Dose-finding studies in clinical drug development.

A correct dose-finding study is of the utmost importance during clinical development of a new drug. It must define the no-effect dose and the mean effective and maximal effective doses. Then taking tolerability into account, the optimal therapeutic dose range can be selected. To define the dosage schedule the duration of action in man must be tested, if possible together with blood concentration measurements. An adequate dose-finding study shows the optimal doses for double-blind trials in Phase II and large scale trials in Phase III, thereby saving time and effort and reducing the number of patients required. The tendency of clinical experts to try to demonstrate superiority of one drug over another by using doses higher than patients really need must be resisted. The price paid in poor tolerability exceeds any potential benefits.