ABSTRACT
BACKGROUND: The large-scale COVID-19 vaccination campaigns in 2021 and 2022 led to a rapid increase in numbers of received adverse event reports in spontaneous reporting systems. As background incidences of naturally occurring medical events became increasingly relevant for causality assessment of potential associations with the vaccines, a novel approach for signal detection was warranted. OBJECTIVES: This article illustrates the Observed-over-Expected (O/E) analysis as an additional method for signal detection and risk assessment in large-scaled spontaneous reporting systems. METHODS: All individual case safety reports (ICSRs) concerning idiopathic peripheral facial paralysis or Bell's palsy following administration of the COVID-19 vaccines (n = 291) manufactured by Pfizer/BioNTech (Comirnaty), Moderna (Spikevax), AstraZeneca (Vaxzevria) and Janssen (JCOVDEN) received by the National Pharmacovigilance Centre Lareb until 24th March 2022 were included in the O/E analysis, within a risk window of 7 and 14 days following immunisation. Dutch background incidence rates from 2019 and exposure of the Dutch population to the vaccines were obtained from the PHARMO institute and RIVM. The data was stratified in age groups, gender and administered dose in order to differentiate between population subgroups. RESULTS: Bell's palsy was reported more frequently than expected in several population subgroups following administration of all four COVID-19 vaccines, including children and adolescents. Among children, a high O/E ratio was found for boys aged 5-14 years after receiving the Pfizer/BioNTech vaccine. Regarding adolescents and young adults, women aged 15-24 years receiving Pfizer/BioNTech and Moderna, and men aged 15-24 years receiving Janssen developed Bell's palsy more often than expected. Furthermore, O/E ratios were high for individuals aged 25-64, regarding females receiving Pfizer, Moderna and AstraZeneca and males receiving Janssen. As facial paralysis was not labelled as an adverse event for the Janssen vaccine, this analysis contributed to signalling the association and warranting further regulatory action. CONCLUSIONS: The O/E method is a useful approach for signal detection of potential adverse reactions when handling large numbers of ICSRs. Further research is needed to attest to the causality on a clinical basis.