Tchetgen Tchetgen Eric J
Departments of Epidemiology and Biostatistics, Harvard University, MA, U.S.A.
Stat Med. 2014 Sep 20;33(21):3601-28. doi: 10.1002/sim.6181. Epub 2014 May 29.
In longitudinal studies, outcomes ascertained at follow-up are typically undefined for individuals who die prior to the follow-up visit. In such settings, outcomes are said to be truncated by death and inference about the effects of a point treatment or exposure, restricted to individuals alive at the follow-up visit, could be biased even if as in experimental studies, treatment assignment were randomized. To account for truncation by death, the survivor average causal effect (SACE) defines the effect of treatment on the outcome for the subset of individuals who would have survived regardless of exposure status. In this paper, the author nonparametrically identifies SACE by leveraging post-exposure longitudinal correlates of survival and outcome that may also mediate the exposure effects on survival and outcome. Nonparametric identification is achieved by supposing that the longitudinal data arise from a certain nonparametric structural equations model and by making the monotonicity assumption that the effect of exposure on survival agrees in its direction across individuals. A novel weighted analysis involving a consistent estimate of the survival process is shown to produce consistent estimates of SACE. A data illustration is given, and the methods are extended to the context of time-varying exposures. We discuss a sensitivity analysis framework that relaxes assumptions about independent errors in the nonparametric structural equations model and may be used to assess the extent to which inference may be altered by a violation of key identifying assumptions.
在纵向研究中,对于在随访前死亡的个体,随访时确定的结局通常是未定义的。在这种情况下,结局被认为因死亡而被截断,并且即使像在实验研究中那样治疗分配是随机的,对于仅限于在随访时存活的个体的点治疗或暴露效应的推断也可能存在偏差。为了考虑因死亡导致的截断,幸存者平均因果效应(SACE)定义了治疗对无论暴露状态如何都会存活的个体子集的结局的影响。在本文中,作者通过利用生存和结局的暴露后纵向相关因素(这些因素也可能介导暴露对生存和结局的影响)以非参数方式识别SACE。非参数识别是通过假设纵向数据来自某个非参数结构方程模型,并做出单调性假设,即暴露对生存的影响在个体间方向一致来实现的。一种涉及生存过程一致估计的新颖加权分析被证明能产生SACE的一致估计。给出了一个数据示例,并将这些方法扩展到时变暴露的背景下。我们讨论了一个敏感性分析框架,该框架放宽了关于非参数结构方程模型中独立误差的假设,可用于评估违反关键识别假设可能改变推断的程度。