Genetic test for CYP2C9 and VKORC1 genes to guide warfarin dosing for patients with VTE holds a promise of being able to reduce clinical complications. However, lack of evidence and uncertainties surrounding this new technology lead to the question of whether gene testing is cost-effective in the societal perspective.

A discrete event simulation model was conducted to evaluate the cost-effectiveness of CYP2C9 and VKORC1 genotype-guided warfarin on the natural history of VTE. The model depicted patients' health states as the disease evolve with time, and captured its associated costs (2007 U.S. dollars) and quality of life. Data was extrapolated with the criteria of including VTE patients of age >=18 years on warfarin with INR target of 2-3. Probabilities, costs and humanistic properties were obtained from the literature, HCUP (NIS & SEDD), and the Medicare Reimbursement Schedule databases. Sensitivity analysis was performed for uncertainty parameters in the model. All costs and benefits were discounted at 3%.

This study had a significant difference in the prevalence of bleeding complication between Standard anticoagulation (6.1%) and the genotype –guided groups (<5.8%). No differences were found in the prevalence of recurrent VTE episode. Approximately, $14,340 was accrued per patient over lifetime follow-up. The CYP2C9, VKORC1 and both CYP2C9 and VKORC1 genotype-guided warfarin anticoagulation projected $179, $186 and $391 additional cost over the cost of standard anticoagulation; and additional QALYs gain of 0.0091, 0.0156 and 0.0171. Considering the threshold of $100,000/QALY, both CYP2C9 and VKORC1 genotype-guided treatment exceeded the threshold, while VKORC1 genotype-guided was indicated to be cost-effective among all strategies. Sensitivity analysis demonstrated 25% of the replications of both CYP2C9 and VKORC1 genotype-guided strategy to be <$100,000/QALY.

In conclusion, the data analysis in this study showed that both CYP2C9 and VKORC1 genotype-guided warfarin anticoagulation therapy is not cost –effective in all population and that patient with higher risk of complications are more likely to benefit from this new innovation. For the genotype-guided test to be cost-effective in the population with VTE, the cost of the test would have to be <$400 or be restricted to patient at high risk for bleeding complications (RR>5.8).