Abstracts

Rationale: The SSQ provides a rich source of information for understanding changes in specific components of seizure severity and bothersomeness. In order to interpret SSQ results in a population of patients with refractory epilepsy, this analysis aimed at defining thresholds of minimal important change (MIC), allowing classification of patients by clinically meaningful response. Methods: Data from two placebo-controlled double-blind phase III trials of adjunctive lacosamide (SP754, SP755) in partial onset seizures were pooled. Patients completed the SSQ at baseline, and the SSQ and the Patient's Global Impression of Change (PGIC) at last assessment (end of maintenance [16/18 weeks] or early discontinuation). The SSQ is a 22-item questionnaire (addressing Aura/Warning, Ictal, and Post-Ictal events) that is scored as 3 composite scores and a total score. Responses range from 0 to 7 with higher scores indicating greater seizure severity. The PGIC is a 1-item instrument with seven ratings from ‘very much improved' (+3) to ‘very much worsened' (-3). To determine responsiveness of SSQ scores to the PGIC, mean SSQ score change from baseline to last assessment by PGIC rating was calculated. Standard anchor-based MIC thresholds were calculated, for each composite score, as the average of the absolute values of the mean score changes from baseline to last assessment associated with the PGIC categories of ‘much improved,' ‘minimally improved,' ‘much worsened,' and ‘minimally worsened' combined (-2, -1, +1 and +2). Results: A total of 776 patients had both SSQ and PGIC data at last assessment. Mean SSQ score changes differentiated among the PGIC ratings. Patients with a PGIC rating of ‘very much improved' (n=70) showed an average SSQ score change of -1; those with 'much improved‘ (n=208) changed to -0.7; and those with ‘minimally improved' (n=183) changed to -0.4. The MIC thresholds were 0.51, 0.39, 0.46, and 0.48 points for the 3 subscales (Activity during seizures, recovery, overall severity/recovery) and Total score, respectively; and 0.34, 0.48, and 0.42 for the emotional, physical and cognitive components of Recovery, respectively. The overall item, representing general impressions of severity and bother, had an MIC of 0.84. Conclusions: The SSQ showed clear differentiation among PGIC improvement ratings. The estimated MIC thresholds for subscales ranged from 0.34 to 0.84, with 0.48 points for the Total score, which averages all seizure components. These MIC data reflect the degree of change in SSQ scores that represent clinically meaningful change from the patients' perspectives, and which can be used in refractory patients to define treatment responders. Sponsored by UCB.