Adding experimental treatment arms to Multi-Arm Multi-Stage platform trials in progress
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Multi-Arm Multi-Stage (MAMS) platform trials are an efficient tool for the comparison of several treatments with a control. Suppose a new treatment becomes available at some stage of a trial already in progress. There are clear benefits to adding the treatment to the current trial for comparison, but how? As flexible as the MAMS framework is, it requires pre-planned options for how the trial proceeds at each stage in order to control the familywise error rate. Thus, as with many adaptive designs, it is difficult to make 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. Using a single stage two-arm trial, we demonstrate the principals of incorporating additional hypotheses into the testing structure. With this framework for adding treatments and hypotheses in place, we show how to update the testing procedure for a MAMS trial in progress to incorporate additional treatment arms. Through simulation, we illustrate the operating characteristics of such procedures.
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