Communicating post-market safety risks of medicines with regulatory safety advisories: an international comparison of policy and perceptions

Background Information about the safety of medicines often emerges after approval. Medicines’ regulators use post-market safety advisories to communicate potential new harms. Advisories can influence medicines use, helping users to weigh benefits and harms. This thesis compared regulatory policy and outcomes for post-market safety communication in Australia, Canada, the United Kingdom (as part of the European Union) and the United States (US). Methods The four regulators were compared using: • A regulatory policy analysis. • An in-depth case study of safety communications for SGLT2 inhibitors (2012-2018). • A content analysis of safety advisories issued for new drugs approved in Australia 2010-2016. • Qualitative interviews exploring prescriber awareness and use of medicines safety information (Boston and Australia). Results Differences in regulatory policy among the European Medicines Agency, the US Food and Drug Administration, Health Canada, and the Therapeutic Goods Administration (TGA) included: their legislated authority for safety advisories, transparency, and interactions with pharmaceutical industry. SGLT2 inhibitor safety advice differed among regulators in number, timing, and strength. TGA advisories were issued for 20.5% of 73 safety concerns communicated by other regulators, for new drugs approved in Australia (2010-2016). Differences were not explained by the seriousness of safety concerns. Prescribers’ awareness of regulatory safety advisories was relatively low, particularly in Australia. While respecting regulators’ institutional authority, regulatory warnings may lack clinical authority. Conclusions There are considerable differences amongst the EMA, FDA, Health Canada and the TGA in policy and use of post-market safety advisories. Recommendations for improving safety and policy are discussed