Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Institute of Mental Health (NIMH)

Funding Opportunity Title
Accelerating Medicines Partnership Schizophrenia (AMP SCZ): Clinical High Risk for Psychosis Clinical Trial Network (U01 Clinical Trial Required)
Activity Code

U01 Research Project Cooperative Agreements

Announcement Type
New
Related Notices

  • July 20, 2023 - Notice of Technical Assistance Webinar for RFA-MH-24-150, "Accelerating Medicines Partnership Schizophrenia (AMP SCZ): Clinical High Risk for Psychosis Clinical Trial Network (U01 Clinical Trial Required)". See Notice NOT-MH-23-365
  • August 31, 2022 - Implementation Changes for Genomic Data Sharing Plans Included with Applications Due on or after January 25, 2023 - See Notice NOT-OD-22-198.
  • August 5, 2022 - Implementation Details for the NIH Data Management and Sharing Policy - see Notice NOT-OD-22-189.

Notice of Funding Opportunity (NOFO) Number
RFA-MH-24-150
Companion Funding Opportunity
RFA-MH-24-151 , U24 Resource-Related Research Project (Cooperative Agreements)
Assistance Listing Number(s)
93.242
Funding Opportunity Purpose

The purpose of this Notice of Funding Opportunity (NOFO) is to support one clinical trial network to evaluate biological, digital, cognitive, and clinical outcome measures in individuals at clinical high risk (CHR) for psychosis in Proof of Principle (PoP) trial(s) using a pharmacological intervention. Unique drug development tools developed through the Accelerating Medicines Partnership Schizophrenia (AMP SCZ) initiative will be evaluated in the PoP trial(s). The compound(s) selected for testing by the AMP SCZ Steering Committee will affect a pathophysiologically relevant mechanism and have the potential to produce a detectable signal on biological, digital, cognitive, or clinical outcome measures within a 12-16 week period of study.

Key Dates

Posted Date
July 12, 2023
Open Date (Earliest Submission Date)
September 17, 2023
Letter of Intent Due Date(s)

September 17, 2023

Application Due Dates Review and Award Cycles
New Renewal / Resubmission / Revision (as allowed) AIDS - New/Renewal/Resubmission/Revision, as allowed Scientific Merit Review Advisory Council Review Earliest Start Date
October 17, 2023 Not Applicable Not Applicable March 2024 May 2024 July 2024

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

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

Expiration Date
October 18, 2023
Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts).

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

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

Table of Contents

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Background

Approximately 100,000 young persons in the United States experience a first episode of psychosis every year. During the same interval, it is estimated that over one million children and adolescents experience problems in perception, thinking, mood, and social functioning suggestive of a pre-psychosis risk state. Given the highly disruptive and disabling nature of psychotic disorders, early intervention is a strategy for preventing psychosis onset among individuals at clinical high risk (CHR), as well as averting other adverse outcomes such as mood syndromes, substance abuse disorders, and functional decline in social, academic, and vocational domains.

Although molecular targets have been identified as having therapeutic potential in the CHR population, testing the validity of these targets at the CHR stage has been hampered by low and variable rates of conversion to psychosis and other outcomes, lack of biomarkers that reliably predict progression, and heterogeneous clinical outcomes for the CHR syndrome, including anxiety, depression, and substance use disorders. The AMP SCZ initiative was launched in 2020 as an international collaboration designed to address these challenges and de-risk the drug development process. This collaborative effort is jointly validating a set of drug development tools and developing predictive algorithms for use in CHR clinical trials, including biomarkers and digital, cognitive, and clinical outcome measures that can be reliably used to predict psychosis and non-psychosis outcomes over periods ranging from 18-24 months.

The AMP SCZ initiative has generated a set of drug development tools (biomarkers, digital, cognitive, and clinical outcome measures, including the Positive Symptoms and Diagnostic Criteria for the Comprehensive Assessment of At Risk Mental States (CAARMS) Harmonized with the Structured Interview for Psychosis-risk Syndromes (SIPS) (PSYCHS), to create algorithms that can reliably and validly distinguish the clinical courses of individuals with CHR (conversion to psychosis, remission, and non-conversion/non-remission). As a follow up to this initiative, the CHR for Psychosis Clinical Trial Network will establish infrastructure to evaluate the utility of these tools in one or two PoP trials utilizing Phase 2 ready compounds that will be selected by the AMP SCZ Steering Committee.

The ultimate goal of this NOFO is to determine whether the biological, digital, cognitive, and clinical outcome measures developed in the AMP SCZ observational study (https://www.ampscz.org/scientists/design/) are viable as drug development tools for use in future Phase 2 studies. Also, a secondary goal is to determine whether the biomarkers can act as pharmacodynamic readouts of drug response and/or provide insights into proposed mechanisms or pathways underlying CHR for psychosis.

Research Objectives

This NOFO solicits applications to establish a multi-site clinical trial network that will evaluate the potential of the selected compound(s) as an experimental manipulation to detect a signal on one or more biological, digital, cognitive, or clinical outcome measures within a 12-16 week time frame and generate novel insights into early intervention in CHR for psychosis. The clinical trial network will be responsible for conducting at least one PoP trial with the possibility of conducting a second, subsequent trial depending on the availability and selection of another suitable pharmacologic agent and the success of the first PoP trial in meeting its predetermined goals and milestones. Therefore, the project period may be less than 5 years if a second trial is not undertaken.

The PoP trial(s) will require recruitment of over 100 CHR participants and evaluation of an investigational pharmacological intervention that will be selected by the AMP SCZ Steering Committee. Drug development tools generated by the AMP SCZ observational study, including the PSYCHS, will be assessed in the trial(s).

The investigative team should have expertise in the range of biological and clinical outcome measures currently being examined in the AMP SCZ observational study, as described in the published protocol (https://www.ampscz.org/scientists/protocols). These measures include clinical, cognitive, neurophysiology (EEG), neuroimaging (structural/functional MRI), genetic, fluid markers, speech and facial expression analysis, digital measures and clinical outcome assessments. Ultimately, a subset of measures to be used in the PoP trial(s) will be determined by the AMP SCZ Steering Committee based on both the results of the ongoing AMP SCZ observational study and the compound(s) selected for the trial(s).

Specifically, the NOFO encourages proposed studies that will:

  • Establish clinical trial network infrastructure with the requisite expertise to conduct a PoP trial and evaluate the predetermined biological and clinical outcome measures.
  • Demonstrate the capability for recruitment of well-characterized CHR subjects in a coordinated clinical trial network, with a broad referral network and high participant flow at each of the clinical sites.
  • Validate, in collaboration with the Clinical Trial Data Processing, Analysis and Coordination Center (CT-DPACC; see below), multimodal biomarker approaches that can detect a signal in response to an investigational pharmacological intervention.
  • Have the capacity to fulfill all of the regulatory requirements for executing a clinical trial, including filing an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA).
  • Have the expertise and capability to add additional exploratory biomarker or digital technologies.

Anticipated outcomes from this program of research include:

  • Rapid recruitment of CHR individuals characterized with a common set of biomarker and clinical and functional outcome assessments.
  • Evaluation of the utility of the clinical outcomes (e.g., PSYCHS) and biomarkers developed in the AMP SCZ observational study.
  • Determining the ability to detect a change in signal on the predetermined biological and clinical outcome measures within the 12-16 week study period in response to a pharmacological intervention.
  • Testing of exploratory biomarker or digital technologies.

The minimal requirements of a CHR Clinical Trial Network under this NOFO are as follows:

1. Research Project(s): A CHR clinical trial network application must demonstrate expertise in conducting a clinical trial at each of the clinical sites. The network should include 10-15 sites with the aim of recruiting a minimum of 100 participants across sites. The PoP trial should plan to include three arms: a placebo arm, a low-dose group, and a high dose group. The proposed network must have a centralized site that serves administrative and organizational functions for the clinical sites. The network sites should have the capability to implement the same biomarker and clinical measures as the AMP SCZ observational study, though only a subset of measures that relate to the compound(s) will be included in the PoP trial. The PSYCHS outcome measure will be utilized for ascertainment of CHR status during the trial; training for investigators that have not previously used the PSYCHS measure will be arranged by the AMP SCZ Steering Committee.

In an effort to leverage the standardization of equipment and protocols that have occurred in the observational study, the clinical trial network should consider inclusion of these standardized technologies (e.g., NeuroSig EEG, Prisma MR scanner, Penn Computerized Neurobehavioral Test Battery (CNB), etc.) or propose alternate standardized technologies for collection of the clinical, biomarker, and digital measures. Proposed networks also should have the capability to collect more specialized or exploratory biomarker or digital technologies related to the selected compound’s mechanism of action at one or more sites to be determined in conjunction with NIMH and the AMP SCZ Steering Committee.

Each network will submit one U01 application that includes subawards to the collaborating sites.

2. Partnership with CT-DPACC: The network funded under this NOFO must agree to partner with a CT-DPACC (to be funded under RFA-MH-24-151), which will be functionally separate from the network. The CT-DPACC will, in partnership with the network, receive raw, participant-level data directly from each of the sites in the network in near real-time and perform quality control. The CT-DPACC will oversee all data management, including organizing and performing on-site monitoring. In addition, CT-DPACC staff will provide program support and implement standard operating procedures that include assisting in the design of protocols, data collection forms, data collection/distribution systems, quality assurance and monitoring systems, data sharing, and report generation.

Applications Not Responsive to the NOFO

Studies that are not responsive to this NOFO and will not be reviewed include the following:

  • Applications that propose a clinical trial network with fewer than 10 sites.
  • Applications that propose a clinical trial design with fewer than 100 participants.
  • Applications that do not include a centralized site that serves administrative functions for the clinical sites.

Technical Assistance

Applicants are strongly encouraged to consult with NIMH staff when developing plans for an application (see Agency Contacts, Section VII). This early contact will provide an opportunity to clarify NIMH policies and guidelines and identify whether the proposed project is consistent with the purpose of this NOFO.

The NIMH has published updated policies and guidance for investigators regarding human research protection, clinical research data, and safety monitoring (NOT-MH-19-027). The application’s PHS Human Subjects and Clinical Trials Information, including the Data and Safety Monitoring Plan, should reflect the policies and guidance in this notice. The NIMH will review plans to protect research participants and data and monitor safety for consistency with NIMH and NIH policies and federal regulations.

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

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

Section II. Award Information

Funding Instrument

Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this NOFO.

Application Types Allowed
New

The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this NOFO.

Clinical Trial?

Required: Only accepting applications that propose clinical trial(s).

Funds Available and Anticipated Number of Awards

NIMH intends to commit up to a total of $15,000,000 in FY24 to fund 1 award.

Award Budget
Application budgets are not limited but need to reflect the actual needs of the proposed project.
Award Project Period

The scope of the proposed project should determine the project period. The maximum project period is 5 years.

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

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Local Governments

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

Federal Government

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

Other

  • Independent School Districts
  • Public Housing Authorities/Indian Housing Authorities
  • Native American Tribal Organizations (other than Federally recognized tribal governments)
  • Faith-based or Community-based Organizations
  • Regional Organizations
Foreign Institutions

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 not allowed.

Required Registrations

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.

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

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

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

Eligible Individuals (Program Director/Principal Investigator)

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

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.

PDs/PIs submitting an application under this NOFO will not be eligible to submit an application as a PD/PI under RFA-MH-24-151.

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

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

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

Section IV. Application and Submission Information

1. Requesting an Application Package

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

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide except where instructed in this notice of funding opportunity to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Letter of Intent

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

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

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

The letter of intent should be sent to:

Email: nimhpeerreview@mail.nih.gov

Page Limitations

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

Instructions for Application Submission

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this NOFO.

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

SF424(R&R) Senior/Key Person Profile

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

In the biosketches, highlight the network PD/PI experience in the establishment, coordination, and management of multi-site clinical trial networks, including success in meeting milestones and timelines. In addition, the biosketches must document and define the PD/PI and all Key Personnel experience, roles, and responsibilities.

R&R or Modular Budget

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

The costs associated with attending annual in-person meetings should be included in the proposed budget for PIs and co-investigators.

R&R Subaward Budget

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Research Strategy - Applicants must comply with all of the instructions below:

Significance: Explain why the proposed approach to establishing a clinical trial network that will evaluate the utility of the clinical, cognitive, biological, and digital outcome measures in a PoP trial is optimal to achieve the scientific objectives of the NOFO.

Innovation: Describe the team's capability of employing unique or novel exploratory biological or digital measures that will enrich the overall dataset in the PoP trial. Explain how the research team plans to use current best practices to recruit and retain participants and partner with the CT-DPACC for the purpose of centralized data analysis and resource sharing.

Approach:

Management plan

Present a Management Plan that describes the following:

  • How the PD(s)/PI(s) will manage the proposed project and who will oversee the day-to-day activities (e.g., a project manager). A project manager may, in addition, strengthen the CHR clinical trial network administration.
  • How the clinical trial network will optimize study start-up efficiency and harmonized data collection across sites.
  • How the clinical sites will manage participants not being co-enrolled in other studies during the PoP trial.
  • How the clinical trial network will manage sites that are not meeting their recruitment targets.
  • How the management will support achievement of the proposed goals and milestones.
  • Organization of the CHR clinical trial network, including its coordination and communication functions among sites, key personnel, reporting relationships, a management plan for fiscal accountability and communication.
  • How collaborations or subcontracts, if proposed, will be managed, including the establishment and execution of the Clinical Trial Agreement (CTA).
  • Plans for shared decision making among the PD/PI, NIMH CHR Steering Committee, and clinical sites regarding personnel, clinical decisions, changes in study protocol, and authorship.

Regulatory plan

Present a Regulatory Plan that describes the following:

  • How the PD(s)/PI(s) will file an IND with the FDA to use the selected compound(s).
  • A plan to execute an intellectual property (IP) agreement with the company providing the compound for the PoP trial, including how contract discussions will be handled.
  • How the clinical trial will be monitored by a Data and Safety Monitoring Board (DSMB) and an independent medical monitor.

Biomarker and clinical outcome assessment

  • The application should anticipate the use of the PSYCHS instrument for ascertainment of CHR status and describe how this outcome measure will be employed at the clinical sites.
  • Describe all the biological, clinical, cognitive and digital assessments available to each of the clinical sites. The final assessment battery will be determined in partnership with NIMH and the AMP SCZ Steering Committee.
  • Outline a strategy for feasibly and efficiently collecting the data in a standardized fashion across clinical sites. The application should include a clear plan for how the network’s information technology systems will support this data collection and ensure interoperability among the network sites and timely transfer of the raw data to the CT-DPACC, harnessing the data processing pipelines established for data transfer in AMP SCZ.
  • Identify possible challenges in enrolling CHR participants to meet the project timeline and implementing the clinical and biomarker assessments and propose strategies to overcome these challenges.

Present a detailed set of milestones and a timeline covering all aspects of the clinical trial network’s activities. Include annual milestones and quarterly recruitment milestones with metrics that will document progress towards the achievement of the ultimate goals. Include plans for critically evaluating and revising these milestones on a regular basis.

Workflow for Data Sharing

  • Describe the data security processes and privacy procedures to be used for collecting, storing, and sharing data from trial participants, including establishing a Global Unique Identifier number (GUID) for each participant to de-identify and protect the anonymity of individual-level data. Clinical sites should use the NIMH GUID? ?infrastructure as the subject identifier.
  • ?The data workflow should be designed to facilitate sharing of subject-level data to the CT-DPACC.
  • Present a plan for maintaining high standards for data completeness and integrity, including establishing data quality metrics and data submission procedures to ensure appropriate quality control.

Collaboration with the CT-DPACC and NIMH CHR Steering Committee

Outline a strategy for maintaining a high level of collaboration with the CT-DPACC on key tasks, including the following:

  • Participating as a member of the NIMH CHR Steering Committee, including weekly virtual meetings.
  • Adopting agreed upon standard operating procedures established in the AMP SCZ observational study to collect and share data with the CT-DPACC.
  • Submitting raw participant-level data to the CT-DPACC.

Study Team Expertise: ?The network should include a multidisciplinary team and the application should reflect the team's background in hands-on involvement in the steps needed for operationalizing a clinical trial, including rapid recruitment and assessment of CHR participants, acquisition of multimodal biomarker and clinical data, as well as study coordination.

Describe the study team members experience and expertise in the following areas:

  • Establishment, coordination, and management of clinical trial networks.
  • Experience working with the CHR population.
  • Recruitment and retention of individuals who meet CHR criteria.
  • Collection of multimodal biomarker and clinical and functional outcome data, including experience with MRI, EEG, Penn CNB, and digital assessments.

Environment: ?Describe features of the network and its constituent sites that will facilitate efficient and optimized clinical trial operations.

Specifically, provide evidence of the ability of the sites to (1) enroll the proposed numbers of CHR participants at the rate anticipated for timely completion of the PoP trial(s); (2) adhere to the data collection protocol; (3) collect and accurately transmit data in real time to the CT-DPACC; and, (4) operate within the proposed organizational structure.

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.

Other Plan(s):

Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages.

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

  • All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.

To advance the goal of advancing research through widespread data sharing among researchers, investigators funded under this NOFO are expected to share those data via the National Institute of Mental Health Data Archive (NDA; see NOT-MH-23-100). Established by the NIH, NDA is a secure informatics platform for scientific collaboration and data sharing that enables the effective communication of detailed research data, tools, and supporting documentation. NDA links data across research projects through its Global Unique Identifier (GUID) and Data Dictionary technology. Investigators funded under this NOFO are expected to use these technologies to submit data to the NDA.

To accomplish this objective, it will be important to formulate a) an enrollment strategy that will obtain the information necessary to generate a GUID for each participant and b) a budget strategy that will cover the costs of data submission. The NDA website provides two tools to help investigators develop appropriate strategies: 1) the NDA Data Submission Cost Model which offers a customizable Excel worksheet that includes tasks and hours for the Program Director/Principal Investigator and Data Manager to budget for data sharing; and 2) plain language text to be considered in your informed consent available from the NDA's Data Contribution page. Investigators are expected to certify the quality of all data generated by grants funded under this NOFO prior to submission to NDA and review their data for accuracy after submission. Submission of descriptive/raw data is expected semi-annually (every January 15 and July 15); submission of all other data is expected at the time of publication or prior to the end of the grant, whichever occurs first (see NDA Sharing Regimen for more information). Investigators are expected to share results, positive and negative, specific to the cohorts and outcome measures studied.For more guidance on submitting data to NDA, refer to the NDA Data Sharing Plan on the NDA website. NDA staff will work with investigators to help them submit data types not yet defined in the NDA Data Dictionary.

Appendix:

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

  • No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.
PHS Human Subjects and Clinical Trials Information

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

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

Study Record: PHS Human Subjects and Clinical Trials Information

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

Delayed Onset Study

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

PHS Assignment Request Form

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

3. Unique Entity Identifier and System for Award Management (SAM)

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

4. Submission Dates and Times

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

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

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

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

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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

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

7. Other Submission Requirements and Information

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

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

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

Use of Common Data Elements in NIH-funded Research

Many NIH ICs encourage the use of common data elements (CDEs) in basic, clinical, and applied research, patient registries, and other human subject research to facilitate broader and more effective use of data and advance research across studies. CDEs are data elements that have been identified and defined for use in multiple data sets across different studies. Use of CDEs can facilitate data sharing and standardization to improve data quality and enable data integration from multiple studies and sources, including electronic health records. NIH ICs have identified CDEs for many clinical domains (e.g., neurological disease), types of studies (e.g. genome-wide association studies (GWAS)), types of outcomes (e.g., patient-reported outcomes), and patient registries (e.g., the Global Rare Diseases Patient Registry and Data Repository). NIH has established a Common Data Element (CDE) Resource Portal" (http://cde.nih.gov/) to assist investigators in identifying NIH-supported CDEs when developing protocols, case report forms, and other instruments for data collection. The Portal provides guidance about and access to NIH-supported CDE initiatives and other tools and resources for the appropriate use of CDEs and data standards in NIH-funded research. Investigators are encouraged to consult the Portal and describe in their applications any use they will make of NIH-supported CDEs in their projects.

NIMH expects investigators for this funding announcement to collect Common Data Elements (CDEs) for mental health human subjects research. Unless NIMH stipulates otherwise during the negotiation of the terms and conditions of a grant award, this Notice applies to all grant applications involving human research participants. The necessary funds for collecting and submitting these CDE data from all research participants to the NIMH Data Archive (NDA) should be included in the requested budget. A cost estimator (https://nda.nih.gov/ndarpublicweb/Documents/NDA_Data_Submission_Costs.xlsx) is available to facilitate the calculation of these costs. NIMH may seek further information regarding CDEs prior to award. Additional information about CDEs can be found at the NIMH webpage on Data Sharing for Applicants and Awardees

Post Submission Materials

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

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

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.

Overall Impact

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

Scored Review Criteria

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

Significance

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

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

Specific to this NOFO:

  • To what extent is the proposed approach to establishing a clinical trial network to run a PoP trial and evaluate the utility of the clinical, cognitive, biological and digital outcome measures optimal to achieve the scientific objectives of the NOFO?

Investigator(s)

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

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?

Specific to this NOFO:

  • To what extent is the PD/PI (or Multi-PDs/PIs) of the network experienced in the establishment, coordination, and management of multi-site clinical trial networks, including successfully meeting milestones and timelines? To what extent does the study team have multidisciplinary expertise and background in hands-on involvement in the steps needed for operationalizing a clinical trial, including rapid recruitment and assessment of CHR participants, collection of multimodal biomarker and clinical data, including experience with MRI, EEG, Penn CNB, and digital assessments?

Innovation

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

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

Specific to this NOFO:

  • To what extent does the application include plans to employ unique or novel exploratory biological or digital measures that will enrich the overall dataset in the PoP trial(s)? research team to use current best practices to recruit and retain participants and partner with the CT-DPACC for the purpose of centralized data analysis and resource sharing? What is the likelihood that the proposed plan will lead to the successful implementation of current best practices to recruit and retain participants and partner with the CT-DPACC for centralized data analysis and resource sharing?

Approach

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

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Does the application adequately address the following, if applicable

Study Design

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

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

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

Data Management and Statistical Analysis

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

Specific to this NOFO:

Management Plan

To what extent does the management plan address the following?

  • How the PD(s)/PI(s) will manage the proposed project and who will oversee the day-to-day activities (e.g., a project manager).
  • How the clinical trial network will optimize study start-up efficiency and harmonized data collection across sites.
  • How the clinical sites will manage participants not being co-enrolled in other studies during the PoP trial.
  • How the clinical trial network will manage sites that are not meeting their recruitment targets.
  • How the management will support achievement of the proposed goals and milestones.
  • Organization of the CHR clinical trial network, including its coordination and communication functions among sites, key personnel, reporting relationships, a management plan for fiscal accountability and communication.
  • How collaborations or subcontracts, if proposed, will be managed, including the establishment and execution of the CTA.
  • Plans for shared decision making among the PD/PI, NIMH CHR Steering Committee, and clinical sites regarding personnel, clinical decisions, changes in study protocol, and authorship.

Regulatory Plan

To what extent does the application include a detailed regulatory plan that describes the following?

  • How the PD(s)/PI(s) will file an IND with the FDA to use the selected compound(s).
  • A plan to execute an IP agreement with the company providing the compound for the PoP trial, including how contract discussions will be handled.
  • How the clinical trial will be monitored by a DSMB and an independent medical monitor.

Biomarker and clinical outcome assessments

To what extent does the application include a description of how the proposed network will define CHR and how the PSYCHS instrument will be used to ascertain CHR status?

How appropriate are the biological, clinical, cognitive and digital assessments available to the clinical trial network for the described project?

To what extent does the application include a strategy for feasibly and efficiently collecting the data in a standardized fashion across clinical network sites and a plan for how the network’s information technology systems will support this data collection and ensure interoperability among the clinical sites and timely transfer of the data from each site to the CT-DPACC, harnessing the data processing pipelines established for data transfer in AMP SCZ?

How well does the application identify possible challenges in enrolling CHR participants to meet the timeline for the project and implementing the biological and clinical outcome measure assessments and propose effective strategies to overcome these challenges?

milestones and timeline covering all aspects of the clinical trial network’s activities appropriate for the described project How well do the milestones and timeline cover all aspects of the clinical trial network’s activities described in the application? This should include annual milestones and quarterly recruitment milestones with metrics that will document progress towards the achievement of the ultimate goals and plans for critically evaluating and revising these milestones on a regular basis.

Collaboration with the CT-DPACC and NIMH CHR Steering Committee

To what extent does the application include a strategy for maintaining a high level of collaboration with the CT-DPACC on key tasks, including participating as a member of the NIMH CHR Steering Committee, adopting agreed upon standard operating procedures established in the AMP SCZ observational study for data collection, and submitting raw participant-level data to the CT-DPACC?

Environment

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 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?

Specific to this NOFO:

  • To what extent is there evidence of the ability of the sites to (1) enroll the proposed numbers of CHR participants at the rate anticipated for timely completion of the PoP trial(s); (2) adhere to the data collection protocol; (3) collect and accurately transmit data in real time to the CT-DPACC; and, (4) operate within the proposed organizational structure?

Additional Review Criteria

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

Study Timeline


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

Are potential challenges and corresponding solutions discussed (e.g., strategies that can be implemented in the event of enrollment shortfalls)?

Protections for Human Subjects

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

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

Inclusion of Women, Minorities, and Individuals Across the Lifespan

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

Vertebrate Animals

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 Animals Section.

Biohazards

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

Resubmissions

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

Renewals

Not Applicable

Revisions

Not Applicable

Additional Review Considerations

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Applications from Foreign Organizations

Not Applicable.

Select Agent Research

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

Resource Sharing Plans

Reviewers will comment on whether the Resource Sharing Plan(s) (i.e., Sharing Model Organisms) or the rationale for not sharing the resources, is reasonable.

Authentication of Key Biological and/or Chemical Resources:

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

Budget and Period of Support

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

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the National Institute of Mental Health, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications will receive a written critique.

Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.

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

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Mental Health Council. The following will be considered in making funding decisions:

  • Scientific and technical merit of the proposed project as determined by scientific peer review.
  • Availability of funds.
  • Relevance of the proposed project to program priorities.

3. Anticipated Announcement and Award Dates

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

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

Section VI. Award Administration Information

1. Award Notices

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

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

Recipients 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 NOFO will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

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

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

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

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

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

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

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:

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

Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS will be required to complete an HHS Assurance of Compliance form (HHS 690) in which the recipient agrees, as a condition of receiving the grant, to administer programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, age, sex and disability, and agreeing to comply with federal conscience laws, where applicable. This includes ensuring that entities take meaningful steps to provide meaningful access to persons with limited English proficiency; and ensuring effective communication with persons with disabilities. Where applicable, Title XI and Section 1557 prohibit discrimination on the basis of sexual orientation, and gender identity, The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. See https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html.

HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this NOFO.

Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 and 2 CFR Part 200.206 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

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 2 CFR Part 200, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the recipient’s 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 recipient’s for the project as a whole, although specific tasks and activities may be shared among the recipient’s and the NIH as defined below.

The PD(s)/PI(s) will have the primary responsibilities as described below:

  • Provide scientific and administrative leadership and coordination of the project at the recipient and sub-recipient institutions and among collaborators.
  • Oversee and perform the scientific activities within the guidelines of this NOFO.
  • Accept close coordination, cooperation, and participation of NIMH program staff in the scientific, technical, and administrative management of the grant.
  • Provide milestones and costs for the grant to the NIMH program staff as requested (usually at the outset of the award and annually thereafter, but also at other times as requested by the program staff).
  • Provide periodic progress reports summarizing CHR clinical trial network activities and achievement of project milestones to NIMH staff as requested.
  • Serve as a voting member of the NIMH CHR Steering Committee (SC) and fulfill related duties outlined below in Areas of Joint Responsibility.
  • Participate in weekly virtual NIMH CHR SC meetings and annual in-person meetings. The PDs/PIs will be responsible for budgeting and providing travel funds for the annual in-person meeting.
  • Adhere to NIMH policies regarding intellectual property and other policies that might be established during the course of this activity.
  • This research project is being funded by NIMH under the auspices of AMP SCZ. All AMP projects operate under the broad principle of delivering pre-competitive advancements to the research and medical fields and enabling the broadest possible access and use of AMP research discoveries. As part of the AMP, research supported by this NOFO is expected to generate raw and processed data. NIMH considers these data as pre-competitive and urges Recipients of funding under this NOFO to avoid making intellectual property (IP) claims derived directly from these data. These data would require a considerable amount of work to be performed beyond the initial data production to demonstrate utility. It is expected that these pre-competitive data, and conclusions derived therefrom, will remain freely available, without requirement for licensing, consistent with achieving the goals of this program. With respect to downstream discoveries, the NIH also supports and recognizes the importance of the subsequent development of IP (e.g., patenting) on those downstream discoveries, especially in therapeutics, which will be necessary to support full investment in products to benefit the public.
  • Accept and implement the common guidelines and procedures approved by the AMP SCZ Steering Committee and NIMH.
  • Recipients will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

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

The NIH Project Scientist(s) will:

  • Provide relevant scientific expertise to the clinical trial network and CT-DPACC.
  • Participate as a voting member of the NIMH CHR SC, attend NIMH CHR SC meetings, and assist in developing PoP trial protocols and quality control procedures in coordination with the CT-DPACC.
  • Participate with other NIMH CHR SC members in the group process of setting research priorities for the acquisition of data by the clinical trial network and for analyses of CHR biomarker and clinical data, annual milestones for the project, and periodic adjustments of research protocols or approaches as warranted.
  • Participate with other NIMH CHR SC members in the group process of setting research priorities (key questions) for aggregation and harmonization of data by the clinical trial network and for analyses of CHR biomarker and clinical data, annual milestones for the project, and periodic adjustments of research protocols or approaches as warranted.
  • Assist with coordination of network activities with the development of evolving tools and technologies in data science, database management, and analysis, with the scientific mission and evolving goals of the NIMH, and with other U.S. efforts that focus on sharing research resources for CHR biomarkers, digital measures, and clinical outcome assessments.
  • Assist in promoting and encouraging the sharing of unique research resources for studies of CHR biomarkers by the scientific community at large.
  • Participate in NIMH CHR SC activities, including conference calls, working groups and special committees.
  • Participate in the project update meetings and conference calls with the PD(s)/PI(s) on a weekly or monthly basis, as dictated by the needs of the project.
  • It is anticipated that decisions in all activities will be reached by consensus of the SC and that NIMH staff will be given the opportunity to offer input to this process. One NIH Project Scientist will participate as a member of the SC and will have one vote.

The NIH Program Officer will:

  • Be responsible for the normal scientific and programmatic stewardship of the award, including programmatic monitoring of the overall project and will be named in the award notice.
  • Be responsible for negotiating, monitoring, and implementing the D ata Vanagement and ’s haring P lan and the milestones to ensure that the goals of the project are being met.
  • Monitor the conduct and progress of the project to ensure milestones are accomplished in accordance with the timeline.
  • Participate in NIMH CHR SC meetings, working groups and/or special committees as a non-voting participant and serve as an administrative liaison.
  • Approve modifications to the research plan and/or study protocol(s), in consultation with the NIMH CHR SC, AMP SCZ Operations Working Group and AMP SCZ Steering Committee based on emerging data and/or other issues that impact progress of the project.
  • Reserve the right to obtain periodic external peer review and recommend reviewers for an assessment of progress and achievement of milestones and deliverables.
  • Monitor performance and compliance with NIH procedures.
  • Negotiate the data types and frequency of new data collection by the clinical trial network, quality control, and cost goals with the recipient s, including options to modify protocols for data collection when certain objectives of this NOFO are not being met or as scientific goals evolve.

Areas of Joint Responsibility include:

NIMH CHR Steering Committee. The NIMH CHR SC will serve as the operational governing board for the clinical trial network and the CT-DPACC. The NIMH CHR SC will include: the PD(s)/PI(s), the PD(s)/PI(s) of the? ?CT-D?P?A?C?C, Project Manager of CT-DPACC, NIMH Project Scientist(s), NIMH Program Officers and members of the NIMH Executive Committee. When a vote is required, a majority of the votes will be required for approval. One PD/PI per project will have one vote, and the NIH Project Scientist(s) will collectively have one vote. In the case of multi-PD/PI projects, there will be one collective vote for the project. NIMH Program Officers will not have a vote.

The NIMH CHR SC will:

  • Coordinate the activities of the CT-DPACC and clinical trial network as well as the distribution of data, algorithms, and other resources to the wider scientific community.
  • Facilitate the development of uniform procedures for data acquisition, data quality, and nomenclature and annotation conventions for data depositions to the NIMH Data Archive (NDA).
  • Advise on research priorities, optimal research designs, and project milestones.
  • Discuss scientific progress and make recommendations regarding the enhancement of research activities and the facilitation of free and open sharing of resources.
  • Participate in AMP SCZ working groups to develop a protocol for the PoP trial(s) based on the compound(s) made available to the AMP SCZ consortium and, as needed, to address the scientific goals of this program. The workgroups should include representatives from the CT-DPACC and clinical trial network, NIMH Project Scientists, NIMH Program Officers, and AMP SCZ public and private partners.
  • Participate in reviewing scientific progress of the project, clinical trial network recruitment, and development of standard operating procedures.
  • Vote to elect the initial chair, who will be responsible for developing meeting agendas and chairing meetings. Every six months a new chair will resume these responsibilities. The chair must be a PD/PI on the award.
  • Meet virtually once per week.
  • Hold teleconferences to address operational issues on a weekly or monthly basis, or as dictated by the needs of the project.
  • Establish workgroups or subcommittees for specific tasks as the NIMH CHR SC deems appropriate. The workgroups or subcommittees will make recommendations to the AMP SCZ Operations Working Group. Then the Operations Working Group will move the agreed upon recommendations to the AMP SCZ Steering Committee, composed of public and private partners, for final vote and decision.

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 members will 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 recipient. This special dispute resolution procedure does not alter the recipient 's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

3. Data Management and Sharing

Note: The NIH Policy for Data Management and Sharing is effective for due dates on or after January 25, 2023.

Consistent with the NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

4. Reporting

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

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. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All recipients 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 2 CFR Part 200.113 and Appendix XII to 45 CFR Part 75 and 2 CFR Part 200, 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 and 2 CFR Part 200 Award Term and Conditions for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

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

Application Submission Contacts

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

Finding Help Online: https://www.era.nih.gov/need-help (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-637-3015

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

Scientific/Research Contact(s)

Jonathan Sabbagh, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-594-2557
Email: jonathan.sabbagh@nih.gov

Peer Review Contact(s)

Nicholas Gaiano, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-827-3420
Email: nick.gaiano@nih.gov

Financial/Grants Management Contact(s)

Rita Sisco
?National Institute of Mental Health (NIMH)
Telephone: 301-443-2805
Email: siscor@nih.gov

Section VIII. Other Information

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

Authority and Regulations

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 and 2 CFR Part 200.

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