LAUSR

Background: We explore frequentist operating characteristics of a Bayesian adaptive design that allows continuous early stopping for futility. In particular, we focus on the power versus sample size relationship when more patients are accrued than originally planned. Methods: We consider the case of a phase II single-arm study and a Bayesian phase II outcome-adaptive randomization design. For the former, analytical calculations are possible; for the latter, simulations are conducted. Results: Results for both cases show a decrease in power with an increasing sample size. It appears that this effect is due to the increasing cumulative probability of incorrectly stopping for futility. Conclusion: The increase in cumulative probability of incorrectly stopping for futility is related to the continuous nature of the early stopping, which increases the number of interim analyses with accrual. The issue can be addressed by, for instance, delaying the start of testing for futility, reducing the number of futility tests to be performed or by setting stricter criteria for concluding futility.