COVID antigen tests carry false positive risk: FDA

Regulatory NewsRegulatory News | 04 November 2020 |  By 

Antigen tests for COVID-19 can yield false positive results, especially when used improperly, said the US Food and Drug Administration (FDA) in a notification sent to clinical laboratory staff and health care providers.
“Remember that positive predictive value (PPV) varies with disease prevalence when interpreting results from diagnostic tests,” said FDA in the 3 November letter. Lower disease prevalence in a given area or population increases the number of false positive results a test will return, explained the agency.
“Like molecular tests, antigen tests are typically highly specific for the SARS-CoV-2 virus. However, all diagnostic tests may be subject to false positive results, especially in low prevalence settings,” added FDA.
By way of example, the letter looks at a hypothetical test with 98% specificity. When prevalence of a disease or condition is 10%, that test has 80% positive predictive value (PPV) and will return 20 false positive results for every 100 positive test results. However, when the same test is used in the scenario of 1% prevalence, PPV drops to just 30%; in this case, 70 out of every 100 positive tests are false positives.
When an antigen test is positive, noted FDA, health care providers and laboratories should consider a reflex confirmatory reverse transcriptase-polymerase chain reaction (RT-PCR) test to confirm results, obtained within 48 hours. This is especially the case in such scenarios as nursing home surveillance testing, where prevalence may be low.
FDA noted that laboratories should follow manufacturers’ instructions for use of antigen tests for COVID-19, referring laboratories to the webpage where emergency use authorizations (EUAs) for each test are posted. “Insufficient cleaning of the workspace, insufficient disinfection of the instrument, or inappropriate use of protective equipment (for example, failing to change gloves between patients) can increase the risk of cross-contamination between specimens with subsequent false positive results,” according to the letter.
Improper storage and handling of test kits, including opening them and then storing them for some time before use, can also affect test results. Tests must also be read within the time window specified, added the agency.
Batch processing of multiple specimens may make it difficult to achieve precise timing of specimen incubation, for example. Also, cross-contamination is possible when multiple tests are run concurrently or sequentially in the same area.

Test interference is also a possibility, particularly when a patient has non-specific antibodies such as rheumatoid factor, or when a specimen is highly viscous.
FDA also reminded laboratories that the conditions of the antigen EUAs specify that laboratories are to report suspected false positives and false negatives, as well as other significant deviations from established performance characteristics to both FDA and the manufacturer of the test in question.
FDA letter


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Tags: coronavirus, FDA, IVD, US

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