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