6.32 Assessing the Effect of Youth Involvement in Adverse Event Reporting during a Clinical Trial of Cannabidiol for Youth WITH AUTISM SPECTRUM DISORDER with Complex Verbal Language

Abstract

Clinical trials in youth with autism spectrum disorder (ASD) have typically neglected the voices of the youth themselves. Besides raising ethical questions, this may also affect the quality of the data obtained. We examined differences in adverse event (AE) reporting between parents and parent-child dyads in an open trial of cannabidiol (CBD). We hypothesized that including youth with ASD in AE reporting would increase the number of total and related AEs independently of response. Twelve youth (ages 7-14 years) with ASD (verbally fluent, IQ ≥ 80) completed a 6-week, Phase 2 open trial of 98% CBD (Epidiolex [V], 100 mg/mL) at 3 or 6 mg/kg/day; target N = 30. An individualized target symptom domain was identified at baseline by clinician consensus from informant report, rating scales, and clinical observation. Responders were defined by Clinical Global Impression Scale–Improvement (CGI-I) ≤ 2 in their target symptom domain. AEs were assessed by phone with parents (weeks 1, 3, 5) and via the UKU (Udvalg for Kliniske Under-sogelser) Side Effects Rating Scale administered by clinicians to dyads (weeks 2, 4, 6). Clinician consensus determined the relatedness of AEs to treatment. Disease-related events (DREs) were considered adverse if the severity or frequency increased. In this interim analysis, we identified response to treatment and AEs, contrasted AE rates (parents vs dyads), and examined the relationship between treatment response and AE profile. All 12 initial participants completed the trial; 4 responded (33%). Clinical Global Impression Scale–Severity (CGI–S) improved significantly from pre- (M = 4.83; SD = 0.39) to posttreatment (M = 3.92; SD = 0.90) (t11 = 3.53; p < 0.004). The most frequent AEs were tiredness (n = 5) and increased emotionality (n = 3). Of 47 total AEs, all were mild and 39 were first reported by dyads. Of 14 related AEs, 9 were first reported by dyads. One DRE occurred: increased severity of restricted, repetitive behaviors. The number of AEs reported by dyads (M = 3.25; SD = 3.14) compared to parents alone (M = 0.67; SD = 0.89) was significantly higher (t11 = 2.18; p = 0.017). Responders and nonresponders did not differ significantly in the number of total or related AEs. This interim analysis suggests that including the input of children with ASD in AE reporting captures a fuller profile of total and related AEs without compromising the study integrity or results.