title: Measuring the rate of progression in Friedreich ataxia: implications for clinical trial design.
abstract: Friedreich ataxia is an autosomal recessive neurodegenerative disorder characterized by ataxia of all four limbs, dysarthria, and arreflexia. A variety of measures are currently used to quantify disease progression, including the Friedreich Ataxia Rating Scale, examiner-rated functional disability scales, self-reported activities of daily living and performance measures such as the timed 25-foot walk, 9-hole pegboard test, PATA speech test, and low-contrast letter acuity vision charts. This study examines the rate of disease progression over one and two years in a cohort of 236 Friedreich ataxia patients using these scales and performance measure composites. The Friedreich Ataxia Rating Scale and performance-measure composites captured disease progression, with a greater sensitivity to change over 2 years than over 1 year. The measures differed in their sensitivity to change and in possible bias. These results help to establish norms for progression in FRDA that can be useful in measuring the long-term success of therapeutic agents and defining sample-size calculations for double-blind clinical trials.
authors.affiliation: Department of Neurology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Lisa S
authors.initials: LS
authors.lastname: Friedman
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Farmer
authors.forename: Susan
authors.initials: S
authors.lastname: Perlman
authors.forename: George
authors.initials: G
authors.lastname: Wilmot
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Gomez
authors.forename: Khalaf O
authors.initials: KO
authors.lastname: Bushara
authors.forename: Katherine D
authors.initials: KD
authors.lastname: Mathews
authors.forename: S H
authors.initials: SH
authors.lastname: Subramony
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ashizawa
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Balcer
authors.forename: Robert B
authors.initials: RB
authors.lastname: Wilson
authors.forename: David R
authors.initials: DR
authors.lastname: Lynch
mesh_terms: D000203:Activities of Daily Living; D000328:Adult; D000368:Aged; D002986:Clinical Trials as Topic; D004272:DNA, Mitochondrial / Q000235:genetics; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D005621:Friedreich Ataxia / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology*; D006801:Humans; D033862:Iron-Binding Proteins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009460:Neurologic Examination; D017354:Point Mutation / Q000235:genetics; D012720:Severity of Illness Index; D013064:Speech Disorders / Q000175:diagnosis; D018911:Trinucleotide Repeats / Q000235:genetics; D016138:Walking; D055815:Young Adult; D000096923:Frataxin
chemical_list: D004272:DNA, Mitochondrial; D033862:Iron-Binding Proteins; D000096923:Frataxin