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The patient-centric development of an inclusive multi-arm multi-stage trial for Parkinson's disease.

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Τίτλος: The patient-centric development of an inclusive multi-arm multi-stage trial for Parkinson's disease.
Συγγραφείς: Zeissler ML; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne NE1 7RU, UK.; National Institute for Health and Care Research (NIHR) Biomedical Research Centre, Newcastle Upon Tyne NE4 5PL, UK.; Faculty of Health, University of Plymouth, Plymouth, PL6 8BT, UK., Burnell M; Medical Research Council Clinical Trials Unit, University College London, London WC1V 6LJ, UK., Barber TR; National Hospital for Neurology and Neurosurgery, London WC1N 3BG, UK., Ben-Shlomo Y; Population Health Sciences, University of Bristol, Bristol BS8 2PS, UK., Clarke CS; Research Department of Primary Care and Population Health, University College London, London NW3 2PF, UK., Collins S; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne NE1 7RU, UK.; National Institute for Health and Care Research (NIHR) Biomedical Research Centre, Newcastle Upon Tyne NE4 5PL, UK.; Faculty of Health, University of Plymouth, Plymouth, PL6 8BT, UK., Counsell C; Institute of Applied Health Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK., Duffen J; Cure Parkinson's, London W1W 6XX, UK., Edwards MJ; Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King's College London, University of London, London SE5 8AB, UK., Ellis-Doyle R; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK., Gonzalez-Robles C; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK., Hockey K; Expert by Experience, London, UK., Jewell A; Expert by Experience, London, UK., Lawton M; Population Health Sciences, University of Bristol, Bristol BS8 2PS, UK., Mills G; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK., Petty R; Faculty of Health, University of Plymouth, Plymouth, PL6 8BT, UK., Salathiel D; Expert by Experience, London, UK., Whipps S; Expert by Experience, London, UK., Whone A; School of Physiology, Pharmacology & Neuroscience, University of Bristol, Bristol BS8 1TD, UK., Gandhi S; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK., Carroll CB; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne NE1 7RU, UK.; National Institute for Health and Care Research (NIHR) Biomedical Research Centre, Newcastle Upon Tyne NE4 5PL, UK.; Faculty of Health, University of Plymouth, Plymouth, PL6 8BT, UK., Foltynie T; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK., Carpenter JR; Medical Research Council Clinical Trials Unit, University College London, London WC1V 6LJ, UK.; London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK., Barker RA; Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0QQ, UK.; Cambridge Stem Cell Institute  Cambridge, CB2 0AW, UK.
Συλλογικό Έργο: EJS ACT-PD Consortium, EJS ACT-PD Consortium
Πηγή: Brain communications [Brain Commun] 2026 Sep 22; Vol. 8 (5), pp. fcag349. Date of Electronic Publication: 2026 Sep 22 (Print Publication: 2026).
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Oxford University Press Country of Publication: England NLM ID: 101755125 Publication Model: eCollection Cited Medium: Internet ISSN: 2632-1297 (Electronic) Linking ISSN: 26321297 NLM ISO Abbreviation: Brain Commun Subsets: PubMed not MEDLINE
Imprint Name(s): Original Publication: [Oxford] : Oxford University Press, [2019]-
Περίληψη: There is an urgent need to speed up clinical trials for potential disease-modifying therapies that slow progression of Parkinson's disease. The Edmond J Safra Accelerating Clinical Trials in Parkinson's Disease (EJS ACT-PD) initiative set out to develop a patient-centric and inclusive platform trial using an innovative multi-arm, multi-stage (MAMS) design. We describe the work of the EJS ACT-PD consortium, which included over 90 experts including people with Parkinson's disease and care partners across six working groups. There were five key challenges: developing an efficient MAMS trial that meets regulatory requirements and is acceptable to people with Parkinson's; mitigating participant heterogeneity; reducing the risk of simultaneous arm closures; introducing different treatment regimens into a MAMS trial; and maximizing deliverability and accessibility of a MAMS trial. The final design was achieved through an iterative process and critical appraisal of data modelling exploring the impact of participant numbers per arm, trial durations, and endpoints. Every aspect of the design was informed by people with Parkinson's disease and care partners whose advice ensured acceptability, deliverability, and accessibility. The EJS ACT-PD trial will start with one placebo and three treatment arms, each with 400 participants, with a primary endpoint at 3 years powered to detect a 30% reduction in rate of progression of MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part I and II summed scores. Interim analyses will test for activity using the summed inverse variance weighted MDS-UPDRS Part I, II, and remote Part III scores. Ineffective arms will be closed, allowing participants to be re-randomized. Cost-effectiveness analysis is embedded. Further promising treatments will be added in future arms, subject to additional funding. To maximize accessibility and inclusivity, the trial will allow for study visits to be conducted remotely based on participant preference. National sites were selected to maximize accessibility and inclusive recruitment with core funded staff placed within experienced trial sites to support training and delivery at less experienced centres. By involving people with Parkinson's and care partners as well as stakeholders with broad scientific expertise, we have developed an inclusive MAMS trial which captures all stages of disease with partial remote delivery and clear design rationales that will significantly speed up the testing of disease-modifying therapies in Parkinson's disease.
(© The Author(s) 2026. Published by Oxford University Press on behalf of the Guarantors of Brain.)
Competing Interests: The authors have no financial disclosures or conflicts of interest to report in relation to this manuscript.
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Contributed Indexing: Investigator: T Foltynie; CB Carroll; RA Barker; JR Carpenter; Y Ben-Shlomo; MJ Edwards; A Whone; C Counsell; CS Clarke; M Burnell; K Hockey; A Jewell; P Gros; T Barber; A Schrag; RS Weil; CH Williams-Gray; MT Hu; L Rochester; P Piccini; H Zetterberg; A Noyce; M Lawton; A Jha; B Huxford; SH Millo; K Ray Chaudhuri; C Siu; M Bartlett; K Pushparatnam; D van Wamelen; AHV Schapira; O Bandmann; SRW Stott; GK Tofaris; E Sammler; H Mortiboys; L Wei; A Wong; S Duty; DT Dexter; E Jabbari; S Mullin; H Morris; D Breen; C Lambert; P Korlipara; M Silverdale; K Bhatia; AJ Yarnall; R Khengar; H Collins; F Hudson; R Croucher; S Bartolomeu-Pires; V Agarwal; J Allison; J Forbes; A Edwards; S Wonnacott; D Athauda; J Duffen; S Gandhi; E Henderson; J Black; K Matthews; V Greaves; E Deeson; L Miller; J Handley; H Matthews; K McFarthing; A Batla; N Bakshi; M Parry; N Ratcliffe; C Drew; N Kapur; A Navangul; S Ali; K Fletcher; C Bale; C Gonzalez-Robles; ML Zeissler; G Mills; R Ellis-Doyle; SL Collins; R Petty
Keywords: Parkinson’s disease; multi-arm multi-stage; patient and public involvement and engagement; trial design
Entry Date(s): Date Created: 20260928 Date Completed: 20260928 Latest Revision: 20260929
Update Code: 20260929
PubMed Central ID: PMC13616524
DOI: 10.1093/braincomms/fcag349
PMID: 42802821
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:2632-1297
DOI:10.1093/braincomms/fcag349