Consistency of atypical antipsychotic superiority to placebo in recent clinical trials

Background: The use of control placebos in clinical trials of new antipsych otic medications is increasingly under examination. The active controlled e quivalence study could offer a potential alternative design, First, however ; it must be clear that any proposed standard control agent has been consis tently superior to placebo in previous studies. Methods: Through a Freedom of Information Act request, WE identified nine p lacebo-controlled trials of risperidone, olanzapine, or quetiapine. Results: Meta-analysis indicated that the pooled estimate of the true popul ation effect size +/- SE was 0.46 +/- 0.06 for categorical response rates a nd >0.53 +/- 0.07 for the continuous Brief Psychiatric Rating Scale change score outcome measure. If the desired detectable effect size is set very co nservatively at a 95% confidence lower bound for the estimate of true effec t size, statistical power fbr random samples of 80 per group drawn from a p opulation of subjects similar to that of the nine meta-analyzed studies is .67 for categorical response rates and >.82 for the continuous measure, bas ed on one-sided alpha =.05 Conclusions: These data suggest substantial confidence that a therapeutic d ose of an atypical antipsychotic will be statistically superior to placebo in an adequately sized randomized trial, when reporting a continuous measur e as the principal outcome. Biol Psychiatry 2001;49. 64-70 (C) 2001 Society of Biological Psychiatry.