Flu testing in the upcoming season
Expect some changes in the flu-testing market in the upcoming season:
- Antigen-based rapid influenza diagnostic tests have to meet new minimum performance standards in 2018-19, after being reclassified as Class II devices by the U.S. Food and Drug Administration in February 2017.
- Molecular-based tests are likely to have more of an impact in 2018-19 than ever before.
Repertoire asked three experts to talk about the implications for distributor sales reps:
- Susan Ward, senior global product manager, point of care, Sekisui Diagnostics.
- Nathan Patton, director of marketing, cobas Liat system, Roche Diagnostics Corporation.
- Jessica Irwin, national distribution manager, non-acute, BD.
- Tammi Ranalli, PhD, VP, Marketing North America, Quidel
Repertoire: First, some questions about the reclassification of antigen-based rapid immunoassay tests (RIDTs) to Class II devices. Did that have any impact on the usage or sale of flu tests during the 2017-18 season? If so, can you elaborate?
Susan Ward: The 2017–18 influenza season saw a perfect storm with regard to influenza testing. Not only was there a very virulent strain (H3N2), there was decreased effectiveness of the vaccine and a FDA reclassification, all of which lead to an increase in flu testing. Sekisui Diagnostics, like many manufacturers, saw a large spike in demand, due to the pandemic season. The reclassification did pave the way for increased demand for tests that met the new criteria. However, the larger demand came from the nature of the long pandemic season itself.
Nathan Patton: Roche is not an RIDT manufacturer, but we think the FDA’s decision supports the importance of increased sensitivity in respiratory testing, and will contribute to improved patient care. Without question, the reclassification led to an increase in provider concern and greater interest in more sensitive testing for acute respiratory infections. Many of our customers were already making a transition from RIDTs to a molecular point of care (POC) test, but the FDA’s position on the less-than-optimal performance of RIDTs clearly created a greater sense of urgency.
Jessica Irwin: Based on reported distributor sales tracings, there was definitely an increase in usage of flu tests during the 2017-2018 season. However, the increase is attributable to higher-than-average disease incidence as measured by the CDC’s flu surveillance program rather than the FDA re-classification. In other words, facilities testing for flu saw an increase in symptomatic patients, which accounted for the increased sales. It is not possible to determine how much, if any, of the increased sales was due to the FDA reclassification.
Tammi Ranalli: Each of Quidel’s market leading antigen-based rapid immunoassay influenza test products (Sofia, Sofia2 and QuickVue) meets the Class II requirements. Thus, as some RIDTs were removed from the market due to not meeting the reclassification specifications, additional customers turned to Quidel to address their testing needs.
Repertoire: Providers were allowed to purchase the non-reclassified (Class I) products until January 12, 2018, and to use them until expiration of shelf life. Do you expect that any of these products will be used during the 2018-19 season?
Ward: Due to the nature of the long pandemic season, many facilities may have quickly exhausted their inventory of the Class I products, which created a high demand for products that met the new criteria. With the high demand from the 2017-18 influenza season, many manufactures rationed the Class II compliant products; therefore, it appears that there would be a very limited amount of non-compliant products on the market.
Patton: We don’t have visibility to provider inventories of RIDTs, but given the size of the market and the extraordinary incidence of flu rates last year, we would not be surprised if many of them already exhausted their inventories. Roche was able to maintain its influenza A/B molecular assay supply for the cobas Liat PCR system for our distribution partners throughout the peak of the 2017-2018 flu season. We were well aware of the impact that supply shortages of flu testing assays were having on many providers.
Irwin: We expect facilities that used a non-compliant product to switch to a compliant flu test this summer/fall, prior to the flu season. It is never easy to adjust protocols and meet regulatory guidelines while in the middle of a flu season. Several products in the market, including the BD VeritorTM Plus System, offer a simplified workflow with CLIA-waived tests to minimize conversion hiccups and increase compliance.
Ranalli: Given the intensity of the 2017-18 respiratory season, it would seem unlikely if providers still had inventory of the non-reclassified products. However, if there are several providers with remaining non-reclassified influenza tests, it would seem reasonable they would take the opportunity now to switch to an approved Class II test before the 2018-19 respiratory season begins and avoid the risk of having to make a test change during the season.
Repertoire: What should distributor reps know about the impact of reclassification on antigen-based RIDTs for the upcoming flu season?
Ward: The reclassification has led to tests with higher sensitivity. However, sensitivity can change based on antigenic drift, circulating strains, age of the patient and other factors, including the quality of the sample. The FDA has put into place new performance criteria, which must be met by manufacturers. The new criteria have led to better performing tests. This will provide clinicians access to products that have proven their performance in a clinical setting, with additional control testing of circulating or emergent strains, thereby providing clinicians assurance that they are utilizing high performing tests, such as the CLIA-waived OSOM Ultra Flu A&B Test.
Patton: Healthcare providers can continue to use existing inventory of the non-reclassified products that they purchased through January 12, 2018. Customers who switch to a new reclassified product will have to do test validation prior to clinical use – the same as they do with any new laboratory test. So distributor reps can guide their customers on optimal planning to account for those procedural requirements. They can find out more about the reclassification in the FDA Fact Sheet.
For customers who haven’t yet switched from non-reclassified RIDTs, this is a great opportunity for distributor reps to educate them on the reason for the FDA’s decision and the benefits of moving to higher sensitivity options, like molecular PCR technology at the point of care.
The reclassification has not had any impact on the tests Roche offers on the cobas Liat system, because the real-time (RT) PCR technology it uses is the existing laboratory standard for confirmatory flu testing and already meets or exceeds the minimum required sensitivity. Roche does not currently sell rapid-antigen testing, so the only direct impact we’ve experienced with the reclassification is increased demand for our cobas Liat system and flu assays.
Irwin: With the FDA reclassification there are two sets of standards – one for tests that reference performance to viral culture and another for tests that reference performance to PCR or NAAT. It is also important to note how many different flu A+B strains were tested and detected. The BD VeritorTM Plus System is a digital immunoassay that references performance for flu A+B to PCR and has shown analytical reactivity to 81 flu A+B strains.
Ranalli: The re-testing of products with the circulating strains is a highly effective way for providers to have confidence in the performance of specific products every respiratory season.
Repertoire: Let’s talk about the market for molecular-based flu tests.
Ward: Over the past several years, the market has seen growth in the use of nucleic acid amplification, or molecular tests, for influenza. These tests are higher performing, but they have a higher price tag, and may have contractual elements or capital investment costs. Due to the higher cost, there is a slow adoption in certain markets. This has challenged manufacturers to develop more cost-effective molecular platforms, such as Silaris™.
The CLIA-waived Silaris™ Influenza A&B Test is a molecular in vitro diagnostic test utilizing polymerase chain reaction (PCR), microfluidics, and lateral flow technology, performed on the Silaris Dock. The Dock is compact and portable, providing a cost-effective option for any healthcare setting, including point-of-care, emergency rooms and core laboratories.
These options in testing have shaped the use of testing algorithms. Many clinicians have adopted a testing algorithm using a high-performing RIDT and confirming all negatives with a molecular system. Some clinicians have made the jump straight to molecular testing. Sekisui supports all customers by offering both the OSOM Ultra Flu A&B Test, which is Class II compliant, and a molecular offering — Silaris Influenza A&B Test. The Silaris Influenza A&B Test will also support a standalone testing option for clinicians.
Patton: The reclassification [of RIDTs to Class II devices] has already begun to generate increased demand for molecular-based flu tests, because it has fueled the conversation about the need for higher sensitivity testing. Molecular tests, such as what Roche offers on the cobas Liat system, already provide an accurate and convenient solution that contributes to improved patient care.
Irwin: Molecular tests have grown in popularity, mainly in acute settings such as hospitals. However, it is important to balance increased costs, increased time to results, and overall complexity vs. the benefits they bring regarding performance. There is an increased number of flu testing systems to address varying needs that healthcare facilities have. For example, we have found that hybrid systems that include a molecular test for critical patients and a rapid flu test for the general population help meet the demand for improved patient outcomes while maximizing clinical efficiencies, such as fast turn-around-times and low operational budgets.
Ranalli: The reclassification provided an impetus for end-users to re-evaluate their influenza testing algorithms and choices. This has resulted in some customers making the choice to implement a molecular test. However, due to the high cost and extended turnaround times that come with a molecular solution, the best in class RIDTs, such as Sofia, Sofia2 and QuickVue, still have a critical role in influenza testing and continue be the best solution for most providers from a patient care and economic perspective.
Repertoire: Anything else Repertoire readers should know about flu and flu testing as they prepare to talk to their customers about the upcoming flu season?
Ward: If the industry learned anything from the 2017–18 influenza season, it is to be prepared and make sure your customers are prepared. Many customers are in a state of flu fatigue, but it is up to us to keep them ready and prepared, because flu is coming. Research and know all the options that are on the market so that when you are talking to your customers about their pain points for testing, you can provide them with the right fit for their needs.
Most customers in the POL and ER setting will be looking for options for molecular testing with little or no capital costs, no contractual obligations and a small footprint to provide additional testing in an affordable manner. CLIA-waived would obviously be a large benefit. Keep up on the latest information on flu and prevalence, and work closely with your manufacturing reps on the latest and greatest tools.
Patton: Our distribution partners should remember that, while the reclassification has to do with clinical performance, the physician office lab is also concerned about the patient experience and operational factors, like workflow. The cobas Liat PCR system can meet the clinical performance goals of the practice, but the system also has low hands-on processing time and fast time-to-result, and it can help improve the patient experience, because there is no need for confirmatory testing after a negative result, not only for influenza, but also RSV and Group A Strep. So the patient doesn’t have to go home and wait for a definitive diagnosis, and clinicians can confidently prescribe appropriate viral or antibiotic therapy for the patient. This directly supports healthcare providers with their antibiotic stewardship efforts so they can appropriately prescribe antibiotics only when necessary.
Irwin: Improving patient outcomes when it comes to flu starts with flu testing, whatever the testing system may be. More than ever, it is important to be diligent when dispensing antibiotics. Flu testing helps prevent the unnecessary prescription of antibiotics. This in turn helps reduce the threat of antimicrobial resistance.
Ranalli: Readers should be asking their influenza test suppliers if they have the capabilities to consistently supply tests at the peak of the coming respiratory season. As experienced in the 2017-18 respiratory season, many test suppliers went on extended backorder status. Quidel is confident in our world-class manufacturing capabilities to meet the supply needs for all of our influenza testing platforms (QuickVue, Sofia, Sofia2, Solana), no matter how robust the season. Since each influenza season is unpredictable in arrival as well as volume, it’s never too early to have the conversation with your suppliers.
By the numbers: The 2017-2018 flu season
Statistics from the Centers for Disease Control and Prevention for the flu season starting Oct. 1, 2017, and ending May 19, 2018 (rounded for simplicity):
- Clinical laboratories tested approximately 1.2 million specimens for influenza virus. Of them, 224,000 (19 percent) tested positive – 151,000 for influenza A and 73,000 for influenza B.
- Nationally, the percentage of clinical laboratory–tested specimens positive for influenza virus peaked for five consecutive weeks from Jan. 13 through Feb. 10.
- Regionally, the week of peak clinical laboratory influenza positivity varied, ranging from the week ending Dec. 30, 2017, to the week ending Feb. 17.
- Public health laboratories tested 98,000 specimens between Oct. 1, 2017 and May 19, 2018. Of them, 54,000 (55 percent) were positive for influenza viruses – 38,303 positive for influenza A and 15,000 for influenza B.
- Whereas influenza A(H3N2) viruses accounted for the majority of circulating viruses, the proportion of influenza A viruses subtyped as A(H1N1)pdm09 ranged regionally from 9 percent in the central United States to approximately 24 percent in the northwestern and southeastern United States.
- From early March to late May, influenza B viruses were more commonly reported than were influenza A viruses. The proportion of influenza B viruses reported regionally ranged from 23 percent in the Midwest to 41 percent in the northwestern United States.
- Among 47,000 (88 percent) patients who tested positive for seasonal influenza virus by public health laboratories and for whom age data were available, approximately 4,000 (8 percent) were aged 0–4 years; 12,000 (25 percent) were 5–24 years; 16,000 (33 percent) were 25–64 years; and 16,000 (34 percent) were 65 years or older.
- Influenza A(H3N2) viruses predominated among all age groups, ranging from 51 percent of viruses among persons aged 5–24 years to 70 percent among persons aged 65 or older.
- The largest proportion of reported influenza B viruses (37 percent) occurred in persons aged 5–24 years.
Source: Centers for Disease Control and Prevention, “Virus Surveillance,” June 8, 2018
Could flu tests go OTC?
Two potential diagnostic tests for influenza designed to be purchased over-the-counter for home use will move into advanced development with new support from the U.S. Department of Health and Human Services.
The Biomedical Advanced Research and Development Authority (BARDA), part of the HHS Office of the Assistant Secretary for Preparedness and Response (ASPR), announced in July that it is partnering with Cue Health Inc., of San Diego, California, and Diassess Inc., of Emeryville, California, to develop these testing devices.
BARDA will provide $14 million to Cue Health and $10 million to Diassess for advanced development of diagnostic tests for influenza A and B viruses that are being developed for purchase over-the-counter or administration by professionals. The agreement with Cue Health can be extended for up to $30 million over 60 months, the agreement with Diassess can be extended for up to a total of $21.9 million over 60 months.
HHS reports that both companies are designing their devices to be able to give results within 25 minutes. Both devices use mobile technology so that patients who test positive for influenza can receive a telemedicine consultation and, if needed, a prescription for antiviral drugs without leaving home. The devices also may include the capability to report de-identified influenza data to local health departments in real-time.
The Diassess testing device would be disposable and battery-powered for use in the field. Cue Health also is developing its device to test for other viruses, including Zika and HIV.