BackgroundTo 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.ObjectiveTo estimate this threshold using two approaches: anchor-based analyses, and clinical consensus via a modified Delphi panel.MethodsFor 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.ResultsFor 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.ConclusionsResults 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.
Keywords: MDS-UPDRS Part III; Parkinson's disease; anchor-based analyses; modified Delphi method; motor progression threshold.
When the symptoms experienced by people with Parkison's disease are observed by others, such as doctors, they are called signs. The MDS-UPDRS Part III is a tool used by doctors to measure how severe motor signs are in people with Parkinson's disease. These signs include slowness, tremor, and rigidity. Doctors can use this tool whilst someone with Parkinson's disease is taking medication to manage their motor symptoms (known as ON medication state), or when the effect of the medication has worn off (known as OFF medication state). People with Parkinson's disease not receiving medication are in OFF medication state. It is important to assess symptoms/signs when the medication is not working to understand how the disease is progressing, and how new potential treatments may slow it down. In this study, the researchers wanted to understand what level of change in the MDS-UPDRS Part III score assessed in OFF medication state shows that the motor signs of someone with early disease have worsened. They looked at data from a clinical trial called PASADENA and found a change of 5 points on the scale to be meaningful for showing that motor signs were getting noticeably worse. They also asked a group of 13 expert doctors what they thought would be a meaningful change of points on this scale. The experts reached an agreement that a change of 5 points on the scale would be meaningful. This information can help doctors and researchers better understand and track Parkinson's disease in its early stages.