Abstract
CYP2C19 genotyping before clopidogrel and DPYD genotyping before fluoropyrimidine chemotherapy both carry strong
guideline support and clear actionability, yet both remain implemented unevenly outside large academic centres with an
established pharmacogenomics service. We review the evidence and guideline basis for each test, then examine the specific
operational barriers -- turnaround time against clinical urgency, result interpretation without an on-site pharmacogenomics
specialist, and reimbursement uncertainty -- that most often stall implementation at a non-academic centre, drawing on a survey
of eighteen non-academic hospital laboratories that had considered but not yet implemented one or both tests. Turnaround time
was the most commonly cited barrier for clopidogrel genotyping, where the clinical decision often cannot wait for a send-away
result, while interpretive confidence was the most commonly cited barrier for DPYD genotyping, where the clinical stakes of a
missed poor-metaboliser result are high but the test is ordered too infrequently for local expertise to develop. We propose different
practical pathways for each test that address its dominant barrier specifically, rather than a single implementation template
applied to both.
References
Lee CR, Luzum JA, Sangkuhl K, et al. "Clinical Pharmacogenetics Implementation Consortium guideline for CYP2C19 genotype and clopidogrel therapy: 2022 update". Clin Pharmacol Ther 112(2022): 959-967.
Amstutz U, Henricks LM, Offer SM, et al. "Clinical Pharmacogenetics Implementation Consortium guideline for dihydropyrimidine dehydrogenase genotype and fluoropyrimidine dosing: 2017 update". Clin Pharmacol Ther 103(2018): 210-216.
Relling MV, Klein TE, Gammal RS, et al. "The Clinical Pharmacogenetics Implementation Consortium: 10 years later". Clin Pharmacol Ther 107(2020): 171-175.
Mega JL, Simon T, Collet JP, et al. "Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI: a meta-analysis". JAMA 304(2010): 1821-1830.
Pereira NL, Farkouh ME, So D, et al. "Effect of genotype-guided oral P2Y12 inhibitor selection vs conventional clopidogrel therapy on ischemic outcomes after percutaneous coronary intervention: the TAILOR-PCI randomized clinical trial". JAMA 324(2020): 761-771.
Henricks LM, Lunenburg CATC, de Man FM, et al. "DPYD genotype-guided dose individualisation of fluoropyrimidine therapy in patients with cancer: a prospective safety analysis". Lancet Oncol 19(2018): 1459-1467.
Meulendijks D, Henricks LM, Sonke GS, et al. "Clinical relevance of DPYD variants c.1679T>G, c.1236G>A/HapB3, and c.1601G>A as predictors of severe fluoropyrimidine-associated toxicity: a systematic review and meta-analysis". Lancet Oncol 16(2015): 1639-1650.
Roberts JD, Wells GA, Le May MR, et al. "Point-of-care genetic testing for personalisation of antiplatelet treatment (RAPID GENE): a prospective, randomised, proof-of-concept trial". Lancet 379(2012): 1705-1711.
Cecchin E, Roncato R, Guchelaar HJ, et al. "Ubiquitous Pharmacogenomics (U-PGx): the time for implementation is now, an horizon2020 program to drive pharmacogenomics into clinical practice". Curr Pharm Biotechnol 18(2017): 204-209.
Swen JJ, van der Wouden CH, Manson LE, et al. "A 12-gene pharmacogenetic panel to prevent adverse drug reactions: an open-label, multicentre, controlled, cluster-randomised crossover implementation study". Lancet 401(2023): 347-356.
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