TY - JOUR
T1 - Towards a multi-arm multi-stage platform trial of disease modifying approaches in Parkinson's disease
AU - Foltynie, Tom
AU - Gandhi, Sonia
AU - Gonzalez-Robles, Cristina
AU - Zeissler, Marie-Louise
AU - Mills, Georgia
AU - Barker, Roger
AU - Carpenter, James
AU - Schrag, Anette
AU - Schapira, Anthony
AU - Bandmann, Oliver
AU - Mullin, Stephen
AU - Duffen, Joy
AU - McFarthing, Kevin
AU - Chataway, Jeremy
AU - Parmar, Mahesh
AU - Carroll, Camille
AU - EJS ACT-PD Consortium
AU - van Wamelen, Daniel
N1 - Funding Information:
To this end, six working groups have been set up, each addressing a particular component of platform design and delivery: trial design, outcome measures, therapy selection, infrastructure, funding and sustainability and patient and public engagement. The consortium includes more than 75 individuals from across the UK, comprising patients and carers, neurologists, geriatricians, clinical triallists, statisticians, funders, methodologists, epidemiologists, health economists, trials pharmacists and a range of experience from clinical and preclinical researchers expert in disease modifying drug development and trial design. The patient perspective is central to the process, with patient/carer members embedded in each working group and thus involved in all decisions based on their collective discussions. Patient/carer consortium members are given training regarding all the technical issues and decisions as part of the process. Sustainability of the programme is supported by the inclusion of an early career researcher in each working group. An additional level of oversight, as well as an international perspective, is provided by panel of international advisors. Engagement with the Medicines and Healthcare products Regulatory Agency (MHRA) and reference to European and USA regulatory developments and requirements ensures that the regulatory perspective is incorporated into the design choices.
Publisher Copyright:
© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.
PY - 2023/7/1
Y1 - 2023/7/1
N2 - 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.
AB - 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.
KW - Humans
KW - COVID-19
KW - Parkinson Disease
UR - http://www.scopus.com/inward/record.url?scp=85164210946&partnerID=8YFLogxK
U2 - 10.1093/brain/awad063
DO - 10.1093/brain/awad063
M3 - Article
C2 - 36856727
SN - 0006-8950
VL - 146
SP - 2717
EP - 2722
JO - Brain : a journal of neurology
JF - Brain : a journal of neurology
IS - 7
ER -