Optimizing clinical trial design for multiple system atrophy: lessons from the rifampicin study.

摘要: Multiple system atrophy (MSA) is a fatal neurodegenerative disorder characterized by autonomic failure and parkinsonism/ataxia; no treatment exists to slow disease progression. A number of factors have prevented or compromised trials targeting modification. major hurdle has been uncertainty about the patients needed achieve adequate power. Information based on natural history studies suggested such numbers be so large that only international multi-center models seemed feasible. When designing rifampicin trial in MSA we sought identify apply strategies would improve power reduce treat allow for an oligocenter approach. Strategies included: (1) inclusion/exclusion criteria designed enroll with relatively early, actively progressing disease; (2) minimizing dropouts; (3) pre-defined interim analysis; (4) approaches scoring variability. The model allowed 50 per arm. Ten selected sites managed reach recruitment goal within 12 months. dropout rate was less than 10 %, enrolling accomplished as reflected progression placebo group. Data from this unfortunately negative can now effectively used more realistically future trials. ways further design feasibility identified include rigorous site selection training, designated primary investigators, improved error trapping, early visits, remedial biomarkers earlier diagnosis tracking