A comparison of methods for constructing confidence intervals after phase II/III clinical trials
A comparison of methods for constructing confidence intervals after phase II/III clinical trials
复制标题
DOI：
10.1002/bimj.201300036
复制
发表时间：
2014-01-01
影响因子：
1.7
通讯作者：
Stallard, Nigel
中科院分区：
文献类型：
--
作者：
Kimani, Peter K.;Todd, Susan;Stallard, Nigel
最近，为了加速药物开发，已经提出了使用适应性无缝设计的试验，例如II/III期临床试验。II/III期临床试验联合收割机将传统的II期和III期合并为一项试验，分两个阶段进行。使用第1阶段数据，进行中期分析以回答II期目的，在收集第2阶段数据后，进行最终确证性分析以回答III期目的。在本文中，我们考虑II/III期临床试验，其中，在第1阶段，几个实验治疗进行了比较，以控制和显然最有效的实验治疗被选择继续到第2阶段。虽然这些试验很有吸引力，因为验证性分析包括第1阶段的II期数据，但用于比较单一实验治疗与对照且没有中期分析的试验的推断方法不再适用。已经开发了几种分析II/III期临床试验的方法。这些方法是最近的，所以很少有文献对它们的特点进行广泛的比较。在本文中，我们回顾和比较各种方法可用于构建置信区间后，II/III期临床试验。
Recently, in order to accelerate drug development, trials that use adaptive seamless designs such as phase II/III clinical trials have been proposed. Phase II/III clinical trials combine traditional phases II and III into a single trial that is conducted in two stages. Using stage 1 data, an interim analysis is performed to answer phase II objectives and after collection of stage 2 data, a final confirmatory analysis is performed to answer phase III objectives. In this paper we consider phase II/III clinical trials in which, at stage 1, several experimental treatments are compared to a control and the apparently most effective experimental treatment is selected to continue to stage 2. Although these trials are attractive because the confirmatory analysis includes phase II data from stage 1, the inference methods used for trials that compare a single experimental treatment to a control and do not have an interim analysis are no longer appropriate. Several methods for analysing phase II/III clinical trials have been developed. These methods are recent and so there is little literature on extensive comparisons of their characteristics. In this paper we review and compare the various methods available for constructing confidence intervals after phase II/III clinical trials.