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

Vasileios Fragoulakis; Jesse J Swen; Margarita-Ioanna Koufaki; Kathrin Blagec; Tanja Blagus; Stefan Böhringer; Anne Cambon-Thomsen; Erika Cecchin; Ka-Chun Cheung; Vera H M Deneer; Mathilde Dupui; Siv Jonsson; Candace Joefield-Roka; Katja S Just; Mats O Karlsson; Lidija Konta; Rudolf Koopmann; Marjolein Kriek; Thorsten Lehr; Lisanne E N Manson; Emmanuelle Rial-Sebbag; Victoria Rollinson; Rossana Roncato; Matthias Samwald; Elke Schaeffeler; Maria Skokou; Matthias Schwab; Daniela Steinberger; Julia C Stingl; Roman Tremmel; Richard M Turner; Mandy H van Rhenen; Cathelijne H van der Wouden; Cristina Lucía Dávila-Fajardo; Vita Dolžan; Munir Pirmohamed; Gere Sunder-Plassmann; Giuseppe Toffoli; Henk-Jan Guchelaar; George P Patrinos; Christina Mitropoulou

doi:10.1016/j.eclinm.2025.103686

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

Vasileios Fragoulakis
, Jesse J Swen
, Margarita-Ioanna Koufaki
, Kathrin Blagec
, Tanja Blagus
, Stefan Böhringer
, Anne Cambon-Thomsen
, Erika Cecchin
, Ka-Chun Cheung
, Vera H M Deneer
, Mathilde Dupui
, Siv Jonsson
, Candace Joefield-Roka
, Katja S Just
, Mats O Karlsson
, Lidija Konta
, Rudolf Koopmann
, Marjolein Kriek
, Thorsten Lehr
, Lisanne E N Manson

Emmanuelle Rial-Sebbag, Victoria Rollinson, Rossana Roncato, Matthias Samwald, Elke Schaeffeler, Maria Skokou, Matthias Schwab, Daniela Steinberger, Julia C Stingl, Roman Tremmel, Richard M Turner, Mandy H van Rhenen, Cathelijne H van der Wouden, Cristina Lucía Dávila-Fajardo, Vita Dolžan, Munir Pirmohamed, Gere Sunder-Plassmann, Giuseppe Toffoli, Henk-Jan Guchelaar, George P Patrinos, Christina Mitropoulou^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Article number	103686
Journal	EClinicalMedicine
Volume	91
DOIs	https://doi.org/10.1016/j.eclinm.2025.103686
Publication status	Published - Jan 2026

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Multinational cost-utility analysis of panel-based pharmacogenetics-guided treatment of patients enrolled in the U-PGx PREPARE studyFinal published version, 998 KBLicence: CC BY-NC

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Fragoulakis, V., Swen, J. J., Koufaki, M.-I., Blagec, K., Blagus, T., Böhringer, S., Cambon-Thomsen, A., Cecchin, E., Cheung, K.-C., Deneer, V. H. M., Dupui, M., Jonsson, S., Joefield-Roka, C., Just, K. S., Karlsson, M. O., Konta, L., Koopmann, R., Kriek, M., Lehr, T., ... Mitropoulou, C. (2026). Multinational cost-utility analysis of panel-based pharmacogenetics-guided treatment of patients enrolled in the U-PGx PREPARE study. EClinicalMedicine, 91, Article 103686. https://doi.org/10.1016/j.eclinm.2025.103686

@article{877b0ddb6a9e43b4bfd3fc26ff663936,

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

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.",

author = "Vasileios Fragoulakis and Swen, \{Jesse J\} and Margarita-Ioanna Koufaki and Kathrin Blagec and Tanja Blagus and Stefan B{\"o}hringer and Anne Cambon-Thomsen and Erika Cecchin and Ka-Chun Cheung and Deneer, \{Vera H M\} and Mathilde Dupui and Siv Jonsson and Candace Joefield-Roka and Just, \{Katja S\} and Karlsson, \{Mats O\} and Lidija Konta and Rudolf Koopmann and Marjolein Kriek and Thorsten Lehr and Manson, \{Lisanne E N\} and Emmanuelle Rial-Sebbag and Victoria Rollinson and Rossana Roncato and Matthias Samwald and Elke Schaeffeler and Maria Skokou and Matthias Schwab and Daniela Steinberger and Stingl, \{Julia C\} and Roman Tremmel and Turner, \{Richard M\} and \{van Rhenen\}, \{Mandy H\} and \{van der Wouden\}, \{Cathelijne H\} and D{\'a}vila-Fajardo, \{Cristina Luc{\'i}a\} and Vita Dol{\v z}an and Munir Pirmohamed and Gere Sunder-Plassmann and Giuseppe Toffoli and Henk-Jan Guchelaar and Patrinos, \{George P\} and Christina Mitropoulou",

note = "{\textcopyright} 2025 The Author(s).",

year = "2026",

month = jan,

doi = "10.1016/j.eclinm.2025.103686",

language = "English",

volume = "91",

journal = "EClinicalMedicine",

issn = "2589-5370",

publisher = "Elsevier",

}

Fragoulakis, V, Swen, JJ, Koufaki, M-I, Blagec, K, Blagus, T, Böhringer, S, Cambon-Thomsen, A, Cecchin, E, Cheung, K-C, Deneer, VHM, Dupui, M, Jonsson, S, Joefield-Roka, C, Just, KS, Karlsson, MO, Konta, L, Koopmann, R, Kriek, M, Lehr, T, Manson, LEN, Rial-Sebbag, E, Rollinson, V, Roncato, R, Samwald, M, Schaeffeler, E, Skokou, M, Schwab, M, Steinberger, D, Stingl, JC, Tremmel, R, Turner, RM, van Rhenen, MH, van der Wouden, CH, Dávila-Fajardo, CL, Dolžan, V, Pirmohamed, M, Sunder-Plassmann, G, Toffoli, G, Guchelaar, H-J, Patrinos, GP & Mitropoulou, C 2026, 'Multinational cost-utility analysis of panel-based pharmacogenetics-guided treatment of patients enrolled in the U-PGx PREPARE study', EClinicalMedicine, vol. 91, 103686. https://doi.org/10.1016/j.eclinm.2025.103686

TY - JOUR

T1 - Multinational cost-utility analysis of panel-based pharmacogenetics-guided treatment of patients enrolled in the U-PGx PREPARE study

AU - Fragoulakis, Vasileios

AU - Swen, Jesse J

AU - Koufaki, Margarita-Ioanna

AU - Blagec, Kathrin

AU - Blagus, Tanja

AU - Böhringer, Stefan

AU - Cambon-Thomsen, Anne

AU - Cecchin, Erika

AU - Cheung, Ka-Chun

AU - Deneer, Vera H M

AU - Dupui, Mathilde

AU - Jonsson, Siv

AU - Joefield-Roka, Candace

AU - Just, Katja S

AU - Karlsson, Mats O

AU - Konta, Lidija

AU - Koopmann, Rudolf

AU - Kriek, Marjolein

AU - Lehr, Thorsten

AU - Manson, Lisanne E N

AU - Rial-Sebbag, Emmanuelle

AU - Rollinson, Victoria

AU - Roncato, Rossana

AU - Samwald, Matthias

AU - Schaeffeler, Elke

AU - Skokou, Maria

AU - Schwab, Matthias

AU - Steinberger, Daniela

AU - Stingl, Julia C

AU - Tremmel, Roman

AU - Turner, Richard M

AU - van Rhenen, Mandy H

AU - van der Wouden, Cathelijne H

AU - Dávila-Fajardo, Cristina Lucía

AU - Dolžan, Vita

AU - Pirmohamed, Munir

AU - Sunder-Plassmann, Gere

AU - Toffoli, Giuseppe

AU - Guchelaar, Henk-Jan

AU - Patrinos, George P

AU - Mitropoulou, Christina

PY - 2026/1

Y1 - 2026/1

N2 - 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.

AB - 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.

U2 - 10.1016/j.eclinm.2025.103686

DO - 10.1016/j.eclinm.2025.103686

M3 - Article

C2 - 41502919

SN - 2589-5370

VL - 91

JO - EClinicalMedicine

JF - EClinicalMedicine

M1 - 103686

ER -

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

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