Pharmacovigilance and Risk Management Sector, European Medicines Agency, 7 Westferry Circus, Canary Wharf, London, E14 4HB, UK.
Drug Saf. 2013 Aug;36(8):687-92. doi: 10.1007/s40264-013-0075-1.
Identification of potential drug safety problems using statistical screening algorithms in routinely collected databases of adverse drug reactions (ADRs) requires decision rules based on thresholds of the chosen parameters. Choosing higher or lower thresholds changes both the sensitivity of the screening and the number of false alarms produced, and thus has an impact on the effectiveness of the detection process.
The aim of this study was to evaluate the impact on the effectiveness of signal detection activities of choosing different warning thresholds for the proportional reporting ratio (PRR) and for the count of reports of any drug-event combination.
Signal detection methods were tested within the EudraVigilance database of suspected ADRs. Using an established set of known ADRs, the number that could be detected and the changes in time gained for earlier investigation of the signal were calculated over a range of signal detection thresholds. These figures were set against the number of false positive signals produced by the statistical signal detection algorithms.
Higher thresholds for the lower confidence bound of the PRR produced fewer false positives but this benefit was offset by important losses of sensitivity in the detection of ADRs. By contrast, increases in the threshold for the count of a specific drug-event combination produced fewer false positives with little loss of either sensitivity or time gained for investigation of adverse events. A threshold of five compared with the current European Medicines Agency threshold of three gave a reduction of 25 % in false positive signals in return for a loss of 12 % in true signals detected early.
Changes in the standard threshold for the count of drug-event combinations can result in a substantial improvement in efficiency of the signal detection process. Initially this change might be applied only to products with a well-established safety profile.
使用统计筛选算法在常规收集的不良反应（ADR）数据库中识别潜在药物安全问题需要基于所选参数阈值的决策规则。选择更高或更低的阈值会同时改变筛选的灵敏度和产生的误报数量，从而对检测过程的有效性产生影响。
本研究旨在评估选择不同的比例报告比（PRR）和任何药物-事件组合报告计数的警告阈值对信号检测活动的有效性的影响。
在 EudraVigilance 疑似 ADR 数据库中测试信号检测方法。使用一组既定的已知 ADR，计算在一系列信号检测阈值范围内可检测到的数量以及更早调查信号的时间变化。将这些数字与统计信号检测算法产生的假阳性信号数量进行比较。
PRR 置信下限的较高阈值产生较少的假阳性，但这一好处被检测 ADR 灵敏度的重要损失所抵消。相比之下，增加特定药物-事件组合计数的阈值会产生较少的假阳性，而对不良事件调查的灵敏度或获得的时间增益几乎没有影响。与当前欧洲药品管理局的阈值 3 相比，阈值为 5 会减少 25%的假阳性信号，但早期检测到的真实信号会减少 12%。
改变药物-事件组合计数的标准阈值可以显著提高信号检测过程的效率。最初，这种变化可能仅适用于具有良好安全记录的产品。
