Predicting the onset of psychosis in patients at clinical high risk: practical guide to probabilistic prognostic reasoning

Abstract

Prediction of psychosis in patients at clinical high risk (CHR) has become a mainstream focus of clinical and research interest worldwide. When using CHR instruments for clinical purposes, the predicted outcome is but only a probability; and, consequently, any therapeutic action following the assessment is based on probabilistic prognostic reasoning. Yet, probabilistic reasoning makes considerable demands on the clinicians. We provide here a scholarly practical guide summarising the key concepts to support clinicians with probabilistic prognostic reasoning in the CHR state. We review risk or cumulative incidence of psychosis in, person-time rate of psychosis, Kaplan-Meier estimates of psychosis risk, measures of prognostic accuracy, sensitivity and specificity in receiver operator characteristic curves, positive and negative predictive values, Bayes' theorem, likelihood ratios, potentials and limits of real-life applications of prognostic probabilistic reasoning in the CHR state. Understanding basic measures used for prognostic probabilistic reasoning is a prerequisite for successfully implementing the early detection and prevention of psychosis in clinical practice. Future refinement of these measures for CHR patients may actually influence risk management, especially as regards initiating or withholding treatment.

Figure 1

Cumulative chance of transition given transition occurs by 2 years. As many studies assessed transition at 2 years of follow-up, we plotted cumulative estimate of transition, given transition occurs by 2 years after presentation. The regression line (solid line) closely fitted the data points (R2=0.995; y=133 (1-e−0.06x)) and indicates that, among ultra-high risk individuals progressing to psychosis in the first 2 years, 25% will develop the disorder by 106 days and 50% by 240 days.

Figure 2

Meta-analytical probability modifying plot, illustrating the relationship between pretest probability of psychosis onset 38 months and post-test probability of psychosis risk at 38 months based on clinical high risk (CHR) psychometric assessment in patients seeking help at high-risk services, computed as the likelihood of a positive (above diagonal line in red; LR+) or negative (below diagonal line in green, LR−) CHR assessment result over the 0–1 range of pretest probability, adapted from. The vertical black line indicates the average pretest probability of psychosis onset in patients referred to high-risk services (15% at 38 months8) which yields a 26% post-test probability of psychosis onset in CHR+ cases and a 1.56% post-test probability of psychosis onset at 38 months in CHR− cases. LR, likelihood ratio.