Impact of Clinical Response on Different Approved Doses in Japan and the United States.

The pharmaceutical industry has increasingly aimed to achieve efficient strategies for simultaneous international and worldwide development of medicines, and there has been a growing need to understand ethnic differences in drug evaluation. Japan is one of the unique countries in which substantial domestic clinical data are required for dose selection as well as for marketing authorization. However, it appears challenging to accumulate a large amount of data in a single country in the recent shift to international drug development. To gain a better understanding of the influence of ethnic factors, the dosages of the products approved in Japan during 2003-2010 were reviewed, and differences in clinical responses between Japan and the United States were evaluated using a modeling approach. Of new medicines (new molecular entities) approved in Japan, 39 products (28.1%) have been approved at a different dose level compared with the United States, of which 13 products have considerable difference, twice or greater. Of those 13 products, only 2 were suggested to have a different clinical response, although limited data availability should be taken into careful consideration. Further investigation is recommended to establish new approaches for appropriate dose selection and thereby increase the efficiency of international drug development.