Clinical equivalence and non-inferiority within health technology assessment.

Abstract

Background: Non-inferiority and clinical equivalence clinical trials can be used to determine whether a health technology is no worse than an existing treatment. This study identified international guidance for conducting non-inferiority and clinical equivalence trials and investigated the current practices in conducting and reporting such trials, especially in the context of Health Technology Assessment (HTA).

Methods: A pragmatic approach was used to identify international guidelines and published literature reporting approaches for the conduct and reporting of non-inferiority or clinical equivalence studies. Guidelines from both HTA and regulatory bodies were considered, and literature reviews from 2010 to 2023 were identified. The results of the reviews were supplemented by stakeholder interviews and synthesised to form a series of recommendations for the UK National Institute for Health and Care Excellence in the appraisal of non-inferiority and equivalence trials.

Results and conclusion: The majority of guidelines (13/15) discussed methods to determine the non-inferiority margin and how the analysis should be conducted. Despite this, the quality of reporting in non-inferiority and clinical equivalence trials is consistently poor. Prior to presentation of trial evidence, HTA submissions that claim non-inferiority or equivalence should present the technical, biological and/or pharmacokinetic reasonings that support the claim.