The case test-negative design for studies of the effectiveness of influenza vaccine
The case test-negative design for studies of the effectiveness of influenza vaccine
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DOI：
10.1016/j.vaccine.2013.04.026
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发表时间：
2013-06-26
期刊：
影响因子：
5.5
通讯作者：
Shay, David K.
中科院分区：
文献类型：
--
作者：
Foppa, Ivo M.;Haber, Michael;Shay, David K.
背景：对病例对照研究设计的修改已成为流行的评估疫苗对病毒感染的有效性（VE）。通过高度特异性的聚合酶链反应（PCR）试验对寻求医疗护理的有症状疾病的受试者进行检测，以检测感兴趣的感染。病例是病毒检测呈阳性的受试者;检测呈阴性的受试者代表对照组。使用这种设计的流感和轮状病毒VE研究通常被称为“测试阴性病例对照”研究，但这种设计尚未得到正式描述或评估。我们明确说明了几个假设的设计和检查条件下，VE估计与它是有效的和无偏的。方法：我们推导出数学表达式的VE估计使用这种设计，并检查其统计特性。我们使用模拟方法来测试的估计的有效性，并说明其性能使用流感VE studyasexam.Results：由于边际比例的情况下，非病例是未知的，在招生，这种设计是不是一个传统的病例对照研究，我们建议的名称为“病例检验阴性”设计。在越来越普遍的假设下，我们发现案例检验阴性设计可以提供无偏的VE估计。然而，在寻求医疗保健的行为之间的差异，病例和非病例的疫苗状态，强大的病毒干扰，或修改的可能性有症状的疾病的疫苗状态可以偏差VE estimates.Conclusions：来自病例检验阴性研究的疫苗有效性估计是有效的，在广泛的假设下是无偏的。然而，如果接种疫苗的病例病情不太严重，寻求护理的频率低于未接种疫苗的病例，则需要对疾病严重程度进行适当的调整，以避免有效性估计的偏倚。仅当流感发病率极高且一过性非特异性免疫持续时间较长时，病毒干扰才会导致病例检测阴性研究的疫苗有效性估计值出现重大偏倚。(C)2013爱思唯尔有限公司版权所有。
Background: A modification to the case-control study design has become popular to assess vaccine effectiveness (VE) against viral infections. Subjects with symptomatic illness seeking medical care are tested by a highly specific polymerase chain reaction (PCR) assay for the detection of the infection of interest. Cases are subjects testing positive for the virus; those testing negative represent the comparison group. Influenza and rotavirus VE studies using this design are often termed "test-negative case-control" studies, but this design has not been formally described or evaluated. We explicitly state several assumptions of the design and examine the conditions under which VE estimates derived with it are valid and unbiased. Methods: We derived mathematical expressions for VE estimators obtained using this design and examined their statistical properties. We used simulation methods to test the validity of the estimators and illustrate their performance using an influenza VE study as an example.Results: Because the marginal ratio of cases to non-cases is unknown during enrollment, this design is not a traditional case-control study; we suggest the name "case test-negative" design. Under sets of increasingly general assumptions, we found that the case test-negative design can provide unbiased VE estimates. However, differences in health care-seeking behavior among cases and non-cases by vaccine status, strong viral interference, or modification of the probability of symptomatic illness by vaccine status can bias VE estimates.Conclusions: Vaccine effectiveness estimates derived from case test-negative studies are valid and unbiased under a wide range of assumptions. However, if vaccinated cases are less severely ill and seek care less frequently than unvaccinated cases, then an appropriate adjustment for illness severity is required to avoid bias in effectiveness estimates. Viral interference will lead to a non-trivial bias in the vaccine effectiveness estimate from case test-negative studies only when incidence of influenza is extremely high and duration of transient non-specific immunity is long. (C) 2013 Elsevier Ltd. All rights reserved.