Academic Journal
Προβολή σε EDS

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

Λεπτομέρειες βιβλιογραφικής εγγραφής
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.
References: Mov Disord. 2024 Feb;39(2):433-438. (PMID: 38140767)
J Parkinsons Dis. 2021;11(3):905-908. (PMID: 33843698)
Neurotherapeutics. 2020 Oct;17(4):1724-1735. (PMID: 33150545)
J Neurol Neurosurg Psychiatry. 2007 Aug;78(8):819-24. (PMID: 17098842)
Neurology. 2018 Sep 4;91(10):e894-e905. (PMID: 30089615)
Lancet Neurol. 2024 Nov;23(11):1097-1107. (PMID: 39307154)
Mov Disord. 2023 Jul;38(7):1363-1364. (PMID: 37087725)
Ann Intern Med. 2020 May 5;172(9):591-598. (PMID: 32227247)
Handb Exp Pharmacol. 2014;225:139-47. (PMID: 25304530)
Future Healthc J. 2021 Jul;8(2):e243-e250. (PMID: 34286192)
Neurorehabil Neural Repair. 2023 May;37(5):328-352. (PMID: 37166181)
J Neurol Neurosurg Psychiatry. 2016 Sep;87(9):1034-6. (PMID: 26800710)
NPJ Parkinsons Dis. 2022 Mar 18;8(1):28. (PMID: 35304493)
Neurology. 2007 Jan 2;68(1):20-8. (PMID: 17200487)
Lancet Neurol. 2017 Nov;16(11):908-916. (PMID: 28958801)
Mov Disord. 2023 Sep;38(9):1716-1727. (PMID: 37400277)
N Engl J Med. 1993 Jan 21;328(3):176-83. (PMID: 8417384)
Mov Disord. 2021 Aug;36(8):1964-1967. (PMID: 33942376)
Mov Disord. 2023 Feb;38(2):342-347. (PMID: 36480107)
Mov Disord. 2007 Oct 15;22(13):1839-51; quiz 1988. (PMID: 17595026)
J Parkinsons Dis. 2015;5(4):947-59. (PMID: 26485428)
J Parkinsons Dis. 2025 Feb;15(1):6-18. (PMID: 39973478)
JAMA. 2015 Feb 10;313(6):584-93. (PMID: 25668262)
Stat Med. 2003 Mar 15;22(5):705-26. (PMID: 12587101)
Neurology. 2016 Apr 12;86(15):1400-1407. (PMID: 26865518)
Neurol Sci. 2018 Nov;39(11):1971-1976. (PMID: 30109466)
Contemp Clin Trials. 2021 Oct;109:106515. (PMID: 34329779)
Neurology. 2014 Jan 28;82(4):308-16. (PMID: 24363137)
Ther Innov Regul Sci. 2020 Nov;54(6):1522-1533. (PMID: 32691362)
Mov Disord. 2012 Sep 1;27(10):1239-42. (PMID: 22886777)
Mov Disord Clin Pract. 2018 Jan-Feb;5(1):47-53. (PMID: 29662921)
Lancet Public Health. 2020 Oct;5(10):e551-e567. (PMID: 33007212)
NPJ Parkinsons Dis. 2020 Jul 9;6:15. (PMID: 32665974)
BMJ Open. 2022 Mar 10;12(3):e055615. (PMID: 35273052)
Mov Disord. 2009 Apr 15;24(5):647-54. (PMID: 19117366)
J Parkinsons Dis. 2022;12(5):1591-1604. (PMID: 35466952)
Neurology. 2006 Mar 14;66(5):664-71. (PMID: 16481597)
J Parkinsons Dis. 2024;14(5):899-912. (PMID: 39031388)
Mov Disord. 2021 Jan;36(1):106-117. (PMID: 33002231)
BMJ Open. 2022 Jul 7;12(7):e064173. (PMID: 35798516)
Mov Disord. 2008 Nov 15;23(15):2129-70. (PMID: 19025984)
Brain. 2023 Jul 3;146(7):2717-2722. (PMID: 36856727)
Brain. 2020 Aug 1;143(8):2490-2501. (PMID: 32844196)
Medicina (Kaunas). 2024 Jun 09;60(6):. (PMID: 38929575)
J Parkinsons Dis. 2023;13(6):1011-1033. (PMID: 37545260)
Int Rev Neurobiol. 2018;139:357-378. (PMID: 30146054)
Mov Disord. 2019 Oct;34(10):1480-1487. (PMID: 31291488)
NIHR Open Res. 2023 Dec 18;3:37. (PMID: 39139271)
Nat Med. 2023 Nov;29(11):2682-2683. (PMID: 37710137)
Trials. 2020 Aug 1;21(1):694. (PMID: 32738919)
J Neurol. 2013 Jan;260(1):228-36. (PMID: 22865238)
Front Aging Neurosci. 2023 Mar 16;15:1109914. (PMID: 37009459)
Trials. 2009 Jun 11;10:39. (PMID: 19519885)
Mov Disord Clin Pract. 2017 Mar 11;4(4):536-544. (PMID: 30363418)
Mov Disord. 2024 Sep;39(9):1468-1477. (PMID: 38925541)
Neurology. 2022 May 3;98(18):754-764. (PMID: 35321926)
Qual Life Res. 2016 Jan;25(1):81-8. (PMID: 26264781)
JAMA. 2021 Sep 14;326(10):926-939. (PMID: 34519802)
Clin Trials. 2017 Oct;14(5):451-461. (PMID: 28830236)
Neurology. 1985 Apr;35(4):522-6. (PMID: 3982637)
Eur J Neurol. 2015 Mar;22(3):457-63. (PMID: 24888502)
J Parkinsons Dis. 2018;8(s1):S3-S8. (PMID: 30584159)
BMC Neurol. 2016 Jun 16;16:92. (PMID: 27312378)
J Parkinsons Dis. 2020;10(2):413-428. (PMID: 32116263)
J Parkinsons Dis. 2024;14(4):809-821. (PMID: 38701161)
Prog Neurobiol. 2011 Dec;95(4):629-35. (PMID: 21930184)
Parkinsonism Relat Disord. 2014 Jan;20(1):99-105. (PMID: 24183678)
Trials. 2012 Sep 15;13:168. (PMID: 22978443)
J Neurol Neurosurg Psychiatry. 2018 Dec;89(12):1279-1287. (PMID: 30464029)
Mov Disord. 2025 Jul;40(7):1307-1317. (PMID: 40249275)
J Parkinsons Dis. 2022;12(1):437-452. (PMID: 34719511)
J Neurol Neurosurg Psychiatry. 2011 Oct;82(10):1112-8. (PMID: 21593513)
Brain. 2004 Mar;127(Pt 3):550-60. (PMID: 14691062)
Lancet Neurol. 2019 May;18(5):459-480. (PMID: 30879893)
Mov Disord. 2018 May;33(5):771-782. (PMID: 29572948)
J Parkinsons Dis. 2023;13(8):1343-1356. (PMID: 38007672)
JAMA Neurol. 2014 Feb;71(2):141-50. (PMID: 24366103)
J Infect Dis. 2012 May 15;205 Suppl 2:S250-7. (PMID: 22448027)
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
FullText Text:
  Availability: 0
CustomLinks:
  – Url: https://resolver.ebsco.com/c/fiv2js/result?sid=EBSCO:cmedm&genre=article&issn=26321297&ISBN=&volume=8&issue=5&date=20260922&spage=fcag349&pages=fcag349&title=Brain communications&atitle=The%20patient-centric%20development%20of%20an%20inclusive%20multi-arm%20multi-stage%20trial%20for%20Parkinson%27s%20disease.&aulast=Zeissler%20ML&id=DOI:10.1093/braincomms/fcag349
    Name: Full Text Finder (for New FTF UI) (ns324271)
    Category: fullText
    Text: Full Text Finder
    MouseOverText: Full Text Finder
Header DbId: cmedm
DbLabel: MEDLINE
An: 42802821
AccessLevel: 3
PubType: Academic Journal
PubTypeId: academicJournal
PreciseRelevancyScore: 0
IllustrationInfo
Items – Name: Title
  Label: Title
  Group: Ti
  Data: The patient-centric development of an inclusive multi-arm multi-stage trial for Parkinson's disease.
– Name: Author
  Label: Authors
  Group: Au
  Data: <searchLink fieldCode="AU" term="%22Zeissler+ML%22">Zeissler ML</searchLink>; 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.<br /><searchLink fieldCode="AU" term="%22Burnell+M%22">Burnell M</searchLink>; Medical Research Council Clinical Trials Unit, University College London, London WC1V 6LJ, UK.<br /><searchLink fieldCode="AU" term="%22Barber+TR%22">Barber TR</searchLink>; National Hospital for Neurology and Neurosurgery, London WC1N 3BG, UK.<br /><searchLink fieldCode="AU" term="%22Ben-Shlomo+Y%22">Ben-Shlomo Y</searchLink>; Population Health Sciences, University of Bristol, Bristol BS8 2PS, UK.<br /><searchLink fieldCode="AU" term="%22Clarke+CS%22">Clarke CS</searchLink>; Research Department of Primary Care and Population Health, University College London, London NW3 2PF, UK.<br /><searchLink fieldCode="AU" term="%22Collins+S%22">Collins S</searchLink>; 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.<br /><searchLink fieldCode="AU" term="%22Counsell+C%22">Counsell C</searchLink>; Institute of Applied Health Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK.<br /><searchLink fieldCode="AU" term="%22Duffen+J%22">Duffen J</searchLink>; Cure Parkinson's, London W1W 6XX, UK.<br /><searchLink fieldCode="AU" term="%22Edwards+MJ%22">Edwards MJ</searchLink>; Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King's College London, University of London, London SE5 8AB, UK.<br /><searchLink fieldCode="AU" term="%22Ellis-Doyle+R%22">Ellis-Doyle R</searchLink>; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.<br /><searchLink fieldCode="AU" term="%22Gonzalez-Robles+C%22">Gonzalez-Robles C</searchLink>; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.<br /><searchLink fieldCode="AU" term="%22Hockey+K%22">Hockey K</searchLink>; Expert by Experience, London, UK.<br /><searchLink fieldCode="AU" term="%22Jewell+A%22">Jewell A</searchLink>; Expert by Experience, London, UK.<br /><searchLink fieldCode="AU" term="%22Lawton+M%22">Lawton M</searchLink>; Population Health Sciences, University of Bristol, Bristol BS8 2PS, UK.<br /><searchLink fieldCode="AU" term="%22Mills+G%22">Mills G</searchLink>; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.<br /><searchLink fieldCode="AU" term="%22Petty+R%22">Petty R</searchLink>; Faculty of Health, University of Plymouth, Plymouth, PL6 8BT, UK.<br /><searchLink fieldCode="AU" term="%22Salathiel+D%22">Salathiel D</searchLink>; Expert by Experience, London, UK.<br /><searchLink fieldCode="AU" term="%22Whipps+S%22">Whipps S</searchLink>; Expert by Experience, London, UK.<br /><searchLink fieldCode="AU" term="%22Whone+A%22">Whone A</searchLink>; School of Physiology, Pharmacology & Neuroscience, University of Bristol, Bristol BS8 1TD, UK.<br /><searchLink fieldCode="AU" term="%22Gandhi+S%22">Gandhi S</searchLink>; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.<br /><searchLink fieldCode="AU" term="%22Carroll+CB%22">Carroll CB</searchLink>; 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.<br /><searchLink fieldCode="AU" term="%22Foltynie+T%22">Foltynie T</searchLink>; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.<br /><searchLink fieldCode="AU" term="%22Carpenter+JR%22">Carpenter JR</searchLink>; Medical Research Council Clinical Trials Unit, University College London, London WC1V 6LJ, UK.; London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK.<br /><searchLink fieldCode="AU" term="%22Barker+RA%22">Barker RA</searchLink>; Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0QQ, UK.; Cambridge Stem Cell Institute  Cambridge, CB2 0AW, UK.
– Name: AuthorCorporate
  Label: Corporate Authors
  Group: Au
  Data: <searchLink fieldCode="CA" term="%22EJS+ACT-PD+Consortium%22">EJS ACT-PD Consortium</searchLink><br /><searchLink fieldCode="CA" term="%22EJS+ACT-PD+Consortium%22">EJS ACT-PD Consortium</searchLink>
– Name: TitleSource
  Label: Source
  Group: Src
  Data: <searchLink fieldCode="JN" term="%22101755125%22">Brain communications</searchLink> [Brain Commun] 2026 Sep 22; Vol. 8 (5), pp. fcag349. <i>Date of Electronic Publication: </i>2026 Sep 22 (<i>Print Publication: </i>2026).
– Name: TypePub
  Label: Publication Type
  Group: TypPub
  Data: Journal Article
– Name: Language
  Label: Language
  Group: Lang
  Data: English
– Name: TitleSource
  Label: Journal Info
  Group: Src
  Data: <i>Publisher: </i><searchLink fieldCode="PB" term="%22Oxford+University+Press%22">Oxford University Press </searchLink><i>Country of Publication: </i>England <i>NLM ID: </i>101755125 <i>Publication Model: </i>eCollection <i>Cited Medium: </i>Internet <i>ISSN: </i>2632-1297 (Electronic) <i>Linking ISSN: </i><searchLink fieldCode="IS" term="%2226321297%22">26321297 </searchLink><i>NLM ISO Abbreviation: </i>Brain Commun <i>Subsets: </i>PubMed not MEDLINE
– Name: PublisherInfo
  Label: Imprint Name(s)
  Group: PubInfo
  Data: <i>Original Publication</i>: [Oxford] : Oxford University Press, [2019]-
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: 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.<br /> (© The Author(s) 2026. Published by Oxford University Press on behalf of the Guarantors of Brain.)
– Name: Abstract
  Label: Competing Interests
  Group: Ab
  Data: The authors have no financial disclosures or conflicts of interest to report in relation to this manuscript.
– Name: Ref
  Label: References
  Group: RefInfo
  Data: Mov Disord. 2024 Feb;39(2):433-438. (PMID: <searchLink fieldCode="PM" term="%2238140767%22">38140767)</searchLink><br />J Parkinsons Dis. 2021;11(3):905-908. (PMID: <searchLink fieldCode="PM" term="%2233843698%22">33843698)</searchLink><br />Neurotherapeutics. 2020 Oct;17(4):1724-1735. (PMID: <searchLink fieldCode="PM" term="%2233150545%22">33150545)</searchLink><br />J Neurol Neurosurg Psychiatry. 2007 Aug;78(8):819-24. (PMID: <searchLink fieldCode="PM" term="%2217098842%22">17098842)</searchLink><br />Neurology. 2018 Sep 4;91(10):e894-e905. (PMID: <searchLink fieldCode="PM" term="%2230089615%22">30089615)</searchLink><br />Lancet Neurol. 2024 Nov;23(11):1097-1107. (PMID: <searchLink fieldCode="PM" term="%2239307154%22">39307154)</searchLink><br />Mov Disord. 2023 Jul;38(7):1363-1364. (PMID: <searchLink fieldCode="PM" term="%2237087725%22">37087725)</searchLink><br />Ann Intern Med. 2020 May 5;172(9):591-598. (PMID: <searchLink fieldCode="PM" term="%2232227247%22">32227247)</searchLink><br />Handb Exp Pharmacol. 2014;225:139-47. (PMID: <searchLink fieldCode="PM" term="%2225304530%22">25304530)</searchLink><br />Future Healthc J. 2021 Jul;8(2):e243-e250. (PMID: <searchLink fieldCode="PM" term="%2234286192%22">34286192)</searchLink><br />Neurorehabil Neural Repair. 2023 May;37(5):328-352. (PMID: <searchLink fieldCode="PM" term="%2237166181%22">37166181)</searchLink><br />J Neurol Neurosurg Psychiatry. 2016 Sep;87(9):1034-6. (PMID: <searchLink fieldCode="PM" term="%2226800710%22">26800710)</searchLink><br />NPJ Parkinsons Dis. 2022 Mar 18;8(1):28. (PMID: <searchLink fieldCode="PM" term="%2235304493%22">35304493)</searchLink><br />Neurology. 2007 Jan 2;68(1):20-8. (PMID: <searchLink fieldCode="PM" term="%2217200487%22">17200487)</searchLink><br />Lancet Neurol. 2017 Nov;16(11):908-916. (PMID: <searchLink fieldCode="PM" term="%2228958801%22">28958801)</searchLink><br />Mov Disord. 2023 Sep;38(9):1716-1727. (PMID: <searchLink fieldCode="PM" term="%2237400277%22">37400277)</searchLink><br />N Engl J Med. 1993 Jan 21;328(3):176-83. (PMID: <searchLink fieldCode="PM" term="%228417384%22">8417384)</searchLink><br />Mov Disord. 2021 Aug;36(8):1964-1967. (PMID: <searchLink fieldCode="PM" term="%2233942376%22">33942376)</searchLink><br />Mov Disord. 2023 Feb;38(2):342-347. (PMID: <searchLink fieldCode="PM" term="%2236480107%22">36480107)</searchLink><br />Mov Disord. 2007 Oct 15;22(13):1839-51; quiz 1988. (PMID: <searchLink fieldCode="PM" term="%2217595026%22">17595026)</searchLink><br />J Parkinsons Dis. 2015;5(4):947-59. (PMID: <searchLink fieldCode="PM" term="%2226485428%22">26485428)</searchLink><br />J Parkinsons Dis. 2025 Feb;15(1):6-18. (PMID: <searchLink fieldCode="PM" term="%2239973478%22">39973478)</searchLink><br />JAMA. 2015 Feb 10;313(6):584-93. (PMID: <searchLink fieldCode="PM" term="%2225668262%22">25668262)</searchLink><br />Stat Med. 2003 Mar 15;22(5):705-26. (PMID: <searchLink fieldCode="PM" term="%2212587101%22">12587101)</searchLink><br />Neurology. 2016 Apr 12;86(15):1400-1407. (PMID: <searchLink fieldCode="PM" term="%2226865518%22">26865518)</searchLink><br />Neurol Sci. 2018 Nov;39(11):1971-1976. (PMID: <searchLink fieldCode="PM" term="%2230109466%22">30109466)</searchLink><br />Contemp Clin Trials. 2021 Oct;109:106515. (PMID: <searchLink fieldCode="PM" term="%2234329779%22">34329779)</searchLink><br />Neurology. 2014 Jan 28;82(4):308-16. (PMID: <searchLink fieldCode="PM" term="%2224363137%22">24363137)</searchLink><br />Ther Innov Regul Sci. 2020 Nov;54(6):1522-1533. (PMID: <searchLink fieldCode="PM" term="%2232691362%22">32691362)</searchLink><br />Mov Disord. 2012 Sep 1;27(10):1239-42. (PMID: <searchLink fieldCode="PM" term="%2222886777%22">22886777)</searchLink><br />Mov Disord Clin Pract. 2018 Jan-Feb;5(1):47-53. (PMID: <searchLink fieldCode="PM" term="%2229662921%22">29662921)</searchLink><br />Lancet Public Health. 2020 Oct;5(10):e551-e567. (PMID: <searchLink fieldCode="PM" term="%2233007212%22">33007212)</searchLink><br />NPJ Parkinsons Dis. 2020 Jul 9;6:15. (PMID: <searchLink fieldCode="PM" term="%2232665974%22">32665974)</searchLink><br />BMJ Open. 2022 Mar 10;12(3):e055615. (PMID: <searchLink fieldCode="PM" term="%2235273052%22">35273052)</searchLink><br />Mov Disord. 2009 Apr 15;24(5):647-54. (PMID: <searchLink fieldCode="PM" term="%2219117366%22">19117366)</searchLink><br />J Parkinsons Dis. 2022;12(5):1591-1604. (PMID: <searchLink fieldCode="PM" term="%2235466952%22">35466952)</searchLink><br />Neurology. 2006 Mar 14;66(5):664-71. (PMID: <searchLink fieldCode="PM" term="%2216481597%22">16481597)</searchLink><br />J Parkinsons Dis. 2024;14(5):899-912. (PMID: <searchLink fieldCode="PM" term="%2239031388%22">39031388)</searchLink><br />Mov Disord. 2021 Jan;36(1):106-117. (PMID: <searchLink fieldCode="PM" term="%2233002231%22">33002231)</searchLink><br />BMJ Open. 2022 Jul 7;12(7):e064173. (PMID: <searchLink fieldCode="PM" term="%2235798516%22">35798516)</searchLink><br />Mov Disord. 2008 Nov 15;23(15):2129-70. (PMID: <searchLink fieldCode="PM" term="%2219025984%22">19025984)</searchLink><br />Brain. 2023 Jul 3;146(7):2717-2722. (PMID: <searchLink fieldCode="PM" term="%2236856727%22">36856727)</searchLink><br />Brain. 2020 Aug 1;143(8):2490-2501. (PMID: <searchLink fieldCode="PM" term="%2232844196%22">32844196)</searchLink><br />Medicina (Kaunas). 2024 Jun 09;60(6):. (PMID: <searchLink fieldCode="PM" term="%2238929575%22">38929575)</searchLink><br />J Parkinsons Dis. 2023;13(6):1011-1033. (PMID: <searchLink fieldCode="PM" term="%2237545260%22">37545260)</searchLink><br />Int Rev Neurobiol. 2018;139:357-378. (PMID: <searchLink fieldCode="PM" term="%2230146054%22">30146054)</searchLink><br />Mov Disord. 2019 Oct;34(10):1480-1487. (PMID: <searchLink fieldCode="PM" term="%2231291488%22">31291488)</searchLink><br />NIHR Open Res. 2023 Dec 18;3:37. (PMID: <searchLink fieldCode="PM" term="%2239139271%22">39139271)</searchLink><br />Nat Med. 2023 Nov;29(11):2682-2683. (PMID: <searchLink fieldCode="PM" term="%2237710137%22">37710137)</searchLink><br />Trials. 2020 Aug 1;21(1):694. (PMID: <searchLink fieldCode="PM" term="%2232738919%22">32738919)</searchLink><br />J Neurol. 2013 Jan;260(1):228-36. (PMID: <searchLink fieldCode="PM" term="%2222865238%22">22865238)</searchLink><br />Front Aging Neurosci. 2023 Mar 16;15:1109914. (PMID: <searchLink fieldCode="PM" term="%2237009459%22">37009459)</searchLink><br />Trials. 2009 Jun 11;10:39. (PMID: <searchLink fieldCode="PM" term="%2219519885%22">19519885)</searchLink><br />Mov Disord Clin Pract. 2017 Mar 11;4(4):536-544. (PMID: <searchLink fieldCode="PM" term="%2230363418%22">30363418)</searchLink><br />Mov Disord. 2024 Sep;39(9):1468-1477. (PMID: <searchLink fieldCode="PM" term="%2238925541%22">38925541)</searchLink><br />Neurology. 2022 May 3;98(18):754-764. (PMID: <searchLink fieldCode="PM" term="%2235321926%22">35321926)</searchLink><br />Qual Life Res. 2016 Jan;25(1):81-8. (PMID: <searchLink fieldCode="PM" term="%2226264781%22">26264781)</searchLink><br />JAMA. 2021 Sep 14;326(10):926-939. (PMID: <searchLink fieldCode="PM" term="%2234519802%22">34519802)</searchLink><br />Clin Trials. 2017 Oct;14(5):451-461. (PMID: <searchLink fieldCode="PM" term="%2228830236%22">28830236)</searchLink><br />Neurology. 1985 Apr;35(4):522-6. (PMID: <searchLink fieldCode="PM" term="%223982637%22">3982637)</searchLink><br />Eur J Neurol. 2015 Mar;22(3):457-63. (PMID: <searchLink fieldCode="PM" term="%2224888502%22">24888502)</searchLink><br />J Parkinsons Dis. 2018;8(s1):S3-S8. (PMID: <searchLink fieldCode="PM" term="%2230584159%22">30584159)</searchLink><br />BMC Neurol. 2016 Jun 16;16:92. (PMID: <searchLink fieldCode="PM" term="%2227312378%22">27312378)</searchLink><br />J Parkinsons Dis. 2020;10(2):413-428. (PMID: <searchLink fieldCode="PM" term="%2232116263%22">32116263)</searchLink><br />J Parkinsons Dis. 2024;14(4):809-821. (PMID: <searchLink fieldCode="PM" term="%2238701161%22">38701161)</searchLink><br />Prog Neurobiol. 2011 Dec;95(4):629-35. (PMID: <searchLink fieldCode="PM" term="%2221930184%22">21930184)</searchLink><br />Parkinsonism Relat Disord. 2014 Jan;20(1):99-105. (PMID: <searchLink fieldCode="PM" term="%2224183678%22">24183678)</searchLink><br />Trials. 2012 Sep 15;13:168. (PMID: <searchLink fieldCode="PM" term="%2222978443%22">22978443)</searchLink><br />J Neurol Neurosurg Psychiatry. 2018 Dec;89(12):1279-1287. (PMID: <searchLink fieldCode="PM" term="%2230464029%22">30464029)</searchLink><br />Mov Disord. 2025 Jul;40(7):1307-1317. (PMID: <searchLink fieldCode="PM" term="%2240249275%22">40249275)</searchLink><br />J Parkinsons Dis. 2022;12(1):437-452. (PMID: <searchLink fieldCode="PM" term="%2234719511%22">34719511)</searchLink><br />J Neurol Neurosurg Psychiatry. 2011 Oct;82(10):1112-8. (PMID: <searchLink fieldCode="PM" term="%2221593513%22">21593513)</searchLink><br />Brain. 2004 Mar;127(Pt 3):550-60. (PMID: <searchLink fieldCode="PM" term="%2214691062%22">14691062)</searchLink><br />Lancet Neurol. 2019 May;18(5):459-480. (PMID: <searchLink fieldCode="PM" term="%2230879893%22">30879893)</searchLink><br />Mov Disord. 2018 May;33(5):771-782. (PMID: <searchLink fieldCode="PM" term="%2229572948%22">29572948)</searchLink><br />J Parkinsons Dis. 2023;13(8):1343-1356. (PMID: <searchLink fieldCode="PM" term="%2238007672%22">38007672)</searchLink><br />JAMA Neurol. 2014 Feb;71(2):141-50. (PMID: <searchLink fieldCode="PM" term="%2224366103%22">24366103)</searchLink><br />J Infect Dis. 2012 May 15;205 Suppl 2:S250-7. (PMID: <searchLink fieldCode="PM" term="%2222448027%22">22448027)</searchLink>
– Name: SubjectMinor
  Label: Contributed Indexing
  Group:
  Data: <i>Investigator: </i>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<br /><i>Keywords: </i>Parkinson’s disease; multi-arm multi-stage; patient and public involvement and engagement; trial design
– Name: DateEntry
  Label: Entry Date(s)
  Group: Date
  Data: <i>Date Created: </i>20260928 <i>Date Completed: </i>20260928 <i>Latest Revision: </i>20260929
– Name: DateUpdate
  Label: Update Code
  Group: Date
  Data: 20260929
– Name: PubmedCentralID
  Label: PubMed Central ID
  Group: ID
  Data: PMC13616524
– Name: DOI
  Label: DOI
  Group: ID
  Data: 10.1093/braincomms/fcag349
– Name: AN
  Label: PMID
  Group: ID
  Data: 42802821
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=cmedm&AN=42802821
RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.1093/braincomms/fcag349
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        StartPage: fcag349
    Titles:
      – TitleFull: The patient-centric development of an inclusive multi-arm multi-stage trial for Parkinson's disease.
        Type: main
  BibRelationships:
    HasContributorRelationships:
      – PersonEntity:
          Name:
            NameFull: Zeissler ML
      – PersonEntity:
          Name:
            NameFull: Burnell M
      – PersonEntity:
          Name:
            NameFull: Barber TR
      – PersonEntity:
          Name:
            NameFull: Ben-Shlomo Y
      – PersonEntity:
          Name:
            NameFull: Clarke CS
      – PersonEntity:
          Name:
            NameFull: Collins S
      – PersonEntity:
          Name:
            NameFull: Counsell C
      – PersonEntity:
          Name:
            NameFull: Duffen J
      – PersonEntity:
          Name:
            NameFull: Edwards MJ
      – PersonEntity:
          Name:
            NameFull: Ellis-Doyle R
      – PersonEntity:
          Name:
            NameFull: Gonzalez-Robles C
      – PersonEntity:
          Name:
            NameFull: Hockey K
      – PersonEntity:
          Name:
            NameFull: Jewell A
      – PersonEntity:
          Name:
            NameFull: Lawton M
      – PersonEntity:
          Name:
            NameFull: Mills G
      – PersonEntity:
          Name:
            NameFull: Petty R
      – PersonEntity:
          Name:
            NameFull: Salathiel D
      – PersonEntity:
          Name:
            NameFull: Whipps S
      – PersonEntity:
          Name:
            NameFull: Whone A
      – PersonEntity:
          Name:
            NameFull: Gandhi S
      – PersonEntity:
          Name:
            NameFull: Carroll CB
      – PersonEntity:
          Name:
            NameFull: Foltynie T
      – PersonEntity:
          Name:
            NameFull: Carpenter JR
      – PersonEntity:
          Name:
            NameFull: Barker RA
    IsPartOfRelationships:
      – BibEntity:
          Dates:
            – D: 22
              M: 09
              Text: 2026 Sep 22
              Type: published
              Y: 2026
          Identifiers:
            – Type: issn-electronic
              Value: 2632-1297
          Numbering:
            – Type: volume
              Value: 8
            – Type: issue
              Value: 5
          Titles:
            – TitleFull: Brain communications
              Type: main
ResultId 1