title: Potential outcome measures and trial design issues for multiple system atrophy.
abstract: Multiple system atrophy (MSA) is a neurodegenerative disorder exhibiting a combination of parkinsonism, cerebellar ataxia, and autonomic failure. A disease-specific scale, the Unified Multiple System Atrophy Rating Scale (UMSARS), has been developed and validated to measure progression of MSA, but its use as an outcome measure for therapeutic trials has not been evaluated. On the basis of twelve months of follow-up from an observational study of 67 patients with probable MSA, we evaluated three disease-specific scores: Activities of Daily Living, Motor Examination, and a combined score from the UMSARS and two general health scores, the Physical Health and Mental Health scores of the SF-36 health survey, for their use as outcome measures in a therapeutic trial. We discuss related design issues and provide sample size estimates. Scores based on the disease-specific UMSARS seemed to be equal or superior to scores based on the SF-36 health survey. They appeared to capture disease progression, were well correlated and required the smallest sample size. The UMSARS Motor Examination score exhibited the most favorable characteristics as an outcome measure for a therapeutic trial in MSA with 1 year of follow-up.
authors.affiliation: Department of Family and Preventive Medicine, University of California, San Diego, La Jolla, California 92093-0717, USA. smay@ucsd.edu
authors.forename: Susanne
authors.initials: S
authors.lastname: May
authors.forename: Sid
authors.initials: S
authors.lastname: Gilman
authors.forename: B Brooke
authors.initials: BB
authors.lastname: Sowell
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Thomas
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Stern
authors.forename: Amy
authors.initials: A
authors.lastname: Colcher
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Tanner
authors.forename: Neng
authors.initials: N
authors.lastname: Huang
authors.forename: Peter
authors.initials: P
authors.lastname: Novak
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Reich
authors.forename: Joseph
authors.initials: J
authors.lastname: Jankovic
authors.forename: William G
authors.initials: WG
authors.lastname: Ondo
authors.forename: Phillip A
authors.initials: PA
authors.lastname: Low
authors.forename: Paola
authors.initials: P
authors.lastname: Sandroni
authors.forename: Axel
authors.initials: A
authors.lastname: Lipp
authors.forename: Frederick J
authors.initials: FJ
authors.lastname: Marshall
authors.forename: Frederick
authors.initials: F
authors.lastname: Wooten
authors.forename: Clifford W
authors.initials: CW
authors.lastname: Shults
mesh_terms: D000368:Aged; D000978:Antiparkinson Agents / Q000627:therapeutic use; D002526:Cerebellar Diseases / Q000503:physiopathology / Q000628:therapy; D002986:Clinical Trials as Topic; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000453:epidemiology / Q000503:physiopathology / Q000628:therapy*; D012107:Research Design; D012307:Risk Factors; D018401:Sample Size; D012959:Socioeconomic Factors; D016896:Treatment Outcome
chemical_list: D000978:Antiparkinson Agents; D007980:Levodopa