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使用三种算法对肺炎球菌疫苗进行安全性监测:不成比例法、经验贝叶斯几何均值法和基于树的扫描统计法。

Safety Surveillance of Pneumococcal Vaccine Using Three Algorithms: Disproportionality Methods, Empirical Bayes Geometric Mean, and Tree-Based Scan Statistic.

作者信息

Lee Hyesung, Kim Ju Hwan, Choe Young June, Shin Ju-Young

机构信息

School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea.

College of Medicine, Hallym University, Chuncheon 24252, Korea.

出版信息

Vaccines (Basel). 2020 May 22;8(2):242. doi: 10.3390/vaccines8020242.

Abstract

Diverse algorithms for signal detection exist. However, inconsistent results are often encountered among the algorithms due to different levels of specificity used in defining the adverse events (AEs) and signal threshold. We aimed to explore potential safety signals for two pneumococcal vaccines in a spontaneous reporting database and compare the results and performances among the algorithms. Safety surveillance was conducted using the Korea national spontaneous reporting database from 1988 to 2017. Safety signals for pneumococcal vaccine and its subtypes were detected using the following the algorithms: disproportionality methods comprising of proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC); empirical Bayes geometric mean (EBGM); and tree-based scan statistics (TSS). Moreover, the performances of these algorithms were measured by comparing detected signals with the known AEs or pneumococcal vaccines (reference standard). Among 10,380 vaccine-related AEs, 1135 reports and 101 AE terms were reported following pneumococcal vaccine. IC generated the most safety signals for pneumococcal vaccine (40/101), followed by PRR and ROR (19/101 each), TSS (15/101), and EBGM (1/101). Similar results were observed for its subtypes. Cellulitis was the only AE detected by all algorithms for pneumococcal vaccine. TSS showed the best balance in the performance: the highest in accuracy, negative predictive value, and area under the curve (70.3%, 67.4%, and 64.2%). Discrepancy in the number of detected signals was observed between algorithms. EBGM and TSS calibrated noise better than disproportionality methods, and TSS showed balanced performance. Nonetheless, these results should be interpreted with caution due to a lack of a gold standard for signal detection.

摘要

存在多种信号检测算法。然而,由于在定义不良事件(AE)和信号阈值时使用的特异性水平不同,这些算法之间经常会出现不一致的结果。我们旨在在一个自发报告数据库中探索两种肺炎球菌疫苗的潜在安全信号,并比较各算法的结果和性能。使用1988年至2017年的韩国国家自发报告数据库进行安全监测。使用以下算法检测肺炎球菌疫苗及其亚型的安全信号:由比例报告比(PRR)、报告比值比(ROR)和信息成分(IC)组成的不成比例方法;经验贝叶斯几何均值(EBGM);以及基于树的扫描统计(TSS)。此外,通过将检测到的信号与已知的AE或肺炎球菌疫苗(参考标准)进行比较来衡量这些算法的性能。在10380例与疫苗相关的AE中,有1135份报告和101个AE术语是在接种肺炎球菌疫苗后报告的。IC产生的肺炎球菌疫苗安全信号最多(40/101),其次是PRR和ROR(各19/101)、TSS(15/101)和EBGM(1/101)。其亚型也观察到类似结果。蜂窝织炎是所有肺炎球菌疫苗算法检测到的唯一AE。TSS在性能上表现出最佳平衡:准确率、阴性预测值和曲线下面积最高(分别为70.3%、67.4%和64.2%)。各算法之间在检测到的信号数量上存在差异。EBGM和TSS比不成比例方法更好地校准了噪声,并且TSS表现出平衡的性能。尽管如此,由于缺乏信号检测的金标准,这些结果应谨慎解释。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea41/7349998/a6667940f589/vaccines-08-00242-g001.jpg

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