title: Exploratory Analysis of Associations Between Postmarketing Safety Events and Approved Doses of New Drugs in Japan.
abstract: While efficient and less onerous for the industry, the globalization of clinical drug development may lead to limited efforts to optimize drugs for regional conditions. We examined the association between clinical development pathways, approved doses, and postmarketing safety risks in Japan for 135 new molecular entities approved between 2004 and 2011. The risk of drug-related deaths seemed higher when pharmaceutical companies chose exactly the same dose as in the United States, even after conducting Japanese dose-ranging studies. We also found a positive association with drug-related deaths when the review process was expedited and when Japanese dose-ranging studies were not conducted for nonexpedited drugs. Our findings suggest that the decisions on regional dose settings and the choice of global clinical development pathways are associated in ways that may influence the postmarketing outcomes in the target populations.
authors.affiliation: Laboratory of Pharmaceutical Regulatory Science, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan.
authors.forename: T K
authors.initials: TK
authors.lastname: Okubo
authors.affiliation: Laboratory of Pharmaceutical Regulatory Science, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Ono
mesh_terms: D004305:Dose-Response Relationship, Drug; D017277:Drug Approval; D006801:Humans; D007564:Japan; D008962:Models, Theoretical; D011358:Product Surveillance, Postmarketing; D014481:United States