Validation of Statistical Signal Detection Procedures in EudraVigilance Post-Authorization Data

Abstract

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.

Safety Signal Detection of Cardiac Disorders Adverse Drug Events for Azithromycin in Pediatric Population Using Health Canada Adverse Event Reporting System Database

“…Although it is hard to accurately determine the confirmed ADE, studies have attempted to provide preliminary analysis. Such additional analysis would have strengthened the findings [20,21]. Further, while we calculated the three indices PRR, ROR, and IC for safety signal, it may be instructive to compare the findings presented herein with other methods.…”

“…Further, while we calculated the three indices PRR, ROR, and IC for safety signal, it may be instructive to compare the findings presented herein with other methods. For example, receiver operating characteristic analysis and other approaches such as those that focus on positive predictive value or false discovery rates would, if performed, complement our analysis [20,22,23].…”

Zoo or Savannah? Choice of Training Ground for Evidence-Based Pharmacovigilance

“…However, this conclusion would only be valid to the extent that the reference were fit-for-purpose, and there is evidence to suggest that it is not: Fig. 2 shows the corresponding graph for historical safety signals from the European Medicines Agency (EMA) [14] backdated to the time around the initial signal investigations, at the end of 2004. Against this reference of emerging safety signals, the pattern is reversed and disproportionality analysis performs significantly better than raw numbers of reports.…”

“…An early example of this was the retrospective analysis of VigiBase Ò by Lindquist et al [20], whereas more recent examples include the studies by Alvarez et al [14] and Strandell et al [21]. The reference set proposed by Alvarez et al [14] is particularly interesting in that it provides dates not just for the regulatory action associated with each signal, but also the first dates that each signal was first discussed by the EMA's signal management team. Retrospective analyses are not suitable for evaluation of manual or semi-manual approaches since experienced safety scientists cannot be blinded to the true status of historical safety signals.…”

Quantitative Signal Detection and Analysis in Pharmacovigilance

“…Nevertheless, there is now increasingly a robust body of evidence that suggests the value of such approaches when used appropriately as a core component of overall signal detection strategy for many organizations. While initially performance characteristics were investigated using retrospective evaluation approaches, such as by Lindquist et al (2000), there are published examples of now labeled adverse events that were highlighted when still unlabeled by QSD as well as prospective evaluation of signals detected (e.g., Alvarez et al, 2010) showing the value of DAs in routine signal detection operations with large repositories of spontaneous reports. Figure 20.4 Dilution bias.…”