biotechnology or pharmaceutical partners should include key personnel who have authority within the company to allocate resources to ensure successful completion of the proposed discovery and development efforts.

Budget (Research Project)

This program strongly encourages resource contributions (financial and in-kind), of the partners within the NCDDG (e.g., biotechnology, pharmaceutical, or disease foundations) for IND-directed toxicology and safety studies, and drug supply for phase I and IIa studies.

The Project Lead will be expected to devote at least 1.8 person months of effort per year to the project.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Research Project)

Introduction to Application: For Resubmission and Revision applications, an Introduction to Application is allowed for each component.

Specific Aims: Provide a concise description of each Project aims.

Research Strategy: The following information should be included in the Research Strategy:

• The major goals and objectives of the project and their relationship to the overall effort of the NCDDG.
• The status of current research efforts, the limitations of existing approaches, and how the research questions posed relate to the objectives of the particular project and the NCDDG as a whole.
• The feasibility of the proposed experiments, the advantages of new methodologies (if any), the potential pitfalls, alternative approaches, the means of assessing success of the research to meet the objectives of the project and the NCDDG as a whole.

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. 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 SF424 (R&R) Application Guide, with the following modification:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
• Data from the NCDDG program should be made available to the research community through publications, or public website, consistent with achieving the goals of the Program.
• Positive or negative data from NIH supported clinical trials should be submitted to the appropriate NIMH Data Archive database as detailed in NOT-MH-19-033.
• Key Elements that should be considered when developing such data sharing plan are detailed at: http://grants.nih.gov/grants/sharing_key_elements_data_sharing_plan.pdf.
• Applicants are expected to 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.
• The applicant should address a plan and timeline for sharing chemical synthesis, preclinical and clinical trials data, and research tools generated by the NCDDG.

Appendix:

Only limited items are allowed in the Appendix.Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Research Project)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

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

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Section 2 - Study Population Characteristics

2.7 Study Timeline

Identify measurable milestones and a timeline of the research activities for the Research Project over the life of the project. Milestones should be well described, quantifiable, and scientifically justified. The milestones should be regarded as criteria for evaluating the progress and direction of the Research Project and should not be just a restatement of the specific aims.

• Where a Phase I study is included, describe the track record of the clinical research team in successfully recruiting subjects into clinical trials and research studies and completing proposed studies within the projected timelines. Cite prior relevant trials or systematic reviews that would help to justify why this trial is needed and inform its design.
• Applicants are strongly encouraged to detail the current status of lead compounds and key lead optimization goals for a development program. (e.g., https://www.nimh.nih.gov/research/research-funded-by-nimh/therapeutics/compound_report_card_143596.pdf)
• as well as go-no-go criteria in a testing funnel for advancing compounds across stages (https://www.nimh.nih.gov/research/research-funded-by-nimh/therapeutics/example_testing_funnel_143597.pdf)
• High-quality and reproducible studies that are reported to the scientific community in a transparent manner are an essential cornerstone of the research enterprise. Attention to principles of study design and transparency are essential to enable reviewers, the scientific community, and NIH to assess the quality of scientific findings.

Section 5 - Other Clinical Trial-related Attachments

5.1 Other Clinical Trial-Related Attachments

1. The Clinical and Data Monitoring Plan is a required attachment.

The filename "Clinical and Data Monitoring Plan.pdf" must be used for this attachment. The file name should be appended with 1, 2, 3, etc., as needed.

For each clinical trial proposed, create a document entitled "Clinical and Data Monitoring Plan".

Each Plan includes 2 parts: The Clinical Monitoring Plan for the quality assurance of the proposed clinical trial through clinical monitoring activities, and the Data Monitoring Plan for the quality controls proposed through data monitoring activities.

The NIH requirements for monitoring clinical trials as described below are in addition to the application's Data and Safety Monitoring Plan (DSMP) which describes how patient safety in the trial will be monitored, and the regulatory requirement in 45 CFR 46 for on-going review and approval of all non-exempt human subjects research by the IRB of record.

Part A: The purpose of the Clinical Monitoring Plan is to verify that the clinical trial is being conducted, and documented in accordance with the Protocol, Standard Operating Procedures (SOPs), Good Clinical Practice (GCP), and the applicable regulatory requirement(s).

Describe the persons/entity responsible for conducting the monitoring (e.g., contracted Clinical Research Associate, Data Coordinating Center, Independent study monitor from the Clinical Coordinating Center).

Describe the frequency of planned monitoring activities (e.g., Study Initiation, Interim Visits, Study Close Out), locations where the monitoring will occur (e.g., participating clinical sites, data center, clinical coordinating center) and what data will be reviewed.

• Provide an overall description of the monitoring plan to ensure adherence to the protocol, adequate documentation of the consenting process, and the quality and consistency of the study intervention(s), including fidelity monitoring for behavioral interventions. Include methods to monitor study intervention and system to record and manage exceptions and deviations. If applicable, describe monitoring of participating facilities such as labs or pharmacies for adequate handling and storage of investigational product(s) and study specimens. Include a description to assure that the investigational product(s) accountability and reconciliation are performed adequately during and at the end of the trial per applicable regulatory requirements.
• Describe plans for handling any deficiencies that are uncovered and in cases of serious deficiencies the appropriate reporting to relevant authorities, including but not limited to the IRB of record, DSMB if one is assigned, FDA if applicable, institutional officials and the NIH.

Part B: The purpose of the Data Monitoring Plan is to ensure that validated systems and controls are in place to assure the integrity of the clinical research data being collected for the proposed study:

• Describe methods and systems for data collection (e.g., Case Report Forms/CRFs), data entry, data verification and data validation. Describe the data query process and frequencies and any planned mitigation strategies in the event of noncompliance.
• Describe methods and systems to ensure data confidentiality and subject privacy.
• Describe process for locking the final trial datasets and the planned procedures on data access and sharing, as appropriate.

Applications proposing Clinical Trials that lack the Clinical and Data Monitoring Plan are considered incomplete and will not be peer reviewed.

2. The Milestone Plan is a required attachment.

The filename "Milestone Plan.pdf" must be used for this attachment. The filename should be appended with 1, 2, 3, etc., as needed.

Applicants are required to provide detailed project performance and timeline objectives. This section must include an overview of the project timeline for the following general milestones, as applicable:

• Finalization of clinical protocol (with program agreement, if applicable)
• Registration of clinical trial in ClinicalTrials.gov
• Completion of regulatory approvals
• Enrollment of the first subject
• Enrollment and randomization, if applicable of 25%, 50%, 75% and 100% of the projected study population, including women, minorities and children (as appropriate)
• Completion of data collection time period
• Completion of primary endpoint and secondary endpoint data analyses
• Completion of final study report
• Reporting of results in ClinicalTrials.gov.

These milestones may be negotiated at the time of the award, as necessary.

Applications that lack the Milestone Plan are considered incomplete and will not be peer reviewed.

3. Common Data Elements Applicability is a required attachment.

The filename "Common Data Elements Applicability.pdf" must be used for this attachment. The filename should be appended with 1, 2, 3, etc., as needed.

Applicants are required to provide a description of their plans to consider applicability of Common Data Elements (CDEs).

Investigators are encouraged to consult the Common Data Element (CDE) Resource Portal and to describe if NIH-supported CDEs will be used in the proposed clinical trial. If CDEs are not applicable, applicants are expected to explain why.

NIH encourages the use of common data elements (CDEs) in clinical 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.

Applications proposing Clinical Trials that lack the 'Common Data Elements Applicability' attachment are considered incomplete and will not be peer reviewed.

4. Clinical Protocol Schedule of Events

The filename "Clinical Protocol Schedule of Events.pdf" must be used for this attachment. The fileanme should be appended with 1, 2, 3, etc., as needed.

The clinical protocol schedule of events is to capture a snapshot of the time it takes for protocol procedures to be completed by an individual participant during the trial.

For example:

Week 1 Screening/Baseline Visit (4 hours)- eligibility criteria, obtain informed consent, screening assessment(s), labs, etc.

Week 2, 4, 6, 8, Study Visits (3 hours) intervention(s), assessment(s), labs, scan(s) etc.

Week 12, and 18 Follow-up Visits (3 hours)- assessment(s), labs, scan(s) etc.

Week 24 End of study visit (2 hours)- assessment(s), labs, scan(s) etc.

This document may be provided in a tabular format.

5. Investigator Brochure or Package Insert

The filename "Investigator Brochure or Package Insert.pdf" must be used for this attachment. The file name should be appended with 1, 2, 3, etc., as needed.

The Investigator Brochure or package insert may be attached for a clinical trial testing a drug or biologic.

6. Material safety data sheet (MSDS)

The filename "Material safety data sheet (MSDS).pdf" must be used for this attachment. The filename should be appended with 1 , 2, 3, etc., as needed.

Labeling information or summary of safety information from prior studies may be attached for a clinical trial testing a significant risk investigational device for which an application for a new Investigational Device Exemption (IDE) will be submitted.

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the SF424 (R&R) Application Guide must be followed.

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov.

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies) using ASSIST or other electronic submission systems. Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

This initiative is not subject to intergovernmental review.

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

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

For information on how your application will be automatically assembled for review and funding consideration after submission go to: http://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.

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) and component Project Leads must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management (SAM). Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

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

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In order to expedite review, applicants are requested to notify the NIMH Referral Office by email at [email protected] when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.

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.

Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

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.

In addition, for applications involving clinical trials

A proposed Clinical Trial application may include study design, methods, and intervention that are not by themselves innovative but address important questions or unmet needs. Additionally, the results of the clinical trial may indicate that further clinical development of the intervention is unwarranted or lead to new avenues of scientific investigation.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the Program to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the Program proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a NCDDG that by its nature is not innovative may be essential to advance a field.

Does the NCDDG address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the NCDDG are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

To what degree does the proposed plan for discovery and testing of novel treatments, research tools, and/or preclinical models support the needs for the targeted disease? What is the likelihood that it will produce a new candidate therapeutic for development?

In addition, for applications involving clinical trials

Are the scientific rationale and need for a clinical trial to test the proposed hypothesis or intervention well supported by preliminary data, clinical and/or preclinical studies, or information in the literature or knowledge of biological mechanisms? For trials focusing on clinical or public health endpoints, is this clinical trial necessary for testing the safety, efficacy or effectiveness of an intervention that could lead to a change in clinical practice, community behaviors or health care policy? Does the project cite prior relevant trials or systematic reviews that would help to justify why this trial is needed and inform its design? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is the trial needed to advance scientific understanding?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the NCDDG? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI , do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Have collaborations been established or consultants identified to provide the appropriate depth and breadth of expertise required for the project? Has the PD/PI demonstrated leadership in development, implementation, and management of comprehensive research programs? Are the staffing, governance, and organizational structure appropriate for conducting the study as proposed and within specified timelines? If private sector collaborators or consultants are identified, is there evidence that they will contribute expertise to advance the project? Are there adequate plans for ensuring effective intra-Group communication, interaction, cohesiveness, and coordination among the PD/PI, Research Project Leaders, and NIH Project Scientists? Do the investigators state their willingness to collaborate extensively within the NCDDG group and share information fully??

In addition, for applications involving clinical trials

With regard to the proposed leadership for the project, do the PD/PI(s) and key personnel have the expertise, experience, and ability to organize, manage and implement the proposed clinical trial and meet milestones and timelines? Do they have appropriate expertise in study coordination, data management and statistics? For a multicenter trial, is the organizational structure appropriate and does the application identify a core of potential center investigators and staffing for a coordinating center?

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed? Are the biological targets, mechanisms, or measures considered to be novel?

In addition, for applications involving clinical trials

Does the design/research plan include innovative elements, as appropriate, that enhance its sensitivity, potential for information or potential to advance scientific knowledge or clinical practice?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the NCDDG? Have investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the NCDDG involves human subjects and/or NIH-defined clinical research, are the plans to address:

1) the protection of human subjects from research risks, and

2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

If preclinical testing is proposed, are the designs sufficiently detailed and rationalized and are such studies relevant to the clinical development path? Are the scientific disciplines represented in Research Projects and Scientific Cores adequate to achieve the NCDDG Program objectives? Is there a sound scientific rationale for the proposed molecular or clinical targets? Are targets, screens, and preclinical models relevant to therapeutic discovery for mental disorders and/or SUDs or AUD?

Are the proposed Phase 1 clinical studies for mental disorders designed to assess target engagement, optimal dosing, safety, and tolerability? Are the proposed Phase 1b/IIa clinical studies for mental disorders designed to establish the relationship between the magnitude and duration of target modulation and potential for clinical efficacy in the proposed study population? Are the proposed PD biomarkers to assess functional pharmacological activity of the novel agent or the use of pharmacogenetic or other biomarkers as patient selection strategies appropriate to the proposed clinical studies of mental disorders? Are the proposed device capabilities and neural targets appropriate for the proposed clinical studies of mental disorders?

If PET ligand development is included, is the target novel and is evidence provided to suggest the strategy is likely to succeed? Is there evidence of feasibility that the target can be detected in the brain region(s) of interest with a radiotracer? Are the desired properties for the radiotracer clearly stated and reasonable for the proposed target?

If device stimulation or biomarker development is included, is the target circuit or neural dynamic signal novel and is evidence provided to suggest the strategy is likely to succeed? Is there evidence of feasibility that the target can be detected in the brain circuits of interest by the proposed physiological signal?

If pharmaceutical or device partnerships are proposed, how will they facilitate the development and evaluation of candidate drugs or therapeutics, tools for clinical research, and model validation for testing therapeutics?

In addition, for applications involving clinical trials

Does the application adequately address the following, if applicable:

Study Design

Is the study design justified and appropriate to address primary and secondary outcome variable(s)/endpoints that will be clear, informative and relevant to the hypothesis being tested? Is the scientific rationale/premise of the study based on previously well-designed preclinical and/or clinical research? Given the methods used to assign participants and deliver interventions, is the study design adequately powered to answer the research question(s), test the proposed hypothesis/hypotheses, and provide interpretable results? Is the trial appropriately designed to conduct the research efficiently? Are the study populations (size, gender, age, demographic group), proposed intervention arms/dose, and duration of the trial, appropriate and well justified?

Are potential ethical issues adequately addressed? Is the process for obtaining informed consent or assent appropriate? Is the eligible population available? Are the plans for recruitment outreach, enrollment, retention, handling dropouts, missed visits, and losses to follow-up appropriate to ensure robust data collection? Are the planned recruitment timelines feasible and is the plan to monitor accrual adequate? Has the need for randomization (or not), masking (if appropriate), controls, and inclusion/exclusion criteria been addressed? Are differences addressed, if applicable, in the intervention effect due to sex/gender and race/ethnicity?

Are the plans to standardize, assure quality of, and monitor adherence to, the trial protocol and data collection or distribution guidelines appropriate? Is there a plan to obtain required study agent(s)? Does the application propose to use existing available resources, as applicable?

Data Management and Statistical Analysis

Are planned analyses and statistical approach appropriate for the proposed study design and methods used to assign participants and deliver interventions? Are the procedures for data management and quality control of data adequate at clinical site(s) or at center laboratories, as applicable? Have the methods for standardization of procedures for data management to assess the effect of the intervention and quality control been addressed? Is there a plan to complete data analysis within the proposed period of the award?

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements? If the proposed research plan includes a chemical series that was developed by a biotechnology or pharmaceutical industry, is there evidence of involvement of industry chemists as collaborators or advisors in the project?

In addition, for applications involving clinical trials

If proposed, are the administrative, data coordinating, enrollment and laboratory/testing centers, appropriate for the trial proposed?

Does the application adequately address the capability and ability to conduct the trial at the proposed site(s) or centers? Are the plans to add or drop enrollment centers, as needed, appropriate?

If international site(s) is/are proposed, does the application adequately address the complexity of executing the clinical trial?

If multi-sites/centers, is there evidence of the ability of the individual site or center to: (1) enroll the proposed numbers; (2) adhere to the protocol; (3) collect and transmit data in an accurate and timely fashion; and, (4) operate within the proposed organizational structure?

As applicable for the program proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Is there evidence of institutional support and competence of the applying Institution to serve as the Administrative Core for the Group? Does the clinical research team demonstrate a track record in successfully recruiting subjects into clinical trials and research studies and completing proposed studies within projected timelines?

Does the Core provide essential facilities or services to two or more Research Projects judged to have scientific merit? Is the quality of the facilities or services provided by the Core adequately strong to support the Projects? Are the qualifications and experience of the personnel involved in the Core sufficiently strong to successfully conduct the work of the Core?

Clinical Data Monitoring Plan

Are the procedures for clinical data monitoring and quality control of data adequate? Are standardized systems and controls in place for data monitoring to ensure data integrity and to assess the effect of the intervention?

Timelines and Milestones

Are appropriate, evaluative milestones clearly defined for the aims associated? Are the milestones feasible and quantifiable with regard to specific aims and timeline? Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)? Are the timelines appropriate for the Research Projects and overall NCDDG program? Are definitive go/no-go milestone studies appropriately powered and are statistical analyses clearly described? Are appropriate, evaluative go/no go decision-making points and quantitative milestones provided and clearly defined? Are the milestones feasible and quantifiable? Are the timelines appropriate? Are the recruitment goals appropriate if clinical studies are proposed?

Study Timeline

Specific to applications proposing clinical trials

Is the study timeline described in detail, taking into account start-up activities, the anticipated rate of enrollment, and planned follow-up assessment? Is the projected timeline feasible and well justified? Does the project incorporate efficiencies and utilize existing resources (e.g., CTSAs, practice-based research networks, electronic medical records, administrative database, or patient registries) to increase the efficiency of participant enrollment and data collection, as appropriate? Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

When the proposed program involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.

For Renewals, the committee will consider the progress made in the last funding period.

For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

As applicable for the program 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.

Not Applicable

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genomic Data Sharing Plan .

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s), convened by appropriate IC 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:

• 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.
• Will receive a written critique.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the appropriate 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.

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.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

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: Grantee institutions must ensure that all protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

Data and SafetyMonitoring 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).

Awardee-selected projects that involve clinical trials or studies involving greater than minimal risk to human subjects require prior approval by NIH prior to initiation.

• The awardee institution will provide NIH with written study protocols that address risks and protections for human subjects in accordance with NIH s Instructions for Preparing the Human Subjects Section of the Research Plan.
• The awardee institution will provide NIH with specific plans for data and safety monitoring, and will notify the IRB and NIH of serious adverse events and unanticipated problems, consistent with NIH DSMP policies.

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.html; and https://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

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 (DHHS) grant administration regulations at 45 CFR Parts 75, 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 awardees 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 award 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 awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

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

• The PD/PI will have primary authority and responsibility to define objectives and approaches and to plan and conduct the research supported in the NCDDG. For every NCDDG Award there will be a "Group". This Group consists of the PD/PI (or all the PD/PIs for multiple PI grants) and key research scientists or collaborators, as defined by the PD/PI(s), in the grant application. The PD/PI(s) will assume responsibility and accountability to the applicant organization and to the NIMH, NIDA and/or NIAAA for performance and proper conduct of all research supported in the NCDDG, including the research conducted in the NIH intramural component, if applicable, in accordance with the Terms and Conditions of Award. The PD/PI(s) will be a member of the Steering Committee (described below).
• Intramural research scientists participating as research collaborators or consultants have the same rights and responsibilities as other members of the Group (see below for Participation of NIH Intramural Scientists).
• The Awardee Institution will retain primary custody of and have primary rights to data as specified under either the NIMH, NIDA and/or NIAAA approved Intellectual Property Patent Rights Agreements for New Chemical Entities (described below) or the data and research resource sharing plans (described above). The Government, via the NIMH, NIDA or NIAAA 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 Group members is encouraged. Publication or oral presentation of work done under this agreement will require appropriate acknowledgment of NIMH, NIDA or NIAAA support, including the assigned cooperative agreement award number.
• Ownership of compound libraries or devices for drug discovery acquired during the course of the research rests with the Group. Prior to award, the Group(s) should formulate a plan for final disposition of the compounds and ownership rights in the event that the compounds are transferred to other parties who make discoveries using them. This plan is to be approved by NIMH, NIDA or NIAAA.
• It is the intention that new chemical entities or devices be fully evaluated as potential candidate drugs for mental health disorders, SUDs or AUD or as potential research tools, after the Group has concluded its evaluation and before the compounds are transferred to other parties for evaluation in other therapeutic areas. The Groups must follow the NIMH, NIDA or NIAAA approved Intellectual Property Patent Rights Agreements for New Chemical Entities (described below) or the data and research resource sharing plans (described above).

NIH staff members will 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 Group and may provide appropriate assistance, including assisting in research planning, suggesting studies within the scope of the Group's objectives and research activities, presenting experimental findings to the Group from published sources or from relevant contract projects, and advising in management and technical performance. The Project Scientist(s) will be a member(s) of the Steering Committee (defined below). 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, NIDA, or NIAAA will be to assist and facilitate and not to direct activities.

The NIMH, NIDA, or NIAAA Project Scientist(s) can recommend to their Institutes to utilize their drug development resources (e.g., CNS receptor screening, chemical synthesis, and toxicology services) in support of the NCDDG Group research activities if such resources are required on an occasional basis. The following is a list of resources that are readily available and may be supplied if they become desirable during performance. It is not anticipated that requests of services will be considered as a continuing need.

• Reference compounds for standardization of test systems, as analytical standards, and for related purposes.
• Data from testing conducted in resource contract laboratories.
• Laboratory testing capacity, whenever appropriate and possible, in NIMH's and NIDA's current contract based preclinical testing programs or in the Bridging Interventional Development Gaps (BrIDGs, http://www.ncats.nih.gov/bridgs) program and Blueprint Neurotherapeutics Network (BPN, https://neuroscienceblueprint.nih.gov/bpdrugs/). The Group is expected to provide sufficient test material for such testing.
• Additional needed resources such as test materials and information that may not otherwise be available to the Group.
• FIH and Phase I studies may be reviewed by the appropriate NIH Institute's Data and Safety Monitoring Board (DSMB) to ensure the safety of participants and the validity and integrity of the data. The study protocol(s) and consent form(s) will be reviewed by the DSMB prior to initiation of the project. The DSMB will review study reports from the NCDDG group on a regular basis to monitor subject enrollment and retention, safety, quality of data collection, and integrity of the study. Based on its review, the DSMB has the authority to stop the study after it has started.
• Additionally, an NIMH, NIDA, or NIAAA Program Official will be responsible for the normal scientific and programmatic stewardship of the award, including monitoring implementation of the data and research resource sharing plans and will be named in the award notice.

Participation of NIH Intramural Scientists. An NIH intramural scientist may not serve as the PD/PI of an NCDDG but may participate in a Group as collaborator, or consultant. However, an Intramural scientist may not receive salary, equipment, supplies, or other remuneration from awards resulting from this FOA. 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. 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. The participation of an intramural scientist is independent of and unrelated to the role of the NIMH, NIDA and/or NIAAA Project Scientist. For NCDDG applications that include NIH intramural components, the intramural resource level will be included in the total cost of the overall application. The involvement of Intramural scientists needs to be consistent with NIH Policy, http://www1.od.nih.gov/oir/sourcebook/ethic-conduct/ethical-conduct-toc.htm.

Areas of Joint Responsibility include:

Steering Committee: A governing Steering Committee composed of the PD/PI(s), key research scientists, collaborators or consultants, outside experts), the NIH Project Scientist(s), and the NIH Program Official (as a non-voting member) will be established in each NCDDG to assist in monitoring and developing the scientific content and direction of the program. When included in the Steering Committee, outside experts are chosen by the PD/PI(s) in consultation with the NIH Project Scientist and Program Official. Each named member of the Steering Committee will have one vote, except the NIH Program Official.

The Steering Committee members will meet periodically to review and monitor progress, plan and design research activities, and establish priorities. The frequency of meetings, not fewer than two per year, will be determined by the PD/PI, who 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 Group within 2 weeks of the meeting.

a. The principal end products of NCDDG activities for NIMH and NIAAA are expected to include: 1) the discovery and testing of new chemical entities, optimization of lead compounds, IND-directed toxicology, safety pharmacology to support phase I studies and identification of clinical candidates for subsequent PoC studies for the treatment of mental disorders or AUD; 2) research tools; 3) models and pharmacodynamic measures to evaluate novel therapeutics; 4) new device technology for neurostimulation. Cost-sharing is encouraged for IND-directed toxicity and safety studies of drug candidates, GMP synthesis, formulation, and IND filing costs.

b. The principal end products of NCDDG activities for NIDA are expected to include: 1) the discovery of ligands for target validation studies and potentially for development as pharmacotherapies for SUDs, 2) research tools to advance research in the treatment development domain, and 3) preclinical models to evaluate novel therapeutics. Studies required for IND-targeted preclinical development (GMP synthesis, formulation, toxicology) are generally beyond the scope of this FOA for NIDA. Such development through the NIH BRiDGS program or private venture capital is encouraged.

c. NIMH and/or NIAAA will retain the option to cross-file or independently file an application for an investigational clinical trial (e.g., an IND application to the United States Food and Drug Administration) of any clinical research tool or invention resulting from these NIH supported cooperative agreements. Reports of data generated by the Group or any of its members required for inclusion in IND applications and for cross-filing purposes shall be submitted promptly by the Principal Investigator to the NIH Institute Project Scientist upon request. Such reports shall include background information, methods, results, and conclusions.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. The three members include: 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 awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

Intellectual Property and Patent Rights for New Chemical Entities:

Since the discovery of new pharmacological treatments for mental disorders, SUDs or SUD is a major objective of this effort and active involvement by pharmaceutical laboratories is encouraged and may be facilitated by the existence of appropriate patent coverage, it is essential that applicants provide plans to address the handling of intellectual property for new chemical entities for the treatment of mental disorders, SUDs or AUD under this FOA.

Successful applicants are required to supply the following confidential materials to the NIMH, NIDA and/or NIAAA Program Officials listed under Section VII. Agency Contacts.

1. Each applicant Group must provide a detailed description of the approach to be used for handling intellectual property and for licensing where appropriate, in particular where the invention may involve investigators from more than one institution. Procedures must be described for resolution of legal problems should they arise. Your attention is drawn to the NIH Extramural Technology Transfer Policies and Documents [http://grants.nih.gov/grants/intell-property.htm].

2. A formal statement of Intellectual Property among all Group members and their institutions as well as a detailed description of procedures to be followed for resolution of legal problems which may develop, must be signed and dated by the organizational official authorized to enter into intellectual property arrangements for each Group member and member institution. The signed agreement should be submitted prior to award to the appropriate NIMH, NIDA and/or NIAAA staff at the addresses provided under Section VII. Agency Contacts.

3. A plan must be developed for disposition of combinatorial and compound libraries generated in Research Projects focused on discovery of new chemical entities as clinical candidates for drug development in conformance with Section VI.2.A - Cooperative Agreement Terms and Conditions of Award and consistent with achieving the goals of the program. The signed document should be submitted prior to award to the appropriate NIMH, NIDA and/or NIAAA staff at the addresses provided under Section VII. Agency Contacts.

4. Prior to the award, the PD/PI must provide a signed statement of acceptance of the participation of NIMH, NIDA or NIAAA staff during performance of the award as outlined under "NIH Staff Responsibilities" in Section VI.2.A - Cooperative Agreement Terms and Conditions of Award.

Note: Do NOT submit documents 1-4 above with the application. However, awards will not be made until these documents are received by NIMH, NIDA or NIAAA.

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

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

Linda Brady, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-443-3563
Email: [email protected]

Tanya Ramey, M.D., Ph.D.
National Institute on Drug Abuse (NIDA)
Telephone: 301-827-5944
[email protected]

Mark Egli, Ph.D.
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-594-6382
Email: [email protected]

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

Dharmendar Rathore, PhD
National Institute on Drug Abuse (NIDA)
Telephone: 301-402-6965
Email: [email protected]

RV Srinivas, Ph.D.
National Institute of Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-451-2067
Email: [email protected]

Terri Jarosik
National Institute of Mental Health (NIMH)
Telephone: 301-443-3858
Email: [email protected]

Yinka Abu
National Institute on Drug Abuse (NIDA)
Telephone: 301-490-3203
Email: [email protected]

Judy Fox
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Telephone: 301-443-4704
Email: [email protected]

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.