论文标题
在存在治疗切换的情况下通过主分层评估因果效应
Assessing causal effects in the presence of treatment switching through principal stratification
论文作者
论文摘要
如果患者的身体状况比某些公差水平差,则临床试验通常允许对照组中的患者切换到治疗臂。例如,在协和临床试验中出现了治疗转换,该试验旨在评估无症状HIV感染患者的抗疾病症的进展或Zidovudine递延治疗的因果关系的影响。意向性治疗分析不能衡量治疗实际收到的影响,而忽略了治疗切换的信息。其他现有方法重建患者在强有力的假设下没有切换的情况下会产生的结果。偏离文献,我们重新定义了使用主要分层的治疗转换问题,并重点介绍了由控制行为所定义的亚种群的患者的因果效应。考虑到(i)切换在连续的时间内发生;我们使用贝叶斯方法进行推理; (ii)对于从未在特定实验中切换的患者,切换时间尚未定义; (iii)生存时间和切换时间受到审查。我们将此框架应用于协和研究来分析合成数据。我们的数据分析表明,齐多夫定立即治疗增加了永无切换的生存时间,而治疗效果在通过切换行为定义的不同类型的患者中是高度异质的。
Clinical trials often allow patients in the control arm to switch to the treatment arm if their physical conditions are worse than certain tolerance levels. For instance, treatment switching arises in the Concorde clinical trial, which aims to assess causal effects on the time-to-disease progression or death of immediate versus deferred treatment with zidovudine among patients with asymptomatic HIV infection. The Intention-To-Treat analysis does not measure the effect of the actual receipt of the treatment and ignores the information on treatment switching. Other existing methods reconstruct the outcome a patient would have had if they had not switched under strong assumptions. Departing from the literature, we re-define the problem of treatment switching using principal stratification and focus on causal effects for patients belonging to subpopulations defined by the switching behavior under control. We use a Bayesian approach to inference, taking into account that (i) switching happens in continuous time; (ii) switching time is not defined for patients who never switch in a particular experiment; and (iii) survival time and switching time are subject to censoring. We apply this framework to analyze synthetic data based on the Concorde study. Our data analysis reveals that immediate treatment with zidovudine increases survival time for never switcher and that treatment effects are highly heterogeneous across different types of patients defined by the switching behavior.