Estimation of and clinical consensus on the meaningful motor progression threshold on MDS-UPDRS Part III

Background To understand changes in the underlying progression of early Parkinson's disease, it is important to derive estimates of the threshold for meaningful motor progression on the MDS-UPDRS Part III in OFF medication state. Objective To estimate this threshold using two approaches: anchor-based analyses, and clinical consensus via a modified Delphi panel. Methods For the anchor-based analyses, data from a Phase II clinical trial were used. Mean and median MDS-UPDRS Part III change scores were calculated for those participants rated as ‘Minimally worse’ on the Clinical Global Impression of Improvement (using the first visit rated as ‘Minimally worse’ or worse, and at Weeks 24 and 52). Cumulative data up to Week 104 were used to assess the difference between motor progressors’ and non-progressors’ change scores on motor-related outcomes. For the modified Delphi panel, a panel of 13 expert clinicians received an online survey in two rounds and provided responses anonymously. Results For the anchor-based analyses, estimates of meaningful change ranged from 4−6 points. Numerically worse change scores were identified on motor-related outcomes for participants who had experienced motor progression compared with those who had not. For the modified Delphi panel, consensus was reached in Round 2, with 92% agreeing that 5 points is suitable to define a clinically meaningful motor progression threshold. Conclusions Results of the anchor-based analyses and modified Delphi panel were consistent, supporting a meaningful motor progression threshold of a worsening of 5 points on the MDS-UPDRS Part III (OFF medication state) in an early Parkinson's disease population.