Masiliūnienė Greta, Stankevičius Edgaras, Kaduševičius Edmundas
Institute of Physiology and Pharmacology, Faculty of Medicine, Medical Academy, Lithuanian University of Health Sciences, A. Mickevičiaus 9, 44307, Kaunas, Lithuania.
Eur J Clin Pharmacol. 2025 Jun 17. doi: 10.1007/s00228-025-03862-2.
Underreporting of adverse drug reactions (ADRs) remains to be a challenge in modern health care. Major reforms in the EU pharmacovigilance system in 2012 introduced the legal basis for consumers to report suspected ADRs. This study was designed to determine trends in overall ADR reporting, the ratio of health care professional (HCP)-to-consumer ADR reporting, and the ratio of serious-to-nonserious ADR reporting for an 11-year period in the selected non-EU and EU countries that had implemented systems for consumers' reporting before the 2012 EU pharmacovigilance legislation and those that did not have.
The national competent authorities of 15 countries (11 EU countries, former EU member the UK, Australia, Canada, and the USA) were contacted via e-mail and asked to provide the total number of ADR reports, numbers of ADRs reported by consumers and HCPs, numbers of serious and nonserious ADRs, and top 5 medication groups causing ADRs by the Anatomical Therapeutic Chemical (ATC) classification system during the period of 2012-2022. Eight countries, namely Belgium, Canada, Finland, Lithuania, the Netherlands, Portugal, Sweden, and the UK, responded and provided the data. The trends of ADR reporting were evaluated with the joinpoint regression analysis method. The annual percent change (APC) and the average annual percent change (AAPC) were estimated.
Over the study period, the overall rates of ADR reporting increased significantly in all the countries except for Belgium, with the greatest AAPC being in Lithuania (AAPC of 32.34) and the lowest, in Canada (AAPC of 10.3). The ratios of HCP-to-consumer ADR reporting were significantly decreasing in all the countries (AAPC range, -43.7 to -24.9) except for Canada where an opposite significant trend toward an increasing HCP reporting rate (AAPC of 3.9) for 2012-2020 was observed. The ratios of serious-to-nonserious ADR reporting were significantly decreasing in more than half of the countries, namely Canada, Finland, Lithuania, the Netherlands, and Portugal, with the greatest negative AAPC being in Lithuania (AAPC of -32.9) and the smallest, in Canada (AAPC of -6.8). Vaccines (J07), immunosuppressants (L04), antineoplastic agents (L01), antibacterials for systemic use (J01), and antithrombotic agents (B01) were found to be the top 5 most frequently reported medications.
This study shows the significant upward trends in overall ADR reporting not only in the countries that implemented consumer ADR reporting systems after the 2012 EU pharmacovigilance legislation but also in countries that had consumer reporting systems before 2012. Moreover, significant downward trends in the ratios of HCP-to-consumer ADR reporting were documented for all EU countries, confirming increasing consumers' involvement in ADR reporting. Further, larger scale studies with the involvement of more countries are needed to better understand the trends in ADR reporting, and multifaceted interventions are warranted to be installed to enhance ADR reporting.
在现代医疗保健中，药品不良反应（ADR）报告不足仍是一项挑战。2012年欧盟药物警戒系统的重大改革为消费者报告疑似药品不良反应引入了法律依据。本研究旨在确定在选定的非欧盟国家和欧盟国家中，在2012年欧盟药物警戒立法之前已实施消费者报告系统的国家以及未实施该系统的国家，11年间药品不良反应总体报告趋势、医疗保健专业人员（HCP）与消费者药品不良反应报告比例以及严重与非严重药品不良反应报告比例。
通过电子邮件联系了15个国家（11个欧盟国家、前欧盟成员国英国、澳大利亚、加拿大和美国）的国家主管当局，要求提供2012 - 2022年期间药品不良反应报告总数、消费者和医疗保健专业人员报告的药品不良反应数量、严重和非严重药品不良反应数量以及根据解剖治疗化学（ATC）分类系统导致药品不良反应的前5类药物组。八个国家，即比利时、加拿大、芬兰、立陶宛、荷兰、葡萄牙、瑞典和英国，做出了回应并提供了数据。采用连接点回归分析方法评估药品不良反应报告趋势。估计了年度百分比变化（APC）和平均年度百分比变化（AAPC）。
在研究期间，除比利时外，所有国家的药品不良反应总体报告率均显著上升，AAPC最高的是立陶宛（3年2.34），最低的是加拿大（10.3）。除加拿大外，所有国家的医疗保健专业人员与消费者药品不良反应报告比例均显著下降（AAPC范围为-43.7至-24.9），在加拿大观察到2012 - 2020年医疗保健专业人员报告率呈相反的显著上升趋势（AAPC为3.9）。在一半以上的国家，即加拿大、芬兰、立陶宛、荷兰和葡萄牙，严重与非严重药品不良反应报告比例显著下降，AAPC最大的是立陶宛（-32.9），最小的是加拿大（-6.8）。疫苗（J07）、免疫抑制剂（L04）、抗肿瘤药（L01）、全身用抗菌药（J01）和抗血栓药（B01）是报告最频繁的前5类药物。
本研究表明，不仅在2012年欧盟药物警戒立法后实施消费者药品不良反应报告系统的国家，而且在2012年前就有消费者报告系统的国家，药品不良反应总体报告均有显著上升趋势。此外记录显示，所有欧盟国家医疗保健专业人员与消费者药品不良反应报告比例均有显著下降趋势，证实消费者在药品不良反应报告中的参与度不断提高。此外，需要开展更多国家参与的更大规模研究，以更好地了解药品不良反应报告趋势，并且有必要采取多方面干预措施来加强药品不良反应报告。
