Jackson Michael L, Rothman Kenneth J
Group Health Research Institute, 1730 Minor Ave, Suite 1600, Seattle, WA 98101-1448, USA.
Research Triangle Institute, 200 Park Office Drive, Research Triangle Park, Durham, NC 27709, USA.
Vaccine. 2015 Mar 10;33(11):1313-6. doi: 10.1016/j.vaccine.2015.01.069. Epub 2015 Feb 7.
The recently developed test-negative design is now standard for observational studies of influenza vaccine effectiveness (VE). It is unclear how influenza test misclassification biases test-negative VE estimates relative to VE estimates from traditional cohort or case-control studies.
We simulated populations whose members may develop acute respiratory illness (ARI) due to influenza and to non-influenza pathogens. In these simulations, vaccination reduces the risk of influenza but not of non-influenza ARI. Influenza test sensitivity and specificity, risks of influenza and non-influenza ARI, and VE were varied across the simulations. In each simulation, we estimated influenza VE using a cohort design, a case-control design, and a test-negative design.
In the absence of influenza test misclassification, all three designs accurately estimated influenza VE. In the presence of misclassification, all three designs underestimated VE. Bias in VE estimates was slightly greater in the test-negative design than in cohort or case-control designs. Assuming the use of highly sensitive and specific reverse-transcriptase polymerase chain reaction tests for influenza, bias in the test-negative studies was trivial across a wide range of realistic values for VE.
Although influenza test misclassification causes more bias in test-negative studies than in traditional cohort or case-control studies, the difference is trivial for realistic combinations of attack rates, test sensitivity/specificity, and VE.
最近开发的检测阴性设计现已成为流感疫苗效力（VE）观察性研究的标准方法。目前尚不清楚流感检测错误分类如何使检测阴性的VE估计值相对于传统队列研究或病例对照研究的VE估计值产生偏差。
我们模拟了其成员可能因流感和非流感病原体而患急性呼吸道疾病（ARI）的人群。在这些模拟中，接种疫苗可降低患流感的风险，但不能降低患非流感ARI的风险。在模拟过程中，我们改变了流感检测的敏感性和特异性、流感和非流感ARI的风险以及VE。在每次模拟中，我们使用队列设计、病例对照设计和检测阴性设计来估计流感VE。
在不存在流感检测错误分类的情况下，所有三种设计均能准确估计流感VE。在存在错误分类的情况下，所有三种设计均低估了VE。检测阴性设计中VE估计值的偏差略大于队列设计或病例对照设计。假设使用高度敏感和特异的流感逆转录酶聚合酶链反应检测方法，在广泛的实际VE值范围内，检测阴性研究中的偏差很小。
尽管流感检测错误分类在检测阴性研究中比在传统队列研究或病例对照研究中造成的偏差更大，但对于发病率、检测敏感性/特异性和VE的实际组合而言，差异很小。
