RÉSUMÉ
In 2011, the UK medical research charity Cure Parkinson's set up the international Linked Clinical Trials (iLCT) committee to help expedite the clinical testing of potentially disease modifying therapies for Parkinson's disease (PD). The first committee meeting was held at the Van Andel Institute in Grand Rapids, Michigan in 2012. This group of PD experts has subsequently met annually to assess and prioritize agents that may slow the progression of this neurodegenerative condition, using a systematic approach based on preclinical, epidemiological and, where possible, clinical data. Over the last 12 years, 171 unique agents have been evaluated by the iLCT committee, and there have been 21 completed clinical studies and 20 ongoing trials associated with the initiative. In this review, we briefly outline the iLCT process as well as the clinical development and outcomes of some of the top prioritized agents. We also discuss a few of the lessons that have been learnt, and we conclude with a perspective on what the next decade may bring, including the introduction of multi-arm, multi-stage clinical trial platforms and the possibility of combination therapies for PD.
Sujet(s)
Essais cliniques comme sujet , Maladie de Parkinson , Humains , Maladie de Parkinson/traitement médicamenteux , Antiparkinsoniens/usage thérapeutiqueRÉSUMÉ
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.
Sujet(s)
COVID-19 , Maladie de Parkinson , HumainsRÉSUMÉ
BACKGROUND: There is growing interest in having objective assessment of health-related outcomes using technology-based devices that provide unbiased measurements which can be used in clinical practice and scientific research. Many studies have investigated the clinical manifestations of Parkinson's disease using such devices. However, clinimetric properties and clinical validation vary among the different devices. METHODS: Given such heterogeneity, we sought to perform a systematic review in order to (i) list, (ii) compare and (iii) classify technological-based devices used to measure motor function in individuals with Parkinson's disease into three groups, namely wearable, non-wearable and hybrid devices. A systematic literature search of the PubMed database resulted in the inclusion of 168 studies. These studies were grouped based on the type of device used. For each device we reviewed availability, use, reliability, validity, and sensitivity to change. The devices were then classified as (i) 'recommended', (ii) 'suggested' or (iii) 'listed' based on the following criteria: (1) used in the assessment of Parkinson's disease (yes/no), (2) used in published studies by people other than the developers (yes/no), and (3) successful clinimetric testing (yes/no). RESULTS: Seventy-three devices were identified, 22 were wearable, 38 were non-wearable, and 13 were hybrid devices. In accordance with our classification method, 9 devices were 'recommended', 34 devices were 'suggested', and 30 devices were classified as 'listed'. Within the wearable devices group, the Mobility Lab sensors from Ambulatory Parkinson's Disease Monitoring (APDM), Physilog®, StepWatch 3, TriTrac RT3 Triaxial accelerometer, McRoberts DynaPort, and Axivity (AX3) were classified as 'recommended'. Within the non-wearable devices group, the Nintendo Wii Balance Board and GAITRite® gait analysis system were classified as 'recommended'. Within the hybrid devices group only the Kinesia® system was classified as 'recommended'.
Sujet(s)
Accélérométrie/instrumentation , Surveillance électronique ambulatoire/instrumentation , Maladie de Parkinson/physiopathologie , Humains , Maladie de Parkinson/rééducation et réadaptation , Reproductibilité des résultatsRÉSUMÉ
BACKGROUND: Currently, assessment of symptoms associated with Parkinson's disease is mainly performed in the clinic. However, these assessments have limitations because they provide only a snapshot of the condition. METHODS: The feasibility and usability of an objective, continuous and relatively unobtrusive system (SENSE-PARK System), which consists of wearable sensors (three worn during the day and one worn at night), a smartphone-based App, a balance board and computer software, was tested 24/7 over 12 weeks in a study including 22 PD patients. During the first four weeks of the study, patients did not get feedback about their performance, during the last eight weeks they did. The study included seven clinical visits with standardized interviews, and regular phone contact. The primary outcome was the number of drop-outs during the study. As secondary outcomes, the Post-Study System Usability Questionnaire (PSSUQ), score and information obtained from the standardized interviews were used to evaluate the usability of the system. RESULTS: All patients completed the study. The participants rated the usability of the SENSE-PARK System with a mean score of 2.67 (±0.49) on the PSSUQ. The interviews revealed that most participants liked using the system and appreciated that it signaled changes in their health condition. CONCLUSIONS: This 12 week controlled study demonstrates that the acceptance level of PD patients using the SENSE-PARK System as a home-based 24/7 assessment is very good. Particular emphasis should be given to a user-friendly design. Motivation to wear such a system can be increased by providing direct feedback about the individual health condition.
Sujet(s)
Surveillance électronique ambulatoire/méthodes , Maladie de Parkinson/diagnostic , Acceptation des soins par les patients , Sujet âgé , Études de faisabilité , Femelle , Humains , Mâle , Adulte d'âge moyen , Surveillance électronique ambulatoire/instrumentation , Études multicentriques comme sujet , Observance par le patient , Satisfaction des patients , Projets pilotesRÉSUMÉ
BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder with fluctuating symptoms. To aid the development of a system to evaluate people with PD (PwP) at home (SENSE-PARK system) there was a need to define parameters and tools to be applied in the assessment of 6 domains: gait, bradykinesia/hypokinesia, tremor, sleep, balance and cognition. OBJECTIVE: To identify relevant parameters and assessment tools of the 6 domains, from the perspective of PwP, caregivers and movement disorders specialists. METHODS: A 2-round Delphi study was conducted to select a core of parameters and assessment tools to be applied. This process included PwP, caregivers and movement disorders specialists. RESULTS: Two hundred and thirty-three PwP, caregivers and physicians completed the first round questionnaire, and 50 the second. Results allowed the identification of parameters and assessment tools to be added to the SENSE-PARK system. The most consensual parameters were: Falls and Near Falls; Capability to Perform Activities of Daily Living; Interference with Activities of Daily Living; Capability to Process Tasks; and Capability to Recall and Retrieve Information. The most cited assessment strategies included Walkers; the Evaluation of Performance Doing Fine Motor Movements; Capability to Eat; Assessment of Sleep Quality; Identification of Circumstances and Triggers for Loose of Balance and Memory Assessment. CONCLUSIONS: An agreed set of measuring parameters, tests, tools and devices was achieved to be part of a system to evaluate PwP at home. A pattern of different perspectives was identified for each stakeholder.
Sujet(s)
Évaluation des besoins , Maladie de Parkinson/diagnostic , Activités de la vie quotidienne , Aidants , Méthode Delphi , Femelle , Humains , Mâle , Adulte d'âge moyen , Maladie de Parkinson/complications , Maladie de Parkinson/physiopathologie , Maladie de Parkinson/psychologieRÉSUMÉ
BACKGROUND: There is a growing interest in the objective assessment of health related outcomes using technology providing quality measurements to be applied not only in daily clinical practice, but also in scientific research. Differences in the understandings of the condition and the terminology used between people with Parkinson's (PwPs), clinicians and technical developers may influence the progress of a participatory design process. OBJECTIVE: This paper reports on a participatory design process to achieve a consensus among PwPs, clinicians and technologists over the selection of a set of symptomatic domains to be continuously assessed, in order to provide results relevant to both PwPs and clinicians. METHODS: The methods used were a Web based user survey, end-user focus groups, ranking by combined methods, a Delphi process performed among clinicians and scientists, and prioritization of the results in a concertation workshop for PwPs, clinicians and technologists. RESULTS: The following symptomatic domains were commonly agreed by PwPs and clinicians to be of central importance in a system of continuous assessment: hypokinesia/bradykinesia, tremor, sway, gait, sleep and cognition. This list satisfied both the needs of the PwPs and the concerns of the clinicians regarding the means of advancing new strategies in assessment and interventions in PD. CONCLUSIONS: A participatory design strategy allowed the definition of a consensual list of symptomatic domains. Both the strategy and the achieved results may be of relevance for similar interdisciplinary approaches in the field of PD using a participatory design involving patients, clinicians and technologists.
Sujet(s)
Groupes de discussion , Maladie de Parkinson/physiopathologie , Plan de recherche , Adulte , Facteurs âges , Sujet âgé , Sujet âgé de 80 ans ou plus , Essais cliniques comme sujet , Femelle , Enquêtes de santé , Humains , Internet , Mâle , Adulte d'âge moyen , Maladie de Parkinson/thérapie , Statistiques comme sujetRÉSUMÉ
Finding new therapies for Parkinson's disease (PD) is a slow process. We assembled an international committee of experts to examine drugs potentially suitable for repurposing to modify PD progression. This committee evaluated multiple drugs currently used, or being developed, in other therapeutic areas, as well as considering several natural, non-pharmaceutical compounds. The committee prioritized which of these putative treatments were most suited to move immediately into pilot clinical trials. Aspects considered included known modes of action, safety, blood-brain-barrier penetration, preclinical data in animal models of PD and the possibility to monitor target engagement in the brain. Of the 26 potential interventions, 10 were considered worth moving forward into small, parallel 'learning' clinical trials in PD patients. These trials could be funded in a multitude of ways through support from industry, research grants and directed philanthropic donations. The committee-based approach to select the candidate compounds might help rapidly identify new potential PD treatment strategies for use in clinical trials.