special subjects
Understanding Medical Tests and Test Results
Screening Tests
Patients often must consider whether to be screened for occult disease. The premises of a successful screening program are that early detection improves a clinically significant outcome in patients with occult disease and that the false-positive results that may occur in screening do not create a burden (eg, costs and adverse effects of confirmatory testing, anxiety provoked by testing, unwarranted treatment) that exceeds such benefit. To minimize these possible burdens, clinicians must choose the proper screening test. Screening is not appropriate when treatments or preventive measures are ineffective or the disease is very uncommon (unless a subpopulation can be identified in which prevalence is higher). Theoretically, the best test for both screening and diagnosis is the one with the highest sensitivityandspecificity. However, such highly accurate tests are often complex, expensive, and invasive (eg, coronary angiography) and are thus not practical for screening large numbers of asymptomatic people. Typically, some tradeoff in sensitivity, specificity, or both must be made when selecting a screening test. Whether a clinician chooses a test that optimizes sensitivity or specificity depends on the consequences of a false-positive or false-negative test result as well as the pre-test probability of disease. An ideal screening test is one that is always positive in nearly every patient with disease so that a negative result confidently excludes disease in healthy patients. For example, in testing for a serious disease for which an effective treatment is available (eg, coronary artery disease), clinicians would be willing to tolerate more false positives than false negatives (lower specificity and high sensitivity). Although high sensitivity is a very important attribute for screening tests, specificity also is important in certain screening strategies. Among populations with a higher prevalence of disease, the PPV of a screening test increases; as prevalence decreases, the post-test or posterior probability of a positive result decreases. Therefore, when screening for disease in high-risk populations, tests with a higher sensitivity are preferred over those with a higher specificity because they are better at ruling out disease (fewer false negatives). On the other hand, in low-risk populations or for uncommon diseases for which therapy has lower benefit or higher risk, tests with a higher specificity are preferred. With the expanding array of available screening tests, clinicians must consider the implications of a panel of such tests. For example, test panels containing 8, 12, or sometimes 20 blood tests are often done when a patient is admitted to the hospital or is first examined by a new clinician. Although this type of testing may be helpful in screening patients for certain diseases, using the large panel of tests has potentially negative consequences. By definition, a test with a specificity of 95% gives false-positive results in 5% of healthy, normal patients. If 2 different tests with such characteristics are done, each for a different occult disease, in a patient who actually does not have either disease, the chance that both tests will be negative is 95%×95%, or about 90%; thus, there is a 10% chance of at least one false-positive result. For 3 such tests, the chance that all 3 would be negative is 95%×95%×95%, or 86%, corresponding to a 14% chance of at least one false-positive result. If 12 different tests for 12 different diseases are done, the chance of obtaining at least one false-positive result is 46%. This high probability underscores the need for caution when deciding to do a screening test panel and when interpreting its results. 