Non-Inferiority Trials

Here some links to resources to give you an introduction to non-inferiority clinical trials.

From The Medical Letter:

“A non-inferiority trial is a comparison with an active control to determine whether the difference in response between the new drug and the active control is small enough (less than some pre-specified margin) to demonstrate that the new treatment is not less effective (or is only slightly less effective) than the control in achieving the primary outcome. Non-inferiority trials are appropriate when a proven effective treatment already exists and assigning some patients to a placebo group would be unethical because the treatment is life-saving or prevents irreversible injury. The FDA recently issued guidelines on how to interpret a non-inferiority trial, how to choose a non-inferiority margin and how to analyze the results – “Guidance for Industry: Non-Inferiority Clinical Trials.” (pdf file) “

From an article in the journal, Trials, entitled, “Through the looking glass: understanding non-inferiority.

“A non-inferiority experiment, by contrast, tries to show that the new intervention is not ‘inferior’ to the previous one, or, more precisely, that the new intervention is ‘not unacceptably worse’ than the intervention used as the control.  …

Trials to show superiority generally penalize the sloppy investigator (although not always; improper handling of missing data can benefit a more toxic, less efficacious treatment, potentially increasing the possibility of a false finding in a superiority trial). By contrast, non-inferiority trials tend to reward the careless. The less rigorously conducted the trial, the easier it can be to show non-inferiority.”

From an article in the European Heart Journal, “Non-inferiority study design: lessons to be learned from cardiovascular trials.”

“The non-inferiority trial design has gained popularity within the last decades to compare a new treatment to the standard active control. In contrast to superiority trials, this design is complex and is based on assumptions that cannot be validated directly. Many readers and even investigators, therefore, have difficulty grasping the full methodological nature of non-inferiority trials. Non-inferiority margins are often arbitrarily chosen such that a favourable margin can bias a trial towards declaring non-inferiority. Pitfalls of non-inferiority trials are not fully appreciated, and without having identified these shortcomings, objective conclusions from non-inferiority trials cannot be made.”


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