Abstract
Background: The Clinical High Risk state for Psychosis (CHR-P) has become the cornerstone of modern preventive psychiatry. The next stage of clinical advancements rests on the ability to formulate a more accurate prognostic estimate at the individual subject level. Individual Participant Data Meta-Analyses (IPD-MA) are robust evidence synthesis methods that can also offer powerful approaches to the development and validation of personalized prognostic models. The aim of the study was to develop and validate an individualized, clinically based prognostic model for forecasting transition to psychosis from a CHR-P stage. Methods: A literature search was performed between January 30, 2016, and February 6, 2016, consulting PubMed, Psychinfo, Picarta, Embase, and ISI Web of Science, using search terms (“ultra high risk” OR “clinical high risk” OR “at risk mental state”) AND [(conver* OR transition* OR onset OR emerg* OR develop*) AND psychosis] for both longitudinal and intervention CHR-P studies. Clinical knowledge was used to a priori select predictors: age, gender, CHR-P subgroup, the severity of attenuated positive psychotic symptoms, the severity of attenuated negative psychotic symptoms, and level of functioning at baseline. The model, thus, developed was validated with an extended form of internal validation. Results: Fifteen of the 43 studies identified agreed to share IPD, for a total sample size of 1,676. There was a high level of heterogeneity between the CHR-P studies with regard to inclusion criteria, type of assessment instruments, transition criteria, preventive treatment offered. The internally validated prognostic performance of the model was higher than chance but only moderate [Harrell’s C-statistic 0.655, 95% confidence interval (CIs), 0.627–0.682]. Conclusion: This is the first IPD-MA conducted in the largest samples of CHR-P ever collected to date. An individualized prognostic model based on clinical predictors available in clinical routine was developed and internally validated, reaching only moderate prognostic performance. Although personalized risk prediction is of great value in the clinical practice, future developments are essential, including the refinement of the prognostic model and its external validation. However, because of the current high diagnostic, prognostic, and therapeutic heterogeneity of CHR-P studies, IPD-MAs in this population may have an limited intrinsic power to deliver robust prognostic models.
Original language | English |
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Article number | 345 |
Pages (from-to) | 1-17 |
Number of pages | 17 |
Journal | Frontiers in Psychiatry |
Volume | 10 |
Issue number | MAY |
DOIs | |
Publication status | Published - 21 May 2019 |
Funding
Pavia, Pavia, Italy, 40 National Institute for Health Research, Biomedical Research Centre for Mental Health, South London and Maudsley NHS Foundation Trust, London, United Kingdom, 41 Department of Psychotic Disorders, GGZ Drenthe Mental Health Care Center, Assen, Netherlands For the open access publication fees, there is funding received from the University of Groningen, NHL Stenden University of Applied Sciences, GGZ Friesland Mental Health Institute, and GGZ Drenthe Mental Health Institute, that will equally share the costs. ADAPT: JA received funding from NIMH and Alberta Heritage Foundation for Medical Research. CAYR: Research at CAYR was supported by a NARSAD Young Investigator Award to MP. DUPS: This project was supported by a research grant from The Netherlands Organization for Health Research and Development (ZonMw, 2630.0001). EDIE-NL: MG received funding from Netherlands Health Research Council, ZonMW (120510001). EDIE-UK: This research was supported by research grants from the North West National Health Service R&D Executive and the Stanley Medical Research Institute. FEPSY: This project was supported by the Swiss National Science Foundation no. 3200-057216.99, no. 3200-057216.99, and no. PBBSB-106936, the Nora van Meeuwen-Haefliger Stiftung, Basel (CH). FETZ: Data analyses were supported by a grant from the Koeln Fortune Program/ Faculty of Medicine, University of Cologne (projects 8/2005 and 27/2006); the Awareness Program was supported from 2000 to 2005 by a grant from the German Federal Ministry for Education and Research, BMBF (grant 01 GI 0235). GRAPE: This work was supported by a grant of the Korea Healthcare Technology R&D Project, Ministry for Health, Welfare and Family Affairs, Republic of Korea (A090096) and by a National Research Foundation of Korea (NRF) grant funded by the Ministry of Science, ICT & Future Planning, Republic of Korea (No. 2010-0026833, No. 2017R1A2B3008214). INSTEP: This study was supported in part by JSPS KAKENHI Grant Number JP16H06395, 16H0639X, 16K21720 & 17H05921, AMED under Grant Number JP18dm0307001 & JP18dm0307004, UTokyo Center for Integrative Science of Human Behavior (CiSHuB), and the International Research Center for Neurointelligence (WPIIRCN) at The University of Tokyo Institutes for Advanced Study (UTIAS). OASIS: PF-P was supported by the King’s College London Confidence in Concept award from the Medical Research Council (MRC) (MC_PC_16048). This study also represents independent research partially funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. PACE: funding support of National Health and Medical Research Council (NHMRC) Program grants 350241 and 566529 and the Colonial Foundation. BN was supported by an NHMRC Senior Research Fellowship (1137687), SW was supported by an NHMRC Clinical Career Developmental Award (359223), and AY was supported by an NHMRC Senior Research Fellowship (566593). PORT: Research activities regarding ARMS individuals included in the PORT program are financed by the Polish Science National Centre, grant no. NN402 1793 34. ROME: MA was supported by the Brain and Behavior Research Foundation (21278) (formerly NARSAD). SAFE: the Ministry of Education, Culture, Sports, Science and Technology (MEXT) Grants-in-Aid for Scientific Research (KAKENHI) Grant Numbers 17790803, 19591336, 22390219, and 25461747, Japan. DUPS-U: None. The funders had no influence on the design, collection, analysis, and interpretation of the data, writing of the report, and decision to submit this article for publication.
Funders | Funder number |
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Faculty of Medicine, University of Cologne | 27/2006, 8/2005 |
International Research Center for Neurointelligence | |
Koeln Fortune Program | |
Netherlands Health Research Council | 120510001 |
Nora van Meeuwen-Haefliger Stiftung | |
North West National Health Service R&D Executive | |
Polish Science National Centre | NN402 1793 34 |
University of Tokyo Institutes for Advanced Study | |
WPIIRCN | |
National Institute of Mental Health | |
Brain and Behavior Research Foundation | 21278 |
Stanley Medical Research Institute | |
King’s College London | |
South London and Maudsley NHS Foundation Trust | |
Japan Agency for Medical Research and Development | JP18dm0307001 & JP18dm0307004 |
National Alliance for Research on Schizophrenia and Depression | |
Medical Research Council | MC_PC_16048 |
National Institute for Health and Care Research | |
National Health and Medical Research Council | 566529, 350241 |
Japan Society for the Promotion of Science | 17H05921, 16H0639X, 16K21720, JP16H06395 |
Ministry of Education, Culture, Sports, Science and Technology | 22390219, 19591336, 17790803, 25461747 |
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung | PBBSB-106936, 3200-057216.99 |
ZonMw | 2630.0001 |
Bundesministerium für Bildung und Forschung | 01 GI 0235 |
Alberta Heritage Foundation for Medical Research | |
Ministry of Science, ICT and Future Planning | 2017R1A2B3008214, 2010-0026833 |
Ministry of Health and Welfare | A090096 |
National Research Foundation of Korea | |
Colonial Foundation | 359223, 1137687, 566593 |
Keywords
- Clinical high risk
- Individual patient data meta-analysis
- Prognosis
- Psychosis
- Risk prediction
- Schizophrenia