Antigen Tests: After Pandemic Success, Time for Bigger Role?
Kathleen Doheny
September 15, 2023
Before the pandemic, most of the public probably had a fleeting and limited familiarity with lateral flow tests (LFTs), also known as rapid antigen tests. Perhaps they used, or awaited the results of, a lateral flow home pregnancy test, which detects human chorionic gonadotropin in urine.
Then came COVID-19, and the need for large-scale testing. By late 2022, more than 3 billion tests for SARS-CoV-2 had been done worldwide. Although testing with reverse-transcription polymerase chain reaction (PCR) is the gold standard for diagnosing COVID, LFTs made possible large-scale testing at low cost with rapid results.
As of September 12, the US Food and Drug Administration (FDA) lists 32 rapid antigen tests with emergency use authorizations (EUAs) for home use.
Now, many experts conclude, it's time to expand the role of LFTs so the technology can help detect a host of other diseases. In a Nature Reviews bioengineering report earlier this year, global experts from the US, the UK, and other countries pointed out that commercial LFTs are currently not available for four of the eight known priority diseases of epidemic potential: Crimean-Congo hemorrhagic fever, Middle East respiratory syndrome coronavirus, Nipah and other henipaviruses, and Rift Valley fever.
It is prime time, these experts and others contend, to build a global network of LFT research and development hubs to strengthen diagnostic capability.
Expansion should not only include more tests for more diseases, some experts say, but also make use of existing technology to provide "full circle" care. After a rapid test, for instance, users could download a mobile phone app, transmit the results to their healthcare provider, and then set up an appointment if needed or get a prescribed medication at the pharmacy.
Medical Community On Board
Clinicians support increased availability of LFTs, said Eric J. Topol, MD, professor and executive vice president of Scripps Research, La Jolla, California, and editor-in-chief of Medscape. "Rapid antigen tests are critical, made a big difference in the pandemic, and will be used increasingly for many other applications in the years ahead," Topol said in an email.
Physicians welcome their potential, agreed William Schaffner, MD, professor of preventive medicine and infectious disease specialist at Vanderbilt University Medical Center, Nashville, Tennessee. At the start of the pandemic, when he was briefed about a lateral flow device in development, he said, "I was blown away by the technology, ease of use, rapidity of getting a result, its reasonable accuracy and its anticipated relatively low price."
Clinicians would probably see many advantages to having more LFTs for more diseases, Schaffner said, because they are of use not only at home but also in doctors' offices and in emergency departments. Their increased use "would help [people] make quick decisions about treatment, especially for flu and COVID."
How LFTs Work
LFTs are capable of targeting antigens, such as for the COVID tests, and antibodies such as immunoglobulin (Ig)G or IgM. The tests are also capable of detecting nucleic acids, although the availability of these tests is currently rare.
First, a sample from blood, urine, saliva or other bodily sources is placed onto a sample pad. It travels to a conjugate pad containing antibodies. If the target being looked for is present, the target and antibodies bind and, as the sample moves along to the test line, produces a positive result line along with the control line (to show that the test worked).
Global Market Outlook
By 2030, the lateral flow assays market is predicted to rise to $14.1 billion, according to a report issued this month by the firm Research and Markets. In 2022, the market was estimated at $9.4 billion, with $3.6 billion of that in the US.
The report details the performances of 55 major competitors, such as Abbott Laboratories, Siemens AG, and QuidelOrtho Corporation, but smaller companies and start-ups are also involved in LFT development.
LFTs: Pros and Cons
Although LFTs give rapid results, their accuracy is lower than that of PCR, especially the sensitivity. For COVID antigen LFTs, the sensitivity ranges from 34.1% to 88.1%, with an overall specificity of 99.6%, according to a Cochrane Review report. The analytical sensitivity performance of PCR testing for COVID is near 100%.
Everyone acknowledges the accuracy challenge of LFTs. The technologies "are generally thought to have limitations of detection that for some applications may present a challenge," said Douglas C. Bryant, president and chief executive officer of QuidelOrtho Corporation, San Diego, California, which counts the QuickVue rapid test for COVID detection among its products.
However, Bryant added, "As we saw during the pandemic, there was a place for more sensitive PCR-based technologies that are often run in a lab and there was a place for the use of rapid tests: The key is knowing the strengths and best use cases when applying the different technologies."
One strength, he said, was that the tests "were shown to be highly effective at detecting active, infectious cases of SARS-CoV-2 and the rapid turnaround time allowed patients to isolate themselves from others quickly to help curb the spread of infection to others." Another advantage, he said, was the ability to screen high-risk populations such as nursing homes to detect positive cases and help prevent outbreaks.
The pandemic familiarized people with the tests, said Jeremy Stackawitz, CEO of Senzo, a start-up in vitro diagnostics company developing an amplified LFT platform for rapid tests for flu, tuberculosis, COVID, and Clostridioides difficile. People liked using them. Physicians generally accepted them. It works great with tele-doc. It works great with personalized medicine.
Now, he said, people used to the COVID self-tests are asking: "Where is my strep test? Where is my sexual health test?"
FDA's Perspective on LFTs
The FDA has no one-size-fits-all standard for evaluating LFTs.
"LFTs are evaluated with respect to their individual indications and the pathway under which they are being reviewed," said James McKinney, an FDA spokesperson. "A performance recommendation for one type of lateral flow test may not be appropriate for another."
EUAs, such as those given for the COVID at-home tests, require different levels of evidence than traditional premarket review, he said, whether de novo marketing authorization, 510(k) premarket notification, or premarket approval. The EUAs are evaluated with a risk-benefit analysis to speed up the time it takes to make the devices available.
And, McKinney said, for some devices, the FDA provides recommendations on the expected performance through guidance documents. For instance, for rapid devices developed to detect influenza A virus antigen, the FDA recommends including enough sample to generate sensitivity of greater than 60% and testing at least 50 samples.
LFTs: The Potential, the Challenges
Stackawitz, the Senzo CEO, predicts that as more LFT self-tests become available, more people will seek care, just as they did with the COVID rapid tests. A 22-year-old who thinks he has chlamydia may balk at going to a doctor right away, he said. However, "if he can go buy a soda and a test at CVS, it's different, it really is. With a little anonymity, people will seek care."
He has a vision shared by other experts: That testing technology will evolve so that after getting the results at home, people would follow through by sending those results to their healthcare provider and obtaining needed care or medication. In his opinion, this is superior to the traditional way, which often involves visiting a doctor with symptoms, going for tests, waiting for results, and then beginning treatment.
"It would make more sense if you came in knowing your results," Stackawitz said. "It's a much smarter pathway, gives better outcomes for the patient, is much quicker and at much less cost. And it frees up time for doctors. I think most physicians would embrace that."
Although rapid testing is gaining well-deserved recognition, funding is an issue, according to the Nature Reviews report. Those experts warned that "a reduction in funding for LFT research post COVID-19 may hamper efforts to capitalize on gains in decentralized testing, especially self-testing, which may be critical to address future pandemic threats."
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