The effects of outcome misclassification and measurement error on the design and analysis of therapeutic equivalence trials

In any clinical trial, the use of imperfect diagnostic procedures or labora tory techniques may lead to misclassification and measurement error in the primary outcome. Although the effects of non-differential outcome misclassi fication and measurement error an conventional superiority trials have been extensively investigated, less is known about the impact of these errors o n the results and interpretation of therapeutic equivalence trials. In this paper we formally investigate the effects of outcome misclassification and measurement error on the estimates of treatment effects, type I error rate , and power of equivalence trials. Our results indicate that, contrary to w hat one may expect based on the well known attenuating effects of non-diffe rential error in conventional studies, these errors do not always favour th e goal of demonstrating equivalence. The magnitude and direction of the inf luence depend on a number of factors including the nature of the outcome va riable, specific formulation of equivalence, size of the error rates, and a ssumptions regarding the true treatment effect. Copyright (C) 2001 John Wil ey & Sons, Ltd.