Public Health and Community Medicine, Tufts University School of Medicine, Boston, MA, USA.
Clin Ther. 2020 Jun;42(6):1110-1129. doi: 10.1016/j.clinthera.2020.03.018. Epub 2020 May 30.
After nearly 12 decades of pharmaceutical catastrophes and the associated groundbreaking regulatory innovations, pharmacovigilance has come down to us in the present day as 3 interlocking core disciplines: case management, signal management, and benefit-risk management. This review provides a state-of-the-art introduction to the great variety of sources of safety information, both dependent on and independent of the Individual Case Safety Report (ICSR), and explains how this content undergoes management-system processes with globally accepted definitions, standards, and structures that make possible the ongoing safe use of a pharmaceutical product throughout its lifecycle. This occurs in the context of: (1) new products coming to market with new risks for drug-drug interactions, and (2) new global threats to safe manufacturing and distribution.
This narrative review, reflective of the author's experience, uses a large-frame system of signal management developed by the Council for International Organizations of Medical Sciences VIII Working Group and modified by the author to include governance. A key feature of the review is the regular inclusion of relevant case studies to provide a backdrop of the unexpected, with resulting tragic outcomes, to the ever-evolving regulatory landscape.
Regarding content, beyond the commonly appreciated sources of safety information that find their way into ICSRs are non-ICSR-based sources, including preclinical data, manufacturing data, findings from subject-matter experts who participate on data-monitoring committees, outside expert panels, advocacy groups, and independent investigator studies. Regarding process, it is important to recognize that governance is crucial in the effective conduct of signal management, in that subject-matter experts are essential to the scientific and medical aspects of decision making, and business and policy executives are essential in determining the final courses of action, as these decisions have implications for the company.
Signal management is an integral part of pharmacovigilance practices that strive to obtain all of the information necessary for maintaining the safety profiles of a company's pharmaceutical and biological products, to support favorable benefit-risk balances, and to ensure safe use by health care providers and their patients.
经过近 12 个十年的制药灾难和相关的开创性监管创新，药物警戒已经发展成为我们今天的 3 个相互关联的核心学科：病例管理、信号管理和获益-风险管理。本综述提供了药物警戒实践的最新介绍，涵盖了各种安全信息来源，包括依赖和独立于个体病例安全报告（ICSR）的信息来源，并解释了如何通过具有全球认可的定义、标准和结构的管理系统流程来管理这些内容，从而实现药物在整个生命周期内的安全使用。这是在以下背景下进行的：（1）新的产品进入市场，带来了药物相互作用的新风险；（2）新的全球安全制造和分销威胁。
本叙事性综述反映了作者的经验，使用了由国际医学组织理事会第八工作组开发并由作者修改以纳入治理的大型信号管理系统。综述的一个关键特征是定期纳入相关案例研究，为不断发展的监管格局提供意想不到的、具有悲惨结果的背景。
关于内容，除了常见的安全信息来源，如 ICSR 中包含的安全信息来源之外，还有非 ICSR 基础的安全信息来源，包括临床前数据、制造数据、参与数据监测委员会的主题专家的发现、外部专家小组、倡导团体和独立研究人员的研究。关于流程，重要的是要认识到治理对于有效的信号管理至关重要，因为主题专家对于决策的科学和医学方面至关重要，而业务和政策主管对于确定最终行动方案至关重要，因为这些决策对公司有影响。
信号管理是药物警戒实践的一个组成部分，旨在获取维持公司药物和生物制品安全概况所需的所有信息，支持有利的获益-风险平衡，并确保医疗保健提供者及其患者的安全使用。
