Defining Clinical Meaningfulness in Huntington's Disease

Background Minimal clinically important difference (MCID) represents the smallest within‐person change on an outcome measure considered meaningful to the patient. Anchor‐based MCID methods evaluate the relationship between changes in an outcome measure and the patient‐reported clinical importance of that change. Objective This study aims to estimate longitudinal MCID for clinically relevant outcome measures for individuals who have Stages 2 or 3 disease as measured by the Huntington's Disease Integrated Staging System (HD‐ISS). Methods Data were drawn from Enroll‐HD, a large global longitudinal, observational study and clinical research platform for HD family members. We analyzed HD participants (N = 11,070) by staging group using time frames ranging from 12 to 36 months. The anchor was the physical component summary score of the 12‐item short‐form health survey. HD‐relevant motor, cognitive, and functional outcome measures were independent, external criterion outcomes. Complex analysis was conducted using multiple, independent, linear mixed effect regression models with decomposition to calculate MCID for each external criterion by group. Results MCID estimates varied by progression stage. MCID estimates increased as stage progression increased and as the time frame increased. MCID values for key HD measures are provided. For example, starting in HD‐ISS stage 2, meaningful group change over 24 months equals an average increase of 3.6 or more points on the Unified Huntington's Disease Rating Scale Total Motor Score. Conclusions This is the first study to examine MCID estimation thresholds for HD. The results can be used to improve clinical interpretation of study outcomes and enable treatment recommendations to support clinical decision‐making and clinical trial methodology. © 2023 International Parkinson and Movement Disorder Society.