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. 2023;13(6):1011-1033.
doi: 10.3233/JPD-230051.

Outcome Measures for Disease-Modifying Trials in Parkinson's Disease: Consensus Paper by the EJS ACT-PD Multi-Arm Multi-Stage Trial Initiative

Cristina Gonzalez-Robles  1 , Rimona S Weil  1 , Daniel van Wamelen  2 , Michèle Bartlett  3 , Matthew Burnell  4 , Caroline S Clarke  1 , Michele T Hu  5 , Brook Huxford  6 , Ashwani Jha  1 , Christian Lambert  1 , Michael Lawton  7 , Georgia Mills  1 , Alastair Noyce  6 , Paola Piccini  8 , Kuhan Pushparatnam  9 , Lynn Rochester  10 , Carroll Siu  11 , Caroline H Williams-Gray  12 , Marie-Louise Zeissler  13 , Henrik Zetterberg  14 , Camille B Carroll  13 , Thomas Foltynie  1 , Anette Schrag  1 ; EJS ACT-PD Consortium
Collaborators, Affiliations

Outcome Measures for Disease-Modifying Trials in Parkinson's Disease: Consensus Paper by the EJS ACT-PD Multi-Arm Multi-Stage Trial Initiative

Cristina Gonzalez-Robles et al. J Parkinsons Dis. 2023.

Abstract

Background: Multi-arm, multi-stage (MAMS) platform trials can accelerate the identification of disease-modifying treatments for Parkinson's disease (PD) but there is no current consensus on the optimal outcome measures (OM) for this approach.

Objective: To provide an up-to-date inventory of OM for disease-modifying PD trials, and a framework for future selection of OM for such trials.

Methods: As part of the Edmond J Safra Accelerating Clinical Trials in Parkinson Disease (EJS ACT-PD) initiative, an expert group with Patient and Public Involvement and Engagement (PPIE) representatives' input reviewed and evaluated available evidence on OM for potential use in trials to delay progression of PD. Each OM was ranked based on aspects such as validity, sensitivity to change, participant burden and practicality for a multi-site trial. Review of evidence and expert opinion led to the present inventory.

Results: An extensive inventory of OM was created, divided into: general, motor and non-motor scales, diaries and fluctuation questionnaires, cognitive, disability and health-related quality of life, capability, quantitative motor, wearable and digital, combined, resource use, imaging and wet biomarkers, and milestone-based. A framework for evaluation of OM is presented to update the inventory in the future. PPIE input highlighted the need for OM which reflect their experience of disease progression and are applicable to diverse populations and disease stages.

Conclusion: We present a range of OM, classified according to a transparent framework, to aid selection of OM for disease-modifying PD trials, whilst allowing for inclusion or re-classification of relevant OM as new evidence emerges.

Keywords: Parkinson’s disease; biomarkers; clinical trials; consensus; neuroprotection; outcome measures.

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Conflict of interest statement

RSW has received speaking honoraria from GE Healthcare and a writing honorarium from Britannia.

DVW reports consultancy and speaker fees from Bial and Britannia.

MTH received payment for Advisory Board attendance/consultancy for Lundbeck, ESCAPE Bio, Evidera, Manus Neurodynamica, Biogen MA, CuraSen Therapeutics, Roche Products Ltd. MTH is an advisory founder of NeuHealth Digital Ltd (company number: 14492037), a digital biomarker platform to remotely manage condition progression for Parkinson’s.

AJ has been involved in the development and clinical assessment of a smartphone-based tool for Parkinson’s disease (cloudUPDRS).

ML received fees for advising on a secondary analysis of a Parkinson’s RCT (GDNF) sponsored by North Bristol NHS trust.

AN has been involved in the development of the Bradykinesia-Akinesia Incoordination (BRAIN) test. AN is an Editorial Board Member of this journal, but was not involved in the peer-review process nor had access to any information regarding its peer-review.

HZ has served at scientific advisory boards and/or as a consultant for Abbvie, Acumen, Alector, Alzinova, ALZPath, Annexon, Apellis, Artery Therapeutics, AZTherapies, CogRx, Denali, Eisai, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave, has given lectures in symposia sponsored by Cellectricon, Fujirebio, Alzecure, Biogen, and Roche, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work).

CBC has received personal fees from AbbVie, Bial, Scient, Orkyn, Abidetex, UCB, Pfizer, EverPharma, Lundbeck, Global Kinetics, Kyowa Kirin, Britannia, and MedScape; and appointments as a Cure Parkinson’s Linked Clinical Trials (LCT) committee member, a Cure Parkinson’s Research Committee member, and a Parkinson’s UK College of Experts Panel member. CBC is an Editorial Board Member of this journal, but was not involved in the peer-review process nor had access to any information regarding its peer-review.

TF has served on Advisory Boards for Peptron, Voyager Therapeutics, Handl therapeutics, Gain therapeutics, Living Cell Technologies, Abbvie, Bluerock, Bayer & Bial. TF has received honoraria for talks sponsored by Bial, Profile Pharma, Boston Scientific & Novo Nordisk. TF is an Editorial Board Member of this journal, but was not involved in the peer-review process nor had access to any information regarding its peer-review. AS is a member of the MDS-UPDRS Development Group, the MDS-NMS Development Group, the NINDS CDE QoL Group, the MDS Rating Scales Review Committee, and the MDS COA Early and Prodromal PD Working Group. AS has been involved in the development of the MDS-UPDRS, the MDS-NMS, and the PQoL.

AS reports consultancy fees from Biogen, Abbvie, Roche, Bial, and GE Healthcare; license fees from University College London; and royalties from Oxford University Press. CGR, MB, MBu, CSC, BH, CL, GM, PP, KP, LR, CS, CWG and MLZ have no conflict of interest to report.

Figures

Fig. 1
Fig. 1
Sources for consensus of outcome measures in disease-modifying trials in Parkinson’s disease. EPDA-UCB, European Parkinson’s Disease Association-UCB Pharma; MA, meta-analysis; MDS, Movement Disorders Society (critique and recommendation papers on different outcome measures); NINDS-CDE, National Institute of Neurological Disorders and Stroke Common Data Elements initiative; OM, Outcome Measures; P-UK, Parkinson’s UK; PPIE, Patient and Public Involvement and Engagement; SR, Systematic review; UoP, University of Plymouth; WG, Working Group.
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