The consequences of proportional hazards based model selection

For testing the efficacy of a treatment in a clinical trial with survival data, the Cox proportional hazards (PH) model is the well‐accepted, conventional tool. When using this model, one typically proceeds by confirming that the required PH assumption holds true. If the PH assumption fails to hold, there are many options available, proposed as alternatives to the Cox PH model. An important question which arises is whether the potential bias introduced by this sequential model fitting procedure merits concern and, if so, what are effective mechanisms for correction. We investigate by means of simulation study and draw attention to the considerable drawbacks, with regard to power, of a simple resampling technique, the permutation adjustment, a natural recourse for addressing such challenges. We also consider a recently proposed two‐stage testing strategy (2008) for ameliorating these effects. Copyright © 2013 John Wiley & Sons, Ltd.