Through the looking glass: understanding non-inferiority

Jennifer Schumi, Janet T Wittes, Jennifer Schumi, Janet T Wittes

Abstract

Non-inferiority trials test whether a new product is not unacceptably worse than a product already in use. This paper introduces concepts related to non-inferiority, and discusses the regulatory views of both the European Medicines Agency and the United States Food and Drug Administration.

Figures

Figure 1
Figure 1
The role of Δ in superiority, equivalence and non-inferiority trials.
Figure 2
Figure 2
Possible outcomes of a non-inferiority trial.
Figure 3
Figure 3
A forest plot and M1.
Figure 4
Figure 4
M2 as a fraction of M1.

References

    1. Temple R, Ellenberg SS. Placebo-controlled trials and active-control trials in the evaluation of new treatments; Part 1: Ethical and scientific issues. Annals of Internal Medicine. 2000;133:455–463.
    1. Ellenberg SS, Temple R. Placebo-controlled trials and active-control trials in the evaluation of new treatments; Part 2: Practical issues and specific cases. Annals of Internal Medicine. 2000;133:464–470.
    1. Wittes J. Active-control trials: a linguistic problem. International Chinese Stat Assoc Bulletin. 2001. pp. 39–40.
    1. Wiens BL, Zhao W. The role of intention to treat in analysis of noninferiority studies. Clin Trials. 2007;4:286–291. doi: 10.1177/1740774507079443.
    1. EMA Committee for Proprietary Medicinal Products (CPMP) Points to Consider on Switching between Superiority and Non-inferiority London. 2000.
    1. United States Food and Drug Administration. Guidance for Industry Non-Inferiority Clinical Trials. 2010.
    1. Rothmann M, Li N, Chen G. et al.Design and analysis of non-inferiority mortality trials in oncology. Stat Med. 2003;22:239–264.
    1. Rothmann MD, Tsou HH. On non-inferiority analysis based on delta-method confidence intervals. J Biopharm Stat. 2003;13:565–583. doi: 10.1081/BIP-120022775.
    1. EMA Committee for Medicinal Products for Human Use (CHMP) Guideline on the Choice of the Non-inferiority Margin London. 2005.
    1. Snappin S, Jiang Q. Controlling the type 1 error rate in non-inferiority trials. Stat Med. 2008;27:371–381. doi: 10.1002/sim.3072.
    1. Snappin S, Jiang Q. Preservation of effect and the regulatory approval of new treatments on the basis of non-inferiority trials. Stat Med. 2008;27:382–391. doi: 10.1002/sim.3073.
    1. Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959;22:719–748.
    1. Yusuf S, Collins R. et al.Why do we need some large, simple randomized trials? Stat Med. 1984;3:409–420. doi: 10.1002/sim.4780030421.
    1. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–188. doi: 10.1016/0197-2456(86)90046-2.
    1. Petitti DB. Meta-analysis, Decision Analysis, and Cost-effectiveness Analysis: Methods for Quantitative Synthesis in Medicine. Oxford: Oxford University Press, 306 pp; 2000.
    1. Teo KK, Yusuf S. et al.Effects of intravenous magnesium in suspected acute myocardial infarction: overview of randomized trials. BMJ. 1991;303:1499–1503. doi: 10.1136/bmj.303.6816.1499.
    1. Fleming TR. Current issues in non-inferiority trials. Stat Med. 2008;27:317–332. doi: 10.1002/sim.2855.
    1. Fleming TR, Powers JH. Issues in noninferiority trials: The evidence in community-acquired pneumonia. Clin Infect Dis. 2008;47(Suppl 3):S108–S120.

Source: PubMed

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