Planned versus attained design in phase II clinical trials

Abstract

The standard phase II trial problem is to decide whether or not to continue the testing of a new agent (or combination). Typically, one tests the null hypothesis H_o:p = p_o against the alternative H_A:p = p_A, where p is the probability of response. There is available a variety of two-stage phase II designs, including optimal designs according to various criteria. Practical considerations in the conduct of multicentre trials, however, make it difficult to follow designs precisely. We investigate several approaches to adapting stopping rules when the attained sample size is not the planned size. We find that a simple approach of testing H_A:p = p_A at the 0·02 level at the first stage and H_o:p = p_o at the 0·055 level at the second stage works well across a variety of powers, p_os and p_As.