Including multiple imputation in a sensitivity analysis for clinical trials with treatment failures

Contemp Clin Trials. 2007 Feb;28(2):130-7. doi: 10.1016/j.cct.2006.06.006. Epub 2006 Jun 28.

Abstract

When treatment failures occur during the course of a clinical trial, the treatment regimen following failure may be changed. This change in therapy complicates comparisons among the original treatment arms. As in some clinical trials with dropouts, intent-to-treat analysis can yield a large bias. We examine the use of multiple imputation to replace observations after treatment failure has occurred. As a sensitivity analysis, this approach is compared to existing methods for handling treatment failures - removing treatment failure subjects, removing data after the onset of treatment failure, and imputation the last observation prior to treatment failure for all subsequent observations - in addition to an analysis of all collected data based on randomized treatment assignment. A data set from the Asthma Clinical Research Network is used to demonstrate the methods.

Publication types

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

MeSH terms

  • Algorithms
  • Anti-Inflammatory Agents / therapeutic use*
  • Asthma / drug therapy*
  • Bronchodilator Agents / therapeutic use*
  • Clinical Trials as Topic / methods*
  • Clinical Trials as Topic / statistics & numerical data
  • Drug Therapy, Combination
  • Humans
  • Markov Chains
  • Monte Carlo Method
  • Patient Dropouts / statistics & numerical data*
  • Randomized Controlled Trials as Topic / methods
  • Regression Analysis
  • Research Design
  • Treatment Failure

Substances

  • Anti-Inflammatory Agents
  • Bronchodilator Agents