处理治疗时机具信息性时,用等待时间作为时变混杂因素可避免因果推断偏差。
Considerations for Estimating Causal Effects of Informatively Timed Treatments
- 将治疗间等待时间视为时变混杂因子,用g方法进行调整。
- 忽略等待时间会导致因果效应估计偏差,尤其在患者可能死亡或删失时。
- 适用于生存分析中动态治疗决策的因果推断,适合流行病学研究者。
流行病学研究常关注一系列治疗决策对生存结局的因果效应。许多情况下,治疗并非在预设随访时间点进行,其时间间隔因人而异,且可能携带未来治疗和结果的信息。现有文献对这一问题及其解决方案认识不足,促使本研究开展。本文正式定义了信息性时机问题,阐明忽略该问题的后果,并展示如何使用g方法分析具信息性时机的序列治疗。我们指出,在此类设置中,相邻治疗间的等待时间应被视为时变混杂因子。通过模拟实例,说明不调整等待时间可能导致偏倚,同时给出在患者可能死亡或删失情形下的调整策略。我们还探讨了离散时间与连续时间模型在调整与识别上的联系。最后提供基于公开软件的实现指南。结论强调:1)考虑治疗时机对有效推断至关重要;2)通过将治疗间等待时间作为时变混杂因子调整,可用g方法纠正信息性时机带来的偏差。
原文摘要 · Abstract (English)
Epidemiological studies are often concerned with estimating causal effects of a sequence of treatment decisions on survival outcomes. In many settings, treatment decisions do not occur at fixed, pre-specified followup times. Rather, timing varies across subjects in ways that may be informative of subsequent treatment decisions and potential outcomes. Awareness of the issue and its potential solutions is lacking in the literature, which motivate this work. Here, we formalize the issue of informative timing, problems associated with ignoring it, and show how g-methods can be used to analyze sequential treatments that are informatively timed. As we describe, in such settings, the waiting times between successive treatment decisions may be properly viewed as a time-varying confounders. Using synthetic examples, we illustrate how g-methods that do not adjust for these waiting times may be biased and how adjustment can be done in scenarios where patients may die or be censored in between treatments. We draw connections between adjustment and identification with discrete-time versus continuous-time models. Finally, we provide implementation guidance and examples using publicly available software. Our concluding message is that 1) considering timing is important for valid inference and 2) correcting for informative timing can be done with g-methods that adjust for waiting times between treatments as time-varying confounders.
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