Implementation of dihydropyrimidine dehydrogenase deficiency testing in Europe

‘The Working Group on the Implementation of DPD-deficiency Testing in Europe’, M de With, A Sadlon, E Cecchin, V Haufroid, F Thomas, M Joerger, R H N van Schaik, R H J Mathijssen, C R Largiadèr*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

14 Citations (Scopus)
23 Downloads (Pure)


BACKGROUND: The main cause for fluoropyrimidine-related toxicity is deficiency of the metabolizing enzyme dihydropyrimidine dehydrogenase (DPD). In 2020, the European Medicines Agency (EMA) recommended two methods for pre-treatment DPD deficiency testing in clinical practice: phenotyping using endogenous uracil concentration or genotyping for DPYD risk variant alleles. This study assessed the DPD testing implementation status in Europe before (2019) and after (2021) the release of the EMA recommendations.

METHODS: The survey was conducted from 16 March 2022 to 31 July 2022. An electronic form with seven closed and three open questions was e-mailed to 251 professionals with DPD testing expertise of 34 European countries. A descriptive analysis was conducted.

RESULTS: We received 79 responses (31%) from 23 countries. Following publication of the EMA recommendations, 87% and 75% of the countries reported an increase in the amount of genotype and phenotype testing, respectively. Implementation of novel local guidelines was reported by 21 responders (27%). Countries reporting reimbursement of both tests increased in 2021, and only four (18%) countries reported no coverage for any testing type. In 2019, major implementation drivers were 'retrospective assessment of fluoropyrimidine-related toxicity' (39%), and in 2021, testing was driven by 'publication of guidelines' (40%). Although the major hurdles remained the same after EMA recommendations-'lack of reimbursement' (26%; 2019 versus 15%; 2021) and 'lack of recognizing the clinical relevance by medical oncologists' (25%; 2019 versus 8%; 2021)-the percentage of specialists citing these decreased. Following EMA recommendations, 25% of responders reported no hurdles at all in the adoption of the new testing practice in the clinics.

CONCLUSIONS: The EMA recommendations have supported the implementation of DPD deficiency testing in Europe. Key factors for successful implementation were test reimbursement and clear clinical guidelines. Further efforts to improve the oncologists' awareness of the clinical relevance of DPD testing in clinical practice are needed.

Original languageEnglish
Article number101197
Number of pages8
JournalESMO Open
Issue number2
Publication statusPublished - Apr 2023

Bibliographical note

Funding Information:
Reimbursement of both genotype and phenotype testing varied significantly across the countries, highlighting in part the different health care systems in Europe ( Figure 4 ). Nevertheless, in 2019, more than half of the countries (55%) reported reimbursements for DPYD genotyping without any additional condition, a number which increased to 68% in 2021. Regional differences were noted in Denmark, whereas in Greece, a center reported reimbursement for genotyping in 2019 in the context of a project funded by the European Union. In Austria, the reimbursement of genotyping depended on the type of hospital and doctor prescribing the test, whereas in Israel, costs were reimbursed for inpatients in 2019 and then by the national health insurance in 2021. Of note, by 2021, neither genotyping nor phenotyping was reimbursed in four countries (Bulgaria, Greece, Lithuania, and Poland). In the countries carrying out phenotype tests, two countries (France and The Netherlands) reported coverage by the national/social health insurance in 2019, with the addition of Germany, Israel, and Spain in 2021 ( Figure 4 ).

Publisher Copyright:
© 2023 The Author(s)


Dive into the research topics of 'Implementation of dihydropyrimidine dehydrogenase deficiency testing in Europe'. Together they form a unique fingerprint.

Cite this