When can non-inferiority trial be used?
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).
What is the main advantage of non-inferiority trials when testing a new drug?
Non-inferiority clinical trials are being performed with an increasing frequency now-a-days, because it helps in finding a new treatment that have approximately the same efficacy, but may offer other benefits such as better safety profile.
What is a non-inferiority trial?
in-FEER-ee-OR-ih-tee TRY-ul) 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 claim 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.
How do you prove non-inferiority?
Traditional statistical methods were designed to demonstrate differences and cannot easily show that a new treatment is similar to an older one. Non-inferiority can be shown if the difference between two treatments does not cross a predefined inferiority margin.
What is a reasonable 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.
How do you interpret non-inferiority trial results?
If the upper bound of the 95% CI falls below the noninferiority margin, ƒ, then the trial has failed to demonstrate noninferiority and has in fact demonstrated inferiority (Figure 3). If the 95% CI crosses ƒ, then the study result is indeterminate.
How do you test for non-inferiority?
In noninferiority testing, a common practice is to set the value of δ to a fraction, f, of the lower limit of a confidence interval of the difference between the current therapy and the placebo obtained from a meta-analysis.
What is non-inferiority limit?
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 difference between a non-inferiority trial and a 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.
How do you evaluate a non-inferiority trial?
By contrast, for a noninferiority trial to be successful in disproving H0, it should maximally demonstrate similarity in the effects between 2 treatments, and any methodologic issues that minimize differences between the 2 treatments will falsely strengthen the evidence for the experimental therapy.
How do you determine non-inferiority?
How do you calculate non-inferiority?
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.
How do you power a non-inferiority trial?
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.
What is the purpose of 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. They may also be used when the new treatment may offer important advantages over currently available standard treatments,…
Does margin for equivalence/noninferiority imply a treatment is effective?
The positioning of the outcome result for each treatment is indicated. Δ: margin for equivalence/noninferiority. Does noninferiority imply a treatment is effective? As previously pointed out, setting an inappropriate margin can cause a noninferiority test to misleadingly conclude a ineffective treatment to be effective.
What is the difference between noninferiority and equivalence trials?
Although noninferiority and equivalence trials have often been both referred to as “equivalence trials,” they are distinct. 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.
Can we test for noninferiority alongside a superiority test?
If a superiority trial fails to reject the null hypothesis but the trial data appear to suggest treatment equivalence, one may also be tempted to infer noninferiority. If there is a possibility for testing noninferiority alongside a superiority test, one should predefine both hypotheses with a justifiable margin for noninferiority in the protocol.