The Use of Active Comparators in Self-Controlled Designs
The Use of Active Comparators in Self-Controlled Designs
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DOI：
10.1093/aje/kwab110
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发表时间：
2021-10-01
影响因子：
5
通讯作者：
Maclure, Malcolm
中科院分区：
文献类型：
--
作者：
Hallas, Jesper;Whitaker, Heather;Maclure, Malcolm
对于药物相关效应的自我对照研究，如果适应症随时间变化，则可能发生时变的适应症混淆。我们描述如何积极比较可能减轻这种偏见，使用经验的例子。本文描述了在病例交叉设计、病例时间控制设计、自控病例序列和序列对称性分析中使用主动比较器的方法。在实证示例中，我们使用1996年至2018年的丹麦数据，以大环内酯类抗生素罗红霉素作为比较物，研究青霉素与静脉血栓栓塞（VTE）之间的关系。上呼吸道感染是静脉血栓栓塞的一过性危险因素，因此具有时间依赖性。青霉素的优势比为3.35(95%可信区间：3.23,3.49)，罗红霉素的优势比为3.56（95%可信区间：3.30,3.83）。我们使用基于wald的方法或相互作用项来估计青霉素与罗红霉素作为比较物的优势比。这两个估计值分别为0.94（95%置信区间：0.87,1.03）和1.03（95%置信区间：0.95,1.13）。病例-时间-对照分析的结果相似，但自控病例序列和序列对称分析均表明青霉素的保护作用较弱，这似乎可以用静脉栓塞只影响青霉素的未来暴露来解释。抗生素与静脉血栓栓塞的强烈关联表明存在指征混淆。这种混淆可以通过使用主动比较器来减轻。
For self-controlled studies of medication-related effects, time-varying confounding by indication can occur if the indication varies over time. We describe how active comparators might mitigate such bias, using an empirical example. Approaches to using active comparators are described for case-crossover design, case-time-control design, self-controlled case-series, and sequence symmetry analyses. In the empirical example, we used Danish data from 1996-2018 to study the association between penicillin and venous thromboembolism (VTE), using roxithromycin, a macrolide antibiotic, as comparator. Upper respiratory infection is a transient risk factor for VTE, thus representing time-dependent confounding by indication. Odds ratios for case-crossover analysis were 3.35 (95% confidence interval: 3.23, 3.49) for penicillin and 3.56 (95% confidence interval: 3.30, 3.83) for roxithromycin. We used a Wald-based method or an interaction term to estimate the odds ratio for penicillin with roxithromycin as comparator. These 2 estimates were 0.94 (95% confidence interval: 0.87, 1.03) and 1.03 (95% confidence interval: 0.95, 1.13). Results were similar for the case-time-control analysis, but both the self-controlled case-series and sequence symmetry analysis suggested a weak protective effect of penicillin, seemingly explained by VTE affecting future exposure exclusively for penicillin. The strong association of antibiotics with VTE suggests presence of confounding by indication. Such confounding can be mitigated by using an active comparator.