Noninferiority trials are intended to show that the effect of a new treatment is not worse than that of an active control by more than a specified margin.
These trials have a number of inherent weaknesses that superiority trials do not: no internal demonstration of assay sensitivity, no single conservative analysis approach, lack of protection from bias by blinding, and difficulty in specifying the noninferiority margin.
Noninferiority trials may be necessary when a placebo group can not be ethically included, but it should be recognized that the results of such trials are not as credible as those from a superiority trial.
Such trials attempt to show that the new treatment has an effect similar to that of the standard, rather than outright superiority.
Trials of this type that make them considerably less credible than superiority trials.
Noninferiority trials may sometimes be necessary when a placebo group can not be ethically included, but it should be recognized that the results of such trials are not as credible as those from a superiority trial.
The major difficulty with noninferiority trials relates to the issue of assay sensitivity, or the ability of a specific clinical trial to demonstrate a difference between treatments if such a difference truly exists.
Blinding does not protect against bias nearly as well in a noninferiority trial as it does in a superiority trial.
In a superiority trial, a blinded investigator can not consciously or subconsciously influence the results to support a preconceived belief in superiority.
In a noninferiority trial there is no protection against a blinded investigator biasing the results toward a preconceived belief in equivalence by assigning similar ratings to the treatment responses of all patients.
Specifying the noninferiority margin is difficult to specify
To avoid this, the equivalence margin is often chosen with reference to the effect of an active control in historical placebo-controlled trials, implying that the new treatment is superior to placebo.
Noninferiority trials typically have smaller sample sizes than active-controlled superiority trials, they can have considerably larger sample sizes than placebo-controlled trials.