Non-inferiority margins employed in clinical trials in Japan.

Abstract

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. We investigated non-inferiority margins by reviewing new drug-development dossiers for drugs approved between January 2010 and December 2012 in Japan. 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, 1·5mmHg 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. 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.