Estimating the proportion of treatment effect explained by a surrogate marker
Estimating the proportion of treatment effect explained by a surrogate marker
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DOI：
10.1002/(sici)1097-0258(19970715)16:13
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发表时间：
1997-07-15
影响因子：
2
通讯作者：
DeGruttola, V
中科院分区：
文献类型：
--
作者：
Lin, DY;Fleming, TR;DeGruttola, V
在本文中，我们通过将生物标记物纳入COX回归模型而使治疗指标的回归系数按比例降低来衡量该生物标记物作为临床事件的替代终点的程度。我们通过将偏似然函数应用于假设相同失效时间变量的两个COX模型来估计这一比例。我们证明了所得到的估计量具有简单的方差估计是渐近正态的。可以通过对点估计的直接正态逼近或通过使用Fieller定理来构造该比例的置信度区间。大量的仿真研究表明，所提出的方法是适合实际应用的。我们提供艾滋病毒/艾滋病临床试验的应用程序。(C)1997年John Wiley&Sons，Ltd.
In this paper, we measure the extent to which a biological marker is a surrogate endpoint for a clinical event by the proportional reduction in the regression coefficient for the treatment indicator due to the inclusion of the marker in the Cox regression model. We estimate this proportion by applying the partial likelihood function to two Cox models postulated on the same failure time variable. We show that the resultant estimator is asymptotically normal with a simple variance estimator. One can construct confidence intervals for the proportion by using the direct normal approximation to the point estimator or by using Fieller's theorem. Extensive simulation studies demonstrate that the proposed methods are appropriate for practical use. We provide applications to HIV/AIDS clinical trials. (C) 1997 by John Wiley & Sons, Ltd.