What is non-inferiority?
What is non-inferiority?
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.
What is non-inferiority or superiority of something?
Of these three comparisons, the non-inferiority has the largest range of successful trial outcomes (equivalence or superiority). The superiority comparison is a subset of the non-inferiority and will have a sample size that is similar to the non-inferiority or a sample size that is much larger.
Can you show 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 a superiority trial?
A superiority trial is designed to detect a difference between treatments. The first step of the analysis is usually a test of statistical significance to evaluate whether the results of the trial are consistent with the assumption of there being no difference in the clinical effect of the two treatments.
What is a non-inferiority limit?
By definition, a non-inferiority trial aims to demonstrate that the test product is not worse than the comparator by more than a small pre-specified amount. This amount is known as the non-inferiority margin, or delta. Clinicians must know who has chosen the margin, and why.
What is a good non-inferiority margin?
In order to demonstrate non-inferiority, the recommended approach is to pre-specify a margin of non- inferiority in the protocol. After study completion, a two-sided 95% confidence interval (or one-sided 97.5% interval) for the true difference between the two agents will be constructed.
What is a non-inferiority p value?
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.
How do you prove non-inferiority?
Non-inferiority can be shown if the difference between two treatments does not cross a predefined inferiority margin. Non-inferiority studies need to be carefully planned; failings in the design of the study may make accepting an inferior treatment more likely.
What phase is a non-inferiority trial?
A non-inferiority phase III trial requires a roughly four times larger sample size than that of a similar standard superiority trial. Because of the large required sample size, we often face feasibility issues to open a non-inferiority trial.
How is non-inferiority margin decided?
If the difference between the new drug and the active comparator does not exceed this prespecified margin, noninferiority can be concluded. This margin must be specified based on clinical and statistical reasoning; however, it is considered as one of the most challenging steps in the design of noninferiority trials.
What is null hypothesis in non-inferiority trial?
The null hypothesis in non-inferiority trials is that new treatment is inferior to standard treatment. If the results of the trial are statistically significant, the null hypothesis can be rejected and the alternative hypothesis that the new treatment is non-inferior to standard treatment can be accepted.
Is there a difference between superiority and non-inferiority?
Guidelines and statistical practice should abandon the sharp division between superiority and non-inferiority phase 3 non-regulatory trials and be more closely aligned to the clinical and public health questions that motivate the trial.
When is a noninferiority trial called a superiority trial?
If the intent of a study is to demonstrate that an experimental treatment is not substantially worse than a control treatment, the study is known as a noninferiority trial. However, there are some complicated issues with trials of this type that make them less reliable than typical superiority trials6-9).
When do you use superiority in a study?
Superiority trials are always used when comparisons are made to placebo or vehicle treatments. In these studies, it is critical that the effect in the treatment group be clearly superior to any effects in the placebo groups.
What does failure to demonstrate superiority over vehicle Mean?
Failure to demonstrate superiority over vehicle suggests that the drug is not effective. Superiority trials are also used for marketing purposes (“our drug is better than your drug” studies). Bioequivalence trials are used to show that a new treatment is identical (within an acceptable range) to a current treatment.