Trends in adverse drug reaction reporting in eight selected countries after the implementation of new pharmacovigilance regulation in 2012: a joinpoint regression analysis

Abstract

Underreporting of adverse drug reactions (ADRs) remains to be a challenge in modern health care. Major reforms in the EU pharmacovigilance system in 2012 introduced the legal basis for consumers to report suspected ADRs. This study was designed to determine trends in overall ADR reporting, the ratio of health care professional (HCP)-to-consumer ADR reporting, and the ratio of serious-to-nonserious ADR reporting for an 11-year period in the selected non-EU and EU countries that had implemented systems for consumers' reporting before the 2012 EU pharmacovigilance legislation and those that did not have. The national competent authorities of 15 countries (11 EU countries, former EU member the UK, Australia, Canada, and the USA) were contacted via e-mail and asked to provide the total number of ADR reports, numbers of ADRs reported by consumers and HCPs, numbers of serious and nonserious ADRs, and top 5 medication groups causing ADRs by the Anatomical Therapeutic Chemical (ATC) classification system during the period of 2012-2022. Eight countries, namely Belgium, Canada, Finland, Lithuania, the Netherlands, Portugal, Sweden, and the UK, responded and provided the data. The trends of ADR reporting were evaluated with the joinpoint regression analysis method. The annual percent change (APC) and the average annual percent change (AAPC) were estimated. Over the study period, the overall rates of ADR reporting increased significantly in all the countries except for Belgium, with the greatest AAPC being in Lithuania (AAPC of 32.34) and the lowest, in Canada (AAPC of 10.3). The ratios of HCP-to-consumer ADR reporting were significantly decreasing in all the countries (AAPC range, -43.7 to -24.9) except for Canada where an opposite significant trend toward an increasing HCP reporting rate (AAPC of 3.9) for 2012-2020 was observed. The ratios of serious-to-nonserious ADR reporting were significantly decreasing in more than half of the countries, namely Canada, Finland, Lithuania, the Netherlands, and Portugal, with the greatest negative AAPC being in Lithuania (AAPC of -32.9) and the smallest, in Canada (AAPC of -6.8). Vaccines (J07), immunosuppressants (L04), antineoplastic agents (L01), antibacterials for systemic use (J01), and antithrombotic agents (B01) were found to be the top 5 most frequently reported medications. This study shows the significant upward trends in overall ADR reporting not only in the countries that implemented consumer ADR reporting systems after the 2012 EU pharmacovigilance legislation but also in countries that had consumer reporting systems before 2012. Moreover, significant downward trends in the ratios of HCP-to-consumer ADR reporting were documented for all EU countries, confirming increasing consumers' involvement in ADR reporting. Further, larger scale studies with the involvement of more countries are needed to better understand the trends in ADR reporting, and multifaceted interventions are warranted to be installed to enhance ADR reporting.