Quo vadis (where are you going) pharmacovigilance?
Quo vadis (where are you going) pharmacovigilance?
复制标题
Quo vadis（你要去哪里）药物警戒？
DOI：
10.1111/bcp.15584
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发表时间：
2023
影响因子：
3.4
通讯作者：
Kulkarni S
中科院分区：
文献类型：
--
作者：
Kulkarni S
药物警戒的目标是确保治疗的安全使用。希波克拉底的不伤害原则（primum non questiere）构成了药物警戒的基础。药物警戒系统是旨在及时识别潜在药物不良反应（ADR）、评价因果关系并将此信息转化为风险缓解策略的流程。它们涵盖了从临床前研究到实际使用的整个治疗生命周期。这些过程包括所有利益攸关方进行严格的风险评估和不断的监督，需要大量的支持和资金来实现共同的安全目标。尽管迄今作出了努力，但发展成果评估继续给保健服务造成重大负担。最近报告的一项利用世界卫生组织（WHO）药物警戒数据库VigiBase的回顾性研究发现，在过去十年中记录了2300万起ADR，其中1.34%是致命的。1到2010年，134个国家加入了世卫组织药物警戒方案。直到20世纪60年代沙利度胺灾难，现代药物警戒的正式系统才以世界卫生组织国际药物监测计划的形式形成。到了20世纪90年代，国际协调理事会成立，这是一个由监管机构（RA）和药品共同努力创建的组织，其使命是在全球范围内统一药品监管要求。根据ADR的自发报告，历史证明了许多药物撤回，截至2003年，撤回了> 75种药物，2包括非那普利、特非那定、阿司咪唑、曲格列酮和西沙必利。总体而言，由于器官或系统毒性（如肝毒性、心脏毒性（主要是QT间期延长）和骨髓毒性）而停药。然而，直到十年前，药物警戒的技术流程几乎没有进展;自发报告过程中存在许多缺陷，包括：医生和患者组对ADR报告不足，3个与临床试验方法学密切相关的问题，包括评价安全性信号的技术不足，4批判性思维有限，很少或没有稽查跟踪，报告质量差，以及技术和数据挖掘应用的使用不足。此外，可能需要在某些人群（如老年人、儿童、孕妇和社会经济弱势群体）中收集安全性数据的具体考虑因素和指南，因为这些群体在临床试验中的代表性通常很差。幸运的是，药物警戒监管的格局正在发生变化，越来越多的国家正在协调努力，建立一个集中的治疗相关危害监测系统。一个这样的例子是在最近的一个主题问题上发表的白色论文，在药品的整个生命周期中为儿科药物警戒提供了实际考虑。5临床试验的设计目的是在明确定义的环境中确定治疗的获益与危害风险，通常是在相对较短的时间内，在明确定义的小样本人群中进行稳健的监测。因此，迫切需要进行上市后（4期）监测研究，以评估新上市化合物在真实的世界中的疗效和安全性。4期研究可以评价治疗在原始适应症中的有效性，但重要的是，它们提供了识别长期和/或罕见严重或非严重ADR的机会。此外，2020年，全球范围内的新疗法和疫苗获得了紧急使用授权和快速批准。
The goal of pharmacovigilance is to ensure that therapies are safe to use. The Hippocratic principle of do no harm (primum non nocere) forms the very foundation of pharmacovigilance. Pharmacovigilance systems are processes designed to identify potential adverse drug reactions (ADRs) in a timely manner, to evaluate causality and to translate this information into risk mitigation strategies. They span the complete life cycle of a therapy beginning from preclinical studies to real-world use. These processes include scrupulous risk assessments and constant surveillance by all stake holders and require significant support and funding to achieve the shared goal of safety. Despite efforts to date, ADRs continue to lead to significant burden on health services. A recently reported retrospective study utilizing VigiBase, the World Health Organization's (WHO) pharmacovigilance database, found that 23 million ADRs were recorded in the last decade, among which 1.34% were fatal. 1 By 2010, 134 countries had joined the WHO pharmacovigilance programme. It was not until the 1960s thalidomide disaster that the formal system of modern pharmacovigilance took shape in the form of the WHO Programme for International Drug Monitoring. By the 1990s, the inception of the International Council for Harmonization, an organization created by the joint efforts of regulatory authorities (RA) and pharmaceuticals, came together with a mission to align pharmaceutical regulatory requirements globally. History is testimony to numerous drug withdrawals based on spontaneous reporting of ADRs, and> 75 drugs were withdrawn by 2003, 2 including phenformin, terfenadine, astemizole, troglitazone and cisapride. Overall, drugs are withdrawn due to organ or system toxicities such as hepatotoxicity, cardiotoxicity (mainly QT prolongation) and myelotoxicity. However, until a decade ago, there was very little progress in the technical processes of pharmacovigilance; a number of flaws exist in the process of spontaneous reporting including: under-reporting of ADRs by physicians and patient groups, 3 issues germane to clinical trials methodology, including inadequate techniques for evaluation of safety signals, 4 limited critical thinking, little or no audit trail, poor quality of reports, and underuse of technology and data mining applications. Additionally, specific considerations and guidelines to gather safety data in certain populations such as the elderly, children, pregnant women and socio-economically disadvantaged groups may be needed as these groups generally tend to be poorly represented in clinical trials. Fortunately, the landscape of pharmacovigilance regulation is changing, and more countries are now harmonizing their efforts towards having a centralized system of surveillance of therapy-related harms. One such example is the white paper published in a recent themed issue, providing practical considerations for paediatric pharmacovigilance, throughout the life cycle of medicinal products. 5 Clinical trials are designed to frame the benefit vs. risk of harm for a therapy in a well-defined setting, typically for a relatively brief period of time and in well-defined, small sample of the population with robust monitoring. Thus, there is a compelling need for postmarketing (Phase 4) surveillance studies to assess the efficacy and safety of newly marketed compounds in the real world. Phase 4 studies can evaluate the effectiveness of therapies in the original indications, but importantly, they offer opportunities for identifying long-term and/or rare serious or non-serious ADRs. In addition, 2020 saw emergency use authorization and rapid approvals of new therapies and vaccines for the global …
影响因子：
3.4
作者：
通讯作者：
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影响因子：
--
作者：
D. Liebling;Emmanuel Cordova;G. Deng;J. McKoy
通讯作者：
J. McKoy
影响因子：
3.4
作者：
Arimone, Yannick;Miremont-Salame, Ghada;Begaud, Bernard
通讯作者：
Begaud, Bernard