Abstract
BACKGROUND: 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. METHODOLOGY: 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. RESULTS: Following panel review, three items reached consensus (≥70% agreement of no revision required) and were included in the final measure: communication, alertness, and disruptive behaviors. To ensure caregivers can help clinicians complete the measure, and to establish levels of change in each item domain considered meaningful from their perspective, the three-item measure was cognitively debriefed with caregivers of individuals with DS or LGS. Caregivers showed that each item was understandable by describing their child using the descriptions provided in the measure and reported that items were relevant or important to assess in DS or LGS. Most caregivers reported that even a minimal change to their child's condition in each domain would be meaningful to them and their child. CONCLUSIONS: This CGI-I Non-seizure Symptoms measure represents relevant non-seizure outcomes considered important to individuals with DS or LGS and their families. The systematic development and refinement approach presented here supports its use in DS and LGS clinical trials.