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 laboratory techniques may lead to misclassification and measurement error in the primary outcome. Although the effects of non-differential outcome misclassification and measurement error on conventional superiority trials have been extensively investigated, less is known about the impact of these errors on 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 what one may expect based on the well known attenuating effects of non-differential error in conventional studies, these errors do not always favour the goal of demonstrating equivalence. The magnitude and direction of the influence depend on a number of factors including the nature of the outcome variable, specific formulation of equivalence, size of the error rates, and assumptions regarding the true treatment effect.
Kim
M Y
MY
Biostatistics Division, Department of Environmental Medicine, New York University School of Medicine, New York, 10016 USA. mimi.kim@med.nyu.edu
Goldberg
J D
JD
D015914:Estrogen Replacement Therapy / Q000009:adverse effects; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000473:pathology; D008875:Middle Aged; D015337:Multicenter Studies as Topic / Q000379:methods; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D013810:Therapeutic Equivalency; D016896:Treatment Outcome