Beyond maximum grade: key regulatory considerations in adverse event reporting.

Abstract

The therapeutic landscape of haematological malignancies has evolved rapidly with the introduction of targeted therapies, immunotherapies, and cell-based and gene-based interventions, leading to improved survival and, in some cases, long-term remission or cure. These advances have exposed limitations in traditional approaches to adverse event assessment and reporting. Building on the 2025 Lancet Haematology Series on adverse event reporting, this Series paper examines how proposed improvements in toxicity reporting can be operationalised and integrated into regulatory decision making across clinical trials and real-world settings. We focus on key challenges and opportunities related to measuring cumulative and long-term toxicity burden, incorporating patient-reported outcomes, improving adverse event reporting quality and efficiency in clinical trials, and leveraging real-world data, registries, and emerging technologies, such as artificial intelligence and natural language processing. We also discuss regulatory perspectives from international agencies, including the European Medicines Agency, the Japanese Pharmaceuticals and Medical Devices Agency, and the Australian Therapeutic Goods Administration.