Association between Post-marketing Safety-related Regulatory Actions and Characteristics of New Drugs Approved in Japan between 2005 and 2016

Abstract

The pharmacovigilance activities of new drugs are usually planned and conducted based on the clinical safety information obtained at approval. Revealing pre- and post-marketing drug characteristics associated with post-marketing safety-related regulatory actions (PSRAs) would help facilitate pharmacovigilance activities as these activities are not sufficient for early detection of safety signals that require warning. Therefore, we investigated the association between PSRAs and characteristics of new drugs in Japan. New active substances approved in Japan between fiscal year 2005 and 2015 were analyzed. PSRAs were defined as "revisions of precautions in drug package insert" instructed by the regulatory authority within the first 5 years after the initial approval (up to 2021). Drug characteristics included therapeutic area, number of Japanese subjects in clinical trials, dose-response study in Japanese subjects, approval lag between Japan and the United States or Europe (US/EU), novelty of the drug, estimated number of target patients, and number of supplemental approvals. Negative binomial regression and path analyses were performed to investigate the association between PSRAs and drug characteristics. PSRAs were more common among antineoplastic agents and drugs with a larger estimated number of target patients and were less common among drugs with a longer approval lag between Japan and the US/EU. Supplemental approval was more common among antineoplastic agents, and there were fewer target patients for novel drugs. For new drugs with the characteristics identified in the present study, it is important to proactively collect post-market safety information by intensifying patient monitoring.