Mukherjee Aritra, Wason James M S, Grayling Michael J
Population Health Sciences Institute, Newcastle University, Ridley 1 Building, Queen Victoria Road, Newcastle Upon Tyne NE1 7RU, UK.
Eur J Cancer. 2022 May;166:270-278. doi: 10.1016/j.ejca.2022.02.010. Epub 2022 Mar 25.
Simon's two-stage design is a widely used adaptive design, particularly in phase II oncology trials due to its simplicity and efficiency. However, its efficiency can be adversely affected when the primary end-point takes time to observe, as is common in practice.
We propose an optimal design, taking the delay in observing treatment outcome into consideration and compare the efficiency gained from using Simon's design over a single-stage design for real-life oncology trials. Based on the results, we provide a general rule-of-thumb for determining whether a two-stage single-arm design can provide any added advantage over a single-stage design, given the recruitment rate and primary end-point length.
We observed an average 15-30% loss in the estimated efficiency gain in real oncology trials that used Simon's design due to the delay in observing the treatment outcome. The delay-optimal design provides some advantage over Simon's design in terms of reduced sample size when the delay is large compared to the recruitment length.
Simon's two-stage design provides large benefit over a single-stage design, in terms of reduced sample size, when the primary end-point length is no more than 10% of the total recruitment time. It provides no efficiency advantage when this ratio is above 50%.
西蒙两阶段设计是一种广泛使用的适应性设计，因其简单性和高效性，尤其在肿瘤学II期试验中应用广泛。然而，正如实际中常见的那样，当主要终点需要时间来观察时，其效率可能会受到不利影响。
我们提出一种优化设计，将观察治疗结果的延迟考虑在内，并比较在实际肿瘤学试验中使用西蒙设计相对于单阶段设计所获得的效率。基于结果，我们给出一个一般经验法则，用于在给定招募率和主要终点时长的情况下，确定两阶段单臂设计是否能比单阶段设计提供任何额外优势。
我们观察到，在实际肿瘤学试验中，由于观察治疗结果的延迟，使用西蒙设计的估计效率增益平均损失15% - 30%。当延迟相对于招募时长较大时，延迟优化设计在减少样本量方面比西蒙设计具有一定优势。
当主要终点时长不超过总招募时间的10%时，西蒙两阶段设计在减少样本量方面比单阶段设计有很大优势。当该比例高于50%时，它没有效率优势。
