Uncovering Pregnancy Exposures in Pharmacovigilance Case Report Databases: A Comprehensive Evaluation of the VigiBase Pregnancy Algorithm.

backgroundInformation on the safety of medicine use during pregnancy is limited at the time of marketing, making post-marketing surveillance essential. However, the lack of a specific indicator for pregnancy-related case reports within the international standard for transmission of individual case safety reports complicates the retrieval of such reports in pharmacovigilance databases. To address this, an algorithm to identify reports of exposures during pregnancy was developed in VigiBase, the World Health Organization global database of adverse event reports.

objectiveWe aimed to evaluate and characterise the VigiBase pregnancy algorithm.

methodsThe rule-based algorithm uses multiple structured data elements in the International Council of Harmonisation (ICH) E2B transmission format that could potentially hold pregnancy-related information, to determine if a case report qualifies as a pregnancy case. Free text information is not considered. Three datasets were used for the evaluation. The "Full dataset" comprised deduplicated VigiBase data up to January 2023. The "Downsampled dataset" was a subsample of the Full dataset, adjusted to increase the prevalence of pregnancy reports by excluding individuals aged 45 years or older and male individuals aged 18 years or older, used to evaluate recall (i.e. sensitivity). The "Random dataset" was a straight random sample of the Full dataset, used to evaluate precision (i.e. positive predictive value). As a baseline for comparison, the Standardised Medical Dictionary for Regulatory Activities (MedDRA

resultsIn the Downsampled dataset with 7874 annotated reports, 253 reports were annotated as pregnancy cases. Of those, the algorithm recalled 75% (95% confidence interval [CI] 69-80), increasing to 91% (95% CI 86-95) when restricting the analysis to reports adhering to the ICH E2B format. Preprocessing obstacles of incomplete mapping of specific pregnancy terms to MedDRA

conclusionsThe VigiBase pregnancy algorithm demonstrates robust performance, highlighting its potential to facilitate pharmacovigilance related to pregnancy. Our evaluation establishes a valuable benchmark for future research and emphasises the need for global harmonisation of standards for reporting pregnancy exposures.