Abstracts

Rationale: The original Total score of the Patient-Weighted Quality of Life in Epilepsy Questionnaire (QOLIE-31-P) is a weighted average of its 7 subscale scores using predefined published weights. This analysis was undertaken to explore use of individual patient subscale distress scores to weight the subscale score, using brivaracetam (BRV) data to test this hypothesis. Methods: QOLIE-31-P data were collected at baseline, end of maintenance or early discontinuation, in 3 pivotal studies of adjunctive BRV in adults with uncontrolled focal (partial-onset) seizures (NCT00490035; NCT00464269; NCT00504881). Original scores using standardized weights were recalculated using weights derived from patient-reported distress scores for each subscale ('new scores'). Mean Total score at each time point, mean change in Total score from baseline to last assessment, and mean subscale weights were reported for each study using the original and new scoring algorithms. Results: QOLIE-31-P Total scores using the original algorithm were consistently higher than (but largely parallel to) those using the new algorithm, regardless of treatment group, time points, and studies (Figure). Mean changes from baseline to last assessment were also similar for both algorithms (e.g. Week 4: 2.48 vs 2.80; Week 8: 3.12 vs 3.28; Week 12: 3.76 vs 4.01; last visit: 3.18 vs 3.60 for study NCT00490035, BRV group, original vs new algorithms). Subscale weights used in the original algorithm vs mean weights derived from distress scores in each study were different across all time points: energy/fatigue 0.12 vs 0.13?"0.14; emotional well-being 0.15 vs 0.12?"0.14; daily activities/social functioning 0.21 vs 0.14?"0.15; cognitive functioning 0.27 vs 0.13?"0.16; medication effects 0.03 vs 0.13; seizure worry 0.08 vs 0.16?"0.18; overall quality of life (QoL) 0.14 vs 0.14?"0.15. Efficacy-related subscales (e.g. seizure worry) were weighted slightly higher by patients in the new algorithm than weights in the original algorithm. Tolerability-related subscales showed varied differences vs weights in the original algorithm. Conclusions: Changing the QOLIE-31-P scoring algorithm to weight scores based on patient-reported distress scores resulted in consistently reduced Total scores across time points and studies. The new scoring algorithm had a varied effect on the weight of subscale scores in the calculation of the Total score. QOLIE-31-P results from clinical trials using the new algorithm could be difficult to interpret, as the new algorithm affects the balance among subscales when weightings change over time. Improvement in efficacy-related subscales with BRV treatment may lead to reduced patient distress; thereby reducing subscale weighting at the next assessment. This could cancel QoL improvement. Conversely, tolerability-related subscales may gain in distress, during treatment initiation. These results suggest that basing subscale weights on patient distress scores at each time point may be less optimal than presenting distress scores as a separate subscale. Funding: UCB Pharma funded