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Flu Season Brings Shut Down of Elective Surgeries and Procedures in United Kingdom’s National Health Service Hospitals

Mounting financial and patient-care problems in UK show NHS may not provide a quality blueprint for fixing US healthcare system flaws

Patients scheduled for elective surgeries—such as hip replacements or penciled in for routine outpatient appointments—have been turned away this winter from National Health Service (NHS) hospitals as the United Kingdom’s (UK’s) public healthcare system suffers another care emergency.

This latest crisis in the UK should provide further evidence to anatomic pathologists and medical laboratory leaders that the United States healthcare system is not alone in facing mounting financial and patient care questions. While an NHS-like single-payer healthcare system in the US is the goal of many reformers, the UK’s current crisis indicates such a system has serious flaws.

UK News Organizations Disagree with Government Leaders as to Cause of Crisis

NHS officials estimate as many as 55,000 elective operations and outpatient procedures were cancelled as hospitals attempted to free up capacity for the sickest patients. The Telegraph reported that the bed shortfall is blamed on a spike in winter flu, with budget cuts to social services for home healthcare, staff shortages, and an aging population further pressuring the healthcare system.

In late January, the NHS’ National Emergency Pressure Panel (NEPP) announced that planned operations, such as elective surgeries, that had been “suspended because of pressure on the NHS in January,” would be able to resume in February, Sky News reported.

Meanwhile, in response to the original decision in January to have hospitals stop performing elective surgeries and similar procedures, an editorial in The Guardian challenged Prime Minister Theresa May’s suggestion that the current crisis was primarily due to the flu epidemic.

“This is not the flu: it is a system-wide crisis brought about by seven years of mounting austerity,” The Guardian’s editors wrote. “Oh, and that is getting worse, too. The official defense is that this is not a crisis because there is a plan … But planning can’t magic up highly trained doctors and nurses. Plans do not make hospital beds. And while vaccination helps, you can’t entirely plan your way out of the impact of flu.”

Doctors Report ‘Intolerable Conditions’ at 68 Hospitals

The crisis reached new heights when specialists in emergency medicine from 68 hospitals sent a letter to the prime minister stating the “current level of safety compromise is at times intolerable, despite the best efforts of staff.” The letter, published in The Guardian, also pointed out media coverage reporting anecdotal accounts of “appalling” situations in many emergency departments “are not outliers.” According the doctors, conditions include:

  • Over 120 patients a day managed in corridors, some dying prematurely;
  • An average of 10-12 hours from decision to admit a patient until they are transferred to a bed;
  • Over 50 patients at a time awaiting beds in the emergency department; and,
  • Patients sleeping in clinics as makeshift wards.

One doctor, Richard Fawcett, MD, drew media attention when he used Twitter to apologized for “third world conditions” caused by overcrowding in the hospital where he works, The Telegraph reported.

Richard Fawcett, MD

Richard Fawcett, MD (above), a consultant in emergency medicine for University Hospitals of North Midlands NHS Trust, drew widespread media attention in England when he apologized to patients on Twitter for the “third world conditions” this winter at the hospital where he works. A Lieutenant Colonel in the British Royal Army, Fawcett has done three deployments to Afghanistan. (Photo copyright: Midlands Air Ambulance Charity.)

NHS officials acknowledged staff criticism but attempted to paint the crisis as temporary. University of North Midlands NHS Trust (UHNM) told BBC News that area hospitals had been under “severe and sustained pressure over the Christmas period,” which had “continued into the new year.”

“Our staff want the very best for our patients and at times they find the situation frustrating, which can be reflected on social media. However, we are a leading trauma, stroke, and cardiac center and have been regularly praised by external independent commentators for the quality of compassionate care provided at our hospitals despite all our pressures,” Dr. John Oxtoby, Consultant Radiologist and Deputy Medical Director, UHNM, told BBC News.

“We have to keep going and turn up in a fit state to do the best job that we can. But it’s been really tough, particularly on more junior staff,” one hospital staff member told The Guardian. “And when they ask me, ‘Will it always be like this and will it get better?’ I cannot say it will improve as the truth is it won’t unless the NHS gets the resources and investment it needs.”

Basic Elements of Care Neglected

This is not the first time the NHS has come under fire for substandard patient care.

Between 400 and 1,200 patients are estimated to have died as result of poor care between January 2005 and March 2008 at Stafford Hospital, reported The Guardian. A 2010 report into care at the hospital, now named County Hospital and run by UHNM, found a litany of problems.

“For many patients, the most basic elements of care were neglected,” inquiry Chairman Sir Robert Francis, QC, told The Guardian. “Some patients needing pain relief either got it late or not at all. Others were left unwashed for up to a month … The standards of hygiene were at times awful, with families forced to remove used bandages and dressings from public areas and clean toilets themselves for fear of catching infections.”

Reports of substandard patient care within the United Kingdom’s National Health Service are not new. British barrister Sir Robert Francis, QC (above), led investigations into the Stafford Hospital scandal, which uncovered that an estimated 400 to 1200 patients died between 2005 and 2008 at the facility due to appalling conditions and lax procedures. (Photo copyright: The Telegraph.)

Why not this crisis in US? Because, even if our system of healthcare has flaws, it is responsive to consumer/patient demand. Whereas, in the UK, the NHS is always budget short and so is always struggling to invest in expanding hospital/physician capacity to meet the steady increase in patient demand.

Dark Daily’s goal in reporting on this story is to help anatomic pathologists and clinical laboratory leaders in the United States understand that every country’s health system—like ours—has its share of unique problems and is not perfect.

—Andrea Downing Peck

Related Information:

NHS Patients Dying in Hospital Corridors, A/E Doctors Tell Theresa May

The Guardian View on the Crisis: It’s Not Just the Flu

Mid Staffs Hospital Scandal: The Essential Guide

NHS Crisis: ‘I Live in Fear I’ll Miss a Seriously Ill Patient and They Will Die’

Hospitals to Delay Non-Urgent Operations

NHS to Lift Suspension of Elective Surgery as Hospital Pressures ‘Ease’

Potential New Clinical Laboratory Urine Test for TB Could Speed Up Diagnosis and Treatment of Disease That Kills 1.7 Million People Each Year

Public health agencies and physicians would gain access to accurate, rapid dip-stick test that could give results similar to a pregnancy test

Tuberculosis is a major killer that ranks alongside HIV/AIDS as a leading cause of death worldwide. This deadly disease takes the lives of more than a million people each year. And, unfortunately, traditional medical laboratory testing using X-rays, blood/skin/sputum specimens, or the new molecular diagnostic systems can be time consuming and expensive.

Now, scientists at George Mason University (GMU) in Virginia have developed a urine test for tuberculosis (TB) that could lead to a dip-stick technology that would accurately and rapidly diagnose the deadly lung disease. Similar to a pregnancy test, if successfully developed for use in clinical settings, the dip-stick could not only enable public health agencies to test for TB more effectively, but also allow primary care physicians and other doctors to easily test their patients for TB at the point of care. However, it also could mean clinical laboratories might find their participation.

Nearly All TB Deaths Occur in Resource Strapped Areas

Such a breakthrough would certainly be a boon to public health and global healthcare, especially in resource strapped areas of the world. According to the World Health Organization (WHO), more than 95% of the 1.7 million TB deaths each year occur in low- and middle-income countries. This is one reason why an inexpensive and easy-to-use detection method for diagnosing the lung disease has long been sought. TB is curable, particularly if diagnosed early.

With that goal in mind, an international team led by Alessandra Luchini, PhD, Associate Professor at GMU, and Lance Liotta, PhD, MD, co-director and co-founder of the GMU Center for Applied Proteomics and Molecular Medicine, developed the potentially revolutionary urine test that uses nanotechnology to measure a sugar molecule in urine that identifies TB with a high degree of accuracy. The scientists published their results in Science Translational Magazine.

George Mason University scientists Alessandra Luchini, PhD

George Mason University scientists Alessandra Luchini, PhD (above left), and Lance Liotta, MD, PhD (above right), head an international team that has developed a nanotechnology that may lead to a simple dipstick urine test to detect tuberculosis. Such a test could greatly impact medical laboratories by reducing the need for traditional lab tests. (Photo copyrights: George Mason University.)

While past attempts at developing an accurate urine test for TB failed to reliably detect low concentrations of the sugar entity lipoarabinomannan (LAM) in HIV-negative, TB-infected patients, the GMU team developed a technology capable of doing so.

According to New Scientist, the GMU team’s test “uses tiny molecular cages embedded with a special dye that can catch and trap these sugar molecules. This makes the test capable of detecting the sugar at low concentrations, making the technique as much as 1,000 times more accurate [than] previous methods for detecting TB in urine.”

“We can measure now what could never be measured before,” Liotta noted in a news release.

World Health Organization Recommends Not Using Serodiagnostic Blood Tests

Common methods to detect TB currently include microscopy of sputum samples—a fast and accurate but expensive detection method (that also can diagnosis drug resistant disease)—or a skin test. A third test for TB, an Interferon-Gamma Release Assay, provides results in less than 24 hours but cannot distinguish between active and latent infection. In 2011, the WHO issued a Policy Recommendation urging countries to stop using serodiagnostic blood tests to diagnose TB, calling these tests unreliable and inaccurate. X-rays, meanwhile, detect only advanced lung damage.

In the GMU study, 48 Peruvian patients were chosen, all with active pulmonary TB, none of whom was infected with HIV or previously had received treatment for TB. According to the research, TB infections were detected with greater than 95% sensitivity, with TB-positive, HIV-negative patients having detectably higher concentrations of LAM in their urine compared to the controls. Patients who had more advanced disease also had elevated LAM concentrations. Eight of nine patients who were smear-negative and culture-positive for TB tested positive for urinary LAM.

“The technology can be configured in a variety of formats to detect a panel of previously undetectable very-low-abundance TB urinary analytes … This technology has broad implications for pulmonary TB screening, transmission control, and treatment management for HIV-negative patients,” the study’s authors told Science.

While The Scientist reports the GMU urine test gives results in about 12 hours, Luchini’s goal is for that timeframe to be dramatically shortened as the test is refined.

“We showed that our technology could be used to measure several different kinds of markers for TB in the urine and could be configured as a rapid test similar to a pregnancy test,” Luchini said in a GMU news release.

According to the university, GMU researchers will continue their work in Peru, where students will begin testing hundreds of patients as part of a research study. Grants from the National Institutes of Health and the Bill and Melinda Gates Foundation are funding their work. Luchini told New Scientist her goal is to make their TB urine test easier to use and to test it on thousands more people.

If successful, she predicts the test could be commercially available for physicians and clinical laboratories to use within three years. GMU’s biotechnology partner Ceres Nanosciences will be commercializing the technology, with the aim of making the test available worldwide, the university said in a statement.

—Andrea Downing Peck

Related Information:

TB, or Not TB? At Last, a Urine Test Can Diagnose It Quickly

Urine Lipoarabinomannan Glycan in HIV-Negative Patients with Pulmonary Tuberculosis Correlates with Disease Severity

Mason Scientists Develop Nanotechnology-based Urine Test that Could Lead to Early TB Detection

Urine Test for TB Yields Results in 12 Hours

Tuberculosis Serodiagnostic Tests Policy Statement 2011

Tuberculosis Mortality Nearly Halved Since 1990

Tuberculosis Fact Sheet

Severe Lack of Volunteers for Clinical Laboratory Studies Has US Alzheimer’s Researchers Employing Innovative Methods to Recruit Participants

Low interest and a lack of diversity among study participants hinders research into one of America’s most fatal and costly chronic diseases

Finding enough people to participate in clinical laboratory trials for Alzheimer’s disease can be a daunting task for researchers. The shortage of participants has compelled scientists to develop innovative ways to locate volunteers for their studies. That includes “Swab-a-Palooza” events to make it easy for individuals to provide samples for this research and get speedy feedback about their ApoE.

“It’s all about recruitment now,” Stephen Salloway, MD, Director of Neurology and the Memory and Aging Program at Butler Hospital in Providence, R.I., and Professor of Clinical Neurosciences and Psychiatry at Brown Medical School, said in an article on the Biomedical Research Forum (BRF) website.

Some researchers are hunting online and offering free genetic testing to interested individuals to ensure they obtain the number of participants needed for their trials. Both the Alzheimer’s Prevention Registry (APR) and the Brain Health Registry (BHR) are using the Internet to compile listings of suitable participants.

The APR is dedicated to uniting Alzheimer’s researchers with individuals interested in participating in clinical trials. The Phoenix-based non-profit organization also educates the public on Alzheimer’s and prevention of the disease. The Brain Health Registry is a web-based research study led by medical researchers at the University of California, San Francisco. Participants complete online questionnaires and tests that provide researchers with information regarding an individual’s health, lifestyle, and cognitive function. The collected data is used to create a listing of potential participants for Alzheimer’s studies.

Using Genetic Testing to Recruit Alzheimer’s Study Participants

GeneMatch is a program led by the Banner Alzheimer’s Institute in the Phoenix area that is part of the APR. The purpose of this national program is to recruit participants for research on Alzheimer’s disease by using genetic testing to match qualified volunteers with research studies. According to their website, 80% of research studies on the disease aren’t completed on time due to a lack of volunteers.

Anyone can register to be part of GeneMatch as long as they live in the United States and are between the ages of 55 and 75. In addition, participants cannot have a diagnosis of cognitive impairment, Alzheimer’s, or dementia.

“We hold local swabbing parties, where the GeneMatch sign-up rate is 95%,” Pierre Tariot, MD, Internal Medicine and Psychiatry, and Director of Banner Alzheimer’s Institute, said in the BRF article. “Jeffrey Cummings calls them Swab-a-Paloozas.”

GeneMatch screens individuals for the Apolipoprotein E (ApoE) and the ApoE-e4 allele which increases the risk for Alzheimer’s disease and is associated with earlier onset of memory loss and other symptoms. At this time, it is not known how this allele is related to the risk of getting the disease, but researchers have discovered the brain tissue of affected individuals have an increased number of protein clumps called amyloid plaques. A buildup of these plaques may lead to the death of neurons and the presence of Alzheimer’s symptoms.

“I spend a lot of time in my community doing outreach. People are very interested and receptive,” said Salloway, who recently hosted a swabbing party for GeneMatch. “At events, I ask everyone to tell five other people about what they learned, and to host swabbing parties themselves.”

The DNA samples obtained by GeneMatch are analyzed by a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory. Over the past two years, GeneMatch has tested over 45,000 individuals for the ApoE-e4 allele and were able to identify 1,000 homozygote and 9,000 heterozygote carriers.

Lack of Diversity Among Study Participants

A paper published in September 2017 by Jeffrey Cummings, MD, Director of the Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas, estimated the number of participants currently needed for Alzheimer’s research is over 55,000. Clinical trials for Alzheimer’s need volunteers who have little or no symptoms of the illness and locating such interested individuals can be complicated.

Jeffrey-Cummings-MD

Jeffrey Cummings, MD (above), is Medical Director at Lou Ruvo Center for Brain Health in Las Vegas. In an interview with Drug Discovery and Development, Cummings said, “There is a huge problem of recruitment for many diseases throughout the nation. The problem goes beyond Alzheimer’s disease; there is a general lack of awareness by the public of either the availability or the importance of clinical trials.” (Photo copyright: Jerry Henkel/Las Vegas Review-Journal.)

Additional obstacles that face Alzheimer’s researchers are the lack of diversity among volunteers for their studies. The participants in GeneMatch are 78% female and there is little representation of African-American and Latino minorities.

“It’s not easy to get healthy individuals to join, and those who do are predominantly highly educated, white, and female,” Jessica Langbaum, PhD, Principal Scientist at Banner Alzheimer’s Institute, said in the BRF article. “That’s okay if the women are the health-info gatherers and send their men for trials, but it will be a problem if we cannot get men into studies.”

Delivering ApoE Genotype Results at Events

Technology that could help locate participants for Alzheimer’s research at open “Swab-a-Palooza” events include a small ApoE analyzer called the Spartan Cube. The small molecular diagnostic device, manufactured by Ottawa-based Spartan Bioscience, Inc., can deliver an ApoE genotype result in less than an hour. The gadget is perfect for outreach gatherings, as people can learn their ApoE genotype while at an event. At this time, the Spartan Cube is used only for research purposes and is not CLIA approved.

The paper by Cummings was a topic of discussion at the Clinical Trials on Alzheimer’s Disease (CTAD), which was held in November in Boston. The CTAD is an annual conference for Alzheimer’s disease researchers to meet and share information about the disease with each other. The 11th CTAD conference will take place in Barcelona, Spain, in October of this year.

More than five million people are living with Alzheimer’s disease in the United States and this number could reach 16 million by 2050, according to the Alzheimer’s Association. It is the sixth leading cause of death in the US and cost the nation $259 billion in 2017. It’s estimated that the costs associated with the disease could reach $1.1 trillion by 2050, which makes finding volunteers for research studies an important endeavor.

—JP Schlingman

 

Related Information:

Don’t Be an Enrollment Loser: Throw Your Own Swab-a-Palooza!

Alzheimer’s Disease Drug Development Pipeline: 2017

A Cure for Alzheimer’s by 2025? An Interview with Jeff Cummings, MD

California Company Creates ‘Uber for Blood’ to Speed the Transport of Life-Saving Medical Laboratory Supplies and Blood Products in Rwanda

High-flying service expected to take flight in other African countries this year, as Tanzania announces launch of ‘world’s largest’ drone network for medical supply and clinical laboratory specimen deliveries

Anatomic pathologists and medical laboratories know that blood is a scarce and life-saving commodity. This is especially true in developing countries. Rising to that need, a California-based logistics company is using drones to provide on-demand access to vital blood supplies in Rwanda and Tanzania, creating a so-called “Uber for blood” delivery service that is poised for deployment to other regions in Africa as well.

Silicon Valley Start-up Zipline is an American automated logistics company based in California that transported more than 5,500 units of blood in 2017 to 12 regional hospitals from a base in the east of Rwanda, reported The Guardian.

The high-flying Silicon Valley startup began operating in the African nation in October 2016 and has cut blood delivery time from four hours to an average of about 30 minutes! Shipments arrive by parachute, dropping within a narrow target landing zone.

Though the Rwandan government, which is funding the project, has not officially released data quantifying the drones’ impact, the fixed-wing drones (called Zips) have been credited with reducing deaths due to malaria, childbirth, and other medical emergencies.

World’s Largest Drone Delivery Network

In August, Zipline announced plans to launch what it claims is the world’s largest drone delivery network in partnership with the government of Tanzania, a country of 56 million people. Zipline will open four distribution centers in the country during the next four years, with the first drones taking to the air in the first quarter of 2018 from the Tanzanian capital city of Dodoma, according to Cargo Forwarder Global (CFG), a cargo and logistics industry news website.

“Every life is precious. The government of Tanzania through the Ministry of Health, Community Development, Gender, Elderly and Children, has made great achievements in improving health services including the availability of medicines in all public health facilities,” Mpoki Ulisubisya, MD, Permanent Secretary of the Tanzania Ministry of Health, stated in a press release. “Our vision is to have a healthy society with improved social well-being that will contribute effectively to personal and national development; working with Zipline will help make that vision a reality.”

Zipline co-founder and CEO Keller Rinaudo (above) speaking at a 2017 TEDTalk on partnering with Rwanda and Tanzania to deliver life-saving medical supplies—including blood and medical laboratory products—by drone up to 500 times each day. Click on image above to view video. (Photo copyright: TEDTalk.)

Zipline co-founder and CEO Keller Rinaudo (above) speaking at a 2017 TEDTalk on partnering with Rwanda and Tanzania to deliver life-saving medical supplies—including blood and medical laboratory products—by drone up to 500 times each day. Click on image above to view video. (Photo copyright: TEDTalk.)

Each of the four distribution centers will be equipped with up to 30 drones, capable of making 500 on-demand delivery flights per day. Drones will provide access to more than 1,000 clinics, many of which lack well-functioning supply chains due to surface roads that “become increasingly bumpy and eventually impassable, particularly during the rainy season,” the CFG website reported.

“We strive to ensure that all 5,640 public health facilities have all the essential medicines, medical supplies, and laboratory reagents they need, wherever they are—even in the most hard-to-reach areas,” Laurean Bwanakunu, Director General of Tanzania’s Medical Stores Department, said in a news release. “But that mission can be a challenge during emergencies, times of unexpected demand, bad weather, or for small but critical orders. Using drones for just-in-time deliveries will allow us to provide health facilities with complete access to vital medical products no matter the circumstance.”

According to Zipline, health workers at remote clinics and hospitals text orders to Zipline for the medical products they need, which are stored in distribution centers. Within minutes, a Zipline Distribution Center can pack and prepare blood and other stored medical products for the 60-mph flight to any delivery site within a 93-mile round trip.

A Zipline worker technician launches a drone in Muhanga. (Photo copyright: Stephanie Aglietti/AFP/Getty Images. Caption copyright: The Guardian.)

A Zipline worker technician launches a drone in Muhanga. (Photo copyright: Stephanie Aglietti/AFP/Getty Images. Caption copyright: The Guardian.)

In a CFG statement, Keller Rinaudo, Zipline’s co-founder and Chief Executive Officer, said the expansion to Tanzania will make East Africa a world leader in drone logistics.

“Millions of people across the world die each year because they can’t get the medicine they need when they need it,” noted Rinaudo. “It’s a problem we can help solve with on-demand drone delivery. Now African nations are showing the world how it’s done.”

Rinaudo told IEEE Spectrum that Zipline expects to expand its operations to several other countries in 2018, though he did not specify where Zips will be flying next. He said the next generation of Zips will be able to fly longer distances, carry larger payloads, and make more deliveries per day.

“Rwanda has shown such remarkable success that a lot of other countries want to follow in its footsteps,” noted Rinaudo. “The problems we’re solving in Rwanda aren’t Rwanda problems, they’re global problems—rural healthcare is a challenge everywhere.”

Drones Delivering Medical Laboratory Specimens Globally

Africa is not the only part of the world where drones are taking flight to deliver blood and medical laboratory specimens. Johns Hopkins University Medicine researchers set a record in America for the longest distance drone delivery of viable medical specimens when its test drone traveled 161 miles across the Arizona desert, an event that Dark Daily reported on in November.

And in Switzerland, an eight-hospital medical group in Lugano partnered with Swiss Post (Switzerland’s postal service) and transportation technology manufacturer Matternet of Menlo Park, Calif., to successfully use drones to transport medical laboratory samples between hospitals, as noted in another Dark Daily report.

As drone technology improves, use of UAVs to transport blood and medical supplies and clinical laboratory specimens from point A to point B will likely become commonplace. They soon could be overflying a neighborhood near you!

—Andrea Downing Peck

 

Related Information:

‘Uber for blood’: How Rwandan Delivery Robots Are Saving Lives

Tanzania Announces World’s Largest National Drone Delivery Network Partnering with Zipline

Tanzania on Way to Becoming Drone Champion

Zipline Expands its Medical Delivery Drones Across East Africa

Johns Hopkins Test Drones Travels 161 Miles to Set Record for Delivery Distance of Clinical Laboratory Specimens

Drones Used to Deliver Clinical Laboratory Specimens in Switzerland

Johns Hopkins University Study Finds Laboratory-Developed Liquid Biopsy Tests Can Give Different Results; Call for ‘Improved Certification’ of Medical Laboratories That Develop These LDTs

Liquid biopsy tests hold much promise. But inconsistencies in their findings provoke scrutiny and calls from researchers for further development before they can be considered reliable enough for diagnostic use

Many commercial developers of liquid biopsy tests tout the accuracy and benefits of their diagnostic technology. However, there are an equal number of medical laboratory experts who believe that this technology is not yet reliable enough for clinical use. Critics also point out that these tests are being offered as Laboratory Developed Tests (LDTs), which are internally developed and validated and have not undergone regulatory review.

Dark Daily has published several e-briefings on researchers who have sent the same patient samples to different genetic testing labs and received back materially different test results. Now, a new study by Johns Hopkins University concludes that liquid biopsy technology “must improve” before it should be relied upon for diagnostic and treatment decision making.

‘Certification for Medical Laboratories Must Improve’

Liquid Biopsy is the term for drawing whole blood and looking for cancer/tumor cells circulating in the blood stream. This is one factor in the imprecision of a liquid biopsy. Did the blood sample drawn actually have tumor cells? After all, only a limited number of tumor cells, if present, are in circulation.

Researchers at The James Buchanan Brady Urological Institute at Johns Hopkins School of Medicine know this and recently compared results of two liquid biopsy tests to determine which one would be more beneficial for patients. They published their findings in the December issue of JAMA Oncology.

Gonzalo Torga, MD (above left), and Kenneth J. Pienta, MD (above right), are the two Johns Hopkins Medicine doctors who conducted the recent study into the efficacy of liquid biopsy laboratory developed tests (LDTs) offered by different medical laboratory companies. They published their findings in JAMA Oncology. (Photos copyright: Johns Hopkins.)

To perform the study, researchers collected blood samples from 40 patients with metastatic prostate cancer and sent the same patient samples to two different Clinical Laboratory Improvement Amendments (CLIA) licensed College of American Pathologists (CAP) accredited laboratories. The labs then performed DNA next-generation sequencing on the samples following the directions of the two liquid biopsy manufacturers.

In reporting the DNA findings and results from the two medical laboratory companies, researchers discovered that the results completely matched in only three of the 40 patients! The Johns Hopkins researchers are concerned that patients could be prescribed certain cancer treatments based on which lab company’s liquid biopsy test their physician orders, instead of an accurate identification of the unique mutations in their tumors.

“Liquid biopsy is a promising technology, with an exceptional potential to impact our ability to treat patients, but it is a new technology that may need more time and experience to improve,” Gonzalo Torga, MD, Postdoctoral Fellow and Instructor at Johns Hopkins, and the lead author of the study, told Forbes. “We can’t tell from these studies which laboratory’s panel is better, but we can say that certification for these laboratories must improve.”

Unlocking New View of Tumors

Two commercial tests were used for the study:

Guardant360 from Guardant Health, Inc., uses digital sequencing to analyze genomic data points at the single molecular level. It examines 73 genes, including all National Comprehensive Cancer Network (NCCN) listed genes. The test searches for DNA fragments among billions of cells and digitally tags each fragment. This process unlocks a view of tumors that is not seen with tissue biopsies, which helps doctors prescribe the best treatment options for a particular patient.

“As a simple blood test, it provides physicians with a streamlined, cost-effective method to identify genomic alterations that can comprehensively influence a patient’s therapy response,” Helmy Eltoukhy, PhD, co-founder and Chief Executive Officer at Guardant Health, told MDBR.

“The only way of keeping ahead of those diseases and tracking those mutations has been through surgery, through doing a tissue biopsy and physically cutting a piece of the tumor out and sequencing it,” Eltoukhy noted in an interview with Xconomy. “What we’re able to do is essentially get the same, or sometimes better performance to tissue biopsy, but through two teaspoons of blood.”

According to the Guardant Health website, it takes just 14 days for a full report from Guardant360 to reach the ordering physician. In addition, the blood test provides samples with an adequate level of cell-free DNA to test 99.8% of the time and reduces errors and false positives found in standard sequencing methods by 1,000 times. It is common for samples used for tissue sequencing to have insufficient DNA for testing 20% to 40% of the time.

“We believe that conquering cancer is at its core a big data problem, and researchers have been data-starved,” explained Eltoukhy in VentureBeat. “Our launch of the world’s first commercial comprehensive liquid biopsy sparked a boom in cancer data acquisition. Every physician who orders one of our tests, and every patient whose tumor DNA we sequence, adds to this larger mission by improving our understanding of this complex disease.”

PlasmaSELECT-R64, manufactured by Personal Genome Diagnostics (PGDx), evaluates a targeted panel of 64 genes that have biological and functional relevance in making treatment decisions. PGDx announced the expanded version of its PlasmaSELECT assay in March of 2017.

“We are proud to launch the revolutionary PlasmaSELECT 64 expanded assay just six months after we introduced the most accurate, clinically actionable liquid biopsy tumor profiling assay to the market,” said Doug Ward, Chief Executive Officer at PGDx, in a press release. “This update is the first liquid biopsy assay that includes MSI (microsatellite instability) testing as a biomarker for high tumor mutational load, thereby providing cancer patients and their oncologists with information on whether they might be candidates for immuno-oncology therapies. The ability to generate DNA tumor profiling non-invasively using blood or plasma offers many advantages and makes genomic testing more accessible and usable.”

Regulations of LDTs Could be Needed to Improve Liquid Biopsy Tests

There are pathologists and clinical laboratory professionals who believe the technology behind liquid biopsies is not yet reliable enough for clinical use. The tests are being offered as LDTs, which are internally developed and validated, and the Food and Drug Administration (FDA) allows LDTs to be sold without regulatory reviews at this time. However, there are discussions regarding if and how to regulate LDTs, the outcome of which could impact how clinical laboratories are allowed to market the LDTs they develop.

Clearly, liquid biopsies are still in their relatively early stages of development. More testing and evaluation is needed to determine their efficacy. However, their potential to revolutionize cancer detection and care is obvious and a strong motivator for LTD developers, which means there will be future developments worth noting.

—JP Schlingman

Related Information:

Oncologists, Beware: Expensive Liquid Biopsy Tests Produce Conflicting Results

One Patient, Two Cancer DNA Tests, Two Different Results

Liquid Biopsy Results Differed Substantially Between Two Providers

Cancer Screening Firm Guardant Health Raises $360 Million to Sequence Tumor DNA of 1 Million Patients

Guardant Health Launches Guardant360 Blood Test in US

With $100M, Guardant Health to Expand Reach of Blood Test for Cancer

Personal Genome Diagnostics’ Expanded PlasmaSELECT 64 Is First Liquid Biopsy Pan-Cancer Profiling Panel to Include MSI Analyses for Immuno-Oncology

‘Liquid Biopsy’ Picks up Cancer Biomarkers in Blood, Study Finds

FDA Reveals New Approach to Laboratory Developed Tests

Using Extracellular Vesicles, Researchers Highlight Viability of Liquid Biopsies for Cancer Biomarker Detection in Clinical Laboratories

Researchers Point to Cost of Services, including Medical Laboratories, for Healthcare Spending Gap Between the US and Other Developed Countries

As healthcare reform continues to impact revenues for medical labs and anatomic pathology groups in an effort to reduce healthcare spending, researchers reinforce claims that prices are to blame, not quantity or quality of care

All facets of the US healthcare system—be it massive health systems, medical clinics, independent anatomic pathology groups, or medical laboratories—are experiencing pressure as healthcare reform attempts to manage ever-growing healthcare spending.

Current healthcare trends in the United States focus on determining medical necessity, adopting personalized medicine, and on determining the value various aspects of care. What these trends have in common is a goal of lowering the cost of care while contributing to improved patient care. However, research dating back as far as 2003 suggests overall prices play a significant role in US healthcare spending, particularly when the cost of care in the US is compared to the cost of care in other developed countries.

US Spends More on Healthcare than Any Other Country

A study published last year was the subject of a recent story in the New York Times about why healthcare costs in the United States are so much higher than in other developed nations. The NYT story referenced multiple studies on the subject that all made a similar conclusion: utilization of healthcare in the US is at or below the median compared with other developed nations, and it is higher prices for these services that causes healthcare in the US to be so expensive.

Health Affairs published one such study in 2003, titled, “It’s the Prices, Stupid: Why the United States is So Different from Other Countries.” Written by Gerard F. Anderson, PhD; Uwe E. Reinhardt, PhD; Peter S. Hussey, PhD; and Varduhi Petrosyan, PhD, the paper compared data from the Organization for Economic Cooperation and Development (OECD) for 30 member countries in 2000.

“The data show that the United States spends more on healthcare than any other country. However, on most measures of health services use, the United States is below the OECD median,” researchers state. “These facts suggest that the difference in spending is caused mostly by higher prices for healthcare goods and services in the United States.”

In a New York Times article, Austin Frakt, PhD (above left), Health Economist with the federal Department of Veterans Affairs, and Aaron E. Carroll, MD (above right), pediatrician and Professor of Pediatrics at Indiana University School of Medicine, collated the various research into healthcare spending conducted in the past decade and a half. (Photo copyrights: JAMA/The Accidental Economist.)

“What was true in 2003 remains so today,” Ashish Jha, MPH, a physician with the Harvard T.H. Chan School of Public Health and the director of the Harvard Global Health Institute, told The New York Times (NYT). “The US just isn’t that different from other developed countries in how much healthcare we use. It is very different in how much we pay for it.”

New Data Shines the Spotlight on Old Concerns

Using data spanning from 1996 to 2013, researchers published similar findings in a 2017 JAMA original investigation. “Healthcare spending increased by $933.5 billion from 1996 to 2013,” stated study authors Joseph L. Dieleman, PhD, Assistant Professor at Institute for Health Metrics and Evaluation; Ellen Squires, MPH, Policy Analyst at Kaiser Family Foundation; and Anthony L. Bui, MPH, MD Candidate at David Geffen School of Medicine, UCLA Health. “Service price and intensity alone accounted for more than 50% of the spending increase, although the association of the five factors with spending varied by type of care and health condition.”

The JAMA study authors noted they could not separate price and care intensity in their data. However, as pointed out by NYT, four other studies published by The National Bureau of Economic Research, the OECD, JAMA, and the Annals of Internal Medicine between 2010 and 2017 also link the cost of care directly with healthcare spending in the US.

“The JAMA study found that, together, [care intensity and pricing] accounted for 63% of the increase in spending from 1996 to 2013,” noted The New York Times, “In other words, most of the explanation for American health spending growth—and why it

has pulled away from health spending in other countries—is that more is done for patients during hospital stays and doctor visits, they’re charged more per service, or both.”

For example, the OECD pilot study from 2010 states, “One of the key findings of the pilot study is that the price level of hospital services in the United States is more than 60% above that of the average price level of 12 countries included in the study.”

The More Things Change the More They Stay the Same

As a cornerstone of economics, transparency in both pricing and quality serves to empower buyers—or in this case patients—to choose products and services based on their overall value. This, in turn, encourages competition and helps to keep prices in check.

However, the US healthcare system offers little transparency—either for patient outcomes or for the prices to be charged—with many patients not having any clue what a service will cost until the bill for their recent hospital stay, lab tests, wellness visit, or ER visit arrives. This has led to increased pressure from employers and patient advocates for hospitals, clinical laboratories, and other service providers to make this information available to the public.

Yet, the opposite scenario is the current reality. Lobbyists and groups representing hospitals, insurers, pharmaceuticals, and other facets of the healthcare system continue to promote legislation at the federal and state levels to keep this information private and away from both the public and their competitors.

The NYT highlights the balance surrounding the issue citing claims of increased innovation with higher prices. However, this only works if the market can support said prices. “Though it’s reasonable to push back on high healthcare prices,” NYT’s noted, “there may be a limit to how far we should.”

—Jon Stone

Related Information:

Why the US Spends So Much More than Other Nations on Health Care

Decomposing Medical Care Expenditure Growth

Comparing Price Levels of Hospital Services Across Countries

The Anatomy of Healthcare in the United States

Price and Utilization: Why We Must Target Both to Curb Health Care Costs

Factors Associated with Increases in US Health Care Spending, 1996–2013

It’s the Prices, Stupid: Why the United States is So Different from Other Countries

US Health Care from a Global Perspective

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