title: Evaluation of two Japanese regulatory actions using medical information databases: a 'Dear Doctor' letter to restrict oseltamivir use in teenagers, and label change caution against co-administration of omeprazole with clopidogrel.
abstract: OBJECTIVE
  The implementation of appropriate epidemiological methodology using medical information databases (MIDs) to evaluate the effects of regulatory actions has been highly anticipated. To assess scientific methods for active pharmacovigilance using MIDs, we conducted a quantitative assessment of the impact of two regulatory actions by the Japanese government: (i) restriction of use of oseltamivir in teenagers in March 2007 and (ii) caution against the co-administration of omeprazole (OPZ) with clopidogrel (CPG) in April 2010.
  
  
  METHODS
  Data were obtained from four hub hospitals in Japan. We measured the seasonal proportion of patients prescribed oseltamivir to those prescribed neuraminidase inhibitors for the 2002/2003 to 2010/2011 seasons. The monthly proportion of patients co-administered OPZ and CPG (OPZ+CPG) to those prescribed CPG was measured from May 2009 to April 2011. We evaluated the changes observed with implementation of the regulatory actions. To estimate the impact of the actions, we conducted segmented regression analysis using interrupted time series data. The impact was assessed by two parameter estimates of the regression model: the change in level for short-term effects and change in trend for long-term effects.
  
  
  CONCLUSIONS
  The use of oseltamivir in the target 10-19 years age group showed a significant and large decline (63·16%) immediately after the intervention (P = 0·0008). No change was observed in OPZ+CPG, although there was a relative inhibitory trend for OPZ+CPG compared with co-administration of lansoprazole or rabeprazole with CPG as the control group. When restricted to new users of CPG, the stratified results were consistent with the overall results.
  
  
  CONCLUSIONS
  The current analysis demonstrates the effectiveness of two regulatory actions. The results of the current study indicate that MID research can contribute to assessing and improving pharmacovigilance activities.
authors.affiliation: Division of Medicinal Safety Science, National Institute of Health Sciences, Tokyo, Japan; Department of Regulatory Science, Graduate School of Pharmaceutical Sciences, Nagoya City University, Aichi, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Hanatani
authors.forename: K
authors.initials: K
authors.lastname: Sai
authors.forename: M
authors.initials: M
authors.lastname: Tohkin
authors.forename: K
authors.initials: K
authors.lastname: Segawa
authors.forename: Y
authors.initials: Y
authors.lastname: Antoku
authors.forename: N
authors.initials: N
authors.lastname: Nakashima
authors.forename: H
authors.initials: H
authors.lastname: Yokoi
authors.forename: K
authors.initials: K
authors.lastname: Ohe
authors.forename: M
authors.initials: M
authors.lastname: Kimura
authors.forename: K
authors.initials: K
authors.lastname: Hori
authors.forename: J
authors.initials: J
authors.lastname: Kawakami
authors.forename: Y
authors.initials: Y
authors.lastname: Saito
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use; D002648:Child; D000077144:Clopidogrel; D016208:Databases, Factual / Q000706:statistics & numerical data; D004347:Drug Interactions; D004335:Drug and Narcotic Control; D006801:Humans; D065186:Interrupted Time Series Analysis; D007564:Japan; D009853:Omeprazole / Q000008:administration & dosage / Q000627:therapeutic use*; D053139:Oseltamivir / Q000008:administration & dosage / Q000627:therapeutic use*; D060735:Pharmacovigilance; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D010818:Practice Patterns, Physicians' / Q000706:statistics & numerical data; D054328:Proton Pump Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D012044:Regression Analysis; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D010975:Platelet Aggregation Inhibitors; D054328:Proton Pump Inhibitors; D053139:Oseltamivir; D000077144:Clopidogrel; D009853:Omeprazole; D013988:Ticlopidine
keywords: clopidogrel; medical information database; omeprazole; oseltamivir; pharmacovigilance; regulatory action