利用比例失衡分析方法分析无细胞百日咳-白喉-破伤风联合疫苗预防接种异常反应可疑信号

The Application of Four Disproportionality Analysis Methods on Vaccine Reaction Signal Detection of the Diphtheria,Tetanus and Acellular Pertussis Combined Vaccine

目的利用数据挖掘技术中的4种常见的比例失衡分析方法（Disproportionality Analysis,DPA）,分析无细胞百日咳-白喉-破伤风联合疫苗（Diaphtheria,Tetanus and Acellular Pertussis Combined Vaccine,DTa P）预防接种异常反应的可疑信号。方法利用DPA频数法中的比例报告比（Proportional Reporting Ratio,PRR）和报告比值比（Reporting Odds Ratio,ROR）及贝叶斯法中的贝叶斯置信传播神经网络（Bayesian Confidence Propagation Neural Network,BCPNN）和模糊贝叶斯伽马-泊松收缩论（Empirical Bayes Gamma-Poisson Shrinker,GPS）方法,对2011~2013年中国疑似预防接种异常反应信息管理系统中报告发生的有明确诊断的DTa P预防接种异常反应进行分析,检测其预防接种异常反应的可疑信号。结果 20 377例有明确诊断的预防接种异常反应个案参与分析,其中DTa P占16.13%。使用PRR和ROR方法提示,2011~2013年DTa P有6个可疑预防接种异常反应信号,使用BCPNN和GPS方法提示,2011~2013年DTa P有4个可疑预防接种异常反应信号。4种方法发现的可疑预防接种异常反应信号集中在接种DTa P后的血管性水肿和无菌性脓肿。结论无菌性脓肿和血管性水肿为已知的DTa P的预防接种异常反应,利用DPA方法发现的可疑信号是风险的警示,但仅仅提示存在报告数量上的关联,是否是真实的安全性问题,需要经过包括医学评估在内的严谨的信号评价过程。

Objective To detect a vaccine reaction signal from diphtheria, tetanus and acellular pertussis combined vaccine （DTaP） using the disproportionality analysis （DPA） data mining technique. Methods The common four DPA methods, including proportional reporting ratio （PRR）, reporting odds ratio （ROR）, Bayesian confidence propagation neural network （BCPNN）, and empirical Bayes Gamma-Poisson shrinker （ GPS）, were used to detect vaccine safety signals. We collected data from the online Chinese na- tional information system for adverse events following immunization surveillance system. Only rare vaccine reaction cases with confirmed clinical diagnosis from 2011 to 2013 were included. Results There were 20, 377 rare vaccine reactions with clinical diagnosis in the system, of which 16.13% were related to DTaP. Six suspicious vaccine safety signals were detected by PRR and ROR while 4 signals were detected by BCPNN and GPS during 2011-2013. The main clinical diagnoses of those signals were angioedema and ster- ile abscess. Conclusion Angioedema and sterile abscess were confirmed vaccine reactions after DTaP vaccination. Suspicious signals were only a risk warning and were used to indicate that there might be a correlation in the number of reported cases. Clinical other related evaluations are necessary to confirm presence of real safety problem.