Hall Gillian C, Davies Paul T G, Karim M Yousuf, Haag Mendel D M, O'Leary Caroline
Grimsdyke House, London, UK.
Northampton General Hospital NHS Trust, Northampton, UK.
Pharmacoepidemiol Drug Saf. 2018 Jan;27(1):52-58. doi: 10.1002/pds.4347. Epub 2017 Nov 20.
To investigate the safety of trivalent seasonal influenza vaccine (TIVc) (Optaflu ), the first cell culture seasonal trivalent influenza vaccine available in Europe.
Codes and unstructured text in adult electronic healthcare records (The Health Improvement Network) were searched for a TIVc brand name or batch number and possible outcomes within a 3 month pre- to 6 month post-TIVc exposure study period (2012-2015). The outcomes were severe allergic reactions, Bell's palsy, convulsions, demyelination, paresthesia, noninfectious encephalitis, neuritis (optic and brachial), vasculitis, inflammatory bowel disease, and thrombocytopenia. Risk periods were defined based on biologically plausible time frame postvaccination when an outcome caused by the vaccine might be expected to occur. Possible outcomes were adjudicated against outcome specific case definitions and a date of onset assigned by using electronic and other medical records. Observed (risk period) to expected (outside risk and preexposure periods) rate ratios, postexposure incidence, and plots of time from exposure to outcome were reported.
Sixteen of 1011 events from 4578 exposures fulfilled a primary case definition and had a date of onset during the study period. Three were in observed time. The observed-to-expected rate ratios were (3.3, 95% CI 0.3, 31.7) for convulsions and (1.5, 95% CI 0.2, 14.9) for thrombocytopenia with 1 outcome each in observed time. There was 1 incident inflammatory bowel disease in observed, but none in expected, time.
The small sample size restricts interpretation; however, no hypothesis of an increased risk of a study outcome was generated. Adjudication of events against case definitions to reduce misclassification of onset and outcomes allowed use of precise risk periods. KEY POINTS This observational study did not generate a hypothesis of an association between the first cell-culture seasonal influenza vaccination available in the European Union and any of the study outcomes (severe allergic reactions, Bell's palsy, convulsions, demyelination, paresthesia, noninfectious encephalitis, neuritis [optic and brachial], vasculitis, inflammatory bowel disease [IBD], and thrombocytopenia). The small sample size limits interpretation of the results. The review of each possible outcome identified from electronic healthcare records against case definitions was included to minimize misclassification of time and outcomes and allow the use of precise risk-periods in an observed-to-expected within cohort analysis. Plots of time from exposure to outcome were included to assess the risk windows.
研究三价季节性流感疫苗（TIVc）（Optaflu）的安全性，这是欧洲首个可用的细胞培养季节性三价流感疫苗。
在成人电子医疗记录（健康改善网络）中搜索TIVc品牌名称或批号以及在TIVc暴露前3个月至暴露后6个月研究期间（2012 - 2015年）可能出现的结果。结果包括严重过敏反应、贝尔麻痹、惊厥、脱髓鞘、感觉异常、非感染性脑炎、神经炎（视神经和臂丛神经）、血管炎、炎症性肠病和血小板减少症。根据接种疫苗后可能预期出现由疫苗引起的结果的生物学合理时间框架来定义风险期。根据特定结果的病例定义对可能的结果进行判定，并通过电子和其他医疗记录确定发病日期。报告观察到的（风险期）与预期的（风险期和暴露前期之外）发生率比、暴露后发病率以及从暴露到结果的时间图。
4578次暴露中的1011个事件中有16个符合主要病例定义且在研究期间有发病日期。3个在观察期内。惊厥的观察到预期发生率比为（3.3，95%可信区间0.3，31.7），血小板减少症的观察到预期发生率比为（1.5，95%可信区间0.2，14.9），观察期内各有1例结果。观察期内有1例炎症性肠病事件，但预期期内无。
样本量小限制了解释；然而，未产生研究结果风险增加的假设。根据病例定义对事件进行判定以减少发病和结果的错误分类，从而能够使用精确的风险期。要点：这项观察性研究未产生关于欧盟首个细胞培养季节性流感疫苗接种与任何研究结果（严重过敏反应、贝尔麻痹、惊厥、脱髓鞘、感觉异常、非感染性脑炎、神经炎[视神经和臂丛神经]、血管炎、炎症性肠病[IBD]和血小板减少症）之间关联的假设。样本量小限制了结果的解释。对从电子医疗记录中确定的每个可能结果根据病例定义进行审查，以尽量减少时间和结果的错误分类，并在队列内观察到预期分析中允许使用精确的风险期。包括从暴露到结果的时间图以评估风险窗口。
