BACKGROUND: Prediction and management of drug safety is a global regulatory issue. Safety-related regulatory actions (SRRAs) are taken mostly when unexpected adverse drug reactions occur. Currently, Japan is reconciled to delayed access to new drugs (ie, launch delay compared to Western countries), but may have been benefiting by free-riding on safety data accumulated in other countries prior to Japanese launch. OBJECTIVE: To identify factors that are significantly associated with SRRAs, and to discuss the challenges that Japan might have to face with increasing access to new drugs. METHODS: The SRRAs of 135 new drugs approved from January 2000 to December 2005 were analyzed to investigate association with launch lag, company and drug characteristics, market size, submission data, and regulatory status. SRRAs were measured in terms of the number of emergency safety information notifications and official safety instructions issued by the Japanese regulatory agency within 3 years after approval. A negative binomial distribution model was used for regression analysis. RESULTS: Longer launch lags and presence of drugs with similar modes of action were associated with fewer SRRAs. Bridging strategy showed increased SRRAs. No significant association was observed between SRRAs and the subject number in clinical data packages. Occurrence of SRRAs was varied among development strategy, preceding products, and regional regulations. CONCLUSIONS: The occurrence of SRRAs was associated with the accumulation of both foreign and domestic postmarketing evidence rather than with clinical trial data upon launch. Considering the paradigm shift to simultaneous global drug development and filing for regulatory approval, this study indicates the importance of intensive data collection in the early postmarketing phase and use of safety information in early markets. However, even if we would be sufficiently cautious about safety risks of new drugs, a population that enjoys first-in-class drugs probably has to bear the risks.
BACKGROUND: Prediction and management of drug safety is a global regulatory issue. Safety-related regulatory actions (SRRAs) are taken mostly when unexpected adverse drug reactions occur. Currently, Japan is reconciled to delayed access to new drugs (ie, launch delay compared to Western countries), but may have been benefiting by free-riding on safety data accumulated in other countries prior to Japanese launch. OBJECTIVE: To identify factors that are significantly associated with SRRAs, and to discuss the challenges that Japan might have to face with increasing access to new drugs. METHODS: The SRRAs of 135 new drugs approved from January 2000 to December 2005 were analyzed to investigate association with launch lag, company and drug characteristics, market size, submission data, and regulatory status. SRRAs were measured in terms of the number of emergency safety information notifications and official safety instructions issued by the Japanese regulatory agency within 3 years after approval. A negative binomial distribution model was used for regression analysis. RESULTS: Longer launch lags and presence of drugs with similar modes of action were associated with fewer SRRAs. Bridging strategy showed increased SRRAs. No significant association was observed between SRRAs and the subject number in clinical data packages. Occurrence of SRRAs was varied among development strategy, preceding products, and regional regulations. CONCLUSIONS: The occurrence of SRRAs was associated with the accumulation of both foreign and domestic postmarketing evidence rather than with clinical trial data upon launch. Considering the paradigm shift to simultaneous global drug development and filing for regulatory approval, this study indicates the importance of intensive data collection in the early postmarketing phase and use of safety information in early markets. However, even if we would be sufficiently cautious about safety risks of new drugs, a population that enjoys first-in-class drugs probably has to bear the risks.