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


METHODS
Insurance 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.


RESULTS
TZDs 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.


CONCLUSIONS
The 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.
COHERE Centre of Health Economic Research, Department of Business and Economics, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark. Electronic address: gih@sam.sdu.dk.
Gisela
G
Hostenkamp
Hamburg Center for Health Economics, University of Hamburg, Esplanade 36, 20354 Hamburg, Germany; CINCH Center for Health Economic Research, University of Duisburg-Essen, Thea-Leymann-Str. 9, 45127 Essen, Germany. Electronic address: katharina.fischer@uni-due.de.
Katharina Elisabeth
KE
Fischer
Holbæk Hospital, Region Zealand, Smedelundsgade 60, 4300 Holbæk, Denmark. Electronic address: knbo@regionsjaelland.dk.
Knut
K
Borch-Johnsen
D003718:Denmark; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004347:Drug Interactions; D004348:Drug Labeling; D011307:Drug Prescriptions; D004363:Drug Utilization; D064420:Drug-Related Side Effects and Adverse Reactions; D005858:Germany; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000077205:Pioglitazone; D000077154:Rosiglitazone; D045162:Thiazolidinediones
D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D000077205:Pioglitazone
Denmark; Drug safety warnings; Germany; Post-marketing surveillance; Regulation; Utilisation