Cover Page The handle

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Cover Page

The handle

http://hdl.handle.net/1887/66796

holds various files of this Leiden University

dissertation.

Author: Bank, P.C.D.

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Improving acceptance of pharmacogenetic

testing in patient care

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The research presented in this thesis was performed at the department of Clinical Pharmacy & Toxicology of the Leiden University Medical Center, Leiden, the Netherlands.

Financial support for the publication of this thesis was provided by the department of Clinical Pharmacy & Toxicology of the Leiden University Medical Center, Leiden, the Netherlands. The research described in this thesis has been made possible by an unrestricted grant from the Royal Dutch Association for the Advancement of Pharmacy, The Hague, The Netherlands. The study performed in chapter 3 has been performed using GenoChip CYP2D6 kits provided by PharmGenomics GmbH, Mainz, Germany. The research described in chapter 4 was funded by an unrestricted grant from Zorg & Zekerheid, Leiden, The Netherlands and was carried out using DMET Plus arrays provided by Affymetrix, Santa Clara, CA, United States of America.

Cover design Mai Tran

Layout Renate Siebes | Proefschrift.nu

Printed by ProefschriftMaken | www.proefschriftmaken.nl

ISBN 978-94-92026-15-6

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Improving acceptance of pharmacogenetic

testing in patient care

Proefschrift

ter verkrijging van

de graad van Doctor aan de Universiteit Leiden,

op gezag van Rector Magnificus prof. mr. C.J.J.M. Stolker,

volgens besluit van het College voor Promoties

te verdedigen op woensdag 14 november 2018

klokke 10.00 uur

door

Paul Christiaan Dirk Bank

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Promotor

Prof. dr. H.-J. Guchelaar

Copromotor

Dr. J.J. Swen

Leden promotiecommissie

Prof. dr. J. Gussekloo

Prof. dr. R.H.N. van Schaik

Erasmus University Medical Center, Rotterdam

Prof. dr. B. Wilffert

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“You inspire me

Like I inspire you”

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Chapter 1 General introduction

11 Part I answers to frequently asked question by clinicians regarding PGx

Chapter 2 Pharmacogenetic biomarkers for predicting drug response

21 Part II Implementation of PGx in clinical practice and its impact on a national level

Chapter 3 GenoChip CYP2D6 macroarray as a method to genotype for

CYP2D6 variants: results of a validation study in a Caucasian

population

53

Chapter 4 Implementation of pharmacist initiated pre-emptive

pharmacogenetic testing in primary care

67

Chapter 5 Nation-wide impact of implementing a preemptive

pharmacogenetic panel approach to guide drug prescribing in

primary care in The Netherlands

85 Part III Harmonization of PGx-test interpretation and therapeutic recommendations

Chapter 6 Fluoropyrimidine toxicity in patients with a dihydropyrimidine

dehydrogenase (DPD) splice site variant: the need for further

revision of dose and schedule

109

Chapter 7 Comparison of the Guidelines of the Clinical

Pharmacogenetics Implementation Consortium and the Dutch

Pharmacogenetics Working Group

125

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Part IV Knowledge, experience and attitudes towards PGx of pharmacists and

pharmacy students

Chapter 8 A nationwide survey of pharmacists’ perception of

pharmacogenetics in the context of a clinical decision support

system containing pharmacogenetics dosing recommendations

165

Chapter 9 A nationwide cross-sectional survey of pharmacy students on

knowledge, experience, and attitudes towards pharmacogenetic

testing in the Netherlands

207 Part V General discussion & Summary

Chapter 10 General discussion

243

Chapter 11 English summary

269 Nederlandse samenvatting

279 About the author

289

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