A New study from Kalorama Information said that the number of urgent care centers in the US is expected to increase from approximately 10,600 currently to more than 12,000 by 2023.

The report, The Market for U.S. Urgent Care projects a growing market for the urgent care center business and a growing market for suppliers selling to them.

To some extent this will not be surprising.  According to the study, urgent care centers charged just $168 per visit on average in 2015.  Hospital-based emergency department visits, on average, charged more than $2,250 per visit in 2015. The charge was approximately $2,200 at some freestanding emergency care clinics. Most of the visits, regardless of facility, were for 20 of the most common diagnoses, and prices for patients with the same diagnosis were, on average, almost 10 times higher at ERs.

“There may be a maturing of urgent care center growth as the industry begins to mature, and locations compete with one another in similar healthcare service quadrants.” said Bruce Carlson, Publisher of Kalorama Information.  “But there will be growth and growth in supply markets.”

Kalorama Information expects to see a compound annual growth rate of more than 3% overall through 2023 in terms of center revenue.

Urgent care clinics came into reality in the 1970s and have grown to meet the needs of both rising healthcare costs and the need of consumers for convenient access to healthcare.  Some of the growth is the result of hospital systems starting urgent care centers to reduce the demand at their hospital emergency rooms, aiming to make those areas of their system more profitable.

Other centers were started by entrepreneurial physicians to grow their income while meeting a market need.

Urgent care centers have evolved into an established segment of the US healthcare industry, with steady growth expected through 2023.

This growth is expected to continue as new partnerships and players emerge in the urgent care space. Walgreens drug stores have joined with UnitedHealth Group MedExpress to open more urgent care centers which would be near or adjacent to Walgreens drugstores.

The effort has reached more than a dozen urgent care centers in six states.

Insurers are happy with urgent care as they see the model as a way to maintain patient health and keep people away from inpatient hospital settings, which are more costly. Such a value-based approach to medicine is increasingly replacing the fee-for-service model that emphasizes volume of medical care delivered.

Urgent care is growing due to patient demand, convenience, and lower costs. A patient seeking medical care does not like to wait for long periods of time to see a provider. Urgent care clinics, with their longer hours and walk-in appointments, fulfill this need for speed in a way traditional physician’s offices usually cannot.

The CDC reports a late peak and possible second wave to what was previously thought to be a weaker flu season compared to recent years. This is important for IVD makers, as respiratory IVD markets are driven to a great extent by the severity of the flu season. While the total number of cases remains below 30M, and thus less than last year, recent weeks saw a small peak and there’s a new strain that is demonstrating virulence.

The CDC reports a late peak and possible second wave to what was previously thought to be a weaker flu season compared to recent years. This is important for IVD makers, as respiratory IVD markets are driven to a great extent by the severity of the flu season. The chart  accompanying depicts the flu cases in thousands for the weeks of 2019.  instead of fully declining, there was a late peak in February. While the total number of cases remains below 30M, and thus less than last year, recent weeks saw a small peak and there’s a new strain that is demonstrating virulence.

Per the CDC:  Since October 1, there have been nearly 26.3 million cases of the flu, as many as 12.4 million flu-related medical visits, and up to 31,200 deaths caused by the flu. Nine children died from the flu last week, bringing the total of pediatric deaths this season to 64. There are two main groups of influenza viruses: influenza A and influenza B.

Respiratory systems such as those that detect flu are a key component of the true molecular point of care market, representing decentralized rapid or CLIA waived systesm. And revenues for respiratory represents nearly sixty percent of this market according to the Market and Potential for Molecular Point of Care Diagnostic Tests 2019
https://kaloramainformation.com/product/the-market-and-potential-for-molecular-point-of-care-diagnostic-tests-2019/

According to that report, the flu season’s severity in 2017/18 created an opportunity for new systems.  This year, a new strain is concerning.  The H3N2 strain belongs to the influenza A family. In addition to the typical symptoms of flu, which include fevers, chills, body aches, and rigors [shaking chills], it additionally has the potential of causing several severe complications, including very high fevers.

CDC estimates that the burden of illness during the 2017–2018 season was also high with an estimated 48.8 million people getting sick with influenza, 22.7 million people going to a health care provider, 959,000 hospitalizations, and 79,400 deaths from influenza (Table 1). The number of cases of influenza-associated illness that occurred last season was the highest since the 2009 H1N1 pandemic, when an estimated 60 million people were sick with influenza6.

While this flu season has not been quite as severe as seasons past, there has been a recent uptick in a less common flu strain, the H3N2 virus, now accounting for over 50 percent of new cases, according to recent data from the CDC. There have been 350,000 hospitalizations according to the agency.

Since near patient-testing systems using PCR technology first appeared on the market, the leading IVD market research publisher Kalorama Information has provided sound market estimates and forecasts for their usage. As these systems move from novel to closer to a routine usage, our 2019 update provides essential information for marketers in IVD.

Kalorama’s report is a true look at the clinical market for molecular systems, both CLIA-waived and those CLIA-moderate that can be used in an office visit. The report incorporates systems in development as of 2019 and updates on competitor laggards in previous editions that have not produced products.

Companies in the molecular point-of-care market include: Abbott, Roche, Biomerieux BioFire and Danaher’s Cepheid, among others.

Kalorama Information’s new report on U.S. long-term care, “The Long Term Care Market: Nursing Homes, Home Care, Hospice Care, and Assisted Living,” finds that growth will be fueled by the diversity of services that can be offered. The industry will near the half-trillion dollar mark in the next five years, growing even with cautious payor activities. Plus, the market research report says, the market exerts an influence on other markets — healthcare provision, devices, and pharmaceuticals. And there’s plenty of room for competitors.

The report is available at https://kaloramainformation.com/product/the-long-term-care-market-nursing-homes-home-care-hospice-care-and-assisted-living-2/

 

The long-term care market is a complex and diverse industry that is evolving yearly. The growth trend is clear and not surprising. The U.S. long-term care industry has experienced steady growth from 2016 through 2018, and this is expected to continue through the forecast period. Aging of the population will increase demand for all forms of long-term care, although ongoing cost containment will continue to pressure the industry. As the demographics of the U.S. population have changed, so have the attitudes toward long-term care. The long-term care industry has met the challenges of the changing industry by diversifying offerings and increasing specialized care.

“There are more than 300 of these providers but only a handful have any significant market share. And the market not covered by top competitors is sizable, so expect new entrants,” said Bruce Carlson, publisher of Kalorama Information, now a part of BioInformatics Inc.

Yet because of the local nature of healthcare services, the scattered demand across the United States, and the variety of established players, there is no one leader in the market yet. Some brands do ring in consumer minds. In revenue terms, Kindred Healthcare led the overall market — and even this significant and diverse competitor’s $5.5 billion in revenues amounts to less than 2% share. Thus, share calculation in this market is impractical. Competitive companies include Genesis HealthCare, Brookdale, Life Care Centers, Golden Living, and Extendicare; others will expand with acquisitions of more large players to pose a greater threat to the leaders.

Baby boomers accounted for approximately 67 million individuals in the United States in 2018, and this enormous group is making decisions about whether senior living is the right option for aging loved ones and themselves.

The industry is growing. Through 2018, the industry overall experienced solid expansion, growing by 4% per year, on average, to reach $344.9 billion. The strongest growth occurred in the home care segment.

Through the forecast period, these trends will continue, with total annual industry growth of 5.1% per year, resulting in overall revenues of $441.7 billion in 2023. Growth will remain steady in all sectors even as reimbursement pressures continue to affect revenues.

The report says the evolution and specialization of residential, community-based, and home healthcare services will continue. The aging of the population, rising rates of chronic disease, longer life expectancies, and advances in public health and medical technology will result in unprecedented numbers of people requiring long-term care services in the near future — even as a shortage of healthcare personnel is occurring. The healthcare industry must begin to work now to reduce the fragmentation that exists both in the continuum of long-term care services and in the system of payment for those services.

About Kalorama Information
Kalorama Information, a division of BioInformatics Inc., supplies the latest in independent medical market research in diagnostics, biotech, pharmaceuticals, medical devices, and healthcare; as well as a full range of custom research services. Reports can be purchased through Kalorama’s website.

We routinely assist the media with healthcare topics. Follow us on TwitterLinkedIn, and our blog on our company website: https://www.kaloramainformation.com/.

MEDICA comes to a close in Dusseldorf, Germany, but not without some interesting developments…more than a few of which could upend healthcare. The MEDICA and related COMPAMED event is one of the oldest and arguably the largest medical trade fair in the world – it attracted more than 5,100 exhibitors from 70 countries in 17 halls this year.  The MEDICA show doesn’t simply focus on one area say pharma or IVD, it covers all aspects of the patient workflow, which means all kinds of healthcare products and services were on display: ambulance manufacturers, diagnostic tests companies, robotics firms and tubing products, healthcare software.  While there is a European and German focus to the meeting, more than a third of the attendees are from outside Europe, according to MEDICIA. EU Regulations were the highlight of a well-attended with Nicole Denjoy of COCIR at Medica Trade Fair.   An Infection Prevention Roundtable with Experts seminar was a highlight of the conferences at the meeting, and there were talks on IT and preventing piracy among others.

Some of the most interesting developments, were on the exhibit floor, where some problem-solving inventions and new products were displayed.  Kalorama information notes the following:

  • Ruling out HIV-2 in HIV Tests –  The choice of antiretroviral therapy for HIV-2 differs from that for HIV-1, underscoring the importance of differentiating between the two. To that end, Avioq launched its VioOne™ HIV Profile™ Supplemental Assay at MEDICA 2018.  The test is an enzyme-linked immunosorbent assay (ELISA) for confirmation and differentiation of individual antibodies directed to various gene products of Human Immunodeficiency Virus Type 1 (HIV-1 Group M & Group O) and Type 2 (HIV-2) in human serum or plasma. The HIV Profile™ is intended as an aid in the diagnosis of infection with HIV-1 and/or HIV-2.  HIV-2 is most common in western Africa and is becoming more common in India, although numbers there are still relatively small. Small numbers of cases have also been seen in Portugal, France, other European countries including the UK and the Americas, largely in individuals of west African origin or their sexual partners.  Kalorama Information is the publisher of such titles as The Worldwide Market for In Vitro Diagnostics, 11th Edition, covers HIV testing markets among other infectious disease categories.
  • Robot Nurse? The Made in Moscow exhibit of Neurobotics company (part of Zelenograd Development Corporation) demonstrated an anthropomorphic robot called “Alice.”  The Alice robot exhibits the ability to read people’s emotions and react accordingly.  The company says It can eventually be used as a nurse, or a physician assistant. Such a robot will be able to perform an initial examination of patients in the future.
  • Wearable “Beat to Beat” Blood Pressure Monitor – The ViCardio device is the world’s first wearable, beat to beat, non-invasive, accurate, blood pressure monitor. It causes no arterial compression, requires no biological calibration and produces an arteriogram equivalent to an invasive intra-arterial line. Using an optical-electronic micro-motion sensor that allows blood pressure to be measured with each beat of the heart in a simple and elegant wrist-based device, ViCardio is a pain-free way of taking regular discrete readings.
  • Using Virtual Reality To Treat Fear of Spiders – Arachnophobia is what experts call the fear of spiders, and a VR/AR system from research-giant Fraunhofer Institute is intended to combat it in a patient-safe way.  Around 3.5 to 6.1 percent of the population suffer from this fear.  Together with partners, Fraunhofer researchers are developing a digital therapy system that will enable treatment in the home environment and provide those affected with a better sense of security. A demonstration of the system was on display during the meeting.
  • A Better-Looking CPAP Mask (Finally?) – ResMed displayed its minimal-contact full face CPAP mask, AirFit F30.  The system sits below the nasal bridge, preventing top-of-the-nose red marks and irritation, and reducing feelings of claustrophobia for some full face wearers. users reduce facial marks, wear glasses in bed and be closer to their partner.    The company also claims that the QuietAir vent included in the product is quieter than ambient noise in the bedroom.
  • Picturing Diagnostics Statistics – A system called Medicus provides a visual interface and translation tools to the often confusing diagnostic statistics.  Diagnostic data is generally one of the hardest types of health data to combine if they’re coming from different sources, due to the challenge of the different standards for clinical data structure, such as HL7 v2, HL7 v3, CDA, FHIR and the different coding standards for health data such as: LOINC, SNOMED, SNOMED-CT, UMLS.   Medicus converts numbers from one structure and provides insight into how to interpret that in other formats while, the company says, preserving as much of its crucial medical context as possible.
  • Know the Patient’s Weight as You Transfer Them – Knowing patient weight is essential for administering treatments and delivering correct care to the patient.  However, with immobile patients this is not easy, with the only solutions being bed weighing scales or hoist scales, both of which can be cumbersome and time consuming.  But often there is no time for a weigh in.  The Patient Transfer Scale aims to fix that – t is a transfer slide with in-built weighing scale, and means patients can be weighed during lateral transfer from trolley to bed, or bed to bed.   The Patient Transfer Scale, or PTS, can be used in the same way as a transfer board with a stop for 3-4 seconds to weigh in.
  • New HIV Rapid – Earlier detection of HIV is essential for survival from the disease, and there is high demand for better rapids.  Owen Mumford Group exhibited its Simplitude™ Pro, what the company claims is the world’s first professional use rapid diagnostic test with a built in safety lancet, blood collection unit, and test strip. The device has been designed to reduce pre-analytical errors and deliver a reliable result.  The Simplitude Pro, planned for 2019, is the result of a strategic partnership between Owen Mumford, a leading player in the medical device industry and Atomo Diagnostics, a product design and manufacturing company based in Australia.
  • Complete FDA-Approved Robot Exoskeleton – Richmond, CA-based Ekso Robotics demonstrated the EksoGT Robot Exoskeleton at the meeting.  The system is the first commercial robot exoskeleton to be approved for use by the FDA in cases of paralysis of one side of the body; usually caused by a stroke-induced brain lesion.
  • Connected Stethoscope – eKuore ONE’s exhibit featured their adjunct stethoscope device and software.  eKuore One allows objective tests using a traditional stethoscope.  The system connects to traditional stereoscopes and turns them into connected devices, that can obtain second opinions and allow for visualization and integration into telemedicine.  Kalorama Information reports on connected devices in the following telemedicine study: https://www.kaloramainformation.com/Telehealth-Patient-Monitoring-11076070
  • Innovative Ear Infection Diagnostic – OtoNexus Medical displayed their ultrasound MEMS transducer that can detect hard-to-diagnose middle-ear infections (Otitis Media) using a non-invasive technology. The capacitative micromachined ultrasound transducer (CUMT) system can determine if there is liquid or air in the ear and distinguish between diseases.   This is important not only for better outcome, but to reduce antibiotic prescription in unnecessary cases.
  • “Gamified” Neuromuscular Stimulation Device – Neuromuscular stimulation doesn’t work if the stimulation process is boring.  That’s the premise behind South Korean healthcare robotics startup Exosystems’s new product.  The firm unveiled its portable product, the exoRehab, a device that helps provide “Personalized Rehabilitation Guidance” for patients in need of neuromuscular rehab.  The exoRehab personalizes its exercises to the patient to make sure the routine is not boring and keeps the patient stimulated.  It allows users to execute rehab training exercises based on their own body data and monitor the health status of their affected area.  Most conventional rehab methods only provide firm, rigid ways to exercise and recover
  • Friendlier Adhesives for Wearables.  The focus on wearable devices and drug delivery systems suggests a need for better skin adhesives, and Dow Silicones Corporation demonstrated its MG7-1020 Soft Skin Adhesive at the meeting.  The company said the product delivers the highest adhesion in the company’s soft skin adhesives — all without the skin irritation and discomfort more commonly associated with the removal of acrylic adhesives.

Kalorama Information is the publisher of such titles as The Worldwide Market for In Vitro Diagnostics, 11th Edition, and The Global Market for Medical Devices, 8th Edition.  The firm will be noting and commenting on events throughout the meeting.   Already of interest are several proposed announcements, new products and displays:

You wake up with an angry stomach, but this time it’s got nothing to do with that questionable leftover poké dish you’d kept in the fridge for a week. No, there’s more to this, but is it enough to put everything on hold to call a doctor and potentially wait all day, missing work, just to find out it’s a minor bug? More importantly, can you really afford it? On the other hand, the notion of consulting internet-based health information services (those that most quickly come to mind will remain unnamed) is antiquated at best, and we have all heard tales of hypochondriacs using such sites to self-diagnose with, in this case, probably stomach cancer. Not only is doing so irresponsible, but it could lead to people engaging in unnecessary and potentially dangerous treatments. So what can you do?

Enter Babylon Health, a London-based firm whose mission is to give everyone across the globe access to affordable health care through an app that combines the expertise of experienced physicians, specialists, and therapists with a sophisticated AI system developed with the latest advances in deep-learning. The company asserts that their artificial intelligence is more than just a database, that it assesses known symptoms and risk factors to provide informed medical information. Babylon’s founder, Ali Parsa, says that the best way to realize his company’s goals is to reduce people’s need to see a doctor, and this technology is engineered to do just that.

In 2017, Babylon ran a trial with a London hospital, in which calls to the National Health Service’s advice line would be handled partly with the company’s AI system. For many less serious conditions, the patients’ needs can be met through self-treatment, and Parsa says that 40% of Babylon’s patients eventually stopped calling for appointments, realizing that they did not need them, three times the proportion of people speaking with human operators. Now available in part from Babylon is GP at Hand, a service in the UK and Rwanda (in which 20% of the adult population has registered) in which patients can consult with Babylon’s chatbot app or talk over video with a human doctor.

Founded in 2011 and based centrally in Berlin (with offices in New York, London, and Munich), Ada Health’s doctors and engineers spent six years developing an AI-based health care app as its primary goal, which is something that company CEO and co-founder Daniel Nathrath says competitors considered an afterthought. From the onset, Ada’s AI was developed to take all of the patient’s information, including established medical history, into consideration, not just symptoms and risk factors. Using machine learning and closed feedback loops, the system acts as a prescreening consultation or to provide a real physician with relevant information prior to a consult, saving time by reducing the need to ask the basic introductory questions. Co-founder and Chief Medical Officer Claire Novorol says that feedback has already proven the app successful in diagnosing both common and rare conditions, and will make further progress as it continues to be trained by real physicians to become a greater compendium of combined medical knowledge.

Just weeks ago, it was announced that Ada Health had launched its Global Health Initiative with partners Foundation Botnar and the Bill and Melinda Gates Foundation; in doing so, Ada will be offering its app in Romanian and Swahili, with the latter expanding its availability to over 100 million people in sub-Saharan Africa.

All this talk in recent years of the advent of artificial intelligence and robots has mostly involved the prospect of humans being replaced by such things, an apprehension that has existed for well over half a century and has given birth to the best (and, honestly, the worst) science fiction. But are we coming closer to science fiction becoming a reality?

Researchers at The Francis Crick Institute recently published a study that used data from over 80,000 patients to train an artificial intelligence to model and predict heart disease mortality, that ultimately proved to be more successful than a model created and used by human experts, being 80% and 70% successful, respectively. The AI-generated model uses 586 variables to assess potential patient outcomes, while the physician-developed model uses just 27, allowing the robotic cardiologist to consider things through its calculations—for instance, the number of home visits to a patient—that may not even cross a human’s mind.

Even Babylon Health has made claims recently that its AI system is as accurate in its diagnostic capabilities as a doctor. The company’s staff fed its chatbot with questions from the official exam for induction into the Royal College of General Practitioners (RCGP), a membership body for family doctors in the UK. The average score to pass in the last five years has been 72%, and Babylon’s chatbot scored 82%.

All that said, while the Crick Institute’s AI has been proven accurate thus far, more studies would need to be conducted and results would need to be replicated in order to claim that it is reliable. And the RCGP has stated that there are flaws in the methodology that Babylon used in challenging its AI system. So there is no need to form the Anti-Robot Resistance just yet.

A major part of the reason that AI looks to be so useful is that there is a worldwide shortage of medical staff—which will reach an estimated 18 million by 2030—particularly among those who specialize. AI would also be quite useful to fill in gaps and cover shortages, especially in regions where the number of clinicians per capita is relatively low, be they in rural regions, low-resource nations, or in remote communities where access may be limited or difficult. Indeed, a third of Ada’s users hail from such places in Africa, Asia, and the Indian subcontinent. Even in more well-off regions, slashed budgets, aging populations, and increases in chronic disease conditions among populations will still place greater strains on health ministries; artificial intelligence will be beneficial by reducing the workload of doctors who can then focus on patients with more pressing conditions. Ultimately, AI should be viewed as a tool rather than a replacement, and it is even possible that its adoption could lead to more jobs being created; people coming to the job market or preparing to change their places in it should train with AI to properly apply it as such.

Finally, according to a study out of MIT, computer scientists say that flesh-and-blood physicians have something that artificial intelligence lacks: gut feelings about a patient’s condition, which researchers have found to influence the number and types of tests doctors order for their patients. Their intuition is especially important in the early period of a patient’s treatment, when there is little data available to analyze in order to make a diagnosis. Researchers also found that how a doctor felt about the patient’s condition affected the number of tests ordered, that if the situation was less than sunny, more tests would be ordered, but a more positive outlook meant fewer tests. To boil it down, artificial intelligence really only serves to spout data and perform rote memorization, just on a much greater scale than we humans are capable of doing ourselves. What AI cannot do, at least not yet, is to think creatively and critically, especially in situations that have never been encountered—after all, how can a computer provide a solution for which is has no data? Martin Marshall, vice chair of the RCGP, stated that, “…[A]t the end of the day, computers are computers, and GPs are highly-trained medical professionals[…] the former may support, but will never replace, the latter.”

Mobasher Butt, Babylon’s medical director, says that that was never his company’s intent, that “[…] AI decisions are supported by real-life GPs to provide the care and emotional support that only humans are capable of.” So, physicians, sigh in relief. Your jobs are not in danger of anything but perhaps becoming a bit easier.

 

Authored by Julie Kirkwood, Kalorama Information Correspondent

Until surprisingly recently, the connections between laboratory instruments and laboratory computers were based on standards developed in the 1990s. For example, one of the standards, ASTM E1394 (later revised and renamed CLSI LIS2) dates back to 1997, the year before Google was invented, when dial-up modems were still used to connect to the internet and laboratory instruments were connected to computers by serial port cables.

This is a standard that laboratory instruments use to receive computerized orders and to collect and aggregate patient results.

“Seriously,” says Serge Jonnaert, president of the IVD Industry Connectivity Consortium. “I kid you not. And the majority of labs still use that standard today to send information from their instruments, albeit no longer over serial port. I mean, the instruments are now network connected, but it still very much uses an LIS1/LIS2 interface standard.”

The main problem with the old standards is that they do not standardize data, and that makes it complicated to set-up laboratory instruments. When a laboratory purchases a new instrument, it typically costs thousands of dollars to have an IT specialist make a custom connection between that instrument to the laboratory information system, or whatever computer system their institution uses.

As far back as 2005, a group of peers who worked in informatics for major vendors in the in vitro diagnostics (IVD) industry came together to work on a solution. They eventually formed a nonprofit organization, called the IVD Industry Connectivity Consortium (IICC), and they set out to rewrite the standards in a way that would promote easy connectivity. If all IVD instruments used a common communication protocol and referred to a common set of numerical codes for test names, sample types, and other useful information, clinical laboratories could easy connect any instrument from any vendor to any type of middleware or laboratory information system (LIS).

Getting Connectivity Standards Adopted in Clinical Laboratories Has Been an Uphill Climb.

In 2016, the consortium finally succeeded in publishing this new standard, called the Laboratory Analytical Workflow (LAW) Protocol, in collaboration with Integrating the Healthcare Enterprise (IHE). A year later, IICC published LIVD, a digital format that defines the digital publication of LOINC using vendor defined IVD tests associated with a set of predefined LOINC codes.

“Whereas before it would have cost anywhere between $6,000 to $15,000 to connect an instrument to an LIS, now it’s truly a plug and play solution,” Jonnaert says.

Most major IVD vendors, including Abbott, Roche, Siemens, and Beckman Coulter, are members of the consortium and have already adopted the both standards, Jonnaert says. The U.S. Food and Drug Administration supports the effort, and in June 2018 the agency issued a  guidance encouraging the use of common numerical codes for test-related data. The Clinical & Laboratory Standards Institute is in the process of recasting the LAW protocol, to be named the CLSI AUTO16 standard for next generation IVD instrument interfaces.

Yet getting these standards adopted in clinical laboratories has been an uphill climb.

For one thing, the major electronic health records vendors are lagging behind in adopting and promoting the new standards, Jonnaert says.

“Instead of taking an industry leadership role on this and saying, ‘Okay, let’s get ahead of this and roll it out,’ they’ve actually said, ‘Well, if our customers tell us to do it, we’ll do it,” Jonnaert says.

Custom connections between laboratory instruments and their computer systems are still a significant revenue stream for them.

So why aren’t customers asking their vendors to adopt the new standards?

Jonnaert believes that laboratory professionals haven’t gotten involved because they consider this an IT issue, and the IT specialists haven’t taken an interest because the laboratory tends to be a lower priority for health system IT departments, which are dealing with bigger issues such as revenue cycle management, avoiding hospital readmissions, and meaningful use.

Some LIS vendors have embraced the standards, though, including Orchard and Sunquest, Jonnaert says. And support from the FDA and the Office of the National Coordinator for Health Information Technology is another big step forward.

In the new guidance, the FDA makes a forceful argument for standardizing data among laboratory instruments and computer systems.

“Efforts to harmonize and standardize information captured and stored in electronic healthcare systems carry important implications for public health, including expediting access to patient diagnostic information for health care providers, reducing burdens on laboratories for connecting new diagnostic systems to Laboratory Information Systems (LIS), and facilitating the use of healthcare information for decision support tools, in addition to many more potential uses,” the guidance says.

The benefits of the new standard reach beyond cost savings for vendors and laboratories, Jonnaert says. When laboratory data is standardized across instruments and locations, the information can be combined and compared in new ways.

“It opens the door to have all the data flow through in a standardized format,” Jonnaert says. “… That’s when you can start looking at doing some major population analytics.”

Laboratory data from all over the United States could be probed to look for, say, a cross-correlation between a biomarker and a disease state. The test results from any laboratory in the country could be pulled together into a single dataset.

“Right now you would not be able to do that on a national level because every single data point from every single lab from every single instrument comes through differently,” Jonnaert says.

Now that the new standard is available, the consortium is encouraging clinical laboratories to ask their vendors about the IICC/IHE LAW profile and also LIVD, the digital format that standardizes predefined codes for test results.

“It’s like in football,” Jonnaert says. “We keep on moving the ball one line at a time and every time we have a little victory, we’re happy.”

In many ways, the IVD market of today does not resemble the market five years ago.  2018 appears to be the year where a number of trends that had been discussed began to gel.  With that in mind, Kalorama Information will be on hand for UBM’s BIOMedDevice Convention in San Jose, CA next month.   In vitro diagnostics represents a 65 billion-dollar market, according to Kalorama Information’s latest report on the worldwide diagnostic industry.  That makes it a large, competitive and growing market.  But the significance of in vitro diagnostics goes beyond the market numbers.  IVD really is significant because of its reach: testing reaches touches clinical lab services, hospital care provision, pharmaceuticals. These add up to a multi-trillion dollar “Influence Market” for IVD.

Among many trends that Kalorama will discuss at the meeting:

  • Direct-to-consumer testing was a scattered array of projects and small startups prior to 2018.  Now, it is a real factor in the business.  With both Lab Corp and Quest making direct to patient pitches, and 23 and Me’s FDA approval for its consumer-ordered BRCA test, there is an actual market for these products.
  • There are nearly 10,000 locations where a patient now can walk in and secure a healthcare visit with no appointment.
  • Novel biomarkers are being discovered.  The track record of PCT in sepsis treatment and and high-sensitivity troponin markers in detecting heart attacks has been evident from their migration on to large analyzer systems.  This year saw developments in tests for traumatic brain injury and Alzheimer’s Disease, including two FDA approvals for microRNA biomarkers for the latter disease.
  • Sequencing: Clinical systems were introduced and smaller footprint instruments have been developed.  Simplified (NGS in a Box) systems have made gains.   How sequencing will fit into clinical diagnostics is still being determined, but it is clear it will have some impact.

There are many factors causing an increase in the rise of diagnostic services to monitor health, which in turn is stoking the growth of the IVD market. Trends such as technological advancements, rising end-user awareness, and miniaturization is driving the demand for point-of-care products and have increased the access to diagnostic tests near patient site. But with growth comes new regulations and implementation dates put forth for medical device manufacturers active in Europe. Compliance deadlines for 2020 and 2022 are looming.

With this in mind, Kalorama announces that Publisher Bruce Carlson will speak at the BIOMedDevice convention in San Jose, CA, December 4-6th, 2018.  The keynote speech:

The IVD Market Opportunity: Fast-Growth Markets, New Products, Disruptive Trends ( https://bmsj18.mapyourshow.com/7_0/sessions/session-details.cfm?ScheduleID=11 ) will be held on December 5th.

Topics covered include:

  • Retail clinics, Direct-to-Consumer marketing, accelerated aging and trends driving new product development in the IVD space
  • Point-of-Care, digital capillary testing, wearable, and other products moving IVD diagnostics forward
  • Medicare Part B Cuts and New FDA Proposals
  • New European IVDR affecting 80% of IVD products – what you need to know
  • Market Statistics for In Vitro Diagnostics and Contract Manufacturing for In Vitro Diagnostics

It’s late January, 2018. It’s the centenary of the opening salvos of the “Spanish” Flu Pandemic, the unsung (and misnomered) villain of the later days of The Great War.  With cases on the rise right now, the 2017-’18 flu season has yet to reach its peak[1], surpassing that of the 2012-’13 season, and young people are being hit particularly hard. Let’s talk flu diagnostics.

(Especially, as Kalorama has just completed a study on molecular point-of-care systems, which is one of several technologies used for flu testing).

The typical way to diagnose an infection by the influenza virus in emergency facilities is with lateral flow immunochromatographic assays; they’re simple, they’re quick, and most importantly, they’re inexpensive. The problem with these tests (also called rapid influenza diagnostic tests, or RIDTs), however, is that they aren’t good. Their sensitivity has been deemed “sub-optimal” by the Centers for Disease Control: in a letter to the New England Journal of Medicine[2], one of their studies evaluated one such test at 51%, and cited in the letter was a study[3] that found another RIDT’s sensitivity rate to be a staggering 27%. While the latter figure seems to be an extreme example, a meta-analysis[4] conducted in 2012 found that RIDTs had, on average, sensitivities of 62.3%.

The gold standard for diagnostics is real-time PCR, but this has a few things going against it. Actually, it’s the diametric opposite of RIDTs: PCR is complex, requiring a lot of preparation and technical knowledge to operate; PCR is time-consuming, because of the preparation and the complexity of its mechanism; PCR is also expensive because of its complexity, but also in terms of patient isolation and management, because of the time it takes to get results.

So for a few years now, big biotech firms have been working on better solutions, employing nucleic acid amplification techniques that make PCR so accurate and engineering them into relatively tiny and simple packages, and as it turns out, they really are much better than RIDTs, and much faster and simpler than PCR. The devices are cartridge-based, requiring minimal input from the user; they turn results out in well under an hour, with most in the 15-30 minute range.

Alere’s Influenza A&B assay for its isothermal i platform, was among the first of its kind to be given a CLIA waiver, allowing the test to be performed at the point of care, where RIDTs are the usual go-to diagnostic solution. The i uses a technique called Nicking Enzyme Amplification Reaction (NEAR), which depends on, as the name implies, nicking enzyme to replicate the nucleic acid at a constant temperature range of 55-59°C. thus eliminating the need for the thermal cycler necessary in PCR. The device is therefore less complex, and the process consumes less time and energy as there is no need to denature DNA into single strands. The Influenza A&B assay produces results from nasal swab in approximately 15 minutes, and Alere reports sensitivities of 97.9% and 92.5% for influenza A (IFV-A) and influenza B (IFV-B), respectively, compared to cell culture.[5]

Cepheid’s Xpert Xpress Flu cartridge, for the GeneXpert platform, was granted a CLIA waiver just weeks ago, on 9 January. Cepheid also produces a joint flu/RSV Xpert assay, on which the studies reviewed for this article focus. The assay, Xpert Xpress Flu/RSV, has been CLIA-waived since 2015, and requires samples to be collected via nasopharyngeal swab (the newer IFV-only is indicated for sample collection with a less invasive nasal swab). Cepheid reports 98.2% and 100% positive agreement for IFV-A and IFV-B, respectively, between the Xpert Xpress Flu/RSV and conventional PCR; positive results are reported in twenty minutes.[6] The GeneXpert system is based on more conventional real-time PCR methodology than the aforementioned isothermal Alere i, but uses solid state heating and forced-air cooling, operating at a temperature range of 50-95°C.[7] There are currently four variants of the system, each named for the number of cartridges that can be simultaneously analyzed – I, II, IV, and XVI – and the Omni, a fully portable system that can operate solely on battery power, is anticipated for a second quarter 2018 launch.

Last, but not least, is Roche’s cobas Liat, which was developed from IQuum’s Lab-in-a-Tube analyzer. Like the GeneXpert, the cobas Liat operates on the more conventional real-time PCR methodology, and while the reagents of the system’s assays are in a compartmentalized tube, it operates on the same principle as the cartridge-based systems, in that the assays are fully self-contained and require minimal user interaction. The cobas Influenza A/B assay was granted a CLIA waiver in September 2015; results from nasopharyngeal swabs are reported in twenty minutes or less. Roche reports 100% sensitivity for both IFV-A and -B, and 96.8% and 94.1% specificity, respectively.[8]

Clinical researchers have conducted evaluations of each of these instruments, and in the literature reviewed for this entry, there is consensus that the devices compare favorably with conventional PCR methodology and are much more reliable than RIDTs.

  • Using PCR as the sole reference of comparison, Cepheid’s Xpert Flu/RSV test was found to have an overall sensitivity of 97.8% (A: 97.0%, B: 100%) and 100% specificity across the board.[9] One 2016 study compared the Xpert Flu/RSV to bioMérieux’s BioFire FilmArray, with an overall positive agreement of 97.3% (100% and 92.3% for IFV-A and IFV-B, respectively),[10] with the investigators concluding that the Xpert Xpress would be useful for diagnosing immunocompetent patients during peak flu season, while the FilmArray, being a more extensive multiplex panel diagnostic, should be designated for sicker patients and those coming in during decreased flu prevalence.

Concern over decreasing test sensitivity due to viral genetic drift in some commercially available flu diagnostics was the basis of a 2016 study, which looked at the Xpert Flu/RSV in addition to a multiplex PCR test that had been reformulated in the wake of the 2014-’15 flu season to be more sensitive. Cepheid’s test was found to have 100% sensitivity and 94.3% specificity for IFV when compared to PCR, though no distinction was made between A and B types.[11]

Finally, a 2017 review compared the Xpert Flu/RSV test to the performance of the ARIES Flu A/B & RSV test by Luminex; the BioFire FilmArray was the reference test used in the comparison.[12] Both assays were found to have 100% sensitivity to both A and B virus types; Cepheid’s test fell slightly short of the ARIES in test specificity, with 95.4%for IFV-A. However, the report’s authors did state that the Xpert has an edge over the ARIES for its substantially quicker turnaround time (20min vs two hours), though both devices require the same hands-on time and are equally easy to use.

  • A direct comparison in 2016 of Roche’s cobas Liat and Alere’s i platforms (using the BioFire FilmArray for reference) found the cobas test to be 100% sensitive and specific across the board in detecting both influenza types.[13] Alere had a relatively poor showing, with 71.3% sensitivity for IFV-A; however, this is likely attributed to low viral load due to samples being collected late in patients’ illnesses. The researchers found the cobas Liat to be a robust platform with performance that favors comparably with that of the FilmArray, though it should be noted that bioMérieux’s multiplex-capable assay detected some comorbidities with respiratory syncytial virus (RSV) and other respiratory pathogens that neither of the other platforms would have picked up. This is significant, as RSV could potentially impact treatment and management of influenza infection.

Another 2016 study also found the cobas Flu A/B test to have high sensitivity and specificity specs. The test detected only two false negatives, both for IFV-A, which were caught by the Cepheid Xpert Flu assay. The errors were likely due to low viral load resulting from the freeze-thaw cycle in sample preparation. The investigators noted two shortcomings of the platform and test: one, only a single test can be conducted at a time, and two, the test is not capable of IFV-A subtyping, unable to distinguish between the various hemagglutinin and neuraminidase proteins found on the viruses’ surfaces.[14]

A larger-scale (n > 1600), multicenter evaluation conducted in 2017[15] also regarded the cobas Flu A/B highly, with >99% sensitivity for both virus types, with the researchers’ summary basically being that the use of POC devices can be a potential boon for patient care as improvement in turnaround times provide a great potential to reduce time to treatment and to reduce length of stay, which will in turn reduce costs to care facilities.

  • A 2014 multicenter evaluation (n > 500) of the Alere i Influenza A&B test analyzed direct nasal swab samples taken from seven sites during the 2012-’13 flu season, compared against R-mix shell vial viral culture.[16] After discrepancy analysis, the i Influenza A&B was reported to have 99.3% and 97.6% sensitivities and 98.1% and 100% specificities for influenza types A and B, respectively.

In 2015, performance of the i was tested using Cepheid’s flu assay for reference,[17] but the results were not favorable to Alere’s test: the i had 80% sensitivity compared to the Xpert for IFV-A, and it fared worse with IFV-B, resulting with 33.3% compared to Xpert and 46.4% compared to conventional PCR. The author of the article said that the i is reasonably sensitive, but that low-viral load specimens contributed to poor detection, especially in the IFV-B test, due possibly to an additional freeze-thaw cycle to which the samples were exposed, resulting in degraded viral DNA, and that it should also be noted that the RIDTs with which these assays are ultimately meant to compete would have returned much worse performance as they are typically reported to show sensitivities in the 10-80% themselves.

An evaluation conducted in 2016 returned better results (93.8%/100% sensitivity for types A and B, respectively)[18] and was more positive in its review, adding that previous studies that have reported poor showings by the assay and others of its type were likely to have done so due to a lack of pediatric samples, which are well known to have higher viral loads than adult samples, and also because many of these studies were undertaken using previously frozen samples, which will have some degree of nucleic acid decay. Sensitivities should be considerably better than what is reported in these studies as care facilities will be using fresh patient samples.

In 2017 a cost analysis was conducted that compared the cost of patient isolation and treatment across multiple treatment centers in the United Kingdom using the Alere i platform and conventional PCR.[19] While sensitivity for the i averaged 77% for both viral types across the four centers, the speed of the results made the real difference; PCR results average an additional 1.1 days over the POC device without proper diagnosis (viz. false positive or negative), meaning 1.1 extra days of isolation and treatment for patients misdiagnosed as being infected, or 1.1 extra days without management for those misdiagnosed as being clear of infection. All told, the Alere i was determined to save £43,000 per 1,000 patients compared to PCR; if assuming 100% accuracy in patient isolation, that figure potentially increases to £261,600. The relatively low sensitivity reflected in the results appeared to be due to human error, involving the use of throat swabs and, to some extent, the storage and handling of reagents.

It can be concluded that molecular POC solutions have great potential over the more commonly used RIDTs, as they are far superior in sensitivity, on par with conventional PCR but with all the speed. There do seem to be caveats, however. These devices are touted to be so simple to use that they require no laboratory expertise. But there appears to be an ongoing theme in these studies that the devices still do require a degree of care to be taken when operating them, as handling reagents and samples a certain way can indeed have a negative impact on an assay’s efficacy, which was especially apparent with the Alere i flu test. Of course, some of this can be mitigated by using fresh patient specimens, which will most often be the case, but it still appears that there yet needs to be a bit of education in protocol, as fool-proof as the tests are supposed to be.

The other issue is cost effectiveness. Frederick Nolte, director of clinical laboratories at the Medical University of South Carolina, and the author of the 2016 report on the direct comparison between Alere’s and Roche’s offerings, said in a recent interview[20] that POC tests are “essentially one hundred percent sensitive” compared to the 80% sensitivity of lateral flow test, but they “[come] at a cost that is four times as much.” There was a cost-benefit study with the Alere i published just last year, but it was in a comparison against conventional PCR, not against the RIDTs that the i is supposed to replace. With the time it takes to prepare and operate a PCR run, it’s almost a given that these tests are going to be more cost effective, this is the wrong contest to hold. Because while RIDTs are not quite the gold standard that PCR is, they are so commonly used because they are cheap, fast, and good enough. These molecular tests are undoubtedly far better than their immunochromatographic counterparts, but the question is, are they better enough? Comparisons against lateral flow tests is where the cost analyses need to be focused. Until then, clinical facilities may not be convinced, even if the science guys are.

[1] United States Centers for Disease Control and Prevention (CDC). 2017-2018 Influenza Season Week 2 ending January 13, 2018.Updated 19 January 2018.

[2] Faix DJ, Sherman SS, Waterman SH. (2009) Rapid-Test Sensitivity for Novel Swine-Origin Influenza A (H1N1) Virus in Humans. New England Journal of Medicine; 361, 728-9. DOI: 10.1056/NEJMc0904264

[3] Uyeki TM, Ramakrishna P, Vukotich C, Stebbins S, Rinaldo CR, Ferng Y, Morse SS, Larson EL, Aiello AE, Davis B, and Monto AS. (2009) Low Sensitivity of Rapid Diagnostic Test for Influenza. Clinical Infectious Diseases; 48(9), e89-e92. DOI: 10.1086/597828

[4] Chartand C, Leeflang MM, Minion J, Brewer T, and Pai M. (2012) Accuracy of Rapid Influenza Diagnostic Tests: A Meta-analysis. Annals of Internal Medicine; 156(7), 500-11. DOI: 10.7326/0003-4819-154-7-201204030-00403

[5]Alere i Influenza A & B product page

[6]Xpert Xpress Flu/RSV datasheet

[7]GeneXpert product brochure

[8]Roche cobas Liat product page

[9] Salez N, Nougairede A, Ninove L, Zandotti C, de Lamballerie X, and Charrel RN. (2015) Prospective and retrospective evaluation of the Cepheid Xpert® Flu/RSV XC assay for rapid detection of influenza A, influenza B, and respiratory syncytial virus. Diagnostic Microbiology and Infectious Disease; 81(4), 256-8. DOI: 10.1016/j.diagmicrobio.2015.01.008

[10] Wahrenbrock MG, Matushek S, Boonlayangoor S, Tesic V, Beavis KG, and Charnot-Katsikas A. (2016) Comparison of Cepheid Xpert Flu/RSV XC and BioFire FilmArray for Detection of Influenza A, Influenza B, and Respiratory Syncytial Virus. Journal of Clinical Microbiology; 54(7), 1902-3. DOI: 10.1128/JCM.00084-16

[11] Huzly D, Korn K, Bierbaum S, Eberle B, Falcone V, Knöll A, Steininger P, and Panning M. (2016) Influenza A virus drift variants reduced the detection sensitivity of a commercial multiplex nucleic acid amplification assay in the season 2014/15. Archives of Virology; 161(9), 2417-23. DOI: 10.1007/s00705-016-2930-8

[12] McMullen P, Boonlayangoor S, Charnot-Katsikas A, Beavis KG, and Tesic V. (2017) The performance of Luminex ARIES® Flu A/B & RSV and Cepheid Xpert® Flu/RSV XC for the detection of influenza A, influenza B, and respiratory syncytial virus in prospective patient samples. Journal of Clinical Virology; 95, 84-5. DOI: 10.1016/j.jcv2017.08.018

[13] Nolte FS, Gauld L, and Barrett SB. (2016) Direct Comparison of Alere i and cobas Liat Influenza A and B Tests for Rapid Detection of Influenza Virus Infection. Journal of Clinical Microbiology; 54(11), 2763-6. DOI: 10.1128/JCM.01586-16.Editor

[14] Melchers WJG, Kuijpers J, Jackson Sickler J, and Rahamat-Langendoen J. (2016) Lab-in-a-tube: Real-time molecular point-of-care diagnostics for influenza A and B using the cobas® Liat® system. Journal of Medical Virology; 89, 1382-6. DOIL 10.1002/jmv.24796

[15] Gibson J, Schecter-Perkins EM, Mitchell P, Mace S, Tian Y, Williams K, Luo R, and Yen-Lieberman B. (2017) Multi-center evaluation of the cobas® Liat® Influenza A/B & RSV assay for rapid point-of-care diagnosis. Journal of Clinical Virology; 95, 5-9. DOI: 10.1016/j.jcv.2017.08.004

[16] Bell J, Bonner A, Cohen DC, Birkhahn R, Yogev R, Triner W, Cohen J, Palavecino E, and Selvarangan R. (2014) Multicenter clinical evaluation of the Alere™ i Influenza A&B isothermal nucleic acid amplification test. Journal of Clinical Virology; 61, 81-6. DOI: 10.1016/j.jcv.2015.06.001

[17] Jokela P, Vuorinen T, Waris M, and Manninen R. (2015) Performance of the Alere i influenza A&B assay and mariPOC test for the rapid detection of influenza A and B viruses. Journal of Clinical Virology; 70, 72-6. DOI: 10.1016/j.jcv.2015.07.294

[18] Nguyen Van JC, Caméléna F, Dahoun M, Pilmis B, Mizrahi A, Lourtet J, Behillil S, Enouf V, and Le Monnier A. (2016) Prospective evaluation of the Alere i Influenza A&B nucleic acid amplification versus XPert Flu/RSV. Diagnostic Microbiology and Infectious Disease; 85, 19-22. DOI: 10.1016/j.diagmicrobio.2015.11.012

[19] Davis S, Allen AJ, O’Leary R, Power M, Price DA, Simpson AJ, Tunbridge A, Vale L, Whiteside M, Evans C, and Raza M. (2017) Diagnostic accuracy and cost analysis of the Alere i Influenza A&B near-patient test using throat swabs. Journal of Hospital Infection; 97(3), 301-9. DOI: 10.1016/j.jhin.2017.05.017

[20] Johnson M. “Cepheid’s CLIA-Waived Multi-Module System Ups Competition in POC MDx; Barriers to Uptake Linger.” GenomeWeb. Published online 11 January 2018.