欧盟药物警戒信息监管体系的分析与借鉴

欧盟的药物警戒信息监管体系对欧洲的药物监管和不良反应监测方面发挥了重要的作用.本文介绍了欧盟药物警戒体系的主要机构,欧盟药物警戒信息体系的组成,包括不良反应报告体系、上市后研究、风险管理策略等.目的是为我国的不良反应监测体系和药物警戒的发展提供借鉴和启示.     

国外药物警戒体系建设现状探究及启示

目的：探讨欧盟、美国、韩国、日本和中国的药物警戒体系建设现状,为我国医疗机构药物警戒体系建设提供建议与参考。方法：对欧盟、美国、韩国和日本药物警戒体系建设现状进行分析,并与我国医疗机构药物警戒体系建设进行对比,提出我国的医疗机构药物警戒建设建议。结果与结论：药物警戒是药品安全监管的重要内容,贯穿药品全生命周期,我国应充分利用医疗机构报告主渠道优势,建立具有我国特色的医疗机构药物警戒体系,并强化风险监测和预警,促进临床安全用药。     

欧盟预防用疫苗药物警戒特殊要求及启示

目的:通过对欧盟预防用疫苗药物警戒特殊要求的介绍,为完善和发展我国疫苗不良反应报告和监测体系提供借鉴和参考。方法:对欧盟药品管理局官方网站有关药物警戒以及预防用疫苗特殊要求的文献资料进行分析研究。结果与结论:欧盟预防用疫苗药物警戒工作在风险管理系统、定期安全性更新报告、上市后安全性研究、信号管理、批次召回或封存等方面值得借鉴和参考,对于我国开展疫苗药物警戒的重要意义、风险管理、病例定义标准化以及安全性沟通等方面提出了思考和启示。     

新政策背景下我国医疗机构药物警戒工作思考

目的:为医疗机构开展药物警戒活动提供参考。方法:检索中国知网数据库药物警戒相关文献，查阅国家药品监督管理局发布实施的药物警戒相关法规文件，以及美国、欧盟、日本药品监管部门官网药物警戒相关内容，通过分析中国医疗机构药物警戒活动现状和国外药物警戒情况，就新政策背景下医疗机构如何开展该项工作提出建议。结果:美国、欧盟、日本药物警戒体系发展较成熟；中国医疗机构作为报告来源主体在法规文件、组织架构、工作机制和分析评价等方面存在不足。结论:应加强医疗机构药物警戒体系建设、软硬件配套建设、分析评价能力建设。     

《药品管理法》中药物警戒制度实施的思考

目的：新修订的《中华人民共和国药品管理法》首次引入建立药物警戒制度,原有的不良反应监测和报告制度已不能满足我国药品监管的要求,需要从法规层面和实际操作层面整体设计。方法：通过查阅国内外文献,WHO、FDA和EMA网站等,比较分析WHO、美国和欧盟的药物警戒制度。结果与结论：对比WHO、美国和欧盟的药物警戒制度发现,我国的药物警戒制度处在刚刚起步阶段,本文从法律法规框架、科学监管体系、建立专业数据库以及加强药品上市许可持有人报告等方面提出了建议和意见。     

基于美欧医疗器械上市后法规要求对我国建立医疗器械警戒制度的思考

本文旨在深入探讨美国和欧盟的医疗器械上市后监管制度,包括风险监管理念、监管法规体系、上市后临床研究、质量管理体系等,总结出开发风险监测工具、落实风险管理、采用合并报告模式、公开风险信息等经验,为我国医疗器械行业有序发展提供参考。我国可以借鉴美欧医疗器械上市后的监管实践,从提高监管机构能力、建设监测哨点和强化法规框架等方面,建立和试点医疗器械警戒制度。     

中药药物警戒初探

目的:对中药药物警戒理论进行初步探讨,为中药药物警戒工作的开展提供依据。方法:整理药物警戒理论的起源、定义和发展,与我国传统药物警戒理论进行对比,并进一步对中药药物警戒工作的主要内容进行探讨。结果:开展药物警戒工作除应对中药的种植、采集、加工炮制乃至生产、上市后进行监管外,还应对合理的临床应用的全过程进行监管,尤其应加强对有毒中药的监控。结论:重视中药使用过程中的安全性问题才能不断地完善中药药物警戒工作。     

欧盟新的药物警戒法规简介与启示

目的对欧盟新药物警戒法进行介绍,为完善我国药品不良反应报告和监测体系提供参考。方法通过查阅国内外文献,应用文献研究的方法进行分析。结果欧盟药物警戒当前所关注的焦点问题主要集中在收集药品安全性信息,分析和挖掘药品数据信息,开展围绕公众健康监管活动以及与利益相关者进行有效沟通。结论我国应借鉴欧盟新药物警戒法,提高我国药品不良反应报告和监测能力。     

药物警戒汇总报告

药物警戒汇总报告是许多国家医疗管理部门要求企业递交的一系列药物警戒文件,包括欧盟的年度安全报告（ASR）及美国的研究新药物年度报告为临床信息汇总报告（IND）。上市后汇总报告包括欧盟、人用药物注册技术国际协调会议（ICH）的定期安全性信息更新报告（PSUR）及美国的定期药物不良事件报告（PADER）。药物警戒汇总报告将继续发展并成为信号检测及评估的较好手段之一。     

美、法两国药物警戒机构设置的特点分析及对我国的启示

目的为我国药物警戒体系的机构设置提供建议。方法对美、法两国药物警戒机构设置的特点进行研究与比较。结果美国与法国的药物警戒机构设置分别属于中央系统和地方系统,两种系统虽然各有其优点与缺陷,但都有值得我国学习和借鉴之处。结论我国建立药物警戒体系需要在组织机构、交流沟通、经费来源及信息技术等方面加以完善与改进。     

Postmarketing Drug Safety Surveillance

Postmarketing drug safety surveillance has undergone many changes, especially over the past decade when international harmonization on safety reporting and risk management strategies were adopted by regulators worldwide. It is important for readers in the field to keep abreast of the most recent occurrences and future trends. This review provides an overview of the latest regulatory initiatives in postmarketing drug safety surveillance and outlines major trends observed in three major economic regions (the European Union, Japan, and the US). The report encompasses regulatory developments in safety reporting, safety signal analyses, and risk management strategies. In addition, an overview of other important areas, such as medication errors, pharmacogenomics, and the future of pharmacovigilance, is also included. Overall, the most important initiative is the application of the concept of risk management programs. Regulatory authorities are currently developing guidance to the industry and healthcare providers through various concept papers and workshops. In addition, global harmonization of safety reporting has taken place within regulatory agencies for some time. These initiatives could strengthen the ability of pharmacovigilance organizations to review and monitor the safety of drug products. Furthermore, automated data-mining techniques have been developed and used to systematically screen adverse drug events for early safety signal detection. The future conduct of postmarketing drug safety surveillance is likely to be evidence-based, technology-driven, and patient-focused.     

欧盟药品不良反应管理和上报指南简介

通过对于欧盟药品不良反应管理和上报指南的介绍,进一步了解欧盟对药品不良反应定义、报告收集、报告确认、报告随访、数据管理、质量管理等不良反应管理流程,为完善和发展我国药品不良反应报告和监测工作提供借鉴和参考。     

A model for decision support in signal triage

Spontaneous reporting of suspected adverse drug reactions (ADRs) has long been a cornerstone of pharmacovigilance. With the increasingly large volume of ADRs, regulatory agencies, scientific/academic organizations and marketing authorization holders have applied statistical tools to assist in signal detection by identifying disproportionate reporting relationships in spontaneous reporting databases. These tools have generated large numbers of signals defined as drug-ADR reporting associations that meet specified statistical criteria.The challenge is to identify which signals are most likely to be medically important and therefore warrant priority for further investigation. Decisions related to signal triage are often complex and are based on a combination of clinical, epidemiological, pharmacological and regulatory criteria. There are no specific regulations, guidelines or standards that provide an objective basis for these decisions.This paper describes preliminary work to identify and quantify the specific factors that contribute to a decision to prioritize a specific drug-ADR combination for further in-depth review. We applied a tool from the discipline of decision analysis to systematically assess the important attributes of spontaneously reported ADRs. A model was created that integrates these assessments and produces rankings for the signals generated from quantitative signalling methods. Although more research is necessary to evaluate the performance of this model fully, preliminary results suggest that the use of formal decision analysis approaches to support signal triage can provide potential benefit and will help meet an important need.     

Implemented Data Mining and Signal Management Systems on Spontaneous Reporting Systems' Databases and their Availability to the Scientific Community - A Systematic Review

Adverse drug reactions' spontaneous reporting systems are an important element in worldwide pharmacovigilance, gathering potentially useful information for post-marketing drug safety surveillance. Data mining and signal management systems, providing the capability of reading and interpreting these systems' raw data (data that has not been subjected to processing or any other manipulation), improve its analysis process. In order for this analysis to be possible, both data mining and signal management systems and raw data should be available to researchers and the scientific community. The purpose of this work was to provide an overview of the spontaneous reporting systems databases reported in literature as having implemented a data mining and signal management system and the implementation itself, evidencing their availability to researchers. A systematic review was carried out, concluding that they are freely provided to researchers within institutions responsible for maintaining the spontaneous reporting systems, but not to most researchers within the scientific community.     

Innovations for the future of pharmacovigilance.

Post-marketing pharmacovigilance involves the review and management of safety information from many sources. Among these sources, spontaneous adverse event reporting systems are among the most challenging and resource-intensive to manage. Traditionally, efforts to monitor spontaneous adverse event reporting systems have focused on review of individual case reports. The science of pharmacovigilance could be enhanced with the availability of systems-based tools that facilitate analysis of aggregate data for purposes of signal detection, signal evaluation and knowledge management. GlaxoSmithKline (GSK) recently implemented Online Signal Management (OSM) as a data-driven framework for managing the pharmacovigilance of marketed products. This pioneering work builds upon the strong history GSK has of innovation in this area. OSM is a software application co-developed by GSK and Lincoln Technologies that integrates traditional pharmacovigilance methods with modern quantitative statistical methods and data visualisation tools. OSM enables the rapid identification of trends from the individual adverse event reports received by GSK. OSM also provides knowledge-management tools to ensure the successful tracking of emerging safety issues. GSK has developed standard procedures and 'best practices' around the use of OSM to ensure the systematic evaluation of complex safety datasets. In summary, the implementation of OSM provides new tools and efficient processes to advance the science of pharmacovigilance.     

Using real-world healthcare data for pharmacovigilance signal detection – the experience of the EU-ADR project

A prospective pharmacovigilance signal detection study, comparing the real-world healthcare data (EU-ADR) and two spontaneous reporting system (SRS) databases, US FDA’s Adverse Event Reporting System and WHO's Vigibase is reported. The study compared drug safety signals found in the EU-ADR and SRS databases. The potential for signal detection in the EU-ADR system was found to be dependent on frequency of the event and utilization of drugs in the general population. The EU-ADR system may have a greater potential for detecting signals for events occurring at higher frequency in general population and those that are commonly not considered as potentially a drug-induced event. Factors influencing various differences between the datasets are discussed along with potential limitations and applications to pharmacovigilance practice.     

欧盟药监局关于药品不良反应重复报告处理指南简介

摘 要 重复报告是指药品不良反应自发呈报系统数据库中,对同一患者的同一个不良反应的不同报告。由于不良反应报告主要采取自发呈报的方式,难以避免重复报告的问题,这给不良反应信号检测工作带来了挑战。本文基于欧盟药监局药品不良反应重复报告指南,介绍欧盟药监局关于药品不良反应自发呈报系统中重复报告数据的检测、确认和管理提出的指导原则和流程,并提出对我国药品不良反应监测的启示,以期对我国的药物警戒工作提供相关的参考。     

Signal detection of methylphenidate by comparing a spontaneous reporting database with a claims database

Data mining is critical for signal detection in pharmacovigilance systems. In this study, we compared signals between spontaneous reporting data and health insurance claims data for a socially issued drug, methylphenidate. We implemented data-mining tools for signal detection in both databases: Reporting Odds Ratios (ROR), Proportional Reporting Ratios (PRR), Chi-squared test, and Information Component (IC), in addition to a Relative Risk (RR) tool in the claims database. The claims database generated 15, 15, 36, 1, and 1 adverse drug reactions (ADRs) by ROR, PRR, chi-square, IC, and RR, respectively. The World Health Organization (WHO) spontaneous database generated 91, 91, 137, and 96 ADRs by ROR, PRR, chi-square, and IC, respectively. We found seven potential matching associations from the claims and WHO databases, but only one of them was present in the Korean spontaneous reporting database. In Korea, spontaneous reporting is still underreported and there is a small amount of data for Koreans. Signal comparison between the claims and WHO databases can provide additional regulatory insight.