| 1. |
- Gonzalez-Robles, Cristina, et al.
(författare)
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Embedding Patient Input in Outcome Measures for Long-Term Disease-Modifying Parkinson Disease Trials
- 2024
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Ingår i: Movement Disorders. - 0885-3185 .- 1531-8257. ; 39:2, s. 433-438
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Tidskriftsartikel (refereegranskat)abstract
- Background: Clinical trials of disease-modifying therapies in PD require valid and responsive primary outcome measures that are relevant to patients. Objectives: The objective is to select a patient-centered primary outcome measure for disease-modification trials over three or more years. Methods: Experts in Parkinson's disease (PD), statistics, and health economics and patient and public involvement and engagement (PPIE) representatives reviewed and discussed potential outcome measures. A larger PPIE group provided input on their key considerations for such an endpoint. Feasibility, clinimetric properties, and relevance to patients were assessed and synthesized. Results: Although initial considerations favored the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III in Off, feasibility, PPIE input, and clinimetric properties supported the MDS-UPDRS Part II. However, PPIE input also highlighted the importance of nonmotor symptoms, especially in the longer term, leading to the selection of the MDS-UPDRS Parts I + II sum score. Conclusions: The MDS-UPDRS Parts I + II sum score was chosen as the primary outcome for large 3-year disease-modification trials. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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| 2. |
- Gonzalez-Robles, Cristina, et al.
(författare)
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Outcome Measures for Disease-Modifying Trials in Parkinson's Disease: Consensus Paper by the EJS ACT-PD Multi-Arm Multi-Stage Trial Initiative
- 2023
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Ingår i: JOURNAL OF PARKINSONS DISEASE. - 1877-7171 .- 1877-718X. ; 13:6, s. 1013-1035
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Tidskriftsartikel (refereegranskat)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 ofOMwas 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.
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| 3. |
- Zarkali, Angeliki, et al.
(författare)
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Neuroimaging and plasma evidence of early white matter loss in Parkinson's disease with poor outcomes.
- 2024
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Ingår i: Brain communications. - 2632-1297. ; 6:3
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Tidskriftsartikel (refereegranskat)abstract
- Parkinson's disease is a common and debilitating neurodegenerative disorder, with over half of patients progressing to postural instability, dementia or death within 10 years of diagnosis. However, the onset and rate of progression to poor outcomes is highly variable, underpinned by heterogeneity in underlying pathological processes. Quantitative and sensitive measures predicting poor outcomes will be critical for targeted treatment, but most studies to date have been limited to a single modality or assessed patients with established cognitive impairment. Here, we used multimodal neuroimaging and plasma measures in 98 patients with Parkinson's disease and 28 age-matched controls followed up over 3 years. We examined: grey matter (cortical thickness and subcortical volume), white matter (fibre cross-section, a measure of macrostructure; and fibre density, a measure of microstructure) at whole-brain and tract level; structural and functional connectivity; and plasma levels of neurofilament light chain and phosphorylated tau 181. We evaluated relationships with subsequent poor outcomes, defined as development of mild cognitive impairment, dementia, frailty or death at any time during follow-up, in people with Parkinson's disease. We show that extensive white matter macrostructural changes are already evident at baseline assessment in people with Parkinson's disease who progress to poor outcomes (n = 31): with up to 19% reduction in fibre cross-section in multiple tracts, and a subnetwork of reduced structural connectivity strength, particularly involving connections between right frontoparietal and left frontal, right frontoparietal and left parietal and right temporo-occipital and left parietal modules. In contrast, grey matter volumes and functional connectivity were preserved in people with Parkinson's disease with poor outcomes. Neurofilament light chain, but not phosphorylated tau 181 levels were increased in people with Parkinson's disease with poor outcomes, and correlated with white matter loss. These findings suggest that imaging sensitive to white matter macrostructure and plasma neurofilament light chain may be useful early markers of poor outcomes in Parkinson's disease. As new targeted treatments for neurodegenerative disease are emerging, these measures show important potential to aid patient selection for treatment and improve stratification for clinical trials.
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