Epilepsy: Basic Designs, Sample Sizes and Experience with Large Multicentre Trials

Abstract

There have been hundreds, perhaps thousands, of studies assessing the efficacy of antiepileptic drugs (AEDs). Coatsworth [1] produced what could claim to be one of the first systematic reviews in medicine. Penry wrote in the foreword that “in keeping with the general philosophy of thorough documentation for better evaluation, a bibliography of publications judged unworthy of profile has been included, in addition to the bibliography of profiled articles”. Coatsworth identified articles from 64 different journals published between 1920 and 1970. Of 120 articles, 43% were based on fewer than 50 patients, 27% on more than 100 and nearly half did not report the duration of the study. Three were multiple crossover studies which employed randomisation, two of which were double-blind and one of which was single-blind. One hundred and six were single group studies with no information about patient evaluation in 74. He concluded “the average reported clinical trial may be characterised as a study of one drug given over a variable period to a group of 20–29 outpatients of differing seizure types. No controls are used, and the drug is varied in dosage by the needs of the patient. Seizure counts, types of seizure and side-effects are the data collected by an unreported evaluator using the clinical examination and laboratory data as his observational methods. The patients were evaluated before the trial and irregularly during the trial. The results of treatment are reported by the percentage of patients improved. In those studies with fair to good results, the investigator’s opinion is that the drug is a valuable addition to the present regimen of antiepileptics.”