Joffe Marshall M, Greene Tom
Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6021, USA.
Biometrics. 2009 Jun;65(2):530-8. doi: 10.1111/j.1541-0420.2008.01106.x.
Four major frameworks have been developed for evaluating surrogate markers in randomized trials: one based on conditional independence of observable variables, another based on direct and indirect effects, a third based on a meta-analysis, and a fourth based on principal stratification. The first two of these fit into a paradigm we call the causal-effects (CE) paradigm, in which, for a good surrogate, the effect of treatment on the surrogate, combined with the effect of the surrogate on the clinical outcome, allow prediction of the effect of the treatment on the clinical outcome. The last two approaches fall into the causal-association (CA) paradigm, in which the effect of the treatment on the surrogate is associated with its effect on the clinical outcome. We consider the CE paradigm first, and consider identifying assumptions and some simple estimation procedures; we then consider the CA paradigm. We examine the relationships among these approaches and associated estimators. We perform a small simulation study to illustrate properties of the various estimators under different scenarios, and conclude with a discussion of the applicability of both paradigms.
一种基于可观测变量的条件独立性,另一种基于直接和间接效应,第三种基于荟萃分析,第四种基于主分层。其中前两种框架属于我们称为因果效应(CE)范式的范畴,在该范式中,对于一个良好的替代指标,治疗对替代指标的效应,与替代指标对临床结局的效应相结合,能够预测治疗对临床结局的效应。后两种方法属于因果关联(CA)范式,在该范式中,治疗对替代指标的效应与其对临床结局的效应相关联。我们首先考虑CE范式,并考虑识别假设和一些简单的估计程序;然后我们考虑CA范式。我们研究这些方法与相关估计量之间的关系。我们进行了一项小型模拟研究,以说明不同场景下各种估计量的性质,并最后讨论这两种范式的适用性。