Ghosh Debashis
Departments of Statistics and Public Health Sciences, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
Biometrics. 2009 Jun;65(2):521-9. doi: 10.1111/j.1541-0420.2008.01109.x.
There has been a recent emphasis on the identification of biomarkers and other biologic measures that may be potentially used as surrogate endpoints in clinical trials. We focus on the setting of data from a single clinical trial. In this article, we consider a framework in which the surrogate must occur before the true endpoint. This suggests viewing the surrogate and true endpoints as semicompeting risks data; this approach is new to the literature on surrogate endpoints and leads to an asymmetrical treatment of the surrogate and true endpoints. However, such a data structure also conceptually complicates many of the previously considered measures of surrogacy in the literature. We propose novel estimation and inferential procedures for the relative effect and adjusted association quantities proposed by Buyse and Molenberghs (1998, Biometrics 54, 1014-1029). The proposed methodology is illustrated with application to simulated data, as well as to data from a leukemia study.
最近人们一直强调识别生物标志物和其他生物学指标,这些指标可能在临床试验中用作替代终点。我们专注于单个临床试验的数据设置。在本文中,我们考虑一个框架,其中替代指标必须在真正的终点之前出现。这意味着将替代指标和真正的终点视为半竞争风险数据;这种方法在替代终点的文献中是新的,并导致对替代指标和真正终点的不对称处理。然而,这样的数据结构在概念上也使文献中许多先前考虑的替代指标测量变得复杂。我们针对Buyse和Molenberghs(1998年,《生物统计学》54卷,1014 - 1029页)提出的相对效应和调整关联量,提出了新颖的估计和推断程序。所提出的方法通过应用于模拟数据以及白血病研究的数据进行了说明。