Biostatistics, School of Community-Based Medicine, University of Manchester, Oxford Road, Manchester M13 9PL, U.K.
Stat Med. 2010 Dec 20;29(29):2994-3003. doi: 10.1002/sim.4070. Epub 2010 Oct 20.
Noncompliance often complicates estimation of treatment efficacy from randomized trials. Under random noncompliance, per protocol analyses or even simple regression adjustments for noncompliance, could be adequate for causal inference, but special methods are needed when noncompliance is related to risk. For survival data, Robins and Tsiatis introduced the semi-parametric structural Causal Accelerated Life Model (CALM) which allows time-dependent departures from randomized treatment in either arm and relates each observed event time to a potential event time that would have been observed if the control treatment had been given throughout the trial. Alternatively, Loeys and Goetghebeur developed a structural Proportional Hazards (C-Prophet) model for when there is all-or-nothing noncompliance in the treatment arm only. Whitebiet al. proposed a 'complier average causal effect' method for Proportional Hazards estimation which allows time-dependent departures from randomized treatment in the active arm. A time-invariant version of this estimator (CHARM) consists of a simple adjustment to the Intention-to-Treat hazard ratio estimate. We used simulation studies mimicking a randomized controlled trial of active treatment versus control with censored time-to-event data, and under both random and non-random time-dependent noncompliance, to evaluate performance of these methods in terms of 95 per cent confidence interval coverage, bias and root mean square errors (RMSE). All methods performed well in terms of bias, even the C-Prophet used after treating time-varying compliance as all-or-nothing. Coverage of the latter method, as implemented in Stata, was too low. The CALM method performed best in terms of bias and coverage but had the largest RMSE.
不依从常常使从随机试验中估计治疗效果变得复杂。在随机不依从的情况下,按方案分析甚至简单的回归调整不依从,对于因果推断可能是足够的,但当不依从与风险相关时,需要特殊的方法。对于生存数据,Robins 和 Tsiatis 引入了半参数结构因果加速寿命模型(CALM),该模型允许在任何一个臂中出现与随机治疗的时间相关的偏离,并且将每个观察到的事件时间与如果在整个试验中给予对照治疗本应观察到的潜在事件时间相关联。或者,Loeys 和 Goetghebeur 为仅在治疗臂中存在全或无不依从的情况开发了结构比例风险(C-Prophet)模型。White 等人提出了一种用于比例风险估计的“依从平均因果效应”方法,该方法允许在活性臂中出现与随机治疗的时间相关的偏离。这个估计器的时不变版本(CHARM)包括对意向治疗风险比估计的简单调整。我们使用模拟研究模拟了一项活性治疗与对照的随机对照试验,数据为删失时间事件数据,并在随机和非随机时间相关不依从的情况下,评估这些方法在 95%置信区间覆盖、偏差和均方根误差(RMSE)方面的性能。所有方法在偏差方面表现良好,即使在将随时间变化的依从性视为全或无时,也使用 C-Prophet。后者方法(在 Stata 中实现)的覆盖范围太低。CALM 方法在偏差和覆盖范围方面表现最好,但 RMSE 最大。