title: Prescribing of rosiglitazone and pioglitazone following safety signals: analysis of trends in dispensing patterns in the Netherlands from 1998 to 2008.
abstract: BACKGROUND
  Relevant safety signals in the EU are regularly communicated in so-called 'Direct Healthcare Professional Communications' (DHPCs) or European Medicines Agency (EMA) press releases. Trends of a decrease in the use of rosiglitazone following regulatory safety warnings have been described in the US. In the EU, however, relatively little is known about dispensing patterns following DHPCs or other safety signals such as EMA press releases.
  
  
  OBJECTIVE
  The objective of this study was to analyse trends in dispensing patterns of rosiglitazone and pioglitazone following DHPCs and EMA press releases in the EU member state, the Netherlands.
  
  
  METHODS
  Data for this study were obtained from the PHARMO Record Linking System, which includes drug dispensing records from community pharmacies of approximately 2.5 million individuals in the Netherlands. Over the period 1998-2008 an auto-regressive, integrated, moving average model (ARIMA) was fitted. The DHPC letters or EMA press releases were used as determinants. Adjustments were made for publication of certain literature. Stratification was performed for dispensings prescribed by general practitioners (GPs) and those prescribed by specialists.
  
  
  RESULTS
  For rosiglitazone, four EMA press releases and two DHPCs were issued; for pioglitazone, one DHPC was issued. The number of rosiglitazone dispensings prescribed by GPs decreased significantly after publication of DHPCs and EMA press releases concerning the risk of macular oedema and risk of fractures (both p-values 0.001). The number of rosiglitazone dispensings decreased statistically significantly after publication of EMA press releases 2 and 3 concerning cardiovascular risks but not for EMA press release 4. Adjustment for certain publications in the literature reduced the effect of communicated safety issues on the proportion of dispensings.
  
  
  CONCLUSIONS
  Although it is difficult to disentangle the effect of DHPCs and EMA press releases from the effect of reports published in the literature, our results suggest that prescribers may react to such safety communications.
authors.affiliation: Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands.
authors.forename: Rikje
authors.initials: R
authors.lastname: Ruiter
authors.forename: Loes E
authors.initials: LE
authors.lastname: Visser
authors.forename: Myrthe P P
authors.initials: MP
authors.lastname: van Herk-Sukel
authors.forename: Petronella H
authors.initials: PH
authors.lastname: Geelhoed-Duijvestijn
authors.forename: Sandra
authors.initials: S
authors.lastname: de Bie
authors.forename: Sabine M J M
authors.initials: SM
authors.lastname: Straus
authors.forename: Peter G M
authors.initials: PG
authors.lastname: Mol
authors.forename: Silvana A
authors.initials: SA
authors.lastname: Romio
authors.forename: Ron M C
authors.initials: RM
authors.lastname: Herings
authors.forename: Bruno H Ch
authors.initials: BH
authors.lastname: Stricker
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems / Q000592:standards*; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D011307:Drug Prescriptions / Q000706:statistics & numerical data*; D004363:Drug Utilization; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D010594:Pharmacies; D000077205:Pioglitazone; D010818:Practice Patterns, Physicians' / Q000639:trends*; D012306:Risk; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D000077205:Pioglitazone