Measuring the Rate of Progression in Friedreich Ataxia: Implications for Clinical Trial Design

作者：Friedman Lisa S; Farmer Jennifer M; Perlman Susan; Wilmot George; Gomez Christopher M; Bushara Khalaf O; Mathews Katherine D; Subramony S H; Ashizawa Tetsuo; Balcer Laura J; Wilson Robert B; Lynch David R^*

来源：Movement Disorders, 2010, 25(4): 426-432.

DOI：10.1002/mds.22912

• ataxia
• natural history study
• clinical neurology examination
• mitochondrial disorder
• trinucleotide repeat disease

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 I 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.

• 出版日期2010-3-15