Background Factors Contributing to Safety Warning Discordance in the Initial Labeling of New Drugs in Japan, the United States, and the European Union.

Abstract

Drug labels summarize essential safety information for healthcare professionals and patients. However, studies have reported a discordance of safety information in drug labeling among countries/regions. We aimed to identify the characteristics of adverse events associated with discordant safety warnings during the initial labeling of new drugs approved at approximately the same time in Japan, the United States, and the European Union. Safety warning discordance/concordance between two countries/regions and the explanatory variables were assessed using multivariable logistic regression. The safety warning concordance rate was 71.0% (152/214) for the United States and the European Union, 59.5% (135/227) for Japan and the United States, and 64.3% (144/224) for Japan and the European Union. A significant association with discordant safety warnings was revealed for "adverse event rate" and "warning status in a similar drug" between the United States and the European Union; "adverse event rate," "adverse event included in important medical event list," and "warning status in a similar drug" between Japan and the United States; and "adverse event included in important medical event list" and "warning status in a similar drug" between Japan and the European Union. Clarifying and publicizing the reasons for safety warnings, along with an awareness of the factors associated with the discordance identified in this study, will help healthcare professionals, patients, marketing authorization holders, and regulatory authorities around the world share the background of country/region-specific warnings, reducing the possibility of confusion among them due to the discrepancies.