Department of Health Convergence, College of Science and Industry Convergence, Ewha Womans University, Seoul, Korea.
Graduate School of Industrial Pharmaceutical Science, College of Pharmacy, Ewha Womans University, Seoul, Korea.
PLoS One. 2024 Nov 22;19(11):e0314363. doi: 10.1371/journal.pone.0314363. eCollection 2024.
Europe, the United States (U.S), and Korea each maintain post-marketing surveillance (PMS) systems to monitor rare or unexpected adverse events. Korea's PMS mainly involves a re-examination system to identify new adverse events not seen in pre-market trials during the early stages of post-marketing drug use, along with the risk management plan (RMP), a comprehensive strategy using methods like signal detection to regularly assess safety and benefit-risk throughout the drug's lifecycle. This study compares the post-marketing safety issues associated with dapagliflozin as identified by the European Medicines Agency (EMA), the U.S Food and Drug Administration (FDA), and in Korea. To identify these safety issues, we reviewed the safety concerns listed in the European Union RMP (EU-RMP), adverse events noted in the Warnings and Precautions section of the U.S FDA drug label, and use-result surveillance results detailed in the Korean Ministry of Food and Drug Safety drug label. Additionally, we used Korean Adverse Event Reporting System (KAERS) data to detect safety signals. We manually matched and compared safety issues identified by the EMA and FDA with those recognized in Korea. For safety issues unique to Korea, we compared KAERS signals with the results from use-result surveillance. We compared 17 EMA/FDA safety issues with 38 KAERS signals and 231 results from use-result surveillance. While there was a significant concordance (71%) between the safety issues identified by the EMA/FDA and those in Korea, Korean safety issues had limitations in capturing long-term outcomes and laboratory results. Some safety issues that were initially recognized in the EU-RMP and FDA drug labels were no longer found in the latest documents. To enhance PMS in Korea, it is necessary to establish more specific laws and regulations and develop detailed guidelines that utilize a variety of real-world data and research methodologies to continuously assess causality throughout the product lifecycle.
欧洲、美国（U.S）和韩国都各自建立了上市后监测（PMS）系统，以监测罕见或意外的不良事件。韩国的 PMS 主要包括一个重新审查系统，用于识别在上市后药物使用早期阶段的临床试验中未观察到的新的不良事件，以及风险管理计划（RMP），这是一种使用信号检测等方法定期评估药物整个生命周期安全性和获益风险的综合策略。本研究比较了欧洲药品管理局（EMA）、美国食品和药物管理局（FDA）以及韩国发现的达格列净的上市后安全性问题。为了识别这些安全性问题，我们审查了欧盟 RMP（EU-RMP）中列出的安全关注、美国 FDA 药物标签警告和注意事项部分中记录的不良事件，以及韩国食品药品安全部药物标签中详细的使用结果监测结果。此外，我们还使用韩国不良事件报告系统（KAERS）数据来检测安全性信号。我们手动匹配和比较了 EMA 和 FDA 识别的安全性问题与韩国认可的问题。对于韩国特有的安全性问题，我们将 KAERS 信号与使用结果监测结果进行了比较。我们比较了 17 个 EMA/FDA 安全性问题、38 个 KAERS 信号和 231 个使用结果监测结果。虽然 EMA/FDA 识别的安全性问题与韩国的安全性问题有显著的一致性（71%），但韩国的安全性问题在捕捉长期结果和实验室结果方面存在局限性。一些最初在 EU-RMP 和 FDA 药物标签中识别的安全性问题在最新文件中已不再出现。为了加强韩国的 PMS，有必要建立更具体的法律法规，并制定详细的指南，利用各种真实世界数据和研究方法，在整个产品生命周期内持续评估因果关系。
