Design Issues in Randomized Phase II/III Trials

Abstract

Phase II trials are used to show sufficient preliminary activity of a new treatment (in single-arm designs or randomized screening designs) or to select among treatments with demonstrated activity (in randomized selection designs). The treatments prioritized in a phase II trial are then tested definitively against a control treatment in a randomized phase III trial. Randomized phase II/III trials use an adaptive trial design that combines these two types of trials in one, with potential gains in time and reduced numbers of patients required to be treated. Two key considerations in designing a phase II/III trial are whether to suspend accrual while the phase II data mature and the choice of phase II target treatment effect. We discuss these phase II/III design parameters, give examples of phase II/III trials, and provide recommendations concerning efficient phase II/III trial designs.