Category: Parkinson’s Disease: Clinical Trials
Objective: The Edmond J Safra ACT-PD initiative (EJS ACT-PD) is developing the first multi-arm multi-stage (MAMS) platform trial for potential disease modifying approaches for Parkinson’s disease in the UK.
Background: MAMS trials investigate multiple treatments in parallel allowing for early stopping and replacement of treatments that are ineffective at interim stages. Only treatments with sufficient efficacy will continue to phase III evaluation. This novel approach requires less time than multiple single stage trials, is cheaper and needs fewer participants on placebo medication.
Method: The EJS ACT-PD trial design (TD) working group (WG) will determine inclusion criteria, stratification methods, placebo allocation and blinding, duration and analysis approaches whilst ensuring inclusivity, minimization of bias and acceptability to patients, sponsors and regulators. The TD WG consists of Parkinson’s and MAMS trial experts, statisticians, epidemiologists, health economists and neurologists as well as three Patient and Public Involvement and Engagement (PPIE) representatives from the PPIE WG. Decisions are informed by an international Delphi study on trial design and modelling of data from existing data sets (e.g. Critical Path for Parkinson’s Consortium database (CODR), Oxford Parkinson’s Discovery Cohort (OPDC), and the Parkinsonism Incidence in North East Scotland (PINE).
Results: Initial discussions favour:
1. An inclusive trial for all with a diagnosis of PD, other than exclusions based on ability to participate, dementia, severe disability or major co-morbidities.
2. Randomisation stratified by age and disease stage.
3. A primary phase 3 outcome within 3-5 years; an interim outcome evaluation at 12-18 months.
The TD WG acknowledges the challenges inherent in such an approach. It will continue to explore the feasibility of these inclusion criteria and to further consider suitable stratification criteria to ensure appropriate balancing of treatment arms.
The TD WG works closely with the other 5 EJS ACT-PD WGs to consider issues regarding infrastructure, treatment selection, outcome measures, PPIE recommendations and funding strategies into the final MAMS protocol.
Conclusion: The creation of an inclusive trial for participants of any age and disease stage, is a key priority for people with Parkinson’s and their care partners. This poses challenges for trial design, but if successful/feasible will make trial outcomes more widely applicable to the real world.
To cite this abstract in AMA style:M-L. Zeissler, M. Burnell, T. Barber, Y. Ben-Shlomo, R. Chapman, C. Clarke, C. Counsell, M. Edwards, R. Ellis-Doyle, C. Gonzales-Robles, A. Jewell, G. Mills, J. Rudiger, D. Salathiel, S. Whipps, A. Whone, T. Foltynie, C. Carroll, R. Barker, J. Carpenter. Designing a multi-arm multi-stage trial for Parkinson’s [abstract]. Mov Disord. 2022; 37 (suppl 2). https://www.mdsabstracts.org/abstract/designing-a-multi-arm-multi-stage-trial-for-parkinsons/. Accessed September 22, 2023.
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