Effects of drop-out on efficacy estimates in five Cochrane reviews of popular antipsychotics for schizophrenia

Abstract

Objective: Our aim was to find out how Cochrane reviews of five popular or frequently prescribed second-generation antipsychotics in the UK (olanzapine, risperidone, quetiapine, amisulpride and aripiprazole) approached the problem of high drop-out in placebo-controlled trials.

Method: We examined the following: (i) whether reviews included data from studies with a level of drop-out exceeding their stated exclusion criterion; (ii) the level of missing data each efficacy outcome in each review relied upon; and (iii) impact of excluding studies with high drop-out.

Results: All reviews included data they stated they would exclude because of unacceptable levels of attrition, four (risperidone, olanzapine, amisulpride, aripiprazole) without clear acknowledgement or justification. Several reviews also excluded data from a number of relatively low-attrition studies because of missing standard deviations.

Conclusion: Cochrane reviews of five popular antipsychotics for schizophrenia misrepresented the available evidence on their efficacy. The impact of including high-attrition studies was difficult to quantify because of the exclusion of relevant low-attrition studies. Further analysis of the efficacy of these drugs in studies with acceptable rates of attrition is required. To reduce the problem of high attrition, trialists should gather follow-up data from people who leave the double-blind process early.