Measuring What Matters: Further Validation for the Tardive Dyskinesia Impact Scale, a Novel Patient-Reported Outcome Measure in Valbenazine Clinical Trials.

Importance: Tardive dyskinesia (TD) is a persistent, potentially disabling, medication-induced movement disorder that has been underrecognized. Involuntary movements in TD have a substantial impact beyond movement on individuals with TD. To quantify TD impact and burden, the Tardive Dyskinesia Impact Scale (TDIS), a new, TD-specific, fit-for-purpose patient-reported outcome (PRO) measure, was developed. Objectives were to examine how TDIS contributes to understanding of TD burden and use of clinician-reported outcomes (ClinROs) and other PROs in clinical trials assessing effects of vesicular monoamine transporter 2 inhibitors on TD. TDIS analyses included assessment of correlations between TDIS and other clinical outcome assessments (PROs and ClinROs), estimation of the minimal clinically importance difference (MCID), and description of the change in TDIS individual items longitudinally and via item response theory. Observations: In KINECT trials, TDIS followed a similar trajectory to Abnormal Involuntary Movement Scale. An MCID of 4 points in TDIS was considered clinically meaningful. Item-level analyses showed that TDIS is reliable and precise for individual items. Most improved items in longitudinal analyses were self-consciousness (mean change: -1.24), embarrassment (-1.19), unwanted attention (-1.00), and mouth noises (-1.05), which exceeded the empirically derived item-level threshold for meaningful change (≥0.8). TDIS showed moderate correlation with treatment response as measured by Patient's Global Impression of Change (r=0.30) and Clinician's Global Impression of Change (r=0.34) scores. Conclusions and Relevance: TDIS is the only disease-specific PRO that has been validated in individuals with TD and complements ClinROs and other PROs by providing a comprehensive picture of TD impact beyond movement symptoms and can measure potential benefit of TD treatments.