When can non-inferiority clinical trial be used?
A study that tests whether a new treatment is not worse than an active treatment it is being compared to. Non-inferiority trials are sometimes done when a placebo (an inactive treatment) cannot be used.
How do you prove non-inferiority?
Traditional statistical methods were designed to demonstrate differences and cannot easily show that a new treatment is similar to an older one. Non-inferiority can be shown if the difference between two treatments does not cross a predefined inferiority margin.
Can you prove superiority in a non-inferiority trial?
In a non-inferiority trial, the focus is on the lower bound margin, what happens at the upper end is not of primary concern in this type of trial design. One can also declare superiority in a non-inferiority trial if the lower limit of CI of the new treatment is above the non-inferiority margin and above zero.
What is the main advantage of non-inferiority trials when testing a new drug?
Advantages of non-inferiority trials A placebo treatment is unethical. The standard treatment is exceptionally effective. The experimental treatment is thought to be equivalent or at least not worse but not superior to the current treatment (i.e. everybody is convinced that a superiority trial would show no difference)
How do you interpret non-inferiority trials?
If the upper bound of the 95% CI falls below the noninferiority margin, ƒ, then the trial has failed to demonstrate noninferiority and has in fact demonstrated inferiority (Figure 3). If the 95% CI crosses ƒ, then the study result is indeterminate.
Do non-inferiority trials have P values?
In non-inferiority trials, investigators are interested in whether new treatment is non-inferior to standard treatment. Only the non-inferior margin to the right side of unity on the forest plot is specified. Therefore, the significance level is usually set as a one-sided p value of 0.025.
What is the FDA’s new guidance on non-inferiority clinical trials?
In November 2016, the FDA released final guidance on Non-Inferiority Clinical Trials to Establish Effectiveness providing researchers guidance on when to use non-inferiority trials to demonstrate effectiveness along with how to choose the non-inferiority margin, test the non-inferiority hypothesis, and provide interpretable results.
What is the difference between an inferiority and non-inferiority trial?
Introduction. In contrast, non-inferiority trials have a null hypothesis that the experimental treatment is inferior to the standard treatment by at least a certain pre-specified amount. The alternative hypothesis to be proven is that the experimental treatment is inferior to the standard treatment by less than that same amount.
What is the non-inferiority margin in a clinical trial?
Non-inferiority Margin The selection of the non-inferiority margin is critical in designing a non-inferiority trial and the majority of the FDA guidance focuses on this. The non-inferiority margin is selected by reviewing historical trials of the active control.
What are the limitations of non-inferiority trials?
If multiple historical trials exist one of the assumptions of the non-inferiority trial is consistency of the effect between the historical studies and the non-inferiority trial. Therefore, if consistency isn’t present between the historical studies this can lead to problems in estimating the active control effect.