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Shifting Our Thinking About Uncommon Disease Trials: The Case of Methotrexate in Scleroderma SINDHU R. JOHNSON, BRIAN M. FELDMAN, JANET E. POPE, and GEORGE A. TOMLINSON
ABSTRACT. Methods. Data from 71 patients with diffuse SSc (n = 35 MTX, n = 36 placebo) in the trial were reanalyzed using Bayesian models. We examined 3 primary outcomes: modified Rodnan skin score (MRSS), University of California Los Angeles (UCLA) skin score, and physician global assessment of overall disease activity. Using noninformative prior probability distributions, the probability of beneficial treatment effects for each outcome and the probability of simultaneous benefit in outcomes were computed. Results. The probability that treatment with MTX results in better mean outcomes than placebo was 94% for MRSS, 96% for UCLA skin score, and 88% for physician global assessment. There was 96% probability that at least 2 of 3 primary outcomes were better on treatment. Conclusion. Bayesian analysis of uncommon disease trials allows for more flexible and clinically relevant interpretations of the data. From the trial data, clinicians can infer that MTX has a high probability of beneficial effects on skin score and global assessment. (J Rheumatol First Release Dec 1 2008; doi:10.3899/jrheum.071169) Key Indexing Terms:
RARE DISEASE TRIALS
From the Division of Rheumatology, University Health Network, The Hospital for Sick Children, Toronto; Departments of Paediatrics, Health Policy Management and Evaluation, and Public Health Sciences, University of Toronto, Toronto; University of Western Ontario, London; and Division of Clinical Decision Making and Health Care, Toronto General Research Institute, Toronto, Ontario, Canada. Dr. Johnson has been awarded an Abbott Scholar Award for Rheumatology Research and Canadian Arthritis Network Fellowship. Dr. Feldman is supported by a Canada Research Chair in Childhood Arthritis. S.R. Johnson, MD, FRCPC, Division of Rheumatology, University Health Network, Department of Health Policy Management and Evaluation, University of Toronto; B.M. Feldman, MD, MSc, FRCPC, Division of Rheumatology, The Hospital for Sick Children, Departments of Paediatrics, Health Policy Management and Evaluation, and Public Health Sciences, University of Toronto; J.E. Pope, MD, MPH, FPCPC, Division of Rheumatology, University of Western Ontario; G.A. Tomlinson, PhD, Departments of Health Policy Management and Evaluation, and Public Health Sciences, University of Toronto, Division of Clinical Decision Making and Health Care, Toronto General Research Institute. Address reprint requests to Dr. S. Johnson, Division of Rheumatology, Toronto Western Hospital, Ground Floor, East Wing, 399 Bathurst Street, Toronto, ON M5T 2S8. E-mail: Sindhu.Johnson@uhn.on.ca Accepted for publication September 22, 2008.
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