A modified varying-stage adaptive phase II/III clinical trial design.
Conventionally, adaptive phase II/III clinical trials are carried out with a strict two-stage design. Recently, a varying-stage adaptive phase II/III clinical trial design has been developed. In this design, following the first stage, an intermediate stage can be adaptively added to obtain more data, so that a more informative decision can be made. Therefore, the number of further investigational stages is determined based upon data accumulated to the interim analysis. This design considers two plausible study endpoints, with one of them initially designated as the primary endpoint. Based on interim results, another endpoint can be switched as the primary endpoint. However, in many therapeutic areas, the primary study endpoint is well established. Therefore, we modify this design to consider one study endpoint only so that it may be more readily applicable in real clinical trial designs. Our simulations show that, the same as the original design, this modified design controls the Type I error rate, and the design parameters such as the threshold probability for the two-stage setting and the alpha allocation ratio in the two-stage setting versus the three-stage setting have a great impact on the design characteristics. However, this modified design requires a larger sample size for the initial stage, and the probability of futility becomes much higher when the threshold probability for the two-stage setting gets smaller. Copyright © 2016 John Wiley & Sons, Ltd.
iStats Inc., Long Island City, NY, USA.
Gaohong
G
Dong
Novartis Pharma AG, Basel, Switzerland.
Marc
M
Vandemeulebroecke
D017322:Clinical Trials, Phase II as Topic / Q000379:methods / Q000706:statistics & numerical data*; D017326:Clinical Trials, Phase III as Topic / Q000379:methods / Q000706:statistics & numerical data*; D003198:Computer Simulation / Q000706:statistics & numerical data*; D023381:Endpoint Determination / Q000379:methods / Q000706:statistics & numerical data; D006801:Humans; D012107:Research Design / Q000706:statistics & numerical data*
adaptive design; family-wise Type I error rate; p-value combination; phase II/III clinical trial design; varying-stage design