Journal of Clinical Epidemiology
Volume 52, Issue 2 , Pages 113-122 , February 1999

Are Randomized Control Trial Outcomes Influenced by the Inclusion of a Placebo Group? A Systematic Review of Nonsteroidal Antiinflammatory Drug Trials for Arthritis Treatment

  • Paula A. Rochon

      Affiliations

    • Kunin-Lunenfeld Applied Research Unit, Baycrest Centre for Geriatric Care, Institute for Clinical Evaluative Sciences, Departments of Medicine and Public Health Sciences, Clinical Epidemiology and Health Care Research Program, University of Toronto, Toronto, Ontario, Canada
    • Corresponding Author InformationAddress correspondence to: Paula A. Rochon, MD, MPH, FRCP(C), Baycrest Centre for Geriatric Care, 3560 Bathurst Street, Toronto, Ontario, Canada, M6A 2E1
  • ,
  • Malcolm A. Binns

      Affiliations

    • Rotman Research Institute, Baycrest Centre for Geriatric Care, Toronto, Ontario, Canada
  • ,
  • Jason A. Litner

      Affiliations

    • Baycrest Centre for Geriatric Care, Toronto, Ontario, Canada
  • ,
  • Geoffrey M. Litner

      Affiliations

    • Baycrest Centre for Geriatric Care, Toronto, Ontario, Canada
  • ,
  • Michelle S. Fischbach

      Affiliations

    • Baycrest Centre for Geriatric Care, Toronto, Ontario, Canada
  • ,
  • David Eisenberg

      Affiliations

    • Center for Alternative Medicine Research, Beth Israel Hospital, Boston, MA USA
    • Harvard Medical School, Boston, MA USA
  • ,
  • Ted J. Kaptchuk

      Affiliations

    • Center for Alternative Medicine Research, Beth Israel Hospital, Boston, MA USA
  • ,
  • William B. Stason

      Affiliations

    • MetaWorks, Boston, MA USA
  • ,
  • Thomas C. Chalmers

      Affiliations

    • MetaWorks, Boston, MA USA

,Accepted 13 October 1998.

References 

  1. Rothman KJ, Michels KB. The continuing unethical use of placebo controls. N Engl J Med. 1994;331:394–398
  2. Gotzsche PC. Is there logic in the placebo?. Lancet. 1994;344:925–926
  3. Chaput de Saintonge DM, Herxheimer A. Harnessing placebo effects in health care. Lancet. 1994;344:995–998
  4. Turner JA, Deyo RA, Loeser JD, Von Korff M, Fordyce WE. The importance of placebo effects in pain treatment and research. JAMA. 1994;271:1609–1614
  5. Kleijnen J, de Craen AJM, van Everdingen J, Krol L. Placebo effect in doubleblind clinical trials (A review of interactions with medications). Lancet. 1994;344:1347–1349
  6. Oh VMS. Magic or medicine? Clinical pharmacological basis of placebo medication. Ann Acad Med Singapore. 1991;20:31–37
  7. Weiner M, Weiner GJ. The kinetics and dynamics of responses to placebo. Clin Pharm Ther 1996; 60: 247–254.
  8. Joyce CRB. Placebo and complementary medicine. Lancet. 1994;344:1279–1281
  9. Thomas KB. The placebo in general practice. Lancet. 1994;344:1066–1067
  10. Laporte JR, Figueras A. Placebo effects in psychiatry. Lancet. 1994;344:1206–1209
  11. Johnson AG. Surgery as a placebo. Lancet. 1994;344:1140–1142
  12. Langley GB, Sheppeard H, Wigley RD. Placebo therapy in rheumatoid arthritis. Clin Exp Rheumatol. 1983;1:17–21
  13. Lasagna L, Mosteller F, von Felsinger JM, Beecher HK. A study of the placebo response. Am J Med. 1954;16:770–779
  14. McQuay H, Carroll D, Moore A. Variation in the placebo effect in randomised controlled trials of analgesics (all is as blind as it seems). Pain. 1995;64:331–335
  15. Traut EF, Passarelli EW. Placebos in the treatment of rheumatoid arthritis and other rheumatic conditions. Ann Rheum Dis. 1957;16:18–21
  16. Gracely RH, Dubner R, Deeter WR, Wolskee PJ. Clinicians’ expectations influence placebo analgesia. Lancet. 1985;1:43
  17. Affleck DC, Eaton MT, Mansfield E. The action of a medication and the physician’s expectations. Nebr State Med J. 1966;51:331–334
  18. Gotzsche PC. Meta-analysis of NSAIDs: Contribution of drugs, doses, trial designs, and meta-analytic techniques. Scand J Rheum 1993; 22: 255–260.
  19. Rosenzweig P, Brohier S, Zipfel A. The placebo effect in healthy volunteers (Influence of experimental conditions on the adverse events profile during phase I studies). Clin Pharmacol Ther. 1993;54:578–583
  20. Skovlund E. Should we tell trial patients that they might receive placebo?. Lancet. 1991;337:1041
  21. Bystritsky A, Waikar SV. Inert placebo versus active medication (Patient blindability in clinical pharmacological trials). J Nerv Ment Dis. 1994;182:485–487
  22. Tangrea JA, Adrianza ME, Helsel WE. Risk factors for the development of placebo adverse reactions in a multicenter clinical trial. Ann Epidemiol. 1994;4:327–331
  23. Levine J, Gordon N. Influence of the method of drug administration on analgesic response. Nature. 1984;312:755–756
  24. Moscucci M, Byrne L, Weintraub M, Cox C. Blinding, unblinding, and the placebo effect (An analysis of patients’ guesses of treatment assignment in a double-blind clinical trial). Clin Pharmacol Ther. 1987;41:259–265
  25. Schapira K, McClelland HA, Griffiths NR, Newell DJ. Study on the effects of tablet colour in the treatment of anxiety states. BMJ. 1970;2:446–449
  26. Bergmann JF, Chassany O, Gandiol J, Deblois P, Kanis JA, Segrestaa JM, Caulin C, Dahan R. A randomized clinical trial of the effect of informed consent on the analgesic activity of placebo and naproxen in cancer pain. Clinical trials and meta-analysis. 1994; 29: 41–47.
  27. de Craen AJM, Roos PJ, de Vries AL, Kleijnen J. Effect of color of drugs (Systematic review of perceived effect of drugs and of their effectiveness). BMJ. 1996;313:1624–1626
  28. Bourne HR. Rational use of placebo. In: Melmon KL, Morelli HF, Eds. Clinical Pharmacology: Basic principles in therapeutics, 2nd ed. New York: Macmillan; 1978: 1052–1062.
  29. Chalmers TC, Berrier J, Hewitt P, Berlin J, Reitman D, Nagalingam R, et al. Meta-analysis of randomized controlled trials as a method of estimating rare complications of non-steroidal antiinflammatory drug therapy. Ailment Pharmacol Ther. 1988;2S:9–26
  30. 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
  31. SAS Institute Inc. SAS Statistical Analysis System (Release 6.11 ed.) Cary, NC: SAS Institute Inc.; 1995.
  32. Rochon PA, Gurwitz JH, Simms RW, Fortin PR, Felson DT, Minaker KL, et al. A study of manufacturer-supported trials of nonsteroidal anti-inflammatory drugs in the treatment of arthritis. Arch Intern Med. 1994;154:157–163
  33. The Standards of Reporting Trials Group. A proposal for structured reporting of randomized controlled trials. JAMA 1994; 272: 1926–1931.
  34. Benson H, McCallie DP. Angina pectoris and the placebo effect. N Engl J Med. 1979;300:1424–1429

PII: S0895-4356(98)00149-8

Journal of Clinical Epidemiology
Volume 52, Issue 2 , Pages 113-122 , February 1999