Unplanned adaptations before breaking the blind.
Occasionally, things go so wrong in a clinical trial that a change must be made. For example, the originally planned primary outcome may be measured completely unreliably. Is there any recourse? One may still be able to salvage the trial using a permutation test if a change is made before breaking the treatment blind. The solution is not a panacea; we discuss the limitations and legitimate grounds for criticism. Still, when it is needed, the procedure is preferable to rigid adherence to a design that makes no sense. Published 2012. This article is a US Government work and is in the public domain in the USA.
European Medicines Agency, 7 Westferry Circus, E14 4HB London, UK. Martin.Posch@ema.europa.eu
Martin
M
Posch
Michael A
MA
Proschan
D015982:Bias; D002986:Clinical Trials as Topic / Q000379:methods / Q000592:standards*; D003627:Data Interpretation, Statistical; D004311:Double-Blind Method; D023381:Endpoint Determination / Q000379:methods / Q000592:standards*; D015340:Epidemiologic Research Design; D006801:Humans; D018401:Sample Size; D016037:Single-Blind Method