Drug safety and the impact of drug warnings: An interrupted time series analysis of diabetes drug prescriptions in Germany and Denmark

- The study analyses the impact of drug warnings across two regulatory settings.
- Drug safety warnings for two anti-diabetic drugs are used as case study.
- National bodies for drug regulation seem to mediate the effect of drug warnings.
- New drugs and approval processes increase the complexity of drug safety regulation.
- This requires a strengthening of channels to exchange drug safety information.

ObjectiveTo analyse the impact of drug safety warnings from the European Medicines Agency (EMA) on drug utilisation and their interaction with information released through national reimbursement bodies.MethodsInsurance claims data on anti-diabetic drug prescriptions in primary care in Germany and Denmark were analysed using interrupted time series analysis, with EMA drug warnings for thiazolidinediones (TZDs) in 2007 and 2011 as the intervention. Monthly drug utilisation data per substance in defined daily dosages (DDD) consumed per 1000 insurees were retrieved from the Danish national drug prescriptions register and one large statutory sickness fund in Germany.ResultsTZDs were generally reimbursed in Germany but restricted to individual reimbursement in Denmark. Consequently, utilisation of TZDs was much higher in Germany in 2007 compared with Denmark. For rosiglitazone, the drug warning had a significant impact on utilisation, reducing the number of DDD per 1000 insurees per day by −0.0105 in Denmark and −0.0312 in Germany (p-values < 0.05). For pioglitazone, neither of the drug warnings had a significant effect on utilisation.ConclusionThe impact of EMA drug warnings differed across countries and might be mediated by information released through national reimbursement bodies and physician associations. Increasing complexity of new drugs and modified approval procedures require a strengthening of information exchange between drug regulation bodies and physicians to ensure patient safety.