Mixed-effects Poisson regression analysis of adverse event reports: The relationship between antidepressants and suicide
Mixed-effects Poisson regression analysis of adverse event reports: The relationship between antidepressants and suicide
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DOI：
10.1002/sim.3241
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发表时间：
2008-05-20
影响因子：
2
通讯作者：
Mann, J. John
中科院分区：
文献类型：
--
作者：
Gibbons, Robert D.;Segawa, Eisuke;Mann, J. John
开发了一种新的统计方法，用于分析来自上市后药物监测数据的自发不良事件（AE）报告。该方法涉及经验贝叶斯（EB）和完全贝叶斯估计率乘数为一类药物中的每种药物，对于一个特定的AE，基于混合效应泊松回归模型。随机效应分布的参数和半参数模型进行检查。该方法适用于美国食品和药物管理局（FDA）的不良事件报告系统（AERS）的数据抗抑郁药和自杀之间的关系。我们获得每种药物（例如抗抑郁药）的比率乘数的点估计值和95%置信（后验）区间，可用于确定特定药物是否与特定AE（例如自杀）相关的风险增加。不包括1.0的置信（后验）区间为药物和不良反应的显著保护或有害关联提供了证据。我们还研究了EB，参数贝叶斯和半参数贝叶斯估计的率乘数和相关的置信区间（后验）。我们对FDA AERS数据的分析结果显示，与较老的抗抑郁药相比，较新的抗抑郁药与较低的自杀不良事件报告率相关。我们建议改进现有的AERS系统，这可能会提高其作为早期预警系统的公共卫生价值。版权所有（c）2008约翰威利父子有限公司。
A new statistical methodology is developed for the analysis of spontaneous adverse event (AE) reports from post-marketing drug surveillance data. The method involves both empirical Bayes (EB) and fully Bayes estimation of rate multipliers for each drug within a class of drugs, for a particular AE, based on a mixed-effects Poisson regression model. Both parametric and semiparametric models for the random-effect distribution are examined. The method is applied to data from Food and Drug Administration (FDA)'s Adverse Event Reporting System (AERS) on the relationship between antidepressants and suicide. We obtain point estimates and 95 per cent confidence (posterior) intervals for the rate multiplier for each drug (e.g. antidepressants), which can be used to determine whether a particular drug has an increased risk of association with a particular AE (e.g. suicide). Confidence (posterior) intervals that do not include 1.0 provide evidence for either significant protective or harmful associations of the drug and the adverse effect. We also examine EB, parametric Bayes, and semiparametric Bayes estimators of the rate multipliers and associated confidence (posterior) intervals. Results of our analysis of the FDA AERS data revealed that newer antidepressants are associated with lower rates of suicide adverse event reports compared with older antidepressants. We recommend improvements to the existing AERS system, which are likely to improve its public health value as an early warning system. Copyright (c) 2008 John Wiley & Sons, Ltd.