LA METODOLOGIA PER LA VALUTAZIONE CLINICA DI NUOVI FARMACI ANTIEPILETTICI: I DATI DELL'ESPERIENZA

In recent years, increasing attention has been focused on the methodological approaches to be used for the evaluation of the clinical effects of antiepileptic drugs. Whereas it should be acknowledged that in certain phases of development useful information can be derived from alternative study designs, the controlled clinical trial still represents the keystone for the scientific demonstration of antiepileptic efficacy. Acute models which may provide valuable preliminary information are based on the assessment of EEG effects in patients with photosensitivity or frequent spontaneous interictal epileptiform abnormalities. Monitoring of the EEG is also valuable to assess therapeutic activity in patients with absence seizures. In other seizure types, conclusive demonstration of therapeutic efficacy requires the investigation of drug-induced changes in seizure frequency under controlled conditions. The randomized, placebo-controlled, double-blind cross-over design has been used frequently but it has intrinsic limitations, related mainly to the difficulty of excluding the occurrence of a sequence effect. Parallel group comparisons are currently preferred by many investigators in epilepsy drug trials but their results are also subject to interpretative problems. Although 'add-on' trials are still traditionally used in the early phases of development, there is an increasing tendency to perform monotherapy studies as early as this is ethically justified. Evaluation of literature data on the large number of trials carried out so far provides invaluable information which can be usefully applied for a rational planning of more powertul and informative studies.