论文标题

疫苗有效性测试阴性设计研究中的双重控制推断

Double Negative Control Inference in Test-Negative Design Studies of Vaccine Effectiveness

论文作者

Li, Kendrick Qijun, Shi, Xu, Miao, Wang, Tchetgen, Eric Tchetgen

论文摘要

测试阴性设计(TND)已成为评估疫苗有效性的标准方法,以应对在现实环境中获取传染病的风险,例如流感,轮状病毒,登革热,以及最近的Covid-19。在一项TND研究中,经历症状和寻求护理的个体将被招募和测试,以定义病例和对照的传染病。尽管TND有可能减少疫苗接种和未接种疫苗的受试者之间的医疗保健行为(HSB)差异(HSB)的潜力,但它仍然存在各种潜在的偏见。首先,由于未观察到的HSB,作为医护人员的职业或以前的感染历史而导致的残留混淆可能仍然存在。其次,由于对TND样品的选择是感染和HSB的普遍结果,因此在调节测试样品的分析时可能存在对撞机分层偏置,这进一步引起了潜在的HSB混淆。在本文中,我们提出了一种新的方法,可以通过仔细利用一对阴性对照暴露和结果变量来识别和估计目标人群的疫苗有效性,以说明TND研究中潜在的隐藏偏见。我们使用密歇根大学卫生系统的数据来说明我们提出的方法,并使用广泛的模拟和研究Covid-19疫苗有效性的应用。

The test-negative design (TND) has become a standard approach to evaluate vaccine effectiveness against the risk of acquiring infectious diseases in real-world settings, such as Influenza, Rotavirus, Dengue fever, and more recently COVID-19. In a TND study, individuals who experience symptoms and seek care are recruited and tested for the infectious disease which defines cases and controls. Despite TND's potential to reduce unobserved differences in healthcare seeking behavior (HSB) between vaccinated and unvaccinated subjects, it remains subject to various potential biases. First, residual confounding may remain due to unobserved HSB, occupation as healthcare worker, or previous infection history. Second, because selection into the TND sample is a common consequence of infection and HSB, collider stratification bias may exist when conditioning the analysis on tested samples, which further induces confounding by latent HSB. In this paper, we present a novel approach to identify and estimate vaccine effectiveness in the target population by carefully leveraging a pair of negative control exposure and outcome variables to account for potential hidden bias in TND studies. We illustrate our proposed method with extensive simulations and an application to study COVID-19 vaccine effectiveness using data from the University of Michigan Health System.

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