In flu season management, POC molecular to the fore

Flu season always proves to be a test of the instruments’ capabilities, Dr. Fader notes. At the peak of this season, between EIA and PCR assays, the Central Texas region was running 1,400 to 1,500 flu tests a week. “We end up with so many specimens coming in one at a time that if the molecular-based instrument runs only one and it’s going to take 30 or 40 minutes, that’s not going to be suitable for hospital-based labs.”

“In those instances, we end up batching and doing probably two runs of the Luminex assay with anywhere from 30 to 60 specimens at a time, just to keep up with the demand.” Baylor Scott & White also receives extra specimens from the CDC because it is one of five sites for a vaccine effectiveness study the agency is sponsoring.

The system’s BioFire molecular instrument tests for a few more viruses and bacteria than the Luminex assay, but it runs only one specimen at a time, while the Luminex instrument handles multiple specimens at once and takes four or five hours to report a result. (Although prices vary by facility, at his system a BioFire instrument is running about $30,000 to $35,000, with a cost per test of about $110 to $140. The Luminex instrument is $40,000 to $60,000 and the cost per test is $50 to $75.)

Perhaps signaling antigen testing’s tenuous grip, the CDC recommends that if a negative EIA result is reported but the clinician still thinks the patient has the flu, the EIA result should not determine whether the patient is prescribed Tamiflu. Dr. Fader notes that at the peak of flu season, sometimes doctors skip the testing entirely. “They will just prescribe Tamiflu or other antiviral agents and not worry about doing the testing.”

Nevertheless, he thinks the EIA test will remain a staple of flu testing for the next few years. “It’s still very useful, especially for pediatric offices where the assays have a relatively high sensitivity, and specificity is very good for all flu assays.” EIA tests are still the most user-friendly, he adds, though Roche’s Cobas Liat and Alere’s i Flu A & B molecular tests are easy assays to run as well.

Competition for patients among outlying clinics has tended to keep the EIA test in use for about 50 percent of the system’s testing. “The clinic will say, ‘If I don’t offer this test, people will go to the other office that does offer the test.’ Whether it’s a good test or not, people will want it. So we’re kind of stuck in that mode.”

Dr. Fader considers this a temporary state of affairs. “We’re in a transition time between the EIA assays and doing most of our testing by molecular methods, and as the cost of instrumentation comes down and more and more assays become CLIA-waived, people will see the benefits of spending the extra money and getting rapid molecular testing.”

Geisinger Health System, where Dr. Wolk directs microbiology, has been one of the leaders in bringing molecular testing in infectious disease to the point of care. The system’s FluWorks program is a laboratory-driven project that places PCR into the hands of Geisinger’s rapid-response laboratories. “There’s a lot of rapid cycle innovation going on in our system to design new care practices, and FluWorks is one of them,” Dr. Wolk explains.

The system’s extensive reach was one of the incentives for developing FluWorks. Geisinger covers 45 counties in central Pennsylvania and includes eight hospitals and eight rapid-response labs staffed by medical technologists who perform testing on site for larger regional physician office practices.

Geisinger’s microbiology tagline, “Cutting-edge practices close to home,” helped inspire FluWorks. “The strategy was to place the most accurate and fastest tests we could find into different geographical regions of our service area, so people can get the same care at any of the clinics or hospitals we serve. Another aspect is the ability to give noncritical patients more options, so they are not forced into emergency rooms when they don’t need emergency care. Finally, we wanted to distribute the laboratory workload across our system, which better prepares us for future outbreaks or pandemics.”

The CDC recommends that clinicians treat patients with symptoms of influenza-like illness as soon as possible and within a certain window, Dr. Wolk notes. “But if you are going to prescribe antivirals to everyone with symptoms, then you will be treating a lot of patients with RSV or other viruses that you don’t need to treat. And the treatment won’t help; it will just add cost. The strategy to identify patients who really need antivirals quickly, perhaps on their way to the pharmacy, will allow our system to block use of antivirals for those who won’t benefit from them.”

Among hospital systems, this is not a common strategy, she adds. “Current urgent cares are performing antigen tests, which are only about 50 to 86 percent accurate. Results do occur in approximately 15 minutes, but for the most part results can be as bad as flipping a coin to determine whether or not the test results are correct.” Geisinger stopped performing antigen testing in 2013. “None of our laboratories are performing antigen testing, and we hold fast to that strategy, despite the pressure for a rapid, but perhaps inaccurate, result. There may be new antigen tests that might be more accurate in the future, but for now, we are holding on to molecular methods as our system’s standard.”

The system’s laboratories complete moderate-complexity molecular flu tests in 60 minutes and hope to drop that to 20–30 minutes next year. In the physician office laboratory sector, “only a few players have launched molecular testing, mostly waived tests.”

Molecular flu testing is quickly moving to the point of care, and Dr. Wolk has some fear about non-laboratorians performing molecular testing in small spaces, such as those found in urgent care clinics. “I am fearful that without the proper environment, cleaning processes, and continuous training, molecular samples could get contaminated with templates from other patient specimens or from nasal sneezing, etc., which could lead to false-positives. Protocols for point-of-care testing must have appropriate cleaning and processing procedures.”

Waived molecular testing should be scrutinized, with prevalence monitored as a way to assess for potential contamination, Dr. Wolk notes. “If a spike in prevalence occurs, that would tip off staff to investigate for contamination.”

It was because of the contamination risk that Geisinger decided to install the waived molecular testing not at the point of care but in an intermediate space. “We chose to move from a centralized molecular test to the next tier of laboratory support, which is the rapid-response labs.” Now that it’s going well there, “our approach will be to select a few smaller clinic practices to launch a waived test platform next year. We plan to monitor all sites for contamination, provide guidelines for cleaning between patients, and install apparatus for specimen processing.”

Shortening turnaround time is their priority, Dr. Wolk says. The system plans to deliver flu results next year directly to patients, with information that describes when an antiviral will help and when it won’t.

The whole effort has to be accompanied by an education campaign to get patients to understand the implications of a fast and accurate test that shows they don’t have the flu. “With the flu program, our primary focus is engaging outpatients in understanding their disease processes and their options for treatment.”

Dr. Wolk believes next year will be the turning point for molecular testing to displace antigen testing. From her perspective, the goal is not necessarily to have the test results at the same time the patients are in the office, encouraging them to wait and increasing the risk they’ll spread germs among each other. Rather, with a 30-minute turnaround, patients can see their provider, have a sample collected, and get the result on their cell phone or other device when they’re on their way home or to the pharmacy. “We are ready to launch this approach next year,” she says.

Inpatients also benefit from rapid respiratory virus testing. With a median collect-to-result time of less than three hours, her laboratory documented that rapid respiratory virus testing supported improvements to mortality, length of stay, ventilator days, antimicrobials, antivirals, and total costs in the ICU population. “And we’re in the process of studying other inpatient groups.”

As this approach to flu testing and results reporting illustrates, the new testing technology may indeed dazzle, but that should not be the point, Dr. Wolk says. “Our whole goal is not technology for the sake of technology, but to get patients on the road to recovery as quickly as possible. With rapid molecular testing in hospitals and at the point of care, patients are our most important focus—if the technology doesn’t inform or benefit the patient, we won’t use it.

“What we’re doing is driven by the technology,” she adds, “but our aim has to stay patient-centric.”

Anne Paxton is a writer and attorney in Seattle.