Model selection versus model averaging in dose finding studies

Abstract

Phase II dose finding studies in clinical drug development are typically conducted to adequately characterize the dose response relationship of a new drug. An important decision is then on the choice of a suitable dose response function to support dose selection for the subsequent Phase III studies. In this paper we compare different approaches for model selection and model averaging using mathematical properties as well as simulations. Accordingly, we review and illustrate asymptotic properties of model selection criteria and investigate their behavior when changing the sample size but keeping the effect size constant. In a large scale simulation study we investigate how the various approaches perform in realistically chosen settings. Finally, the different methods are illustrated with a recently conducted Phase II dosefinding study in patients with chronic obstructive pulmonary disease.