Bayesian Approach for Assessing Non-Inferiority in Three-Arm Trials for Risk Ratio and Odds Ratio

Abstract

In this article, we consider three-arm noninferiority (NI) trial that includes an experimental, a reference, and a placebo arm. While the risk difference (RD) is the most common and well-explored functional form for testing efficacy (or effectiveness), for binary outcomes, recent FDA guideline suggested other measures, such as relative risk (RR) and odds ratio (OR) on the basis of which NI can be claimed. However, developing test based on these different functions of binary outcomes are challenging since the construction and interpretation of NI margin for such functions are not trivial extensions of RD-based approach. Recently, we have proposed Frequentist approach for testing NI for these functionals. In this article, we further develop Bayesian approaches for testing NI based on effect retention approach for RR and OR. Bayesian paradigm provides a natural path to integrate historical trials’ information, as well as it allows using patients’/clinicians’ opinions as prior information via sequential learning. In addition we discuss, in detail, the sample size/power calculation which could be readily used while designing such trials in practice.

Keywords:

• Assay sensitivity
• Binary outcome
• Fraction margin
• Markov chain Monte Carlo
• Noninferiority margin
• Risk/odds ratio
• Three-arm trial

Acknowledgments

Authors would also like to thank two anonymous referees, AE, and the editorial team, whose comments provided additional insights and have greatly improved the scope and presentation of the article.

Additional information

Funding

The research of first author is partly supported by PCORI contract number ME-1409-21410 and NIH grant number P30-ES020957.