Wang Shirley V, Abdurrob Abdurrahman, Spoendlin Julia, Lewis Edwin, Newcomer Sophia R, Fireman Bruce, Daley Matthew F, Glanz Jason M, Duffy Jonathan, Weintraub Eric S, Kulldorff Martin
Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital; Department of Medicine, Harvard Medical School, Boston, MA, USA.
Kaiser Permanente Vaccine Study Center, Kaiser Permanente Division of Research, Oakland, CA, USA.
Pharmacoepidemiol Drug Saf. 2018 Apr;27(4):405-412. doi: 10.1002/pds.4399. Epub 2018 Feb 13.
The 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.
We 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.
Initial 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), P value = θ.226.
We 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.
美国医学研究所和卫生与公众服务部已经认识到开发研究儿童免疫接种计划安全性方法的必要性。推荐的儿童免疫接种计划在一次就诊中包含多种疫苗。一个关键问题是同时（同一天）接种与分开接种的安全性。本文探讨了使用自我对照设计来研究同时接种安全性的观察性研究的方法学挑战。
我们提出了一个过程，用于区分几种同时接种的疫苗中哪一种会导致不良事件风险增加，同时针对效应修饰风险因素与同时接种疫苗组合之间的关系所导致的混杂因素进行调整。我们通过重新审视麻疹 - 腮腺炎 - 风疹（MMR）疫苗接种后7至10天癫痫发作风险的已知增加，并评估其他疫苗的潜在独立或修饰作用来说明该方法。
初步分析表明，百白破疫苗（DTaP）对癫痫发作既有独立作用又有增强作用。在考虑了接种年龄与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会增加癫痫发作风险；发病率比，95%置信区间为(1.2(0.9 - 1.6))，P值(= 0.226)。
我们已经表明，当使用自我对照设计来研究同时接种的安全性时，针对时间不变的效应修饰风险因素进行调整可能至关重要，例如接种时的年龄，由于推荐的免疫接种计划，这些因素在结构上与接种模式相关。
