Fang Fang, Fan Xiaoyin, Zhang Ying
East China Normal University, Shanghai, 200241, China.
Novartis Pharmaceuticals, 45 Sidney Street, Cambridge, MA, 02139, USA.
Contemp Clin Trials Commun. 2016 Jul 16;4:90-98. doi: 10.1016/j.conctc.2016.06.011. eCollection 2016 Dec 15.
In migraine trials pain relief responses from a headache at specific time points and sustained pain relief response over a period of time are important efficacy measures. When there are missing records of individual time point pain scores and/or headache recurrences during a migraine trial, the common approach used in practice to estimate the sustained response is statistically inconsistent even if the data are missing completely at random. Methods dealing with nonignorable longitudinal missing data usually assume certain models for the missing mechanism which can not be checked as they involve unobserved data. Taking advantage of the specific definition of the 'sustained pain relief' response, we propose two estimating methods based on intuitive imputation, which do not require model assumptions on the missing probability or specification of the correlation structure among the longitudinal observations. The consistency of the proposed methods is discussed in theory and their empirical performances are assessed through intensive simulation studies. The simulation results show that the proposed methods perform well in terms of reducing bias and mean square error except in several extreme cases which are unlikely to happen in real trials. The application of the proposed methods is illustrated in a real data analysis.
在偏头痛试验中，特定时间点头痛的疼痛缓解反应以及一段时间内的持续疼痛缓解反应是重要的疗效指标。当偏头痛试验期间存在个体时间点疼痛评分和/或头痛复发的缺失记录时，实践中用于估计持续反应的常用方法在统计上是不一致的，即使数据是完全随机缺失的。处理不可忽略的纵向缺失数据的方法通常对缺失机制假设某些模型，而这些模型无法检验，因为它们涉及未观测到的数据。利用“持续疼痛缓解”反应的特定定义，我们提出了两种基于直观插补的估计方法，这两种方法不需要对缺失概率进行模型假设，也不需要指定纵向观测值之间的相关结构。从理论上讨论了所提方法的一致性，并通过大量模拟研究评估了它们的实证性能。模拟结果表明，所提方法在减少偏差和均方误差方面表现良好，除了在实际试验中不太可能发生的几种极端情况下。在所进行的实际数据分析中展示了所提方法的应用。
