Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, The Netherlands.
Dutch Medicines Evaluation Board, Utrecht, The Netherlands.
Pharmacoepidemiol Drug Saf. 2018 Jul;27(7):789-796. doi: 10.1002/pds.4446. Epub 2018 May 24.
Investigation of drug safety signals is one of the major tasks in pharmacovigilance. Among many potential signals identified, only a few reflect adverse drug reactions requiring regulatory actions, such as product information (PI) update. Limited information is available regarding the signal characteristics that might predict PI update following signal evaluation. The objective of this study was to identify signal characteristics associated with PI updates following signal evaluation by the European Medicines Agency Pharmacovigilance Risk Assessment Committee during 2012 to 2016.
A comparative study was performed based on data from 172 safety signals. Characteristics of signals were extracted from the European Pharmacovigilance Issues Tracking Tool database. Multivariable logistic regression analysis was used to assess the relationship between signal characteristics and the decision to update the PI.
Multivariable logistic regression analysis showed that the presence of evidence in multiple types of data sources (adjusted odds ratio [OR] 7.8 95% CI [1.5, 40.1]); mechanistic plausibility of the drug-event association (adjusted OR 3.9 95% CI [1.9, 8.0]); seriousness of the event (adjusted OR 4.2 95% CI [1.3, 13.9]); and age of drugs ≤5 years (adjusted OR 3.9 95% CI [1.2, 12.7]) were associated with the decision to change the PI (P < 0.05).
This study identified 4 characteristics of drug safety signals that have shown to be associated with PI changes as outcome of signal evaluation. These characteristics may be used as criteria for selection and prioritization of potential signals that are more likely to necessitate product information updates.
药物安全性信号的调查是药物警戒的主要任务之一。在众多已确定的潜在信号中，只有少数信号反映了需要监管行动的药物不良反应，例如产品信息（PI）更新。关于可能预测信号评估后 PI 更新的信号特征的信息有限。本研究的目的是确定 2012 年至 2016 年期间欧洲药品管理局药物警戒风险评估委员会在信号评估后与 PI 更新相关的信号特征。
基于来自 172 个安全性信号的数据进行了一项比较研究。从欧洲药物警戒问题跟踪工具数据库中提取信号特征。多变量逻辑回归分析用于评估信号特征与决定更新 PI 之间的关系。
多变量逻辑回归分析表明，存在多种类型数据源的证据（调整后的优势比[OR]7.8，95%置信区间[1.5，40.1]）；药物-事件关联的机制合理性（调整后的 OR 3.9，95%置信区间[1.9，8.0]）；事件的严重性（调整后的 OR 4.2，95%置信区间[1.3，13.9]）；和药物年龄≤5 年（调整后的 OR 3.9，95%置信区间[1.2，12.7]）与改变 PI 的决定相关（P<0.05）。
本研究确定了与信号评估后 PI 变化相关的 4 个药物安全性信号特征。这些特征可作为更有可能需要产品信息更新的潜在信号选择和优先化的标准。
