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

Tracking 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. Individual 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. We 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. Further 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.

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Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Sheng Luo PhD. reports financial support was provided by Michael J Fox Foundation for Parkinson's Research. Sheng Luo, PhD reports a relationship with Bial that includes: funding grants. Glenn T Stebbins reports a relationship with Contera Pharma that includes: consulting or advisory. Glenn T. Stebbins reports a relationship with Eli Lilly and Company that includes: consulting or advisory. Glenn T. Stebbins reports a relationship with Neurocrine Biosciences Inc that includes: consulting or advisory. Glenn T. Stebbins reports a relationship with Pfizer that includes: consulting or advisory. Glenn T. Stebbins reports a relationship with Vima Therapeutics that includes: consulting or advisory. Tanya Simuni reports a relationship with AskBio that includes: consulting or advisory. Tanya Simuni reports a relationship with Amneal Pharmaceuticals that includes: consulting or advisory and funding grants. Tanya Simuni reports a relationship with Blue Rock Therapeutics that includes: consulting or advisory. Tanya Simuni reports a relationship with Denali Therapeutics Inc that includes: consulting or advisory. Tanya Simuni reports a relationship with Kyowa Kirin Inc that includes: consulting or advisory. Tanya Simuni reports a relationship with NeuroDerm Ltd that includes: consulting or advisory and funding grants. Tanya Simuni reports a relationship with Prevail Therapeutics that includes: consulting or advisory and funding grants. Tanya Simuni reports a relationship with Roche that includes: consulting or advisory and funding grants. Tanya Simuni reports a relationship with Sanofi that includes: consulting or advisory. Tanya Simuni reports a relationship with Sinopia Biosciences Inc that includes: consulting or advisory. Tanya Simuni reports a relationship with Konseka that includes: consulting or advisory. Tanya Simuni reports a relationship with Biogen that includes: funding grants. Jesse M Cedarbaum reports a relationship with MiCure that includes: consulting or advisory. Jesse M Cedarbaum reports a relationship with The Marcus Foundation that includes: funding grants. Jesse M Cedarbaum reports a relationship with Aligning Science Across Parkinson's that includes: funding grants. None If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.