Validating new symptom emergence as a patient-centric outcome measure for PD clinical trials.

Abstract

IntroductionTracking of emergent symptoms (ES) in de novo Parkinson Disease (PD) patients using Parts Ib and II of the MDS-UPDRS rating scale has been proposed as an outcome measure for PD clinical trials, based on observations in the Safety, Tolerability and Efficacy Assessment of Isradipine for PD (STEADY-PD3) clinical trial.MethodsIndividual item-level data was extracted from the SURE-PD3 study (coded as "PD-1018" in the C-path pooled dataset). We sought to confirm the observations made in the STEADY-PD3 dataset by analyzing data from a different Phase 3 clinical trial, the Phase 3 Study of Urate Elevation in Parkinson Disease (SURE-PD3), in which MDS-UPDRS was assessed more frequently than the 12-month intervals in STEADY-PD3, using similar methodology.ResultsWe were able to broadly validate results that demonstrated the frequency of ES, lack of impact of the introduction of symptomatic medications, and in the reduction in sample size required to demonstrate slowing of disease progression at a group level compared with the traditional total MDS-UPDRS summed score scoring methods. Counts of ES generally correlated modestly with summed MDS-UPRDS scores, both for the various sub-parts and for the overall scale as well. However, instability of individual item responses, especially during the first 6 months of observation complicated the assessment of the temporal evolution and stability of ES over time in the course of the SURE-PD3 study.ConclusionFurther validation using data sets with frequent administration of MDS-UPDRS is necessary to assess value of this approach as an outcome measure in PD clinical trials.