Non-inferiority margins employed in clinical trials in Japan.
WHAT IS KNOWN AND OBJECTIVE
Determination of the non-inferiority margin is one of the major and most difficult considerations when planning a non-inferiority clinical trial. This article aims to list the non-inferiority margins employed in recent clinical drug-development trials in Japan.


METHODS
We investigated non-inferiority margins by reviewing new drug-development dossiers for drugs approved between January 2010 and December 2012 in Japan.


RESULTS AND DISCUSSION
We identified 174 non-inferiority trials, where the efficacy of the test drug was compared to that of a control drug. We have described 70 clinical endpoints and the corresponding non-inferiority margins. In antidiabetes drug trials, a margin of 0·4% mean difference in haemoglobin A1c level was used most frequently. In trials for glaucoma and ocular hypertension, 1·5 mmHg mean difference in intra-ocular pressure value was the commonest margin. A 10% margin of proportion difference was the most frequently chosen in trials of anti-infection drugs. We have provided a short description of the methods used to determine the non-inferiority margin.


WHAT IS NEW AND CONCLUSION
We report on the non-inferiority margins used for a range of endpoints in recent drug-development trials for a number of different diseases. We hope that the details would be helpful to those appraising, reporting or designing non-inferiority trials.
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D018849:Controlled Clinical Trials as Topic D015195:Drug Design D023381:Endpoint Determination D006801:Humans D007564:Japan D012107:Research Design
endpoint common technical document new drug development pharmaceuticals and medical devices agency