European Medicines Agency, London, UK.
Drug Saf. 2010 Jun 1;33(6):475-87. doi: 10.2165/11534410-000000000-00000.
Screening large databases of spontaneous case reports of possible adverse drug reactions (ADRs) is an established method of identifying hitherto unknown adverse effects of medicinal products; however, there is a lack of consensus concerning the value of formal statistical screening procedures in guiding such a process. This study was performed to clarify the nature of any added benefits and additional effort required when established pharmacovigilance techniques are supplemented with statistical screening.
To evaluate whether statistical signal detection in spontaneous reporting data can lead to earlier detection of drug safety problems and to assess the additional regulatory work entailed.
Using the EudraVigilance post-authorization module (EVPM), a screening procedure based on the proportional reporting ratio (PRR) was applied retrospectively to examine if regulatory investigations concerning ADRs in a predefined set of products could have been initiated earlier than occurred in practice. During the same time period, between September 2003 and March 2007, the number of PRR-based signals of disproportionate reporting (SDR) that arose in the same set of products was calculated and evaluated to determine the number requiring investigation. The outcome is expressed as the ratio of the number of SDRs requiring investigation compared with the number of signals pre-empted by the statistical screening approach. In those cases where the signal was discovered earlier, the delay was calculated between identification by the PRR method and by the method that originally identified the signal.
In 191 chemically different products, 532 adverse reactions were added to the summary of product characteristics during the study period. Of these, 405 were designated as important medical events (IMEs) based on a comprehensive predefined list. Of the IMEs, 217 (53.6%) were identified earlier by the statistical screening technique, 79 (19.6%) were detected after the date at which they were raised by standard pharmacovigilance methods and 109 (26.9%) were not signalled during the study period. 1561 SDRs requiring further evaluation were detected during the study period, giving a ratio of 7.2 assessments for each signal pre-empted. The mean delay between the discovery of signals using the statistical methods in the EVPM and established methods in the 217 cases detected earlier was 2.45 years. A review resulted in clear explanation for why the statistical method had not pre-empted detection in all but 77 of 188 cases.
The form of statistical signal detection tested in this study can provide significant early warning in a large proportion of drug safety problems; however, it cannot detect all safety issues more quickly than other pharmacovigilance processes and hence it should be used in addition to, rather than as an alternative to, established methods.
筛选大量自发报告的可能药物不良反应（ADR）数据库是识别药品未知不良反应的一种既定方法。然而，在指导这一过程时，对于正式的统计筛选程序的价值，尚未达成共识。本研究旨在阐明在补充统计筛选时，采用既定药物警戒技术所带来的任何附加益处和额外工作。
评估在自发报告数据中进行统计信号检测是否可以更早地发现药物安全性问题，并评估所涉及的额外监管工作。
使用 EudraVigilance 事后授权模块（EVPM），基于比例报告比（PRR）的筛选程序进行回顾性应用，以检查针对预定义产品集内的 ADR 进行的监管调查是否可以比实际更早开始。在同一时期，即 2003 年 9 月至 2007 年 3 月期间，计算并评估了同一产品集中出现的比例不合理报告（SDR）的基于 PRR 的信号数量，以确定需要进行调查的数量。结果表示为需要调查的 SDR 数量与通过统计筛选方法预先阻止的信号数量之比。在那些信号更早被发现的情况下，计算了 PRR 方法和最初识别信号的方法之间的识别延迟。
在 191 种化学不同的产品中，研究期间将 532 种不良反应添加到产品特性摘要中。其中，根据预先确定的综合清单，405 种被指定为重要医学事件（IME）。在这些 IME 中，217 种（53.6%）通过统计筛选技术更早地被识别，79 种（19.6%）在使用标准药物警戒方法提出的日期之后被检测到，109 种（26.9%）在研究期间未发出信号。在研究期间共检测到 1561 个需要进一步评估的 SDR，每个信号预先阻止的评估次数为 7.2 次。在使用 EVPM 中的统计方法和较早发现的 217 个信号的既定方法之间发现信号的平均延迟为 2.45 年。审查结果明确解释了为什么在 188 个案例中，除了 77 个案例外，统计方法没有预先阻止检测。
本研究中测试的统计信号检测形式可以在很大比例的药物安全问题中提供重大预警；然而，它不能比其他药物警戒过程更快地检测到所有安全问题，因此应与既定方法一起使用，而不是替代既定方法。
