Depletion-of-susceptibles bias in influenza vaccine waning studies: how to ensure robust results.
Depletion-of-susceptibles bias in influenza vaccine waning studies: how to ensure robust results.
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DOI：
10.1017/s0950268819001961
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发表时间：
2019-11-27
影响因子：
4.2
通讯作者：
Fireman, B
中科院分区：
文献类型：
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作者：
Lipsitch, M;Goldstein, E;Fireman, B
疫苗有效性研究存在偏差，因为不同群体的感染风险人群或感染风险特别高的人群的比率不同（易感人群耗尽偏差），这一问题也可能导致对有效性减弱的有偏差估计，包括在不存在有效性减弱的情况下对有效性减弱的虚假推断。确定减弱的另一种研究设计是只研究接种疫苗的人，每天比较接种疫苗日期较早或较晚的人的发病率，以评估疫苗保护减弱作为疫苗接种时间的函数（即与较晚接种疫苗相比，较早接种疫苗是否会导致较低的后续保护）。先前的研究表明，在什么条件下，这种替代方法会产生正确的衰落估计。在此，我们正式定义了易感物减少过程，并从数学上表明，对于流感疫苗减少研究，在流感季节开始前的不同时间接种疫苗的个体中，在特定日历时间比较发病率的随机试验或相应的观察性研究，在零假设下，作为疫苗接种时间的函数，其减少的推断不会容易受到易感物减少偏差的影响。而且，如果经济确实出现衰退，人们会低估衰退的程度。因此，这样的设计在某种意义上是可靠的，即在该推理框架中发现的减弱反映了疫苗诱导的免疫力的实际减弱。我们建议在未来的研究中采用这样的设计，无论是观察性的还是随机的。
Vaccine effectiveness studies are subject to biases due to depletion-of-persons at risk of infection, or at especially high risk of infection, at different rates from different groups (depletion-of-susceptibles bias), a problem that can also lead to biased estimates of waning effectiveness, including spurious inference of waning when none exists. An alternative study design to identify waning is to study only vaccinated persons, and compare for each day the incidence in persons with earlier or later dates of vaccination to assess waning in vaccine protection as a function of vaccination time (namely whether earlier vaccination would result in lower subsequent protection compared to later vaccination). Prior studies suggested under what conditions this alternative would yield correct estimates of waning. Here we define the depletion-of-susceptibles process formally and show mathematically that for influenza vaccine waning studies, a randomised trial or corresponding observational study that compares incidence at a specific calendar time among individuals vaccinated at different times before the influenza season begins will not be vulnerable to depletion-of-susceptibles bias in its inference of waning as a function of vaccination time under the null hypothesis that none exists, and will - if waning does actually occur - underestimate the extent of waning. Such a design is thus robust in the sense that a finding of waning in that inference framework reflects actual waning of vaccine-induced immunity. We recommend such a design for future studies of waning, whether observational or randomised.