Prodromal Marker Progression in Idiopathic Rapid Eye Movement Sleep Behavior Disorder: Sample Size for Clinical Trials.

Abstract

To estimate prodromal marker progression in idiopathic rapid eye movement sleep behavior disorder patients with prodromal Parkinson's disease (PD) to calculate sample size for neuroprotective trials. Patients with polysomnogram-proven idiopathic rapid eye movement sleep behavior disorder were assessed for prodromal PD using Movement Disorder Society criteria. We prospectively measured progression rates of numerous clinical variables, including motor, cognitive, special sensory, and autonomic variables and calculated the sample size required to demonstrate slowing of progression under 3 effectiveness assumptions (30%, 50%, and 70% slowing). Overall, the variables that progressed with lowest sample size requirements were motor variables (234 participants required per group for 50% efficacy over 2 years). By contrast, cognitive, special sensory, and autonomic variables showed modest progression with high variability, resulting in high sample sizes. The most efficient design was a time-to-event analysis using milestones of motor and cognitive decline (126 per group). In idiopathic rapid eye movement sleep behavior disorder, time-to-event analysis assessing milestones of decline is the most efficient trial design for neuroprotective therapy. © 2019 International Parkinson and Movement Disorder Society.