Methods for addressing "innocent bystanders" when evaluating safety of concomitant vaccines.
Methods for addressing "innocent bystanders" when evaluating safety of concomitant vaccines.
复制标题
在评估伴随疫苗的安全性时解决“无辜旁观者”的方法。
DOI：
10.1002/pds.4399
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发表时间：
2018
影响因子：
2.6
通讯作者：
Kulldorff,Martin
中科院分区：
文献类型：
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作者：
Wang,ShirleyV;Abdurrob,Abdurrahman;Spoendlin,Julia;Lewis,Edwin;Newcomer,SophiaR;Fireman,Bruce;Daley,MatthewF;Glanz,JasonM;Duffy,Jonathan;Weintraub,EricS;Kulldorff,Martin
目的医学研究所和卫生与公众服务部已经认识到需要开发研究儿童免疫接种计划安全性的方法。建议的儿童免疫计划包括一次就诊多种疫苗。一个关键问题是同时（同一天）疫苗接种与单独一天疫苗接种的安全性。本文解决了观察性研究的方法学挑战，使用自我对照设计来调查伴随疫苗接种的安全性。方法我们提出了一个过程，用于区分几种同时接种的疫苗中的哪一种导致不良事件风险增加，同时调整由于效果改变风险因素和伴随疫苗组合之间的关系而产生的混杂因素。我们通过重新检查麻疹-腮腺炎-风疹 (MMR) 疫苗接种后 7 至 10 天已知的癫痫发作风险增加并评估其他疫苗的潜在独立或修饰作用来说明该方法。结果初步分析表明 DTaP 对癫痫发作既有独立作用又有增强作用。在考虑了疫苗接种年龄和疫苗组合之间的关系后，几乎没有证据表明同一天接种 DTaP 和 MMR 会增加癫痫发作的风险；发病率比，95% 置信区间 1.2 (0.9–1.6)，P 值 = θ.226。结论我们已经表明，当使用自我对照设计来调查伴随疫苗接种的安全性时，调整时不变效应修改风险因素（例如接种时的年龄）至关重要，这些风险因素在结构上与推荐的免疫计划的疫苗接种模式相关。
PurposeThe need to develop methods for studying the safety of childhood immunization schedules has been recognized by the Institute of Medicine and Department of Health and Human Services. The recommended childhood immunization schedule includes multiple vaccines in a visit. A key concern is safety of concomitant (same day) versus separate day vaccination. This paper addresses a methodological challenge for observational studies using a self‐controlled design to investigate the safety of concomitant vaccination.MethodsWe propose a process for distinguishing which of several concomitantly administered vaccines is responsible for increased risk of an adverse event while adjusting for confounding due to relationships between effect modifying risk factors and concomitant vaccine combinations. We illustrate the approach by re‐examining the known increase in risk of seizure 7 to 10 days after measles‐mumps‐rubella (MMR) vaccination and evaluating potential independent or modifying effects of other vaccines.ResultsInitial analyses suggested that DTaP had both an independent and potentiating effect on seizure. After accounting for the relationship between age at vaccination and vaccine combination, there was little evidence for increased risk of seizure with same day administration of DTaP and MMR; incidence rate ratio, 95% confidence interval 1.2 (0.9–1.6),Pvalue = θ.226.ConclusionWe have shown that when using a self‐controlled design to investigate safety of concomitant vaccination, it can be critically important to adjust for time‐invariant effect modifying risk factors, such as age at time of vaccination, which are structurally related to vaccination patterns due to recommended immunization schedules.