Signal Detection by Disproportionality Analysis in the Monitoring of COVID-19 Vaccine Safety in Switzerland: An International Journal of Medical Toxicology and Drug Experience

ABSTRACT

Introduction: Initial knowledge on the COVID-19 vaccines' safety from randomised clinical trials was limited and concerned mostly common adverse events related to vaccine immunogenicity occurring rapidly after vaccination [1,2]. Since these vaccines have been approved and used in large scale, the Swiss Agency for Therapeutic Products Swissmedic has been conducting an intensive surveillance activity on their safety, based on the collection and analysis of spontaneous reports from healthcare professionals and patients. Objective: Signal detection in spontaneous reports associated with COVID-19 vaccines first relies on a case-by-case analysis by clinically qualified assessors who take into account detailed information provided by reporters. However, with the number of reports increasing, the clinical review could benefit from the use of statistical methods for signal detection, such as disproportionality analysis [3]. Methods: In light of this, the Institute of Pharmacological Sciences of Southern Switzerland, in close collaboration with Swissmedic, set up and routinely perform a signal detection activity by disproportionality analysis in VigiBase, the global database of the World Health Organization (WHO) Programme for International Drug Monitoring, using spontaneous reports originating from Switzerland and concerning adverse events following immunization (AEFIs) associated with the Moderna (Spikevax) and Pfizer/BioNTech (Comirnaty) COVID-19 vaccines. These included the measurement of the reporting odds ratios (RORs) for COVID-19 vaccine/AEFI combinations meeting two predefined statistical signal detection criteria, namely a minimum of 5 reports concerning a COVID-19 vaccine/AEFI combination and a ROR lower limit of the 95% confidence interval[1. Excluding AEFIs either already labelled in the Swiss information for healthcare professionals, or already debated internationally, a panel of pharmacovigilance and clinical pharmacology experts are examining and discussing findings on novel and unexpected COVID-19 vaccine/AEFI combinations, in order to promptly detect potential safety signals that could warrant further investigation. Results: Since the start of the signal detection activity in August 2021, an early signal of disproportionate reporting in VigiBase for paraesthesia with the Moderna (Spikevax) vaccine was detected in Switzerland. This occurred a few months before the same signal was assessed and validated by the European Medicines Agency, which ultimately added paraesthesia to the European summary of product characteristics for the Moderna (Spikevax) vaccine [4]. Conclusion: Disproportionality analysis has some limitations such as lack of information about incidence rate of the adverse event in the population, and the existence of reporting biases. Nevertheless, continued research on newly identified safety signals can provide valuable information to support public health, guide regulatory decisions and design specific follow-up confirmatory studies.