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

Clinical Autonomic Research : Official Journal of the Clinical Autonomic Research Society
Wolfgang Singer, Phillip A Low

Abstract

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 disease modification. A major hurdle has been uncertainty about the number of patients needed to achieve adequate power. Information based on natural history studies suggested such numbers to be so large that only international multi-center models seemed feasible. When designing the rifampicin trial in MSA we sought to identify and apply strategies that would improve power and reduce the number needed to treat to allow for an oligocenter approach. Strategies included: (1) inclusion/exclusion criteria designed to enroll patients with relatively early, actively progressing disease; (2) minimizing dropouts; (3) pre-defined interim analysis; and (4) approaches to reduce scoring variability. The model allowed for the number needed to treat to be only 50 patients per treatment arm. Ten selected sites managed to reach the recruitment goal within 12 months. The dropout rate was less than 10%, and the goal of enrolling patients with actively progressing disease was accomplished as reflected by the...Continue Reading

References

Jan 30, 2004·Lancet Neurology·Gregor K WenningWerner Poewe
Sep 29, 2004·Movement Disorders : Official Journal of the Movement Disorder Society·Gregor K WenningUNKNOWN Multiple System Atrophy Study Group
Sep 15, 2005·Movement Disorders : Official Journal of the Movement Disorder Society·Felix GeserUNKNOWN European MSA Study Group
Nov 18, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Clifford W ShultsEliezer Masliah
Oct 5, 2007·Movement Disorders : Official Journal of the Movement Disorder Society·Susanne MayUNKNOWN North American Multiple System Atrophy Study Group
Nov 17, 2009·Lancet Neurology·Nadia StefanovaGregor Karl Wenning
Oct 4, 2011·Trends in Neurosciences·Kiren UbhiEliezer Masliah
Dec 12, 2012·Annals of Neurology·Lorraine V KaliaAnthony E Lang
Dec 21, 2012·Nature Reviews. Neuroscience·Hilal A LashuelEliezer Masliah
Mar 7, 2014·Progress in Neurobiology·Daniela Kuzdas-WoodGregor K Wenning

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Citations

Jun 19, 2016·Progress in Neurobiology·Lucy Norcliffe-KaufmannHoracio Kaufmann
Nov 5, 2015·Clinical Autonomic Research : Official Journal of the Clinical Autonomic Research Society·Melissa St AubinR Corey O'Connor
Sep 22, 2017·Neurology·Nicolas N MadiganEduardo E Benarroch
Feb 9, 2021·Clinical Autonomic Research : Official Journal of the Clinical Autonomic Research Society·Jose-Alberto PalmaHoracio Kaufmann

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