Torre Carla, Cary Maria, Borges Fábio Cardoso, Ferreira Paula S, Alarcão Joana, Leufkens Hubert G, Costa João, Martins Ana Paula
Centre for Health Evaluation and Research (CEFAR), National Association of Pharmacies, Lisbon, Portugal.
Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal.
Front Med (Lausanne). 2019 Jul 19;6:147. doi: 10.3389/fmed.2019.00147. eCollection 2019.
Intensive monitoring (IM) is one of the methods of post-marketing active surveillance based upon event monitoring, which has received interest in the current medicines regulatory landscape. For a specific period of time, IM involves primary data collection and is actively focused on gathering longitudinal information, mainly safety, since the first day of drug use. To describe IM systems and studies' data published over 11-years period (2006-2016). Specifically, we reviewed study population/event surveillance, methodological approaches, limitations, and its applications in the real-world evidence generation data. We completed a systematic search of MEDLINE and EMBASE to identify studies published from 2006 to 2016, that used IM methodology. We extracted data using a standardized form and results were analyzed descriptively. The methodological quality of selected studies was assessed using the modified Downs and Black checklist. From 1,400 screened citations, we identified 86 papers, corresponding to 69 different studies. Seventy percent of reviewed studies corresponded to established IM systems, of which, more than half were prescription event monitoring (PEM) and modified-PEM. Among non-established IM systems, vaccines were the most common studied drugs ( = 14). The median cohort size ranged from 488 (hospitals) to 10,479 (PEM) patients. Patients and caregivers were the event data source in 39.1% of studies. The mean overall quality score was similar between established and non-established IM. Over the study period, IM studies were implemented in 26 countries with different maturity levels of post-marketing surveillance systems. We identified two major limitations: only 20% of studies were conducted at hospital-level, which is a matter of concern, insofar as healthcare systems are facing a lack of access to new medicines at ambulatory care level. Additionally, IM access to data of drug exposure cohorts, either at identification or at follow-up stages, could somehow constitute a barrier, given the complexity of managerial, linkable, and privacy data issues.
强化监测（IM）是基于事件监测的上市后主动监测方法之一，在当前药品监管环境中受到关注。在特定时间段内，IM涉及原始数据收集，并从用药第一天起就积极专注于收集纵向信息，主要是安全性信息。描述11年期间（2006 - 2016年）发表的IM系统和研究的数据。具体而言，我们回顾了研究人群/事件监测、方法学方法、局限性及其在真实世界证据生成数据中的应用。我们对MEDLINE和EMBASE进行了系统检索，以识别2006年至2016年发表的使用IM方法的研究。我们使用标准化表格提取数据，并对结果进行描述性分析。使用修改后的唐斯和布莱克清单评估所选研究的方法学质量。从1400篇筛选的文献中，我们识别出86篇论文，对应69项不同的研究。70%的综述研究对应已建立的IM系统，其中一半以上是处方事件监测（PEM）和改良PEM。在未建立的IM系统中，疫苗是最常研究的药物（n = 14）。队列规模中位数范围为488名（医院）至10479名（PEM）患者。患者和护理人员是39.1%的研究中的事件数据源。已建立和未建立的IM之间的平均总体质量得分相似。在研究期间，IM研究在26个上市后监测系统成熟度不同的国家实施。我们确定了两个主要局限性：只有20%的研究在医院层面进行，鉴于医疗保健系统在门诊护理层面难以获取新药，这是一个令人担忧的问题。此外，考虑到管理、可链接和隐私数据问题的复杂性，IM在识别或随访阶段获取药物暴露队列数据可能会构成某种障碍。
