Abstract：
Inferentially seamless 2/3 designs are increasingly popular in clinical trials. It is important to understand their relative advantages compared with separate phase 2 and phase 3 trials, and to understand the consequences of design choices such as the proportion of patients included in the phase 2 portion of the design. Extending previous work in this area, we perform a simulation study across multiple numbers of arms and efficacy response curves. We consider a design space crossing the choice of a separate versus seamless design with the choice of allocating 0%-100% of available patients in phase 2, with the remainder in phase 3. The seamless designs achieve greater power than their separate trial counterparts. Importantly, the optimal seamless design is more robust than the optimal separate program, meaning that one range of values for the proportion of patients used in phase 2 (30%-50% of the total phase 2/3 sample size) is nearly optimal for a wide range of response scenarios. In contrast, a percentage of patients used in phase 2 for separate trials may be optimal for some alternative scenarios but decidedly inferior for other alternative scenarios. When operationally and scientifically viable, seamless trials provide superior performance compared with separate phase 2 and phase 3 trials. The results also provide guidance for the implementation of these trials in practice.
摘要：
推断无缝2/3设计在临床试验中越来越受欢迎。重要的是要了解它们与单独的第二阶段和第三阶段试验相比的相对优势，并了解设计选择的后果，例如设计第二阶段部分中包含的患者比例。扩展这方面的先前工作，我们对多个臂和疗效反应曲线进行了模拟研究.我们考虑的设计空间跨越了单独设计与无缝设计的选择，选择在第2阶段分配0％-100％的可用患者，其余患者在第3阶段。无缝设计比单独的试验对应物实现更大的功率。重要的是,最优无缝设计比最优单独方案更健壮，这意味着2期使用的患者比例的一个值范围(占总2/3期样本量的30%-50%)对于广泛的应答方案几乎是最佳的.相比之下,在2期单独试验中使用的患者百分比对于某些替代方案可能是最佳的,但对于其他替代方案则明显较差.当操作和科学上可行时，无缝试验提供卓越的性能相比，单独的阶段2和阶段3试验。研究结果也为这些试验在实践中的实施提供了指导。
