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Improving Prognostic Accuracy in Subjects at Clinical High Risk for Psychosis: Systematic Review of Predictive Models and Meta-analytical Sequential Testing Simulation.

ABSTRACT: Discriminating subjects at clinical high risk (CHR) for psychosis who will develop psychosis from those who will not is a prerequisite for preventive treatments. However, it is not yet possible to make any personalized prediction of psychosis onset relying only on the initial clinical baseline assessment. Here, we first present a systematic review of prognostic accuracy parameters of predictive modeling studies using clinical, biological, neurocognitive, environmental, and combinations of predictors. In a second step, we performed statistical simulations to test different probabilistic sequential 3-stage testing strategies aimed at improving prognostic accuracy on top of the clinical baseline assessment. The systematic review revealed that the best environmental predictive model yielded a modest positive predictive value (PPV) (63%). Conversely, the best predictive models in other domains (clinical, biological, neurocognitive, and combined models) yielded PPVs of above 82%. Using only data from validated models, 3-stage simulations showed that the highest PPV was achieved by sequentially using a combined (clinical + electroencephalography), then structural magnetic resonance imaging and then a blood markers model. Specifically, PPV was estimated to be 98% (number needed to treat, NNT = 2) for an individual with 3 positive sequential tests, 71%-82% (NNT = 3) with 2 positive tests, 12%-21% (NNT = 11-18) with 1 positive test, and 1% (NNT = 219) for an individual with no positive tests. This work suggests that sequentially testing CHR subjects with predictive models across multiple domains may substantially improve psychosis prediction following the initial CHR assessment. Multistage sequential testing may allow individual risk stratification of CHR individuals and optimize the prediction of psychosis.

SUBMITTER: Schmidt A

PROVIDER: S-EPMC5605272 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Publications

Improving Prognostic Accuracy in Subjects at Clinical High Risk for Psychosis: Systematic Review of Predictive Models and Meta-analytical Sequential Testing Simulation.

Schmidt André A Cappucciati Marco M Radua Joaquim J Rutigliano Grazia G Rocchetti Matteo M Dell'Osso Liliana L Politi Pierluigi P Borgwardt Stefan S Reilly Thomas T Valmaggia Lucia L McGuire Philip P Fusar-Poli Paolo P

Schizophrenia bulletin 20170301 2

Discriminating subjects at clinical high risk (CHR) for psychosis who will develop psychosis from those who will not is a prerequisite for preventive treatments. However, it is not yet possible to make any personalized prediction of psychosis onset relying only on the initial clinical baseline assessment. Here, we first present a systematic review of prognostic accuracy parameters of predictive modeling studies using clinical, biological, neurocognitive, environmental, and combinations of predic ...[more]

PMID: 27535081

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Project description:BACKGROUND:Genomic prediction (GP) is used in animal and plant breeding to help identify the best genotypes for selection. One of the most important measures of the effectiveness and reliability of GP in plant breeding is predictive accuracy. An accurate estimate of this measure is thus central to GP. Moreover, regression models are the models of choice for analyzing field trial data in plant breeding. However, models that use the classical likelihood typically perform poorly, often resulting in biased parameter estimates, when their underlying assumptions are violated. This typically happens when data are contaminated with outliers. These biases often translate into inaccurate estimates of heritability and predictive accuracy, compromising the performance of GP. Since phenotypic data are susceptible to contamination, improving the methods for estimating heritability and predictive accuracy can enhance the performance of GP. Robust statistical methods provide an intuitively appealing and a theoretically well justified framework for overcoming some of the drawbacks of classical regression, most notably the departure from the normality assumption. We compare the performance of robust and classical approaches to two recently published methods for estimating heritability and predictive accuracy of GP using simulation of several plausible scenarios of random and block data contamination with outliers and commercial maize and rye breeding datasets. RESULTS:The robust approach generally performed as good as or better than the classical approach in phenotypic data analysis and in estimating the predictive accuracy of heritability and genomic prediction under both the random and block contamination scenarios. Notably, it consistently outperformed the classical approach under the random contamination scenario. Analyses of the empirical maize and rye datasets further reinforce the stability and reliability of the robust approach in the presence of outliers or missing data. CONCLUSIONS:The proposed robust approach enhances the predictive accuracy of heritability and genomic prediction by minimizing the deleterious effects of outliers for a broad range of simulation scenarios and empirical breeding datasets. Accordingly, plant breeders should seriously consider regularly using the robust alongside the classical approach and increasing the number of replicates to three or more, to further enhance the accuracy of the robust approach.

Dataset Information

Improving Prognostic Accuracy in Subjects at Clinical High Risk for Psychosis: Systematic Review of Predictive Models and Meta-analytical Sequential Testing Simulation.

Publications

Improving Prognostic Accuracy in Subjects at Clinical High Risk for Psychosis: Systematic Review of Predictive Models and Meta-analytical Sequential Testing Simulation.

Similar Datasets

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