Estimating heterogeneity of treatment effect in psychiatric clinical trials
Siegel, J. S.; Zhong, J.; Tomioka, S.; Ogirala, A.; Faraone, S. V.; Szabo, S. T.; Koblan, K.; Hopkins, S. C.
Show abstract
Currently, placebo-controlled clinical trials report mean change and effect sizes, which masks information about heterogeneity of treatment effects (HTE). Here, we present a method to estimate HTE and evaluate the null hypothesis (H0) that a drug has equal benefit for all participants (HTE=0). We developed measure termed estimated heterogeneity of treatment effect or eHTE, which estimates variability in drug response by comparing distributions between study arms. This approach was tested across numerous large placebo-controlled clinical trials. In contrast with variance-based methods which have not identified heterogeneity in psychiatric trials, reproducible instances of treatment heterogeneity were found. For example, heterogeneous response was found in a trial of venlafaxine for depression (peHTE=0.034), and two trials of dasotraline for binge eating disorder (Phase 2, peHTE=0.002; Phase 3, 4mg peHTE=0.011; Phase 3, 6mg peHTE=0.003). Significant response heterogeneity was detected in other datasets as well, often despite no difference in variance between placebo and drug arms. The implications of eHTE as a clinical trial outcomes independent from central tendency of the group is considered and the important of the eHTE method and results for drug developers, providers, and patients is discussed.
Matching journals
The top 8 journals account for 50% of the predicted probability mass.