Screened selection design for randomised phase II oncology trials: an example in chronic lymphocytic leukaemia.
Screened selection design for randomised phase II oncology trials: an example in chronic lymphocytic leukaemia.
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DOI：
10.1186/1471-2288-13-87
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发表时间：
2013-07-03
影响因子：
4
通讯作者：
Billingham L
中科院分区：
文献类型：
--
作者：
Yap C;Pettitt A;Billingham L
由于慢性淋巴细胞白血病试验的患者有限，因此II期试验中的统计方法必须有效地选择方案，以便随后在更大规模的III期试验中进行评价。我们提出了筛选选择设计（SSD），这是一个实用的多阶段，随机II期设计的两个实验组。首先通过在每只手臂上应用Simon的两阶段设计（1989）来评估活动。如果两者都是活动的，则应用Simon，Wittes和Ellenberg（SWE）（1985）提出的玩赢家选择策略来选择上级手臂。设计的变体，修改的SSD，还允许仅当具有较高响应率的臂的活动率大于临床相关值时才推荐具有较高响应率的臂。的操作特性进行了探讨，通过模拟研究，并比较贝叶斯选择方法。模拟显示，使用申报SSD，可以保留SWE中所需的样本量，并获得至少90%的选择正确上级臂的相似概率;以及降低选择无效臂的概率的额外吸引人的受益。这种方法类似于贝叶斯选择策略。如果两组的基础率都是理想的，但相当，则改良SSD在选择任何一组时的性能都明显优于其他设计，从而允许在决策过程中考虑其他因素。尽管其正确选择上级臂的概率可能会降低，但其性能仍然相当好。SSD提供了一种易于实施的随机II期设计，该设计选择了最有希望的治疗方法，这些治疗方法已显示出足够的活性证据，并具有可用的R代码以评估其操作特征。
As there are limited patients for chronic lymphocytic leukaemia trials, it is important that statistical methodologies in Phase II efficiently select regimens for subsequent evaluation in larger-scale Phase III trials. We propose the screened selection design (SSD), which is a practical multi-stage, randomised Phase II design for two experimental arms. Activity is first evaluated by applying Simon’s two-stage design (1989) on each arm. If both are active, the play-the-winner selection strategy proposed by Simon, Wittes and Ellenberg (SWE) (1985) is applied to select the superior arm. A variant of the design, Modified SSD, also allows the arm with the higher response rates to be recommended only if its activity rate is greater by a clinically-relevant value. The operating characteristics are explored via a simulation study and compared to a Bayesian Selection approach. Simulations showed that with the proposed SSD, it is possible to retain the sample size as required in SWE and obtain similar probabilities of selecting the correct superior arm of at least 90%; with the additional attractive benefit of reducing the probability of selecting ineffective arms. This approach is comparable to a Bayesian Selection Strategy. The Modified SSD performs substantially better than the other designs in selecting neither arm if the underlying rates for both arms are desirable but equivalent, allowing for other factors to be considered in the decision making process. Though its probability of correctly selecting a superior arm might be reduced, it still performs reasonably well. It also reduces the probability of selecting an inferior arm. SSD provides an easy to implement randomised Phase II design that selects the most promising treatment that has shown sufficient evidence of activity, with available R codes to evaluate its operating characteristics.
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影响因子：
20.3
作者：
Estey, EH;Thall, PF
通讯作者：
Thall, PF
影响因子：
1.1
作者：
Jung SH;George SL
通讯作者：
George SL
影响因子：
45.3
作者：
Pettitt, Andrew R.;Jackson, Richard;Hillmen, Peter
通讯作者：
Hillmen, Peter
影响因子：
1.9
作者：
LIU, PY;DAHLBERG, S;CROWLEY, J
通讯作者：
CROWLEY, J
影响因子：
1.9
作者：
Bryant, J;Day, R
通讯作者：
Day, R