Properties of adaptive clinical trial signature design in the presence of gene and gene-treatment interaction

Traditional phase III clinical trials are powered to detect an overall treatment effect. However, it has increasingly been shown that many treatments are effective only for a subset of a population. The adaptive signature design uses genomic/proteomic information to prospectively predict a subset of patients more sensitive to treatment. Tests for overall treatment effect and for treatment effect in the predicted subset are conducted. In this work properties of the adaptive signature design are investigated through simulation. It was found that models which excluded expression main effect terms had higher empirical power than models which included them.