To enhance interpretation of change on the composite Unified Huntington’s Disease Rating Scale (cUHDRS).

The cUHDRS was developed to assess disease progression in early-to-moderate manifest Huntington’s disease (HD). It consists of four assessments: Total Functional Capacity, Total Motor Score, Symbol Digit Modalities Test and Stroop Word Reading. Composite endpoints can be difficult to interpret; thus, qualitative and quantitative evidence was generated to aid interpretation of cUHDRS clinically meaningful change.

Qualitative evidence was reviewed to identify the importance of the concepts measured by each individual scale. This included a targeted literature review and patient/caregiver interviews. To better understand the relative contribution of each scale, meaningful change estimates were produced for each constituent measure, using a 1-category worsening on the CGI-S over 12 months (REGISTRY), and was compared to the denominators of the z-scores used in the cUHDRS scoring algorithm. To demonstrate how the cUHDRS score relates to daily functional ability, cUHDRS scores across manifest HD patients were split into deciles and the proportion of patients achieving each item on the Functional Assessment was calculated (ENROLL-HD). Finally, meaningful within-patient change estimates (over 12 months) were produced for the cUHDRS using 1-category worsening on CGI-S (REGISTRY) and a decline of 10 points on Independence Scale (ENROLL-HD) as anchors.

The cUHDRS score uses logical weighting for its constituent scales and produces a score that associates strongly with functional ability. A worsening of 1.2 points can be considered clinically meaningful.