The effects of non-compliance on intent-to-treat analysis of equivalence trials

Division of Biostatistics, Department of Environmental Medicine, New York University School of Medicine, New York, NY, USA.
Statistics in Medicine (Impact Factor: 2.04). 04/2006; 25(7):1183-99. DOI: 10.1002/sim.2230
Source: PubMed

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.

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