EVALUATION OF DRUG-TREATMENT OUTCOME IN EPILEPSY - A CLINICAL PERSPECTIVE

This article provides a comprehensive discussion of clinical outcome m easures used in trials aimed at assessing the efficacy and safety of a ntiepileptic drugs. For efficacy, assessment still relies on careful d ocumentation of changes in ictal as determined by seizure counts based on patientss recall, direct clinical observation and (for absence sei zures ) EEG monitoring. In selected cases, assessment of seizure sever ity may also be indicated. The precise choice of outcome measures is l argerly dependent upon the specific trial design. In short-term regula tory trials,parameters such as time to nth seizure after randomization (or after achievement of target dosage) may be used as an index of an tiepileptic efficacy, but the clinical relevance of such measures is q uestionable. In add-on trials in refractory patients, changes in seizu re counts and proportion of patients achieving 50%, 75% and 100% reduc tion in seizure frequency may be appropriate. For long-term monotherap y trials in newly diagnosed patients, proportion of patients achieving prolonged remission (1-year or longer) usually represents the most cl inically meaningful efficacy outcome, Retention of patients on the all ocated treatment over time is also a valuable measure, but it should b e regarded as a composite endpoint because decision to continue treatm ent is dependent on both efficacy and tolerability. At present, there is no universally accepted method for evaluating side effects, particu larly those which can not be documented objectively. Spontaneous repor ts of symptoms or use of specific checklists have advantages and disad vantages. Studies aimed at ensuring greater standardization in safety assesment should be encouraged, especially with respect to need of obt aining quantitative estimates, and information on both prevalence and incidence of side effects should be reported in all trials.