gms | German Medical Science

24th Annual Meeting of the German Drug Utilisation Research Group (GAA)

Gesellschaft für Arzneimittelanwendungsforschung und Arzneimittelepidemiologie

30.11. - 01.12.2017, Erfurt

Impact of a European Referral Process on the Prescription Volume of combined hormonal contraceptives

Meeting Abstract

Gesellschaft für Arzneimittelanwendungsforschung und Arzneimittelepidemiologie e.V. (GAA). 24. Jahrestagung der Gesellschaft für Arzneimittelanwendungsforschung und Arzneimittelepidemiologie. Erfurt, 30.11.-01.12.2017. Düsseldorf: German Medical Science GMS Publishing House; 2017. Doc17gaa110

doi: 10.3205/17gaa110, urn:nbn:de:0183-17gaa1105

Published: December 5, 2017

© 2017 Selke Krulichová et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.


Outline

Text

Background: Hormonal contraceptives have been available since the 1960s. They ususally contain an estrogen and a gestagen, which is why they are commonly referred to as combined hormonal contraceptives (CHC). Over time, compositions have been changed in order to reduce side effects, in particular cardiovascular and thromboembolic events (VTE). However, since several studies have shown increased risk for newer combinations (3rd/4th generation), a European referral process was started on initiative of the French marketing authority. Increase of risk was confirmed for 3rd generation gestagens and for

drospirenone. For chlormadinone, dienogest and nomegestrol no conclusions could be made based on available evidence. Manufacturers of 3rd and 4th generation CHC were required to include risk notices in the package insert. It was anticipated that this should lead to decreased prescribing of these products. In the meantime, labeling by generations was replaced by risk classes. Risk class III shows higher risk vor VTE than class I; for risk class III no final evaluation of VTE risk is available yet. The CHC subject to the referral are grouped in risk classes I (norgestimate), III (desogestrel, gestodene, drospirenone), and X (nomegestrol, chlormadinone, dienogest).

The study aims to ascertain whether the referral process and its implementation led to changes in prescribing of CHC.

Materials and Methods: Data: anonymised prescription data for German women covered by AOK (Actrapid®). (1.1 million women aged 10 to under 20: contraceptives are reimbursable only for this age bracket.)

The analysis distinguished four phases:

  • A 01 Jan 2011-31 Dec 2012: pre-intervention
  • B 01 Jan 2013-31 Dec 2013: referral phase
  • C 01 Jan 2014-31 Dec 2014: implementation of EMA requirements
  • D 01 Jan 2015-31 Oct 2015: post-intervention

Data werde subjected to descriptive statistics. For the effects of the interventions time series were analysed using ARIMA-based models. Possible factors were evaluated using logistic regression. For statistical analyses, NCSS 9 and R 3.3.2 were used.

Results: The share of recipients of class I CHC (as a percentage of all CHC recipients) increased markedly between 2011 and 2013 and again from 2014 (+11%). By contrast, the share of those receiving risk class III drugs decreased steadily (-64%). The share of risk class X recipients also shows a substantial increase (+54%). Time trend analysis shows a statistically significant decrease of risk clas III for the first month of the referral phase, compared to the previous month. We were able to show that the previously observed decrease was slightly augmented by the referral process (interpreted as a factor).

The second intervention, i.e., the implementation of the requirements for the package inserts, did not show a statistically significant impact on prescribing. For risk class X products there was a small, but statistically significant impact of the referral on the development of prescribing - however, in the opposite direction, i.e., prescribing increased stronger than before the referral. As in the case of risk class III, no additional effect of the implementation was observed.

Conclusion: The issue has been studied in several countries with varying results. The decrease in risk class III precriptions already observed prior to the referral can be explained by the previous discussion on CHC safety. Given this, neither the start of the referral nor the implementation can be expected to have a sudden impact. Still, we were able to show a further augmentation of the previously observed decrease of drugs in risk class III (which contains several of the 3rd generation drugs). Conversely, the previously observed increase of risk class X drugs was also augmented, contrary to intentions. The fact that a separate effect of the second intervention (implementation) could not be proven statistically may also be due to the relatively short time-span between the two interventions.

A practical conclusion is that routine data can indeed be used for the analyis of impact of interventions. However, they provide only indirect evidence for a causal connection between the occasion and the change of prescribing patterns, since not all possibly relevant factors can be observed. In any case, it is advisable to monitor prescribing patterns as a feedback for regulatory or political interventions.

This study was supported by Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM), Förderkennzeichen V16770/68605/2016-2017.


References

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