Influence of methodology on outcomes of randomised clozapine trials

The aim of this study was to clarify the impact of various methodological q uality factors on reported outcome of randomised clozapine trials. Trials c omparing the atypical antipsychotic clozapine with other antipsychotic drug s were identified in extensive electronic searches. Two independent reviewe rs extracted data on methodology and primary outcomes, and assessed trial q uality by use of three sets of criteria (Cochrane, Delphi, and Jadad). Ther e was no association between trial quality, as measured by any of the crite ria sets, and primary measures of outcome. Trials with the best score for r andomisation and concealment according to the Delphi scale had a significan tly lower relative risk for relapse in clozapine-treated groups, and studie s with well reported random order generation according to Jadad criteria te nded to have better odds ratios for clinical improvement on clozapine. Thes e findings strengthen the evidence of true clozapine superiority in these a spects, No other quality items correlated to the primary outcomes. Inadequa te randomisation techniques may be a source of bias in clozapine studies, b ut much more research is needed on the connections between trial quality an d trial outcome.