A Primer on Medical Testing

As with many hot topics, “medical testing” is a deceptively simple term for a complex process. This particular subject owes its current notoriety to the COVID-19 public health emergency, but medical testing will be with us long after the pandemic ends. Since you will need to discuss medical testing with your physician at some point, you might find a better understanding of the terms helpful.

Accuracy — It’s Complicated!

Ideally, testing would definitively establish whether one is sick, immune, or contagious. Perfect tests would be 100-percent sensitive (everyone with the disease/condition tests positive) and 100-percent specific (everyone without the disease/condition tests negative).

Sadly, we do not live in this ideal world of yes/ no binary outcomes. Even with good tests, it is possible to get a false positive (i.e., positive result even in the absence of the disease or condition) or a false negative (i.e., a negative result even when the disease or condition is present). Both outcomes are problematic. In clinical medicine, a false positive can lead to additional testing and, possibly, unnecessary treatment. A false negative test can delay proper treatment.

In public health, these outcomes can result in unnecessary restrictions on those free of disease or inappropriate clearance for those with disease. To put this issue in perspective, if a test has 95-percent sensitivity and 95-percent specificity, 5-percent of those with the disease or condition will test negative and 5-percent of those without will test positive. If we test 10 million people, one million tests total will be incorrect.

In addition to sensitivity and specificity, prevalence (the number who actually have the disease/condition) has a huge impact. Succinctly put, the more common something is, the more likely a positive test is a true positive (positive predictive value) and the less common it is, the more likely a negative test is a true negative (negative predictive value).

Screening

Both in clinical medicine and public health, health care workers use predictive values to develop clinical guidelines that define who needs to be screened and when. A common clinical example is mammography for women. Start too soon and many tests will show false positives resulting in the risk of unnecessary procedures, scarring, infections, and worry for women and their families. Start too late and you are less likely to detect breast cancer at an early stage when treatment is more likely to be effective and the disease potentially curable. This is why doctors discuss when to begin testing for many conditions on an individual basis. For other conditions, such as high blood pressure, where there is no real risk from screening and treatment options are safe, these tests are universal.

We often hear now that more testing for COVID-19 will accelerate the return to normal. It will, but testing is complex and we need to talk about what this really means.

Testing for a virus falls into one of two basic categories: tests for antibodies (proteins the body produces to fight infections) and tests for antigens (proteins produced by an infectious agent). At the time of this writing, the sensitivity and specificity for many COVID-19 tests (unfortunately, this is not uncommon) have been sub-optimal for both the virus (antigen) and antibodies. Further complicating the issue is “cross-reactivity.” Antigen tests may detect an antigen from a related infectious agent, making test interpretation more difficult. In addition, antigen tests vary widely in accuracy and can remain positive even after someone is no longer infectious. Antibody tests suffer similar problems. A positive antibody test for an infectious virus may indicate an immune response to prior infection or a similar virus, but not current immunity. In other words, the presence of antibodies does not guarantee protection against reinfection. Moreover, antibodies may be detectable early in an infection while the individual remains infectious.

There has been rapid progress, but many questions remain to be answered. Meanwhile, I hope this primer has provided a better idea of the challenges that policy makers, the public health officials who advise them, and your physician face when it comes to medical testing. In addition, you should be equipped to make a more informed decision the next time your physician advises medical testing.

Leo M. Hattrup, M.D., received a bachelor’s degree from Wichita State University, a master’s in public health from Harvard University, and a doctorate from Vanderbilt University. He is retired from the U.S. Air Force in which he spent the majority of his career in aerospace medicine. He is board certified in aerospace and occupational medicine. He is a certificated flight instructor and enjoys flying airplanes, helicopters, and gliders. July/August 2020