Exploring changes in treatment effects across design stages in adaptive trials

Pharm Stat. 2009 Jan-Mar;8(1):62-72. doi: 10.1002/pst.332.

Abstract

The recently published Committee for Medicinal Products for Human Use reflection paper on flexible designs highlights a controversial issue regarding the interpretation of adaptive trials. The guideline suggests that a test for heterogeneity should be preplanned and if treatment effect estimates differ significantly between design stages then data collected before and after the interim analysis might not be combined in a formal analysis. In this paper we investigate error rates for such a procedure in the presence of calendar-time effects. Furthermore, we present an alternative testing strategy based on change point methods. In a simulation study we demonstrate that our procedure performs well in comparison to that suggested by the guideline.

MeSH terms

  • Clinical Trials as Topic / methods*
  • Computer Simulation
  • Data Interpretation, Statistical*
  • Guidelines as Topic
  • Humans
  • Meta-Analysis as Topic
  • Research Design
  • Treatment Outcome