Development and Refinement of the Clinical Global Impression of Improvement for Non-seizure Symptoms Measure in Dravet Syndrome and Lennox-Gastaut Syndrome

Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) are rare, severe, childhood-onset developmental and epileptic encephalopathies characterized by treatment-resistant epilepsy and varying intellectual disability levels. Clinical outcome assessments (COAs) describe how patients feel, function, or survive, thus providing valuable information on a therapy’s efficacy and impact. Individuals with DS or LGS are heterogeneous, and many have limited verbal abilities and intellectual disability. Existing epilepsy-specific COA measures are unsuitable for DS and LGS clinical trials as many items demonstrate floor effects in these populations. As patients often cannot self-report symptoms, caregiver feedback on the measures’ relevance and understandability is critical when developing COAs to ensure their suitability for the intended population, and that caregivers can help clinicians complete the measures when necessary. We aimed to develop a novel clinician-reported outcomes measure, to be completed in consultation with caregivers at clinic visits, to assess non-seizure symptoms in individuals with DS or LGS using a Clinical Global Impression of Improvement (CGI–I) approach: the CGI-I Non-seizure Symptoms measure. A 13-item initial draft measure was reviewed by experts in a three-round Delphi panel to confirm each item’s relevance and refine descriptions, reduce overlap, and limit respondent burden. Following panel review, three items reached consensus (≥70