Towards a multi-arm multi-stage platform trial of disease modifying approaches in Parkinson’s disease
Authors list
Tom Foltynie Sonia Gandhi Cristina Gonzalez-Robles Marie-Louise Zeissler Georgia Mills Roger Barker James Carpenter Anette Schrag Anthony Schapira Oliver Bandmann Stephen Mullin Joy Duffen Kevin McFarthing Jeremy Chataway Mahesh Parmar Camille Carroll Yoav Ben Shlomo Mark Edwards Alan Whone Carl Counsell Caroline Clarke Matthew Burnell Dorothy Salathiel Sue Whipps Anna Jewell Tom Barber Rimona Weil Caroline Williams Gray Michele Hu Lynn Rochester Paola Piccini Henrik Zetterberg Alastair Noyce Ray Chaudhuri Michael Lawton Ashwani Jha Carroll Siu Michèle Bartlett Daniel van Wamelen Simon Stott George Tofaris Esther Sammler Heather Mortiboys Li Wei Alan Wong Susan Duty David Dexter Paula Scurfield Edwin Jabbari Huw Morris David Breen Chris Lambert Prasad Korlipara Monty Silverdale Kailash Bhatia Alison Yarnall Raj Khengar Helen Collins Fleur Hudson Gareth Baxendale Rebecca Croucher Sandra Bartolomeur-Pires Jennifer Allison Antony Morgan Sheila Wonnacott Dilan Athauda Emily Henderson Shona Clegg Karen Matthews Eric Deeson Laurel Miller Joel Handley Helen Matthews Amit Batla Nikul Bakshi Beckie Port Romy Ellis-Doyle Sally L Collins Judith Rudiger Rebecca Chapman Jesse Cedarbaum Anthony Lang Brain Fiske Richard Wyse Adam Boxer Denise Wilson Jean Christophe Corvol Jennifer Harris Toggle all authors (88)
Abstract
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 PD, a multi-arm platform trial must also specifically consider the heterogeneous nature of PD, 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 PD 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 pre-defined subgroups of interest, alongside evaluating the impact of each treatment on the broader population of PD 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.
Journal details
Journal Brain
Volume 146
Issue number 7
Pages 2717-2722
Available online
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Full text links
Publisher website (DOI) 10.1093/brain/awad063
Europe PubMed Central 36856727
Pubmed 36856727
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