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      Clinical prediction models in psychiatry: a systematic review of two decades of progress and challenges

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          Abstract

          Recent years have seen the rapid proliferation of clinical prediction models aiming to support risk stratification and individualized care within psychiatry. Despite growing interest, attempts to synthesize current evidence in the nascent field of precision psychiatry have remained scarce. This systematic review therefore sought to summarize progress towards clinical implementation of prediction modeling for psychiatric outcomes. We searched MEDLINE, PubMed, Embase, and PsychINFO databases from inception to September 30, 2020, for English-language articles that developed and/or validated multivariable models to predict (at an individual level) onset, course, or treatment response for non-organic psychiatric disorders (PROSPERO: CRD42020216530). Individual prediction models were evaluated based on three key criteria: (i) mitigation of bias and overfitting; (ii) generalizability, and (iii) clinical utility. The Prediction model Risk Of Bias ASsessment Tool (PROBAST) was used to formally appraise each study’s risk of bias. 228 studies detailing 308 prediction models were ultimately eligible for inclusion. 94.5% of developed prediction models were deemed to be at high risk of bias, largely due to inadequate or inappropriate analytic decisions. Insufficient internal validation efforts (within the development sample) were also observed, while only one-fifth of models underwent external validation in an independent sample. Finally, our search identified just one published model whose potential utility in clinical practice was formally assessed. Our findings illustrated significant growth in precision psychiatry with promising progress towards real-world application. Nevertheless, these efforts have been inhibited by a preponderance of bias and overfitting, while the generalizability and clinical utility of many published models has yet to be formally established. Through improved methodological rigor during initial development, robust evaluations of reproducibility via independent validation, and evidence-based implementation frameworks, future research has the potential to generate risk prediction tools capable of enhancing clinical decision-making in psychiatric care.

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          Most cited references44

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          Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication.

          Little is known about lifetime prevalence or age of onset of DSM-IV disorders. To estimate lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the recently completed National Comorbidity Survey Replication. Nationally representative face-to-face household survey conducted between February 2001 and April 2003 using the fully structured World Health Organization World Mental Health Survey version of the Composite International Diagnostic Interview. Nine thousand two hundred eighty-two English-speaking respondents aged 18 years and older. Lifetime DSM-IV anxiety, mood, impulse-control, and substance use disorders. Lifetime prevalence estimates are as follows: anxiety disorders, 28.8%; mood disorders, 20.8%; impulse-control disorders, 24.8%; substance use disorders, 14.6%; any disorder, 46.4%. Median age of onset is much earlier for anxiety (11 years) and impulse-control (11 years) disorders than for substance use (20 years) and mood (30 years) disorders. Half of all lifetime cases start by age 14 years and three fourths by age 24 years. Later onsets are mostly of comorbid conditions, with estimated lifetime risk of any disorder at age 75 years (50.8%) only slightly higher than observed lifetime prevalence (46.4%). Lifetime prevalence estimates are higher in recent cohorts than in earlier cohorts and have fairly stable intercohort differences across the life course that vary in substantively plausible ways among sociodemographic subgroups. About half of Americans will meet the criteria for a DSM-IV disorder sometime in their life, with first onset usually in childhood or adolescence. Interventions aimed at prevention or early treatment need to focus on youth.
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            Stop explaining black box machine learning models for high stakes decisions and use interpretable models instead

            Black box machine learning models are currently being used for high stakes decision-making throughout society, causing problems throughout healthcare, criminal justice, and in other domains. People have hoped that creating methods for explaining these black box models will alleviate some of these problems, but trying to explain black box models, rather than creating models that are interpretable in the first place, is likely to perpetuate bad practices and can potentially cause catastrophic harm to society. There is a way forward - it is to design models that are inherently interpretable. This manuscript clarifies the chasm between explaining black boxes and using inherently interpretable models, outlines several key reasons why explainable black boxes should be avoided in high-stakes decisions, identifies challenges to interpretable machine learning, and provides several example applications where interpretable models could potentially replace black box models in criminal justice, healthcare, and computer vision.
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              Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD): the TRIPOD statement

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                Author and article information

                Contributors
                andrea.danese@kcl.ac.uk
                Journal
                Mol Psychiatry
                Mol Psychiatry
                Molecular Psychiatry
                Nature Publishing Group UK (London )
                1359-4184
                1476-5578
                1 April 2022
                1 April 2022
                2022
                : 27
                : 6
                : 2700-2708
                Affiliations
                [1 ]GRID grid.13097.3c, ISNI 0000 0001 2322 6764, Department of Psychology, Institute of Psychiatry, Psychology & Neuroscience, , King’s College London, ; London, UK
                [2 ]GRID grid.13097.3c, ISNI 0000 0001 2322 6764, Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, , King’s College London, ; London, UK
                [3 ]GRID grid.47100.32, ISNI 0000000419368710, Yale Child Study Center, , Yale School of Medicine, ; New Haven, CT 06520 USA
                [4 ]GRID grid.13097.3c, ISNI 0000 0001 2322 6764, Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, , King’s College London, ; London, UK
                [5 ]GRID grid.4991.5, ISNI 0000 0004 1936 8948, Department of Psychiatry, , University of Oxford, ; Oxford, UK
                [6 ]GRID grid.13097.3c, ISNI 0000 0001 2322 6764, Early Psychosis: Interventions and Clinical-detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, , King’s College London, ; London, UK
                [7 ]GRID grid.37640.36, ISNI 0000 0000 9439 0839, OASIS Service, South London and Maudsley NHS Foundation Trust, ; London, UK
                [8 ]GRID grid.8982.b, ISNI 0000 0004 1762 5736, Department of Brain and Behavioral Sciences, , University of Pavia, ; Pavia, Italy
                [9 ]GRID grid.37640.36, ISNI 0000 0000 9439 0839, National Institute for Health Research, Maudsley Biomedical Research Centre, , South London and Maudsley NHS Foundation Trust, ; London, UK
                [10 ]GRID grid.10419.3d, ISNI 0000000089452978, Department of Biomedical Data Sciences, , Leiden University Medical Centre, ; Leiden, The Netherlands
                [11 ]GRID grid.5645.2, ISNI 000000040459992X, Department of Public Health, , Erasmus MC, ; Rotterdam, The Netherlands
                [12 ]GRID grid.13097.3c, ISNI 0000 0001 2322 6764, Department of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology & Neuroscience, , King’s College London, ; London, UK
                [13 ]GRID grid.37640.36, ISNI 0000 0000 9439 0839, National and Specialist CAMHS Clinic for Trauma, Anxiety, and Depression, , South London and Maudsley NHS Foundation Trust, ; London, UK
                Author information
                http://orcid.org/0000-0001-7169-997X
                http://orcid.org/0000-0002-4153-5728
                http://orcid.org/0000-0003-3582-6788
                http://orcid.org/0000-0001-7987-6619
                http://orcid.org/0000-0001-8718-5412
                Article
                1528
                10.1038/s41380-022-01528-4
                9156409
                35365801
                1a5000bd-997f-4724-9520-d274b025f776
                © The Author(s) 2022

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 23 July 2021
                : 3 March 2022
                : 14 March 2022
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100000265, RCUK | Medical Research Council (MRC);
                Award ID: MR/P005918/1
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/501100000272, DH | National Institute for Health Research (NIHR);
                Funded by: FundRef https://doi.org/10.13039/100004440, Wellcome Trust (Wellcome);
                Award ID: 202836/Z/16/Z
                Award Recipient :
                Categories
                Systematic Review
                Custom metadata
                © The Author(s), under exclusive licence to Springer Nature Limited 2022

                Molecular medicine
                psychology,psychiatric disorders
                Molecular medicine
                psychology, psychiatric disorders

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