Understanding the Work of the Pharmacovigilance Risk Assessment Committee (PRAC): A Quantitative Review of the Post-Authorisation Safety Evaluation of Antidiabetic Drugs from 2012 to 2022.

Abstract

Background: The Pharmacovigilance Risk Assessment Committee (PRAC) plays a central role in the European Union's pharmacovigilance system, evaluating drug safety through several procedures and activities. Despite its central role, few studies have quantitatively investigated the PRAC's activities from a system's perspective.

Objective: This study aims to map PRAC's evaluation of safety signals and concerns using antidiabetic products as a case. It characterises the drugs and adverse events involved, analyses the PRAC-led regulatory procedures where the safety signals and concerns were evaluated, and provides a comprehensive review of PRAC meeting minutes.

Methods: From PRAC meeting minutes, we retrieved information on all antidiabetic drug-related adverse events discussed from 2012 to 2022. We identified drug-adverse event evaluations based on the discussion content. These were described by drug classes, System Organ Classes, PRAC procedures, and the evaluation outcomes corresponding to recommendations for regulatory actions. We also analysed the sequence of PRAC-led procedures and activities addressing drug-adverse event pairs across meeting minutes.

Results: A total of 321 drug-adverse event pairs were identified, with 14 pairs associated with drug classes. Second-generation antidiabetic agents, including sodium-glucose transport protein-2 inhibitors, glucagon-like peptide-1 receptor agonists, and dipeptidyl peptidase 4 inhibitors, were the most frequently discussed. Of these, 62 pairs underwent multiple evaluations, resulting in a total of 413 evaluations. In 48% of evaluations, no regulatory action was required. Most evaluations (97%) were concluded in a single procedure, and 66% were concluded in one meeting. Periodic safety update reports accounted for 54% of drug-adverse event evaluations and updates to product information were the most frequent outcome. Signal assessment and prioritisation procedures, while less common, resulted in more diverse recommendations for regulatory action. Referrals were infrequent (N = 5) and were often triggered by the signal assessment and prioritisation procedure.

Conclusions: Periodic safety update reports are the primary source for PRAC evaluations of safety signals although they are not intended for notification of new urgent safety information. Compared with periodic safety update reports, the signal assessment and prioritisation procedure evaluates fewer signals but leads to a wider range of regulatory actions, from risk minimisation measures to referrals. This difference may be attributed to the fact that signals detected in periodic safety update reports are not intended for urgent safety issues, these should be assessed through the signal assessment and prioritisation procedure, as the latter involves real-time signal management, whereas the periodic safety update reports are conducted at predefined intervals.