Non-inferiority trials: the ‘at least as good as’ criterion with dichotomous data

Abstract

SUMMARYThe 'at least as good as' criterion, introduced by Laster and Johnson for a continuous response variate, is developed here for applications with dichotomous data. This approach is adaptive in nature, as the margin of non-inferiority is not taken as a ÿxed di erence; it varies as a function of the positive control response. When the non-inferiority margin is referenced as a high fraction of the positive control response, the procedure is seen to be uniformly more e cient than the ÿxed margin approach, yielding smaller sample sizes when sizing non-inferiority trials under identically speciÿed conditions. Extending this method to proportions is straightforward, but highlights special considerations in the design of non-inferiority trials versus superiority trials, including potential trade-o s in statistical e ciency and interpretability.

Autologous blood versus fibrin glue for conjunctival autograft adherence in sutureless pterygium surgery: a randomised controlled trial

“…The primary outcomes were compared between the two groups using the z test for difference in proportions adapted for non-inferiority hypothesis 14 15. The hypothesis testing used a non-inferiority margin (δ) of 5%.…”

Sample Size Estimation for Non-Inferiority Trials: Frequentist Approach versus Decision Theory Approach

“…In the traditional frequentist approach of sample size calculation for non-inferiority trials, the costs and health consequences, beyond the main therapeutic effect, are not taken into consideration. [4] In this paper we argue and illustrate, using an exemplifying case study, that decision theory may provide a more comprehensive, and hence more appropriate, approach to sample size calculation for non-inferiority trials.…”

“…[3] The sample size of a non-inferiority trial is calculated based on the non-inferiority margin, the intended power, and the significance level. [4,6] Conceptually, it is calculated what sample size is needed to prove, with statistical significance and a certain power, that the loss of therapeutic effect of the new therapy compared to the standard therapy is not larger than what is deemed maximally acceptable. An accepted difference in main therapeutic effect, the non-inferiority margin, is introduced in order to enable testing for statistical significance.…”

Issues with Statistical Risks for Testing Methods in Noninferiority Trial Without a Placebo ARM

“…A widely used method, often referred to as the fixed margin method, begins with setting a numerical value to the noninferiority margin in advance of conducting the noninferiority study so that the noninferiority hypothesis to test is well defined prior to observing any results in the completed trial. Choice of is a difficult task in practice (Chow and Shao, 2006;Hauschke, 2005;Hung et al, 2003Hung et al, , 2005Laster and Johnson, 2003;Laster et al, 2006;Ng, 2001;Tsong et al, 2003;Wiens, 2002). Depending on the set objective of the noninferiority trial, the margin is often chosen as a mixture of a statistical margin and a clinical margin.…”