A three-outcome design for phase II clinical trials

The goal of a phase II trial is to make a preliminary determination regardi ng the activity and tolerability of a new treatment and thus to determine w hether the treatment warrants further study in the phase III setting. Phase II clinical trials are typically designed in the hypothesis testing framew ork with two possible outcomes, either reject the null hypothesis H-0 or re ject the alternative hypothesis H-alpha, based on the observed activity lev el. However, in cases where the observed activity is "borderline," the deci sion regarding the future of the agent is not as clear as the prespecified hypothesis test would indicate. In this paper we propose an alternative des ign that allows for three outcomes: reject H-0, reject H-alpha, or reject n either. We describe the theoretical properties of this design and illustrat e it with several examples. We focus on the clinical implications of the th ree-outcome design. (C) Elsevier Science Inc. 2001.