title: Analysis of pharmaceutical safety-related regulatory actions in Japan: do tradeoffs exist between safer drugs and launch delay?
abstract: 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.
authors.affiliation: Pharmaceutical Regulatory Science, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Yamada
authors.forename: Makiko
authors.initials: M
authors.lastname: Kusama
authors.forename: Yuka
authors.initials: Y
authors.lastname: Hirai
authors.forename: Frank
authors.initials: F
authors.lastname: Arnold
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Sugiyama
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Ono
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems; D017277:Drug Approval / Q000379:methods / Q000706:statistics & numerical data*; D055808:Drug Discovery / Q000191:economics / Q000331:legislation & jurisprudence / Q000379:methods*; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D007564:Japan; D004364:Pharmaceutical Preparations / Q000191:economics; D013997:Time Factors
chemical_list: D004364:Pharmaceutical Preparations