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

A Study of Manufacturer-Supported Trials of Nonsteroidal Anti-inflammatory Drugs in the Treatment... Abstract 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) References 1. Beary JF. Pharmaceutical ads in journals . Ann Intern Med . 1992;117:616.Crossref 2. Relman AS. Dealing with conflicts of interest . N Engl J Med . 1984;310:1182-1183.Crossref 3. Rawlins MD. Doctors and the drug makers . Lancet . 1984;2:276-278.Crossref 4. Davidson RA. Source of funding and outcome of clinical trials . J Gen Intern Med . 1986;1:155-158.Crossref 5. Gøtzsche PC. Methodology and overt and hidden bias in reports of 196 double-blind trials of nonsteroidal antiinflammatory drugs in rheumatoid arthritis . Controlled Clin Trials . 1989;10:31-56.Crossref 6. Baum C, Kennedy DL, Forbes JB. Utilization of nonsteroidal anti-inflammatory drugs . Arthritis Rheum . 1985;28:686-692.Crossref 7. Committee on Safety of Medicines. Non-steroidal anti-inflammatory drugs and serious gastrointestinal adverse reactions, 1 . BMJ . 1986;292:614.Crossref 8. Rochon PA, Fortin PR, Dear KBG, Minaker KL, Chalmers TC. Reporting of age data in clinical trials of arthritis: deficiencies and solutions . Arch Intern Med . 1993;153:243-248.Crossref 9. Physicians'Desk Reference . 46th ed. Montvale, NJ: Medical Economics Co Inc; 1992;1:2561. 10. Canadian Pharmaceutical Association. Compendium of Pharmaceuticals and Specialties . 27th ed. Ottawa, Ontario: Canadian Pharmaceutical Association and Specialties; 1992;1. 11. Joint Formulary Committee 1989-1990 . British National Formulary . London, England: British Medical Association and Pharmaceutical Press; 1990;19:559. 12. Verzeichnis von Fertigarneimitteln der Mitglieder des Bundesverbandes der Pharmazeutischen Industrie e.V. Rote Liste 1991 . Wurt, Germany: Aulendorf Cantor; 1991:1. 13. Farmindustria . Repertorio Farmaceutico Italiano . 4th edition. Milano, Italia; Associazione Nazionale dell'Industria Farmaceutica; 1990;1. 14. Chalmers TC, Smith H Jr, Blackburn B, et al. A method for assessing the quality of a randomized control trial . Controlled Clin Trials . 1981;2:31-49.Crossref 15. Food and Drug Administration. Guidelines for the Clinical Evaluation of Anti-inflammatory and Antirheumatic Drugs (Adults and Children) . Washington, DC: US Dept of Health and Human Services, Public Health Service, Food and Drug Administration; 1991. 16. Ingelfinger JA, Mosteller F, Thibodeau LA, Ware JH. Biostatistics in Clinical Medicine . 2nd ed. New York, NY: Macmillan Publishing Co Inc; 1987;1:339. 17. Fries JF, Williams CA, Bloch DA. The relative toxicity of nonsteroidal anti-inflammatory drugs . Arthritis Rheum . 1991;34:1353-1360.Crossref 18. Dickerson K. The existence of publication bias and risk factors for its occurrence . JAMA . 1990;263:1385-1389.Crossref 19. Levy G. Publication bias: its implications for clinical pharmacology . Clin Pharmacol Ther . 1992;52:115-119.Crossref 20. Lauritsen K, Havelund T, Laursen LS, Rask-Madsen J. Withholding unfavorable results in drug company sponsored clinical trials . Lancet . 1987;1:1091.Crossref 21. Mindel JS. Failure of controlled clinical trial data to reach the literature . Clin Pharmacol Ther . 1992;52:4-5.Crossref 22. Hillman AL, Eisenberg JM, Pauly MV, et al. Avoiding bias in the conduct and reporting of cost-effectiveness research sponsored by pharmaceutical companies . N Engl J Med . 1991;324:1362-1365.Crossref 23. Anderson J, Felson DT, Meenan RF. Secular changes in published clinical trials of second-line agents in rheumatoid arthritis . Arthritis Rheum . 1991;34:1304-1309.Crossref 24. Reitman D, Sacks HS, Chalmers TC. Technical quality assessment of randomized control trials (RCTs) . Controlled Clin Trials . 1987;8:282. 25. Bero LA, Galbraith BA, Rennie D. The publication of sponsored symposiums in medical journals . N Engl J Med . 1992;327:1135-1140.Crossref 26. International Committee of Medical Journal Editors. Uniform requirements for manuscripts submitted to biomedical journals . Can Med Assoc J . 1992;146: 861-868. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Internal Medicine American Medical Association

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

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Publisher
American Medical Association
Copyright
Copyright © 1994 American Medical Association. All Rights Reserved.
ISSN
0003-9926
eISSN
1538-3679
DOI
10.1001/archinte.1994.00420020059007
Publisher site
See Article on Publisher Site

Abstract

Abstract 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) References 1. Beary JF. Pharmaceutical ads in journals . Ann Intern Med . 1992;117:616.Crossref 2. Relman AS. Dealing with conflicts of interest . N Engl J Med . 1984;310:1182-1183.Crossref 3. Rawlins MD. Doctors and the drug makers . Lancet . 1984;2:276-278.Crossref 4. Davidson RA. Source of funding and outcome of clinical trials . J Gen Intern Med . 1986;1:155-158.Crossref 5. Gøtzsche PC. Methodology and overt and hidden bias in reports of 196 double-blind trials of nonsteroidal antiinflammatory drugs in rheumatoid arthritis . Controlled Clin Trials . 1989;10:31-56.Crossref 6. Baum C, Kennedy DL, Forbes JB. Utilization of nonsteroidal anti-inflammatory drugs . Arthritis Rheum . 1985;28:686-692.Crossref 7. Committee on Safety of Medicines. Non-steroidal anti-inflammatory drugs and serious gastrointestinal adverse reactions, 1 . BMJ . 1986;292:614.Crossref 8. Rochon PA, Fortin PR, Dear KBG, Minaker KL, Chalmers TC. Reporting of age data in clinical trials of arthritis: deficiencies and solutions . Arch Intern Med . 1993;153:243-248.Crossref 9. Physicians'Desk Reference . 46th ed. Montvale, NJ: Medical Economics Co Inc; 1992;1:2561. 10. Canadian Pharmaceutical Association. Compendium of Pharmaceuticals and Specialties . 27th ed. Ottawa, Ontario: Canadian Pharmaceutical Association and Specialties; 1992;1. 11. Joint Formulary Committee 1989-1990 . British National Formulary . London, England: British Medical Association and Pharmaceutical Press; 1990;19:559. 12. Verzeichnis von Fertigarneimitteln der Mitglieder des Bundesverbandes der Pharmazeutischen Industrie e.V. Rote Liste 1991 . Wurt, Germany: Aulendorf Cantor; 1991:1. 13. Farmindustria . Repertorio Farmaceutico Italiano . 4th edition. Milano, Italia; Associazione Nazionale dell'Industria Farmaceutica; 1990;1. 14. Chalmers TC, Smith H Jr, Blackburn B, et al. A method for assessing the quality of a randomized control trial . Controlled Clin Trials . 1981;2:31-49.Crossref 15. Food and Drug Administration. Guidelines for the Clinical Evaluation of Anti-inflammatory and Antirheumatic Drugs (Adults and Children) . Washington, DC: US Dept of Health and Human Services, Public Health Service, Food and Drug Administration; 1991. 16. Ingelfinger JA, Mosteller F, Thibodeau LA, Ware JH. Biostatistics in Clinical Medicine . 2nd ed. New York, NY: Macmillan Publishing Co Inc; 1987;1:339. 17. Fries JF, Williams CA, Bloch DA. The relative toxicity of nonsteroidal anti-inflammatory drugs . Arthritis Rheum . 1991;34:1353-1360.Crossref 18. Dickerson K. The existence of publication bias and risk factors for its occurrence . JAMA . 1990;263:1385-1389.Crossref 19. Levy G. Publication bias: its implications for clinical pharmacology . Clin Pharmacol Ther . 1992;52:115-119.Crossref 20. Lauritsen K, Havelund T, Laursen LS, Rask-Madsen J. Withholding unfavorable results in drug company sponsored clinical trials . Lancet . 1987;1:1091.Crossref 21. Mindel JS. Failure of controlled clinical trial data to reach the literature . Clin Pharmacol Ther . 1992;52:4-5.Crossref 22. Hillman AL, Eisenberg JM, Pauly MV, et al. Avoiding bias in the conduct and reporting of cost-effectiveness research sponsored by pharmaceutical companies . N Engl J Med . 1991;324:1362-1365.Crossref 23. Anderson J, Felson DT, Meenan RF. Secular changes in published clinical trials of second-line agents in rheumatoid arthritis . Arthritis Rheum . 1991;34:1304-1309.Crossref 24. Reitman D, Sacks HS, Chalmers TC. Technical quality assessment of randomized control trials (RCTs) . Controlled Clin Trials . 1987;8:282. 25. Bero LA, Galbraith BA, Rennie D. The publication of sponsored symposiums in medical journals . N Engl J Med . 1992;327:1135-1140.Crossref 26. International Committee of Medical Journal Editors. Uniform requirements for manuscripts submitted to biomedical journals . Can Med Assoc J . 1992;146: 861-868.

Journal

Archives of Internal MedicineAmerican Medical Association

Published: Jan 24, 1994

References