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Titolo:
INNOVATIVE MONOTHERAPY TRIAL DESIGNS FOR THE ASSESSMENT OF ANTIEPILEPTIC DRUGS - A CRITICAL-APPRAISAL
Autore:
PERUCCA E;
Indirizzi:
UNIV PAVIA,DEPT PHARMACOL & THERAPEUT,CLIN PHARMACOL UNIT,PIAZZA BOTTA 10 I-27100 PAVIA ITALY
Titolo Testata:
European Journal of Clinical Pharmacology
fascicolo: 1, volume: 54, anno: 1998,
pagine: 1 - 5
SICI:
0031-6970(1998)54:1<1:IMTDFT>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
MULTICENTER COMPARATIVE TRIAL; NEWLY-DIAGNOSED EPILEPSY; PARTIAL-ONSET SEIZURES; TONIC CLONIC SEIZURES; SODIUM VALPROATE; FELBAMATE MONOTHERAPY; PRESURGICAL EVALUATION; CARBAMAZEPINE; PHENYTOIN; PHENOBARBITONE;
Keywords:
RANDOMIZED CONTROLLED TRIAL; ANTIEPILEPTIC DRUGS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
44
Recensione:
Indirizzi per estratti:
Citazione:
E. Perucca, "INNOVATIVE MONOTHERAPY TRIAL DESIGNS FOR THE ASSESSMENT OF ANTIEPILEPTIC DRUGS - A CRITICAL-APPRAISAL", European Journal of Clinical Pharmacology, 54(1), 1998, pp. 1-5

Abstract

Although new antiepileptic drugs are assessed initially by adding them to pre-existing treatment, it is only through monotherapy studies that their therapeutic potential can be characterized in full. Since long-term treatment with a placebo alone is ethically unacceptable in epilepsy, the classical monotherapy assessment of antiepileptic drugs involves randomization of newly diagnosed patients to treatment with the investigational drug or an established active control: followed by longterm monitoring to determine seizure remission rates and potential adverse effects. These protocols, however, are time-consuming and they are unlikely to demonstrate a superior efficacy), of the new agent overa comparator. In turn. a ''no-difference'' outcome in terms of seizure control does not allow one to exclude the possibility that all the treatments were equally ineffective: and may therefore not be regarded as proof of efficacy by regulatory authorities. To circumvent these problems, innovative designs for the early monotherapy evaluation of newantiepileptic drugs have been developed in recent years. These protocols, often referred to as ''regulatory trials'', involve short-term studies in which a full dosage of the investigational agent is compared with a placebo or with a suboptimal dosage of an active control (possibly the investigational agent itself). To minimize the risks associated with an ineffective treatment, provisions are made that require exitfrom the trial if seizures are inadequately controlled. Efficacy endpoints are time to the n(th) seizure and patients' retention on the allocated treatment. These studies have been conducted in patients undergoing discontinuation of treatment for presurgical assessment, in newlydiagnosed patients, and in patients whose concomitant anticonvulsantswere withdrawn for trial purposes. While these trials allow statistical demonstration of superior efficacy over a comparator, allocation ofpatients to ineffective or suboptimal treatments raises serious ethical concerns. The scientific value of these studies is also doubtful, because dosing schedules and duration of treatment are hardly relevant to routine clinical practice. Clinicians do not need to know whether anew drug given for a few days is better than nothing, but how that given for a few with established agents given in optimized dosages for long periods of time. The ethical and scientific justification for regulatory trials should be reassessed, and steps are urgently needed to stimulate implementation of long-term randomized comparative trials under conditions that are more relevant to clinical needs.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/11/20 alle ore 19:27:05