By Peter Loftus
Determining if you have the flu isn't always easy -- even with a trip to the ER.
Doctors often skip the type of diagnostic tests that can deliver results within minutes of a nasal swab, believing they're unreliable. More accurate tests take longer to return results, and doctors sometimes prefer to prescribe antiviral drugs or other treatment based on symptoms rather than wait.
New regulations from the U.S. Food and Drug Administration are designed to change that, raising standards and requiring manufacturers to stop selling older rapid flu tests that don't meet the new standards by Jan. 12. The deadline was set in early 2017, well before the current flu season emerged as the most severe in nearly a decade.
The main problem with the older tests: Too many false negatives. The tests diagnose the flu by identifying viral proteins called antigens, but they can't detect lower levels of viral material as well as more advanced diagnostics. This means many patients who have the flu might not get the right treatment, prolonging the illness and, at times, leading to complications such as pneumonia or bronchitis.
The 2009-10 flu pandemic, when a new virus led to more than 60 million cases of flu in the U.S., highlighted the ineffectiveness of the rapid antigen tests because of the sheer number of suspected cases missed, according to the FDA. The agency's new standard for rapid antigen tests is that they can give false negatives in no more than 20% of tests; previously there weren't established performance criteria for the tests.
New diagnostics are starting to become available. Earlier this month, the FDA cleared Quidel Corp.'s QuickVue Influenza A+B test, the company said. Abbott Laboratories' Alere unit and Becton, Dickinson & Co. also say they have antigen-based tests that meet the raised standards.
Some companies have also introduced another rapid flu diagnostic they say is more accurate: molecular-based tests, which detect viral nucleic acid in patient specimens.
Roche Holding AG's diagnostics unit launched the cobas Liat test in 2015, and Abbott's Alere i test was introduced in 2014.
Jesse Papenburg, a pediatric infectious-disease specialist at the Research Institute of the McGill University Health Centre in Montreal, and his colleagues analyzed studies of various rapid flu tests and found the molecular-based tests missed fewer flu cases than the older antigen-based tests. The analysis, published last year in the Annals of Internal Medicine journal, was funded by a Canadian health agency and Becton, Dickinson.
While there is a recognition within the medical community that the new tests are more accurate, diagnostics makers still face challenges.
Rapid molecular tests take between 15 and 30 minutes, while rapid antigen tests generally take less than 15 minutes for results. (Tests typically housed in laboratories can take several hours or longer.)
The tests are also more expensive. Rapid antigen tests cost about $10 to $15 per test, while molecular-based tests cost about $25 to $50, according to Jack Meehan, a diagnostics stock analyst at Barclays.
Misdiagnoses associated with the older antigen tests, meanwhile, have left many doctors comfortable making treatment decisions without a confirmed diagnosis, particularly if the flu is known to be circulating in the community.
What's more, the U.S. Centers for Disease Control and Prevention says doctors don't need a flu test confirming infection to decide whether to prescribe antivirals, and that doctors can make decisions on signs, symptoms and epidemiologic factors. Patients who are hospitalized with suspected flu complications should be tested with molecular-based tests because they are more accurate, said Tim Uyeki, chief medical officer of the CDC's influenza division. Starting patients on antivirals within two days of getting sick could shorten the duration of illness by about one or two days and reduce complications, according to the CDC.
"You don't need a rapid or positive test to treat influenza if you suspect an individual has influenza," said Dr. Pedro Piedra, professor of molecular virology, microbiology and pediatrics at Baylor College of Medicine in Houston. "Fever and cough during influenza season are two signs and symptoms that will increase the likelihood you'll have flu."
Still, some doctors say rapid and more accurate tests can be useful, noting that relying on symptoms alone can lead to incorrect diagnoses in patients who have other infections.
In a clinical trial of a flu drug recently approved in Japan, drugmaker Shionogi & Co. found that 55% of 590 American participants, whose doctors had just diagnosed them with the flu, actually tested negative for the virus when they were tested using the more accurate, longer test.
"A diagnosis of flu is often made on the basis of clinical symptoms alone," such as a cold or a running fever, said Anthony Fauci, the director of the National Institute of Allergy and Infectious Disease. "Therefore, people who have symptoms of flu but who really do not have flu might be incorrectly diagnosed."
Treating patients who don't have the flu with antiviral drugs like Tamiflu can expose them to gastrointestinal problems, skin reactions and other side effects.
To help prevent those kinds of misdiagnoses, companies are also introducing rapid diagnostics that test for multiple pathogens.
Danaher Corp.'s Cepheid unit received FDA clearance last year for its Xpert Xpress Flu/RSV, which can detect flu as well as respiratory syncytial virus, or RSV. RSV, which causes cold-like symptoms, is mild for most patients but can be serious for infants and older adults. Cepheid said the new test can deliver results in 30 minutes or less -- twice as fast as an older model.
BioMerieux's BioFire Diagnostics unit sells a molecular-based test to detect flu and several other viral and bacterial pathogens. It introduced a rapid version of the test, the FilmArray Respiratory Panel EZ, in 2016, which delivers results in about one hour, said Wade Stevenson, senior vice president of global marketing. The company is working on versions with quicker turnaround times.
--Preetika Rana contributed to this article.