Validation of Statistical Signal Detection Procedures in EudraVigilance Post-Authorization Data A Retrospective Evaluation of the Potential for Earlier Signalling
Validation of Statistical Signal Detection Procedures in EudraVigilance Post-Authorization Data A Retrospective Evaluation of the Potential for Earlier Signalling
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DOI：
10.2165/11534410-000000000-00000
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发表时间：
2010-01-01
期刊：
影响因子：
4.2
通讯作者：
Slattery, Jim
中科院分区：
文献类型：
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作者：
Alvarez, Yolanda;Hidalgo, Ana;Slattery, Jim
背景资料：筛选可能的药物不良反应（ADR）自发病例报告的大型数据库是识别迄今未知的药品不良反应的既定方法;然而，关于正式统计筛选程序在指导这一过程中的价值缺乏共识。本研究的目的是澄清任何额外的好处和额外的努力时，建立药物警戒技术补充统计screen.Objective：为了评估是否统计信号检测自发报告数据可以导致早期发现药物安全性问题，并评估额外的监管工作所需要的性质。方法：使用EudraVigilance授权后模块（EVPM），基于比例报告率（PRR）的筛选程序回顾性地应用，以检查是否可以在预定义的一组产品中启动有关ADR的监管调查，实践在同一时间段内，即2003年9月至2007年3月，计算并评价了同一产品组中出现的基于PRR的不成比例报告（SDR）信号的数量，以确定需要调查的数量。结果表示为需要调查的SDR数量与统计筛选方法预先排除的信号数量的比值。在这些情况下，信号被发现较早，延迟之间的识别计算由PRR的方法和最初确定的signal.Results的方法：在191化学不同的产品，532不良反应被添加到总结的产品特性在研究期间。其中，405起事件根据全面的预定义列表被指定为重要医学事件（IME）。在这些IME中，217起（53.6%）是通过统计筛选技术早期发现的，79起（19.6%）是在通过标准药物警戒方法提出的日期后检测到的，109起（26.9%）在研究期间未发出信号。在研究期间，检测到1561个需要进一步评价的SDR，每个预先排除的信号的评估比率为7.2。使用EVPM中的统计方法发现信号与早期检测到的217例病例中的既定方法之间的平均延迟为2.45年。一项审查结果清楚地解释了为什么统计方法没有先发制人的检测，但77 188 cases.Conclusions：在这项研究中测试的统计信号检测的形式可以提供显着的早期预警在很大比例的药物安全问题;然而，它不能比其他药物警戒过程更快地检测所有安全性问题，因此它应作为药物警戒过程的补充，而不是作为既定方法的替代。
Background: 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.Objective: 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.Methods: 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.Results: 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.Conclusions: 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.