Safety information in drug labeling: a comparison of the USA, the UK, and Japan.
OBJECTIVE
Despite globalization of drug approvals, there is a disparity in drug safety regulations among the USA, Europe, and Japan. We sought to determine differences in safety information on drug labels among the three regions.


METHODS
This was a cross-sectional study with quantitative survey of safety information on labels of 189 new molecular entities approved in the USA, the UK, and Japan. Outcome measures were the proportions of total safety information (PSI), of contraindications (PCI), and of boxed warnings (PBW) to all information on the label. We identified a boxed warning (BW) on US and Japanese labels through a manual search. These measures were analyzed according to therapeutic indications.


RESULTS
On the Japanese labels, PSI was smaller than that on the US and UK labels for cardiovascular diseases. For neoplastic and immunologic diseases, PSI on the Japanese labels was larger than that on the UK labels. For nervous system diseases, PSI on the US labels was larger than that on the UK and the Japanese labels. PCI showed contrasting results with PSI except for neoplastic and immunologic diseases. BWs showed a poorer concordance between the USA and Japan in hematologic and genitourinary diseases than in other therapeutic areas.


CONCLUSIONS
Substantial differences in safety information exist depending upon outcome measures and therapeutic areas among the US, the UK, and the Japanese labels. This underscores the need for further analyses to determine causes of these differences to optimize drug safety regulations.
Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Rumiko
R
Shimazawa
Masayuki
M
Ikeda
D016907:Adverse Drug Reaction Reporting Systems / Q000331:legislation & jurisprudence / Q000592:standards*; D000075202:Contraindications; D003430:Cross-Sectional Studies; D004345:Drug Industry / Q000331:legislation & jurisprudence / Q000592:standards*; D004348:Drug Labeling / Q000331:legislation & jurisprudence / Q000592:standards*; D004358:Drug Therapy; D004335:Drug and Narcotic Control / Q000331:legislation & jurisprudence; D064420:Drug-Related Side Effects and Adverse Reactions; D019983:Guideline Adherence; D017408:Guidelines as Topic; D006801:Humans; D007564:Japan; D061214:Patient Safety; D017891:Pharmacoepidemiology; D018570:Risk Assessment; D012307:Risk Factors; D006113:United Kingdom; D014481:United States