Randomized Two-Stage Phase II Clinical Trial Designs Based on Barnard's Exact Test

Abstract

In areas such as oncology, two-stage designs are often preferred as compared to one-stage designs due to the ability to stop the trial early when faced with evidence of lack of sufficient efficacy and the associated sample size savings. We present exact two-stage designs based on Barnard's exact test for differences in proportions and compare the designs to those proposed by Kepner (2010) and Jung (2010). In addition, we present tables of decision rules under a variety of assumed realities for use in trial planning. The procedure is recommended for use due to the substantial sample size savings experienced.

Key Words:

• Barnard test
• Clinical trials
• Minimax design
• Optimal design
• Phase II design

Notes

Note. N is the maximum sample size, and ESS is the expected sample size under the null hypothesis.