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Noninferiority Trials

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Principles and Practice of Clinical Trials

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Abstract

In this chapter we provide an overview of non-inferiority trials. We first introduce two motivating examples and describe scenarios for when a non-inferiority trial is appropriate. We next describe the procedures for defining the margin of non-inferiority from both regulatory and public health perspectives and then provide practical guidance for how to design a non-inferiority trial and analyze the resulting data, paying particular attention to regulatory and other published guidelines. We go on to discuss particular challenges unique to non-inferiority trials including the importance of assay sensitivity, the enigma of effect preservation, switching between non-inferiority and superiority, the interpretation of results when event rate assumptions are incorrect, and the place of interim analyses and safety monitoring. We conclude the chapter by addressing alternative methodologies and innovative perspectives on non-inferiority trials that have been proposed in an attempt to mitigate these challenges, including Bayesian approaches, alternative three-arm and pragmatic designs, and methods that address different treatment durations and the averted infections ratio.

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Author information

Authors and Affiliations

  1. UCSF Center for Tuberculosis, University of California San Francisco, San Francisco, CA, USA

    Patrick P. J. Phillips

  2. Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA

    Patrick P. J. Phillips & David V. Glidden

Authors
  1. Patrick P. J. Phillips
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  2. David V. Glidden
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Corresponding author

Correspondence to Patrick P. J. Phillips .

Editor information

Editors and Affiliations

  1. Department of Surgery, Division of Surgical Oncology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Steven Piantadosi

  2. Department of Epidemiology, School of Public Health, Johns Hopkins University, Baltimore, MD, USA

    Curtis L. Meinert

Section Editor information

  1. Statistician, MRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, London, UK

    Babak Choodari-Oskooei

  2. MRC Clinical Trials Unit and Institute of Clinical Trials and Methodology, University College of London, London, England

    Mahesh Parmar

  3. The Johns Hopkins Center for Clinical Trials and Evidence Synthesis, Johns Hopkins School of Public Health, Baltimore, MA, USA

    Curtis L. Meinert

  4. Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Steven Piantadosi

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Phillips, P.P.J., Glidden, D.V. (2022). Noninferiority Trials. In: Piantadosi, S., Meinert, C.L. (eds) Principles and Practice of Clinical Trials. Springer, Cham. https://doi.org/10.1007/978-3-319-52636-2_98

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