Urgent care locations have grown over the past decade, Kalorama estimates the urgent care locations in the United States to be 9,900, growing from nearly 7,000 in 2013.  That’s spectacular growth, driven by a need for more healthcare services, improved insured populations and resistance to physician office waiting times.  Because of these undisputable positives, it’s common to see the urgent care industry presented only with rose-colored glasses.  Thus it should be stated that market growth is not without limits, in fact, a report from Kalorama Information suggests the “period of extensive location growth” for these centers may have passed.  This is according to a recent report U.S. Urgent Care Center Market: https://kaloramainformation.com/product/the-u-s-market-for-urgent-care-centers/ 

What distinguishes urgent care centers is that they are a walk in clinic offering extended hour access for acute illness and injury care that is either beyond the scope or availability of the typical primary care practice but offer less services than an emergency room would.   Estimates of locations vary as there are varying definitions of what an urgent care center is.

Growth cannot be without limits.  In fact, a report from Kalorama Information suggests  the “period of extensive location growth” for these centers may have passed.

The urgent care business model involves providing a full range of services of nonemergency acute care. UCCs differ from traditional physicians’ offices with procedure rooms for lacerations and fractures, a radiology department for x-ray services, and a laboratory.  There is a need for these locations, but the industry will not be a “boom mode” forever.  There are limiters to growth as well as drivers, and there is increasing visibility on those limiters.   The fastest growth, Kalorama estimates, happened in the early part of this decade, between 2011 and 2017.

The Beginnings of Market Crowding

“There are certainly areas of the country where an urgent care center has popped up on almost every intersection,” says the Journal of Urgent Care in a recent article.  Indeed, there is a growth trend but also visible limits to urgent care center growth. There are enough U.S. potential patients for each urgent care to have patient population of 30,000, Kalorama estimates,  where many industry experts suggest a 50,000 patient area is optimal for a successful urgent care practice.  This will be a limiter on the growth of urgent care center locations. It might be said that the current urgent care industry is satisfactory for meeting the needs of the U.S. population, but Kalorama does believe that there’s room to grow in rural areas and for more efficient operators to expand.  No market operates at such a perfected level of supply and demand and, in some markets, say with a greater income level or where hospitals have closed, urgent care has worked beyond these estimates.

“In Charleston, SC, for example, there are over 45 urgent care centers serving a population of 127,000. There are more than 120 urgent care centers serving the 1.6 million people of Phoenix, AZ. This begs the question: are markets too saturated? ”  – The Journal of Urgent Care

This trend has been seen with bank branches – explosive growth followed by retrenchment.  Between 2010 and 2019, the number of full-service bank branches fell from almost 95,000 to just over 83,000, according to a Quartz analysis of data from the Federal Deposit Insurance Corp. (FDIC). That is a loss of 12%.

The fastest source of pure growth for urgent care locations will be in rural areas lacking urgent care, rather than in urban areas. In urban areas, clinic growth by specific chains or successful upstarts will tend to come at the expense of another chain.

Furthermore, patient traffic is often seasonal, being higher in urban areas and in winter months. Such patient droughts favor larger operators who can keep afloat during a slow season to await a busier one.

Variance in Quality and Performance

As we’ve indicated, some of the growth in urgent cares is coming from centers located nearby an existing urgent care.  Even if both centers survive, metrics will drop in one or both.   In the next five years, those competition battles will play out across the nation.  Some urgent care locations and many urgent care chains are highly successful.  But not all are.    Patient volumes, revenue per patient, total clinic revenue, services offered, as well as testing capabilities and pharmacy services will all vary between urgent care centers.  As to who will win out, utilization of the best techniques will go a long way to determine which center in a market wins out.

Qualities of a High-Growth Urgent Care Center

Not on this list, but important, is the role of urgent care consultants.  Guidance from urgent care consultants, physicians with previous experience in urgent care or a national chain is a likely indicator of performance.

What does this variance in performance has to do with growth?  Simply said, it means not all centers will be here in a few years.  This will be a limiter on the growth of locations in the market. An exact estimate of successful and poor performing urgent care centers is difficult. It is possible that at least one-fourth of U.S. urgent care locations are operating at poor performance levels with under-average patient visits and per-clinic revenues.  The competition could eliminate poor performers.

A Senior Problem?

Urgent care may have an issue with seniors, and if that is the case, it is a trend the industry will need to reckon with for future growth potential.  A PNC Healthcare consumer survey found that 85 percent of seniors choose to see primary care physicians first. Only 11 percent of that population goes first to an urgent care center. A report by FAIR Health, a nonprofit that studies insurance claims, found that 60% of patient visits come from those 50 years old or younger.

Currently, Urgent care demographics lean towards younger and middle-aged customers, who to some degree are escaping physicians that older patients prefer.   This isn’t to say that education programs and outreach couldn’t change this current trend, but so far urgent care is an option to avoid clogged waiting rooms and utilized by young and middle-aged, usually working persons and their children.

A report by FAIR Health found that 60% of patient visits come from those 50 years old or younger.

Why is this an issue? Care for seniors is where the largest dollars in healthcare are. Seniors are the growth area of healthcare spending. Urgent care centers will need to compete for that aging democratic to capture greater dollars per patient and accelerate growth to the most optimistic projections.  This trend is troubling for the long term growth of urgent care centers, since spending is more likely to come from senior care than any other group.  For instance, Information from the Department of Health and Human Services indicates that seniors spend $11,000 per year on healthcare vs. $1,900-7,000 from those under 65.

Competition from Retail Clinics and Other Venues

Just as urgent cares could fact their growing pain era, there are new forms of competition.  Starting with retail clinics, but also from patient-friendly policies at doctor’s offices that can accommodate off-business hours.   As for retail clinics, there are at least 2,000 locations across the U.S., mostly at drug stores and each one pulls to a degree from existing or potential urgent care.  Some confuse these in-store health service locations, usually staffed by a nurse practitioner with urgent cares but they are not, they are competition, taking some of the high-volume visits away from urgent care.   For retail clinics, according to Kalorama’s reporting on that industry –  Total revenues are expected to continue to rise, driven by growth of each of the key metrics used to derive these estimates (patients treated, treatment fees, as well as clinic locations). Additionally, while the first clinics priced services extremely competitively to build business, as the clinics become more accepted, prices have gradually risen.

Growth in Retail Clinics

Although in most cases, this price increase will be smaller than the double-digit annual increases of healthcare service products and prices offered by other providers, it will nonetheless be necessary as retail clinics increasingly optimize their business models to maximize profitability and keep pace with ongoing increases in their own operating costs. For instance, the salaries for nurse practitioners continue to rise as demand for their services grows.

On the Bright Side…

Of course there are positives for urgent care:  Growth is fueled by the need for alternatives for patients and healthcare providers. For patients, traditional physician office hours and crowded waiting rooms are not meeting needs. The time it takes to schedule a new patient physician appointment in 15 major metropolitan areas has increased by 30 percent since 2014, according to a new survey conducted by Merritt Hawkins, a national physician search firm and a company of AMN Healthcare.

The result is confirmed by other studies.  The supply of doctors is also limited and the U.S. is feeling the pinch. Across the U.S., shortages of both general practice and specialist physicians are resulting in delays to treatment and long waiting times.  And COVID-19 vaccines will be a likely boon for urgent care being front-line, accessible and able to serve those:

Kalorama Information’s Report: The Market for U.S. Urgent Care Centers

Kalorama Information has a detailed report on urgent care center markets. The report is available at: https://kaloramainformation.com/product/the-u-s-market-for-urgent-care-centers/

Siemens Healthineers yesterday announced its SARS-CoV-2 IgG Antibody Test (sCOVG)1 has proven to measure neutralizing antibodies and has achieved CE Mark. The test is an enhanced version of the assay which became available globally this summer, including in the U.S. It demonstrates the ability to detect neutralizing antibodies and reports quantitative results measuring the amount of neutralizing antibodies present in a patient’s blood sample. The company has submitted an application to FDA under Emergency Use Authorization.

To measure a vaccine’s effectiveness, it is critical to identify both the presence of these neutralizing antibodies as well as quantitatively assess the likely level needed to protect against future encounters with the virus.

Neutralizing antibodies are critical in the fight against COVID-19 because they defend cells from infection by the virus. A virus typically produces an immune response of many antibodies that act as an army to help fight off the virus; however, only a small subset of those antibodies are capable of neutralization—blocking the virus from infecting additional cells. Those neutralizing antibodies develop either in response to natural infection or to vaccination, then subsequently bind to the virus and block infection. To measure a vaccine’s effectiveness, it is critical to identify both the presence of these neutralizing antibodies as well as quantitatively assess the likely level needed to protect against future encounters with the virus.   Siemens Healthineers says its antibody test will make learning this information possible as vaccines are rolled out and exposure to COVID-19 is tested against immunization and the level of immunity a vaccine provides.

The Siemens Healthineers said its SARS-CoV-2 IgG antibody tests are available on one of the largest installed bases of automated immunoassay analyzers worldwide, and the largest in the U.S. This includes the Atellica® Solution and ADVIA Centaur® XP and XPT families of analyzers and the Dimension Vista® and Dimension® EXL™ systems.

Kalorama Information has recently produced a report on COVID-19 testing.  The report is available at: https://kaloramainformation.com/product/covid-19-update-clinical-testing-telehealth-vaccines-and-other-markets/

Surprising effectiveness levels for COVID-19 vaccine candidates have been reported in the news lately, with Pfizer and Moderna releasing company data.   This rightly gives many hope, and also may lead to a question as to whether the PCR and immunoassay testing for the disease we are seeing in 2020 will continue much longer.  It may be natural to suspect that if a vaccine is available, there will be less cases thus less reasons to test. But this isn’t normally the interplay between vaccines and diseases.

In its COVID-19 update report, Kalorama Information estimated that test volume was up in labs and among IVD vendors, and new technologies are becoming available. The firm, a sister company to LabPulse.com, projects a $10.5 billion market for COVID-19-related tests. This is an increase of over $1 billion dollars from the firm’s August update with much of the increase based on the production and usage of antigen tests.

It is possible a vaccine solution will be developed, and it may be widely funded and distributed. Many candidates from major pharmaceuticals are in advanced phases.  Unless the disease “goes away” or is or heading there, the need for testing remains. Patients will present with symptoms, and they will need testing.  We’d also note the following:

  • Despite the presence of one of the most widely-used adult vaccines, hundreds of millions are earned by IVD companies selling flu tests.  Kalorama details this market each year in its global IVD market report.
  • This question of vaccines eliminating testing was raised with cervical cancer vaccines in relation to histology stains and HPV testing, which has only grown since the launch of Gardasil and other vaccines.
  • Vaccine use will not be universal: a recent online survey of adults residing in the U.S. found that close to 70% of those surveyed would accept a COVID-19 vaccine if one were widely available. Results of the study were published in the journal Vaccine on August 20. Nor is the problem unique to the US: German daily Süddeutsche Zeitung newspaper reported just over 60% of people in Germany would be willing to get vaccinated against COVID-19.
  • As Kalorama analyst Justin Saeks indicates “It is also possible that as the case with many novel viruses, the virus passes through the population, on a very large scale or there may be mutations. So far, journal literature is leading the other direction, that mutations are not as likely because of error correction systems in the viral DNA.”  yet the point remains -for market modelers and diagnostic industry watchers, it is still possible that COVID-19 might form strains and variants or co-infect with RSV and influenza in typical ways.
  • Antibody tests have been developed and are in a sense ready and waiting.  Labs will likely see higher demand for antibody tests after a vaccine is available to test effectiveness post-vaccination and to test for how long immunity lasts.
  • Patients presenting with symptoms will still need testing, at minimum COVID-19 remains a major testing application for 2021 and likely into 2022.
  • Combination tests such as those offered by Quidel, Quest, Lab Corp, Cepheid and other makers group  COVID-19 among other tests.  This will be useful to rule-out COVID-19 even after a period of wide vaccine usage.  The ability to run COVID-19 as a panel as opposed to a single test will facilitate more testing.

It is fair to say that a a vaccine may reduce the great expansion of testing, especially testing that extends to asymptomatic populations.   Reopening plans in the United States and developed companies will drive markets, and that create additional unknowns beyond the medical concerns.  Right now though, all indications are in the opposite direction, that broad testing is gaining popularity.    This is facilitated by rapid antigen tests, most of which are performed at the point of care, detect viral particles rather than antibodies in the patient.  They are seeing usage, though perhaps not to the level advocated by some proponents.  In some models, everyone would be tested or every school student or worker.

One enterprising plan was recently detailed in The Atlantic Monthly, based on Harvard epidemiology professor Michael Mina (https://www.theatlantic.com/health/archive/2020/08/how-to-test-every-american-for-covid-19-every-day/615217/) The plan involves extensive use of low cost/ high volume rapid tests in schools and workplaces. Test in this scenario would be used in great numbers and performed daily.

Likely a more moderate practice continues – some schools, some workplaces engage in this kind of testing, with industry-based and regional variances.

The attractiveness is seen in the South Korea example.  The nation is a different governmental system than the United States, but also a model for a testing protocol that would involve test volume increases. A new study indicates that point-of-care testing played an important role in reducing the spread of SARS-CoV-2 there compared to the U.S., which has experienced 47 times the number of cases and almost 80 times the number of deaths. South Korea’s response to the COVID-19 pandemic has been widely lauded — and is becoming heavily studied.

If vaccines do provide some decline in the overwhelming demand for testing, perhaps the laboratory industry could use it.  Even in the fall of 2020, there are capacity limitations, questions about testing accuracy, and challenges with sample collection. But creative solutions have been emerging at labs to help ease the load during a difficult time.

 

 

In 2020, the global market for preventive vaccines is valued at $37.4 billion, up overall from $30.7 billion in 2015.  The finding was made in Kalorama Information’s report, Vaccines 2020 (https://kaloramainformation.com/product/vaccines-2020-world-market-analysis-players-trends/).  Strong continued growth in the global vaccines market is expected through 2025, specifically:

  •  Growth at high double-digit rates.
  •  Sales of adult vaccines are expected to increase revenues at a faster pace than pediatric vaccines.
  • The United States comprises the single largest market for vaccines

More details are available in Kalorama’s report, including regional breakouts, disease-based market breakouts and forecasts, trends and other information.  COVID-19 vaccines are not part of this market number, though Kalorama does forecast these in its report.

A mainstay of preventative medicine for over 70 years, a vaccine is a biological preparation used to trigger an immune response to a selected disease. The term derives from Edward Jenner’s use of cowpox (“vacca” means cow in Latin), which, when administered to humans, protected them against smallpox. Vaccines can be either prophylactic or therapeutic.

“Despite a small decline between 2019 and 2020 due to COVID-19 and lockdowns, the vaccine market has grown seven billion dollars in the last five years.”

Because of the large number of deadly diseases that have been virtually eliminated through the proliferation of effective vaccines, vaccination is generally viewed as one of the greatest public health achievements during the 20th century. As a result of widespread public vaccination, vaccine-preventable diseases and their resulting deaths are now rare in the developed nations and declining worldwide. Immunizations have eradicated smallpox; eliminated poliomyelitis in the Americas; and controlled measles, rubella, tetanus, diphtheria, Haemophilus influenzae type b, and other infectious diseases.

However, risks are associated with all immunobiologics. No vaccine is completely safe or 100% effective. Vaccination risks range from common, minor, and local adverse effects to rare, severe, and life-threatening conditions. For example, some autoimmune diseases like acute disseminated encephalomyelitis, Guillain-Barré syndrome, transverse myelitis and multiple sclerosis are known to be connected to vaccines. In addition, some studies have linked a significant rise in autism to certain vaccines, although there is no widespread agreement on this. Thus, recommendations for immunization practices balance scientific evidence of benefits for each person and to society against the potential costs and risks of vaccination programs. These risks, however, have led to a rising number of individuals declining vaccination for themselves and their children, which in turn is believed to have contributed to recent increases in several serious, highly infectious conditions including mumps.

The European market is presently the second largest global vaccine market, with nearly twenty percent of the market.    S

In 2020, the global market for human preventive vaccines experienced mixed performance in 2020 due to the impact of COVID-19. Sales overall declined from $38.4 billion in 2019 to $37.4 billion in 2020.

Despite the overall decreased market performance, in 2020, the report said some segments reported increases, including:
• Influenza vaccines
• Rotavirus vaccines
• Shingles vaccines

Through 2025, growth will be fueled by favorable demographics (population growth, rising life expectancy), continued new product introductions, indication expansions for some products and rising usage, particularly in India and China. However, mitigating against growth will be continuing concerns about vaccine safety and refusal to immunize. This report contains an expanded section on this topic.

In its COVID-19 Update report, Kalorama Information said that volume was up in labs and among IVD vendors, new technologies are available.  Kalorama projects a 10.5 billion-dollar market for COVID-19.  This is a 1 billion dollar increase from previous estimates.

For most aspects of the diagnostic testing process, there has still been a learning curve for all involved. Even in the fall of 2020, there are capacity limitations, questions about testing accuracy, and challenges with sample collection. But creative solutions have been emerging at labs to help ease the load during a difficult time.  With over a million deaths worldwide, the COVID-19 crisis has continued to unfold with great challenges for the healthcare system and its suppliers.

Although a sensitivity of roughly 80% seems striking as a low number, in fact the negative predictive value can still be sufficient if the disease prevalence is appropriately matched.

Rapid antigen tests are one of the factors driving growth; these tests can offer some major benefits in the effort to control the SARS-CoV-2 pandemic. The decision to apply antigen tests in certain situation as opposed to others is complicated and is still being completely sorted out. The decision to apply antigen testing depends on variables including:

  • Sensitivity and specificity of the test
  • Prevalence/ outbreak of COVID-19 in the given population
  • Remote location, availability of laboratories/ hospitals
  • Turnaround time of the test
  • Cost of the test
  • Ability to perform serial testing

The momentum of cases and tests, since our Kalorama’s COVID-19 Update in May has not slowed, sadly.  There are over 45 million cases worldwide; 9 million of them in the United States. The trend is troubling as well, and there are fears of increases as the U.S. influenza season has arrived. (perhaps mitigated, perhaps not by reports of a milder flu season based on the experience in the southern hemisphere).

The scarcity of various diagnostic test related products during the COVID-19 pandemic has further driven home the reality that different testing methods are best allocated for different situations. While antigen tests have been criticized for the lower performance characteristics compared to antibody and molecular tests, these metrics are not always the most significant. Antigen tests often can have sensitivity lower than 85% while the specificity needs to be fairly high, in the range of 98% or higher.   Although a sensitivity of roughly 80% seems striking as a low number, in fact the negative predictive value can still be sufficient if the disease prevalence is appropriately matched.

Marketed Tests

Marketed tests include:

  • Abbott Laboratories -BinaxNow COVID-19 Ag Card & Navica app
  • Access Bio -CareStart COVID-19 Antigen
  • BD-BD Veritor System for Rapid Detection of SARS-CoV-2
  • BIOHIT -HealthCare SARS-CoV-2 Antigen Rapid Test Kit
  • Confirm BioSciences -Verasure COVID-19 Antigen Rapid Swab Test
  • Dynamiker Biotechnology – Dynamiker SARS-CoV-2 Ag Rapid Test
  • Edinburgh Genetics – ActivXpress+ COVID-19 Antigen Complete Testing Kit
  • FenHe Technology -reOpenTest COVID-19 Rapid Antigen Test
  • JOYSBIO Biotechnology – COVID-19 Antigen Rapid Test Kit (Colloidal Gold)
  • LumiraDx – SARS-CoV-2 Ag Test
  • Menarini Diagnostica/ Boditech Med – iChroma COVID-19
  • OraSure Technologies – at-home test
  • Roche – SARS-CoV-2 Rapid Antigen Test
  • Sensitest – Corona Antigen Rapid Test
  • Sona Nanotech – Sona COVID-19 Rapid Antigen Test
  • Tigsun Diagnostics – COVID-19 Antigen Saliva Rapid Test

Unique and Proprietary Technologies

In addition to the standard formats such as lateral flow and ELISA, there are also a number of unique technologies being applied for SARS-CoV-2 antigen testing. These include the following examples of companies and their products/ technologies that are either available or in development:

  • AmonMed Biotechnology – Rare Earth Nano Fluorescence Immunochromatography Avacta/ Adeptrix with Cytiva (Danaher) – working on rapid
  • POC saliva test for self-testing and large scale population screening
  • Celltrion – Magnetic Force-assisted Electrochemical Sandwich Immunoassay (MESIA) technology – CLIA high and medium complexity
  • E25Bio – paper based nasal swab test
  • Ellume – working with Qiagen on test cartridges for home use, POC, and high throughput system
  • Genspeed Biotech – micro-ELISA
  • Luminostics – antigen immunoassay that uses glow-in-the-dark nanomaterials
  • New Gene (Hangzhou) Bioengineering – novel ligand-receptor chromatography test kit

In October, the FDA provided a template to help test developers applying for EUA for SARS-CoV-2 antigen tests. The template provides a range of recommendations as well, for example in order to show the test suppliers how to handle their validation data. Many of these are suggested but not required.   The template recommends that antigen tests should have a sensitivity of at least 80%, but noted that serial testing could allow for results of lower-performing tests (e.g. 70% sensitivity) to be calculated cumulatively.

Vendor Moves

The shift to antigen testing introduces different vendors into the COVID-19 market than are present in PCR. BD and Quidel for instance, are players in antigen testing and have systems with significant placements worldwide.

The scarcity of various diagnostic test related products during the COVID-19 pandemic has further driven home the reality that different testing methods are best allocated for different situations. While antigen tests have been criticized for the lower performance characteristics compared to antibody and molecular tests, these metrics are not always the most significant. Antigen tests often can have sensitivity lower than 85% while the specificity needs to be fairly high, in the range of 98% or higher.   Although a sensitivity of roughly 80% seems striking as a low number, in fact the negative predictive value can still be sufficient if the disease prevalence is appropriately matched.

Becton Dickinson (BD) BD and Quidel, as well as Roche and Abbott are significant players in antigen testing; there are scores of others.  On July 6, 2020 BD announced that the U.S. Food and Drug Administration (FDA) granted Emergency Use Authorization (EUA) for a rapid, point-of-care, SARS-CoV-2 diagnostic test for use with its broadly available BD Veritor™ Plus System. The launch of this new assay that delivers results in 15 minutes on a portable instrument. BD Veritor™ System, which is slightly larger than a cell phone, is currently in use at more than 25,000 hospitals, clinician offices, urgent care centers and retail pharmacies in all 50 U.S. states, per the company.

Earlier in the year, Quidel earned an EUA for The Sofia SARS Antigen Fluorescent Immunoassay (FIA) uses advanced immunofluorescence-based lateral flow technology in a sandwich design for qualitative detection of nucleocapsid protein from SARS-CoV-2. Now the company has received a U.S. Food and Drug Administration emergency use authorization (EUA) for a rapid diagnostic that can simultaneously identify influenza A, influenza B, and the novel coronavirus. The ABC Test, also known as the Sofia 2 Flu + SARS Antigen FIA, is a cartridge-based, point-of-care diagnostic that works with both nasopharyngeal and nasal swab specimens. The test is designed for use in individuals with suspected respiratory viral infection within five days of symptom onset, according to the company. The three-way test works with the Sofia 2 Fluorescent Immunoassay Analyzer (FIA) and provides results within 15 minutes.

Abbott: On August, 26th, 2020, Abbott Launched its sixth COVID-19 test, the BinaxNOW™ COVID-19 Ag Card rapid antigen test – a fast, reliable, affordable and portable rapid test that Abbott will produce at mass scale to greatly expand access to testing to people who need it. The company said they would ship millions in September, ramping production to 50 million tests a month in October. This test offers results in 15 minutes and is available as an aid to diagnose the virus that causes COVID-19. The BinaxNOW test can be displayed on an optional app for iPhone and Android devices called NAVICA™. This first-of-its-kind app will allow people who test negative to have a temporary encrypted digital health pass that displays their results.

Roche Diagnostics has a rapid antigen test and recently announced that it intends to launch a high-volume SARS-CoV-2 Antigen test as an aid in the diagnosis of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. The test is planned to be made available at the end of 2020 for markets accepting the CE Mark. Roche also intends to file for Emergency Use Authorisation (EUA) from the U.S. Food and Drug Administration (FDA). The Elecsys® SARS-CoV-2 Antigen test is a highly accurate laboratory immunoassay for the in vitro qualitative detection of the nucleocapsid antigen of SARS-CoV-2. The test is performed by healthcare professionals and uses nasopharyngeal or oropharyngeal swab samples from patients with signs and symptoms suggestive of COVID-19, or people with either known or suspected exposure to SARS-CoV-2.

On November 5th, Ortho Clinical Diagnostics announced that the FDA   accepted the company’s Emergency Use Notification (EUN) for the new VITROS® SARS-CoV-2 Antigen test, designed to detect active SARS-CoV-2 infection. The company has also submitted an Emergency Use Authorization (EUA).    The company said that with high sensitivity and specificity,ii Ortho’s SARS-CoV-2 antigen test offers exceptional utility for mass-scale testing where appropriate. The company is promoting it’s ability to detect infectious patients based on viral load. Per OrthoClinical Diagnostics, studies showed that samples with PCR cycle threshold (CT— a measure of viral load) levels at 30 – 33 or greater carry little to no live virus, suggesting these patients may no longer be infectious. Compared to PCR, the company says Ortho’s test may be better able to identify individuals with COVID-19 who are infectious because the test is offered with 100 percent sensitivity with samples with a CT count of less than 34.

Kalorama’s report says the jury is out on how much antigen tests like those by Quidel or Ortho are replacing and would replace molecular detection methods. They have different purposes for the most part. Right now the most likely path is that both methods would see usage into 2021, until the disease were to recede or significant and widely distributed pharmaceutical solutions were available.  Kalorama’s report is available at: https://kaloramainformation.com/product/covid-19-update-clinical-testing-telehealth-vaccines-and-other-markets/

 

 

The microbiome is a rapidly growing market. Understanding the detailed roles and functions of the microbiome is important as it is linked to a multitude of critical areas from human health to environmental sustainability.

(A recent report on “Analytics of the Microbiome” by Arogyam covers all aspects of the microbiome landscape.  A free preview of the high value, actionable insights packed microbiome report is available here:  https://www.arogyam.biz/download-summary).  Arogyam is not a part of Kalorama Information; we are pleased to share this information that may be of interest to our readers.

Microbiome Publications

Publications are a testament to the interest and amount of research activity in the field and are therefore an indicator of market demand.  Publication of scientific papers focused on microbiome research has been surging with over 40K publications and a steady growth of 25%+ in the past three years. A Chinese funding agency is the leading body that has been supporting a lot of published research, notable given the current climate with China.

Microbiome Grants

Grants are a close representation of the market opportunity in the academic community.  Microbiome research grants continue to increase with $1billion USD being awarded to research in the area. Infectious disease and cancer researchers are the top award recipients. The US and EU have the most funding.

Microbiome Clinical Trials

Investigation of clinical trials is a crucial framework to recognize the influence and impact of the microbiome on human health and diseases.  COVID-19 has not dented the number of ongoing clinical trials focused on the microbiome, 2020 is on pace to grow to up to 200 clinical trials. It has an unprecedented influence in the Oncology therapy area. Infectious disease is the top indicator.

Microbiome Startup Activities

Understanding startup activities in not just human health but also across industries such as agriculture, food and beverage is critical to unravel investor enthusiasm.  Exponential growth in investment has been seen. 2020 has been a landmark time, over $1.6 billion USD has already been raised even before the year is complete. Investors are betting big in companies in agriculture, food, and infectious disease.

Report abstract can be downloaded here:

https://www.arogyam.biz/download-summary

And purchased here:

https://www.arogyam.biz/shop

Aruna Rajan is a guest blogger on Kalorama Information, and is Founder & CEO Arogyam LLC.

 

It’s an oft-told story that the fortune of Swedish chemist and businessman Alfred Nobel was founded on patented explosives, including dynamite. While his products were used beneficially in mining and construction applications, their wartime use in munitions gave him concern that he would be remembered solely as a ‘merchant of death’. Consequently, Nobel set aside the vast majority of his fortune to establish the prizes that bear his name, awarded to those who have had the greatest benefit on mankind in various fields of endeavor, including the Peace Prize and the Chemistry Prize. This year’s Chemistry Prize was awarded jointly to Emmanuelle Charpentier of France and Jennifer Doudna of the US for their parallel developments of genome editing, namely their groundbreaking 2012 works on CRISPR. Like dynamite, CRISPR offers the twin potential to provide both great risks and rewards to human life.

These and other concerns have produced a variety of moratoria on certain types of research, particularly with respect to human subjects. Nevertheless, the promise of the technology is so great that scientists have a broad array of perfectly ethical and beneficial avenues of research to follow, and are doing so at an ever-increasing rate. In a recently published report from BioInformatics, The 2020 Market for CRISPR/Cas Genome Editing Products, a survey of 328 researchers working with the technology revealed that the number of CRISPR experiments being carried out per month is expected to increase by an average of 16.2% over the next 18 months. The study also offers information on CRISPR workflows, applications and perceptions of vendors and service providers in the space.

CRISPR (clustered regularly interspaced short palindromic repeats) represents a technology developed from the mechanisms underlying a naturally occurring bacterial ability to protect themselves from foreign genetic elements, such as from a viral infection.  From this natural defense has arisen a technology for gene editing, allowing researchers to alter the genetic code with precision, using instruments already found in many life science labs. A gene can be deleted from its location in an organism’s DNA, or novel genes can be inserted into the code. Depending on the application, these changes can be performed on a single cell, or into an entire tissue or organism with an appropriate delivery method.

From the original publications just 8 years ago, a vibrant research community has grown to make use of the technology (as has a vibrant legal industry assessing the patent situation). This revolutionary tool in research and industry does raise some issues of safety. While scientists are generally focused on the positive aspects of treating genetic diseases, developing novel gene therapies, or developing GMO crops with beneficial properties, the legal, ethical and regulatory framework has been slow to develop. This concern is not entirely theoretical or artificial – in 2018, Chinese researcher He Jiankui claimed that he had created the first human genetically edited babies, altering the germline CCR5 gene of twin girls during the embryo stage in an attempt to make them resistant to HIV. Widely condemned by the global scientific community for violating scientific principles and ethical norms, he was fired and sentenced to three years in prison. But in some ways, the genie is now out of the bottle.

What is a Lab-Developed Test?

In vitro diagnostic (IVD) tests are manufactured and sold by diagnostic companies following approval (or clearance) by the appropriate regulatory agencies.  IVD tests are then distributed and used by many different clinical laboratories. In contrast, a laboratory developed test (LDTs) is developed by a clinical laboratory for use specifically in that laboratory.

There are thousands of FDA cleared or approved diagnostic tests, especially when you consider the large numbers of tests that are available for each analyte.  So, why would clinical laboratories develop their own tests?  The answer is simple.  Despite the large number of FDA-cleared or -approved tests and CE-IVD marked tests, there remain many tests that are simply not available commercially for clinical labs to purchase.  If a clinical laboratory wants to offer one of these tests, the lab must develop its own test.

Laboratory developed tests (LDTs) are not a recent phenomenon but due to the urgent need for testing of SARS-CoV-2, there has been a flood of new tests and the regulatory guidance has changed dramatically. Historically, these tests were low-volume, simple and well characterized for low-risk diagnostic applications. Today, high-risk, complex tests have been developed as LDTs, and are being used to provide clinical results to physicians and their patients.

Kalorama’s Report Estimates a 12 Billion Dollar Market  for LDTs

he market for LDTs offered as services is worth over $12 billion, as indicated in this sample below from tbe Kalorama Information’s newest report:

 

LDT Revenue Growth

 

The LDT clinical services market is a large field that covers a wide range of activities, and this is reflected in the topics covered in this report.  This report includes discussions of:

  • Overview of laboratory developed tests (LDTs), including technologies used in LDTs and products sold to laboratories developing and performing LDTs
  • Clinical applications for which LDTs are used
  • Market drivers and challenges in the LDT market
  • Sales for 2020 and projected to 2025 – LDT clinical diagnostic test services
  • Sales for 2020 and projected to 2025 – Products sold to laboratories offering LDTs
  • Profiles of companies in the LDT market

Information used to calculate the market sizes for the LDT clinical diagnostic service market were derived from a wide range of sources including public information about company sales; interviews with market participants including executives, marketing managers and product managers; Kalorama’s databases; and other industry sources.

This Market is Driven by Regulation and Changes in Regulation

The FDA has indicated that it would like to increase oversight of laboratory develop tests for many years.  In July 2014, the FDA notified Congress that it plans to issue a draft guidance entitled “Framework for Regulatory Oversight of Laboratory Developed Tests (LDTs).  On September 30, 2014, the FDA posted two draft guidances to its web site:  “Draft Guidance for Industry, Food and Drug Administration Staff, and Clinical Laboratories: Framework for Regulatory Oversight of Laboratory Developed Tests (LDTs)” and “Draft Guidance for Industry, Food and Drug Administration Staff, and Clinical Laboratories: FDA Notification and Medical Device Reporting for Laboratory Developed Tests (LDTs).”  The comment period for both of these documents lasted until February 2, 2015.

This has created considerable uncertainty.  While has not been possible to know what the final guidance documents would say, it was clear that the FDA wants to increase oversight of LDTs, and to require 510(k) clearance or PMA approval of many LDTs.

The future of regulation of LDTs is even more uncertain now.  In November 2016, in the wake of uncertainty following the presidential election, the FDA indicated that it would delay finalizing the draft guidance on LDTs.  On January 13, 2017, the FDA issued a “Discussion Paper on Laboratory Developed Tests (LDTs).”  This discussion paper synthesizes feedback that the FDA received on the 2014 draft guidance and proposes a prospective oversight framework.  Some of the proposals in the discussion paper include “grandfathering” LDTs (except when required to protect public health), exempting certain categories of new or significantly modified LDTs, reduced time-frame for phasing in regulation of LDTs with risk-based and phased-in oversight, evidence standards, third-party review, clinical collaboratives, transparency, quality system requirements, and post-market surveillance.

Due to the need for coronavirus testing discussed above, the regulatory process is again being scrutinized. It has been planned that the FDA would step up oversight of LDTs after the 2016 election. However, that is not happen. The regulatory boat was stagnant.

At the start of the pandemic, FDA stressed the  need for availability of coronavirus tests developed by laboratories and commercial manufacturers to meet the testing needs.

In March 2020, a bipartisan-backed bill called the Verifying Accurate, Leading-edge IVCT Development (VALID) Act was introduced to Congress. The VALID Act would create a new risk-based oversight framework for in vitro clinical tests, a category that was owned by LDTs and test kits.  That was followed by a bill introduced later in the month by Senator Rand Paul called the Verified Innovative Testing in America Laboratories (VITAL) Act which would take regulation of LDTs out of the FDA’s hands.

In September 2020, the FDA was directed by the U.S. Department of Health and Human Services (HHS) to drop its pursuit of regulation of LDTs. Both the ACLA and the Association for Molecular Pathology backed the move of HHS.  HHS stated that the move is a part of their ongoing department wide review of regulatory flexibilities enacted since the start of COVID-19. There continues to be mixed responses to the latest HHS move. Critics are concerned that this could negatively impact the accuracy of individual labs’ tests, allowing unreliable tests to come to market. This is probably not the last that we will hear about this controversy.

This a Unique Market to Quantify

Estimating revenues for products sold to these laboratories is more challenging as a result of many factors.  For example, a laboratory may purchase an instrument with the intention of using that instrument to perform FDA cleared or approved tests and also LDTs on that instrument.  Alternatively, a laboratory may purchase a research instrument, and then validate and use LDTs on that instrument as well as potentially performing some studies.  Also, clinical laboratories may use consumable reagents for applications that were not intended by the manufacturer.  For example, a clinical laboratory may use an FDA cleared or approved test on a non-approved type of specimen after the required validations have been completed for the LDT.  In this example, the reagents used by the clinical lab for the LDT may be reported by the diagnostic company as an IVD product, and not as a component of an LDT.  These are just a few of the challenges to be faced when estimating the size of the market for products sold to clinical laboratories for use in LDTs.

Oncology LDTs Lead

Much of the focus and attention in recent years has been on the emergence and growing use of complex LDTs based on technologies such as polymerase chain reaction (PCR), microarrays, and next generation sequencing.  To generate test results that were not previously possible, LDTs are being developed and used in many different applications.  The largest segments of this market are oncology, genetic (inherited) disorders, and infectious disease, but laboratory developed tests can be developed and used for virtually all disorders.

Urgent care’s story in the United States has been all about growth.  They offer walk-in care and a range of services, expanded hours and limited wait times.  They usually have imaging equipment and multiple providers and are in a freestanding location or a dedicated store within a retail strip mall.  With approximately 10,000 locations across the country, urgent care clinics (UCCs),  are an increasingly important part of the U.S. health care marketplace.

The concept is not new.  There are many urgent care centers in operation 30 years or more.  There are urgent care centers operating longer than the primary practices surrounding them.  But in a sense, urgent care as it exists now is new in that the awareness and utilization of these centers increased greatly.

Growth, with Limits

Urgent care centers are expected to grow in three distinct ways, according to the latest Kalorama Information report.   They will grow in the number of locations, there will be more patients visiting them each day, and the centers will earn more revenue from them.  The three factors have a multiplier effect.  This will lead to a 24.8 billion-dollar market in 2020 and growth near eight percent.

However, urgent care growth will be limited by the competition and saturation of markets, and competition from retail clinics, and extended hours at physician offices.  The sheer amount of locations is draining the available patient population.  Some insurance carriers will no longer pay urgent care fees in saturated markets such as NY/NJ and Florida.  This compounded by the trend of seniors tending to use physician care rather than urgent care does set a limit on the amount of locations there can be in the U.S. in the future.  The market is not mature, but the maturation point is visible.

“76.6% of the U.S. population resides within a 10-minute drive to an urgent care center.” – Urgent Care Association

This is good news for urgent cares, but also means there are limits to growth.    The industry will not be a “boom mode” forever.  The fastest growth, Kalorama estimates, happened in the early part of this decade, between 2011 and 2017.  There are limiters to growth as well as drivers, and there is increasing visibility on those limiters. It is estimated a population of 50,000 is needed to fuel an urgent care center.  The U.S. has already past the saturation point in urban areas, though rural areas with limited healthcare remain sources of growth.

Urgent Care and Its Competitors

What distinguishes urgent care centers is that they are a walk in clinic offering extended hour access for acute illness and injury care that is either beyond the scope or availability of the typical primary care practice but offer less services than an emergency room would.

The urgent care clinic concept has shown potential to provide affordable, accessible and quality medical care to consumers who otherwise would have to wait hours, days, or even weeks for care. They also provide an alternative to costly, time-consuming emergency room care for sicknesses that could have been prevented if basic health care services had been available.

Table 1-1: Urgent Care Centers vs. Retail Clinics and Physician Practices

Characteristic Urgent Care Center Retail Clinic Physician Practice
Accepts insurance Yes Yes Yes
Appointment required No No Yes
Extended hours Yes Yes Sometimes
Located in a retail store, typically a drug store No Yes No
Freestanding or in its own space Yes No Yes
Physician on-site Yes No Yes
Treats broken bones Yes No Yes
X-ray and/or ultrasound on-site Yes No Rarely
Treats cuts & lacerations Yes No Yes
Treats complicated conditions No No Yes
Specialists on-site No No Sometimes

Urgent care’s sales pitch is its savings over ER.  For example, a 2010 Health Affairs report pointed to cost saving potential, finding that up to 27% of emergency department cases could be seen in urgent care; such a transition would generate up to $4.4 billion in annual cost savings.  This has mostly held.  A more recent white paper from the Urgent Care Association of America estimated that the cost savings of using urgent care centers versus emergency departments could amount to as high as about $18.5 billion per year.

For these reasons, rising rates of utilization are leading to substantial profits for providers, which is in turn fuelling further expansion. More than half of US centers have been open more than 5 years, however, new centers continue to open and existing UCCs continue to expand.

The urgent care business model involves providing a full range of services of nonemergency acute care. UCCs differ from traditional physicians’ offices with procedure rooms for lacerations and fractures, a radiology department for x-ray services, and a laboratory.

More information can be found at Kalorama Information’s report: https://kaloramainformation.com/product/the-u-s-market-for-urgent-care-centers/

It’s beyond theory.  The microbiome is one of many trends that align well with the IVD market.  It is explored in Kalorama Information’s study of the in vitro diagnostic market, The Worldwide Market for In Vitro Diagnostic Tests along with other trends such as automation and gene editing.   The continuous search of the etiology of diseases as part of the body’s systemic response to change has led to a consideration of the gut microbiome as part of disease processes.  While still in the early phase of development a number of companies have developed assays for the study of the microbiome and there is a proliferation of microbiome related therapeutics.

Bacteria in the gut, mouth and plaque (biofilms) have been implicated in a number of diseases including diabetes, obesity, autoimmune, cancer, diarrhea, and mental disorders.  Thousands of species of microbes—bacteria, viruses, fungi, and protozoa—inhabit every internal and external surface of the human body.  The microbiome’s complicated relationship with its human host is increasingly considered crucial to health.  Imbalances in the microbiome’s diverse microbial communities, which interact constantly with cells in the human body, may contribute to chronic health conditions, including diabetes, asthma and allergies, obesity and the metabolic syndrome, digestive disorders including irritable bowel syndrome (IBS), and autoimmune disorders like multiple sclerosis and rheumatoid arthritis.

The microbiome skincare market is expected to continue to grow by double digits in every country researched (United States, Germany, Korea, Japan, Thailand, and China).  The primary drivers for its growth are the natural wellness trend, the fear of chemicals, increasing influence of environmental stressors, and pharmaceutical company investment.  In fact, recent television ads for skin care soaps in N. America state the product “keeps the skin’s natural microbiome intact.”  There are of course probiotics and books that direct consumers to maintain a healthy gut for overall wellness.

While still in the early phase of development a number of companies have developed assays for the study of the microbiome and there is a proliferation of microbiome related therapeutics.

Intense research into the relationship of a person’s population of normal flora and pathogenic invaders with the etiology and progression of disease states has been developed into microbiome-based molecular tests.  Some IVD companies are already developing a greater appreciation for the microbiome’s contributions to human biochemistry and have launched tests to measure changes in the microbiome to monitor disease progress.  At this time, most testing is available from service providers and for research.  There are however at least two CE Marked test kits available from Genetic Analysis (Oslo, Norway) and Luxia Scientific (France)

Researchers also evaluate specific diseases associated with disturbances in the microbiome, including gastrointestinal diseases such as Crohn’s disease, ulcerative colitis, irritable bowel syndromes, and obesity, as well as urogenital conditions, those that involve the reproductive system, and skin diseases like eczema, psoriasis, acne, obesity, diabetes, autoimmune disorder, acute diarrhea, cancer, mental disorder, and others.

Of interest are the CE Marked tests from Genetic Analysis (Oslo, Norway).  Genetic Analysis was awarded the CE Mark for its Dysbiosis test for microbiome imbalance in irritated bowel syndrome.  Genetic Analysis has developed GA-map technology, the first gene-based routine test for the mapping and aide in diagnosis of diseases associated with dysbiosis and imbalances in the bacteria in the digestive system.  Genetic Analysis was established in 2008 and is based on research done by Professor Knut Rudi at Norwegian University of Life Sciences.

In 2018, Luxia Scientific (Paris, France) was awarded the CE Mark for its 1test1 that analyzes the bacterial content of the gut microbiome.  Leveraging 16S rRNA sequencing, it provides information about bacterial diversity and the relative abundance of many bacterial groups that provide beneficial health benefits, (according to Luxia).   In March 2018, Luxia announced an exclusive distribution agreement with Life Genomics (Sweden) whereby Life Genomics will exclusively distribute Luxia’s 1test1 test in Sweden, Denmark, Finland, Iceland, and Norway.

Other IVD industry initiatives include:  OraSure Technologies (Bethlehem, PA) is best known for its point-of-care diagnostic tests for infectious diseases and molecular sample collection devices.  In January 2019, OraSure acquired CoreBiome (St. Paul, MN) an early-stage microbiome services provider for customers in the pharmaceutical, agricultural, and research communities.  The company’s slogan is “Powering microbiome science with big data”.  CoreBiome’s technology provides information-rich characterization of microbial diversity and function, paired with machine learning and expert analytics.  CoreBiome’s BoosterShot platform allows researchers to efficiently run high-resolution DNA sequencing on thousands of microbiome samples.  OraSure indicated that CoreBiome’s microbial genomics technology will complement the company’s DNA Genotek’s molecular sampling business.

Bio-Rad Laboratories entered into a collaboration with Genetic Analysis AS (Oslo, Norway) and Bioaster, a French microbiology research institute, to study gut microbiome alterations in metabolic disorders.  The project will look for microbiota signatures of dysbiosis in metabolic disorders like diabetes and obesity in order to pursue diagnostics development.  It will use Bioaster’s deep and 16S-targeted sequencing technologies and advanced pipelines of data analysis for highlighting new gut microbiome biomarkers, according to a statement.

Bio-Rad acquired the distribution rights for the CE Marked GA-Map test made by Genetic Analysis (Oslo, Norway).  The assay tests for gut microbiota and detects bacterial imbalances to diagnose and manage conditions such as inflammatory bowel disease and irritable bowel syndrome to detect imbalances in the gut microbiome.  GA-map uses 16S rRNA amplification and a number of proprietary analysis technologies.

Thermo Fisher launched the Applied Biosystems Axiom Microbiome Array for simultaneous detection of archaea, bacteria, fungi, protozoa and viruses in human and non-human samples. Developed in collaboration with the Lawrence Livermore National Laboratory (LLNL), the array is designed to increase the understanding of microorganisms, while accelerating the translation of these insights into human health and agricultural applications.

According to Thermo Fisher, a major advantage of the array, which incorporates sequences for over 12,595 species in the National Center for Biotechnology Information (NCBI) archive, is the simultaneous detection of protozoa and viruses and ease of analysis, a capability that is not available with 16S or other platforms.  Most recently, the Axiom Microbiome Array won the R&D 100 Award, which honors great R&D pioneers and their revolutionary ideas in science and technology.  Awarded by R&D magazine, and considered the “Oscars of Innovation”, the R&D 100 Awards recognize and celebrate the top 100 technology products of the year.