Differences between the United States and Japan in labels of oncological drugs.

PURPOSE: Our study addresses how the information in the labels differed between United States (US) and Japan, what factors were associated with the decision to place the boxed warning on the label, and the relation of both countries in terms of drug label policy.

METHODS: We investigated adverse drug reactions (ADRs) in boxed warnings for 44 oncological drug labels approved from 2004 to 2014 in both Japan and the US. We applied conditional logistic regression to examine how likely it was for each ADR to be included in a boxed warning.

RESULTS: There were substantial differences in all sections of the labels. The concordance rate between US and Japanese labels was 44.1% for serious adverse reactions and 30.5% for boxed warnings. Our regression analysis indicated that deaths and/or terminations related to specific ADRs reported in clinical trials were significantly associated with inclusion of the ADR in boxed warnings in Japan, but not in the US. The boxed warnings of similar drugs seemed to affect those of follow-on drugs in both countries. US drug labels were likely to influence Japanese labels, but not vice versa.

CONCLUSION: This study suggests that the observed differences are not solely due to differences in clinical outcomes between the two countries, but rather due to differences in regulatory considerations and historical factors in both local and global contexts. Further research is needed to examine the impact of these differences on public health and to determine how and to what extent we should intervene with this status quo. Copyright © 2016 John Wiley & Sons, Ltd.