[Skip to Content]
[Skip to Content Landing]
Users' Guides to the Medical Literature
December 26, 2012

How to Use a Noninferiority TrialUsers' Guides to the Medical Literature

Author Affiliations

Users' Guides to the Medical Literature Section Editor: Drummond Rennie, MD, Deputy Editor, JAMA.

Author Affiliations: Departments of Clinical Epidemiology and Biostatistics (Mr Mulla and Drs You and Guyatt) and Medicine (Drs You and Guyatt), Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada; Department of Internal Medicine and Clinical Epidemiology, Princess Alexandra Hospital, Brisbane, Australia (Dr Scott); Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada (Drs Jackevicius and You); Department of Pharmacy Practice and Administration, College of Pharmacy, Western University of Health Sciences, Pomona, California (Dr Jackevicius); Institute of Health Policy, Management, and Evaluation, Faculty of Medicine, University of Toronto, (Dr Jackevicius); and University Health Network (Dr Jackevicius), Toronto, Ontario, Canada; and Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California (Dr Jackevicius).

JAMA. 2012;308(24):2605-2611. doi:10.1001/2012.jama.11235

Clinical investigators are increasingly testing treatments that have the primary benefit of decreased burden or harms relative to an existing standard. The goal of the resulting randomized trials—called noninferiority trials—is to establish that the novel treatment's effectiveness is not substantially less than the existing standard. Conclusions from these trials are, however, based on noninferiority thresholds specified by authors whose judgments may not coincide with those of patients and clinicians. This article highlights issues related to validity, interpretation, and applicability of results specific to noninferiority trials. Suboptimal administration of standard treatment or exclusive reliance on the analyze-as-randomized approach that is standard for conventional superiority trials may produce misleading results in noninferiority trials. Clinicians should judge whether the novel treatment's impact on effectiveness outcomes—the prime reason for wanting to prescribe it—is sufficiently close to that of standard treatment that they are comfortable substituting it for the existing standard. Trading off desirable and undesirable consequences is an individual decision: given the benefits of a novel treatment, some patients may perceive the uncertainty regarding a reduction in treatment effectiveness as acceptable while others may not.