When the probability of IHD is very low, however, a negative test result is simply confirmatory, whereas a positive test result might not be clinically useful and could be misleading if falsely positive. The importance of relying on clinical judgment and refraining from testing in very low-risk populations is well illustrated by a thought experiment proposed by Diamond and Kaul in a letter to the editor of The New England Journal of Medicine: As an example, suppose we have a test marker with 80% sensitivity and 80% specificity (typical of car- diac stress tests). Given 100 individuals with a 10% disease prevalence, there will be 8 true positives (10030.130.8) and 18 false positives (10030.930.2). If we refer only these 26 positive responders for angiography, the observed diagnostic yield is only 31% (8/26). Moreover, the test s sensitivity will appear to be 100% (all diseased subjects having a positive test), and its specificity will appear to be 0% (all non-diseased subjects also having a positive test). Hence, the more we rely on a test, the less well it appears to perform. (p. 93)90 The likelihood of CAD proposed above differs substantially from that in the populations from which the estimates of noninvasive test performance were derived; the overall prev- alence of CAD from a meta-analysis was 60%.91 Instead, contemporary age-, sex-, and symptom-based IHD probabil- ity estimates can be gleaned from a multicenter cohort of 14 048 patients with suspected IHD undergoing CCTA.92 2.2.1.2. Safety and Other Considerations Potentially Affecting Test Selection All forms of noninvasive stress testing carry some risk. Maximal exercise testing is associated with a low but finite incidence of cardiac arrest, AMI, and even death. 