Can non-inferiority trials show superiority?

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.

How can you differentiate between superiority and non-inferiority clinical trial?

In comparison studies with a current therapy, non-inferiority is used to demonstrate that the new therapy provides at least the same benefit to the patient. Superiority trials are always used when comparisons are made to placebo or vehicle treatments.

What is an acceptable 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 does superiority mean in clinical trials?

When the aim of the randomized controlled trial (RCT) is to show that one treatment is superior to another, a statistical test is employed and the trial (test) is called a superiority trial (test). Often a nonsignificant superiority test is wrongly interpreted as proof of no difference between the two treatments.

What are superiority and non-inferiority trials?

A superiority trial is designed to show that a new treatment is better than an active control or placebo. A non-inferiority trial is different as it is designed not to show that treatments are equal, or ‘not different’, but that the new treatment is not unacceptably worse than, or ‘non-inferior’ to, an active control.

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 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.

How do you read a non-inferiority margin?

The calculated CI does not know whether its purpose is to judge superiority or non-inferiority. If it sits wholly above zero, then it has shown superiority. If it sits wholly above -Δ, then it has shown non-inferiority. A non-inferiority trial can have five possible types of outcomes as depicted in Figure 2.

What is a superiority margin?

There is a percentage above 70% at which the difference between the two treatments is no longer considered ignorable. The difference between these two percentages is called the margin of superiority.

What is a non superiority trial?

Introduction. Unlike superiority trials that are designed to show that one treatment is better than another, a non-inferiority trial is designed to show that a new treatment is ‘not unacceptably worse’ than the current standard therapy.

What are non-inferiority trials?

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 meant by non-inferiority trial?

Is there a multiplicity issue between Ni and superiority tests?

It has been shown that no multiplicity issue exists between NI and superiority tests of the primary endpoint.

Should we test noninferiority of experimental drugs after establishing superiority?

Background: In a clinical study to evaluate noninferiority (NI) of an experimental drug relative to an established therapy, it is common to further test superiority of the experimental drug after NI is established. It has been shown that no multiplicity issue exists between NI and superiority tests of the primary endpoint.

Is the Hochberg method conservative for superiority testing?

When the test statistic used for superiority testing of the primary endpoint is the same as that for the NI testing, a multiplicity adjustment method using the popular Hochberg procedure is shown to be potentially conservative.