Cost‐effectiveness of <i>DPYD</i> genotyping prior to fluoropyrimidine‐based treatment for colorectal cancer in Wales

BACKGROUND: Regulatory guidance in the United Kingdom advises DPYD genotyping prior to fluoropyrimidine-based treatment. This economic evaluation estimated the costs and outcomes associated with DPYD screening prior to prescribing fluoropyrimidines for colorectal cancer in Wales and also considers additional variants to those included in standard DPYD testing. METHODS: Decision-analytic models were developed to compare the cost-effectiveness of pharmacogenomic-guided prescribing, where patients with actionable variants are prescribed reduced-dose fluoropyrimidines or an alternative drug, against a strategy of prescribing a standard licensed dose irrespective of genetic status. Incremental net health benefit (INHB) was assessed at a cost-effectiveness threshold of £20 000 per quality-adjusted life year (QALY) gained. Probabilistic and univariate sensitivity and scenario analyses characterized modelling uncertainty and assessed the responsiveness of the results to a range of assumptions. RESULTS: Screening prior to prescribing was modelled to be cost-saving, result in fewer adverse drug reactions and be associated with more QALYs than prescribing all patients standard dose fluoropyrimidines. Testing for c.1905+1G>A, c.1679T>G, c.2846A>T, c.1129-5923C>G and c.1236G>A was associated with an estimated INHB of 0.0118 QALYs (95% central range -0.0490, 0.0575) and 0.96 probability of being cost-effective. Screening for additional variants, including c.557A>G increased the INHB. The results were robust across a range of sensitivity analyses. CONCLUSION: DPYD screening prior to the prescription of fluoropyrimidines is likely to be a cost-effective use of National Health Service resources. Testing for additional variants at minimal additional cost has important implications for reducing the burden of adverse drug reactions and health inequalities in ethnically diverse societies.