Design of platform trials with a change in the control treatment arm

Platform trials are a more efficient way of testing multiple treatments compared to running separate trials. In this paper we consider platform trials where, if a treatment is found to be superior to the control, it will become the new standard of care (and the control in the platform). The remaining treatments are then tested against this new control. In such a setting, one can either keep the information on both the new standard of care and the other active treatments before the control is changed or one could discard this information when testing for benefit of the remaining treatments. We will show analytically and numerically that retaining the information collected before the change in control can be detrimental to the power of the study. Specifically, we consider the overall power, the probability that the active treatment with the greatest treatment effect is found during the trial. We also consider the conditional power of the active treatments, the probability a given treatment can be found superior against the current control. We prove when, in a multi-arm multi-stage trial where no arms are added, retaining the information is detrimental to both overall and conditional power of the remaining treatments. This loss of power is studied for a motivating example. We then discuss the effect on platform trials in which arms are added later. On the basis of these observations we discuss different aspects to consider when deciding whether to run a continuous platform trial or whether one may be better running a new trial.