title: Exploring changes in treatment effects across design stages in adaptive trials.
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.
authors.affiliation: Warwick Medical School, University of Warwick, Coventry, UK. t.friede@warwick.ac.uk
authors.forename: Tim
authors.initials: T
authors.lastname: Friede
authors.forename: Robin
authors.initials: R
authors.lastname: Henderson
mesh_terms: D002986:Clinical Trials as Topic / Q000379:methods*; D003198:Computer Simulation; D003627:Data Interpretation, Statistical; D017408:Guidelines as Topic; D006801:Humans; D015201:Meta-Analysis as Topic; D012107:Research Design; D016896:Treatment Outcome