Conducting the non-inferiority test for the means with unknown coefficient of variation in a three-arm trial

BMC Medical Research Methodology

Research

Wei-Hwa Wu¹  Hsin-Neng Hsieh²  Hung-Yi Lu²  Wei-Ya Wu³  Meng-Chih Lee⁴ 

[1] Department of Finance, Ming Chuan University, Taipei City, Taiwan;Department of Statistics and Information Science, Fu Jen Catholic University, New Taipei City, Taiwan;East District Public Health Center, Taichung City, Taiwan;Taichung Hospital, Ministry of Health and Welfare, Taichung City, Taiwan;College of Management, Chaoyang University of Technology, Taichung City, Taiwan;

关键词: Heteroskedasticity;    Coefficient of variation;    p;    Non-inferiority test;    Searls’ estimator;   

DOI  :  10.1186/s12874-023-01990-w

 received in 2022-09-01, accepted in 2023-07-13,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundThe non-inferiority test is a reasonable approach to assessing a new treatment in a three-arm trial. The three-arm trial consists of a placebo, reference, and an experimental treatment. The non-inferiority is often measured by the mean differences between the experimental and the placebo groups relative to the mean differences between the reference and the placebo groups.MethodsTo cope with possible estimation distortion due to the allowance of heteroskedasticity, we adjust the measurement of non-inferiority by the incorporation of coefficient of variation (CV) of the experimental, the reference and the placebo groups. In this research, we propose a generalized p\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$p$$\end{document}-value based method (GPV-based method) to facilitate non-inferiority tests for the means with unknown coefficient of variation in a three-arm trial.ResultsThe simulation results show that the GPV-based method can not only adequately control type I error rate at nominal level better but also provide power higher than those from Delta method and the empirical bootstrap method, which verifies the feasibility of our adjustment.ConclusionsWe revise the measurement of non-inferiority by deducting the CV of each kind of treatment from the average effect of trials. CVs are included in the non-inferiority explicitly to help prevent possible estimating distortion if heteroskedasticity is allowed. Through the simulation study, the performance of GPV-based method for facilitating non-inferiority tests for the means with unknown CV in a three-arm trial is better than those from empirical bootstrap method and Delta method for small, medium and large sample sizes. Hence, the GPV-based method is recommended to be used to conduct the non-inferiority test for the means with unknown CV in a three-arm trial. The GPV-based method still performs well in non-normality cases.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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