Impact of Information Leakage in Platform Trials With Survival Endpoints on Type I Error Control

ABSTRACT

Platform trials evaluate multiple treatments within a single trial infrastructure. Such designs have gained a lot of attraction in clinical research. If information gained from platform trials should provide confirmatory evidence for regulatory decisions, control of the Type I error rate is key. One critical issue is information leakage, for example, if any information of the ongoing trial is available, especially if it may impact the further conduct of treatments still in the platform trial and bias their results. This paper evaluates the potential impact of information leakage on the control of the Type I error rate in platform trials with time‐to‐event endpoints such as overall survival. We explore different strategies how information on the treatment effect of an still ongoing treatment could be obtained if a pre‐planned analysis for another arm is conducted. This (leaked) information might be used to decide whether to continue the other arm as planned or conduct its final analysis immediately. By means of clinical trial simulations we evaluate the impact of different levels of information leakage on the Type I error rate. We show how the conditional error principle can be applied to estimate worst case Type I error rate inflation for the different forms of information leakage. We do not aim to quantify the exact maximum Type I error rate inflation but rather to raise awareness of the potential risk for estimation of comparative results. Finally, we discuss the regulatory implications of information leakage and propose strategies to mitigate these risks.