A Multi-State Model for Designing Clinical Trials for Testing Overall Survival Allowing for Crossover after Progression

However, in many cancer clinical trials, patients pass through various disease states prior to death and because of this may receive treatments other than originally assigned. For example, patients may crossover from the control treatment to the experimental treatment at progression.

Even without crossover, the survival pattern after progression may be very different than the pattern prior to progression. The proportional hazards assumption will not hold in these situations and the design power calculated on this assumption will not be correct. In this article, we describe a simple and intuitive multi-state model allowing for progression, death before progression, post-progression survival, and crossover after progression and apply this model to the design of clinical trials for comparing the OS of two treatments.