Assessment of factors associated with dose differences between Japan and the United States.

Although it is well known that there are differences in approved doses between Japan and the United States, there has been no comprehensive research into the causes thereof. This study furthers the discussion of our previous investigation in 2010, with particular focus on pharmaceutical industry strategy and regulatory policy, among drugs approved in Japan between 2001 and 2009. Dose differences were observed in 73 of 190 drugs. Non-Japanese firms were more likely to have a similar dose approved between Japan and the United States, the association being more pronounced when limiting the analysis to drugs for which a Japanese dose-finding study was not conducted. Furthermore, dose differences were less frequent when non-Japanese efficacy data were included in the application data package. No relation between potential intrinsic ethnic difference and dose difference could be identified. The results suggest that the pathway of drug development is more strongly associated with dose difference than are drug characteristics.