Evaluating health-related quality of life outcomes in clinical trials of antiepileptic drug therapy

Purpose: To provide an overview of condition-specific health-related quality of life (HRQL) assessment in clinical trials of antiepileptic drug (AED) therapy in adults. We describe the key measurement issues in HRQL evaluation, identify the instruments that have been used in this population, summarize the psychometric characteristics of these instruments, propose areas of HRQL most likely to change with treatment, and offer recommendations for further research. Methods: We conducted a comprehensive review of the literature using repeated searches of the MEDLINE database together with a review of reference lists from published papers. Psychometric information on the instruments was gathered from published literature. Results: Three epilepsy-specific HRQL measures were identified: the Epilepsy-Surgery Inventory (ESI-55), the Liverpool Assessment Battery, and the Quality of Life in Epilepsy Inventory (QOLIE, the 89-, 31-, and IO-item versions). One new measure, the Epilepsy Foundation of America (EFA) Concerns Index was also found. The psychometric characteristics of these instruments are discussed in relationship to performance or expected performance in a clinical trial setting. A review of descriptive studies and trials to date suggests that subscales reflecting the psychological and social domains of HRQL may be most sensitive to treatment designed to increase seizure-free periods, reduce seizure severity, and minimize undesirable side effects. Conclusions: Although evaluation of HRQL outcomes in clinical trials of epilepsy is still in its infancy, several reliable and valid condition-specific measures are available for understanding the impact of disease and treatment on HRQL. Further research is needed to determine minimal clinically important change scores and to assess the psychometric stability of measures across cultures and mode of administration (self, interview, telephone). Studies of patient preferences for health outcomes in the form of utilities will provide needed data for evaluating the cost-effectiveness of new treatments.