Multinational cost-utility analysis of panel-based pharmacogenetics-guided treatment of patients enrolled in the U-PGx PREPARE study

EClinicalMedicine, vol. 91, pp. 103686

Abstract

Background: Pharmacogenetics (PGx) aims to revolutionize healthcare by individualizing drug doses and medication choices. However, clinical uptake will require positive evaluation evidence of both clinical utility and cost-effectiveness. We have recently demonstrated the clinical utility of this approach, using a panel-based PGx-guided treatment of patients from various indications recruited in seven countries (PREPARE study). Methods: Here, we provide economic evidence from a multinational cost-utility analysis of PGx-guided treatment in 6930 patients participating in the PREPARE study. The study was conducted from March 2017 to June 2020. We used the national healthcare system's perspective in each participating country, including only direct medical costs that budget holders cover. A Visual Analog Scale was used to measure utility and the quality of life was estimated by averaging the Visual Analog Scale scores of participants over four specific time points in the study, namely baseline visit (day 1), week 4, week 12, and 18 months from the baseline visit. Findings: Our analysis showed that the PGx-guided treatment is marginally cost-effective at the threshold of €11,000 QALYs. Cost drivers were hospitalization and ADRs costs, accounting for most of the resources used in both groups (46% and 37.5% in the PGx-guided group versus 49% and 48% in the control group, respectively), as a result of the average duration of hospitalization [1.51 days (95% CI: 1.23-1.82) for the PGx-guided group and 2.37 days (95% CI: 1.95-2.89) for the control group, resulting in a mean difference of 0.86 days (95% CI: 0.37-1.44). The difference in QALYs gained was 0.00178 (95% CI: 0.00176-0.00180). The ICER was €12,020 (95% CI: €10,957-€13,356) per QALY on average (SD: €116). When comparing cost and effectiveness of actionable PGx-guided versus actionable control patients, the total cost for the PGx-guided group was €491 (95% CI: €384-€613), versus €767 (95% CI: €583-€982) in the control group, with an incremental cost difference of €276 (95% CI: €62-€511), favoring the PGx-guided group. Also, the difference in effectiveness was 0.007 QALYs (95% CI: -0.021 to 0.033). Lastly, the difference in the mean total cost was estimated to be €21.4 (95% CI: €19.5-€23.8), while without considering the PGx test cost, indicative of a pre-emptive genetic testing approach, the PGx-guided treatment becomes a cost-saving option, with an estimated savings of approximately €103.6 (€124-€21.4) per patient. Interpretation: These data suggest that panel-based PGx testing is cost-effective, which, together with the clinically beneficial outcomes already demonstrated in the PREPARE study, provides additional evidence of the need to implement PGx into clinical practice. Funding: European Union Horizon 2020.

Authors 41

1. Vasileios Fragoulakis

   Golden Helix Foundation

   Affiliation as printed

   The Golden Helix Foundation, London, UK

2. Jesse Joachim Swen Aachen Department of Clinical Pharmacy and Toxicology

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Department of Clinical Pharmacy and Toxicology, Leiden University Medical Centre, Leiden, Netherlands

3. Margarita-Ioanna Koufaki

   University of Patras · Golden Helix Foundation

   Affiliation as printed

   The Golden Helix Foundation, London, UK

   University of Patras, School of Health Sciences, Department of Pharmacy, Division of Pharmacology and Biosciences, Laboratory of Pharmacogenomics and Individualised Therapy, Patras, Greece

4. Kathrin Blagec

   Medical University of Vienna

   Affiliation as printed

   Centre for Medical Statistics, Informatics and Intelligent Systems, Institute of Artificial Intelligence, Medical University of Vienna, Vienna, Austria

5. Tanja Blagus

   University of Ljubljana

   Affiliation as printed

   Pharmacogenetics Laboratory, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia

6. Stefan Böhringer Aachen Department of Biomedical Data Sciences

   Leiden University · Leiden University Medical Center · Golden Helix Foundation

   Affiliation as printed

   Department of Biomedical Data Sciences, Leiden University Medical Centre, Leiden, Netherlands

   The Golden Helix Foundation, London, UK

7. Anne Cambon‐Thomsen

   Inserm · Université de Toulouse · Centre d'Epidémiologie et de Recherche en santé des POPulations de Toulouse

   Affiliation as printed

   CNRS, Centre for Epidemiology and Research in Population Health (CERPOP), Université de Toulouse, INSERM, Toulouse, France

8. Erika Cecchin

   Centro di Riferimento Oncologico

   Affiliation as printed

   Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy

9. Ka‐Chun Cheung

   Royal Dutch Pharmacists Association

   Affiliation as printed

   Medicines Information Centre, Royal Dutch Pharmacists Association (KNMP), The Hague, Netherlands

10. Vera H.M. Deneer

    Utrecht University · University Medical Center Utrecht

    Affiliation as printed

    Division Laboratories, Pharmacy and Biomedical Genetics, Hospital Pharmacy, University Medical Centre Utrecht, Utrecht, Netherlands

    Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Netherlands

11. Mathilde Dupui

    Centre Hospitalier Universitaire de Toulouse

    Affiliation as printed

    Service de Pharmacologie Médicale et Clinique, CEIP-addictovigilance de Toulouse, Faculté de Médecine, CHU, Toulouse, France

12. Siv Jönsson

    Uppsala University

    Affiliation as printed

    Department of Pharmacy, Uppsala University, Uppsala, Sweden

13. Candace Joefield‐Roka

    Medical University of Vienna

    Affiliation as printed

    Department of Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria

14. Katja Susanne Just Aachen Institute of Clinical Pharmacology

    Universitätsklinikum Aachen · RWTH Aachen University

    Affiliation as printed

    Institute of Clinical Pharmacology, University Hospital RWTH Aachen, Aachen, Germany

15. Mats O. Karlsson

    Uppsala University

    Affiliation as printed

    Department of Pharmacy, Uppsala University, Uppsala, Sweden

16. Lidija Konta
    Affiliation as printed

    Bio.logis Digital Health, Frankfurt am Main, Germany

    Diagnosticum Centre for Humangenetics, Frankfurt am Main, Germany

17. Rudolf Koopmann
    Affiliation as printed

    Bio.logis Digital Health, Frankfurt am Main, Germany

    Diagnosticum Centre for Humangenetics, Frankfurt am Main, Germany

18. Marjolein Kriek Aachen Department of Clinical Genetics

    Leiden University · Leiden University Medical Center

    Affiliation as printed

    Department of Clinical Genetics, Leiden University Medical Centre, Leiden, Netherlands

19. Thorsten Lehr

    Saarland University

    Affiliation as printed

    Clinical Pharmacy, Saarland University, Saarbrücken, Germany

20. Lisanne E. N. Manson Aachen Department of Clinical Pharmacy and Toxicology

    Leiden University · Leiden University Medical Center

    Affiliation as printed

    Department of Clinical Pharmacy and Toxicology, Leiden University Medical Centre, Leiden, Netherlands

21. Emmanuelle Rial‐Sebbag

    Université Toulouse III - Paul Sabatier · Université de Toulouse

    Affiliation as printed

    Universite de Toulouse III Paul Sabatier, Toulouse, France

22. Victoria Rollinson

    University of Liverpool

    Affiliation as printed

    Department of Pharmacology and Therapeutics, Wolfson Centre for Personalised Medicine, The University of Liverpool, Liverpool, UK

23. Rossana Roncato

    Centro di Riferimento Oncologico

    Affiliation as printed

    Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy

24. Matthias Samwald

    Medical University of Vienna

    Affiliation as printed

    Centre for Medical Statistics, Informatics and Intelligent Systems, Institute of Artificial Intelligence, Medical University of Vienna, Vienna, Austria

25. Elke Schaeffeler

    Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology · University of Tübingen

    Affiliation as printed

    Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany

    iFIT Cluster of Excellence (EXC2180)-Image Guided and Functionally Instructed Tumor Therapies, University of Tuebingen, Tuebingen, Germany

26. Μαρία Σκώκου

    University of Patras

    Affiliation as printed

    University of Patras, School of Health Sciences, Department of Pharmacy, Division of Pharmacology and Biosciences, Laboratory of Pharmacogenomics and Individualised Therapy, Patras, Greece

27. Matthias Georg Schwab

    Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology · University of Tübingen

    Affiliation as printed

    Department of Clinical Pharmacology, University of Tuebingen, Tuebingen, Germany

    Department of Pharmacy and Biochemistry, University of Tuebingen, Tuebingen, Germany

    Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany

    iFIT Cluster of Excellence (EXC2180)-Image Guided and Functionally Instructed Tumor Therapies, University of Tuebingen, Tuebingen, Germany

28. Daniela Steinberger
    Affiliation as printed

    Bio.logis Digital Health, Frankfurt am Main, Germany

    Diagnosticum Centre for Humangenetics, Frankfurt am Main, Germany

29. Julia Stingl

    Heidelberg University · University Hospital Heidelberg

    Affiliation as printed

    Department of Clinical Pharmacology and Pharmacoepidemiology, University Hospital Heidelberg, Germany

30. Roman Tremmel

    Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology

    Affiliation as printed

    Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany

31. Richard Myles Turner

    University of Liverpool

    Affiliation as printed

    Department of Pharmacology and Therapeutics, Wolfson Centre for Personalised Medicine, The University of Liverpool, Liverpool, UK

    GSK, Stevenage, Hertfordshire, UK

32. Mandy H. van Rhenen

    Royal Dutch Pharmacists Association

    Affiliation as printed

    Medicines Information Centre, Royal Dutch Pharmacists Association (KNMP), The Hague, Netherlands

33. Cathelijne H. van der Wouden Aachen Department of Clinical Pharmacy and Toxicology

    Leiden University · Leiden University Medical Center

    Affiliation as printed

    Department of Clinical Pharmacy and Toxicology, Leiden University Medical Centre, Leiden, Netherlands

34. Cristina Lucía Dávila-Fajardo

    Instituto de Investigación Biosanitaria de Granada · Hospital Universitario Virgen de las Nieves

    Affiliation as printed

    Clinical Pharmacy Department, Hospital Universitario Virgen de las Nieves, Instituto de Investigación Biosanitaria Granada, Granada, Spain

35. Vita Dolžan

    University of Ljubljana

    Affiliation as printed

    Pharmacogenetics Laboratory, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia

36. Munir Pirmohamed

    University of Liverpool

    Affiliation as printed

    Department of Pharmacology and Therapeutics, Wolfson Centre for Personalised Medicine, The University of Liverpool, Liverpool, UK

37. Gere Sunder–Plassmann

    Medical University of Vienna

    Affiliation as printed

    Department of Medicine III, Division of Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria

38. Giuseppe Toffoli

    Centro di Riferimento Oncologico

    Affiliation as printed

    Experimental and Clinical Pharmacology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy

39. Henk‐Jan Guchelaar Aachen Department of Clinical Pharmacy and Toxicology

    Leiden University · Leiden University Medical Center

    Affiliation as printed

    Department of Clinical Pharmacy and Toxicology, Leiden University Medical Centre, Leiden, Netherlands

40. George P. Patrinos

    University of Patras · United Arab Emirates University · Erasmus MC · Pasteur Hellenic Institute · Erasmus University Rotterdam

    Affiliation as printed

    Department of Genetics and Genomics, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, Abu Dhabi, United Arab Emirates

    Erasmus University Medical Centre, Faculty of Medicine and Health Sciences, Department of Pathology-Clinical Bioinformatics Unit, Rotterdam, Netherlands

    Hellenic Pasteur Institute, Athens, Greece

    University of Patras, School of Health Sciences, Department of Pharmacy, Division of Pharmacology and Biosciences, Laboratory of Pharmacogenomics and Individualised Therapy, Patras, Greece

    Zayed Centre for Health Sciences, United Arab Emirates University, Al-Ain, Abu Dhabi, United Arab Emirates

41. Christina Mitropoulou corresponding

    United Arab Emirates University · Golden Helix Foundation

    Affiliation as printed

    Department of Genetics and Genomics, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, Abu Dhabi, United Arab Emirates

    The Golden Helix Foundation, London, UK