Towards a multi-arm multi-stage platform trial of disease modifying approaches in Parkinson’s disease
Authors: Foltynie Tom , Gandhi Sonia , Gonzalez-Robles Cristina , Zeissler Marie-Louise , Mills Georgia , Barker Roger , Carpenter James , Schrag Anette , Schapira Anthony , Bandmann Oliver , Mullin Stephen , Duffen Joy , McFarthing Kevin , Chataway Jeremy , Parmar Mahesh , Carroll Camille ,   the EJS ACT-PD Consortium, Shlomo Yoav Ben , Edwards Mark , Whone Alan , Counsell Carl , Clarke Caroline , Burnell Matthew , Salathiel Dorothy , Whipps Sue , Jewell Anna , Barber Tom , Weil Rimona , Gray Caroline Williams , Hu Michele , Rochester Lynn , Piccini Paola , Zetterberg Henrik , Noyce Alastair , Chaudhuri Ray , Lawton Michael , Jha Ashwani , Siu Carroll , Bartlett Michèle , van Wamelen Daniel , Stott Simon , Tofaris George , Sammler Esther , Mortiboys Heather , Wei Li , Wong Alan , Duty Susan , Dexter David , Scurfield Paula , Jabbari Edwin , Morris Huw , Breen David , Lambert Chris , Korlipara Prasad , Silverdale Monty , Bhatia Kailash , Yarnall Alison , Khengar Raj , Collins Helen , Hudson Fleur , Baxendale Gareth , Croucher Rebecca , Bartolomeur-Pires Sandra , Allison Jennifer , Morgan Antony , Wonnacott Sheila , Athauda Dilan , Henderson Emily , Clegg Shona , Matthews Karen , Deeson Eric , Miller Laurel , Handley Joel , Matthews Helen , Batla Amit , Bakshi Nikul , Port Beckie , Ellis-Doyle Romy , Collins Sally L , Rudiger Judith , Chapman Rebecca , Cedarbaum Jesse , Lang Anthony , Fiske Brain , Wyse Richard , Boxer Adam , Wilson Denise , Corvol Jean Christophe , Harris Jennifer 
Published: March 2023

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 multi-arm 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.