Measuring the rate of progression in Friedreich ataxia: Implications for clinical trial design

Authors

  • Lisa S. Friedman BS,

    1. Department of Neurology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    2. Department of Pediatrics, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    3. Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
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  • Jennifer M. Farmer MS,

    1. Department of Neurology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    2. Department of Pediatrics, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    3. Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
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  • Susan Perlman MD,

    1. Department of Neurology, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California, USA
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  • George Wilmot MD, PhD,

    1. Department of Neurology, Emory University, Atlanta, Georgia, USA
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  • Christopher M. Gomez MD PhD,

    1. Department of Neurology, University of Minnesota, Minneapolis, Minnesota, USA
    2. Department of Neurology, University of Chicago, Chicago, Illinois, USA
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  • Khalaf O. Bushara MD,

    1. Department of Neurology, University of Minnesota, Minneapolis, Minnesota, USA
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  • Katherine D. Mathews MD,

    1. Departments of Neurology and Pediatrics, University of Iowa, Iowa City, Iowa, USA
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  • S. H. Subramony MD,

    1. Department of Neurology, University of Texas Medical Branch, Galveston, Texas, USA
    2. Department of Neurology, University of Mississippi, Jackson, Mississippi, USA
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  • Tetsuo Ashizawa MD,

    1. Department of Neurology, University of Texas Medical Branch, Galveston, Texas, USA
    2. Department of Neurology, University of Florida, Gainesville, Florida, USA
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  • Laura J. Balcer MD, MSCE,

    1. Department of Neurology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
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  • Robert B. Wilson MD, PhD,

    1. Department of Pathology and Laboratory Medicine, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
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  • David R. Lynch

    Corresponding author
    1. Department of Neurology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    2. Department of Pediatrics, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    3. Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
    • Department of Neurology, Abramson Research Center, Children's Hospital of Philadelphia, Room 502, 3615 Civic Center Blvd, Philadelphia 19104, PA
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  • Potential conflict of interest: The authors report no conflict of interest related to this study.

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. © 2010 Movement Disorder Society

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