Characteristics and temporal trends of EU teratological safety signals and information dissemination to healthcare professionals in the Netherlands-A contribution of the ConcePTION project.

aimAlthough regulatory responses to safety signals have been studied, pregnancy-specific data and their dissemination to medical professionals remain unclear. This study examined the characteristics and temporal trends of teratological safety signals prompting the European Medicines Agency to implement risk minimization measures. A secondary aim was to investigate how information on these signals, independent of regulatory communication, was disseminated to medical professionals in the Netherlands.

methodsTeratological safety signals from 2002 to 2022 were retrieved from the European Pharmacovigilance Issues Tracking Tool. For each signal, we recorded the dates of market authorization, first spontaneous report, scientific publication, regulatory decision and dissemination through the Teratology Information Service (TIS) and Dutch professional journals. The source of the signal (spontaneous reports, scientific literature or otherwise) was assessed. Time intervals between events were calculated and visualized.

resultsTwenty-four safety signals pertaining to fetal teratogenesis were identified. At the time of regulatory action, medicines had been on the market for a median of 23.9 years (range 3.2-59.3). Cases or studies published in the scientific literature were the origin for most (n = 18, 75%) teratological safety signals. Amendments of the product information was a regulatory action for all signals; eight (33%) also triggered Direct Healthcare Professional Communications. Apart from these regulatory communications, information may have reached healthcare professionals through scientific literature or other channels, sometimes before and sometimes alongside regulatory decisions.

conclusionTeratological safety signals are predominantly scientific literature-driven and often arise decades after marketing. Scientific publications and TIS may provide early guidance, frequently preceding regulatory decisions.