Li Xianbin, Caffo Brian S
U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
J Biopharm Stat. 2011 Mar;21(2):271-81. doi: 10.1080/10543406.2011.550109.
Composite endpoints are commonly used in clinical trials. When there are missing values in their individual components, inappropriate handling of the missingness may create inefficient or even biased estimates of the proportions of successes in composite endpoints. Assuming missingness is completely at random or dependent on baseline covariates, we derived a maximum likelihood estimator of the proportion of successes in a three-component composite endpoint and closed-form variance for the proportion, and compared two groups in the difference in proportions and in the logarithm of a relative risk. Sample size and statistical power were studied. Simulation studies were used to evaluate the performance of the developed methods. With a moderate sample size the developed methods works satisfactorily.
复合终点在临床试验中常用。当其各个组成部分存在缺失值时，对缺失情况的不当处理可能会导致对复合终点中成功比例的估计效率低下甚至产生偏差。假设缺失完全是随机的或依赖于基线协变量，我们推导了一个三分组成复合终点中成功比例的最大似然估计量以及该比例的闭式方差，并比较了两组在比例差异和相对风险对数方面的情况。研究了样本量和统计功效。通过模拟研究来评估所开发方法的性能。在中等样本量下，所开发的方法表现令人满意。
