Factors distinguishing important identified risks from important potential risks in orphan and nonorphan drugs: An analysis of safety specifications of Japan and European Union risk management plans

• Published in: Pharmacoepidemiology and drug safety 2018-11, Vol.27 (11), p.1231-1238
• Main Authors: Hirota, Saeko, Yamaguchi, Takuhiro
• Format: Article
• Language: English
• Subjects: Clinical trials; Drugs; pharmacoepidemiology; pharmacovigilance; rare diseases; Risk factors; Risk management; risk management plan; Safety; safety specification; Side effects; Specifications
• ISSN: 1053-8569; 1099-1557
• DOI: 10.1002/pds.4646

Purpose The purposes of the study are to compare safety specifications between Japan and the European Union (EU) and to identify the factors affecting categorization of important identified or potential risks. Methods Safety specifications were collected from orphan and nonorphan drugs approved in Japan between 2014 and 2016, and in the EU as of October 2017. Outcome was defined dichotomously as listed as important identified risks or potential risks. A mixed‐effects logistic regression was performed to estimate odds ratios of being listed as important identified risks. Results This study included 20 orphan and 33 nonorphan drugs. The number of safety specifications per drug and the distribution of risk categories were significantly different between Japan and the EU regardless of orphan status. In orphan drugs, the occurrence of serious adverse events (AEs) during clinical trials for new drug applications was associated with a higher probability of being listed as important identified risks in Japan, while AE rate (%) was positively associated with being listed as important identified risks in the EU. For nonorphan drugs in Japan, AE occurring at a high rate, adverse drug reactions (ADRs) listed as important identified risks in EU risk management plans, and clinically significant ADRs known in similar drugs were likely to be listed as important identified risks, whereas a ≥1.4 risk ratio was associated with a higher probability of being listed as important identified risks in the EU. Conclusions Factors affecting risk categories were different between Japan and the EU, which might contribute to the difference in safety specifications between these 2 regions.