Case Study: An Adaptive Design that Uses a Utility Function to Identify the Best Dose in a Crossover Setting
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*Kenneth Liu, Merck 


This is a case study of a recent clinical trial that combines proof-of-concept with dose finding. Proof-of-concept in clinical trials has traditionally focused on identification of a maximum tolerated dose with the assumption that the higher doses provide better efficacy. However adverse events associated with a maximum tolerated dose may have a negative effect on efficacy. We present an adaptive dose-finding strategy which concentrates assignments at and around the dose which has the best efficacy/tolerability profile based on a utility function. The strategy is applied to a three period crossover design to improve power and allow for inclusion of an active control. Operating characteristics over various missing data and efficacy/tolerability scenarios were studied via simulation. Advantages and disadvantages of this adaptive design versus traditional trial designs will be discussed.