NEW YORK ─ Already a growth market before the pandemic, decentralized testing may have received a sustainable boost during the past year and a half, according to some experts.
In the early days of the COVID-19 pandemic, laboratory-based molecular testing was the gold standard for diagnosing individuals who had the SARS-CoV-2 virus.
But as the pandemic dragged on, tests which didn't have to rely on a lab to get results quickly moved to the forefront. Lab-based tests, often leveraging PCR technology, can provide high sensitivity, but rapid antigen tests that can be done in a wide variety of settings, even at home, can provide results in about 15 minutes, making them crucial tools for identifying individuals who may have COVID-19 and managing them appropriately.
Now, some say that the pandemic may accelerate efforts to continue developing decentralized testing technologies to treat not just the coronavirus, but a host of unrelated ailments.
"What's very clear is that since the onset of the pandemic, the acceptance and acceleration of decentralized care models have radically increased, and the drive toward more efficient, more effective, decentralized models will enable more effective chronic disease management," said Ian Parfrement, head of point-of-care testing at Roche Diagnostics.
Such has been the success of decentralized tests for COVID-19 that they are now widely used in schools and airports, as well as for cruises, and at sports events and other entertainment venues. And when the pandemic becomes endemic, many industry executives believe the demand for these tests will remain high.
To be sure, not everyone believes that COVID-19 will result in a burgeoning demand for decentralized testing in broader diagnostics space. Vijay Kumar, an analyst at ISI Evercore, noted, "What we're seeing right now is a point-of-care testing ramp that is driven by necessity, and that might change in a post-pandemic world."
Robert Boorstein, medical director of Brooklyn-based Lenco Diagnostic Laboratory, added that while "the considerable demand we're seeing for point-of-care and near-patient testing for COVID is probably going to continue for some time," what's happened during the pandemic had "a unique impact" not seen with other medical conditions.
The unprecedented demand for COVID testing and availability of point-of-care tests "is not inevitably going to lead to an uptick in point-of-care testing for other diseases," he said, and "each disease and indication is going to have to stand on its own in terms of clinical utility and not just on the availability of methods or equipment."
However, decentralized testing had already been gaining traction prior to the pandemic, with the emergence of freestanding urgent-care centers and mini-clinics in retail locations, and the use of self-collection for tests run in laboratories.
"What has seemed to people outside the industry like a tsunami of innovation because of the pandemic is really just an unveiling of different technologies for decentralized tests that have been in development," QuantuMDx's cofounder and CEO Jonathan O'Halloran said in an interview.
In addition to the availability of decentralized lateral flow point-of-care tests for a range of illnesses, numerous companies have developed near-patient molecular platforms that can be used outside laboratories. They include tests from Roche, Danaher's Cepheid, Abbott, Quidel, Qiagen, Meridian Bioscience, DiaSorin, and Mesa Biotech, now part of Thermo Fisher Scientific.
New entrants in the near-patient MDx market segment include MatMaCorp, the developer of a fully integrated, handheld qPCR system; Nuclein, the developer of a disposable, handheld system that does not use assay cartridges; and Visby Medical whose system also performs handheld qPCR and is disposable.
Recent acquisitions also reflect IVD companies' belief in future demand for decentralized molecular tests, and include Roche Diagnostics' acquisition of GenMark for $1.8 billion and Thermo Fisher Scientific's acquisition of Mesa Biotech for up to $550 million.
The modular design of GenMark's ePlex MDx system enables testing for respiratory pathogens in around 90 minutes in various settings that extend from small, decentralized sites to large central laboratories, while Mesa Biotech sells a PCR-based rapid point-of-care platform for infectious disease diagnostics, including tests for SARS-CoV-2, influenza A and B, respiratory syncytial virus, and strep A.
POC testing for COVID-19
The COVID-19 pandemic has highlighted the clinical value of decentralized tests.
FDA issued the first Emergency Use Authorization for an at-home test in November 2020 to Lucira Health's loop-mediated isothermal amplification-based Lucira COVID-19 All-in-One Test Kit. The next month the agency granted the first EUA to an over-the-counter, at-home COVID-19 test to the Ellume COVID-19 Home Test, a rapid antigen test. Since then, the FDA has granted EUAs for numerous point-of-care and near-patient tests to detect SARS-CoV-2.
Earlier this month, President Joe Biden gave rapid antigen tests that can be used at home a shot in the arm by announcing his COVID-19 Action Plan, which includes initiatives to support an increase in decentralized testing for SARS-CoV-2.
The majority point-of-care and near-patient tests that have been authorized by the FDA for diagnosing COVID-19 are rapid antigen tests. The proposition behind these tests is that although they may have lower sensitivity than molecular tests for SARS-CoV-2, they provide quicker results, allowing clinicians and individuals who may be infected with the virus to take immediate action, rather than wait for a day or longer for results from a lab-based molecular test.
Advocates of rapid antigen tests for COVID-19 also say that if used repeatedly, they can achieve sensitivity that rivals molecular tests. Additionally, they say, molecular tests may actually be too sensitive, detecting trace amounts of the virus in an individual when the person is not infectious.
While most decentralized tests are not molecular, some molecular tests exists that allow clinicians to use them at or near the patient's side. For example, Danaher subsidiary Cepheid recently obtained CE marking for two of its PCR-based assays for HIV-1, enabling their use to test infants, adolescents, and adults in both laboratory and near-patient settings. Further, Novacyt recently launched VersaLab Portable, an eight-piece portable molecular testing lab in a lightweight carrying case for rapid-turnaround and on-site PCR testing, initially for COVID-19 testing. And Diagnostics for the Real World's SAMBA II SARS-CoV-2 molecular test is being implemented in the emergency departments of UK hospitals.
One near-term potential application for decentralized molecular tests is for the detection and differentiation of SARS-CoV-2, influenza A, influenza B, and other respiratory pathogens, but the uptake for such tests during the upcoming flu season remains to be seen, according to Parfrement.
He said the disease indications likely to witness the most decentralized testing uptake include infectious diseases, such as sexually transmitted diseases, and cardiology and cardiometabolic diseases.
Diseases where immediate decisions on isolation or treatment, or both, are made in the emergency room or hospital ward "are certainly ripe for such switch-over" to point of care from laboratory testing, Davide Manissero, chief medical officer, infectious diseases, at Qiagen, said in an interview. Such tests are most suitable in instances where rapid time-to-results is critical.
Point-of-care testing under direct clinical supervision "will certainly evolve and expand for acute respiratory, urinary, and gastrointestinal infections, as well early sepsis identification," Manissero said.
Qiagen is seeing its near-patient QiaStat-Dx multiplexed syndromic testing panels being used in hospital emergency rooms and intensive care units to improve antimicrobial stewardship, time to discharge, and length of stay, he added.
Meantime, Hologic recently entered the market for near-patient molecular testing with the acquisition of Finland-based Mobidiag for approximately $795 million, a firm that markets tests for acute care conditions such as gastrointestinal and respiratory infections, antimicrobial resistance management, and healthcare-associated infections.
While COVID-19 testing has led to an earnings bonanza for Hologic during the pandemic, the acquisition had been on the drawing board before SARS-CoV-2 became a household term, said Kevin Thornal, Hologic's division president of diagnostic solutions.
"In general, testing near the patient is an added benefit for society, patients, and healthcare providers," he said. "We have been working on near-patient testing for a long time and multiple options are available, including at-home collection with testing completed on our molecular systems, and desktop molecular and microarray testing that can be done in various locations closer to the patient."
Health systems stand to benefit most when they implement both near-patient and laboratory testing, he said, adding, "With desktop testing, you can get an answer quickly, but you are often limited to a handful of results each hour."
As a result, many of Hologic's hospital customers are installing its new Novodiag near-patient systems for testing that complements testing conducted on its high-throughput Panther molecular diagnostic systems.
UK-based QuantuMDx is a recent entrant to the near-patient syndromic testing market and has been developing its diagnostic platform, called Q-POC, since 2008. The firm is taking aim at a wide range of point-of-care settings, including intensive care units, birthing centers, doctors' clinics, and pharmacies.
Its CEO O'Halloran noted that such MDx syndromic panels for pathogen detection, some of which include drug resistance markers, provide a higher barrier to entry for new companies than many lateral flow point-of-care tests. "Developing a multiplex molecular platform [for decentralized testing] is really difficult to do," he said. "In addition to multiplexing, you need high performance and to deliver results at speed and the right price."
Such near-patient multiplex-testing will continue to gain traction as more patients present with symptoms that make it difficult to differentiate one infection from another, Kumar said. Overall, the systems are likely to find most uptake for respiratory and gastrointestinal disease testing, he said, noting that testing panels with a menu of about 10 organisms are more acceptable to payors than larger panels.
Some industry players said that point-of-care testing for sexually transmitted diseases appears poised for an uptick in demand. Increases in STI testing are unlikely to come at the expense of central laboratory testing, but "there is certainly a place for rapid STI testing in high prevalence settings, sexually transmitted disease clinics, university health programs, and perhaps the military," Boorstein said.
O'Halloran added that the opportunity for decentralized STI testing is partly driven by patient behavior. "People want to get in and out of the testing facilities as quickly as possible," he said, adding many patients who take a laboratory test cannot be reached to provide their results, something an office-based or at-home test would solve.
Other indications that appear poised for an increase in adoption at the point of care include blood-based cardiovascular biomarker tests for ambulances and emergency departments. Though high-sensitivity troponin tests in laboratories have been available, point-of-care tests with such high levels of performance have not. However, Siemens Healthineers recently began shipping its first Atellica VTLi Patient-side Immunoassay Analyzers with a high-sensitivity test for troponin I, a protein biomarker of acute myocardial infarction, to hospital emergency departments in Europe.
Testing at home
For its over-the-counter and at-home tests, Siemens Healthineers looks to the most prevalent diseases presented by patients at doctor's offices, such as urinary tract infections and gastrointestinal health problems, Christoph Pedain, head of point-of-care diagnostics at the firm, said.
Convenience and timely access to testing are the main drivers of adoption for many of these decentralized testing applications. "Over-the-counter and at-home testing, in particular, can vastly improve the patient experience," he said, and drive both testing and treatment compliance.
Pedain added that at-home testing has the potential to enable better monitoring of chronic diseases, such as diabetes, some cancers, and neurodegenerative diseases, such as Parkinson's and dementia, which require long-term comparability of test results.
"That's a harder nut to crack than testing for a single event such as a UTI or [sexually transmitted disease] that often involves one test and prescription of a treatment," he said. However, "one of the big diagnostic industry developments over the next decade will involve the creation of networks that make data comparable and usable, even if it's collected in a very decentral way, and in some cases collected by nonprofessionals." Ensuring that patient data is reported in electronic medical records is another important challenge ahead for the development of at-home tests, Pedain added.
Additionally, during the pandemic, countries with well-developed communications infrastructures are witnessing a rise in the use of telehealth consultations, helping increase demand for in vitro diagnostic testing in the home, he noted.
Roche has also seen an acceleration in the adoption of telemedicine and virtual technologies for home use. "These technologies will be needed to manage the endemic disease burden moving forward, and to manage the backlog of testing and treatment that has built up" since the beginning of the pandemic, Parfrement said.
There has to be a clear benefit to having a decentralized test for each use case, he noted. "Where there is a strong medical need, where decision-making can be taken on the back of those results, and the results are of an appropriate quality for that particular use case, you can have a very compelling position where point of care is adopted," he said. "Once you have those things, all other components can fall into place, whether that is reimbursement or clinician acceptance."
Usability is also a critical issue, O'Halloran said. "That's something we've all learned from the pandemic — that the ease-of-use requirements for point-of-care tests are different depending on whether a test is run out of the home, pharmacy, clinic, hospital, or the lab. Tests done by individuals at home have the toughest user requirements because of the potential for user error."
Indeed, the main issue with running tests at home is sampling, he said, adding that recent studies show such testing can lead to "huge sampling variations."
ISI Evercore's Kumar said that the adoption of at-home testing for SARS-CoV-2 and other indications may continue to be hindered by the performance of lateral flow testing technology, the modality most suited to such testing. The sensitivity of lateral flow antigen tests tends to be "somewhere between 80 and 90 percent, and specificity is often in the 90s," he noted. "That is going to be an issue for many indications because it has the potential to leave out a large percentage of cases that need to be detected."
He noted that in the US market, at-home tests in general are not currently reimbursed, and prices of such tests for SARS-CoV-2, for example, are too high for many people, representing another barrier to adoption.
Ellume's over-the-counter antigen test for SARS-CoV-2 currently costs consumers between $35 and $50 per test, and a BinaxNow test package of two antigen tests costs $24.
The emergence of at-home test companies has shown that a portion of the population will absorb the expense of testing, but having to pay out of pocket could become a significant obstacle to the overall adoption of these assays, O'Halloran said, adding that "reimbursement for home testing is going to be really complex" and consumers may have to continue to pay completely out of pocket for such tests.
Boorstein noted that numerous operational and logistical issues make insurance coverage of home self-testing problematic. "At some level you need to distinguish between self-ordered tests and physician ordered tests," he said. "In general, self-ordered tests are not reimbursed regardless of where the test is done. Further, it is difficult to assure reliable test performance, accurate test reporting, that the results are for the insured, that appropriate physicians get notified about the results, and in the case of infectious diseases, that there is appropriate notification [to] government health authorities."
In his view, he said, many at-home tests are meant to be purchased and used anonymously. "If this is not the case, as it can’t be if you want insurance coverage, tracking and data management may double the cost of the test," Boorstein added.
Qiagen's Manissero said there are also noteworthy differences in near-patient molecular testing and direct-to-consumer testing. "Sensitivity and specificity [of lateral flow tests] often are sub-optimal when compared to molecular and/or laboratory-based approaches and technologies," he said. "Additionally, sample quality when self-sampling can impact test results, as we have experienced with SARS-CoV-2. An evolution toward home testing technologies with improved limits of detection and standardized sample collection procedures is required — and actually ongoing — to expand the utility and reliability of such tests."
Going forward, direct-to-consumer testing "will influence communicable and noncommunicable disease testing and monitoring, where reasonable delays in treatment initiation, or change, are not linked to worse outcome but [where] the ease of use and accessibility would increase diagnostic uptake," he said.
Among the candidates for such testing are sexually transmitted disease assays, asymptomatic or paucisymptomatic COVID testing, and the monitoring of noncommunicable disease such as diabetes and monitoring of the international normalized ratio in patients taking an anticoagulant prophylaxis, he said.
For at-home tests to progress, they must improve on enabling clearer interpretation of results to allow immediate clinical decisions, Manissero said. "Closer-to-patient diagnostic solutions will remain unimpactful without a clear link to management decisions. This will require a closer interaction between labs and clinicians to improve diagnostics as well as antibiotic stewardship, which is a key milestone we need to collectively achieve," he said.
Another driver of decentralized testing is the ongoing rise in antimicrobial resistance, Accelerate Diagnostics' chief strategy officer, John Meduri, said in an interview. "We see emerging companies developing point-of-care rapid tests to help differentiate bacterial from viral infections, so that physicians have an early indication about whether to treat with antibiotics," he said.
Accelerate Diagnostics recently launched Phenotest BC kit AST configuration, which provides rapid antimicrobial susceptibility test results and complements the rapid ID systems that are moving closer to patients. Accelerate is targeting laboratory ID systems with its new AST configuration but, according to Meduri, it is also targeting decentralized settings that conduct culture and ID testing along with susceptibility testing at the point of need outside intensive care units.
Antimicrobial resistance "is a pandemic within the pandemic" that will drive future demand for both laboratory and decentralized testing, Meduri added.