Hu Na, Huang Lan, Tiwari Ram C
Department of Statistics, University of Missouri, MO 65201, Columbia, U.S.A.
Office of Biostatistics, CDER, FDA, Silver Spring, 20993, MD, U.S.A.
Stat Med. 2015 Aug 30;34(19):2725-42. doi: 10.1002/sim.6510. Epub 2015 Apr 29.
In the recent two decades, data mining methods for signal detection have been developed for drug safety surveillance, using large post-market safety data. Several of these methods assume that the number of reports for each drug-adverse event combination is a Poisson random variable with mean proportional to the unknown reporting rate of the drug-adverse event pair. Here, a Bayesian method based on the Poisson-Dirichlet process (DP) model is proposed for signal detection from large databases, such as the Food and Drug Administration's Adverse Event Reporting System (AERS) database. Instead of using a parametric distribution as a common prior for the reporting rates, as is the case with existing Bayesian or empirical Bayesian methods, a nonparametric prior, namely, the DP, is used. The precision parameter and the baseline distribution of the DP, which characterize the process, are modeled hierarchically. The performance of the Poisson-DP model is compared with some other models, through an intensive simulation study using a Bayesian model selection and frequentist performance characteristics such as type-I error, false discovery rate, sensitivity, and power. For illustration, the proposed model and its extension to address a large amount of zero counts are used to analyze statin drugs for signals using the 2006-2011 AERS data.
在最近二十年里,已开发出用于信号检测的数据挖掘方法,利用大量上市后安全性数据进行药物安全监测。其中一些方法假定每种药物-不良事件组合的报告数量是一个泊松随机变量,其均值与药物-不良事件对的未知报告率成正比。在此,提出一种基于泊松-狄利克雷过程(DP)模型的贝叶斯方法,用于从大型数据库(如美国食品药品监督管理局的不良事件报告系统(AERS)数据库)中进行信号检测。与现有贝叶斯方法或经验贝叶斯方法不同,不是使用参数分布作为报告率的常见先验,而是使用非参数先验,即DP。对表征该过程的DP的精度参数和基线分布进行分层建模。通过使用贝叶斯模型选择以及诸如I型错误、错误发现率、灵敏度和功效等频率主义性能特征的密集模拟研究,将泊松-DP模型的性能与其他一些模型进行比较。为了说明,所提出的模型及其针对大量零计数的扩展用于使用2006 - 2011年AERS数据对他汀类药物进行信号分析。