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Towards a multi-arm multi-stage platform trial of disease modifying approaches in Parkinson’s disease

Lookup NU author(s): Dr Marie-Louise Zeissler, Professor Camille CarrollORCiD, Professor Lynn RochesterORCiD, Professor Alison Yarnall, Sally Collins



This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).


© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.An increase in the efficiency of clinical trial conduct has been successfully demonstrated in the oncology field, by the use of multi-arm, multi-stage trials allowing the evaluation of multiple therapeutic candidates simultaneously, and seamless recruitment to phase 3 for those candidates passing an interim signal of efficacy. Replicating this complex innovative trial design in diseases such as Parkinson’s disease is appealing, but in addition to the challenges associated with any trial assessing a single potentially disease modifying intervention in Parkinson’s disease, a multiarm platform trial must also specifically consider the heterogeneous nature of the disease, alongside the desire to potentially test multiple treatments with different mechanisms of action. In a multi-arm trial, there is a need to appropriately stratify treatment arms to ensure each are comparable with a shared placebo/standard of care arm; however, in Parkinson’s disease there may be a preference to enrich an arm with a subgroup of patients that may be most likely to respond to a specific treatment approach. The solution to this conundrum lies in having clearly defined criteria for inclusion in each treatment arm as well as an analysis plan that takes account of predefined subgroups of interest, alongside evaluating the impact of each treatment on the broader population of Parkinson’s disease patients. Beyond this, there must be robust processes of treatment selection, and consensus derived measures to confirm target engagement and interim assessments of efficacy, as well as consideration of the infrastructure needed to support recruitment, and the long-term funding and sustainability of the platform. This has to incorporate the diverse priorities of clinicians, triallists, regulatory authorities and above all the views of people with Parkinson’s disease.

Publication metadata

Author(s): Foltynie T, Gandhi S, Gonzalez-Robles C, Zeissler M-L, Mills G, Barker R, Carpenter J, Schrag A, Schapira A, Bandmann O, Mullin S, Duffen J, McFarthing K, Chataway J, Parmar M, Carroll C, Shlomo YB, Edwards M, Whone A, Counsell C, Clarke C, Burnell M, Salathiel D, Whipps S, Jewell A, Barber T, Weil R, Gray CW, Hu M, Rochester L, Piccini P, Zetterberg H, Noyce A, Chaudhuri R, Lawton M, Jha A, Siu C, Bartlett M, van Wamelen D, Stott S, Tofaris G, Sammler E, Mortiboys H, Wei L, Wong A, Duty S, Dexter D, Scurfield P, Jabbari E, Morris H, Breen D, Lambert C, Korlipara P, Silverdale M, Bhatia K, Yarnall A, Khengar R, Collins H, Hudson F, Baxendale G, Croucher R, Bartolomeur-Pires S, Allison J, Morgan A, Wonnacott S, Athauda D, Henderson E, Clegg S, Matthews K, Deeson E, Miller L, Handley J, Matthews H, Batla A, Bakshi N, Port B, Ellis-Doyle R, Collins SL, Rudiger J, Chapman R, Cedarbaum J, Lang A, Fiske B, Wyse R, Boxer A, Wilson D, Corvol JC, Harris J

Publication type: Review

Publication status: Published

Journal: Brain

Year: 2023

Volume: 146

Issue: 7

Pages: 2717-2722

Print publication date: 01/07/2023

Online publication date: 28/02/2023

Acceptance date: 08/01/2023

ISSN (print): 0006-8950

ISSN (electronic): 1460-2156

Publisher: Oxford University Press


DOI: 10.1093/brain/awad063

PubMed id: 36856727