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Department of Neurology (Dr. Noseworthy), Mayo Clinic and Foundation, Rochester, MN; the Department of Clinical Neurological Sciences (Drs. Noseworthy and Ebers, and M. Vandervoort), University of Western Ontario, London, ON; the Division of Neurology, Department of Medicine (R. Farquhar), University of British Columbia, Vancouver, BC; and the Hamilton Civic Hospitals Research Center (E. Yetisir and R. Roberts), McMaster University, Hamilton, ON, Canada.
In the randomized, placebo-controlled, physician-blinded Canadian cooperative trial of cyclophosphamide and plasma exchange, neither active treatment regimens (group I: IV cyclophosphamide and prednisone; group II: weekly plasma exchange, oral cyclophosphamide, and prednisone) were superior to placebo (group III: sham plasma exchange and placebo medications) using the blinded, evaluating neurologists' assessments of disease course (primary analysis). All patients were examined by both a blinded and an unblinded neurologist at each assessment in this trial. We compared the blinded and unblinded neurologists' judgment of treatment response and analyzed the clinical behavior of patients who correctly guessed their treatment. The unblinded (but not the blinded) neurologists' scores demonstrated an apparent treatment benefit at 6, 12, and 24 months for the group II patients (not group I or placebo; p <0.05, two-tailed). There were no significant differences in the time to treatment failure or in the proportions of patients improved, stable, or worse between the group II and group III patients who correctly guessed their treatment assignments and those who did not. Physician blinding prevented an erroneous conclusion about treatment efficacy (false positive, type 1 error).
Address correspondence and reprint requests to Dr. J.H. Noseworthy, Department of Neurology, Mayo Clinic and Foundation, 200 First Street SW, Rochester, MN 55905.
Supported in part by grants from the Medical Research Council of Canada and the Multiple Sclerosis Society of Canada
Presented in part at the 44th annual meeting of the American Academy of Neurology, San Diego, CA, May 1992.
Received April 1, 1993. Accepted for publication in final form June 15, 1993.
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