For the approval of any new medicinal product quality, safety and effi
cacy are essential requirements. This manuscript focusses on the clini
cal development programme. For the investigation of antiepileptic drug
s some international guidelines are of special importance. They are ba
sed on the knowledge of many experts and can be seen as a consensus on
minimal requirements; deviations must be thoroughly justified. In pha
ses II and III, usually randomised, double-blind add-on studies versus
placebo in patients with therapy-resistant seizures are used to get a
n impression of the efficacy and certain safety issues. A clear dose-r
esponse relationship may be a good indication for efficacy. However, a
ssessment of safety of the new product in add-on studies is difficult.
Therefore comparative phase III monotherapy studies versus establishe
d 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 p
layed 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 considere
d clinically relevant must be thoroughly argued. The definition of res
ponder should focus on major benefit for the patients involved.