Prioritisation of clinically actionable gene-drug pairs for cost-effectiveness analysis in Singapore

Labeit, Alexander Michael; Briones, Jamaica Roanne; Aminkeng, Folefac; Chai, Jia Hui; CherGoh, Boon; Goh, Liuh Ling; Leong, Khai Pang; Lo, Elaine; Ngiam, Kee Yuan; Tai, E. Shyong; Tan, Karen M. L.; Tan, Doreen Su-Yin; Winther, Michael David; Yan, Benedict; Zemlyanska, Yaroslava; Wee, Hwee Lin

Publication type:	Conference other
Type of review:	Peer review (abstract)
Title:	Prioritisation of clinically actionable gene-drug pairs for cost-effectiveness analysis in Singapore
Authors:	Labeit, Alexander Michael Briones, Jamaica Roanne Aminkeng, Folefac Chai, Jia Hui CherGoh, Boon Goh, Liuh Ling Leong, Khai Pang Lo, Elaine Ngiam, Kee Yuan Tai, E. Shyong Tan, Karen M. L. Tan, Doreen Su-Yin Winther, Michael David Yan, Benedict Zemlyanska, Yaroslava Wee, Hwee Lin
et. al:	No
Proceedings:	PGRN-ASHG 2021 Symposium Advancements in Global Pharmacogenomics Through Collaborations
Page(s):	71
Pages to:	72
Conference details:	PGRN-ASHG 2021 Symposium, online, 18 October 2021
Issue Date:	2021
Publisher / Ed. Institution:	Pharmacogenomics Global Research Network
Language:	English
Subject (DDC):	362.1041: Health economics
Abstract:	Purpose: Pharmacogenetic (PGx) test involves identification of presence or absence of gene variant(s) toguide individualised therapy. An analysis of the UK Biobank reported that 99.5% of participants have at least one actionable pharmacogenetic variant, with an average of 3.7 actionable pharmacogenetic variants involving an average of 12.2 drugs. As such, PGx panel testing, which allows analysis of multiple genes inone assay, can be potentially more cost-effective than conducting PGx tests individually. Moreover, ancestry differences in the prevalence of PGx allele frequencies mean that non-European health systems should curate a panel tailored to local needs. This study details the process of incorporating both clinical and economic considerations to prioritise gene-drug pairs for cost-effectiveness analyses (CEA). This is done as an initial step in curating a pre-emptive PGx panel test for adults in Singapore, a multi-ethnic Asiancity state. Methods: Clinically important gene-drug pairs were initially determined through literature review and were confirmed by the Clinical Pharmacogenomics Implementation Working Group (CPIWG) at the National University Hospital, comprising an oncologist, endocrinologist, endocrine surgeon, pharmacists and pathologist. These gene-drug pairs were then assessed against a selection framework which involves both clinical and economic criteria. Clinical criteria were (1) high evidence for pharmacogenetic testing, (e.g., consistent recommendations across PGx guidelines) (2) high frequency of gene variant; (3) clinical utility (i.e., will result in a change of patient management), while economic criteria were (4) frequency of drug usage; (5) availability of local and international data to conduct CEA (e.g., odds ratio of gene-drug association in specific ancestry group and local cost of managing adverse drug reactions). Results: The CPIWG shortlisted 25 clinically actionable gene-drug pairs based on literature review and local clinical practice. Of those, ten gene-drug pairs (in no particular order) were prioritised for cost- effectiveness evaluation: (1) HLA-B58:01–allopurinol, (2) TPMT/NUDT15–azathioprine, (3&4) DPYD–capecitabine/ fluorouracil, (5) HLA-B15:02– carbamazepine, (6) CYP2C19 clopidogrel, (7&8) CYP2D6– codeine/ tramadol, (9) SLCO1B1–simvastatin; (10) CYP2C9/VKORC1–warfarin. To elaborate on reasons in deprioritising other gene-drug pairs: NUDT15/TPMT–mercaptopurine since it is used in paediatric conditions; UGT1A1–irinotecan dosing recommendations require further discussion and planning; CYP2D6 antidepressants because it is difficult to attribute therapeutic failure as a consequence of carryingthe variant allele, since factors such as non-adherence to treatment or drug-drug interactions may influencetherapeutic outcomes. Lastly, HLA-B*57:01–abacavir, DPYD–tegafur, NUDT15/TPMT–thioguanine and CYP2C19–voriconazole owing to a low volume of prescriptions. Conclusion: The selection framework highlights issues faced in curating PGx panels for implementation. This challenge can be addressed through a systematic approach in prioritising gene-drug pairs for CEA, theresults of which will be used to determine possible inclusion in a pre-emptive PGx panel test.
URI:	https://www.pgrn.org/resources/Documents/PGRN%20ProgramBook.pdf https://digitalcollection.zhaw.ch/handle/11475/29255
Fulltext version:	Published version
License (according to publishing contract):	Licence according to publishing contract
Departement:	School of Management and Law
Organisational Unit:	Winterthur Institute of Health Economics (WIG)
Appears in collections:	Publikationen School of Management and Law

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Labeit, A. M., Briones, J. R., Aminkeng, F., Chai, J. H., CherGoh, B., Goh, L. L., Leong, K. P., Lo, E., Ngiam, K. Y., Tai, E. S., Tan, K. M. L., Tan, D. S.-Y., Winther, M. D., Yan, B., Zemlyanska, Y., & Wee, H. L. (2021). Prioritisation of clinically actionable gene-drug pairs for cost-effectiveness analysis in Singapore [Conference presentation]. PGRN-ASHG 2021 Symposium Advancements in Global Pharmacogenomics through Collaborations, 71–72. https://www.pgrn.org/resources/Documents/PGRN%20ProgramBook.pdf

Labeit, A.M. et al. (2021) ‘Prioritisation of clinically actionable gene-drug pairs for cost-effectiveness analysis in Singapore’, in PGRN-ASHG 2021 Symposium Advancements in Global Pharmacogenomics Through Collaborations. Pharmacogenomics Global Research Network, pp. 71–72. Available at: https://www.pgrn.org/resources/Documents/PGRN%20ProgramBook.pdf.

A. M. Labeit et al., “Prioritisation of clinically actionable gene-drug pairs for cost-effectiveness analysis in Singapore,” in PGRN-ASHG 2021 Symposium Advancements in Global Pharmacogenomics Through Collaborations, 2021, pp. 71–72. [Online]. Available: https://www.pgrn.org/resources/Documents/PGRN%20ProgramBook.pdf

LABEIT, Alexander Michael, Jamaica Roanne BRIONES, Folefac AMINKENG, Jia Hui CHAI, Boon CHERGOH, Liuh Ling GOH, Khai Pang LEONG, Elaine LO, Kee Yuan NGIAM, E. Shyong TAI, Karen M. L. TAN, Doreen Su-Yin TAN, Michael David WINTHER, Benedict YAN, Yaroslava ZEMLYANSKA und Hwee Lin WEE, 2021. Prioritisation of clinically actionable gene-drug pairs for cost-effectiveness analysis in Singapore. In: PGRN-ASHG 2021 Symposium Advancements in Global Pharmacogenomics Through Collaborations [online]. Conference presentation. Pharmacogenomics Global Research Network. 2021. S. 71–72. Verfügbar unter: https://www.pgrn.org/resources/Documents/PGRN%20ProgramBook.pdf

Labeit, Alexander Michael, Jamaica Roanne Briones, Folefac Aminkeng, Jia Hui Chai, Boon CherGoh, Liuh Ling Goh, Khai Pang Leong, et al. 2021. “Prioritisation of Clinically Actionable Gene-Drug Pairs for Cost-Effectiveness Analysis in Singapore.” Conference presentation. In PGRN-ASHG 2021 Symposium Advancements in Global Pharmacogenomics through Collaborations, 71–72. Pharmacogenomics Global Research Network. https://www.pgrn.org/resources/Documents/PGRN%20ProgramBook.pdf.

Labeit, Alexander Michael, et al. “Prioritisation of Clinically Actionable Gene-Drug Pairs for Cost-Effectiveness Analysis in Singapore.” PGRN-ASHG 2021 Symposium Advancements in Global Pharmacogenomics through Collaborations, Pharmacogenomics Global Research Network, 2021, pp. 71–72, https://www.pgrn.org/resources/Documents/PGRN%20ProgramBook.pdf.