The evolution of antiepileptic drug development and regulation.

The early years of antiepileptic drug development were characterised by observation and serendipity, rather than a rational, targeted approach to drug development. Control of seizures was seen as the primary aim of therapy, with much less focus on safety and tolerability. However, experience with thalidomide in the 1960s brought safety to the fore, resulting in an era of much tighter regulatory control that still persists today. A direct consequence of this was an increased emphasis on the importance of evidence from randomised controlled trials. Despite the continuing reliance on randomised controlled trials for regulatory approval and the formulation of evidence-based guidelines, the modern era has seen an increasing acknowledgment of their limitations and the need for complementary sources of 'real-world' evidence. Such sources include registries and studies that are designed to provide a much broader assessment of a drug's overall effectiveness; for example, by incorporating patient-reported outcomes to assess the effects of treatment on quality of life or functional status. Such changes reflect a more patient-centric approach to treatment, since it is now recognised that epilepsy can only be effectively managed if patients' individual real-life needs are addressed, since a key to successful treatment is long-term compliance. Alongside these changes in approach, the modern era has witnessed important advances in antiepileptic drugs themselves, either through development of novel molecules, or targeted, structural improvements of older agents.