Greene Tom, Joffe Marshall, Hu Bo, Li Liang, Boucher Ken
Int J Biostat. 2013 May 7;9(2):291-306. doi: 10.1515/ijb-2012-0013.
Statistical analysis of longitudinal outcomes is often complicated by the absence of observable values in patients who die prior to their scheduled measurement. In such cases, the longitudinal data are said to be "truncated by death" to emphasize that the longitudinal measurements are not simply missing, but are undefined after death. Recently, the truncation by death problem has been investigated using the framework of principal stratification to define the target estimand as the survivor average causal effect (SACE), which in the context of a two-group randomized clinical trial is the mean difference in the longitudinal outcome between the treatment and control groups for the principal stratum of always-survivors. The SACE is not identified without untestable assumptions. These assumptions have often been formulated in terms of a monotonicity constraint requiring that the treatment does not reduce survival in any patient, in conjunction with assumed values for mean differences in the longitudinal outcome between certain principal strata. In this paper, we introduce an alternative estimand, the balanced-SACE, which is defined as the average causal effect on the longitudinal outcome in a particular subset of the always-survivors that is balanced with respect to the potential survival times under the treatment and control. We propose a simple estimator of the balanced-SACE that compares the longitudinal outcomes between equivalent fractions of the longest surviving patients between the treatment and control groups and does not require a monotonicity assumption. We provide expressions for the large sample bias of the estimator, along with sensitivity analyses and strategies to minimize this bias. We consider statistical inference under a bootstrap resampling procedure.
纵向结局的统计分析常常因在预定测量之前死亡的患者缺乏可观测值而变得复杂。在这种情况下,纵向数据被称为“因死亡而截断”,以强调纵向测量并非简单缺失,而是在死亡后无定义。最近,利用主分层框架对因死亡而截断的问题进行了研究,将目标估计量定义为幸存者平均因果效应(SACE),在两组随机临床试验的背景下,它是始终存活者主层中治疗组和对照组纵向结局的平均差异。如果没有不可检验的假设,SACE是无法识别的。这些假设通常根据单调性约束来制定,要求治疗不会降低任何患者的生存率,并结合某些主层之间纵向结局平均差异的假设值。在本文中,我们引入了一种替代估计量,即平衡SACE,它被定义为在始终存活者的特定子集中对纵向结局的平均因果效应,该子集在治疗和对照下的潜在生存时间方面是平衡的。我们提出了一种简单的平衡SACE估计器,它比较治疗组和对照组中最长存活患者的等效分数之间的纵向结局,并且不需要单调性假设。我们给出了估计器大样本偏差的表达式,以及敏感性分析和最小化此偏差的策略。我们考虑在自助重采样程序下进行统计推断。