Methodological comparison of marginal structural model, time-varying Cox regression, and propensity score methods: the example of antidepressant use and the risk of hip fracture
Methodological comparison of marginal structural model, time-varying Cox regression, and propensity score methods: the example of antidepressant use and the risk of hip fracture
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DOI：
10.1002/pds.3864
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发表时间：
2016-03-01
影响因子：
2.6
通讯作者：
Klungel, Olaf H.
中科院分区：
文献类型：
--
作者：
Ali, M. Sanni;Groenwold, Rolf H. H.;Klungel, Olaf H.
背景：包括时变治疗在内的观察性研究容易出现混淆。我们比较了时变Cox回归分析、倾向评分（PS）方法和边际结构模型（MSMs）在抗抑郁药[选择性血清素再摄取抑制剂（SSRIs）]使用和髋部骨折风险的研究。方法从2001-2009年荷兰Mondriaan和西班牙BIFAP全科数据库中提取首次服用抗抑郁药（SSRI或三环类抗抑郁药）的患者队列。使用时变Cox回归、分层和协变量调整（使用PS和MSM）来估计SSRI与未SSRI对髋部骨折风险的净（总）影响。在MSM中，用滤波权值的逆概率来解释滤波。结果Mondriaan组使用SSRI类药物与未使用SSRI类药物髋部骨折的粗危险比（HR）为1.75 (95%CI: 1.12, 2.72)， BIFAP组为2.09（1.89,2.32）。采用时变Cox回归、分层和PS协变量校正后，Mondriaan组的hr分别升高[2.59（1.63,4.12）、2.64（1.63,4.25）和2.82 (1.63,4.25)]，BIFAP组的hr分别降低[1.56（1.40,1.73）、1.54（1.39,1.71）和1.61(1.45,1.78)]。权重稳定的MSMs在Mondriaan中得到的HR为2.15(1.30,3.55)，在biap中得到的HR为1.63(1.28,2.07)，在未考虑审查的Mondriaan中得到的HR为2.13(1.32,3.45)，在BIFAP中得到的HR为1.66（1.30,2.12）。结论在本实证研究中，不同方法对时间相关混淆的控制差异较小。在数据库之间观察到的治疗效果估计的差异可能归因于数据集中不同的混杂信息，说明关于（时变）混杂的足够信息对于防止偏倚至关重要。版权所有：John Wiley & Sons， Ltd。
BackgroundObservational studies including time-varying treatments are prone to confounding. We compared time-varying Cox regression analysis, propensity score (PS) methods, and marginal structural models (MSMs) in a study of antidepressant [selective serotonin reuptake inhibitors (SSRIs)] use and the risk of hip fracture.MethodsA cohort of patients with a first prescription for antidepressants (SSRI or tricyclic antidepressants) was extracted from the Dutch Mondriaan and Spanish Base de datos para la Investigacion Farmacoepidemiologica en Atencion Primaria (BIFAP) general practice databases for the period 2001-2009. The net (total) effect of SSRI versus no SSRI on the risk of hip fracture was estimated using time-varying Cox regression, stratification and covariate adjustment using the PS, and MSM. In MSM, censoring was accounted for by inverse probability of censoring weights.ResultsThe crude hazard ratio (HR) of SSRI use versus no SSRI use on hip fracture was 1.75 (95%CI: 1.12, 2.72) in Mondriaan and 2.09 (1.89, 2.32) in BIFAP. After confounding adjustment using time-varying Cox regression, stratification, and covariate adjustment using the PS, HRs increased in Mondriaan [2.59 (1.63, 4.12), 2.64 (1.63, 4.25), and 2.82 (1.63, 4.25), respectively] and decreased in BIFAP [1.56 (1.40, 1.73), 1.54 (1.39, 1.71), and 1.61 (1.45, 1.78), respectively]. MSMs with stabilized weights yielded HR 2.15 (1.30, 3.55) in Mondriaan and 1.63 (1.28, 2.07) in BIFAP when accounting for censoring and 2.13 (1.32, 3.45) in Mondriaan and 1.66 (1.30, 2.12) in BIFAP without accounting for censoring.ConclusionsIn this empirical study, differences between the different methods to control for time-dependent confounding were small. The observed differences in treatment effect estimates between the databases are likely attributable to different confounding information in the datasets, illustrating that adequate information on (time-varying) confounding is crucial to prevent bias. Copyright (c) 2016 John Wiley & Sons, Ltd.