Early HTA in pharmacogenomics: A case example in cardiovascular drugs

Objectives: ACE inhibitors (ACEi) are commonly used cardiovascular drugs. These drugs can cause the severe and possibly lethal adverse drug reaction (ADR) angioedema in a very small part (0.2%) of the patients. A pharmacogenomic test could be used to identify patients at risk for this severe ADR and advise them to use another drug. The goal of this study is to assess the test characteristics (cost, sensitivity and specificity) in order for it to be a cost effective test for preventing ACEi-induced angioedema. Furthermore, we assessed the influence of only testing part of the population carrying risk factors for 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 simulation. Results: With a willingness-to-pay (WTP) threshold of € 20,000 and € 80,000 per QALY, a 100% sensitive and specific test may have a maximum cost of € 1.29 and € 1.92, respectively. A decrease in specificity has a 10-fold higher impact on the ICER than sensitivity as additional drug costs of false positives rapidly overcome the benefit of preventing angioedema. In order to warrant a € 1.00 test price, specificity needs to be > 95% whilst sensitivity may drop to 70% provided that specificity remains > 98%. African people have a 3.88 times higher risk of developing angioedema than Caucasian people. When only genotyping this population, the maximum test price (100% sensitive and specific) would be € 3.21 and € 5.67 at a WTP threshold of € 20,000 and € 80,000, respectively. Conclusions: A theoretical pharmacogenomic test for ACEi-induced angioedema is only cost-effective at very high specificity, decent sensitivity and a low price. If only used in patients with a high risk on angioedema, the maximum test price could increase to a somewhat more realistic 5 Euro figure.