William L. Greene, MD; John Concato, MD, MPH; Alvan R. Feinstein, MD
Grant Support: Dr. Greene was a Robert Wood Johnson Clinical Scholar at Yale University School of Medicine at the time this work was done. Dr. Concato is supported by a Career Development Award from the Veterans Affairs Health Services Research and Development Service.
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Current Author Addresses: Dr. Greene: Medical Affairs Department, Genentech, Inc., Mailstop 84, 1 DNA Way, South San Francisco, CA 94080.
Drs. Concato and Feinstein: Robert Wood Johnson Clinical Scholars Program, Yale University School of Medicine, 333 Cedar Street, SHM IE-61, New Haven, CT 06510.
Most clinical studies are done to show comparative superiority, but many reports now claim equivalence between the investigated entities. These assertions may not always be supported by the methods used and the results obtained.
To assess the justification and support for claims of clinical or therapeutic equivalence in medical journals.
A search of MEDLINE for articles published from 1992 through 1996.
From 1209 citations that contained the word equivalence in the title or abstract or contained the Medical Subject Heading therapeutic equivalency, we excluded 1121 studies reporting nonoriginal research, purely laboratory or other nonhuman research, and studies in which equivalence was not the main claim. The remaining 88 eligible papers were evaluated for five methodologic attributes.
Only 45 (51%) of the 88 reports were specifically aimed at studying equivalence; the others either tried to show superiority or did not state a research aim. The quantitative distinctions regarded as “equivalent” ranged from 0% to 21% for direct increments and from 0% to 76% for proportionate differences. An equivalence boundary was set and confirmed with an appropriate statistical test in only 23% of reports. In 67% of reports, equivalence was declared after a failed test for comparative superiority, and in 10%, the claim of equivalence was not statistically evaluated. The sample size needed to confirm results had been calculated in advance for only 33% of reports. Sample size was 20 patients per group or fewer in 25% of reports.
Many studies of clinical equivalence do not set boundaries for equivalence. Claims of “difference” or “similarity” are often made not by thoughtful examination of the data but by tests of statistical significance that are often misapplied or accompanied by inadequate sample sizes. These methodologic flaws can lead to false claims, inconsistencies, and harm to patients.
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Greene WL, Concato J, Feinstein AR. Claims of Equivalence in Medical Research: Are They Supported by the Evidence?. Ann Intern Med. 2000;132:715–722. doi: 10.7326/0003-4819-132-9-200005020-00006
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Published: Ann Intern Med. 2000;132(9):715-722.
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