January 24, 1994

A Study of Manufacturer-Supported Trials of Nonsteroidal Anti-inflammatory Drugs in the Treatment of Arthritis

Author Affiliations

From the Geriatric Research Education and Clinical Center, Brockton/West Roxbury Veterans Affairs Medical Center, Division on Aging, Harvard Medical School, Boston, Mass (Drs Rochon and Minaker); Program for the Analysis of Clinical Strategies, Gerontology Division, Brigham and Women's Hospital, Harvard Medical School (Dr Gurwitz); Arthritis Center, Boston University School of Medicine (Drs Simms and Felson); Department of Medicine and Division of Clinical Epidemiology, Montreal (Quebec) General Hospital, McGill University (Dr Fortin); and Technology Assessment Group, Harvard School of Public Health (Dr Chalmers). Dr Rochon is now with Baycrest Centre for Geriatric Care and Mount Sinai Hospital, Division of Geriatric Medicine, Department of Medicine, University of Toronto (Ontario).

Arch Intern Med. 1994;154(2):157-163. doi:10.1001/archinte.1994.00420020059007

Background:  To study the relation between reported drug performance in published trials and support of the trials by the manufacturer of the drug under evaluation, we studied a sample of trials of nonsteroidal anti-inflammatory drugs (NSAIDs) used in the treatment of arthritis.

Methods:  All randomized control trials of NSAIDs published between September 1987 and May 1990 identified by MEDLINE were reviewed. If an article met the following criteria (n=61), it was selected: trials involving adult patients with osteoarthritis or rheumatoid arthritis (n=180), use of nonsalicylate NSAIDs marketed in the United States (n=101), randomized control trial (n=81), duration of the trial 4 or more days (n=78), and use of an efficacy outcome measure (n=61). Reviewers, "blinded" to manufacturer status, evaluated the narrative interpretation of results and extracted numeric data on efficacy and toxicity. Manufacturer-associated trials were defined as those that acknowledged an association with a pharmaceutical manufacturer. Because of the scarcity of non—manufacturer-associated trials (n=9), we report only on the manufacturer-associated articles.

Results:  Fifty-two publications (85.2%) representing 56 trials were associated with a manufacturer. The manufacturer-associated drug was reported as comparable with (71.4%) or superior to (28.6%) the comparison drug in all 56 trials. These narrative claims of superiority were usually justified with trial data. Of the trials identifying one drug as less toxic (n=22), the manufacturer-associated drug's safety was reported as superior to the comparison drug in 86.4% of cases. Justification for the narrative interpretation of the trial findings regarding less toxicity was provided in only 12(54.5%) of 22 trials.

Conclusion:  The manufacturer-associated NSAID is almost always reported as being equal or superior in efficacy and toxicity to the comparison drug. These claims of superiority, especially in regard to side effect profiles, are often not supported by trial data. These data raise concerns about selective publication or biased interpretation of results in manufacturer-associated trials.(Arch Intern Med. 1994;154:157-163)