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

Abstract

Objective: Combined hormonal contraceptives (CHC) exhibit differing risks for cardiovascular and thrombotic events (VTE). A European referral process confirmed higher VTE risks for 3^rd 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 authorization 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.

Methods: German prescription data for 1.1 million women below 20 years of age were used to analyze 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.

Results: 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.

Conclusion: 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, although 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.

Keywords:

• ARIMA
• Combined hormonal contraceptives
• Intervention analysis
• Pharmacoepidemiology
• Thromboembolism
• Claims data
• Germany

Transparency

Declaration of funding

The study was supported by Federal Institute for Drugs and Medical Devices (BfArM) [V-16770/68605/2016-2017].

Declaration of financial/other interests

The authors and CMRO peer reviewers on this manuscript have no financial/other relationships to disclose.

Acknowledgments

The authors wish to thank AOK Research Institute (WIdO) for providing data for the analysis and Professor Reinhard Schuster, University of Lübeck, for valuable hints concerning modeling.

Notes

Ϯ Time series analyses of prevalences was limited up until October 2015. Annual prevalences are shown only up to 2015, inclusively.