Part 1. Overview Information

This Notice of Fuding Opportunity (NOFO) requires a Plan for Enhancing Diverse Perspectives (PEDP).

Key Dates

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

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

No late applications will be accepted for this Notice of Funding Opportunity (NOFO).

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

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

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



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

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

 Background

In 2019, the National Institute of Mental Health (NIMH) established the Early Psychosis Intervention Network (EPINET) to advance learning health methods in treatment programs that offer evidence-based Coordinated Specialty Care (CSC) to persons in the early stages of psychotic illness. EPINET scientific hubs and a national data coordinating center have established infrastructure to support data sharing, program evaluation, and quality improvement activities across connected CSC programs, along with embedded research projects aimed at advancing knowledge about first episode psychosis populations, interventions, and recovery outcomes. These complementary activities align with the Institute of Medicine vision of learning health care in which health systems provide effective treatments, evaluate care processes and outcomes systematically, strive for continuous improvement and innovation in care delivery, and utilize data collected in clinical practice to drive the process of scientific discovery.

This Notice of Funding Opportunity (NOFO), along with companion announcement RFA-MH-24-106, will continue NIMH support for practice-oriented research that aims to improve early identification, clinical assessment, intervention effectiveness, service delivery, and long-term outcomes for youth and young adults experiencing an initial episode of psychosis. The NOFO seeks applications for research within the learning health care framework to promote measurement-based care in real-world settings, personalized interventions to improve engagement and outcomes, and new approaches to eliminate disparities in early psychosis diagnosis and intervention for populations with health disparities as defined by the National Institute on Minority Health and Health Disparities. This agenda is consistent with Research Strategies 3.3 and 4.1 – 4.3 from the NIMH Strategic Plan for Research, which focus on testing interventions for effectiveness in community practice settings and improving access, quality, and impact of mental health services for all Americans. It also addresses mental health equity and implementation research goals outlined in the 2023 White House Report on Mental Health Research Priorities.

Purpose

The purpose of this NOFO is to solicit Program Project (P01) applications from scientific hubs to support learning health care research in clinics offering evidence-based Coordinated Specialty Care (CSC) to persons in the early stages of psychotic illness. For this NOFO, “early psychosis” is defined as the period spanning the onset of an affective or non-affective psychotic disorder and up to 5 years following the first episode of psychosis (FEP). Each scientific hub will link multiple early psychosis service programs through (1) the EPINET Core Assessment Battery (CAB) of early psychosis clinical features, CSC services, and treatment outcomes; (2) informatics tools to collect de-identified, person-level data across sites; and (3) a unified approach for analyzing pooled data and disseminating promising findings rapidly across the network. In this re-issued NOFO, NIMH encourages applications from new and existing scientific hubs, including those that partner with state mental health authorities on the implementation, sustainment, and continuous improvement of CSC programs in state-supported health systems. The P01 activity code supports research that has multiple distinct but complementary and/or synergistic projects built around a clearly defined unifying central theme or well-defined overall objective. 

Research Objectives

This NOFO will support practice-oriented research in a diverse set of “hub and spoke” CSC networks across the United States. For this initiative, a “hub” is the research anchor site of CSC services delivered across multiple clinical programs and provides scientific and technical expertise to support uniform assessment and data collection, data integration, data analysis, and data presentation across connected sites. “Spokes” are clinical programs that provide evidence-based care within the CSC model and are connected to the central hub through standard clinical measures included in the CAB, information technology, and a uniform data processing system. 

Scientific hubs must partner with 5 or more early psychosis intervention programs that offer CSC, practice measurement-based care (i.e., standardized clinical assessment, systematic monitoring of key outcomes, and timely feedback to clinicians about patients’ progress), and are committed to practice-oriented research aimed at improving CSC services and patient outcomes. In aggregate, CSC programs within each network should enroll >125 persons each year in CSC services. To support data-driven learning health care in CSC programs, newly enrolled patients in CSC programs will be subject to CAB data collection at admission and subsequent longitudinal assessments at a minimum of every 6 months as part of routine care. CSC programs within the network must enroll enough patients with early psychosis each year to support two learning health research projects.   

NIMH strongly suggests applications to be submitted with input from service user, clinical provider, and scientific partners in connected clinics. Responsive applications must include an Administrative Core and two practice-oriented research projects to advance learning health care in early psychosis, as described below.

Scope of Research Projects

Depending on the research question and design requirements (e.g., state of the science, power and sample size estimation), applications might propose learning health research projects that are informed by existing pilot data and are adequately powered, analogous to the scope of research addressed in the NIMH R01 NOFOs for Clinical Trials to Test the Effectiveness of Treatment, Preventive, and Services Interventions (PAR-21-130) or for Innovative Mental Health Services Research Not Involving Clinical Trials (PAR-23-095). In other cases where preliminary data are required, projects might be designed to examine the feasibility of the research approach, (e.g., feasibility of recruiting and retaining participants); to refine and pilot test the experimental protocols, including assessment protocols and the experimental intervention protocol, as relevant; and to yield pilot data necessary for informing next steps and for enhancing the probability of obtaining meaningful results in subsequent, well-powered studies. The scope of research for such pilot research projects is generally analogous to the scope of research described in the NIMH R34 Research Mechanisms for Pilot Effectiveness Trials for Treatment, Preventive and Services Interventions (PAR-21-131) or for Pilot Services Research not Involving Clinical Trials (PAR-23-105).

EPINET Research Consortium

Program Projects selected for funding will join scientific hubs established through RFA-MH-24-105 to form an EPINET research consortium. The consortium will provide a forum for key personnel across scientific hubs to exchange views on learning health care principles, gaps in knowledge, and common challenges in conducting practice-oriented research in early psychosis treatment systems. Consortium members will identify strategies for optimizing the EPINET Core Assessment Battery for use in community CSC programs, including approaches for increasing participants’ willingness to complete longitudinal clinical assessments. At the behest of P01 consortium members, the national data coordinating center described in companion announcement RFA-MH-24-106 will support the organization of annual in-person consortium meetings and recurring conference calls between annual meetings. These meetings will allow consortium investigators to discuss emerging methods for clinical assessment and data capture in real-world learning health care settings, as well as data analytic strategies appropriate for aggregated CAB data.   

Program Project Structure

Applications submitted to this NOFO must include an Overall section, an Administrative Core responsible for the overall organization and management of the research program, and two learning health research projects. In addition, P01 Projects are expected to form an EPINET research consortium with scientific hubs established through RFA-MH-24-105.

Administrative Core (Required)

The Administrative Core is responsible for the overall organization and management of the research program, including (1) partnering with Coordinated Specialty Care programs for FEP that are adopting learning health care practices; (2) promoting effective communication and collaboration among service users, clinicians, program administrators, and scientists to boost participation in co-designed practice research; (3) fostering scientific interaction, sharing of resources, and monitoring of progress across research projects; and (4) implementing the CAB across participating CSC programs and acquiring high quality practice data to support learning health research. In addition, the Administrative Core will establish an efficient and effective process for quarterly submission of de-identified, patient-level CAB data to the EPINET National Data Coordinating Center (ENDCC; see companion announcement RFA-MH-24-106) and bi-annual submission of raw and analyzed data from learning health research projects.

Responsibilities of the Administrative Core include:

1. Recruiting 5 or more Coordinated Specialty Care programs for FEP that are adopting learning health care practices and are committed to practice-oriented research aimed at improving CSC services and patient outcomes. In aggregate, CSC programs within each network will enroll >125 persons each year in CSC services.
2. Establishing an Administrative Core Executive Committee with representatives from affiliated CSC programs and P01 learning health research projects to include CSC service users, family members, practitioners, and Research Project Leaders.
3. Developing an organizational structure that facilitates scientific interaction between P01 research projects, sharing of resources, and monitoring of progress across the program project.
4. Proposing a data collection strategy that is consistent with all applicable laws and regulations, institutional policies, and/or Institutional Review Board approvals that permit sharing of de-identified, individual-level CAB data collected as part of routine care in Coordinated Specialty Care programs, as well as research or quality improvement data collected in learning health research projects. The data collection strategy should describe how study data will be shared with the National Institute of Mental Health Data Archive (NDA; see NOT-MH-23-100) in accord with requirements of the NDA Submission Agreement. 
5. Describing plans for implementing the CAB across participating CSC programs, including an informatics platform that will acquire high quality clinical practice data from all newly enrolled patients at admission and longitudinal assessments, and promoting utilization of CAB data across learning health research projects.
6. Collaborating with the ENDCC over the course of the award to develop a secure method of contact between network investigators and individual patients, moderated by clinical care staff at participating clinics, regarding voluntary participation in prospective research studies. 
7. Establishing an efficient and effective process for (a) quarterly submission of de-identified, patient-level CAB data; (b) annual submission of Program-Level CAB data; and (c) bi-annual submission of raw and analyzed data from learning health research projects to the ENDCC. Clinical practice and research project data will support an integrated national database for large-scale research on early psychosis clinical features, CSC services, and treatment outcomes. This process should align with ENDCC data submission and quality protocols described in companion announcement RFA-MH-24-106.

 Administrative Core Leadership

The Leader of the Administrative Core must be the PD/PI of the overall program project. This Leader is responsible for defining the central theme or well-defined overall objective; developing and coordinating the Program; ensuring interaction and collaboration among scientists and CSC practice partners; managing day-to-day activities across the program project and monitoring overall progress, including participant enrollment, longitudinal CAB data collection, and the completeness and quality of CAB and other prospective research data. In addition, the Administrative Core Leader is the principal contact for the ENDCC regarding data quality and transmission issues. This additional oversight will speed transfer of de-identified, patient and program-level data to the ENDCC and minimize delays in assembling datasets to establish national CSC performance metrics and to support multi-network studies.

Administrative Core Executive Committee

The Administrative Core Executive Committee will include  representatives from affiliated CSC programs and P01 learning health research projects. The Executive Committee will (1) promote effective communication and collaboration among CSC practice-research partners; (2) assure alignment of learning health clinical and scientific objectives across the network; (3) facilitate meaningful innovation in clinical assessment, data management, data sharing, and CSC performance reporting; and (4) enhance the participation of FEP patients, family members, clinicians, and administrators in proposed research activities.

 Administrative Core Interaction with the EPINET National Data Coordinating Center (ENDCC)

Each scientific hub will generate a large dataset that contains de-identified, person-level CAB information from all newly enrolled patients receiving services in associated CSC clinics, as well as Program-Level CAB data and raw and analyzed data from learning health research projects. As described in companion NOFO, RFA-MH-24-106, the ENDCC will develop the infrastructure necessary for combining separate network datasets into a national repository of early psychosis common data elements, clinical measures, and data processing tools. In addition, the ENDCC will maintain an integrated national database to hold de-identified person-level CAB data from many thousands of patients who receive CSC services each year, as well as raw and analyzed data from learning health research projects.

Scientific hubs will submit de-identified, person-level CAB data from all newly enrolled patients receiving services in associated CSC clinics to the ENDCC on a quarterly basis, as well as Program Level CAB information on an annual basis, and raw and analyzed data from learning health research projects on a bi-annual basis. CAB data submitted by scientific hubs via the Administrative Core will include characteristics of individuals served in network clinics, duration of CSC participation, CSC services delivered, program characteristics, and clinical outcomes. The ENDCC will deposit all data submitted by scientific hubs into the NIMH Data Archive (NDA) within 6 months of collection. De-identified CAB data submitted by scientific hubs will become part of a readily accessible early psychosis data resource that will be made available to qualified investigators through the NDA.

Program Directors/Principal Investigators (PDs/PIs) from the scientific hubs selected for funding will join scientific hubs established through RFA-MH-24-105 to form an EPINET research consortium and establish a schedule for annual in-person consortium meetings, and recurring conference calls between annual meetings, to share views on learning health care principles, gaps in knowledge, and common challenges in conducting practice-oriented research in early psychosis treatment systems. The ENDCC will provide technical and logistical support to scientific hubs’ PDs/PIs for organizing annual in person consortium meetings as well as recurring conference calls between annual meetings.The P01's Administrative Core will communicate with the ENDCC around consortium meetings and lead the scientific hub’s planning for consortium-related activities.

Learning Health Research Projects

The P01 program project activity code supports research that has multiple distinct but complementary and/or synergistic projects built around a unifying central theme or well-defined overall objective. For this NOFO, two complementary and/or synergistic research projects are required that elucidate aspects of the central theme of data-driven learning health care in FEP treatment systems. 

Each project should reflect a self-standing scientifically meritorious research effort led by an independent investigator. The individual projects should complement one another so that the research ideas, efforts, and outcomes of the overall program demonstrate the clinical utility and scientific impact of embedded research in early psychosis learning health care systems.

Clinical Practice Data Research Project (Required)

Applications should include one research project that focuses on the practice-to-knowledge component of learning health care. That is, the research project should use standardized measures of early psychosis clinical features, interventions, and treatment outcomes to examine service delivery across CSC programs and to identify opportunities for sustaining and/or improving evidence-based care. Such research might seek to identify mutable factors that impact access, continuity, utilization, quality, value, and outcomes of CSC, including disparities in outcomes, or scalability of services. Scientific hubs must use the CAB as the principal source of longitudinal clinical practice data for all newly enrolled patients and the Program Level Core Assessment Battery to collect information about CSC program characteristics. Supplementing CAB data with additional measures is permissible but should be justified based on the program evaluation, quality improvement, and/or implementation question being addressed and the design of the proposed study. Data science, predictive analytic, and other computational methods can be applied to CAB data to study FEP populations, clinical workflows, and the quality of CSC services in real-world settings. Examples of possible topics for this component of learning health research include, but are not limited to, the following:

• Examination of the optimal intensity, frequency, or duration of CSC treatment for different patient subgroups.
• Examination of variation in the types of CSC treatment elements, or level of receipt of various treatment elements, as predictors of patients’ clinical or functional outcomes.
• Relationship between level of fidelity to evidence-based CSC and patients’ clinical or functional outcomes.
• Identification of factors associated with patient and family member engagement in CSC.
• Identification of risk factors associated with patient and family member disengagement in CSC.
• Assessing sources of disparities and health inequity among CSC patients and families.

Prospective Practice-Oriented Research Project (Required)

Applications should include one research project that addresses the knowledge-to-practice component of learning health care. For example, prospective research, which may include clinical trials, to explore service innovations that address unmet needs among persons with FEP or aim to support or expand the CSC workforce. The prospective study should include plans for rapid implementation of promising practices across the CSC network to enhance routine care. Scientific hubs are strongly encouraged to use data collected via the CAB as the foundation for prospective studies. Additional measures are permissible but should be justified based on the clinical question, research design, and scientific and public health significance of the proposed study. Examples of possible topics for this component of learning health research include, but are not limited to, the following:

• Developing and testing new approaches to eliminate disparities in early psychosis diagnosis and intervention for populations with health disparities (as defined by the National Institute on Minority Health and Health Disparities), and to promote health equity in CSC programs.
• Developing and testing strategies to enhance treatment engagement and prevent disengagement in CSC patients most at risk.
• Developing and testing strategies to improve functional outcomes in FEP (e.g., promoting school participation, employment, and career planning and progression among CSC participants and/or preventing homelessness and/or criminal justice involvement).
• Developing and testing scalable strategies for training, supervising, promoting, and retaining CSC team members.
• Developing and testing hybrid CSC service delivery models that optimally integrate in-person and telehealth strategies to meet the needs of service users, family members, and providers.
• Developing and testing primary care and health prevention services, integrated into CSC programs, to address premature mortality in people with early psychosis.

Research Team Responsibilities

The PD/PI of the overall project will be responsible for the scientific, operational, administrative, and budgetary leadership of the Program. This individual will lead the Administrative Core and be responsible for defining the central theme or well-defined overall objective; developing and coordinating the Program; ensuring interaction and collaboration among scientists and CSC practice partners; managing day-to-day activities; and monitoring overall progress of the P01 Project, including participant enrollment, longitudinal CAB data collection, and the completeness and quality of CAB and other prospective research data. The PD/PI will also lead one of the learning health research projects. Applications involving multiple PDs/PIs could include Early Stage Investigators.

Leaders of the individual research projects, which could include Early Stage Investigators, will be responsible for the scientific, administrative, budgetary, and operational aspects of the research project and for coordination with the PD/PI and other Research Project Leaders. All investigators should contribute to and share the responsibilities of fulfilling the P01 Program Project goals and objectives.

Guidance Regarding Clinical Trials

Consistent with the NIMH experimental therapeutics approach, all P01 projects that involve clinical trials, including projects that involve developing/testing preventive, therapeutic, or services interventions, must be designed to not only examine the intervention effects on outcomes of interest, but to also inform understanding of the intervention’s mechanisms of action. As such, the scope of work must include specification of intervention target mechanism(s) and assessment of intervention-induced changes in the presumed target mechanism(s) that are hypothesized to account for the intervention outcomes (see Support for Clinical Trials at NIMH).

Applications Not Responsive to this NOFO

The following applications will be considered non-responsive and will not be reviewed:

• Applications from scientific hubs that partner with fewer than five clinical programs that offer evidence-based Coordinated Specialty Care to persons in the early stages of psychotic illness, or projects with fewer than 125 persons enrolled each year across associated CSC programs.  
• Applications lacking letters of support affirming Coordinated Specialty Care clinics’ commitment to the learning health principles of measurement-based care (i.e., standardized clinical assessment, systematic monitoring of key outcomes, and timely feedback to clinicians about patients’ progress) and commitment to practice-oriented research aimed at improving CSC services and patient outcomes.
• Applications that lack plans for an Administrative Core Executive Committee that includes representatives from affiliated CSC programs and P01 research projects and an organizational structure to facilitate scientific interaction. 
• Applications lacking plans for implementing the EPINET Core Assessment Battery and the Program Level Core Assessment Battery across network clinics, including an informatics platform that will acquire high quality clinical practice data from all newly enrolled patients at admission and longitudinal assessments in a manner that permits sharing with the NIMH Data Archive.
• Applications that do not propose complementary research projects that elucidate aspects of the central theme of data-driven learning health care in FEP treatment systems (i.e., one Clinical Practice Data Research Project and one Prospective Patient-Oriented Research Project).
• Applications lacking a plan for quarterly submission of de-identified, patient-level CAB data, annual submission of de-identified Program Level CAB data, and bi-annual submission of raw and analyzed data from learning health research projects.to the ENDCC.
• Applications that lack a plan for collaborating with the ENDCC to develop a secure method of contact between network investigators and individual patients, moderated by clinical care staff at participating clinics, regarding voluntary participation in prospective research studies. 
• Applications that lack plans for participating in the EPINET research consortium, including attendance at annual in-person consortium meetings, as well as recurring conference calls between annual meetings.
• Applications that do not contain a Plan for Enhancing Diverse Perspectives (PEDP).
• Applications that fail to include annual milestones.

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

Technical Assistance

Potential applicants are strongly encouraged to contact NIMH Program Officials before the application due date to discuss a potential P01 application [see section VII Agency Contacts].

In addition to any individual consultation with program staff, NIMH intends to hold a web-based pre-application webinar for applicants to RFA-MH-25-200. Information on how to attend the optional webinar will be published through a Guide Notice.

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

Plan for Enhancing Diverse Perspectives (PEDP)

The NIH recognizes that teams comprised of investigators with diverse perspectives working together and capitalizing on innovative ideas and distinct viewpoints outperform homogeneous teams. There are many benefits that flow from a scientific workforce rich with diverse perspectives, including: fostering scientific innovation, enhancing global competitiveness, contributing to robust learning environments, improving the quality of the research, advancing the likelihood that underserved populations participate in, and benefit from research, and enhancing public trust.

To support the best science, the NIH encourages inclusivity in research guided by the consideration of diverse perspectives. Broadly, diverse perspectives can include but are not limited to the educational background and scientific expertise of the people who perform the research; the populations who participate as human subjects in research studies; and the places where research is done.

This NOFO requires a Plan for Enhancing Diverse Perspectives (PEDP), which will be assessed as part of the scientific and technical peer review evaluation.  Assessment of applications containing a PEDP are based on the scientific and technical merit of the proposed project. Consistent with federal law, the race, ethnicity, or sex of a researcher, award participant, or trainee will not be considered during the application review process or when making funding decisions.  Applications that fail to include a PEDP will be considered incomplete and will be administratively withdrawn before review.

The PEDP will be submitted as Other Project Information as an attachment (see Section IV).  Applicants are strongly encouraged to read the NOFO instructions carefully and view the available PEDP Guidance materials.

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

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions

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

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

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Local Governments

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

Federal Governments

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

Other

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

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

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

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 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 How to Apply - Application Guide.

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

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

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

Section IV. Application and Submission Information

1. Requesting an Application Package

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

2. Content and Form of Application Submission

It is critical that applicants follow the Multi-Project (M) Instructions in the How to Apply - Application Guide, except where instructed in this notice of funding opportunity to do otherwise and where instructions in the How to Apply - Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. Conformance to the requirements in the How to Apply - Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Letter of Intent

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

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

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

The letter of intent should be sent to:

Email: [email protected]

Page Limitations

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

Instructions for the Submission of Multi-Component Applications

The following section supplements the instructions found in How to Apply- Application Guide and should be used for preparing a multi-component application.

The application must consist of the following components:

• Overall
• Administrative Core
• Project: Clinical Practice Data Research Project
• Project: Prospective Practice-Oriented Research Project

Overall Component

When preparing the application, use Component Type ‘Overall’.

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions, as noted.

SF424(R&R) Cover (Overall)

Complete entire form.

PHS 398 Cover Page Supplement (Overall)

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

Research & Related Other Project Information (Overall)

Follow standard instructions.

Environment: 

If applicable, describe how the program will benefit from any special features in the environment or distinctive resources that will enhance the overall program. For example, availability of unique cohorts; collaborations with state or local mental health authorities around implementation of evidence-based interventions; or access to other forms of patient-linked data such as state all-payer administrative databases, commercial insurance administrative databases, social media data, and National Death Index-acquired data.

Other Attachments:

Plan for Enhancing Diverse Perspectives (PEDP)

• In an "Other Attachment" entitled "Plan for Enhancing Diverse Perspectives," all applicants must include a summary of actionable strategies to advance the scientific and technical merit of the proposed project through expanded inclusivity.
• Applicants should align their proposed strategies for PEDP with the research strategy section, providing a holistic and integrated view of how enhancing diverse perspectives and inclusivity are buoyed throughout the application.
• The PEDP will vary depending on the scientific aims, expertise required, the environment and performance site(s), as well as how the project aims are structured.
• The PEDP may be no more than 2 pages in length and should include:
  • Actionable strategies using defined approaches for the inclusion of diverse perspectives in the project;
  • Description of how the PEDP will advance the scientific and technical merit of the proposed project;
  • Anticipated timeline of proposed PEDP activities;
  • Evaluation methods for assessing the progress and success of PEDP activities.

Examples of items that advance inclusivity in research and may be appropriate for a PEDP can include, but are not limited to:

• Partnerships with different types of institutions and organizations (e.g., research-intensive; undergraduate-focused; HBCUs; emerging research institutions; community-based organizations).
• Project frameworks that enable communities and researchers to work collaboratively as equal partners in all phases of the research process.
• Outreach and planned engagement activities to enhance recruitment of individuals from diverse groups as human subjects in clinical trials, including those from underrepresented backgrounds.
• Description of planned partnerships that may enhance geographic and regional diversity.
• Outreach and recruiting activities intended to diversify the pool of applicants for research training programs, such as outreach to prospective applicants from groups underrepresented in the biomedical sciences, for example, individuals from underrepresented racial and ethnic groups, those with disabilities, those from disadvantaged backgrounds, and women.
• Plans to utilize the project infrastructure (i.e., research and structure) to enhance the research environment and support career-advancing opportunities for junior, early- and mid-career researchers.
• Transdisciplinary research projects and collaborations among researchers from fields beyond the biological sciences, such as physics, engineering, mathematics, computational biology, computer and data sciences, as well as bioethics.

Examples of items that are not appropriate in a PEDP include, but are not limited to:

• Selection or hiring of personnel for a research team based on their race, ethnicity, or sex.
• A training or mentorship program limited to certain researchers based on their race, ethnicity, or sex.

For further information on the Plan for Enhancing Diverse Perspectives (PEDP), please see PEDP Guidance materials.

Project/Performance Site Locations (Overall)

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.

Research and Related Senior/Key Person Profile (Overall)

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

Within the biosketches, highlight the expertise of the PD(s)/PI(s) in specialized areas relevant to the Program Project and the capabilities to lead large research enterprises, as well as his/her ability to organize, administer and direct the overall program project, the Administrative Core, and one Research Project. Present the record of the PD(s)/PI(s) in interacting and working with other investigators at their institution and elsewhere. Early Stage Investigators may serve as PD(s)/PI(s) on applications involving multiple PD(s)/PI(s). 

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.

Budget (Overall)

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

Each proposed Project Director/Principal Investigator (PD/PI) for the P01 must commit a minimum effort of 3 person months per year overall to the Program Project and be a leader of the Administrative Core and one of the research projects. The 3-person months should be a total of the PD/PI’s efforts on his/her project and the Administrative Core. The 3 persons month requirement applies to everyone listed as a P01 PD/PI in a multiple PD/PI P01 Program Project. 

PEDP implementation costs:

Applicants may include allowable costs associated with PEDP implementation (as outlined in the Grants Policy Statement section 7): https://grants.nih.gov/grants/policy/nihgps/html5/section_7/7.1_general.htm.

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.

PHS 398 Research Plan (Overall)

Introduction to Application: For Resubmission and Revision applications, an Introduction to Application is required in the Overall component.

Specific Aims: Provide a concise description of the overall goals and specific aims of the Program Project and summarize expected outcomes. Outline how the Administrative Core and each individual research project will contribute to these goals and aims.

Research Strategy: Include the following in the overall research strategy:

Significance: Describe the overall significance and potential impact of the coordinated and/or synergistic P01 research program on data-driven learning health care in FEP treatment systems in relation to the state-of-the-art of the field.

Approach: Provide the following:

Background and Statement of Objectives: Present the background, rationale, and major research objectives related to the Program’s central scientific theme of data-driven learning health care in early psychosis treatment programs. Explain how proposed activities will facilitate (1) measurement-based treatment; (2) continuous improvement and innovation in care delivery; and (3) practice-based research in Coordinated Specialty Care settings. Explain the strategy for achieving the objectives defined for the overall program and how the Administrative Core and research projects relate to that strategy. 

Organization and Coordination of the Program Project: Describe the relationships among the Administrative Core and the individual learning health care research projects. Explain how the Clinical Practice Data Research Project and the Prospective Practice-Oriented Research Project are complementary. Discuss how the Administrative Core and research projects will work together to address the overall goals and aims of the Program more effectively than if the projects were done independently. Explain how information, personnel, methods, etc., will be shared between the Administrative Core and the research projects to create synergy within the overall Program.

Collaborations Among Key Personnel: Discuss the roles, responsibilities, and expertise of the Program Principal Investigator/Project Director and Research Project Leaders. Clearly describe mechanisms for promoting and/or enhancing communication, coordination, and collaboration among key personnel associated with the Administrative Core and research projects. Describe any prior collaborative arrangements between investigators that are relevant to the current application.

Letters of Support: Include letters of support relevant to the overall Project here. Letters detailing contributions to individual components are to be placed in their respective individual Research Project and Core components.

Resource Sharing Plan:
Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply - Application Guide.

Other Plan(s): 

All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions:

• All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.
• To advance the goal of facilitating research through widespread data sharing among researchers, investigators funded under this NOFO must shared-identified, person-level CAB data collected from all newly enrolled patients receiving services in associated Coordinated Specialty Care programs, as well as Program-Level CAB data and raw and analyzed data from learning health research projects via the NIMH Data Archive (NDA) (see NOT-MH-23-100). Established by the NIH, the NDA is a secure informatics platform for scientific collaboration and data-sharing that enables the effective communication of detailed research results, tools, and supporting documentation.
• Investigators funded under this NOFO must use NDA Global Unique Identifier (GUID) and Data Dictionary technologies to submit data to the NDA via the ENDCC. 

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in How to Apply- Application Guide; any instructions provided here are in addition to the How to Apply - 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 How to Apply - Application Guide, with the following additional instructions:

If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, 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 How to Apply - Application Guide must be followed.

Delayed Onset Study

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

PHS Assignment Request Form (Overall)

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

Administrative Core

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. 

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. If required, the Data Management and Sharing (DMS) Plan must be provided in the Overall component.

SF424 (R&R) Cover (Admin 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 (Admin Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Admin 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) (Admin 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 (Admin Core)

• In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Admin 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 required that the PD/PI of the overall P01 application will be the primary leader of the Administrative Core. Multiple leads are allowed for the Administrative Core, including Early Stage Investigators.

Budget (Admin Core)

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

Each proposed Project Director/Principal Investigator (PD/PI) for the P01 must commit a minimum effort of 3 person months per year overall to the Program Project and be a leader of the Administrative Core and one of the research projects. The 3 person months should be a total of the PD/PI’s efforts on his/her project and the Administrative Core. The 3 persons month requirement applies to everyone listed as a P01 PD/PI in a multiple PD/PI P01 Program Project. 

The Leader of the Administrative Core must commit a cumulative minimum effort of 1 person month per year to the Administrative Core. Multiple leaders are allowed for the Administrative Core. If there are multiple leaders for this Core, the combined effort of the identified Administrative Core Leaders must total at least 1 person month per year.

Include costs for:

• Support for CAB data collection at participating early psychosis clinics, analysis of pooled practice data, and translation of clinical service data into usable information for network practice-research partners (e.g., informatics infrastructure, data analytic tools and strategies, personnel, etc.).
• Support for quarterly CAB data submissions and annual Program Level CAB data submissions to the ENDCC.
• Support for Investigator meetings, Administrative Core Executive Committee meetings, and EPINET Research Consortium meetings, including travel for the Program Project’s overall PD/PI(s), Administrative Core Director(s), and Research Project Leaders to participate in annual EPINET Research Consortium meetings.

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 (Admin Core)

Specific Aims: Provide a concise description of the goals of the Administrative Core and how these relate to overall Program Project objectives and aims of the individual research projects. Describe leadership elements that will foster integration of scientific efforts and rapid dissemination of research  findings across the network and to the scientific community.

Research Strategy: Include:

Significance: Describe how the activities of the Administrative Core will implement the overall vision of the Program Project as an integrated investigation of  data-driven learning health care in FEP treatment systems.

Approach: Describe the facilities, resources, services, and professional skills that the Core will provide to the overall Program Project. Clearly describe plans for organizational and administrative management of the overall program, including structures that will support communication, coordination, and collaboration across research projects and the affiliated Coordinated Specialty Care clinics. Explain which approaches will be used for managing day-to-day program activities, managing contractual agreements (if applicable), allocating funds, and resolving disputes. Describe methods for assuring effective use of Administrative Core resources by the research projects (e.g., utilization of CAB clinical practice data across the learning health research projects), as well as procedures for internal quality control of ongoing research, monitoring the timeline for achieving research milestones, and regular evaluation of progress across the Program Project.

Describe the chain of responsibility for decision-making, beginning with the PD/PI, and including the leaders of the research projects. Indicate where, in the chain of responsibility, the Administrative Core Executive Committee would be used and describe its function in ensuring clinical relevance and/or quality control in the research efforts.

Clearly describe the Administrative Core Leader’s leadership capabilities, including examples of prior experience leading large research endeavors. Describe the roles of administrative, scientific, technical, and support staff in the operation of the Administrative Core.

Additional information required in the Administrative Core Research Strategy:

• Community Clinical Programs:  Describe each early psychosis clinic (a minimum of five are required) that will comprise the network, including the population served, program characteristics, and how clinics use or will use the  EPINET Core Assessment Battery (CAB)  to evaluate Coordinated Specialty Care processes and outcomes. Present data illustrating the clinics’ patient flow, i.e., new patients enrolled each year, number of individuals receiving services each year, and number of persons discharged each year. Address each clinics’ capability and commitment to enrolling participants in learning health research projects and sharing de-identified, patient-level CAB data with the scientific hub, the EPINET National Data Coordinating Center, and the NDA. Present clear evidence that the scientific hub leadership has been/will be able to work effectively with participating clinical programs to accomplish the research proposed in the projects.
• Administrative Core Executive Committee. Describe plans for establishing an Executive Committee comprised of representatives from affiliated CSC program and P01 learning health research projects to include a wide range of practice-research partners (e.g., FEP patients, family members, clinicians, administrators, and Research Project Leaders). While individuals should not be named, the anticipated composition, in terms of requisite areas of expertise, and the schedule for convening Administrative Core Executive Committee should be detailed.
• EPINET Core Assessment Battery (CAB) Implementation Plan. Describe the Administrative Core’s plan for implementing the EPINET CAB  across participating CSC programs as a component of routine care. Describe an informatics platform that will acquire high quality clinical practice data from all newly enrolled patients at admission and longitudinal assessments in a manner that permits sharing with the NIMH Data Archive. The implementation plan should address the following:
  • Describe a data collection strategy that is consistent with all applicable laws and regulations, institutional policies, and/or Institutional Review Board approvals that permit sharing of de-identified, individual-level CAB data collected as part of routine care in Coordinated Specialty Care programs, as well as research or quality improvement data collected in learning health research projects. Describe how study data will be shared with the National Institute of Mental Health Data Archive (NDA; see  NOT-MH-23-100 ) in accord with requirements of the NDA Data Submission Agreement .
  • Propose an informatics platform to collect, aggregate, and analyze clinical encounter data collected from 5 or more CSC programs, including characteristics of individuals served in network clinics, duration of CSC participation, CSC services delivered, clinical outcomes, and program characteristics. Whenever possible, the Core should leverage health information technology systems already present in CSC clinics to achieve feasible and efficient data collection across the network.
  • Describe plans to maintain appropriate security processes and privacy procedures to store and analyze data from all newly enrolled early psychosis patients at CSC admission and subsequent longitudinal assessments. These procedures will include establishing either a Global Universal Identifier (GUID) or Pseudo GUID for each patient to de-identify and protect the anonymity of individual-level patient data.
  • Outline plans for the Core to maintain high standards for data completeness and integrity, and in collaboration with participating clinics, establishing data quality metrics and data submission procedures to ensure appropriate quality control. Staff at the NIMH Data Archive (NDA) will assist the Core in exporting Global Unique Identifier (GUID) infrastructure to CSC clinics in the network. 
  • Propose analytic platforms and data visualization tools that rapidly translate large amounts of clinical service data into usable information for practice-research partners. Propose data reporting tools that support measurement-based care, CSC fidelity monitoring, quality improvement and program evaluation analyses, along with other program management functions.
  • Propose a plan for collaborating with the ENDCC to develop a secure method of contact between network investigators and individual CSC patients, moderated by clinical care staff at participating clinics, regarding voluntary participation in prospective research studies.
• CAB and Research Project Data Sharing. Describe an efficient and effective internal process for preparing data for sharing with the ENDCC, including quarterly submission of de-identified, high quality, and complete patient-level CAB data, annual submission of Program-Level CAB data, and bi-annual submission of raw and analyzed data from learning health research projects.
• Timeline and Milestones (required). Include a graphic Timeline and a descriptive Milestones section for the Administrative Core. Identify Milestones along the timeline that are well described, quantifiable, and are scientifically justified benchmarks at critical junctures as well as annual indicators of progress. Include alternative strategies should any research project fail to perform as expected. 
• EPINET Research Consortium. Describe plans for participating in annual in-person meetings of the EPINET Research Consortium, and recurring conference calls between annual meetings, with other scientific hubs. Include potential topics of interest that may facilitate exchange of views about learning health care principles, gaps in knowledge, common challenges in conducting practice-oriented research in early psychosis treatment systems, and emerging methods for clinical assessment and data capture in real-world learning health care settings.

Letters of Support: Letters of support are required from participating CSC clinics to affirm the clinic’s commitment to (1) standardized clinical assessment, systematic monitoring of key outcomes, and quality improvement activities as part of routine care; (2) sharing de-identified, patient-level CAB data with the scientific hub, the EPINET National Data Coordinating Center, and the NDA; and (3) participation in practice-oriented research aimed at improving CSC services and patient outcomes.

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. 

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

Clinical Practice Data Research Project 

When preparing your application, use Component Type ‘Clinical Practice Data Research Project.’

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

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. If required, the Data Management and Sharing (DMS) Plan must be provided in the Overall component.

SF424 (R&R) Cover (Clinical Practice Data 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 (Clinical Practice Data Research Project)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Clinical Practice Data 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) (Clinical Practice Data 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 (Clinical Practice Data 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.
• Within the biosketches, highlight the experience of the Project Leader in leading multi-disciplinary research teams, with expertise in specialized areas relevant to the Research Project, and bringing novel and significant projects to fruition as the principal investigator. Highlight how the Research Project Lead(s) bring complementary and integrated expertise to the overall Program Project.
• The Project Director/Principal Investigator (PD/PI) for the P01 must lead either the Clinical Practice Data Research Project or the Prospective Practice-Oriented Research Project. 
• Project Leaders of the Clinical Practice Data Research Project could include Early Stage Investigators. 

Budget (Clinical Practice Data Research Project)

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

The Research Project Leader(s) must commit a total minimum effort of 1.8 person months per year to Clinical Practice Data Research Project. Multiple project leads are allowed for this Research Project. If there are multiple leads on this Research Project, the combined efforts of the identified Research Project leads must total at least 1.8 person months per year. Do not include costs for staffing that are already included in the Administrative Core.

The budget for the Clinical Practice Data Research Project should reflect the scope of the science proposed. 

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 (Clinical Practice Data Research Project)

Specific Aims: The specific aims should provide a concise description of the aims the project.

Research Strategy: This section of the application can be organized with the headers below for ease and clarity of review.

Significance: Describe overall goals and the impact of the science proposed in the Clinical Practice Data Research Project in relation to the state-of-the-art of the field. Explain the contribution of the project to the overall goals of the Program Project and how the project will interact with and benefit from other components of the P01.

Innovation: Describe the unique and innovative contributions that will be made by the research project. Explain how these contributions will synergize with the rest of the Program Project to achieve more than what could be achieved through an independent Research Project. Describe how the Research Project proposes novel solutions to challenges in implementing and sustaining data-driven learning health care in FEP treatment systems. Describe how input from a wide range of practice-research partners on the Administrative Core Executive Committee will contribute to the Clinical Practice Data Research Project.

Approach: Describe how the Clinical Practice Data Research Project addresses the practice-to-knowledge component of learning health care, including factors that impact access, continuity, utilization, quality, value, and outcomes of CSC, including disparities in outcomes, or scalability of services. Explain how longitudinal clinical practice data and CSC program information collected via the  EPINET Core Assessment Battery  and the  Program Level Core Assessment Battery will be used to  study FEP populations, clinical workflows, and the quality of CSC services in real-world settings. Describe how data science, predictive analytic, or other computational methods can be applied to CAB data to identify opportunities for sustaining and/or improving evidence-based care in CSC programs. If additional measures are proposed for the Clinical Practice Data Research Project, justify the selection of  measures based on the program evaluation, quality improvement, and/or implementation question being addressed and the design of the proposed study. Discuss plans for using results from the Clinical Practice Data Research Project to inform CSC clinical practices and future research directions consistent with the Program’s focus on continuously improving learning health care.

• In cases where preliminary data are required, the scope of research should be based on NIMH R34 research mechanisms described in PAR-21-131, Pilot Effectiveness Trials for Treatment, Preventive and Services Interventions, or PAR-23-105, Innovative Pilot Mental Health Services Research not Involving Clinical Trials.
• For learning health research projects that are informed by existing pilot data and are adequately powered, the scope of research should be based on NIMH R01 research mechanisms described in PAR-21-130, Clinical Trials to Test the Effectiveness of Treatment, Preventive, and Services Interventions, or PAR-23-095, Innovative Mental Health Services Research Not Involving Clinical Trials.
• Justify the scale and scope of the study in terms of (1) pilot data, from the Program Project team's prior studies or from the extant literature, to support well-justified hypotheses and the overall approach; and (2) power and sample size estimations. The application should also describe the feasibility of the proposed research study, the advantages of any new methodologies, potential pitfalls, and alternative approaches for the project and how these might impact on progress in the overall P01 Program Project.

Research Projects Involving Clinical Trials: Consistent with the NIMH experimental therapeutics approach (see NIMH Support for Clinical Trials), applications that propose studies that test the effectiveness of interventions or service delivery approaches must address whether the intervention engages the proximal target(s)/mechanism(s) presumed to underlie the intervention effects (the mechanism that accounts for changes in clinical/functional outcomes, changes in provider behavior, etc.). The applications should include the following: (1) the conceptual framework that clearly identifies the target(s)/mechanism(s) and the empirical evidence linking the target(s)/mechanism(s) to the clinical symptoms, functional deficits, or patient-, provider- or system-level behaviors/processes that the intervention seeks to improve; (2) plans for assessing engagement of the target(s)/mechanism(s), including the specific measures, the assessment schedule, and the justification for the assessment strategy (e.g., evidence regarding the validity and feasibility of the proposed measures in the effectiveness context); and (3) a statistical analysis plan and corresponding power calculations for data analyses that will be used to examine whether the intervention engages the target(s) and whether intervention-induced changes in the target(s) are associated with clinical benefit (i.e., mediation).  In the case of multi-component interventions, the application should specify the conceptual basis, assessment plan, and analytic strategy, as detailed above, for the target(s)/mechanism(s) corresponding to each intervention component, as appropriate, in the effectiveness context.

Letters of Support: Include letters of support relevant to the specific research project. 

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. All information on the sharing of resources should be consolidated in the Administrative Core.

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 (Clinical Practice Data 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.

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.

Prospective Practice-Oriented Research Project 

When preparing your application, use Component Type ‘Prospective Practice-Oriented Research Project.’

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

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. If required, the Data Management and Sharing (DMS) Plan must be provided in the Overall component.

SF424 (R&R) Cover (Prospective Practice-Oriented 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 (Prospective Practice-Oriented Research Project)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Prospective Practice-Oriented 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) (Prospective Practice-Oriented 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 (Prospective Practice-Oriented 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.
• Within the biosketches, highlight the experience of the Research Project Lead(s) in leading multi-disciplinary research teams with expertise in the specialized areas relevant to the Research Project, and have a successful record of bringing novel and significant projects to fruition as the principal investigator. Highlight how the Research Project Lead(s) bring complementary and integrated expertise to the overall Program Project. 
• The Project Director/Principal Investigator (PD/PI) for the P01 must lead either the Clinical Practice Data Research Project or the Prospective Practice-Oriented Research Project.
• Project Leaders of the Practice-Oriented Research Project could include Early Stage Investigators. 

Budget (Prospective Practice-Oriented Research Project)

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

The Research Project Leader(s) must commit a total minimum effort of 1.8 person months per year to the Practice-Oriented Research Project. Multiple project leads are allowed for Projects. If there are multiple leads on this Research Project, the combined efforts of the identified Research Project Leads must total at least 1.8 person months per year. Do not include costs for staffing that are already included in the Administrative Core.

The budget for the Prospective Practice-Oriented Research Project should reflect the scope of the science proposed. 

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 (Prospective Practice-Oriented Research Project)

 Specific Aims: The specific aims should provide a concise description of the aims the project

Research Strategy: This section of the application can be organized with the headers below for ease and clarity of review. 

Significance: Describe overall goals and the impact of the science proposed in the Prospective Practice-Oriented Research Project in relation to the state-of-the-art of the field. Explain the contribution of the Research Project to the overall goals of the Program Project and how the Research Project will interact with and benefit from other components of the P01.

Innovation: Describe the unique and innovative contributions that will be made by the Research Project. Explain how these contributions will synergize with the rest of the Program Project to achieve more than what could be achieved through an independent research project. Describe how the Research project proposes novel solutions to challenges in implementing and sustaining data-driven learning health care in FEP treatment systems. Describe how input from a wide range of practice-research partners on the Administrative Core Executive Committee will contribute to the Prospective Practice-Oriented Research Project.

Approach: Describe how the Prospective Practice-Oriented Research Project addresses the knowledge-to-practice component of learning health care, including prospective research to explore service innovations that address unmet needs among persons with FEP or aim to support/expand the CSC workforce. Explain how longitudinal clinical practice data and CSC program information collected via the  EPINET Core Assessment Battery  and the  Program Level Core Assessment Battery will be employed in prospective research, including projects that aim to develop or test new approaches to increase the equity, effectiveness, quality, and clinical impact of CSC services in real-world settings. If additional measures are proposed for the prospective Research Project, justify the selection of  measures based on the research question and design of the proposed study. Discuss plans for using results from the Prospective Practice-Oriented Research Project to inform CSC clinical practices and future research directions consistent with the Program’s focus on continuously improving learning health care. Include plans for rapid implementation and sustainment of promising practices across the CSC network to enhance routine care.

• In cases where preliminary data are required, the scope of research should be based on NIMH R34 research mechanisms described in PAR-21-131, Pilot Effectiveness Trials for Treatment, Preventive and Services Interventions, or PAR-23-105, Innovative Pilot Mental Health Services Research not Involving Clinical Trials.
• For learning health research projects that are informed by existing pilot data and are adequately powered, the scope of research should be based on NIMH R01 research mechanisms described in PAR-21-130, Clinical Trials to Test the Effectiveness of Treatment, Preventive, and Services Interventions, or PAR-23-095, Innovative Mental Health Services Research Not Involving Clinical Trials.

Justify the scale and scope of the study in terms of (1) pilot data, from the Program Project team's prior studies or from the extant literature, to support well-justified hypotheses and the overall approach; and (2) power and sample size estimations. The application should also describe the feasibility of the proposed research study, the advantages of any new methodologies, potential pitfalls, and alternative approaches for the project and how these might impact on progress in the overall P01 Program Project.

Research Projects Involving Clinical Trials: Consistent with the NIMH experimental therapeutics approach (see NIMH Support for Clinical Trials), applications that propose studies that test the effectiveness of interventions or service delivery approaches must address whether the intervention engages the proximal target(s)/mechanism(s) presumed to underlie the intervention effects (the mechanism that accounts for changes in clinical/functional outcomes, changes in provider behavior, etc.). Include the following: 1) the conceptual framework that clearly identifies the target(s)/mechanism(s) and the empirical evidence linking the target(s)/mechanism(s) to the clinical symptoms, functional deficits, or patient-, provider- or system-level behaviors/processes that the intervention seeks to improve; (2) plans for assessing engagement of the target(s)/mechanism(s), including the specific measures, the assessment schedule, and the justification for the assessment strategy (e.g., evidence regarding the validity and feasibility of the proposed measures in the effectiveness context); and (3) a statistical analysis plan and corresponding power calculations for data analyses that will be used to examine whether the intervention engages the target(s) and whether intervention-induced changes in the target(s) are associated with clinical benefit (i.e., mediation).  In the case of multi-component interventions, the application should specify the conceptual basis, assessment plan, and analytic strategy, as detailed above, for the target(s)/mechanism(s) corresponding to each intervention component, as appropriate, in the effectiveness context.

Letters of Support: Include letters of support relevant to the specific research project.  

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.  All information on the sharing of resources should be consolidated in the Administrative Core. 

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 (Prospective Practice-Oriented 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.

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.

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

See Part 2. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

4. Submission Dates and Times

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

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies) 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 Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

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

Information on the submission process and a definition of on-time submission are provided in How to Apply- 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 Section 7.9.1 Selected Items of Cost.

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

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

Applications must include a PEDP submitted as Other Project Information as an attachment. Applications that fail to include a PEDP will be considered incomplete and will be administratively withdrawn before review.

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.

Applications must include a PEDP submitted as Other Project Information as an attachment. Applications that fail to include a PEDP will be considered incomplete and will be withdrawn before review.

Use of Common Data Elements in NIH-funded Research

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

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

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

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

Post Submission Materials

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

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. Applications submitted to 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.

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).

As part of the overall impact score, reviewers should consider and indicate how the Plan for Enhancing Diverse Perspectives affects the scientific merit of the project.

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?

Specific to this NOFO:

• To what extent is the coordinated and/or synergistic program of research scientifically compelling? 

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? For trials focusing on mechanistic, behavioral, physiological, biochemical, or other biomedical endpoints, is this trial needed to advance scientific understanding?

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?

Specific to this NOFO:

• To what extent does the PD(s)/PI(s) have a successful record of working collaboratively with multi-disciplinary teams with expertise in specialized areas relevant to the research project?
• To what extent do the Research Project Leaders have a successful record of working with multi-disciplinary teams with expertise in specialized areas relevant to the research project? 
• To what extent do the Research Project Leaders bring complementary and integrated expertise to the overall Program Project?

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?

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?

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?

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?

Specific to this NOFO:

• To what extent will the proposed activities facilitate (1) measurement-based treatment; (2) continuous improvement and innovation in care delivery; and (3) practice-based research in Coordinated Specialty Care settings?

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?

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?

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?

Additional Review Criteria - Overall

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

Milestones

• To what extent are the proposed timelines and milestones feasible, scientifically justified, and quantifiable regarding the specific aims for each research project, the Administrative Core, and the Program Project as a whole?

Administrative Core

• How well do the organizational plans and management activities of the Administrative Core support the overall vision of the Program Project as an integrated investigation of data-driven learning health care in FEP treatment systems?
• How strong are the Administrative Core’s plans for implementing the EPINET Core Assessment Battery (CAB) as part of routine care, including informatics approaches and security/privacy procedures that permit storing, analyzing, and sharing high quality longitudinal clinical practice data via the NIMH Data Archive? 
• How likely is it that the proposed data reporting tools based on CAB data will promote measurement-based care, fidelity monitoring, and quality improvement/program evaluation analyses in CSC programs?

Clinical Practice Data Research Project

• To what extent does input from a wide range of practice-research partner members of the Administrative Core Executive Committee contribute to the Clinical Practice Data Research Project?
• How strong is the plan to use clinical practice data to identify opportunities for implementing, sustaining, and/or improving evidence-based care in FEP treatment systems?
• If additional measures are proposed to supplement the EPINET Core Assessment Battery, does the application provide a strong rationale for doing so?
• Is the scale and scope of the study adequately justified in terms of pilot data and power and sample size estimations?

Prospective Practice-Oriented Research Project

• To what extent does input from a wide range of practice-research partner members of the Administrative Core Executive Committee contribute to the Prospective Practice-Oriented Research Project?
• How strong are the plans to incorporate clinical practice data from the CAB and PL-CAB into the Prospective Practice-Oriented Research Project?
• If additional measures are proposed to supplement the EPINET Core Assessment Battery, does the application provide a strong rationale for doing so?
• Is the scale and scope of the study adequately justified in terms of pilot data and power and sample size estimations?

For Projects That Involve Clinical Trials

• How well does the application justify the practical effect of the intervention or service approach in terms of the estimated hypothesized effect size (in terms of key outcomes, such as clinical benefit, safety/tolerability, value and efficiency, or scalability), compared with already available approaches? Does the application adequately address both (1) the empirical basis for the anticipated effect size (e.g., citing data regarding the magnitude of the association between the target and the clinical endpoint of interest and/or effect sizes obtained in prior efficacy studies), and (2) the clinical meaningfulness of the anticipated increment in effects compared to existing approaches?
• How well does the study design address whether the intervention engages the mechanism(s) presumed to underlie the intervention effects (the mechanism(s) that accounts for changes in clinical/functional outcomes, changes in provider behavior, etc.)? To what extent does the application include (1) a well-supported empirical framework that clearly identifies the target(s)/mechanism(s); (2) well justified plans for assessing engagement of the target(s)/mechanism(s); and (3) an appropriate analytic strategy that will be used to examine whether the intervention engages the target(s)/mechanism(s) and whether intervention-induced changes in the target(s)/mechanism(s) are associated with clinical benefit (e.g., through mediational analysis for fully-powered Signature Projects or through preliminary examination in Exploratory Research Projects)?

Study Timeline

Specific to applications involving 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)?

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 three points: (1) a complete description of all proposed procedures including the species, strains, ages, sex, and total numbers of animals to be used; (2) justifications that the species is appropriate for the proposed research and why the research goals cannot be accomplished using an alternative non-animal model; and (3) interventions including analgesia, anesthesia, sedation, palliative care, and humane endpoints that will be used to limit any unavoidable discomfort, distress, pain and injury in the conduct of scientifically valuable research. Methods of euthanasia and justification for selected methods, if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals, is also required but is found in a separate section of the application. 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 - Overall

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) (e.g., 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 NIMH, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

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

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

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

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 NOFO. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:

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

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

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

3. Anticipated Announcement and Award Dates

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

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

Section VI. Award Administration Information

1. Award Notices

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

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

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

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

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

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

Institutional Review Board or Independent Ethics Committee Approval: 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 recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

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

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

2. Administrative and National Policy Requirements

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

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

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

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

Not Applicable

3. Data Management and Sharing

Consistent with the 2023 NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described. 

• When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement Section 8.4.1 Reporting. To learn more about post-award monitoring and reporting, see the NIH Grants & Funding website, see Post-Award Monitoring and Reporting.

• Recipients will provide updates at least annually on implementation of the PEDP.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement Section 8.6 Closeout. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 2 CFR Part 200.301.

Section VII. Agency Contacts

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

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

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

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-480-7075

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

Joel Sherrill, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-4432477
Email: [email protected] 

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

Tamara Kees
National Institute of Mental Health (NIMH)
Telephone: 301-443-8811
Email: [email protected]

Section VIII. Other Information

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

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 2 CFR Part 200.