Saturday, March 06, 2010

Non-inferiority clinical trials - now comes FDA's draft guidance

In contrary to adaptive design clinical trials, non-inferiority (NI) design has been there for many years (15-20 years) and many studies have been conducted using non-inferiority design. Many products have been approved by regulatory agencies with based on the pivotal studies in non-inferiority design.

Even though there have been tons of presentations, workshops, and text books about the non-inferiority clinical trials, there is no formal guidance from FDA regarding the inferiority clinical trials (until this week).

This week, FDA issues its draft guidance for industry: non-inferiority clinical trials. The guidance gives advice on when NI studies can be interpretable, on how to choose the NI margin, and how to analyze the results.

NI is considered a special case of equivalence trial with NI comparing to only lower or upper bound of the confidence interval (but not both). While there are many other issues to be considered when design a NI trial, the selection of the NI margin continue to be a key issue in NI design. For a confirmatory trial for licensure, NI margin must be discussed with regulatory agencies and must be agreed by them. Generally, the wider the margin, the easier the NI trial to be successful. the smaller the margin, the larger the sample size. 

It is good to see that the guidance includes a question/answer on "in the situation where a placebo-controlled trial would be considered unethical, but a non-inferiority study cannot be performed, what are the options?" Unfortunately, the answer to this question is somehow not clear.

Further readings:

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