采用重复测量的边际结构模型对未测量的混杂因素进行敏感性分析。

Sensitivity analyses for unmeasured confounding assuming a marginal structural model for repeated measures.

作者信息

Brumback Babette A, Hernán Miguel A, Haneuse Sebastien J P A, Robins James M

机构信息

Department of Biostatistics, UCLA School of Public Health, Los Angeles, CA 90095, USA.

出版信息

Stat Med. 2004 Mar 15;23(5):749-67. doi: 10.1002/sim.1657.

Abstract

Robins introduced marginal structural models (MSMs) and inverse probability of treatment weighted (IPTW) estimators for the causal effect of a time-varying treatment on the mean of repeated measures. We investigate the sensitivity of IPTW estimators to unmeasured confounding. We examine a new framework for sensitivity analyses based on a nonidentifiable model that quantifies unmeasured confounding in terms of a sensitivity parameter and a user-specified function. We present augmented IPTW estimators of MSM parameters and prove their consistency for the causal effect of an MSM, assuming a correct confounding bias function for unmeasured confounding. We apply the methods to assess sensitivity of the analysis of Hernán et al., who used an MSM to estimate the causal effect of zidovudine therapy on repeated CD4 counts among HIV-infected men in the Multicenter AIDS Cohort Study. Under the assumption of no unmeasured confounders, a 95 per cent confidence interval for the treatment effect includes zero. We show that under the assumption of a moderate amount of unmeasured confounding, a 95 per cent confidence interval for the treatment effect no longer includes zero. Thus, the analysis of Hernán et al. is somewhat sensitive to unmeasured confounding. We hope that our research will encourage and facilitate analyses of sensitivity to unmeasured confounding in other applications.

摘要

罗宾斯引入了边际结构模型(MSMs)以及用于时变治疗对重复测量均值的因果效应的逆概率治疗加权(IPTW)估计量。我们研究了IPTW估计量对未测量混杂因素的敏感性。我们考察了一个基于不可识别模型的敏感性分析新框架,该模型根据一个敏感性参数和用户指定函数来量化未测量的混杂因素。我们给出了MSM参数的增强IPTW估计量,并证明了在假设未测量混杂因素的混杂偏差函数正确的情况下,它们对于MSM因果效应的一致性。我们应用这些方法来评估埃尔南等人分析的敏感性,他们在多中心艾滋病队列研究中使用MSM来估计齐多夫定治疗对HIV感染男性重复CD4计数的因果效应。在无未测量混杂因素的假设下,治疗效果的95%置信区间包含零。我们表明,在存在适度未测量混杂因素的假设下,治疗效果的95%置信区间不再包含零。因此,埃尔南等人的分析对未测量混杂因素有些敏感。我们希望我们的研究将鼓励并促进在其他应用中对未测量混杂因素敏感性的分析。

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