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Choosing the correct outcome measure for any clinical research study in the field of movement disorders depends on the disease being studied and the research question being asked.The clinical features of the movement disorder will impact which outcome measure; when it will be measured and how it will be measured. For example, clinical studies investigating Parkinson's disease (PD) requires knowledge of the myriad of motor and non-motor features of the disease, not only in choosing the correct scale but also the potential impact of other disease features on the proposed outcome measures. The heterogeneity of PD will also affect the type of outcome measure if focussed on one component of the disease for example, tremor versus non-tremor dominant. Outcomes used in dystonia need to be tailored to the body distribution of dystonia such as focal or generalized, as well as other components such as pain and tremor. Some movement disorders are progressive and worsen over time, such that the outcome measure used will impact the trial design. Thus, in early untreated PD, studies using a motor score (eg, MDS-UPDRS III) as a surrogate for "disease progression" when investigating a potential neuroprotective agent, could require a trial to last months to years as the change in MDS-UPDRS III in the early stages of disease is small and non-linear (eg, 3-4 points/year). 1 While later in the disease, the same outcome, MDS UPDRS III, is a measure of symptomatic effects of an intervention and a shorter duration of trial is sufficient. Likewise the effect of symptomatic medications needs to be incorporated into any study investigating potential disease-modification in PD when the MDS-UPDRS is used as an outcome measure. Other challenges to take into consideration include knowledge of the natural history of the movement disorder such as fluctuations in symptoms. This may occur with disorders such as Tics and Tourette's syndrome, and truly paroxysmal movement disorders that may impact the timing and type of outcome measure used. Likewise, fluctuations or changes in symptoms due to symptomatic therapy in PD with motor and non-motor fluctuations is also a major variable to consider when choosing an outcome measure. The natural history of other symptoms in PD may also fluctuate, including psychosis, dyskinesia and many non motor issues that may impact type and timing of outcome measures. 2 Thus knowledge of the seminology is key to designing and incorporating the correct outcome measures.
Choosing the correct outcome measure for any clinical research study in the field of movement disorders depends on the disease being studied and the research question being asked.The clinical features of the movement disorder will impact which outcome measure; when it will be measured and how it will be measured. For example, clinical studies investigating Parkinson's disease (PD) requires knowledge of the myriad of motor and non-motor features of the disease, not only in choosing the correct scale but also the potential impact of other disease features on the proposed outcome measures. The heterogeneity of PD will also affect the type of outcome measure if focussed on one component of the disease for example, tremor versus non-tremor dominant. Outcomes used in dystonia need to be tailored to the body distribution of dystonia such as focal or generalized, as well as other components such as pain and tremor. Some movement disorders are progressive and worsen over time, such that the outcome measure used will impact the trial design. Thus, in early untreated PD, studies using a motor score (eg, MDS-UPDRS III) as a surrogate for "disease progression" when investigating a potential neuroprotective agent, could require a trial to last months to years as the change in MDS-UPDRS III in the early stages of disease is small and non-linear (eg, 3-4 points/year). 1 While later in the disease, the same outcome, MDS UPDRS III, is a measure of symptomatic effects of an intervention and a shorter duration of trial is sufficient. Likewise the effect of symptomatic medications needs to be incorporated into any study investigating potential disease-modification in PD when the MDS-UPDRS is used as an outcome measure. Other challenges to take into consideration include knowledge of the natural history of the movement disorder such as fluctuations in symptoms. This may occur with disorders such as Tics and Tourette's syndrome, and truly paroxysmal movement disorders that may impact the timing and type of outcome measure used. Likewise, fluctuations or changes in symptoms due to symptomatic therapy in PD with motor and non-motor fluctuations is also a major variable to consider when choosing an outcome measure. The natural history of other symptoms in PD may also fluctuate, including psychosis, dyskinesia and many non motor issues that may impact type and timing of outcome measures. 2 Thus knowledge of the seminology is key to designing and incorporating the correct outcome measures.
Traditional drug development in Parkinson's disease (PD) faces significant challenges because of its protracted timeline and high costs. In response, innovative master protocols are emerging and designed to address multiple research questions within a single overarching protocol. These trials may offer advantages such as increased efficiency, agility in adding new treatment arms, and potential cost savings. However, they also present organizational, methodological, funding, regulatory, and sponsorship challenges. We review the potential of master protocols, focusing on platform trials, for disease modifying therapies in PD. These trials share a common control group and allow for the termination or addition of treatment arms during a trial with non‐predetermined end. Specific issues exist for a platform trial in the PD field considering the heterogeneity of patients in terms of phenotype, genotype and staging, the confounding effects of symptomatic treatments, and the choice of outcome measures with no consensus on a non‐clinical biomarker to serve as a surrogate and the slowness of PD progression. We illustrate these aspects using the examples of the main PD platform trials currently in development with each one targeting distinct goals, populations, and outcomes. Overall, platform trials hold promise in expediting the evaluation of potential therapies for PD. However, it remains to be proven whether these theoretical benefits will translate into increased production of high‐quality trial data. Success also depends on the willingness of pharmaceutical companies to engage in such trials and whether this approach will ultimately hasten the identification and licensing of effective disease‐modifying drugs. © 2024 International Parkinson and Movement Disorder Society.
Outcomes derived from digital health technologies (DHTs) are promising candidate markers for monitoring Parkinson's disease (PD) progression. They have the potential to represent a significant shift in clinical research and therapeutic development in PD. However, their ability to track disease progression is yet to be established. This systematic review aimed to identify digital biomarkers capable of tracking early PD progression (disease duration <5 years) by reviewing longitudinal studies (minimum follow‐up of 6 months). We evaluated study design and quality, population features, reported DHTs and their performance to track progression. Of 1507 records screened, 15 studies were selected, published between 2009 and 2023, with the majority coming from the last 5 years. Of the 15, 11 were observational and four were interventional trials (follow‐up range: 6–60 months). Twelve different DHTs were used (8 required active tests, 8 in‐hospital use), capturing features related to motor function and daily activities, including five DHTs focused on gait/posture. Rating scales were used as comparators in all but one study. Three DHTs detected longitudinal changes when scales did not, with one study showing larger effect sizes for change over time of selected DHT features compared to rating scales. Four studies showed longitudinal correlations among DHT features and rating scales. Preliminary promising data suggest that DHT‐derived outcomes may help reduce sample sizes in disease‐modifying trials. There is a need to standardize study methodologies and facilitate data sharing to confirm these results and further validate the sensitivity of DHTs to track disease progression in PD. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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