Discrepancies in the Evidence and Recommendation Levels of Pregnancy Information in Prescription Drug Labeling in the United States, United Kingdom, Japan, and Korea

Objective: To compare the evidence-of-risk and recommendation levels of new drugs' label information in pregnancy among US, UK, Japan, and Korea. Despite the importance of drug labels in guiding decisions, officially approved prescribing information in drug labels is often inconsistent across countries and contains misleading content. Women are unintentionally exposed to drugs during early stages of unplanned or unrecognized pregnancies when treated for medical conditions. Methods: We selected 81 drugs approved in all 4 countries mentioned above from 2008 to 2016. Evidence level was classified into five categories ("Definite," "Probable," "Possible," "Unlikely," and "Unclassified"), and recommendation level was classified into four categories ("Contraindicated," "Cautious," "Compatible," and "Unclassified"). We calculated kappa coefficient with 95% confidence intervals (CIs) to estimate the agreement of each category. Results: For evidence level, "Unclassified" was the highest in Japan (33.3%), while representing a much smaller proportion in US (2.5%), UK (6.2%), and Korea (6.2%; p < 0.01). For recommendation level, "Contraindicated" was the lowest in US (9.9%), while it was greater in UK (50.6%), Japan (50.6%), and Korea (42.0%; p < 0.01). Korea-UK presented substantial agreement for both evidence-of-risk (kappa = 0.80, 95% CI: 0.67-0.94) and recommendation level (kappa = 0.64, 95% CI: 0.46-0.82), while Korea-Japan and Korea-US were in fair or moderate agreement. Conclusions: Label information in pregnancy was discrepant among the four countries. Discrepancies in labeling information among countries may cause confusion to patients and healthcare professionals alike. To better assist healthcare professionals and patients in the use of prescription drugs, global harmonization of safety information is needed to minimize confusion with potential risk.