Curtailed two-stage design for comparing two arms in randomized phase II clinical trials

ABSTRACT

In phase II clinical trials, patients are recruited sequentially and consequently the time required to complete the clinical trial will become long if the accrual rate is low. To speed up the drug development process and account for ethical issues, stochastically and non-stochastically curtailed two-stage designs have been proposed in single-arm phase II clinical trials. More recently, randomized phase II clinical trials are being increasingly recommended to avoid biased evaluation of the treatment effect when compared with a historical control. The current patient population and the historical one may be quite heterogeneous. Moreover, it is impossible to randomly assign patients for treatments. Consequently, various two-stage designs have been presented for comparing two arms. Since the sample size required in a randomized phase II trial is usually larger than that required in a single-arm phase II trial, we introduce the concept of curtailed sampling procedure to develop curtailed two-stage design for two-armed, randomized phase II clinical trials. The proposed design does not require pairwise patient response comparison, yet it allows a trial to be stopped early as soon as the difference in therapeutic effect of the experimental therapy and the standard at the end of a trial is foreknown. Copyright © 2017 Taylor & Francis Group, LLC

KEYWORDS:

• Curtailed two-stage design
• design parameters
• expected sample size

Acknowledgment

The authors thank the reviewers for providing comments to help condense numerous sections of and incorporate edits in the content for clarity. They also thank the Editor in Chief who coordinated the review of this paper. The work was funded in part by the project grant NSC 102-2118-M-343-001 supported by the Ministry of Science and Technology (formerly the National Science Council) of Taiwan.