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Analyzing noninferiority trials: it is time for advantage deficit assessment – an observational study of published noninferiority trials

Authors Gladstone BP, Vach W

Received 23 September 2014

Accepted for publication 13 November 2014

Published 27 January 2015 Volume 2015:7 Pages 11—21


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Professor Greg Martin

Beryl Primrose Gladstone, Werner Vach

Clinical Epidemiology Group, Center for Medical Biometry and Medical Informatics, Medical Center, University of Freiburg, Freiburg, Germany

Abstract: The concept of noninferiority (NI) trials is based on a belief that the new therapy may potentially offer a benefit for the patient or society in spite of it having a slightly lower efficacy. We introduce advantage deficit assessment (ADA), a simple framework similar to the benefit-risk assessment in superiority trials. ADA balances the advantage gained against the deficit in efficacy on a two-dimensional plane. It requires that NI trials provide quantitative information on both the advantage as well as on efficacy on scales, which can be compared in a meaningful manner. From this perspective, we study the feasibility of ADA among a set of NI trials published in four major medical journals. Among 113 published NI trials, about half assessed and reported at least one claimed advantage. For most other studies, an assessment seems to be feasible if considered in the planning of the study. Many studies claiming noninferiority report a positive gain in advantage. These trials have the potential to demonstrate a significant net benefit in an ADA, substantially changing the final judgment of the study results. ADA seems promising as it overcomes the current limitation of NI trials to demonstrate “only” noninferiority and brings them back to the mainstream of superiority trials by aiming to demonstrate a positive net benefit. ADA seems to be feasible in the majority of NI trials.

Keywords: noninferiority, new treatment, potential advantage, advantage deficit assessment, benefit-risk assessment, loss of efficacy

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