Notice Number: NOT-MH-19-003
Key Dates
Release Date: December 11, 2018
None
Issued by
National Institute of Mental Health (NIMH)
Purpose
NIMH issues this Notice to highlight interest in receiving grant applications for clinical research that will advance diagnosis, risk assessment, and indicated prevention methods for persons at Clinical High Risk (CHR) for psychosis. It is estimated that each year, over one million adolescents and young adults in the United States experience problems in perception, thinking, and behavior suggestive of a pre-psychosis risk state. Given the highly disruptive and disabling nature of psychotic disorders, early intervention is recommended to prevent or delay psychosis onset among at-risk individuals and to lessen the impact of co-occurring problems such as depression, anxiety, substance use, and impaired social and role functioning. Deployment-focused studies are needed to translate research-based approaches to CHR diagnosis, clinical staging, and indicated prevention for implementation in U.S. community treatment settings.
The Substance Abuse and Mental Health Services Administration (SAMHSA) recently established 21 early interventions programs for CHR through funding opportunity announcement SM-18-012, "Community Programs for Outreach and Intervention with Youth and Young Adults at Clinical High Risk for Psychosis (CHR-P)." CHR-P calls for “state-of-the-science services in real-world community settings,” and emphasizes standardized approaches to CHR screening, diagnosis, and psychosis risk assessment. CHR-P programs are required to implement stepped-care models for CHR that feature lower intensity/lower risk evidence-based treatments as first-line interventions, with decisions regarding treatment completion, maintenance therapy, or step-up to more intensive care based on objective measures of treatment response. The overall goals of CHR-P are to (1) improve service users’ symptomatic and behavioral functioning; (2) enable youth and young adults to resume age-appropriate social, academic, and/or vocational activities; (3) delay or prevent the onset of psychosis; and (4) minimize the duration of untreated psychosis for those who develop psychotic symptoms.
NIMH encourages research focused on interventions for persons at clinical high risk for psychosis, including, but not limited to, projects that leverage partnerships between SAMHSA CHR-P grant recipients and mental health researchers to evaluate the effectiveness of stepped-care interventions for CHR in community treatment settings. NIMH is particularly interested in high-quality clinical research that will advance Research Strategies 3.2, 3.3, and 4.2 from the NIMH Strategic Plan for Research, which focus on tailoring interventions to optimize outcomes, testing interventions for effectiveness in community practice settings, and establishing research-practice partnerships to improve implementation of evidence-based mental health services. In addition, this Notice encourages research that addresses goals of the federal Interdepartmental Serious Mental Illness Coordinating Committee (ISMICC), which prioritizes evidence-based practices for screening, early identification, diagnosis, and preventive intervention for children, youth, and young adults at-risk for developing a serious mental illness.
Examples of studies encouraged through this Notice include, but are not limited to, those that:
- Develop and test novel strategies for adapting research-based diagnostic interviews, e.g., the Structured Interview of Psychosis-Risk Syndromes, for practical application in community treatment settings, with high interrater reliability;
- Develop and test novel strategies for adapting research-based CHR risk stratification tools, e.g., individualized risk calculators for psychosis, for practical application in community treatment settings, with high interrater reliability for individual predictor variables;
- Develop and test variants of existing biomarkers of psychosis risk that can be practically implemented in real-world clinics, e.g., validating computerized or online versions of cognitive measures to eliminate the need for in-person testing; applying computer-based natural language processing to analyze CHR patients’ speech in real time;
- Develop and test novel strategies that integrate the Polygenic Risk Score (PRS) in a multimodal biomarker approach for CHR risk stratification, risk prediction, or forecasting treatment response;
- Identify and test interventions of varying complexity, intensity, and duration that target symptoms and functional impairments that characterize different CHR states, with data on the effectiveness, risks, and benefits of various intervention strategies;
- Develop and validate algorithms for matching individuals to interventions of appropriate intensity and duration, depending on initial CHR status and treatment response;
- Identify and test predictors of individual treatment response at each stage of care, including promising psychosis risk biomarkers, to inform subsequent personalization of CHR interventions; and
- Develop and test strategies to mitigate patient, provider, or clinic-level factors that may hinder implementation of promising therapies in community treatment settings.
The Funding Opportunity Announcements (FOAs) summarized below and any future re-issuances can be used to pursue CHR clinical research Any application that proposes to develop and conduct a study of stepped-care approaches for CHR should follow all requirements of the relevant clinical trial FOA.
Measurement Development and Validation Studies
These FOAs can be used to support the development and testing of novel strategies for adapting research-based diagnostic assessments and risk stratification tools for practical application in community treatment settings. These FOAs also support refinement and testing of variants of existing biomarkers of disease risk that can be practically implemented in real-world clinical settings. Note that PA-19-052, PA-19-056, PAR-17-264, and PAR-18-929 do not support clinical trials.
- PA-19-052 (Parent R03 NIH Small Research Grant Program, Clinical Trial Not Allowed)
- PA-19-056 (Parent R01 NIH Research Project Grant, Clinical Trial Not Allowed)
- PAR-17-264 (R01 Innovative Mental Health Services Research Not Involving Clinical Trials)
- PAR-18-929 (R01 High-Priority Areas for Research Leveraging EHR and Large-Scale Data, Clinical Trial Not Allowed)
- PAR-18-267 (R34 Pilot Services Research Grants Not Involving Interventions, Clinical Trials Optional)
- PA-18-566 (R43/R44 Complex Technologies and Therapeutics Development for Mental Health Research and Practice, Clinical Trials Optional)
- PA-18-579 (R41/R42 Complex Technologies and Therapeutics Development for Mental Health Research and Practice, Clinical Trials Optional)
Pilot Effectiveness Trials
These FOAs encourage pilot research for effectiveness studies on preventive and therapeutic interventions with previously demonstrated efficacy, for use with broader target populations or for use in community practice settings. These FOAs also support pilot research on the development and preliminary testing of innovative services interventions. Applications should evaluate the feasibility, tolerability, acceptability and safety of approaches to improve mental health/functional outcomes, to modify risk factors, or to improve service delivery, and for obtaining the preliminary data needed as a pre-requisite to a larger-scale intervention trial (e.g., comparative effectiveness study, pragmatic clinical trial) or large-scale services study.
- RFA-MH-18-706(R34 Pilot Effectiveness Trials for Treatment, Preventive and Services Interventions, Clinical Trial Required)
- PAR-18-431(R34 Pilot Effectiveness Trials for Post-Acute Interventions and Services to Optimize Longer-term Outcomes, Clinical Trial Required)
Clinical Trials to Test the Effectiveness of Treatment, Preventive, and Services Interventions
These FOAs aim to support clinical trials to establish the effectiveness of interventions and to test hypotheses regarding moderators, mediators, and mechanisms of action of these interventions. These FOAs support clinical trials designed to test the therapeutic value of treatment and preventive interventions for which there is already evidence of efficacy, for use in community and practice settings. These FOAs also support clinical trials to test patient, provider, organizational, or systems-level services interventions to improve service access, continuity, quality, equity, and/or value of services. Intervention research covered under these announcements are explicitly focused on practice-relevant questions.
- RFA-MH-18-701(R01 Clinical Trial Required)
- RFA-MH-18-700(Collaborative R01 Clinical Trial Required)
- PAR-18-430(R01 Effectiveness Trials for Post-Acute Interventions and Services to Optimize Longer-term Outcomes - Clinical Trial Required)
Investigators interested in pursuing clinical trial research should thoroughly review the
NIMH Clinical Trials Funding Opportunity Announcements website. Applicants considering such an application are strongly encouraged to consult with
NIMH Program Officialsas early in advance as possible prior to submission
Inquiries
Please direct all inquiries to:
Susan T. Azrin, Ph.D.
National Institute of Mental Health (NIMH)
Telephone: 301-443-3267
Email: Susan.Azrin@nih.gov
and Human Services (HHS)
