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Curr Med Res Opin. 2018 Oct 26:1-16. doi: 10.1080/03007995.2018.1541317. [Epub ahead of print]

Impact of EU risk assessment process and administrative regulations for manufacturers of combined hormonal contraceptive prescribing. An analysis of developments in Germany and the implications.

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a Institute for Medical Biophysics, Medical Faculty in Hradec Králové, Charles-University , Šimkova 870 , 50038 Hradec Králové , Czech Republic.
b AOK Research Institute (WIdO) , Rosenthaler Straße 31 , 10178 Berlin , Germany.
c PMV research group, Clinic and Policlinic for Psychiatry, Psychosomatics and Psychotherapy of Children and Adolescents, Cologne University , Germany.
d Strathclyde Institute of Pharmacy and Biomedical Sciences, Strathclyde University , Glasgow G4 ORE , UK.
e Health Economics Centre, Liverpool University Management School , Chatham Street , Liverpool , UK.
f Department of Laboratory Medicine, Division of Clinical Pharmacology , Karolinska Institute, Karolinska University Hospital Huddinge , SE-141 86 , Stockholm , Sweden.
g Department of Public Health Pharmacy and Management , School of Pharmacy, Sefako Makgatho Health Sciences University , Garankuwa , South Africa.



Combined hormonal contraceptives (CHC) exhibit differing risks for cardiovascular and thrombotic events (VTE). A European referral process confirmed higher VTE risks for 3rd generation gestagens and drospirenone. CHC are now grouped in risk classes (RC) I, II and III, with RC III having a higher risk than RC I and X (risk not yet known). Marketing authorisation holders were obliged to implement pharmacovigilance measures and risk minimization measures including changes of prescribing information. The study assessed whether these activities induced changes in prescription patterns.


German prescription data for 1.1 million women below 20 were used to analyse the effects of interventions and potential influence factors using logistic regression. Descriptive statistics were calculated for prescriptions for 3.3 million women from January 2011 to March 2016.


Shares of RC I and RC X recipients rose substantially over the observation period, while RC III recipient share showed a steady decrease. The referral induced a slightly faster decrease in RC III and increase in RC X. The implementation of pharmacovigilance measures manifested no additional effect.


The decrease in RC III share already observed before the referral process can be explained with pre-existing discussions around CHC. The effect attributable to the referral was statistically significant, though very small. While evidence for a connection between interventions and prescription change is only indirect, the study shows that routine data are suitable for impact analyses, and monitoring prescribing patterns can be recommended as feedback after regulatory or political interventions. This is being followed up.


ARIMA; Germany; claims data; combined hormonal contraceptives; intervention analysis; pharmacoepidemiology; thromboembolism

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