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

Tom Foltynie (Lead / Corresponding author), 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, EJS ACT-PD Consortium, Yoav Ben Shlomo, Mark Edwards, Alan WhoneCarl 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

Research output: Contribution to journalReview articlepeer-review

6 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)2717-2722
Number of pages6
JournalBrain
Volume146
Issue number7
Early online date28 Feb 2023
DOIs
Publication statusPublished - Jul 2023

Keywords

  • complex innovative trial design
  • multi-arm
  • multi-stage
  • Parkinson’s disease
  • platform trial

ASJC Scopus subject areas

  • Clinical Neurology

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