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

doi:10.1007/s11739-020-02450-9

Review

. 2020 Sep;15(6):1085-1091.

doi: 10.1007/s11739-020-02450-9. Epub 2020 Jul 23.

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

Roumeliotis Stefanos^{1

2}, D 'Arrigo Graziella³, Tripepi Giovanni³

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. st_roumeliotis@Hotmail.com.
² Institute of Clinical Physiology (IFC-CNR), Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension, Ospedali Riuniti, via Vallone Petrara, Reggio Calabria, Italy. st_roumeliotis@Hotmail.com.
³ Institute of Clinical Physiology (IFC-CNR), Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension, Ospedali Riuniti, via Vallone Petrara, Reggio Calabria, Italy.

PMID: 32705494
DOI: 10.1007/s11739-020-02450-9

Review

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

Roumeliotis Stefanos et al. Intern Emerg Med. 2020 Sep.

. 2020 Sep;15(6):1085-1091.

doi: 10.1007/s11739-020-02450-9. Epub 2020 Jul 23.

Authors

Roumeliotis Stefanos^{1

2}, D 'Arrigo Graziella³, Tripepi Giovanni³

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. st_roumeliotis@Hotmail.com.
² Institute of Clinical Physiology (IFC-CNR), Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension, Ospedali Riuniti, via Vallone Petrara, Reggio Calabria, Italy. st_roumeliotis@Hotmail.com.
³ Institute of Clinical Physiology (IFC-CNR), Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension, Ospedali Riuniti, via Vallone Petrara, Reggio Calabria, Italy.

PMID: 32705494
DOI: 10.1007/s11739-020-02450-9

Erratum in

Correction to: Methodological aspects of superiority, equivalence, and non-inferiority trials.
Roumeliotis S, D'Arrigo G, Tripepi G. Roumeliotis S, et al. Intern Emerg Med. 2021 Jan;16(1):247. doi: 10.1007/s11739-020-02479-w. Intern Emerg Med. 2021. PMID: 32960430 No abstract available.

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.

Keywords: Equivalence; Non-inferiority; Randomized-controlled trial; Superiority.

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References

1. Lesaffre E (2018) Noninferiority clinical trials: the good, the bad, and the ugly. Semin Liver Dis 38(2):97–102. https://doi.org/10.1055/s-0038-1655777 - DOI - PubMed
1. Lesaffre E (2008) Superiority, equivalence, and non-inferiority trials. Bull NYU Hosp Jt Dis 66(2):150–154 - PubMed
1. Wiens BL (2002) Choosing an equivalence limit for noninferiority or equivalence studies. Control Clin Trials 23(1):2–14. https://doi.org/10.1016/s0197-2456(01)00196-9 - DOI - PubMed
1. Tamayo-Sarver JH, Albert JM, Tamayo-Sarver M, Cydulka RK (2005) Advanced statistics: how to determine whether your intervention is different, at least as effective as, or equivalent: a basic introduction. Acad Emerg Med 12(6):536–542. https://doi.org/10.1197/j.aem.2005.01.010 - DOI - PubMed
1. Altman DG, Schulz KF, Moher D, Egger M, Davidoff F, Elbourne D, Gotzsche PC, Lang T, Consort G (2001) The revised CONSORT statement for reporting randomized trials: explanation and elaboration. Ann Intern Med 134(8):663–694. https://doi.org/10.7326/0003-4819-134-8-200104170-00012 - DOI - PubMed

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[1] Lesaffre E (2018) Noninferiority clinical trials: the good, the bad, and the ugly. Semin Liver Dis 38(2):97–102. https://doi.org/10.1055/s-0038-1655777 - DOI - PubMed

[2] Lesaffre E (2018) Noninferiority clinical trials: the good, the bad, and the ugly. Semin Liver Dis 38(2):97–102. https://doi.org/10.1055/s-0038-1655777 - DOI - PubMed

[3] Lesaffre E (2008) Superiority, equivalence, and non-inferiority trials. Bull NYU Hosp Jt Dis 66(2):150–154 - PubMed

[4] Lesaffre E (2008) Superiority, equivalence, and non-inferiority trials. Bull NYU Hosp Jt Dis 66(2):150–154 - PubMed

[5] Wiens BL (2002) Choosing an equivalence limit for noninferiority or equivalence studies. Control Clin Trials 23(1):2–14. https://doi.org/10.1016/s0197-2456(01)00196-9 - DOI - PubMed

[6] Wiens BL (2002) Choosing an equivalence limit for noninferiority or equivalence studies. Control Clin Trials 23(1):2–14. https://doi.org/10.1016/s0197-2456(01)00196-9 - DOI - PubMed

[7] Tamayo-Sarver JH, Albert JM, Tamayo-Sarver M, Cydulka RK (2005) Advanced statistics: how to determine whether your intervention is different, at least as effective as, or equivalent: a basic introduction. Acad Emerg Med 12(6):536–542. https://doi.org/10.1197/j.aem.2005.01.010 - DOI - PubMed

[8] Tamayo-Sarver JH, Albert JM, Tamayo-Sarver M, Cydulka RK (2005) Advanced statistics: how to determine whether your intervention is different, at least as effective as, or equivalent: a basic introduction. Acad Emerg Med 12(6):536–542. https://doi.org/10.1197/j.aem.2005.01.010 - DOI - PubMed

[9] Altman DG, Schulz KF, Moher D, Egger M, Davidoff F, Elbourne D, Gotzsche PC, Lang T, Consort G (2001) The revised CONSORT statement for reporting randomized trials: explanation and elaboration. Ann Intern Med 134(8):663–694. https://doi.org/10.7326/0003-4819-134-8-200104170-00012 - DOI - PubMed

[10] Altman DG, Schulz KF, Moher D, Egger M, Davidoff F, Elbourne D, Gotzsche PC, Lang T, Consort G (2001) The revised CONSORT statement for reporting randomized trials: explanation and elaboration. Ann Intern Med 134(8):663–694. https://doi.org/10.7326/0003-4819-134-8-200104170-00012 - DOI - PubMed

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

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

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