Develop an indication-specific Visual Analogue Scale (VAS) for Fragile X Syndrome (FXS) clinical trials.

Current outcome assessments for CNS-based trials have clear limitations which are further magnified in rare disease trials. There is a pressing need to create novel outcomes that have improved specificity, assess constructs proximal to the targeted mechanism, and include input from key stakeholders.

We integrated information from existing literature, our clinical experiences in FXS, and transcripts from qualitative interviews with caregivers of individuals with FXS, for relevant symptoms and domains of concern, to develop an indication-specific VAS.

Through our comprehensive and integrated approach, we created a two-part indication-specific VAS. Part 1 allows caregivers to generate their three primary concerns for the subject. This open-ended approach is family/patient-centered and allows caregivers’ concerns to be clearly captured. It also allows flexibility in consideration of the heterogeneity of the condition, which is a common theme across rare diseases. Building from prior work on conceptual models of outcome assessments, a trained clinician then maps each caregiver-generated concern onto one impact concept relevant to FXS (e.g., communication, activities of daily living, anxiety). Part 2 includes FXS-specific domains that were developed based on the literature review, clinical experience, and qualitative interviews with caregivers. The domains were also selected to cover constructs not well-measured with published scales. For both parts, caregivers rate, on the VAS, the subject’s behavior.

The novel methodological approach used to develop this indication-specific scale is highly relevant to rare disease trials, as it includes information from multiple perspectives, and allows for specific and granular assessment of target symptoms. The current work involves an indication-specific VAS, but the methodological approach can be used as a model for other rare disease trials, to continue to improve and refine existing outcome assessments and rating scales.