The following article is based on a poster presentation from ADPD 2025, “Scoring discrepancies in MDS-UPDRS part III in clinical trials of Parkinson’s Disease undergoing Independent Review.”
Download the poster here.
Parkinson’s Disease (PD) is a progressive neurological disorder affecting millions worldwide. Clinical trials are essential for developing new treatments and improving the quality of life for those with PD. The Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part III is a widely used tool to measure changes in motor function over time in these trials. Despite its reliability, motor assessments by experienced raters can still be prone to subjective interpretation and scoring errors.
To address this issue, Independent Review (IRev) is often used in clinical trials to independently verify primary endpoint data. This project evaluated IRev data collected in PD trials using the MDS-UPDRS part III, with the following objectives:
- Evaluate the frequency of MDS-UPDRS part III scoring discrepancies identified by independent reviewers in PD clinical trials.
- Identify items most prone to discrepancies during IRev.
- Assess whether the frequency of discrepant scores varies by disease severity measured by the MDS-UPDRS part III total score.
Methods
Aggregated MDS-UPDRS part III data from three multi-national double-blind clinical trials of PD were analyzed. The data included 20,239 assessments independently reviewed via video recording by a team of trained and calibrated clinicians (ICC 0.86). Assessments were divided into quartiles based on the severity of motor symptoms, and discrepancy rates were calculated for each severity group.
Results
Approximately 25% of assessments reviewed had at least one scoring discrepancy following IRev. Discrepancies were highest for Hoehn and Yahr (H&Y), finger tapping, and hand movements, and lowest for rest tremor amplitude items, freezing of gait, and speech. Assessments with lower part III total scores had the highest rate of discrepancies. Differences among severity quartiles were statistically significant, with discrepancy rates decreasing as motor symptom scores increased (F= 18.57; df = 3, 20159; p<.001).
Implications for Clinical Trials
Despite robust training, the high frequency of scoring discrepancies, particularly for subjects in earlier disease stage, underscores the need for continued efforts to improve the accuracy and reliability of motor assessments in PD clinical trials. This could involve additional training for raters, application of data surveillance methodologies, or even development of more objective assessment tools. Particular attention should be paid to assessments of subjects with milder motor symptoms, as these individuals are more likely to be rated inaccurately.
Conclusion
This study provides valuable insights into the frequency and nature of scoring discrepancies in MDS-UPDRS part III assessments in PD clinical trials. By addressing these issues, researchers can enhance the quality of data collected in PD trials, paving the way for more effective treatments and better outcomes for individuals living with Parkinson’s Disease.
References:
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