title: Lessons from gefitinib-induced interstitial lung disease in Japan: Problems in approval, pharmacovigilance, and regulatory decision-making procedures.
abstract: OBJECTIVE
  The objective of this study was to identify problems in the approval, pharmacovigilance, and post-approval regulatory decision-making procedures involving gefitinib and to propose countermeasures to prevent further drug-induced suffering in Japan in the future.
  
  
  METHODS
  We comprehensively reviewed reports regarding gefitinib published during the period from 2000 to 2006 by regulatory agencies, the manufacturer of the gefitinib-containing drug, cancer clinical study groups, and a scientific society.
  
  
  RESULTS
  We identified the following major problems in the approval, pharmacovigilance, and regulatory decision-making procedures: 1) the results of animal experiments and pre-marketing clinical trials, and reports of adverse drug reactions from other countries were not properly reflected in the label; 2) indications for the drug were expanded without strict evaluation of the external validity of pre-marketing clinical trials; and 3) despite many serious cases of interstitial lung disease (ILD) being spontaneously reported, well-designed post-marketing surveillance was not immediately performed.
  
  
  CONCLUSIONS
  We propose a mandatory total registry of all drug users and surveillance (i.e. a prospective outcome study) as one of the rational solutions for preventing further drug-induced suffering in Japan.
authors.affiliation: Clinical Trial Design and Management, Translational Research Center, Kyoto University Hospital, Kyoto, ( Japan ).
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nishimura
authors.affiliation: Clinical Trial Design and Management, Translational Research Center, Kyoto University Hospital, Kyoto, ( Japan ).
authors.forename: Harue
authors.initials: H
authors.lastname: Tada
authors.affiliation: Clinical Trial Design and Management, Translational Research Center, Kyoto University Hospital, Kyoto, ( Japan ).
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Nakagawa
authors.affiliation: Clinical Trial Design and Management, Translational Research Center, Kyoto University Hospital, Kyoto, ( Japan ).
authors.forename: Satoshi
authors.initials: S
authors.lastname: Teramukai
authors.affiliation: Pharmacoepidemiology, Graduate School of Public Health, Kyoto University , Kyoto, ( Japan ).
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Matsui
authors.affiliation: Clinical Trial Design and Management, Translational Research Center, Kyoto University Hospital, Kyoto, ( Japan ).
authors.forename: Masanori
authors.initials: M
authors.lastname: Fukushima
keywords: Decision making; Gefitinib; Japan; Lung diseases; Product surveillance; interstitial; organizational; postmarketing