Semiparametric regression for the weighted composite endpoint of recurrent and terminal events
Semiparametric regression for the weighted composite endpoint of recurrent and terminal events
复制标题
DOI：
10.1093/biostatistics/kxv050
复制
发表时间：
2016-04-01
期刊：
影响因子：
2.1
通讯作者：
Lin, D. Y.
中科院分区：
文献类型：
--
作者：
Mao, Lu;Lin, D. Y.
在临床和流行病学研究中经常遇到复发事件数据。当复发事件因死亡而终止时，会出现主要并发症。为了评估协变量对这两种事件的总体影响，我们将加权复合终点定义为按每个事件的相对严重程度适当加权的复发事件和终止事件的累积数量。我们提出了一个半参数比例速率模型，该模型规定（可能时变的）协变量对加权复合端点的速率函数具有乘法效应，同时使速率函数的形式以及循环事件和终端事件之间的依赖关系完全不确定。我们对回归参数和累积频率函数构造了适当的估计量。我们证明了估计量是一致的和渐近正态的，方差可以一致估计。我们还开发了图形和数值程序来检查模型的充分性。然后，我们证明了所提出的方法在模拟研究中的实用性。最后，我们提供了一个主要的心血管临床试验的应用程序。
Recurrent event data are commonly encountered in clinical and epidemiological studies. A major complication arises when recurrent events are terminated by death. To assess the overall effects of covariates on the two types of events, we define a weighted composite endpoint as the cumulative number of recurrent and terminal events properly weighted by the relative severity of each event. We propose a semiparametric proportional rates model which specifies that the (possibly time-varying) covariates have multiplicative effects on the rate function of the weighted composite endpoint while leaving the form of the rate function and the dependence among recurrent and terminal events completely unspecified. We construct appropriate estimators for the regression parameters and the cumulative frequency function. We show that the estimators are consistent and asymptotically normal with variances that can be consistently estimated. We also develop graphical and numerical procedures for checking the adequacy of the model. We then demonstrate the usefulness of the proposed methods in simulation studies. Finally, we provide an application to a major cardiovascular clinical trial.