In vitro diagnostic testing costs little to the healthcare system and contributes much to clinical practice. For some time this has been stated as educated conjecture; a recent study of U.S and German physicians offers proof. The study found that 66% of clinical decisions made were based on a diagnostic test, while the costs of those tests were just 2.3% of healthcare expenditure (Rohr U., Binder C, PLoS One. 2016). When the cost-effectiveness of in vitro diagnostic testing is then considered along with beneficial effects on treatment outcomes, therapy choices, and hospital management, there should be little surprise about the amount of interest in IVDs and the amount of activity in the market for them.
Market and Growth
IVD testing is a 69 billion-dollar market worldwide, as seen in this figure:
The industry continues to push issues and develop solutions for diseases that fall into the paradigm of early testing benefiting outcomes. It can even claim that some known healthcare problems in some way are the result of a lack of testing. Anti-microbial resistance continues to be an area where IVD shines; there is a growing realization that blind prescribing of antibiotics could be reduced with faster and more targeted testing.
IVD testing is a 69 billion-dollar market worldwide, as seen in this figure
Despite great attention and much action, the opioid crisis continues to plague the United States and countries of the world. 2018 total overdose numbers remained over 70,000, per CDC statistics, indicating that the problem is still severe. The American Association of Clinical Chemistry released a position statement at their 2019 convention, calling for increased collaboration between clinical laboratories and other stakeholders. Early detection of cancer and the popularity of consumer genetic tests are also likely contributors to increased recognition of IVD testing.
While this is happening, various worldwide payor schemes are pressuring prices. The response is consolidation of lab operations and facilities. Same with IVD vendors. Consolidation remains the rule in the industry among both customers and vendors. Top-tier IVD companies accounted for some $55 billion of IVD product sales last year. Part of this development is related to organic company growth but also to strategic acquisitions that add revenue streams and product innovations.
Indeed, the top tier plus next-tier companies listed in the market tables in Chapter 2 of this report – less than 40 companies – account for a majority of the world market for IVDs. The remainder is held by 100s of companies, some of which specialize in specific test segments and others that serve their local markets.
That should foretell no lack of dynamism in the industry. Beyond the market numbers, the pace of mergers and acquisitions is brisk. There are also IVD startups and ventures. According to an August 2019 estimate from EY Parthenon there were $3 billion dollars invested in IVD-related businesses and more than 170 investment rounds between May 2018 and April 2019. There were also over 9 IPOs worldwide, raising $500M for diagnostic-related ventures. These new ventures create technology that may fail or may create the next Foundation Medicines, Aleres or Pacific Biosciences that will be consumed by a larger player in the future. Or like Illumina, they may yet grow to become technology leaders and dominant in their own right.
This technology innovation produced by these companies and ventures will run up against another trend: value-based testing. What clear benefit does a given new technology add to the status quo of practice? How does a discovered biomarker relate to the doctor and the patient? The EU IVDR directives insert clinical validity into requirements directly into permission to market a product in Europe, with staggering processes and paperwork requirements, and an upshfiting of classification where contagious conditions or expensive treatments are involved. In the United States and other nations, expect these trends to enter in the payment process if not the regulatory one. Because in vitro diagnostics are so integral to patient care, particularly for oncology, developers must be aware of how quality and efficacy data pertaining to their device will be used.
The diagnostics industry spends a fair amount on research and development compared to other industries. (Roche spent $1.4 billion on diagnostics R&D in 2018, bioMérieux spent $326 million and Sysmex $158 million.) These investments and technology-driven M&A activity pay off. The industry now uses technologies that would not have been thought of when the first edition appeared two decades ago. Their influence is felt in personalized medicine, inherited diseases, pathogen detection, antibiotic resistance testing, blood banking and much more to come. Yet innovation has come with challenges, and the industry is also subject to regulation, price scrutiny and value-proving as much as any part of the healthcare system and perhaps more.
COVID-19 Takes Center Stage in IVD Market
As the COVID-19 pandemic continues to grow, attention has been focused on how to effectively scale up the diagnostic testing that is needed to correctly handle patients and track the disease’s spread. Countries have been trying to apply the lessons learned in the regions that were hit first. China appears to have dramatically slowed the disease, and one of the key aspects of that effort has been large-scale diagnostic testing. In the United States, there had been regulatory hiccups as well as problems with the initial CDC test kits sent out, which resulted in delays and significant concern about the ability to scale up in the necessary timeframe. In addition, there have been shortages of associated products needed to run the tests, such as controls and RNA extraction kits. Gradually the companies and labs have been addressing these needs.
COVID-19 Tests Blooming, Other Testing Down
While molecular tests for SARS-Cov-2 and all related test supplies are in the most extreme demand, the effect of hospital elective surgery closures and social distancing is taking a hit on traditional testing. Quest Diagnostics released an 8K reporting: “The Company’s operating results in January and February were consistent with the guidance for full year 2020 provided on January 30, 2020. However, in March, the Company experienced, and anticipates it will continue to experience, a material decline in testing volumes due to the COVID-19 pandemic. During the last two weeks of March, volumes declined in excess of 40% inclusive of COVID-19 testing. Federal, state and local governmental policies and initiatives designed to reduce the transmission of COVID-19 have resulted in, among other things, this has lead to a significant reduction in physician office visits, and also
During the last two weeks of March, volumes declined in excess of 40% inclusive of COVID-19 testing. – Quest Diagnostics April 2020 8K.
“The cancelation of elective medical procedures, customers closing or severely curtailing their operations (voluntarily or in response to government orders), and the adoption of work-from-home or shelter-in-place policies, all of which have had, and we believe will continue to have, an impact on the Company’s operating results, cash flows and financial condition.” This is consistent with reports Kalorama has received from other IVD vendors. General chemistries, traditional immunoassays such as TSH and allergy tests, diabetes and hematology testing could be among those that will see reduced markets, at least while social distancing measures are in place.
When Will Surgeries – and Related Diagnostic Testing – Resume?
Most of the expected drop in IVD testing if from the broad cancellation of surgeries If elective surgeries continue, so should testing and a market for IVD diagnostics. As of April 3, thirty-three governors had recommended postponing elective surgeries or signed executive orders that ban nonessential procedures It is likely that surgeries should start to resume in 8-10 weeks and earlier, some ramp up is probable, for several reasons:
COVID-19 appears to be appexing at different times in different places, even in the U.S. Washington State for instance, returned ventilators from the national stockpile because the state’s governor felt they were more needed by other states. In such a situation, a logical answer would be to open up surgeries.
“Elective” is too broad and perhaps national instructions will change – surgeries could include replacement of a faulty heart valve, removal of a serious cancerous tumor, or a pediatric hernia repair. If delayed they can be harmful or life threatening.
Surgeries for children present a more compelling case, noting an American Hospital Association statement, they “are in an active phase of their life growth and development.” The resulting decline in their health could make them more vulnerable to COVID-19. Given the lower (though not universal) risk of COVID-19 contraction and death for younger individuals, these surgeries might be prioritized.
PPE supply should improve in coming weeks as factories worldwide provide more supply, removing a key obstacle to opening surgeries. making decisions about opening up wings much greater.
There is pressure to open up closed, bankrupt and partially shut-down hospitals, even on a temprorary basis, this could free up space for non-COVID procedures.
The AHA and other pressure groups are sounding an alarm that they will tolerate a temporary but not long restriciton, “Where possible, we cannot completely cease caring for illness in our community that is not directly related to the COVID-19 crisis. Our ability to respond to patients must not be prevented by arbitrary directives.” So reads an AHA statement to hospital directors.
Even if no other factors change the situation, some elective procedures will simply and automatically move to essential – tumor removals gallbladder removal, hernia all change in condition over time and become life-threatening.
Not all hospitals are completely shutting down elective surgeries. North Dakota’s governor has not yet issued a ban, though even that state is seeing postponements of surgeries. UC Davis Medical Center continues to operate some on a case-by-case basis oncology-related, such as cancerous tumor removals, injury repair, burns and post-injury care.
Asymptomatic and Presymptomatic Spread Will Focus Attention on Testing
That SARS 2.0 spreads asymptomatically has been established now in several studies, and this is a factor for the rapid spread of the disease and also is driving new policies. This means that a patient can be infected with the virus and not know it, and that makes it difficult to control, SARS-CoV-2 behaves like a typical respiratory coronavirus in the basic mechanisms of infection and replication. But several mutations allow it to bind tighter to its host receptor and increase its transmissibility, which is thought to make it more infectious. A recent study in The New England Journal of Medicine suggests that the stability of SARS-CoV-2 is very similar to that of SARS-CoV1, the virus that caused the 2002-2003 SARS global outbreak. But, researchers believe people can carry high viral loads of the SARS-CoV-2 in the upper respiratory tract without recognizing any symptoms, allowing them to shed and transmit the virus while asymptomatic. This more efficient form of transmission may occur from replication in the upper respiratory tract, although currently the cause is unknown. This feature never occurred in previous respiratory viral outbreaks.
“Not everyone needs to be tested, but everyone with symptoms does.” – Harvey V. Fineberg, M.D., Ph.D.
Absent tests carriers are invisible and themselves have no knowledge of their positive status. This should focus attention on testing. Also, the attention on South Korea which has tested aggressively – 461,233 tests as of April 5th, 2020 – is a boon for IVD as part of a solution to the crisis and for the role of diagnostics in healthcare in general. Harvey V. Fineberg, M.D., Ph.D makes the case in an NJEM article – “Ten Weeks to Crush the Curve” to make millions of diagnostic tests available. “Not everyone needs to be tested, but everyone with symptoms does.” The nation needs to gear up to perform millions of diagnostic tests in the next 2 weeks. This was key to success in South Korea. https://www.nejm.org/doi/full/10.1056/NEJMe2007263?query=featured_coronavirus
IVD Market Highlights
Cancer and Infectious Disease Drive IVD Sales: Tissue-based testing for cancer and molecular tests for both cancer and infectious diseases are the growth engine among larger segments; growing at 50% higher than the overall market. Concern over sepsis and respiratory conditions should ensure that infectious disease will remain in the fast-growth categories. Specialty immunoassays, continuous glucose tests, mass spectrometry and inherited diseases are other large and high-growth segments.
Clear Majority of Market Outside US: 58% of the market is now outside of US. Developed markets (N. America/Europe/Japan) still make up the bulk of IVD sales but growth is dependent on developing nation IVD markets. Among these markets are China, India, Korea, Turkey, and Brazil but IVD vendors are finding new emergent nations, like the Philippines at 9% revenue growth or Malaysia, with 8% growth. There are others. Both Colombia and Romania are charting better-than-world growth rates with 6% CAGR. There is also an IVD market recovery in Europe and growth in Japan. Chapter 3 has estimates of the global IVD market.
Mass Spectrometry (MS) Has Arrived: MS is a significant category in the market, especially in developed markets, for the identification of bacteria, fungi and mycobacteria. The MALDI-TOF market has exploded in recent years in microbiology labs, thanks largely to the IVD regulatory approval of the VITEK MS and MALDI Biotyper Histopathology is a new area of interest – Bruker Corp is developing technology to make MALDI imaging viable in histopathology. Throughput and operational complexity are limits, despite this fast growth in usage.
Migration, Customer Protection in the Core Laboratory: Major chemistry vendors are developing improved models selling their existing customers on staying with them – to preserve and expand revenue, as well as create barrier entry against other vendors in a shrinking lab environment. Footprint improvements, IT enhancements, EMR, automation and expanded menus are part of this change. While this is not part of traditional IVD commercialization, web-based and TV marketing has helped in a few categories and usage of such mechanisms would boost this category.
Companies Buy to Grow: No one company owns all the technology to compete in an increasingly complex world. Chapter 2 lists over 60 recent mergers and acquisitions related to IVD. Significant recent deals. Last year Abbott brought POC leader Alere into its operations, completing an acquisition finalized in 2017. Beckman Coulter Life Sciences acquired Cytobank in June 2019, a privately held, single cell data analysis, software as a service (SaaS) company. Beckman Coulter Life Sciences recently acquired Labcyte, best known for its Echo acoustic droplet ejection technology. In June 2019, Meridian Bioscience completed its purchase of GenePOC with an eye towards a syndromic testing strategy. Thermo Fisher Scientific acquired Slovakia-based mass spectrometry software developer HighChem, Ltd. in June 2019.
Hospitals Driving Point of Care: It is a mistake to think that point of care is only used by physicians or self-testing. Hospitals are by far the biggest users of rapid IVD tests, and decentralizing certain tests for improved outcomes can boost the right system if the cost case can be made. The direct-to-consumer trend, recently successful in genomic type tests, is one to watch. OTC HIV, cholesterol and colon cancer tests are available alongside well-established pregnancy and glucose tests. Individuals can purchase lab tests in retail outlets or via the Internet.
The world market for diagnostics is estimated at $69.2 billion in 2019 and is expected to grow 4% annually to $85.2 billion by 2024. This includes all laboratory and hospital-based products, and OTC product sales. Previous editions had growth at 6%. What to make of the recent lower single-digit growth? Faster growth is possible; if the potential of sequencing and personalized medicine testing is fully realized, such rates might return. For the next five years, slowdowns in instrument purchasing decisions, the effects of PAMA legislation in the United States, cold markets in Europe, decreasing reimbursement for glucose and low-cost competition (in an essential IVD market), as well as the migration of previously low volume tests to integrated analyzers (that decreases the cost per test) must be weighed against the positives of an aging population, increasing procedures and test improvements. The consolidation of lab customers is also a concern.
All of the major IVD companies reported double-digit increases in their sales in China with growth in the other top emerging markets: Brazil, Turkey, Korea, India, Saudi Arabia and Mexico. Other emerging markets of interest for IVD vendors were Colombia, UAE, South Africa and the Eastern Europe region. These countries continue to invest in healthcare infrastructure and insurance coverage for a growing more affluent middle class.
The market continues to grow, but what the dollars represent is changing. Twenty years ago, clinical chemistry and immunoassays were most of testing. Still today, the traditional core lab test segments – chemistry/immunoassay, hematology and coagulation – make up 34% of the dollar value of the IVD market in 2019, while they are over sixty percent of tests run. As molecular, infectious disease, and cancer tests increase in importance, the market share of these core tests will decrease to 29% in 2024.
Trends to Watch in the In Vitro Diagnostics Market
The following long-term trends will tend to inform what the future IVD market size in various segments will reach.
China and Top Emerging Nations IVD Markets
China is the world’s largest and one of the fastest-growing IVD markets. Thus it is a target by all major IVD vendors for replacing some revenue lost to slower growth in developed healthcare markets. The global industry has increased activities here in the past decade, and companies not only sell IVDs but manufacture and distribute here as well. In 2019, the Chinese market for IVD reagents was estimated at approximately $3.8 billion and is expected to show annual growth of 8% over the next five years.
Expanding beyond the top seven emerging markets is essential for growth in the global IVD industry. Eastern Europe, LATAM (outside of Brazil) and Eastern Europe represent next-tier emerging regions.
With a longer-term focus, Africa must be part of 5- and 10-year business plans for companies not already in the region. There are already global companies in the region. More than half of global population growth between now and 2050 is expected to occur in Africa, according to the U.N. The American Association for Clinical Chemistry announced an expansion of their Global Lab Quality Initiative (GLQI) to Africa next year. The program circulates testing best practices, providing method verification workshops and other training and education. For 8 years, the GLQI has worked with partner associations in Latin America and the Pacific region. A quality control workshop is slated for Ethiopia in 2020, and a newborn screening workshop is planned in Morocco in the coming year.
Next-Generation Sequencing and IVD Markets
Next-generation sequencing accompanied by data analysis algorithms can allow clinicians and researchers to uncover the hidden aspects of antibiotic resistance, cancer pathways and rare and chronic diseases. This could mean precision medicine is beginning to put one-size-fits-all medicine in the archives of therapeutics. Their usage will be a large factor in the future growth of diagnostics. On average, more than 14 Genetic Testing Units (GTUs) per day are entering the commercial market, a pace faster than in previous high-growth years. Most disease processes involve a number of genes and cell pathways. New multi-gene diagnostics tests by whole genome and next-generation sequencing that examine thousands of specific gene sequences might one day hold the key to assessing disease risk, diagnosing diseases and guiding precision medicine treatment decisions. However, artificial intelligence algorithms are needed to interpret the mass of test data produced by these tests.
The testing of cell free and tumor DNA (liquid biopsy) is becoming an important tool for early and metastatic cancer detection. The technology is also playing a part in pathogen epidemiology. Established and new molecular techniques are being developed to realize the dream of unequivocal near patient and point-of-care testing for infectious diseases and acute care analytes. This is important for resource-poor situations worldwide.
And then there is the emerging science of linkages between the human microbiome and the manifestation of a whole host of diseases. This phenomenon is creating a new approach to disease detection and therapeutics. Molecular tests, especially for inherited diseases and some FISH analyses, are extremely complex. The tests provide raw data, the interpretation of which sometimes baffles even the most experienced molecular biologists. New sequencing technologies are expanding the number of causative genes known for genetic disorders. Gene identification is a first step for future development of a targeted therapeutic especially for cancer and rare diseases. Exosomes carry nucleic acids and proteins from their host cells and are widely considered to be essential for biomarker discovery for personalized healthcare diagnostics. Tumor cells, for instance, release exosomes which contain tumor specific RNAs that can be isolated easier from biofluids such as blood and urine than from biopsies. It is expected that exosome-based tests in routine genomic diagnostics will provide an alternative to tissue biopsies and create new opportunities in molecular testing, especially for cancer liquid biopsy analysis.
Direct-to-Consumer IVD Markets
There has been an explosion of genetic test services that aim to predict a person’s risk of developing various chronic diseases such as diabetes, cardiovascular conditions, arthritis, Alzheimer’s, breast cancer, celiac disease and psychological syndromes. For a long time these test services flew under the radar, but with increased consumer demand, the US FDA leaped into action. The most advanced company is 23andMe (Mountainview, CA). Although the FDA approval for these 23andMe services may have surprised some, the company has fastidiously conducted studies to prove the utility of its human genome direct-to-consumer test services. The company’s over-the-counter use tests are intended for use on genomic DNA isolated from human specimens collected by the user. March 2019, 23andMe began offering a new genetic Health Predisposition report that offers customers insight into their likelihood of developing type 2 diabetes. March 2018, 23andMe received FDA clearance for the BRCA1/BRCA2 (Selected Variants) Genetic Health Risk report. This was the first-ever FDA authorization for a direct-to-consumer genetic test for cancer risk. Yet, despite the well-known benefits of genomics to improve patient outcomes, access to genomic information in healthcare remains limited. It is generally accepted that a critical step in the commercialization of a test modality is the availability of quality control standards.
Information Technology and AI
Laboratory IT and Clinical scoring systems and algorithms have been used in medical practice for some time; recently there has been an increase in the application of machine learning (artificial intelligence) to improve these tools. While traditional algorithms require all calculations to be pre-programmed, machine-learning algorithms deduce the optimal set of calculations by searching for patterns in large collections of patient data. Chapter 4 details products and partnerships in AI.
There have been extraordinary advances in artificial intelligence, the end-game for information technology. Similar to the product commercialization process that is evident in the liquid biopsy market, IVD companies’ efforts have been supported by the US FDA’s efforts to give products expedited review. This helps patients have more timely access to devices and technology that provide more effective treatment or diagnosis for life-threatening diseases.
More products have been cleared for clinical use, more new research use only applications have come to market and many more are in development – companies are collaborating to improve the power of data analysis for patient care. Over the past several years, healthcare has witnessed a transformation with a shift from paper-based records systems to electronic records and incorporation of digital health monitoring devices and advanced patient screening systems. These advances have resulted in a data explosion, which can best be manipulated and analyzed using artificial intelligence (AI) technology.
Evidence to support AI’s use in diagnostics is building: an August 2019 in JAMA Network Open found that a novel artificial intelligence algorithm outperformed pathologists in differentiating ductal carcinoma in situ (DCIS) from atypical hyperplasia, a job that is “considered the most diagnostically difficult task in clinical practice,” researchers wrote in the paper published online. The researchers compared the performance of machine learning with the interpretation of digitized images by 87 practicing pathologists. A machine-learning algorithm that analyzed two features (tissue distribution and structure) had lower sensitivity than the pathologists when it came to distinguishing between invasive and noninvasive cancer.
New Venues – Urgent & Retail Care, “Microhospitals”
IVD marketers cannot ignore the trend of healthcare following the patient. Urgent care centers are not new but have taken on new importance as convenient healthcare options. Kalorama Information’s recent report, The Market for Urgent Care Centers, projects that there will be 1,000 new urgent care centers in the next five years. Some of these will compete for patients with existing locations and all may not survive, but they will add an estimated $3 billion extra into that market, and create millions of dollars in new sales to these new centers of equipment, including point-of-care IVDs. Retail clinics within CVS and Walgreens chains in the U.S. are venues for respiratory disease testing and some POCs. These new venues will drive some test business to reference labs as well. Watch urgent care opening up near retail pharmacies in the same location rather than an inside clinic.
There is a new opportunity opening for clinical laboratories: micro-hospitals. Micro-hospitals feature 8 to 10 inpatient beds (but can have as many as 50 beds), and range from 15,000 to 50,000 square feet, whereas full-service hospitals are 100,000 square feet or more. At a cost of $7 million to $30 million, micro-hospitals are significantly less expensive than large hospitals to bring to market. For patients, micro-hospitals offer the 24-hour care that cannot be found at healthcare clinics located inside drugstores or urgent care clinics.
The Current Status of Global Blood Collection and Blood Testing IVD Market
The following statistics regarding blood collection are notable:
• Volunteer Donors Worldwide: According to WHO statistics, 78 countries collect over 90% of their blood supply from voluntary unpaid blood donors, and 56 of those countries do so for all of their blood supply; however, 58 countries collect more than 50% of their blood supply from family/replacement or paid donors.
• Blood Collected: Around 117.4 million units of donated blood are collected globally each year, with 42% of the blood collected going to middle- and low-income countries, home of 80% of the world’s population. About 12,700 blood centers in 170 countries report collecting a total of 100 million donations; the median number of annual donations per center is 23,000 in high-income countries, compared to 4,100 in their middle- and low-income counterparts. This rate boils down to 32.6 donations per 1,000 people in high-income countries, compared to 15.1 per mil in middle-income countries, and 4.4‰ in low-income countries.
• Practice Changes in Transfusions: Whole blood transfusions are increasingly being replaced by blood component therapy; there is strong demand for platelets and Type AB plasma. These blood products are used for trauma patients, burn victims, and cancer patients. Red blood cells are needed for accident and gunshot victims, as well as in elective surgeries.
• United States: According to AABB (formerly American Association of Blood Banks) there are 2,400 accredited blood centers in the U.S. By the association’s data, the number of blood units collected in the United States has decreased to 13.6 million in 2013 from the 15.5 million in 2011. However, according to the WHO, donations fell from 13.6 million in 2011 to 6.1 million in 2012, and even further to 5.6 million in 2013. All blood collected in the United States comes from unpaid voluntary donors; half is collected by community blood centers, 44% by the American Red Cross, and the last 6% is collected by hospital blood banks.
• Asia Boosts Blood Collection: The WHO Southeast Asia Region estimates 15.9 million units are collected in contingent nations per year, a great improvement over the 9.4 million units collected, as detailed in this report’s previous edition. However, with a requirement of 18 million units, they are still short.
• India Improves but Not Enough: India, with its huge population of over 1.3 billion, has 2,903 blood banks, of which 1,043 are public and 1,860 are private, including those run by charitable trusts. Together, they collected 11.1 million in 2016-’17; while this is a 12% increase from 2013-’14, it still falls short of the estimated 13 million units needed.
• China Update: 100% of China’s blood supply is collected from voluntary unpaid blood donors. However, a significant proportion of the blood supply is still dependent on family/replacement donors. China had a total of 459 blood centers in 2010, including 355 stand-alone centers and 104 hospital-based centers. 100% of donated blood is screened for transfusion-transmissible infections (TTIs): HIV, hepatitis B, hepatitis C and syphilis. A total of 355 (77.3%) blood centers can prepare blood components (red cell, platelet concentrates, fresh frozen plasma). About 0.92% of the population donates blood, when 1-3% is needed.
• Africa – Safety: The WHO believes that safety of the blood supply is a priority for all countries and a particular challenge in sub-Saharan Africa. In addition to well-known transfusion-transmitted pathogens such as HIV, HBV, HCV and bacteria, risk remains high due to pathogens that are endemic to African countries such as chikungunya, dengue, malaria, and Leishmania, for which screening assays may not be readily available.
Biotin Interference in Immunoassay Detection Errors
Biotin has become a popular over-the-counter supplement in recent years for a variety of uses, medical or otherwise; the vitamin enhances skin and digestive health, and a deficiency can lead to neurological disorder. Pregnant and lactating women often take it as a dietary supplement, as it is important in perinatal development.
The recommended daily intake of biotin is 300 μg, but these supplements can sometimes be sold in megadoses of five to 10 mg, or even more. Being a part of the B complex of vitamins, biotin is also called Vitamin B7, but is also referred to occasionally by its former name, Vitamin H, which can be confusing for patients; it is also often found in multivitamins, which patients may tend to overlook. Immunoassays efficiently separate immobilized antigens from free antigens using biotin-based methods in their mechanisms. A protein called streptavidin is used as the binding sites on particles that conjugate to biotinylated antibodies that have themselves bound to target antigens in the assays. However, if there is excess biotin in the sample being tested, it too can bind to the streptavidin, and the now-unbound biotinylated antibodies can be washed away in the regular processing of the immunoassay, leading to an artificially lower signal. In a sandwich assay, this indicates a lower concentration of the target molecule, or a higher concentration in a competitive assay.
While biotin interference has been an issue for decades, a 2017 article published in the New England Journal of Medicine reports that false laboratory results and misdiagnoses have been on the rise recently: seventeen cases of thyroid assays errors were reported in the previous year, more than the five years before that. Patients, who included six children in treatment for metabolic disease and a 55-year-old man with multiple sclerosis, were diagnosed with Grave’s disease, and three of the children were given thyroid treatment before the error was caught. None were symptomatic of the disease and were all found to be taking multivitamins or biotin supplements to treat their conditions.
Watch Point of Care
Point of care (POC) testing attractions heavy venture capital and company interest. POC testing blends clinical & traditional medical engineering with telecommunications, information, and computer science, opening niche markets for POC testing and devices.
Diagnostics and patient monitoring will play a larger role in POC testing. Newer technologies entering developing countries, such as smartphone-linked diagnostic devices, can make huge differences.
POC testing’s past success hinged on developing tests that employed user-friendly techniques and alternative samples. Future success for point of care testing depends on value-added dimensions to POC tests, already in progress. Currently, all high-end glucose monitoring devices offer software and connectivity that allows diabetics to better manage their health. Test services for HbA1c, paternity, coagulation, and other tests provide physician consultation apps.
POC testing has contributed heavily to diagnostics market growth over the past 10 years. Health insurance giants Aetna, UnitedHealth, Kasier Permanente – together with research organizations and IT companies – are collaborating to personalize medicine using big data.
IVD Mergers and Acquisitions on the Increase
As companies in in vitro diagnostics seek to reach additional markets, new partners and technologies are needed. There were more than 60 recent mergers and acquisitions in IVD in the past year, and there have been hundreds in the last five years. These are covered in detail in our report, IVD Mergers and Acquisitions
Roche Roche remains the world’s largest biotech company, with truly differentiated medicines in oncology, immunology, infectious diseases, ophthalmology and diseases of the central nervous system. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management. One of the ways Roche drives business growth is through mergers & acquisitions (M&A), so the company seems perpetually active in this area. Roche’s recent acquisitions include the following: • In June 2018, it was announced that Roche would be buying complete control in Foundation Medicine for $2.4 billion; Roche had already owned a majority stake in the company, valued at $5.3 billion. Roche appears to be interested primarily in the company’s genomic data, as this is the second data-related acquisition Roche has made in 2018, having picked up Flatiron Health. The merger will seek to accelerate broad availability of comprehensive genomic (CGP) profiling in oncology, with the companies leveraging expertise in genomics and molecular information to enhance the development of personalized medicines and care for patients with cancer. Foundation will continue to operate independently, as part of the deal. • Roche in April 2018, for $1.9 billion, completed the acquisition of Flatiron Health – a maker of oncology-focused electronic health records – to help accelerate industry-wide development and delivery of breakthrough medicines for patients with cancer. The addition of Flatiron, a healthcare technology and services company whose offerings are designed to support cancer care providers and life science companies, expands Roche’s presence in personalized medicine and oncology. Roche, reinforcing its capabilities in information technology, is partnering with Flatiron Health for the development of oncology-focused electronic health records. Flatiron Health will continue its operations as a separate legal entity.
• Roche completed in February 2018 the acquisition of biotech Ignyta for $1.7 billion, giving Roche rights to a drug, entrectinib, currently in testing for cancers that contain specific types of genetic mutations — NTRK or ROS1 fusions. Ignyta develops potentially life-saving, precisely targeted therapeutics (Rx) guided by diagnostic (Dx) tests to patients with cancer. • Roche acquired Viewics, Inc. in November 2017, allowing Roche to expand its leading position in the integrated core laboratory with business analytics capabilities. The Viewics solution allows for efficient integration of Big Data from a variety of IT systems in the laboratory and beyond, pioneering a new way in extracting, cleansing, transforming, and augmenting data. This cloud-based solution is secure, infrastructure-agnostic, interactive, and accessible from multiple devices (e.g., smart phones, tablets, desktop computers).
Abbott’s Molecular Diagnostics Business Post-Acquisition of Alere
The acquisition of Alere was finally completed in October 2017 after the deal went through many ups and downs since the initial announcement was made in February 2016. After the $5.3 billion acquisition, Alere became a subsidiary of Abbott. In 2017 Alere generated revenues of approximately $2.3 billion of which the divested cardiovascular and toxicology product sales were approximately $1,200 million. Therefore Abbott inherited potential Alere revenues of approximately $1,100 million and reported Alere revenue of $540 million in Q4 2017.
Eurofins expands its transplantation testing footprint
For $55M; acquires Singular Bio’s single-molecule, cell-free DNA analysis technology, enables lower cost NIPS testing
GenePOC purchase completed with an eye towards a syndromic testing strategy
HighChem is a provider of mass spectrometry software
Beckman Coulter Life Sciences
Cytobank, a single cell data analysis, SaaS company
Disclosed during an earnings call that it had acquired an undisclosed company that will expand its genomic reagents product portfolio
Caris Life Sciences
The goal: to redefine how pharma and biotech companies identify and rapidly enroll patients in precision oncology trials
Warp Drive Bio’s bioinformatics platform
To advance efforts against drug-resistant bacterial infections
For $1.7 billion, completed acquisition of Brammer Bio, involved in viral vector manufacturing for gene and cell therapies
Launched APIS Assay Technologies Ltd., a company that aims to improve the success rate of biomarker commercialization
Cisbio develops and manufactures kits and reagents for life sciences and diagnostics
Immunoassays Hang On
Immunoassays are important in the IVD instrument market and have been crucial in clinical lab medicine since the mid-1960s. Immunoassays are used to diagnose and monitor diseases & conditions. Among the different types of immunoassays:
Immunoassays employing mass spectrometry
Since the publication of the human genome, immunoassays have been revitalized, generally referred to as post-genomic medicine. Post-genomic medicine employs tests based on protein, and nucelic acid targets derived from human genome research. Gene identification comes first, followed by detecting physiological elements such as proteins, hormones, and enzymes expressed by genes.
Proteins, enzymes, coenzymes, and other cellular elements are major players in metabolic pathways that promote and predict disease evolution. This combination of genes, proteins, and pathways makes for a comprehensive toolbox for post-genomic science.
Coagulation: A Mixed Bag
Hemostasis (stopping blood flow) regulates blood flow and clot formation with enzymes and proteins, relying on coagulation, fibrinolysis, and platelet aggregation. Anticoagulant drugs prevent platelets from clumping, reducing the risk of arteries clogging and in turn stroke or heart attack.
The coagulation discipline is in the limelight thanks thanks to the discovery that coagulation factors are independent from the development of myocardial infections, strokes and deep vein thrombosis, cancer, inflammatory syndromes, and obstetric complcations. Conditions in which coagulation factors are implicated include:
Post-surgical bleeding due to Aspirin or Plavix
In vitro diagnostics market’s coagulation segment is a mixed bag of routine tests and intensive investigation of abnormal tests with genetic markers and special immunoassays run on dedicated coagulation analyzers and core lab chemistry & immunoassay instruments.
Histology: Traditional Key to Cancer Testing Threatened
Histology and cytology study tissues and cells, respectively. Histoligical analyses of tissue involve pre-analytical sample preparation and advanced staining.
Histology processes cervical fluids, sputum, and tissue that has been biopsied. Specimens are stained on glass slides to characterize targeted cellular constructions, tissue morphology, and cell componenets. Technologists read the slides using microscropy, while pathogists examine slides with suspicious cells. Histological tests primarily test tissue for cancer, or cervical fluid for infectious agents. Biopsied organs or tissues are processed and analyzed similarly.
Pathologists identify tumor sources in most cancer cases, sometimes confirming cancer without finding the sources. Pathologists employ different techniques to improvide difficult diagnoses, including in situ hybridization (ISH), immunohistochemistry (IHC), immunofluorescence (IF), and molecular analysis of tumor cells.
In Vitro Diagnostics Market Research
The latest in IVD market research covered in Kalorama Information’s reports.
From Patients to Providers: Transmitting Information in IVD
Diagnostics are about information delivery. Transmitting usable, valid info to healthcare providers and patients is crucial to lab operations. Significant trends in IVD include:
Worldwide reorganization of decentralized healthcare delivery
Advancement of outcomes-based disease management within test economics
Access to worldwide databases & experts via smartphone
Routine laboratory tests in chemistry, immunoassays, urinalysis, microbiology, coagulation, and HPV cytology are consolidating into the core lab. More analytes previously found only on dedicated immunoanalyzers have migated to consolidated work stations, including
HE4 cancer marker
Markers for Graves’ dease
Traditional specialization barriers including microbiology, hematology, blood banking, immunology, and anatomical pathology are fading, making the core laboratory a lab medicine hub. Economic pressures, labor shortages, and continual additions of new diagnostic tests to lab menus are expanding the core laboratory. At least 80 immunoassays are currently available in clinical workstations. The Worldwide Market for In Vitro Diagnostic (IVD) Tests, 10th Edition predicts that automation is likely in the core lab’s future.
Smaller hospitals are amalgamating routine tests from different disciplines into one core laboratory. New tabletop diagnostic instruments for small labs are multianalyte workstations running chemistries and many immunoassays. Current diagnostic instruments for clinical chemistry, immunoassays, hematlogy, coagulation, urinalysis, and microbiology can link to laboratory information systems and central lab tracks.
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