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

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

The sample size required for a non-inferiority clinical trial can be calculated using the formula in Figure 1 [5],[6]. Table 4 gives common Normal deviates for different percentiles. For example, for β = 0.1, we would have x = 0.1 and Z1-x = 1.282, while for α = 0.05, we would have x = 0.025 and Z1-x = 1.96.

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.

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.

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 a 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. Clinicians must know who has chosen the margin, and why.

What is the meaning of 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 the null hypothesis for non-inferiority trial?

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 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.

What is inferiority margin?

Abstract. Noninferiority trials are used to assess whether the effect of a new drug is not worse than an active comparator by more than a noninferiority margin. If the difference between the new drug and the active comparator does not exceed this prespecified margin, noninferiority can be concluded.

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

How to calculate the sample size of a non inferiority trial?

In this paper, the steps for condu … Practical guide to sample size calculations: non-inferiority and equivalence trials Pharm Stat. Jan-Feb 2016;15(1):80-9.doi: 10.1002/pst.1716. Epub 2015 Nov 25.

How to calculate Sample Size for equivalence trials?

Practical guide to sample size calculations: non-inferiority and equivalence trials Pharm Stat. Jan-Feb 2016;15(1):80-9.doi: 10.1002/pst.1716. Epub 2015 Nov 25. Authors Laura Flight 1 , Steven A Julious 1

How does the noninferiority margin affect sample size?

The noninferiority margin is another major factor that influences sample size, and the greater the tolerance that is allowed, the smaller the sample size that is needed. However, an inflated margin may cause considerable loss of statistical power if noninferiority can be accepted only by a smaller margin (Table 1).

How to do a sample size calculation in hand?

A number of components are required to facilitate a suitable sample size calculation. In this paper, the steps for conducting sample size calculations for non-inferiority and equivalence trials are summarised. Practical advice and examples are provided that illustrate how to carry out the calculations by hand and using the app SampSize.