Biostatistics & Programming, Sanofi K.K, Tokyo Opera City Tower, 3-20-2, Nishi Shinjuku, Shinjuku-ku, Tokyo, 163-1488, Japan.
Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tennodai, 1-1-1, Tsukuba-shi, Ibaraki, 305-8575, Japan.
Eur J Clin Pharmacol. 2020 Sep;76(9):1311-1319. doi: 10.1007/s00228-020-02909-w. Epub 2020 Jun 1.
A Bayesian confidence propagation neural network (BCPNN) is a signal detection method used by the World Health Organization Uppsala Monitoring Centre to analyze spontaneous reporting system databases. We modify the BCPNN to increase its sensitivity for detecting potential adverse drug reactions (ADRs).
In a BCPNN, the information component (IC) is defined as an index of disproportionality between the observed and expected number of reported drugs and events. Our proposed method adjusts the IC value by borrowing information about events that have occurred in drugs defined as similar to the target drug. We compare the performance of our method with that of a traditional BCPNN through a simulation study.
The false positive rate of the proposed method was lower than that of the traditional BCPNN method and close to the nominal value, 0.025, around the true difference in ICs between the target drug and similar drugs equal to 0. The sensitivity of the proposed method was much higher than that of the traditional BCPNN method in case in which the difference in ICs between the target drug and similar drugs ranges from 0 to 2. When applied to a database managed by Japanese regulatory authority, the proposed method could detect known ADRs earlier than the traditional method.
The proposed method is a novel criterion for early detection of signals if similar drugs have the same tendencies. The proposed BCPNN tends to have higher sensitivity when the true difference is greater than 0.
贝叶斯置信传播神经网络(BCPNN)是世界卫生组织乌普萨拉监测中心用于分析自发报告系统数据库的一种信号检测方法。我们对 BCPNN 进行了修改,以提高其检测潜在药物不良反应(ADR)的灵敏度。
在 BCPNN 中,信息分量(IC)被定义为观察到的和预期的报告药物和事件数量之间的比例失调的指标。我们提出的方法通过借用与目标药物相似的药物中发生的事件的信息来调整 IC 值。我们通过模拟研究比较了我们的方法与传统 BCPNN 的性能。
与传统 BCPNN 方法相比,我们的方法的假阳性率更低,接近名义值 0.025,接近目标药物和相似药物之间的 IC 差异的真实值为 0。当目标药物和相似药物之间的 IC 差异在 0 到 2 之间时,我们的方法的灵敏度明显高于传统 BCPNN 方法。当应用于日本监管机构管理的数据库时,与传统方法相比,我们的方法可以更早地检测到已知的 ADR。
如果相似药物具有相同的趋势,我们的方法是一种用于早期检测信号的新准则。当真实差异大于 0 时,所提出的 BCPNN 往往具有更高的灵敏度。