OBJECTIVES: Fragile X Syndrome (FXS) is a rare X-linked condition associated with physical and behavioral manifestations. Qualitative research was conducted with both the caregivers of children with FXS participating in ZYN2-CL-016 (CONNECT-FX), a phase 3 study of ZYN002 (transdermal cannabidiol) versus placebo (NCT03614663), as well as in the real-world setting. The objective was to establish the content validity of the ABC-C_FXS to support the use of the Social Avoidance [SA], Irritability, and Socially Unresponsive/Lethargic [SUL] subscales to measure change in FXS behavioral problems.

METHODS: A caregiver-survey (CS) was administered at baseline in CONNECT-FX to identify the behavioral problems that most impacted their child and family (N=212). Concept elicitation (CE) (N=10) and cognitive interviews (N=25) were conducted with caregivers of children with FXS. Thematic analysis was conducted. Saturation of concepts (CS and CE interviews) and item comprehension (cognitive interviews) were examined.

RESULTS: Mean age was 10 [range 3-17] years and was consistent across the studies. The most frequently reported behavior problems in the CS were seeking isolation/preferring to be alone (43%), being socially unresponsive (43%), and aggression (42%). In the CE interviews, the most frequent behavioral problems described by caregivers were seeks isolation (70%), lack of interaction (60%), and aggression (60%). Saturation of concepts was reached in both the CS and CE interviews. Cognitive interviews showed that caregivers could understand and interpret the ABC-C_FXS and deemed its content relevant.

CONCLUSIONS: The CS and CE interviews demonstrated that behavior problems consistent with items in the ABC-C_FXS SA, SUL, and Irritability subscales were the most frequently reported by caregivers and the most impactful on the family. Content validity evidence from this qualitative research supports the use of ABC-C_FXS, with a focus on the SA, SUL, and Irritability subscales as a measure of efficacy in CONNECT-FX.