Background: Developmental and epileptic encephalopathies (DEE) are severe early-onset epilepsy syndromes with limited treatment options. The representativeness of racial and ethnic (RE) enrollment in DEE clinical trials remains unclear, raising concerns about the generalizability of findings and potential health disparities.
Objectives: This study assessed the RE distribution of participants in U.S. based DEE clinical trials in comparison to the RE distribution in general population data.
Methods: A retrospective, cross-sectional analysis was conducted using ClinicalTrials.gov to identify DEE clinical trials conducted only in the United States from 2009-2023. The reporting of RE in DEE trials was examined by key trial characteristics. For trials reporting RE data, the RE distributions were summarized and compared to population-based data obtained from the 2023 U.S. census using Fisher’s exact test. A subgroup analysis of RE distributions in pediatric trials ( < 18 years of age) was conducted.
Results: There were 42 DEE clinical trials and 31 (72.1%) reported RE data for 1,212 participants. The reporting of RE was highest in academic sponsored trials (n=7, 100%) and in trials for CDKL5 (n= 2, 100%) followed by Tuberous Sclerosis Complex (n=11, 85%), and Dravet Syndrome (n=3, 75%) disease outcomes. Overall, 86% were non-Hispanic, 85.7% White, 13.2% Hispanic, 4.6% Asian, 3.5% unreported, 3.0% multiracial, 2.4% Black, 0.4% Native Hawaiian/Pacific Islander (NH/PI), and 0.4% American Indian/Alaska Native (AI/AN). Compared to US Census data, White, non-Hispanic, and NH/PI were significantly overrepresented (+25%, +5.4% and +0.6%; p< 0.05). Alternatively, multiracial, Black, Hispanic, Asian, and AI/AN were significantly underrepresented (-9.8%, -9.7%, -6.2%, -3.4%, and -0.6%; p < 0.05). In pediatric trials (n = 13, 41.9%), 78.7% were White, 77.4% non-Hispanic, 20% Hispanic, 6.5% Asian, 6.5% unreported, 6.0% Black, 2.0% multiracial, 1.0% AI/AN, and 0.5% NH/PI. Similarly, White, non-Hispanic, and NH/PI were also significantly overrepresented. Alternatively, Asian participants were overrepresented (+1.3%, p < 0.05) compared to the general U.S. population. Multiracial, Black, Hispanic and AI/AN were significantly underrepresented when compared to U.S. census data (-17.0%, -7.2%, -6.3%, -0.2%; p< 0.05).
Conclusions: The majority of U.S. based DEE clinical trials are reporting RE enrollment; however, trials are significantly under-enrolling specific RE groups when compared to US census data. Similar enrollment disparities were observed among pediatric trials. Targeted strategies are needed to enhance diversity and advance equitable clinical trial enrollment for individuals with DEEs.
