Department of Mathematics, Faculty of Science, Vrije Universiteit Amsterdam, Amsterdam, North-Holland, The Netherlands.
Department of Statistics, TU Dortmund University, Dortmund, North-Rhine Westphalia, Germany.
Stat Med. 2024 May 20;43(11):2216-2238. doi: 10.1002/sim.10063. Epub 2024 Mar 28.
A frequently addressed issue in clinical trials is the comparison of censored paired survival outcomes, for example, when individuals were matched based on their characteristics prior to the analysis. In this regard, a proper incorporation of the dependence structure of the paired censored outcomes is required and, up to now, appropriate methods are only rarely available in the literature. Moreover, existing methods are not motivated by the strive for insights by means of an easy-to-interpret parameter. Hence, we seek to develop a new estimand-driven method to compare the effectiveness of two treatments in the context of right-censored survival data with matched pairs. With the help of competing risks techniques, the so-called relative treatment effect is estimated. This estimand describes the probability that individuals under Treatment 1 have a longer lifetime than comparable individuals under Treatment 2. We derive hypothesis tests and confidence intervals based on a studentized version of the estimator, where resampling-based inference is established by means of a randomization method. In a simulation study, we demonstrate for numerous sample sizes and different amounts of censoring that the developed test exhibits a good power. Finally, we apply the methodology to a well-known benchmark data set from a trial with patients suffering from diabetic retinopathy.
在临床试验中，经常会涉及到配对生存结局的比较，例如，当个体在分析前根据其特征进行匹配时。在这方面，需要适当考虑配对删失结局的依存结构，而到目前为止，文献中很少有合适的方法。此外，现有的方法并不是为了通过易于解释的参数来获得深入的见解。因此，我们试图开发一种新的基于估计量的方法，用于比较右删失生存数据中配对的两种治疗方法的效果。借助竞争风险技术，估计所谓的相对治疗效果。该估计量描述了在治疗 1 下的个体比在治疗 2 下的可比个体有更长寿命的概率。我们基于估计量的学生化版本推导出假设检验和置信区间，其中通过随机化方法建立基于重抽样的推断。在一项模拟研究中，我们针对多种样本量和不同程度的删失情况表明，所开发的检验具有良好的功效。最后，我们将该方法应用于来自糖尿病视网膜病变患者试验的一个著名基准数据集。
