Objective: To investigate the landscape of clinical outcome assessments (COAs) used in epileptic encephalopathies (EEs) and developmental epileptic encephalopathies (DEEs).

Background: EEs and DEEs are rare conditions characterized by difficult-to-treat seizures and intellectual or developmental disability. The heterogeneity of these conditions creates unique challenges for outcome measurement, particularly in clinical trials. To assess trends in the COA landscape, a targeted literature review was conducted to identify COAs used in EE and DEE clinical trials.

Design/Methods: A search was conducted in ClinicalTrials.gov to identify interventional studies in EEs and DEEs. Findings were supplemented by searches in PubMed (titles/abstracts only), PROLABELS, and Food and Drug Administration (FDA) COA guidance materials, pairing EE/DEE and COA search terms when applicable. No limits on year of publication were applied. All results were reviewed, and relevant data were extracted and analyzed to identify trends in COA use.

Results: The search identified 153 trials (ClinicalTrials.gov), 405 articles (PubMed), and 92 FDA drug labels (PROLABELS). Following screening, 105 trials, 26 article abstracts, and 19 labels met the criteria for data extraction. Excluding safety measures, 113 COAs were identified. Consistent with FDA guidance, seizure assessments and diaries were utilized most frequently, followed by clinician- or caregiver-rated global impression measures. Observer-reported outcomes and clinician-reported outcomes were more common than patient-reported outcomes. Approximately 25% of COAs were disease-specific. Additionally, common domains in COAs reviewed included cognition (n=22), motor functioning (n=14), multi-domains or quality of life (n=14), or communication (n=6). Several COAs utilized a global impression approach to assess within-patient change in domains, such as seizure severity or non-seizure concepts.

Conclusions: Importantly, disease-specific measures, including global impression items intended to capture change in multiple domains, were identified. These findings may suggest that a disease-specific global impression approach is becoming increasingly common in these heterogeneous conditions to accompany seizure assessments and diaries.