Early HTA in pharmacogenomics: A case example in cardiovascular drugs

Background: ACE inhibitors (ACEi) are commonly used cardiovascular drugs. In a small percentage (0.2%) of patients, these drugs can cause a severe and possibly lethal adverse drug reaction (ADR), angioedema. A pharmacogenetic test could be used to identify patients at risk for this severe ADR and advise them to use another drug. Objectives: The aim of this study was to assess the sensitivity, specificity and cost of a hypothetic pharmacogenetic test in order for it to be cost-effective in preventing ACEi-induced angioedema. Furthermore, we assessed the influence of testing only a part of the population carrying risk factors of angioedema. Methods: A decision tree was used, as angioedema usually occurs within the first year after starting an ACEi and data on long-term risk is scarce. Test characteristics were assessed using Monte Carlo simulations. Results: With a willingness-to-pay (WTP) threshold of €20.000 and €80.000 per quality-adjusted life year (QALY), a 100% sensitive and specific test may have a maximum cost of €1.30 and €1.95, respectively. A decrease in specificity has a 10-fold higher impact on the incremental cost-effectiveness ratio (ICER) than sensitivity, as additional drug costs of false positives rapidly overcome the benefit of preventing angioedema. In order to warrant a €1,00 price, specificity needs to be >95%, whilst sensitivity may drop to 70%, provided that specificity remains >98%. African Americans have a 3.88 times higher risk of developing angioedema than Caucasians. When only genotyping this population, the maximum test price (100% sensitive and specific) would be €5,04 and €7,57 at a WTP threshold of €20.000 and €80.000, respectively. Conclusions: A theoretical pharmacogenetic test for ACEi-induced angioedema is only cost-effective at a very high specificity, decent sensitivity and a low price. If only used in patients with a high risk of angioedema, the maximum test price could increase to a somewhat more realistic €5 figure.