How do you determine non-inferiority margin?

How do you determine 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 non-inferiority margin?

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.

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.

What is non-inferiority criteria?

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.

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 does non-inferiority mean?

When is a non-inferiority trial needed?

Advantages of non-inferiority trials A non-inferiority trial is appropriate when: A placebo treatment is unethical. 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)

When is a non-inferiority trial used?

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 do you read a non-inferiority trial?

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).

What is non-inferiority hypothesis?

The null hypothesis in non-inferiority trials is that new treatment is inferior to standard treatment. The alternative hypothesis is the new treatment is non-inferior to standard treatment.

What is the null hypothesis for a non-inferiority trial?

Can you calculate number needed to treat in a non-inferiority trial?

In general, non-inferiority trials require fewer patients than a standardized superiority trial. So hold on then: The vast majority of superiority trials aren’t large enough to assess the number needed to harm (NNH)—only the number needed to treat (NNT).

How do you select the non-inferiority margin in a clinical trial?

The selection of the non-inferiority margin is based upon a combination of statistical reasoning and clinical judgement. A three-armed trial with test, reference and placebo allows some within-trial validation of the choice of non-inferiority margin and is therefore the recommended design; it should be used wherever possible.

What is the difference between fixed margin and unconditional type 1 error rate?

The fixed-margin approach based on the lower limit may be ultra-conservative with unconditional Type 1 error rate much smaller than target α / 2 level, while the margin based on the point estimate is liberal. We derive the Type 1 error rate as a function of variances of the effect estimates in the historical and the current non-inferiority trials.

What is type 1 error probability?

The type 1 error probability in (6) is an unconditional error because the probability incorporates the statistical uncertainty of the estimate of NI margin Δ ˆ λ [ 11, 12 ]. If the margin is treated as a fixed known constant after it is estimated, the conditional error probability is controlled at level α / 2.

What is the margin of equivalence?

In practical terms, the margin is the maximum clinically acceptable difference that one is willing to accept in return for the secondary benefits of the new therapy. The equivalence margin, denoted by δ, is the most distinctive feature of equivalence/noninferiority testing.