VIctoria Abbing

223 Pages·2015·4.67 MB·English

Understanding differences in findings
from pharmacoepidemiological studies
The case of antidepressant and benzodiazepine use
and hip fracture
Victoria Abbing-Karahagopian
Funding
Most of the studies in this thesis were conducted as part of the IMI-PROTECT consortium
(Pharmacoepidemiological Research on Outcomes of Therapeutics by a European Con-
sorTium, www.imi-protect.eu) which is a public-private partnership coordinated by the
European Medicines Agency.
The IMI-PROTECT project has received support from the Innovative Medicine Initiative
Joint Undertaking (www.imi.europa.eu) under Grant Agreement n° 115004, resources of
which are composed of financial contribution from the European Union’s Seventh Frame-
work Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution. In the
context of the IMI Joint Undertaking (IMI JU), the Department of Pharmacoepidemiology
and Clinical Pharmacology, Utrecht University, also received a direct financial contribution
from Pfizer. The views expressed are those of the authors only and not of their respective
institution or company.
Printing of this thesis was kindly supported by the Nederlands Bijwerkingen Fonds [NBF,
Dutch side effects fund].
ISBN: 978-94-6169-797-4
Layout and Printing: Optima Grafische Communicatie (www.ogc.nl)
Cover painting by Arthur Pinajian 1914 – 1999.
Courtesy of Pinajian Estate Collection (PinajianArt.com - http://pinajianart.com)
Copyright © 2016 by V. Abbing-Karahagopian. The copyright of the articles that have been
published has been transferred to the respective journals.
Understanding differences in findings from
PharmacoePidemiological stUdies
the case of antidepressant and benzodiazepine use and hip fracture

VariaBiliteit in Uitkomsten Van
farmacoePidemiologisch onderzoek:
de associatie tussen antidepressiva- en benzodiazepinegebruik en heupfracturen
als casus

(met een samenvatting in het Nederlands)

Proefschrift
ter verkrijging van de graad van doctor aan de Universiteit Utrecht
op gezag van de rector magnificus, prof. dr. G.J. van der Zwaan,
ingevolge het besluit van het college voor promoties in het openbaar te
verdedigen op dinsdag 19 januari 2016 des middags te 12.45 uur
door
Victoria Abbing-Karahagopian
geboren op 9 april 1971
te Beiroet, Libanon
Promotoren: Prof. dr. A.C.G. Egberts
Prof. dr. H.G.M. Leufkens
Copromotoren: Dr. M.L. De Bruin
Dr. T.P. van Staa
In memory of one and a half million Armenians killed
during the Genocide in 1915 by the Ottoman government.

To future generations claiming their right for a dignified life,
education and living their own culture.

taBle of contents
chapter 1 | introduction 9
1.1 General introduction 11
1.2 Bridging differences in outcomes of pharmacoepidemiological 25
studies: design and first results of the PROTECT project.
chapter 2 | Variability in medication use patterns and health outcomes in europe 41
2.1 Antidepressant prescribing in five European countries: application of 43
common definitions to assess the prevalence, clinical observations and
methodological implications.
2.2 Exposure to benzodiazepines and related drugs in seven European 59
electronic healthcare databases: a cross-national descriptive study
from the PROTECT-EU Project
2.3 Incidence rates and trends of hip/femur fractures in five European 79
countries: comparison using e-healthcare records databases
chapter 3 | Understanding findings of pharmacoepidemiological studies: complexity 95
of concomitant exposures
3.1 Understanding inconsistency in the results from observational 99
pharmacoepidemiological studies: the case of antidepressant use and
risk of hip fracture
3.2 Concomitant medication use and its implications on the 125
hazard pattern in pharmacoepidemiological studies: example of
antidepressants, benzodiazepines and fracture risk
3.3 Concomitant users of antidepressants and benzodiazepines: does 141
different timing of initiation modify the risk of osteoporotic fracture?
chapter 4 | general discussion 157
chapter 5 | summary & samenvatting 181
appendices | Acknowledgements 201
List of co-authors 209
List of publications 215
About the author 221

1
Introduction
chapter