Evaluation of drug treatment outcome in epilepsy: a clinical perspective.

This article provides a comprehensive discussion of clinical outcome measures used in trials aimed at assessing the efficacy and safety of antiepileptic drugs. For efficacy, assessment still relies on careful documentation of changes in ictal activity as determined by seizure counts based on patients recall, direct clinical observation and (for absence seizures) EEG monitoring. In selected cases, assessment of seizure severity may also be indicated. The precise choice of outcome measures is largely dependent upon the specific trial design. In short-term regulatory trials, parameters such as time to nth seizure after randomization (or after achievement of target dosage) may be used as an index of antiepileptic efficacy, but the clinical relevance of such measures is questionable. In add-on trials in refractory patients, changes, in seizure counts and proportion of patients achieving 50%, 75% and 100% reduction in seizure frequency may be appropriate. For long-term monotherapy trials in newly diagnosed patients, proportion of patients achieving prolonged remission (1-year or longer) usually represents the most clinically meaningful efficacy outcome. Retention of patients on the allocated treatment over time is also a valuable measure, but it should be regarded as a composite endpoint because decision to continue treatment is dependent on both efficacy and tolerability. At present, there is no universally accepted method for evaluating side effects, particularly those which can not be documented objectively. Spontaneous reports of symptoms or use of specific checklists have advantages and disadvantages. Studies aimed at ensuring greater standardization in safety assessment should be encouraged, especially with respect to need of obtaining quantitative estimates, and information on both prevalence and incidence of side effects should be reported in all trials.