Outcome Selection for Research Studies in Movement Disorders

Abstract

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.