Impact of the Inclusion of Covid-19 Vaccines in the National Pharmacovigilance Database on the Measurement of Disproportionality: An International Journal of Medical Toxicology and Drug Experience

ABSTRACT

Introduction: During the strengthened Covid-19 vaccine safety surveillance, the Moroccan pharmacovigilance center has collected a higher number of adverse events following immunization (AEFI) reports. More than half of the Individual Case Safety Reports (ICSRs) collected in the National pharmacovigilance database since its cre-ation are linked to Covid-19 vaccines [1]. Objective: To assess the impact of the inclusion of the AEFI related to Covid-19 vaccines on the measures of disproportionality in the National pharmacovigilance database. Methods: Measurement of disproportionality by the calculation of the Reporting odds ratio (ROR) [2] for the "Drug-Effect" pairs collected at the National pharmacovigilance database (data from March 16, 2022) with and without inclusion of Covid-19 vaccines. Using "VigiLyze" (Uppsala Monitoring Center) we calculated the RORs and exported to "Excel" the list of "Drug-Effect" pairs for which the lower limit of the 95% confidence interval of the ROR is greater than 1. Then, on the list obtained, we recalculated by Excel the RORs after excluding the Covid-19 vaccines from the database. Results: Among the 69,814 cases of adverse effects recorded in the National pharmacovigilance database from March 16, 2022, 36,541 cases (52.6%) concerned Covid-19 vaccines (Table 1). The measurement of the disproportionality showed that 88% of the RORs increased and 5% decreased after inclusion of Covid-19 vaccines in database. The median of the ROR change factor following this inclusion (RORCovid vaccines included/RORCovid vaccines excluded) was 2.1 (1.8-2.1);this can be explained by the higher proportion of Covid-19 vaccines cases (half of the database). Also, the degree of this influence depends on the frequency of AEFI to Covid-19 vaccines. Thus, the ROR had decreased with inclusion of cases of covid-19 vaccines for most common reactions and had been multiplied by a factor more than 2 for the low-reported reactions with Covid-19 vaccines. Conclusion: The inclusion of Covid-19 vaccines in the National pharmacovigilance database has influenced the measures of disproportionality, which would influence signal detection. This bias must be taken into account when a type of drug or vaccine is very represented in a database. The proposed solution is to specify database for these types of products or to improve VigiLyze to be able to perform disproportionality measurements from parts of the national database.