Two-Stage Adaptive Seamless Trial Design With Different Study Objectives/Endpoints

Abstract

In recent years, the use of adaptive design methods in clinical research and development based on accrued data has become very popular due to its flexibility and efficiency in modifying trial and/or statistical procedures of on-going clinical trials. One of the most commonly considered adaptive designs in clinical trials is probably the two-stage adaptive seamless (e.g., phase I/II or phase II/III) trial design that combines two separate studies (phase I and phase II or phase II and phase III) into one single study. In many cases, study objectives and/or study endpoints considered in a two-stage adaptive seamless design may be similar but different. In this case, it is a concern that how the sample size calculation/allocation should be done for achieving the study objectives originally set for the two stages (separate studies). In this presentation, formulas for sample size calculation/allocation are derived for cases when the study endpoints are continuous, discrete (e.g., binary responses), and time-to-event data assuming that there is a well-established relationship between the study endpoints at different stages. Key Words: Target patient population; Two-stage seamless design; Sample size calculation/allocation; Binary response; Time-to-event data.