Background: The non-inferiority trials are becoming increasingly popular in public health and clinical research. The choice of the non-inferiority margin is the cornerstone of the non-inferiority trial. When the effect of active control intervention is unknown, it can be interesting to choose the non-inferiority margin as a function of the active control intervention effect. In this case, the uncertainty surrounding non-inferiority margin should be taken into account in statistical tests.
Methods: It was proposed in this study two procedures for the non-inferiority test with a flexible margin for the continuous endpoint. The proposed test procedures are based on the asymptotic test and confidence interval approach. Simulations have been used to assess the performances and properties of the proposed test procedures. An application was done on clinical real data. The purpose of this study was to assess the effectiveness and safety of clinical monitoring alone versus laboratory and clinical monitoring in HIV infected adults patients.
Results: The two proposed test procedures have good properties for large sample sizes. It has been found that the confidence interval level determines approximately the level of significance. The The 80%, 90% and 95% two-sided confidence interval levels led approximately to a type I error of 5%, 2:5% and 1%
respectively. For small sample sizes, the test with 80% confidence interval level was the most powerful.
Conclusions: This study highlights the choice of non-inferiority margin as flexible and depending on the reference treatment in an active trial of non-inferiority. The results of the study show that the proposed methods are applicable in the practice.
Trial registration : The trial data used in this study was from the "Stratall ANRS 12110 / ESTHER", registered with ClinicalTrials.gov, number NCT00301561. Date : March 13, 2006, url : https://clinicaltrials.gov/ct2/show/NCT00301561.