Early Psychosis Intervention Network (EPINET): Learning Health Care Research to Improve Mental Health Services and Outcomes (P01 Clinical Trial Optional)

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.