Outcome measures for the assessment of new antiepileptic drugs.

For the approval of any new medicinal product quality, safety and efficacy are essential requirements. This manuscript focuses on the clinical development programme. For the investigation of antiepileptic drugs some international guidelines are of special importance. They are based on the knowledge of many experts and can be seen as a consensus on minimal requirements; deviations must be thoroughly justified. In phases II and III, usually randomised, double-blind add-on studies versus placebo in patients with therapy-resistant seizures are used to get an impression of the efficacy and certain safety issues. A clear dose-response relationship may be a good indication for efficacy. However, assessment of safety of the new product in add-on studies is difficult. Therefore comparative phase III monotherapy studies versus established antiepileptic drugs are essential to confirm the results obtained in add-on studies and are needed for a proper judgement of the efficacy/safety balance. The percentage of reduction of seizure frequency has played a dominating role as efficacy criterium. Nowadays preference is being given to the percentage responders. Which parameter is the most relevant for the given group of patients and what change is considered clinically relevant must be thoroughly argued. The definition of responder should focus on major benefit for the patients involved.