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

Stat Med. 2006 Apr 15;25(7):1183-99. doi: 10.1002/sim.2230.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Data Interpretation, Statistical*
  • Drug Evaluation / methods*
  • Humans
  • Models, Statistical*
  • Patient Compliance / statistics & numerical data*
  • Patient Dropouts
  • Randomized Controlled Trials as Topic / methods*
  • Refusal to Participate
  • Research Design*
  • Sensitivity and Specificity
  • Therapeutic Equivalency*
  • Treatment Outcome