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

Cristina Gonzalez-Robles, Rimona S Weil, Daniel van Wamelen, Michèle Bartlett, Matthew Burnell, Caroline S Clarke, Michele T Hu, Brook Huxford, Ashwani Jha, Christian Lambert, Michael Lawton, Georgia Mills, Alastair Noyce, Paola Piccini, Kuhan Pushparatnam, Lynn Rochester, Carroll Siu, Caroline H Williams-Gray, Marie-Louise Zeissler, Henrik ZetterbergCamille B Carroll, Thomas Foltynie, Anette Schrag, EJS ACT-PD Consortium, Esther Sammler

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    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.

    Original languageEnglish
    Pages (from-to)1011-1033
    Number of pages23
    JournalJournal of Parkinson's Disease
    Volume13
    Issue number6
    DOIs
    Publication statusPublished - 8 Sept 2023

    Keywords

    • Humans
    • Consensus
    • Disease Progression
    • Outcome Assessment, Health Care
    • Parkinson Disease/drug therapy
    • Quality of Life

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