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Methodological aspects of superiority, equivalence, and non-inferiority trials

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A Correction to this article was published on 22 September 2020

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Abstract

Depending on the scientific hypothesis to be addressed, randomized-controlled trials (RCT) are accordingly designed. RCTs that aim to determine whether a novel, experimental therapeutic intervention (either a drug or a treatment) is superior to a placebo or control intervention, are called superiority trials. Less common are the non-inferiority RCTs, designed to assess whether a new intervention is not unacceptably worse than an already existing reference intervention. An equivalence RCT is designed to investigate whether a novel treatment is equivalently effective to another, already existing, control intervention. In equivalence and non-inferiority RCTs, the efficacy of the reference intervention (active comparator) is already established, and therefore, an untreated control group would not be ethical. In this review, using a series of examples derived from equivalence and non-inferiority/superiority RCTs, we describe the main differences and methodological aspects among these three different types of RCTs.

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Change history

  • 22 September 2020

    In the original publication of the article, the given name and family name of the author were swapped. The correct author name is given in this erratum.

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Authors and Affiliations

  1. Division of Nephrology and Hypertension, 1st Department of Internal Medicine, School of Medicine, AHEPA Hospital, Aristotle University of Thessaloniki, St. Kyriakidi 1, 54636, Thessaloniki, Greece

    Roumeliotis Stefanos

  2. Institute of Clinical Physiology (IFC-CNR), Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension, Ospedali Riuniti, via Vallone Petrara, Reggio Calabria, Italy

    Roumeliotis Stefanos, D.’Arrigo Graziella & Tripepi Giovanni

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  1. Roumeliotis Stefanos
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  2. D.’Arrigo Graziella
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  3. Tripepi Giovanni
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Correspondence to Roumeliotis Stefanos.

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Stefanos, R., Graziella, D. & Giovanni, T. Methodological aspects of superiority, equivalence, and non-inferiority trials. Intern Emerg Med 15, 1085–1091 (2020). https://doi.org/10.1007/s11739-020-02450-9

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