A Comparison of Signals of Designated Medical Events and Non-designated Medical Events: Results from a Scoping Review

Abstract

Introduction and objective The European Medicines Agency (EMA) maintains a list of designated medical events (DMEs), events that are inherently serious and are prioritized for signal detection, irrespective of statistical criteria. We have analysed the results of our previously published scoping review to determine whether DME signals differ from those of other adverse events in terms of time to communication and characteristics of supporting reports of suspected adverse drug reactions. Methods For all signals, we obtained the launch year of medicinal products from textbooks or regulatory agencies, extracted the year of the first report in VigiBase and calculated the interval between the first report and communication (time to communication, TTC). We further retrieved the average completeness (via vigiGrade) of the reports in each case series in the years before the communication. We categorised as DME signals those concerning an event in the EMA’s list. We described the two groups of signals using medians and interquartile ranges (IQR) and compared them using the Brunner–Munzel test, calculating 95% confidence intervals (95% CI) and P values. Results Of 4520 signals, 919 concerned DMEs and 3601 concerned non-DMEs. Signals of DMEs were supported by a median of 15 reports (IQR 6–38 reports) with a completeness score of 0.52 (IQR 0.43–0.62) and signals of non-DMEs by 20 reports (IQR 6–84 reports) with a completeness score of 0.46 (IQR 0.38–0.56). The probability that a random DME signal was supported by fewer reports than non-DME signals was 0.56 (95% CI 0.54–0.58, P < 0.001) and that of one having lower average completeness was 0.39 (95% CI 0.36–0.41, P < 0.001). The median TTCs of DME and non-DME signals did not differ (10 years), but the TTC was as low as 2 years when signals (irrespective of classification) were supported by reports whose average completeness was > 0.80. Conclusions Signals of designated medical events were supported by fewer reports and higher completeness scores than signals of other adverse events. Although statistically significant, the differences in effect sizes between the two groups were small. This suggests that listing certain adverse events as DMEs is not having the expected effect of encouraging a focus on reports of the types of suspected adverse reactions that deserve special attention. Further enhancing the completeness of the reports of suspected adverse drug reactions supporting signals of designated medical events might shorten their time to communication and reduce the number of reports required to support them. Supplementary Information The online version contains supplementary material available at 10.1007/s40264-024-01403-x.

An analysis of international strategies for monitoring and preventability described in medicinal product information: a study protocol

“…Using previously published datasets of signals of ADRs [11, 16], we shall retrieve, for each signal: (a) the medicinal products (active ingredient, coded to WHODrug Global [17], and defined by [18]) and their earliest launch dates; (b) adverse events involved (coded to MedDRA, the Medical Dictionary for Regulatory Activities®); (c) the country of communication. To minimize the effect of strength of evidence on the known discrepancies of product information [9], we shall restrict the evidence-base of signals to those categorized as arising solely from clinical assessments of reports of ADRs.…”