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Non-inferiority trials: determining whether alternative treatments are good enough

Ian A Scott
Med J Aust 2009; 190 (6): 326-330.

Summary

  • Ian A Scott1,2

  • 1 Department of Internal Medicine and Clinical Epidemiology, Princess Alexandra Hospital, Brisbane, QLD.
  • 2 School of Medicine, University of Queensland, Brisbane, QLD.


Competing interests:

None identified.

  • 1. The SPACE Collaborative Group. 30 day results from the SPACE trial of stent-protected angioplasty versus carotid endarterectomy in symptomatic patients: a randomised non-inferiority result. Lancet 2006; 368: 1239-1247.
  • 2. Walsh TJ, Pappas P, Winston DJ, et al for the National Institute of Allergy and Infectious Diseases Mycoses Study Group. Voriconazole compared with liposomal amphotericin B for empirical antifungal therapy in patients with neutropenia and persistent fever. N Engl J Med 2002; 346: 225-234.
  • 3. Pfeffer MA, McMurray JJV, Velazquez EJ, et al for the Valsartan in Acute Myocardial Infarction Trial Investigators. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med 2003; 349: 1893-1906.
  • 4. Righini M, Le Gal G, Aujesky D, et al. Diagnosis of pulmonary embolism by multidetector CT alone or combined with venous ultrasonography of the leg: a randomised non-inferiority trial. Lancet 2008; 371: 1343-1352.
  • 5. Kinley H, Czoski-Murray C, George S, et al on behalf of the OpCheck Study Group. Effectiveness of appropriately trained nurses in preoperative assessment: randomised controlled equivalence/non-inferiority trial. BMJ 2002; 325: 1323-1327.
  • 6. Pater C. Equivalence and noninferiority trials — are they viable alternatives for registration of new drugs? (III). Curr Control Trials Cardiovasc Med 2004; 5: 8.
  • 7. Begg C, Cho M, Eastwood S, et al. Improving the quality of reporting of randomized controlled trials: the CONSORT statement. JAMA 1996; 276: 637-639.
  • 8. Piaggio G, Elbourne DR, Altman DG, et al; CONSORT Group. Reporting of noninferiority and equivalence randomized trials: an extension of the CONSORT statement. JAMA 2006; 295: 1152-1160.
  • 9. Keech A, Gebski V, Pike R. Interpreting and reporting clinical trials: a guide to the CONSORT statement and the principles of randomised controlled trials. Sydney: MJA Books, 2007.
  • 10. Executive Steering Committee on behalf of the SPORTIF III Investigators. Stroke prevention with the oral direct thrombin inhibitor ximelagatran compared with warfarin in patients with non-valvular atrial fibrillation (SPORTIF III): randomised controlled trial. Lancet 2003; 362: 1691-1698.
  • 11. Albers GW, Diener HC, Frison L, et al; SPORTIF Executive Steering Committee for the SPORTIF V Investigators. Ximelagatran vs warfarin for stroke prevention in patients with nonvalvular atrial fibrillation: a randomized trial. JAMA 2005; 293: 690-698.
  • 12. Halperin JL; Executive Steering Committee, SPORTIF III and V Study Investigators. Ximelagatran compared with warfarin for prevention of thromboembolism in patients with nonvalvular atrial fibrillation: rationale, objectives, and design of a pair of clinical studies and baseline patient characteristics (SPORTIF III and V). Am Heart J 2003; 146: 431-438.
  • 13. Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation. Analysis of pooled data from five randomised controlled trials. Arch Intern Med 1994; 154: 1449-1457.
  • 14. Kaul S, Diamond GA, Weintraub WS. Trials and tribulations of non-inferiority: the ximelagatran experience. J Am Coll Cardiol 2005; 46: 1986-1995.
  • 15. Committee for Medicinal Products for Human Use. Guideline on the choice of the non-inferiority margin. London: European Medicines Agency, 2005. http://www.emea.europa.eu/pdfs/human/ewp/215899en.pdf (accessed Aug 2008).
  • 16. Lange S, Freitag G. Choice of delta: requirements and reality — results of a systematic review. Biom J 2005; 47: 12-27.
  • 17. Wyrwich KW, Spertus JA, Kroenke K, et al. Clinically important differences in health status for patients with heart disease: an expert consensus panel report. Am Heart J 2004; 147: 615-622.
  • 18. Kaul S, Diamond GA. Good enough: a primer on the analysis and interpretation of noninferiority trials. Ann Intern Med 2006; 145: 62-69.
  • 19. Wood L, Egger M, Gluud LL, et al. Empirical evidence of bias in treatment effect estimates in controlled trials with different interventions and outcomes: meta-epidemiological study. BMJ 2008; 336: 601-608.
  • 20. 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.
  • 21. Le Henanff A, Giraudeau B, Baron G, Ravaud P. Quality of reporting of noninferiority and equivalence randomized trials. JAMA 2006; 295: 1147-1151.
  • 22. Garattini S, Bertele V. Non-inferiority trials are unethical because they disregard patients’ interests. Lancet 2007; 370: 1875-1877.
  • 23. Tramèr MR, Reynolds DJ, Moore RA, McQuay HJ. When placebo controlled trials are essential and equivalence trials are inadequate. BMJ 1998; 317: 875-880.
  • 24. Gotzsche PC. Lessons from and cautions about noninferiority and equivalence randomised trials. JAMA 2006; 295: 1172-1174.
  • 25. Garrett AD. Therapeutic equivalence: fallacies and falsification. Stat Med 2003; 22: 741-762.

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