October 10, 2019 | Due to opposing market forces and technology innovation in both the central lab and point-of-care diagnostics settings, overall diagnostic testing is trending more slowly toward decentralization than some might expect, according to Berkeley, California-based diagnostics consultant Lucy Hattingh. Adoption of point-of-care testing (POCT) is being driven largely by the specific disease management demands in different healthcare settings. In China, meanwhile, a rapidly advancing economy and series of anti-corruption campaigns have removed two of the biggest implementation hurdles for in vitro diagnostic (IVD) devices, says China IVD specialist Nathaniel Whitney.
Hattingh and Whitney were both presenters at the 11th Annual Next-Generation Dx Summit in August, and more recently spoke to Diagnostics World News to expound on what they shared from the podium.
“I don’t see central labs disappearing any time soon,” says Hattingh. POCT typically costs more than central lab testing on a per-test basis, so a legitimate clinical need for fast results is a prerequisite. It is also “much more difficult” to make the economic case for a point-of-care test since the economic benefit is often systemwide, which requires more financial impact studies to demonstrate.
While frontline care providers will generally favor having more rapid test results, “payers will tend to put the brakes on it unless it costs less,” Hattingh says. Turnaround time and throughput are two other opposing forces at play—ranging from one-at-a-time tests delivering results in under an hour (e.g., Abbott’s ID NOW and Roche’s Cobas Liat for molecular POCT) to those taking three or more hours but at a pace of many hundreds per day (e.g., Roche Cobas 8800 and Hologic’s Panther Plus).
The competitive advantage of the decentralized POCT platforms is that they get away from the practice of sample batching, a common cause of delays in results reporting, in favor of rapid diagnostic tests available on demand, says Hattingh. On the other hand, central labs are becoming highly automated— speeding up even complex testing methodologies such as molecular testing—which has resulted in economies of scale and lower labor costs.
Hospitals are an established market for POCT, such as troponin testing that has been associated with reduced length of stay, decreased admission rates, and fewer costly procedures with a 25% savings per patient according to studies, says Hattingh. Ditto flu testing in the emergency department (ED), which has “changed patient triage and isolation [practices], liberated capacity, and reduced antibiotic use and increased antiviral use.”
While doctors want to offer immediate service, the lab is responsible for the quality of results and understandably have concerns, she says, especially since healthcare professionals must learn how to operate several instruments and do it right every time. In many instances, care pathways themselves must be changed to reap the benefit of more immediate availability of results from POCT systems.
In hospitals, user training and the implementation of instrument fail-safe features to allay lab concerns about results quality are two hurdles to the adoption of POCT, says Hattingh, citing in-person visits she made to three dozen institutions in the U.S. and Europe last year. “Hospitals that successfully deployed molecular testing at the point of care had to make a significant commitment to doing it.”
Hattingh’s focus was on hospital EDs, where instrumentation had to be placed in a “cloakroom-size” room due to space pressures. Implementing POCT in an ED or intensive care unit (ICU) can become a complex undertaking involving staff training on potentially multiple POC instruments that all work differently, she notes, and having lab techs located in the ED or ICU to provide reliable testing often proved impractical from a time management standpoint. Many hospitals eventually opted to have devices reside on the central lab end of a vacuum tube to overcome training and quality issues and at the same time provide a rapid result.
Fail-safe features on POC devices inevitably involve blocking access when users fail to stay current with required training, Hattingh says, which often just frustrates doctors and nurses. Some sort of software dashboard, she believes, could alert the central lab of result outliers so it can investigate and take corrective action at problem locations, supporting the deployment of POC systems at hospitals where POCT is decentralized.
Outside the hospital, diabetes is the biggest disease driver of POCT usage for diagnosing and monitoring among U.S. family physicians, says Hattingh, citing survey results published in 2016. Diagnostic tests for urinary tract infections and strep throat are also used by more than half of the doctors. It’s unclear if the lesser-used point-of-care tests reflect clinical need and disease burden or awareness of the availability of these tests among physicians.
“A lot of family physicians that I have spoken to have a very low level of awareness of diagnostics,” says Hattingh, in part because diagnostic companies generally limit their marketing and sales calls to labs. In most cases, their clinical practice also isn’t oriented toward diagnostics beyond sending samples to a lab.
In the retail pharmacy space, it seems reasonable that providers would embrace the revenue opportunity of POCT given that the U.S. Food and Drug Administration has waived 120 tests for use by non-laboratory trained personnel, Hattingh says. Testing for influenza and strep, as well as screening for diseases like human immunodeficiency virus (HIV) and hepatitis, are among the ways pharmacists can contribute to patient care.
That would certainly expand access to care in the U.S., where the Department of Health and Human Services has predicted the shortage of primary care physicians will reach 20,000 by next year, Hattingh says. “Most people live within five miles of a pharmacy such as CVS or Walgreens.”
One important limiting factor in this healthcare segment relates to the Clinical Laboratory Improvement Amendments of 1988 (CLIA) law, since requirements for obtaining a CLIA certificate can vary significantly state to state, she says. That would make compliance challenging for retail pharmacies that operate nationwide.
Another hurdle for retail pharmacies wanting to get in the POCT business would be the need for collaboration agreements with nearby physicians, Hattingh adds. “Pharmacists can do flu tests but without collaboration agreements in place with local physicians they’re not allowed to tell people what the results are or prescribe a medicine.”
Central labs already have in place the protocols and standard operating procedures required by CLIA to ensure the quality of their testing results, says Hattingh. On the other hand, growing adoption of POCT is a potential business threat.
Hattingh says she suspects national labs will want to partner with a retail pharmacy to mitigate that threat. Walgreens, which originally intended to team up with Theranos, clearly sees the synergies. If a large national reference lab located its collection centers in a national pharmacy chain and provided POCT services on-site, there could be opportunities and benefits for both—as well as patients, she speculates.
The buzz in the market suggests that scenario may soon be a reality. It is rumored that Walgreens will acquire LabCorp, which is opening hundreds of patient service centers at Walgreens stores over the next few years.
Public health clinics, which often serve indigent populations and people with drug addictions and sexually transmitted diseases, would make ideal sites for POC molecular testing for HIV, chlamydia and gonorrhea, says Hattingh. But that’s unlikely to happen until the capital outlay gets under $5,000.
Patient follow-up is key obstacle driving the need for POCT for clinics in low- and middle-income countries and resource-limited settings where communication networks are unreliable and people may be highly mobile or travel great distances for care, she adds.
China has one of the largest economies in the world and its gross domestic product will soon surpass that of the U.S., says Whitney. But it remains a developing country outside the cities where POCT, until quite recently, played a relatively insignificant role. Even today, IVD testing is concentrated in large laboratories affiliated with 2,418 top-tier (aka class III) hospitals in the major cities.
Come 4 a.m. at any of China’s class III hospitals, people start to line up for care, including lab testing. It is not uncommon for these facilities to be doing 20,000 or more tests per day on automated immunoassay and chemistry analyzers. “There is little but growing confidence in the healthcare available in the [18,633] lower level city hospitals,” Whitney says.
The over 600,000 village clinics will remain a “potential” market some time, he continues. POCT is more likely to emerge among the community health centers that have been “popping up on every street corner in the cities since healthcare reform.”
Before China committed to healthcare reform and improvements in medical infrastructure and health insurance system a decade ago, diagnostics in the countryside—outside of rapid tests for pregnancy and ovulation—was comprised of stethoscopes, thermometers and mercury manometers, he continues. The POCT market still shows few signs of market strength outside of urbanized areas.
Multiple factors are driving a shift toward greater overall reliance on POCT. China has a population of 1.4 billion people, over 95% concentrated in the eastern one-third of the country, and they’re getting old faster than anywhere else in the world, says Whitney. One-quarter of the working population, ages 16 and up, will soon be over the age of 60.
After China abandoned its one-child policy in 2016, many women in their late 30s and early 40s tried for a second child, he says. The wave of pregnancies in older women has heightened demand for prenatal and newborn testing.
Until recently, doctors could also work only in hospitals, Whitney continues. But as of April 2019, doctors in 10 cities are now permitted to open a private clinic—another positive sign for POCT. “A lot of doctors still feel more secure staying with the big hospitals, but I think that will be changing.”
China’s IVD market is second only to the U.S., says Whitney, and sales revenue growth is on the upswing. Thanks to the recovery from a succession of anti-corruption campaigns, the market forces have been playing a major role with brand being most important. The first, in 2005, followed the court trial and eventual execution of the State Food and Drug Administration director for corruption and allowing the sale of possibly tainted products into the China market.
Whitney himself was involved in health system reforms implemented about 10 years ago which, among other things, gave added insurance protection to patients with critical illnesses, set recommended patient charges, implemented laboratory quality programs and toyed with medical reimbursement using diagnostic groups where testing would become a cost rather than a profit generator for the lab. Within the last few years, China also instituted a two-invoice system—manufacturer to dealer and dealer to user—to replace a sometimes corrupt, multi-layered distribution system, he says.
The top five IVD manufacturers, he notes, are all multi-national corporations—Roche, Abbott, Danaher, Siemens and Sysmex. But Whitney is intrigued by several smaller molecular POCT companies, including Ustar Biotechnologies based in Hangzhou, China that he discovered in a project of the Bill & Melinda Gates Foundation called “Diagnostic Cost Analysis for the Developing World.”
Ustar has an economical polymerase chain reaction immunoassay product that uses a lateral flow strip for detecting tuberculosis that is ideal for testing in low-cost and remote facilities, he says. It gets much of its development support from the Gates Foundation. The Foundation for Innovative New Diagnostics in Geneva looked at Ustar but had committed financial support to Cepheid, a Swiss company. “Cepheid has placed a lot of instruments in China but there has not been a strong market for its tests because the cartridges are too expensive.”
Another attractive option among many quality Chinese manufacturers, in Whitney’s opinion, is MNCHIP Technologies based in Tianjin, China. The company has a POC device resembling a CD player that reads microfluidic disks containing freeze-dried chemicals specific to 17 different test panels.
Trade war tariffs the U.S. has imposed on China may ultimately be most harmful to U.S. product manufacturers, says Whitney. “If this goes on for a long time and we keep saying that China is the enemy, the danger is that the Chinese population may start to shy away from U.S.-made products,” which are currently a powerful status symbol in a nation heavily invested in maintaining “face” among their peers. It’s why three-fourths of cars on the roads of Beijing are foreign brands—and why Roche has 20% of the IVD market.
It will be challenging enough to get new technologies accepted into the Chinese marketplace, says Whitney. He wouldn’t be surprised if the time constraints on physicians and lab staff at class III facilities leave little time to study the latest molecular technologies or new markers. Lack of experience with these may also create a slowdown in getting innovative molecular products reviewed for regulatory approval. Outside the cities, education will be required for the physicians to know when to order the test and how to interpret the results.
While remote diagnosis is possible, busy physicians at the class III hospitals likely wouldn’t make time to provide interpretation for their colleagues in the countryside without a means to get paid for their time and expertise. This is perhaps where artificial intelligence will come in, says Whitney, provided a software tool can be properly trained to do much of the interpretation work.