论文标题
使用Kaplan-Meier估计器的转换进行单臂生存研究的样本量计算
Sample size calculations for single-arm survival studies using transformations of the Kaplan-Meier estimator
论文作者
论文摘要
在具有生存结果的单臂临床试验中,Kaplan-Meier估计量及其置信区间被广泛用于评估生存概率和中位生存时间。由于Kaplan-Meier估计量的渐近正态性是一个常见的结果,因此尚未深入研究样本量计算方法。现有的样本量计算方法建立在使用日志变换的Kaplan-Meier估计器的渐近正态性上。但是,对数转换的估计量的小样本特性在小样本量(这是单臂试验中的典型情况)中非常差,并且现有方法使用不适当的标准正常近似来计算样本量。这些问题会严重影响结果的准确性。在本文中,我们提出了基于有效的标准正常近似值来确定样本量的替代方法,这些方法具有几种转换,即使样本量较小,也可能会提供准确的正常近似值。在通过模拟的数值评估中,某些提出的方法提供了更准确的结果,并且使用Arcsine Square-root转换所提出的方法的经验能力往往比其他转换更接近规定的功率。当将方法应用于三个临床试验的数据时,支持这些结果。
In single-arm clinical trials with survival outcomes, the Kaplan-Meier estimator and its confidence interval are widely used to assess survival probability and median survival time. Since the asymptotic normality of the Kaplan-Meier estimator is a common result, the sample size calculation methods have not been studied in depth. An existing sample size calculation method is founded on the asymptotic normality of the Kaplan-Meier estimator using the log transformation. However, the small sample properties of the log transformed estimator are quite poor in small sample sizes (which are typical situations in single-arm trials), and the existing method uses an inappropriate standard normal approximation to calculate sample sizes. These issues can seriously influence the accuracy of results. In this paper, we propose alternative methods to determine sample sizes based on a valid standard normal approximation with several transformations that may give an accurate normal approximation even with small sample sizes. In numerical evaluations via simulations, some of the proposed methods provided more accurate results, and the empirical power of the proposed method with the arcsine square-root transformation tended to be closer to a prescribed power than the other transformations. These results were supported when methods were applied to data from three clinical trials.