OBJECTIVES: KCNQ2-DEE is a rare, pediatric condition that manifests as several significant functional and developmental impairments. Disease-specific clinical outcome assessment (COA) instruments evaluate treatment benefits in the KCNQ2-DEE population and inform drug development, however no validated COAs have been developed for KCNQ2-DEE clinical trial applications at this time.

METHODS: A search was conducted on the ePROVIDE PROQOLID database to identify and summarize the characteristics of existing COA instruments relevant to children with KCNQ2-DEE. Characteristics evaluated included domains and items evaluated by the scale, respondent type (patient, caregiver, clinician, or observer), response scaling, and disease-specific or generic measure to explore potential suitability for use in clinical trials.

RESULTS: A total of 78 COAs were identified in the PROQOLID database from three relevant disease areas associated with KCNQ2-DEE: Epilepsy, Cerebral Palsy (CP), and Infantile Neuroaxonal Dystrophy (IAD). For Epilepsy, 17 PROs, 12 ObsROs, 1 ClinRO, and 2 Performance tests were identified. For CP, 8 PROs, 20 ObsROs, 6 ClinROs, 2 Performance tests, and 1 composite instrument was identified. For IAD, the database included 3 PRO and 6 ObsROs. All instruments were reviewed for suitability to measure treatments effects and disease progression in KCNQ2-DEE. Concepts of importance to outcomes researchers and/or health economic benefit ratings (e.g., the ability to walk, dress) were measured infrequently; whereas complex emotions, such as engagement or communication with parents was less frequently captured. Although numerous PROs were identified in the PROQOLID database, they are not appropriate for severely disabled children who are nonverbal and of low reading age. ObsROs were identified in each category and were the source of further evaluation.

CONCLUSIONS: No single COA identified in the review appeared to have robust content validity for assessing treatment benefit in KCNQ2-DEE. An indication-specific tool is needed to be developed that provides comprehensive and patient-centric outcomes measurement for KCNQ2-DEE patients and their caregivers.