Stopping for efficacy in single-arm phase II clinical trials

Abstract

Phase II clinical trials investigate whether a new drug or treatment has sufficient evidence of effectiveness against the disease under study. Two-stage designs are popular for phase II since they can stop in the first stage if the drug is ineffective. Investigators often face difficulties in determining the target response rates, and adaptive designs can help to set the target response rate tested in the second stage based on the number of responses observed in the first stage. Popular adaptive designs consider two alternate response rates, and they generally minimise the expected sample size at the maximum uninterested response rate. Moreover, these designs consider only futility as the reason for early stopping and have high expected sample sizes if the provided drug is effective. Motivated by this problem, we propose an adaptive design that enables us to terminate the single-arm trial at the first stage for efficacy and conclude which alternate response rate to choose. Comparing the proposed design with a popular adaptive design from literature reveals that the expected sample size decreases notably if any of the two target response rates are correct. In contrast, the expected sample size remains almost the same under the null hypothesis.

Keywords:

• Phase II trial
• two-stage design
• optimal design
• single-arm trial
• sample size

Acknowledgments

The authors would like to thank the reviewers for their useful suggestions to improve the paper. The first author also would like to thank the Ministry of Science and Technology, Government of Bangladesh, for providing him the National Science and Technology Fellowship during this work.

Disclosure statement

No potential conflict of interest was reported by the author(s).