Signal Detection in EUROmediCAT: Identification and Evaluation of Medication-Congenital Anomaly Associations and Use of VigiBase as a Complementary Source of Reference
Signal Detection in EUROmediCAT: Identification and Evaluation of Medication-Congenital Anomaly Associations and Use of VigiBase as a Complementary Source of Reference
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DOI：
10.1007/s40264-021-01073-z
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发表时间：
2021-05-09
期刊：
影响因子：
4.2
通讯作者：
Morris, Joan K.
中科院分区：
文献类型：
--
作者：
Cavadino, Alana;Sandberg, Lovisa;Morris, Joan K.
简介 关于怀孕期间用药安全性的知识通常很少。孕妇通常被排除在临床试验之外，并且依赖于上市后监测来识别致畸药物。目的 本研究旨在利用 EUROmediCAT 关于先天性异常妊娠药物暴露的注册数据来识别潜在致畸药物的信号，并调查使用 VigiBase 药物不良事件报告来评估这些信号。方法 在 EUROmediCAT（21,636 例先天性异常病例，32,619 例药物暴露）中识别出药物与先天性异常关联的信号，然后通过审查统计报告模式和 VigiBase 病例报告，在 VigiBase 的子集中（45,749 例病例和 165,121 例药物暴露）进行调查。在推荐信号作为进一步独立调查的保证之前，考虑了文献证据以及两个数据集的定量和定性方面。结果 EUROmediCAT 分析确定了 49 个药物与先天异常关联的信号。结合 VigiBase 和文献的调查，这些药物分为以下几类：四种非特异性药物； 11 可能是由于母体疾病； 11种已确定的致畸剂；之前的 EUROMediCAT 研究中审查了两项，但附加证据有限； 13 个没有足够的依据来建议采取后续行动。建议对八个信号进行独立调查：pregnen (4) 具有肢体减少的衍生物；硝基呋喃衍生物可治疗腭裂和动脉导管未闭；水杨酸及其衍生物导致小肠其他部位闭锁或狭窄以及法洛四联症；卡马西平合并房室间隔缺损和严重先天性心脏病；以及后尿道瓣膜和/或梅腹选择性β2-肾上腺素受体激动剂。结论 EUROmediCAT 数据应继续用于信号检测，并辅以来自 VigiBase 的信息和对现有文献的回顾，以确定信号的优先级，以进行进一步的独立评估。
Introduction Knowledge on the safety of medication use during pregnancy is often sparse. Pregnant women are generally excluded from clinical trials, and there is a dependence on post-marketing surveillance to identify teratogenic medications. Aims This study aimed to identify signals of potentially teratogenic medications using EUROmediCAT registry data on medication exposure in pregnancies with a congenital anomaly, and to investigate the use of VigiBase reports of adverse events of medications in the evaluation of these signals. Methods Signals of medication-congenital anomaly associations were identified in EUROmediCAT (21,636 congenital anomaly cases with 32,619 medication exposures), then investigated in a subset of VigiBase (45,749 cases and 165,121 exposures), by reviewing statistical reporting patterns and VigiBase case reports. Evidence from the literature and quantitative and qualitative aspects of both datasets were considered before recommending signals as warranting further independent investigation. Results EUROmediCAT analysis identified 49 signals of medication-congenital anomaly associations. Incorporating investigation in VigiBase and the literature, these were categorised as follows: four non-specific medications; 11 likely due to maternal disease; 11 well-established teratogens; two reviewed in previous EUROmediCAT studies with limited additional evidence; and 13 with insufficient basis for recommending follow-up. Independent investigations are recommended for eight signals: pregnen (4) derivatives with limb reduction; nitrofuran derivatives with cleft palate and patent ductus arteriosus; salicylic acid and derivatives with atresia or stenosis of other parts of the small intestine and tetralogy of Fallot; carbamazepine with atrioventricular septal defect and severe congenital heart defect; and selective beta-2-adrenoreceptor agonists with posterior urethral valve and/or prune belly. Conclusion EUROmediCAT data should continue to be used for signal detection, accompanied by information from VigiBase and review of the existing literature to prioritise signals for further independent evaluation.