Foltynie, Tom;
Gandhi, Sonia;
Gonzalez-Robles, Cristina;
Zeissler, Marie-Louise;
Mills, Georgia;
Barker, Roger;
Carpenter, James;
... EJS ACT-PD Consortium; + view all
(2023)
Towards a multi-arm multi-stage platform trial of disease modifying approaches in Parkinson's disease.
Brain
, Article awad063. 10.1093/brain/awad063.
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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.
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