False Positives, Multiple Testing and Incidental Findings

Three ways testing can create a problem

Testing is meant to clarify. These three effects explain why more testing is not always better. This page is information only and does not say whether you should have any test.

• A false positive: a test says a condition may be present when it is not. MedlinePlus defines it as a result showing you have a disease or condition when you do not, and says no test is perfect. [1]
• Multiple testing: the more tests or repeat rounds, the more chances for a false alarm.
• An incidental finding: an unexpected result found while looking for something else.

False positives

The NHS says screening tests are not 100% accurate: people can be told they have a problem when they do not, which may lead to unnecessary further tests or treatment. A false negative can also miss a problem. [2] The National Cancer Institute says a false-positive cancer screening result can cause anxiety and is usually followed by more tests. [3] The PSA blood test may be elevated without cancer, and the follow-up biopsy can cause infections, pain and bleeding. [4]

Multiple testing: how false alarms add up

Each extra round is another chance for a false alarm. Two published examples from breast cancer screening show the scale.

• In Norway, a study of 231,310 women who had 715,311 screening mammograms estimated that 20.0% (95% CI 19.7% to 20.4%) would have a false-positive result over 20 years of biennial screening starting at age 50 to 51, and about 4.1% would have an invasive procedure with a benign outcome. [5]
• In a U.S. study of 903,495 women, the 10-year chance of at least one false-positive recall with annual screening was 49.6% with tomosynthesis versus 56.3% with digital mammography. Biennial screening, older age and non-dense breasts reduced false-positive probabilities more than the type of machine did. [6]

These are observational data from screening programs, and they show frequency, not whether screening is worthwhile. The same arithmetic applies to broad panels of blood markers: MedlinePlus notes it is common for healthy people to sometimes have results outside the reference range. [1] Proper evidence not found: no readable plain-language source quantifying this effect for lab panels was located, so no figure is given. For the underlying mathematics of positives see sensitivity, specificity and predictive values.

Incidental findings

Scans and genetic tests can reveal things nobody was looking for. Figures from research imaging:

• In 1,426 research imaging exams at one center, 39.8% had at least one incidental finding. Only 6.2% of exams with a finding led to clinical action, and the authors judged clear medical benefit in 1.1% and clear burden in 0.5%, with benefit or burden often unclear (4.6%). Findings were most frequent with abdominal and pelvic CT and rose with age. [7]
• In 16,400 research brain MRIs, neuroradiologists reported 3.7% as abnormal with follow-up recommended. The authors concluded about 4% of research participants had a potentially significant incidental finding. [8]

Some findings matter and many do not, and distinguishing them can require further tests with their own risks. Whole-body scans in healthy people raise this question; see full-body MRI and screening in healthy people. For genetic results, see genetic test false positives and clinical confirmation and genetic privacy and incidental findings.

Specific places where this matters

The FDA listed a 2022 safety communication that genetic non-invasive prenatal screening tests may have false results. [9] Screening results of this kind are normally followed by diagnostic confirmation before decisions are made. [2]

Reducing the downside

• Ask what would change if the test were positive and what follow-up would involve.
• Ask whether the test is meant for people with symptoms or without. See overdiagnosis and screening vs diagnosis.
• Avoid repeating tests simply to see whether a number moves; results vary naturally. See reference ranges and repeatability.