Objective: The Edmond J Safra Accelerating Clinical Trials in Parkinson Disease (PD) initiative (EJS ACT-PD) aims to accelerate the identification of disease modifying treatment for PD through a multiarm, multistage (MAMS) platform trial approach.

Background: Outcome measures (OM) in PD range from clinical scales and patient-reported OM, to imaging, wet biomarkers and digital OM. Apart from accurately reflecting disease progression, OM have to be acceptable to both regulatory agencies and patients, accessible and feasible.

Method: As part of EJS ACT-PD, an OM Working Group (WG) was established to reach consensus on a primary OM for a phase III MAMS trial in PD, as well as consider validated secondary OM, and interim OM for early stopping of futile treatment arms.

Results: Possible OM are being evaluated using a summary table of potentially relevant OM, including the MDS-UPDRS, PD non-motor scales, disability and health-related quality of life OM, timed tests, wearable and other digital OM, combined OM, health-economic measures, imaging and wet biomarkers.
The primary OM will also be based on a review of OM in previous neuroprotective trials in PD, analysis of the natural history of PD extracted from the Critical Path for Parkinson’s (CPP) Consortium’s database of studies in PD, Patient and Public Involvement and Engagement (PPIE) input, and consideration of regulatory issues. It will likely be a part or combination of parts of the MDS-UPDRS, given its familiarity, extensive validation, and acceptability to regulators. PPIE feedback highlights the need to improve upon this by developing  new milestone-based OM, to better reflect disease progression and suit the trial’s key purpose.
All OM need to consider the diversity of recruited patients and disease stages, and secondary OM will account for different patient characteristics. The interim OM might vary between treatment arms, to reflect target engagement and its potential translation into a disease-modifying effect.

Conclusion: The process for selecting OM appropriate for use in a MAMS platform trial in PD must be transparent, evidence-based and derived from consensus, to consider scientific and regulatory needs, patient and carer priorities, existing trial infrastructure and long-term sustainability. We present an adaptable model to include new evidence and OM, and allow for the testing of promising exploratory OM.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/challenges-in-outcome-measure-selection-in-multi-arm-multi-stage-clinical-trials-in-parkinson-disease/