title: Different contributions of internal reviewers and external experts to labelling decisions on therapeutic indications in new drug reviews in Japan.
abstract: OBJECTIVE
  External experts play an important role in shaping regulatory decisions in the new drug review process in the United States, Europe and Japan. No rigorous study has been performed addressing how and to what extent external experts, in contrast to internal reviewers in the agency, influence the regulatory decisions during new drug reviews. We examined their contributions in Japanese regulatory reviews in contrast to the internal reviewers, focusing on the labelling decision on therapeutic indications.
  
  
  METHODS
  With the data set of 219 new molecular entities (NMEs) approved in Japan from 2000 to 2009, we observed how proposed indications in labelling were modified in a stepwise manner during the review process and conducted multinomial logistic analysis to examine the possible mechanism behind.
  
  
  CONCLUSIONS
  We found that interim assessment of indications by the internal reviewers was modified substantially by the influence of the external experts in about 20% of the 219 NMEs. Our analysis suggested that internal reviewers provided their opinion mainly based on strict review discipline, whereas external experts added flexibility and reality to their reviews. Our analysis revealed different evaluations between internal reviewers and external experts during regulatory discussions in new drug reviews and how the external panel contributes to changing internal decisions.
  
  
  CONCLUSIONS
  This study provides a new and quantitative approach to better label setting by emphasizing the contributions of each stakeholder in new drug reviews, which would improve the efficiency, quality and transparency of new drug reviews to enhance public health.
authors.affiliation: Laboratory of Pharmaceutical Regulatory Science, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Yokota
authors.forename: M
authors.initials: M
authors.lastname: Kusama
authors.forename: N
authors.initials: N
authors.lastname: Matsuki
authors.forename: S
authors.initials: S
authors.lastname: Ono
mesh_terms: D017277:Drug Approval / Q000706:statistics & numerical data*; D004348:Drug Labeling / Q000706:statistics & numerical data*; D004358:Drug Therapy / Q000592:standards; D006801:Humans; D007564:Japan; D016015:Logistic Models
keywords: Japan; decision-making; drug review; external experts; regulatory