What is a clinically important change in the Unified Dyskinesia Rating Scale in Parkinson's disease?

• We determined a Clinically Important Change (CIC) in phase II trials for dyskinesia in PD.
• We used a standard i.v. levodopa infusion model and the UDysRS part III Impairment scale to determine a CIC.
• A 2.32-point change was the CIC that best distinguished between perception and remission of dyskinesia.
• Patient-reported outcomes for dyskinesia can be applied in early human PD studies.
• Knowing the CIC in phase II trials will help finding new treatments for dyskinesia in PD.

IntroductionDyskinesia remain a significant problem in Parkinson Disease (PD). The translation process of novel drug targets for dyskinesia has proven difficult with several failures at phase III level. Determining the ‘clinically important change’ (CIC) for dyskinesia rating scales in phase II clinical trials may assist in optimizing drug development of new anti-dyskinetic treatments. We used a standard phase IIa acute levodopa infusion paradigm to determine for the first time the CIC for dyskinesia using the new UDysRS.MethodsWe performed a randomized, double-blind, placebo-controlled crossover study with eleven PD patients with stable bothersome dyskinesia. We used the following patient-reported clinically important events as CIC anchors: onset, maximum intensity, remission of dyskinesia. Objective dyskinesia scores using the UDysRS part III Impairment were determined at these same events by blinded video-rating. The CIC was determined using the ‘within-patient’ score change and a sensitivity- and specificity-based approach.ResultsPatients were most aware of ‘onset of dyskinesia’, followed by ‘remission of dyskinesia’. An 11.1-point median change (UDysRS Part III Impairment, p < 0.0001) was the CIC for patient-reported remission of dyskinesia from a practically defined-OFF state. A 2.32-point change (UDysRS Part III Impairment) had the best specificity and sensitivity to distinguish between patient-reported remission and perception of dyskinesia.ConclusionsIn this study, we provide the first report of a CIC for the UDysRS Part III Impairment. Early knowledge of a CIC may help inform the decision to advance into phase III trials and contribute for a higher yield of success in finding new anti-dyskinetic treatments.