论文标题
使用优先的复合终点对匹配的净福利和匹配的获胜比率的强大统计推断
Robust statistical inference for the matched net benefit and the matched win ratio using prioritized composite endpoints
论文作者
论文摘要
作为复合终点的第一个事实分析的替代方案,{\ it净益处}(nb)和{\ it win at at at atio}(WR)(WR)(WR)(使用基于临床重要性的优先组件结果来评估治疗效果)。但是,NB和WR的统计推断依赖于大样本假设,这可能导致无效的测试统计量和不足,不满意的置信区间,尤其是当样本量很小或获胜比例接近0或1时。 在本文中,我们开发了一种系统的方法来解决成对样本设计中的这些限制。我们首先在无治疗差异的无效假设下引入了一个新的测试统计数据。然后,我们提出计算样本量的公式。最后,我们开发了这两个估计器的置信区间估计。为了估计置信区间,我们使用{\ IT方差估计方法恢复}(Mover),将两个单独的个体置信区间组合到混合间隔中以进行估计。我们通过模拟研究评估了提出的测试统计统计统计统计统计量和置换置信区间估计的性能。 我们证明,当样本较大时,当获胜比例的比例远离0和1时,搬运置信区间与大样本置信区间一样好。此外,当样本的比例较小时,搬运工的表现优于竞争对手,或者在范围内或附近的竞争对手时,竞争对手是0和1。我们使用三个方法(以及其竞争者进行了三个示例)(以及使用三个研究者)。
As alternatives to the time-to-first-event analysis of composite endpoints, the {\it net benefit} (NB) and the {\it win ratio} (WR) -- which assess treatment effects using prioritized component outcomes based on clinical importance -- have been proposed. However, statistical inference of NB and WR relies on a large-sample assumptions, which can lead to an invalid test statistic and inadequate, unsatisfactory confidence intervals, especially when the sample size is small or the proportion of wins is near 0 or 1. In this paper, we develop a systematic approach to address these limitations in a paired-sample design. We first introduce a new test statistic under the null hypothesis of no treatment difference. Then, we present the formula to calculate the sample size. Finally, we develop the confidence interval estimations of these two estimators. To estimate the confidence intervals, we use the {\it method of variance estimates recovery} (MOVER), that combines two separate individual-proportion confidence intervals into a hybrid interval for the estimand of interest. We assess the performance of the proposed test statistic and MOVER confidence interval estimations through simulation studies. We demonstrate that the MOVER confidence intervals are as good as the large-sample confidence intervals when the sample is large and when the proportions of wins is bounded away from 0 and 1. Moreover, the MOVER intervals outperform their competitors when the sample is small or the proportions are at or near the boundaries 0 and 1. We illustrate the method (and its competitors) using three examples from randomized clinical studies.