Outcome Measures for Disease-Modifying Trials in Parkinson’s Disease: Consensus Paper by the EJS ACT-PD Multi-Arm Multi-Stage Trial Initiative

Abstract

Background: Multi-arm, multi-stage (MAMS) platform trials can accelerate the identification of disease-modifying treatments for Parkinson’s disease (PD) but there is no current consensus on the optimal outcome measures (OM) for this approach. Objective: To provide an up-to-date inventory of OM for disease-modifying PD trials, and a framework for future selection of OM for such trials. Methods: As part of the Edmond J Safra Accelerating Clinical Trials in Parkinson Disease (EJS ACT-PD) initiative, an expert group with Patient and Public Involvement and Engagement (PPIE) representatives’ input reviewed and evaluated available evidence on OM for potential use in trials to delay progression of PD. Each OM was ranked based on aspects such as validity, sensitivity to change, participant burden and practicality for a multi-site trial. Review of evidence and expert opinion led to the present inventory. Results: An extensive inventory of OM was created, divided into: general, motor and non-motor scales, diaries and fluctuation questionnaires, cognitive, disability and health-related quality of life, capability, quantitative motor, wearable and digital, combined, resource use, imaging and wet biomarkers, and milestone-based. A framework for evaluation of OM is presented to update the inventory in the future. PPIE input highlighted the need for OM which reflect their experience of disease progression and are applicable to diverse populations and disease stages. Conclusion: We present a range of OM, classified according to a transparent framework, to aid selection of OM for disease-modifying PD trials, whilst allowing for inclusion or re-classification of relevant OM as new evidence emerges.

Long‐Term Medication Profiles in Parkinson's Disease under Subthalamic Deep Brain Stimulation: A Controlled Study

“…It would be tempting to speculate that subthalamic DBS has a disease‐modifying property indicated by the divergent LEDD trajectories of the two groups, as LEDD has been used in past clinical trials as a surrogate for such effects. 18 , 19 , 20 However, this is not conclusive from our data as (1) LEDDs differed between the two groups at baseline and (2) the divergent trajectories were only observed up to 10 years of follow‐up.…”

Embedding Patient Input in Outcome Measures for Long‐Term Disease‐Modifying Parkinson Disease Trials

“…An inventory of possible OM for such trials and a framework for future adaptation are reported elsewhere. 2…”