## Why use a non-inferiority trial?

Why noninferiority trials? Noninferiority trials may be performed to demonstrate that a new treatment is better than an assumed placebo in situations where conducting a placebo control trial is unethical.

**How is non-inferiority margin determined?**

The outcome of a non-inferiority trial is usually assessed by a two-sided 95% confidence interval, showing a credible range for the true difference between the test product (test: T) and the active comparator (reference: R).

**How do you calculate sample size for non-inferiority trials?**

To calculate the sample size, we can use Table 5, which gives calculated sample sizes for various standardised non-inferiority limits (δNI = dNI/σ). The percentage mean differences are given for the case where it is anticipated that there may be a non-zero difference between treatments, that is, µA−µB = 0.

### What is a non-inferiority study design?

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 interpret non-inferiority trial results?**

The Guidance states: ‘…a successful non-inferiority study shows rigorously that the test drug has an effect greater than zero if it excludes a NI margin of M1, so long as M1 is well chosen and represents an effect that the control drug actually would have had (versus a placebo, had there been a placebo group).

**How do you interpret non-inferiority trials?**

In a noninferiority trial, the null hypothesis states that the primary end point for the new treatment is worse than that of the active control by a prespecified margin, and rejection of the null hypothesis at a prespecified level of statistical significance permits a conclusion of noninferiority.

## What does a non-inferiority margin mean?

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.

**How do you interpret a non-inferiority confidence interval?**

If a confidence interval sits entirely above zero, the trial would conclude that the test intervention is superior and hence also non-inferior to the control. If the lower bound CI sits above the NI margin but is less than zero (CI spans zero), the test intervention is non-inferior but not superior to control.

**What is the p value for non-inferiority?**

0.025

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 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.