title: The effects of non-compliance on intent-to-treat analysis of equivalence trials.
abstract: The standard approach for analysing a randomized clinical trial is based on intent-to-treat (ITT) where subjects are analysed according to their assigned treatment group regardless of actual adherence to the treatment protocol. For therapeutic equivalence trials, it is a common concern that an ITT analysis increases the chance of erroneously concluding equivalence. In this paper, we formally investigate the impact of non-compliance on an ITT analysis of equivalence trials with a binary outcome. We assume 'all-or-none' compliance and independence between compliance and the outcome. Our results indicate that non-compliance does not always make it easier to demonstrate equivalence. The direction and magnitude of changes in the type I error rate and power of the study depend on the patterns of non-compliance, event probabilities, the margin of equivalence and other factors.
authors.affiliation: Division of Biostatistics, Department of Environmental Medicine, New York University School of Medicine, New York, NY, USA. danielle_sheng@merck.com
authors.forename: Dan
authors.initials: D
authors.lastname: Sheng
authors.forename: Mimi Y
authors.initials: MY
authors.lastname: Kim
mesh_terms: D003627:Data Interpretation, Statistical; D004341:Drug Evaluation / Q000379:methods*; D006801:Humans; D015233:Models, Statistical; D010349:Patient Compliance / Q000706:statistics & numerical data*; D010352:Patient Dropouts; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D045808:Refusal to Participate; D012107:Research Design; D012680:Sensitivity and Specificity; D013810:Therapeutic Equivalency; D016896:Treatment Outcome