Qualitative assessment of the clinical meaningfulness of MDS-UPDRS part III items in early-stage Parkinson's

Introduction Developers of disease-modifying therapies (DMTs) for early-stage Parkinson's are in dialogue with regulators to identify the relative merits of the Movement Disorder Society – Unified Parkinson's Disease Rating Scale (MDS-UPDRS) for detecting clinically meaningful changes in patients’ daily functioning during early-stage disease. We report the first qualitative assessment of MDS-UPDRS part III items’ clinical meaningfulness for use in DMT pivotal trials. Methods Semi-structured interviews were conducted with 40 patients and 20 movement disorder neurologists. Evidence was synthesized using an interpretation framework to evaluate items according to four appraisal components. Results Based on synthesized evidence for each appraisal component: Patient feedback indicated all items were at least somewhat meaningful to patients ; 12/18 items were classified as “highly meaningful” given their linkage to motor/daily activities functioning. See Interactive Supplement . 4/18 items were endorsed by >90% of neurologists as clinically relevant in early-stage Parkinson's (“highly relevant”). Evidence from neurologists was supportive of 6/18 items in terms of their usefulness for capturing disease progression (“highly useful”). Neurologist feedback suggested response option distinction/assessment specificity is inconsistent across items. Together, qualitative evidence endorsed the value of items 3.3 Rigidity, 3.4 Finger tapping, 3.5 Hand movements, 3.6 Pronation-supination, 3.7 Toe tapping, and 3.8 Leg agility across all four appraisal components. Conclusions A subset of limb-related rigidity/bradykinesia items may be most clinically meaningful for detecting changes in early-stage Parkinson's. Consolidation of quantitative data with evidence from this large qualitative sample will inform final decision-making for a primary efficacy outcome measure in DMT pivotal trials.