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Optimal Use of the Non-Inferiority Trial Design

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Abstract

Superiority trials are conducted to test the hypothesis that a treatment or strategy A is superior to (i.e., better than) treatment strategy B in reducing the impact of disease. However, A may be considerably safer, more convenient, or cheaper than B. These features may make A more attractive than B even if the burden of disease is reduced comparably by the two treatments, or even a bit worse by A over B. In this context, non-inferiority trials have become increasingly popular to test the hypothesis that a new treatment is not ‘unacceptably worse’ than an active comparator by more than a predefined non-inferiority margin. Non-inferiority trials have unique design features and methodology and require a different analysis than traditional superiority trials. The main aim of this overview is to analyze the role of non-inferiority trials in the development of new treatments, involving some scientific, statistical, and practical considerations. We elucidate some aspects of non-inferiority trials that contribute to the validity of the results. The unique design features and methodology of non-inferiority trials are summarized and key findings to consider when evaluating a non-inferiority trial are illustrated.

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Authors and Affiliations

  1. Department of Medicine and Surgery, University of Insubria, Varese, Italy

    Fabio Angeli

  2. Department of Medicine and Cardiopulmonary Rehabilitation, Maugeri Care and Research Institute, IRCCS Tradate, Varese, Italy

    Fabio Angeli & Sergio Masnaghetti

  3. Fondazione Umbra Cuore e Ipertensione-ONLUS, Division of Cardiology, Hospital S. Maria della Misericordia, Perugia, Italy

    Paolo Verdecchia

  4. Department of Medicine, University of Perugia, 06156, Perugia, Italy

    Gaetano Vaudo & Gianpaolo Reboldi

Authors
  1. Fabio Angeli
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  2. Paolo Verdecchia
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  3. Gaetano Vaudo
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  4. Sergio Masnaghetti
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  5. Gianpaolo Reboldi
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Corresponding author

Correspondence to Gianpaolo Reboldi.

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No external funding was used in the preparation of this article.

Conflict of interest

Fabio Angeli Paolo Verdecchia, Gaetano Vaudo, Sergio Masnaghetti, and Gianpaolo Reboldi have no conflicts of interest that are directly relevant to the content of this article.

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Angeli, F., Verdecchia, P., Vaudo, G. et al. Optimal Use of the Non-Inferiority Trial Design. Pharm Med 34, 159–165 (2020). https://doi.org/10.1007/s40290-020-00334-z

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  • DOI: https://doi.org/10.1007/s40290-020-00334-z

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