Between-Arm Comparisons in Randomized Phase II Trials

Abstract

In a Phase II trial, we may randomize patients to multiple arms of experimental therapies and evaluate their efficacy to determine if any of them is worthy of a large scale Phase III trial. Usually the primary objective of such a study is to identify experimental therapies that are efficacious compared to a historical control. Each arm is independently evaluated using a standard design a for single-arm Phase II trial, e.g., Simon's optimal or minimax design. When more than one arm is accepted through such a randomized trial, we may want to select the winner(s) among them. There are methods for between-arm comparisons in the literature, but most of them have drawbacks. They have a large false selection (type I error) probability when the competing arms have a small difference in efficacy, or the statistical tests used in the selection procedure do not properly reflect the small sample sizes and multi-stage design of the trials. In this paper, we propose between-arm comparison methods for selection in randomized Phase II trials addressing these issues.

Key Words:

• Pick-the-winner
• Two-stage design
• Type I error
• Type II error
• Uniformly minimum variance unbiased estimator