Adding experimental treatment arms to Multi-Arm Multi-Stage platform trials in progress

Abstract

Multi-Arm Multi-Stage (MAMS) platform trials are an efficient tool for the comparison of several treatments. Suppose we wish to add a treatment to a trial already in progress, to access the benefits of a MAMS design. How should this be done? The MAMS framework requires pre-planned options for how the trial proceeds at each stage in order to control the family-wise error rate. Thus, it is difficult to make both planned and unplanned design modifications. The conditional error approach is a tool that allows unplanned design modifications while maintaining the overall error rate. In this work, we use the conditional error approach to allow adding new arms to a MAMS trial in progress. We demonstrate the principles of incorporating additional hypotheses into the testing structure. Using this framework, we show how to update the testing procedure for a MAMS trial in progress to incorporate additional treatment arms. Simulations illustrate the possible operating characteristics of such procedures using a fixed rule for how and when the design modification is made.