Estimating the potential impact of implementing pre‐emptive pharmacogenetic testing in primary care across the UK

Abstract

Pharmacogenetics (PGx) in the UK is currently implemented in secondary care for a small group of high-risk medicines. However, most prescribing takes place in primary care, with a large group of medicines influenced by commonly occurring genetic variations. The goal of this study is to quantitatively estimate the volumes of medicines impacted by implementation of a population-level, pre-emptive pharmacogenetic screening programme for nine genes related to medicines frequently dispensed in primary care in 2019.Methods: A large community pharmacy database was analysed to estimate the national incidence of first prescriptions for 56 PGx drugs used in the UK for the period 1 January-31 December 2019. These estimated prescription volumes were combined with phenotype frequency data to estimate the occurrence of actionable drug-gene interactions (DGI) in daily practice in community pharmacies.Results: In between 19.1 and 21.1% (n = 5 233 353-5 780 595) of all new prescriptions for 56 drugs (n = 27 411 288 new prescriptions/year), an actionable drug-gene interaction (DGI) was present according to the guidelines of the Dutch Pharmacogenetics Working Group and/or the Clinical Pharmacogenetics Implementation Consortium. In these cases, the DGI would result in either increased monitoring, guarding against a maximum ceiling dose or an optional or immediate drug/dose change. An immediate dose adjustment or change in drug regimen accounted for 8.6-9.1% (n = 2 354 058-2 500 283) of these prescriptions.Conclusions: Actionable drug-gene interactions frequently occur in UK primary care, with a large opportunity to optimise prescribing.

Pharmacogenomics spotlight commentary: From the United Kingdom to global populations

“…Youssef et al estimated that around 4 million people would need to be tested annually in primary care in the UK. 2 Clearly, this may not be practicable, and suitable eligibility criteria will need to be specified to contain volume and costs. This may involve prioritizing patients based on other risk factors, limiting testing to situations where high doses are indicated, or to medicines associated with the most severe or common adverse drug reactions.…”

“…1 In this Spotlight Commentary, we discuss several articles recently published in the British Journal of Clinical Pharmacology, which highlight the potential for pharmacogenomics actionability within the UK prescribing sphere, clearly demonstrating scope for improvement in clinical care. [2][3][4] Global research has also highlighted the importance of validating the genomic evidence base across diverse groups, which will be crucial to the ethical implementation of a stratified medicine programme within the United Kingdom as well as in other nations across the globe.…”

Genetic landscape of 125 pharmacogenes in Chinese from the Chinese Millionome Database

“…Increasing whole genome sequences data provide a goldmine for genetic studies on the disease etiology and drug therapeutics. Genetic variants of cytochrome P450 (CYP) genes performed an important role in the inter-individual differences of drug response 1 , and clinical implementation of several CYP variation-drug pairs such as CYP2C19*2–3 and clopidogrel, CYP2C9*2–3 and warfarin, and CYP3A5*3 and tacrolimus has been applied substantially worldwide 2 , 3 . Recently, pharmacogenes other than CYP such as ABCC2 (ATP-binding cassette subfamily C member 2) transporters, UGT2B7 (uridine-5'-diphosphate (UDP) glucuronosyltransferase family 2 member B7) and F2R (coagulation factor II (thrombin) receptor) were found to be of importance in the drug efficacy and adverse drug reactions 4 – 6 .…”

Pharmacogenomic Testing to Support Prescribing in Primary Care: a Structured Review of Implementation Models

“…58% of all adult patients, and 89% of those over 70 years of age, are prescribed one such medicine, with 47% prescribed two or more and 7% prescribed five or more. 19–21% of all new prescriptions are for medicines where there is a corresponding PGx dosing guideline [ 13 , 14 ].…”