真实世界数据在药物警戒工作中的应用

随着医疗健康数据的快速增长,真实世界数据（real world data,RWD）分析为药物警戒工作带来了新的机遇,成为传统药品不良反应监测模式的有益补充。本文通过介绍几种主要的RWD类型,包括电子健康档案数据、医疗保险数据、注册登记数据、社交媒体数据和多源整合数据的定义和常见数据库举例,并对各种类型数据应用于相关药品安全性监测和评价的案例进行分析,总结了RWD在药物警戒中的应用范畴、优势和局限性,以期为我国利用RWD开展药物警戒活动相关研究的探索和实践提供参考。     

药物警戒方法概述

药物警戒是有关药物不良反应及任何其他药物相关问题的检出、评估、理解和防范的科学与活动。这一定义包含了药物流行病学的研究方法在药物警戒中的应用。本文简述目前主要应用于药物警戒的研究方法。     

我国药物警戒文献计量学分析

我国对药物警戒以及药物警戒所用方法的研究起步较晚，为了深入了解我国关于药物警戒的研究情况，本文通过中文期刊全文数据库（CNKI）与中文科技期刊数据库（VIP）检索出的相关文献，对文献的时间分布、期刊分布、作者分布及文献涉及的内容等方面进行研究，并就我国的药物警戒现状进行了归纳与分析。     

药品不良反应数据挖掘技术在药物警戒的应用

随着信息技术的发展,医药电子数据海量增长,药品不良事件报告大幅增加,给药物警戒研究带来了巨大的挑战。而数据挖掘技术可以自动从真实世界数据中撷取药品不良反应风险信号。因此,对海量不良事件报告数据进行高效数据挖掘是实现药品不良反应自动检测的必要措施。本研究通过介绍当前主要的大型药品不良事件报告数据库和相关数据挖掘方法,对药品不良反应数据挖掘技术在药物警戒中的应用及其局限性进行综述,为药物警戒相关机构和科研人员提供参考。     

药物流行病学与药物警戒

药物流行病学学科的形成，起源于药物警戒的开展。经过不断地发展，现在的药物流行病学早已不仅仅是药物警戒，而药物警戒仍是药物流行病学研究的一个重要方面。本文就药物流行病学的专业特征和面临的任务，特别是药物流行病学与药物警戒之间的关系，作如下交流。     

文献计量法在中药药物警戒领域中的应用价值及展望

目的 介绍文献计量法(bibliometric methods)在中药药物警戒领域(pharmacovigilance of Chinese medicine,PVCM)中的应用。方法 系统检索中国知网、万方数据、维普网、SinoMed及PubMed数据库,检索时间均从各数据库建库至2021年8月24日,并纳入应用文献计量法开展的针对中药药物警戒领域相关原始研究文献的二次研究进行分析,以了解文献计量法用于中药药物警戒领域的现况。结合相关具体实例,对文献计量法定义、应用价值、选题切入点及实施进行总结和讨论。结果 目前已发表的中药药物警戒相关文献计量研究共50篇,涉及研究选题范围主要限定于中成药临床用药不良反应。引入文献计量法对中药药物警戒领域相关文献进行系统全面的梳理与分析,可从微观和宏观层面为研究人员掌握中药药物警戒领域研究现状、跟踪学科前沿、推断研究热点、预测学科发展方向等提供循证证据。结论 应注重并规范开展更多、涉及选题范围更广的高质量中药药物警戒相关文献计量研究,为中药药物警戒领域更好、更全面发展提供证据支持。     

国际药物警戒风险管理领域知识图谱研究——基于WOS期刊文献计量分析

本文以Web of Science核心数据库中2002—2021年药物警戒风险管理领域相关文献作为样本数据，使用Excel和Cite Space软件对相关文献的研究趋势、文献来源、研究主体和研究热点进行文献计量分析，构建国际药物警戒风险管理领域知识图谱。研究发现国际药物警戒风险管理领域研究整体呈现较明显的阶段性递增特征；研究机构形成美国、法国、荷兰和意大利四大合作群，合作关系较紧密的群体一般呈高校-高校、高校-医疗机构、政府机关-医疗机构3种模式，且机构间合作关系逐渐增强；研究热点集中在药品不良反应、信号检测和药物流行病学等方面。借鉴国际药物警戒风险管理研究成果，我国药物警戒风险管理领域的发展可从研究主体和研究热点方面得到启示。     

ENCePP发布了关十药物流行病学与药物警戒的研究方法标准指导手册

欧洲药品局和欧洲药物流行病学与药物警戒网络中心（ENCePP）发布了ENCePP药物流行病学方法标准指导手册。这个重要的工作可以为药物流行病学和药物警戒的调查研究提供现有主要方法的指导。ENCePP想通过发布这部指导手册使进行多中心的、独立的、有说服力的、针对药品安全性的研究更加容易,从而达到加强对已授权药品的监测的目的。     

药物警戒与临床药学服务

药物警戒（pharmacovigilance）作为药物流行病学的分支学科,是在流行病学水平研究药品相关事件或药品不良反应（ADR）[1]。WHO在《药物警戒重要性》专著中表述药物警戒定义为＂发现、评价、认识和防范药品不良作用或其他任何与药物相关问题（drug related problems,DRP s）的科学和实践＂,     

基于医院信息系统开展药物警戒的探索

目的 基于HIS系统建立药物警戒体系,探索医疗机构开展药物警戒工作模式.方法 基于DTHealth系统和东华电子病历系统,采用Brower/Server架构,web-service、Net.Framework1.1技术以及后关系型数据库cache、SQLserver2000数据库,将药物警戒平台嵌入医院HIS系统,实现包括数据采集、输入、打印、导出、管理等一体化功能,监测药物购入到患者使用及用药后ADR上报的全过程.结果 药物警戒系统的应用显著提高了不良反应监测效果,有效减少了由药品质量问题和不合理用药带来的危害.结论 基于HIS系统可有效开展医疗机构药物警戒工作,在保证患者安全用药方面起到重要作用.     

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.     

Core concepts in pharmacoepidemiology: Validation of health outcomes of interest within real-world healthcare databases

Real-world healthcare data, including administrative and electronic medical record databases, provide a rich source of data for the conduct of pharmacoepidemiologic studies but carry the potential for misclassification of health outcomes of interest (HOIs). Validation studies are important ways to quantify the degree of error associated with case-identifying algorithms for HOIs and are crucial for interpreting study findings within real-world data. This review provides a rationale, framework, and step-by-step approach to validating case-identifying algorithms for HOIs within healthcare databases. Key steps in validating a case-identifying algorithm within a healthcare database include: (1) selecting the appropriate health outcome; (2) determining the reference standard against which to validate the algorithm; (3) developing the algorithm using diagnosis codes, diagnostic tests or their results, procedures, drug therapies, patient-reported symptoms or diagnoses, or some combinations of these parameters; (4) selection of patients and sample sizes for validation; (5) collecting data to confirm the HOI; (6) confirming the HOI; and (7) assessing the algorithm's performance. Additional strategies for algorithm refinement and methods to correct for bias due to misclassification of outcomes are discussed. The review concludes by discussing factors affecting the transportability of case-identifying algorithms and the need for ongoing validation as data elements within healthcare databases, such as diagnosis codes, change over time or new variables, such as patient-generated health data, are included in these data sources.     

如何利用观察性医药数据库进行药物流行病学的安全风险管理研究

摘 要 目的:回顾和比较观察性医药卫生数据库的特性,并讨论如何应用它们进行药物流行病学的药品安全风险管理研究。方法：通过美国医学索引Medline, PubMED, 国际药学文摘等公开出版物作为信息来源,检索相关信息和药物流行病学文献,查找其相关的观察性医药数据库,讨论和分析这些数据库的主要特性,回答如何利用观察性医药数据库来进行药物流行病学研究,为药品安全风险管理服务;介绍作者个人的独特研究经验。结果：通过本次回顾总结,从选择的公开发表文献中可找到几十种公众或机构专有的医药数据库。每种医药数据库都具有其特性、优势和局限性。将这些数据库分类为自发性报告系统数据、电子病历数据、医保数据、健康医疗相关的调查数据、疾病病种随访注册数据和其他数据等五大类。对如何应用医保数据进行特殊的药物流行病学研究进行了专项案例讨论,同时也阐述了常见的一些典型医保数据及其可链接性、数据有效性、患者隐私保护等问题。结论：本次回顾研究发现多种专业医药数据库均可用于药物流行病学研究,并为读者提供了针对特定研究目的选用和比较潜在数据库的多种有用信息。     

Evolving paradigms in pharmacovigilance

All medicines have adverse effects as well as benefits. The aim of pharmacovigilance is to protect public health by monitoring medicines to identify and evaluate issues and ensure that the overall benefits outweigh the potential risks. The tools and processes used in pharmacovigilance are continually evolving. Increasingly sophisticated tools are being designed to evaluate safety data from clinical trials to enhance the likelihood of detecting safety signals ahead of product registration. Methods include integration of safety data throughout development, meta-analytical techniques, quantitative and qualitative methods for evaluation of adverse event data and graphical tools to explore laboratory and biometric data. Electronic data capture facilitates monitoring of ongoing studies so that it is possible to promptly identify potential issues and manage patient safety. In addition, GSK employs a number of proactive methods for post-marketing signal detection and knowledge management using state-of-the-art statistical and analytical tools. Using these tools, together with safety data collected through pharmacoepidemiologic studies, literature and spontaneous reporting, potential adverse drug reactions can be better identified in marketed products. In summary, the information outlined in this paper provides a valuable benchmark for risk management and pharmacovigilance in pharmaceutical development.     

A basic study design for expedited safety signal evaluation based on electronic healthcare data

Active drug safety monitoring based on longitudinal electronic healthcare databases (a Sentinel System), as outlined in recent FDA‐commissioned reports, consists of several interlocked processes, including signal generation, signal strengthening, and signal evaluation. Once a signal of a potential drug safety issue is generated, signal strengthening and signal evaluation have to follow in short sequence in order to quickly provide as much information about the triggering drug‐event association as possible. This paper proposes a basic study design based on the incident user cohort design for expedited signal evaluation in longitudinal healthcare databases. It will not resolve all methodological issues nor will it fit all study questions arising within the framework of a Sentinel System. It should rather be seen as a guidance that will fit the majority of situations and serve as a starting point for adaptations to specific studies. Such an approach will expedite and structure the process of study development and highlight specific assumptions, which is particularly valuable in a Sentinel System where signals are by definition preliminary and evaluation of signals is time critical. Copyright © 2010 John Wiley & Sons, Ltd.     

Pharmacovigilance in children: detecting adverse drug reactions in routine electronic healthcare records. A systematic review

Aims

A systematic review of the literature published in English over 10 years was undertaken in order to describe the use of electronic healthcare data in the identification of potential adverse drug reactions (ADRs) in children.

Methods

MEDLINE and EMBASE were searched using MESH headings and text words. Titles, keywords and abstracts were checked for age <18 years, potential ADRs and electronic healthcare data. Information extracted included age, data source, pharmacovigilance method, medicines and ADRs. Studies were quality assessed.

Results

From 14 804 titles, 314 had a full text review and 71 were included in the final review. Fifty were published in North America, 10 in Scandinavia. Study size ranged from less than 1000 children to more than 10 million. Sixty per cent of studies used data from one source. Comparative observational studies were most commonly reported (66.2%) with 15% using passive surveillance. Electronic healthcare data set linkage and the quality of the data source were poorly reported. ADRs were classified using the International Classification of Disease (ICD10). Multi-system reactions were most commonly studied, followed by central nervous system and mental and behavioural disorders. Vaccines were most frequently prescribed followed by corticosteroids, general anaesthetics and antidepressants.

Conclusions

Routine electronic healthcare records were increasingly reported to be used for pharmacovigilance in children. This growing and important health protection activity could be enhanced by consistent reporting of studies to improve the identification, interpretation and generalizability of the evidence base.     

《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。     

Effective integration of pharmacovigilance systems at public health facilities in resource-limited settings: A qualitative study

BackgroundPharmacovigilance systems increase access to safe medicines and healthcare, but their integration in public healthcare remains a challenge in many countries. The main barriers to pharmacovigilance integration are attributed to high patient load and limited capacities.ObjectiveTo explore the challenges associated with the effective integration of pharmacovigilance systems in public healthcare in a developing country such as Namibia.MethodsA nationwide qualitative assessment of integration of pharmacovigilance systems particularly spontaneous adverse drug reaction (ADR) reporting at public health facility level was conducted. Key informant interviews were conducted among pivotal healthcare professionals involved in pharmacovigilance. The main outcomes were themes on challenges and strategies for effective integration of PV services at the facility level. Qualitative data were collected over a one-month period (i.e., March 2019), and thematically analysed.ResultsEight (8) key informants were recruited; the majority were pharmacists (n = 7) and male (n = 5). The main challenges affecting the effective integration of pharmacovigilance systems reporting at public health facilities were “weak pharmacovigilance policies and structures”, “negative attitude of healthcare workers towards pharmacovigilance”, and “limited capacity and support for implementation of pharmacovigilance activities”. The main strategies for effective integration of PV systems at facilities included local capacity-building through continuing profession education and support, advocacy, stakeholder engagement, facility/region based pharmacovigilance champions, and facility-based policies for universal and inclusive reporting, (i.e. patients and health workers at all levels) as well as development of workable standard operational procedures.ConclusionsThe pharmacovigilance systems at healthcare facilities in Namibia were observed to have sub-optimal policies, structures and support systems, and lack health care worker buy-in. There is a need for a policy framework to ensure effective and sustainable integration of pharmacovigilance activities at public healthcare facilities.