title: Fatal adverse drug reactions of anticancer drugs detected by all-case post-marketing surveillance in Japan.
abstract: OBJECTIVE
  All-case post-marketing surveillance of newly approved anticancer drugs is usually conducted on all patients in Japan. The present study investigates whether all-case post-marketing surveillance identifies fatal adverse drug reactions undetected before market entry.
  
  
  METHODS
  We examined fatal adverse drug reactions identified via all-case post-marketing surveillance by reviewing the disclosed post-marketing surveillance results, and determined the time points in which the fatal adverse drug reactions were initially reported by reviewing drug labels. We additionally scanned emergency alerts on the Japanese regulatory authority website to assess the relationship between all-case post-marketing surveillance and regulatory action.
  
  
  RESULTS
  Twenty-five all-case post-marketing surveillances were performed between January 1999 and December 2009. Eight all-case post-marketing surveillances with final results included information on all fatal cases. Of these, the median number of patients was 1287 (range: 106-4998), the median number of fatal adverse drug reactions was 14.5 (range: 4-23). Of the 111 fatal adverse drug reactions detected in the eight post-marketing surveillances, only 28 (25.0%) and 22 (19.6%) were described on the initial global and the initial Japanese drug label, respectively, and 58 (52.3%) fatal adverse drug reactions were first described in the all-case post-marketing surveillance reports. Despite this, the regulatory authority issued only four warning letters, and two of these were prompted by case reports from the all-case post-marketing surveillance.
  
  
  CONCLUSIONS
  All-case post-marketing surveillance of newly approved anticancer drugs in Japan was useful for the rigorous compilation of non-specific adverse drug reactions, but it rarely detected clinically significant fatal adverse drug reactions.
authors.affiliation: Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo Division of Internal Medicine, Jyoban Hospital, Tokiwakai jin_ichi@hotmail.com.
authors.forename: Jinichi
authors.initials: J
authors.lastname: Mori
authors.affiliation: Division of Internal Medicine, Jyoban Hospital, Tokiwakai Division of Social Communication System for Advanced Clinical Research, Institute of Medical Science, The University of Tokyo, Tokyo.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Tanimoto
authors.affiliation: Division of Hematology, Teikyo University Chiba Medical Center, Chiba, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Miura
authors.affiliation: Division of Social Communication System for Advanced Clinical Research, Institute of Medical Science, The University of Tokyo, Tokyo.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kami
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000401:mortality*; D005260:Female; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D011358:Product Surveillance, Postmarketing
chemical_list: D000970:Antineoplastic Agents
keywords: adverse drug reaction reporting systems; antineoplastic agents; post-marketing drug surveillance