By training a computer to analyze blood samples, and then automating the expert assessment process, the AI processed months’ worth of blood samples in a single day
New technologies and techniques for acquiring and transporting biological samples for clinical laboratory testing receive much attention. But what of the quality of the samples themselves? Blood products are expensive, as hospital medical laboratories that manage blood banks know all too well. Thus, any improvement to how labs store blood products and confidently determine their viability for transfusion is useful.
One such improvement is coming out of Canada. Researchers at the University of Alberta (U of A) in collaboration with scientists and academic institutions in five countries are looking into ways artificial intelligence (AI) and deep learning can be used to efficiently and quickly analyze red blood cells (RBCs). The results of the study may alter the way donated blood is evaluated and selected for transfusion to patients, according to an article in Folio, a U of A publication, titled, “AI Could Lead to Faster, Better Analysis of Donated Blood, Study Shows.”
Improving Blood Diagnostics through Precision Medicine and Deep Learning
“This project is an excellent example of how we are using our world-class expertise in precision health to contribute to the interdisciplinary work required to make fundamental changes in blood diagnostics,” said Jason Acker, PhD, a senior scientist at Canadian Blood Services’ Centre for Innovation, Professor of Laboratory Medicine and Pathology at the University of Alberta, and one of the lead authors of the study, in the Folio article.
The research took more than three years to complete and involved 19 experts from 12 academic institutions and blood collection facilities located in Canada, Germany, Switzerland, the United Kingdom, and the US.
“Our study shows that artificial intelligence gives us better information about the red blood cell morphology, which is the study of how these cells are shaped, much faster than human experts,” said Jason Acker, PhD (above), Senior Research Scientist, Canadian Blood Services, and Professor of Laboratory Medicine and Pathology at the University of Alberta, in an article published on the Canadian Blood Services website. “We anticipate this technology will improve diagnostics for clinicians as well as quality assurance for blood operators such as Canadian Blood Services in the coming years,” he added. Clinical laboratories in the US may also benefit from this new blood viability process. (Photo copyright: University of Alberta.)
To perform the study, the scientists first collected and manually categorized 52,000 red blood cell images. Those images were then used to train an algorithm that mimics the way a human mind works. The computer system was next tasked with analyzing the shape of RBCs for quality purposes.
Removing Human Bias from RBC Classification
“I was happy to collaborate with a group of people with diverse backgrounds and expertise,” said Tracey Turner, a senior research assistant in Acker’s laboratory and one of the authors of the study, in a Canadian Blood Services (CBS) article. “Annotating and reviewing over 52,000 images took a long time, however, it allowed me to see firsthand how much bias there is in manual classification of cell shape by humans and the benefit machine classification could bring.”
According to the CBS article, a red blood cell lasts about 115 days in the human body and the shape of the RBC reveals its age. Newer, healthier RBCs are shaped like discs with smooth edges. As they age, those edges become jagged and the cell eventually transforms into a sphere and loses the ability to perform its duty of transporting oxygen throughout the body.
Blood donations are processed, packed, and stored for later use. Once outside the body, the RBCs begin to change their shape and deteriorate. RBCs can only be stored for a maximum of 42 days before they lose the ability to function properly when transfused into a patient.
Scientists routinely examine the shape of RBCs to assess the quality of the cell units for transfusion to patients and, in some cases, diagnose and assess individuals with certain disorders and diseases. Typically, microscope examinations of red blood cells are performed by experts in medical laboratories to determine the quality of the stored blood. The RBCs are classified by shape and then assigned a morphology index score. This can be a complex, time-consuming, and laborious process.
“One of the amazing things about machine learning is that it allows us to see relationships we wouldn’t otherwise be able to see,” Acker said. “We categorize the cells into the buckets we’ve identified, but when we categorize, we take away information.”
Human analysis, apparently, is subjective and different professionals can arrive at different results after examining the same blood samples.
“Machines are naive of bias, and AI reveals some characteristics we wouldn’t have identified and is able to place red blood cells on a more nuanced spectrum of change in shape,” Acker explained.
The researchers discovered that the AI could accurately analyze and categorize the quality of the red blood cells. This ability to perform RBC morphology assessment could have critical implications for transfusion medicine.
“The computer actually did a better job than we could, and it was able to pick up subtle differences in a way that we can’t as humans,” Acker said.
“It’s not surprising that the red cells don’t just go from one shape to another. This computer showed that there’s actually a gradual progression of shape in samples from blood products, and it’s able to better classify these changes,” he added. “It radically changes the speed at which we can make these assessments of blood product quality.”
More Precision Matching Blood Donors to Recipients
According to the World Health Organization (WHO), approximately 118.5 million blood donations are collected globally each year. There is a considerable contrast in the level of access to blood products between high- and low-income nations, which makes accurate assessment of stored blood even more critical. About 40% of all blood donations are collected in high-income countries that home to only about 16% of the world’s population.
More studies and clinical trials will be necessary to determine if U of A’s approach to using AI to assess the quality of RBCs can safely transfer to clinical use. But these early results promise much in future precision medicine treatments.
“What this research is leading us to is the fact that we have the ability to be much more precise in how we match blood donors and recipients based on specific characteristics of blood cells,” Acker stated. “Through this study we have developed machine learning tools that are going to help inform how this change in clinical practice evolves.”
The AI tools being developed at the U of A could ultimately benefit patients as well as blood collection centers, and at hospitals where clinical laboratories typically manage the blood banking services, by making the process of matching transfusion recipients to donors more precise and ultimately safer.
CEOs of NorDx Laboratories, Sonora Quest Laboratories, and HealthPartners/Park Nicollet Laboratories expect demand for SARS-CoV-2 tests to only increase in coming months
The short answer is that large volumes of COVID-19 testing will be needed for the remaining weeks of 2020 and substantial COVID-19 testing will occur throughout 2021 and even into 2022. This has major implications for all clinical laboratories in the United States as they plan budgets for 2021 and attempt to manage their supply chain in coming weeks. The additional challenge in coming months is the surge in respiratory virus testing that is typical of an average influenza season.
Stan Schofield (above center), President of NorDx, a regional laboratory corporation that supports an integrated delivery system at MaineHealth in Portland, Maine.
Rick L. Panning (above right), MBA, MLS(ASCP)CM, retired as of Oct. 2 from the position of Senior Administrative Director of Laboratory Services for HealthPartners and Park Nicollet in Minneapolis-St. Paul, Minnesota.
Each panelist was asked how his parent health system and clinical laboratory was preparing to respond to the COVID-19 pandemic through the end of 2020 and into 2021.
First to answer was Panning, whose laboratory serves the Minneapolis-Saint Paul market.
A distinguishing feature of healthcare in the Twin Cities is that it is at the forefront of operational and clinical integration. Competition among health networks is intense and consumer-focused services are essential if a hospital or physician office is to retain its patients and expand market share.
Panning first explained how the pandemic is intensifying in Minnesota. “Our state has been on a two-week path of rising COVID-19 case numbers,” he said. “That rise is mirrored by increased hospitalizations for COVID-19 and ICU bed utilization is going up dramatically. The number of hospitalized COVID-19 patients has doubled during this time and Minnesota is surrounded by states that are even in worse shape than us.”
These trends are matched by the outpatient/outreach experience. “We are also seeing more patients use virtual visits to our clinics, compared to recent months,” noted Panning. “About 35% of clinical visits are virtual because people do not want to physically go into a clinic or doctor’s office.
“Given these recent developments, we’ve had to expand our network of specimen collection sites because of social distancing requirements,” explained Panning. “Each patient collection requires more space, along with more time to clean and sterilize that space before it can be used for the next patient. Our lab and our parent health system are focused on what we call crisis standards of care.
“For all these reasons, our planning points to an ongoing demand for COVID-19 testing,” he added. “Influenza season is arriving, and the pandemic is accelerating. Given that evidence, and the guidance from state and federal officials, we expect our clinical laboratory will be providing significant numbers of COVID-19 tests for the balance of this year and probably far into 2021.”
COVID-19 Vaccine Could Increase Antibody and Rapid Molecular Testing
Arizona is seeing comparable increases in new daily COVID-19 cases. “There’s been a strong uptick that coincides with the governor’s decision to loosen restrictions that allowed bars and exercise clubs to open,” stated Dexter. “We’ve gone from a 3.8% positivity rate up to 7% as of last night. By the end of this week, we could be a 10% positivity rate.”
Looking at the balance of 2020 and into 2021, Dexter said, “Our lab is in the midst of budget planning. We are budgeting to support an increase in COVID-19 PCR testing in both November and December. Arizona state officials believe that COVID-19 cases will peak at the end of January and we’ll start seeing the downside in February of 2021.”
The possible availability of a SARS-CoV-2 vaccine is another factor in planning at Dexter’s clinical laboratory. “If such a vaccine becomes available, we think there will be a significant increase in antibody testing, probably starting in second quarter and continuing for the balance of 2021. There will also be a need for rapid COVID-19 molecular tests. Today, such tests are simply unavailable. Because of supply chain difficulties, we predict that they won’t be available in sufficient quantities until probably late 2021.”
COVID-19 Testing Supply Shortages Predicted as Demand Increases
At NorDx Laboratories in Portland, Maine, the expectation is that the COVID-19 pandemic will continue even into 2022. “Our team believes that people will be wearing masks for 18 more months and that COVID-19 testing with influenza is going to be the big demand this winter,” observed Schofield. “The demand for both COVID-19 and influenza testing will press all of us up against the wall because there are not enough reagents, plastics, and plates to handle the demand that we see building even now.
“Our hospitals are already preparing for a second surge of COVID-19 cases,” he said.
COVID-19 patients will be concentrated in only three or four hospitals. The other hospitals will handle routine work. Administration does not want to have COVID-19 patients spread out over 12 or 14 hospitals, as happened last March and April.
“Administration of the health system and our clinical laboratory think that the COVID-19 test volume and demand for these tests will be tough on our lab for another 12 months. This will be particularly true for COVID-19 molecular tests.”
As described above, the CEOs of these three major clinical laboratories believe that the demand for COVID-19 testing will continue well into 2021, and possibly also into 2022. A recording of the full session was captured by the virtual Executive War College and, as a public service to the medical laboratory and pathology profession, access to this recording will be provided to any lab professional who contacts info@darkreport.com and provides their email address, name, title, and organization.
Robert L. Michel, Panelist—Publisher, Editor-in-Chief, The Dark Report and Dark Daily, Spicewood, Texas.
Given the importance of sound strategic planning for all clinical laboratories and pathology groups during their fall budget process, the virtual Executive War College is opening this session to all professionals in laboratory medicine, in vitro diagnostics, and lab informatics.
University of Alberta researchers developed CIDER-Seq tool and protocols for the study, which they have made freely available to all scientists
Here’s another promising new technology which, given more research into effectiveness and safety, may soon lead to improved clinical laboratory cancer diagnostics. Oncology research scientists have focused much attention on understanding the role of extrachromosomal circular DNA (eccDNA) in human cancer. Now, a new gene sequencing method may help expand their knowledge about that and other circular DNA found in the genomes of bacteria, viruses, and other cells.
University of Alberta (UA) researchers have invented a new way for sequencing circular DNA, according to a recent study published in the journal Nature Protocols. As with any new technological method, this new tool—called CIDER-Seq—will need to be time-tested, but it does hold promise for providing valuable insights into the role these “mysterious loops” play not only in human disease, but in agricultural viruses as well.
A New Tool for Understanding DNA
DNA is considered “circular” when it has a closed loop with no ends. It differs from “linear” DNA chromosomes found in human cell nuclei. Circular DNA include:
Devang Mehta, PhD (above), Postdoctoral Fellow in the University of Alberta’s Department of Biological Sciences, and lead author of the UA study, describes the breakthrough in his team’s on-going work researching the role of eccDNA molecules. “We devised a new molecular biology method and a new bioinformatics algorithm to finally obtain full-length sequences of eccDNA,” he said in a news release. “Our method finally allows us to sequence these molecules completely and gives us and other researchers a tool to better understand what they actually do in the cell.” (Photo copyright: ecrLife.)
According to the UA study, circular DNA enrichment sequencing (CIDER-Seq) “is a technique to enrich and accurately sequence circular DNA without the need for polymerase chain reaction amplification, cloning, and computational sequence assembly.”
CIDER-Seq uses DNA sequencing technology from Pacific Biosciences, Inc. (PacBio) of Menlo Park, Calif. PacBio (NASDAQ:PACB) is an American biotechnology company founded in 2004 that develops and manufactures gene sequencing systems.
Understanding Circular DNA in Any Human or Plant Cell, Including Cancer
Because many viruses that infect crops have circular DNA, Mehta believes the new tool may be particularly helpful to agricultural scientists. His team of researchers, he noted in the UA news release, used an earlier version of CIDER-Seq to study crop plants in Kenya which were genetically engineered to resist circular DNA viruses.
“Our key advance is that, through our method, scientists can finally gain an unbiased, high-resolution understanding of circular DNA in any type of cell. With our invention of CIDER-Seq, we can start to begin to understand the function of these mysterious circular DNAs in human and plant cells,” Mehta said.
However, this technological advance may be equally welcomed by researchers investigating the role of eccDNA in human cancer. Though both healthy and diseased cells may contain circular DNA, the New York Times noted that the “mysterious loops” are “surprisingly common in cancer cells and play a bigger role in many types of cancers than was previously recognized.” The article goes on to state that until now there have not been effective methods for sequencing circular DNA.
In Clinical Chemistry, a panel of eccDNA experts discussed the critical role circular DNA plays in cancer, referred to as extrachromosomal DNA (ecDNA). “Importantly, in cancer cells, ecDNAs seem to be more transcriptionally active than their chromosomal counterparts and have been suspected to confer growth and survival advantage to cancer cells,” the article states.
According to the New York Times, scientists first discovered the existence of circular DNA in the 1960s when “little clumps of DNA” were detected alongside chromosomes. Today, researchers believe circular DNA is more common in the human genome than first realized and could be linked to a variety of conditions and diseases, not solely to cancer.
CIDER-Seq Research May Lead to New Clinical Laboratory Biomarkers
Birgitte Regenberg, PhD, Associate Professor in Ecology and Evolution at the University of Copenhagen, pioneered methods for detecting circular DNA. She told the New York Times, “I think we’re just opening our eyes up.”
Though she says the research has been “cancer-centered,” Regenberg maintains the role circular DNA plays in human biology may prove to be much broader.
“It’s like when a horse has blinders: The blinders focus the science, but they also prevent some things from being understood,” she said.
Clinical laboratory leaders should keep an eye on the use of CIDER-Seq technology. It may lead to the development of new biomarkers for cancer and other diseases.
This is another example of technology companies working to develop medical laboratory testing that consumers can use without requiring a doctor’s order for the test
Here’s new technology that could be a gamechanger in the fight against COVID-19 if further research allows it to be used in patient care. The goal of the researchers involved is to enable individuals to test for the SARS-CoV-2 coronavirus from home with the assistance of a smartphone app enhanced by artificial intelligence (AI).
Such an approach could bypass clinical laboratories by allowing potentially infected people to confirm their exposure to the coronavirus and then consult directly with healthcare providers for diagnosis and treatment.
The at-home test is being developed through a partnership between French pharmaceutical company Sanofi and San Jose, Calif.-based Luminostics, creator of a smartphone-based diagnostic platform that “can detect or measure bacteria, viruses, proteins, and hormones from swabs, saliva, urine, and blood,” according to the company’s website.
Users who wish to self-test collect a specimen from their nose via a swab and then insert that swab into a device attached to a smartphone. The device uses chemicals and nanoparticles to examine the collected sample. If the individual has the virus, the nanoparticles in the specimen glow in a way visible to smartphone cameras. The device generates data and AI in the smartphone app processes a report. The app informs the user of the results of this COVID-19 test, and it also enables the user to connect to a doctor directly through telehealth video conferencing to discuss a diagnosis.
“This partnering project could lead to another important milestone in Sanofi’s fight against COVID-19,” said Alan Main, Sanofi’s Executive Vice President, Consumer Healthcare, and Chair of the Global Self-Care Federation, in a press release. “The development of a self-testing solution with Luminostics could help provide clarity to individuals—in minutes—on whether or not they are infected.” (Photo copyright: Global Self-Care Federation.)
According to the press release, the diagnostic platform is composed of:
an iOS/Android app to instruct a user on how to run the test, capture and process data to display test results, and then to connect users with a telehealth service based on the results;
a reusable adapter compatible with most types of smartphones; and
consumables for specimen collection, preparation, and processing.
The COVID-19 test results are available within 30 minutes or less after collecting the sample, notes the Sanofi press release. Advantages cited for having a fast, over-the-counter (OTC) solution for COVID-19 testing include:
easy access and availability;
reduced contact with others, which lowers infection risk; and
timely decision-making for any necessary treatments.
The two companies plan to have their COVID-19 home-testing application available for the public before the end of the year, subject to government regulatory clearances. They intend to make their OTC solution available through consumer and retail outlets as well as ecommerce sites.
Can Sound Be Used to Diagnose COVID-19?
Another smartphone app under development records the sound of coughs to determine if an individual has contracted COVID-19. Researchers at the Swiss Federal Institute of Technology Lausanne (École Polytechnique Fédérale de Lausanne or EPFL) in Switzerland created the Cough-based COVID-19 Fast Screening Project (Coughvid), which utilizes a mobile application and AI to analyze the sound of a person’s cough to determine if it resembles that of a person infected with the SARS-CoV-2 coronavirus.
The inspiration for this project came from doctors who reported that their COVID-19 patients have a cough with a very distinctive sound that differs from other illnesses. The cough associated with COVID-19, according the EPFL website, is a dry cough that has a chirping intake of breath at the end.
“The World Health Organization (WHO) has reported that 67.7% of COVID-19 patients exhibit a ‘dry cough,’ meaning that no mucus is produced, unlike the typical ‘wet cough’ that occurs during a cold or allergies. Dry coughs can be distinguished from wet coughs by the sound they produce, which raises the question of whether the analysis of the cough sounds can give some insights about COVID-19. Such cough sounds analysis has proven successful in diagnosing respiratory conditions like pertussis [Whooping Cough], asthma, and pneumonia,” states the EPFL website.
“We have a lot of contact with medical doctors and some of them told us that they usually were able to distinguish, quite well, from the sound of the cough, if patients were probably infected,” Tomas Teijeiro Campo, PhD, Postdoc Researcher with EPFL and one of the Coughvid researchers, told Business Insider.
The Coughvid app is in its early developmental stages and the researchers behind the study are still collecting data to train their AI. To date, the scientists have gathered more than 15,000 cough samples of which 1,000 came from people who had been diagnosed with COVID-19. The app is intended to be used as a tool to help people decide whether to seek out a COVID-19 clinical laboratory test or medical treatment.
“For now, we have this nice hypothesis. There are other work groups working on more or less the same approach, so we think it has a point,” said Teijeiro Campo. “Soon we will be able to say more clearly if it’s something that’s right for the moment.”
With additional research, innovative technologies such as these could change how clinical laboratories interact with diagnosticians and patients during pandemics. And, if proven accurate and efficient, smartphone apps in the diagnosis process could become a standard, potentially altering the path of biological specimens flowing to medical laboratories.
Because of ‘shelter in place’ orders, many anatomic pathologists are reviewing digital images from home during the COVID-19 outbreak and demonstrating the value of whole slide imaging, digital pathology, and CMS’ recent amended remote sign-out policy
COVID-19 is already triggering many permanent changes in the way healthcare is organized and delivered in the United States. However, not until the SARS-CoV-2 pandemic eases will the full extent of these changes become visible. This will be particularly true for anatomic pathology and the profession’s expanded use of telepathology, digital pathology, and whole-slide imaging.
Since early March, specimen referrals and revenues have collapsed at anatomic pathology groups and laboratories across the nation. Dark Daily’s sister publication, The Dark Report (TDR), was first to quantify the magnitude of this collapse in tissue referrals to pathology groups. In an interview with The Dark Report, Kyle Fetter, Executive Vice President and General Manager of Diagnostic Services at XIFIN, Inc., explained that pathology clients using XIFIN’s revenue cycle management services were seeing an average 40% decrease in specimens. And, for certain pathology sub-specialties, the drop-off in specimen referrals was as much as 90%. (See TDR, “From Mid-March, Labs Saw Big Drop in Revenue,” April 20, 2020.)
The College of American Pathologists (CAP) appealed to the Centers for Medicare and Medicaid Services (CMS) to allow pathologists to work remotely. In response, CMS issued a memorandum which stated, “Due to the public health emergency posed by COVID-19 and the urgent need to expand laboratory capacity, CMS is exercising its enforcement discretion to adopt a temporary policy of relaxed enforcement in connection with laboratories located at temporary testing sites under the conditions outlined herein.”
Since then, many physicians, including pathologists, have quickly adapted to working remotely in some form.
Push for Remote Pathology Services Acknowledges Anatomic Pathologist Shortage
The CMS memorandum (QSO-20-21-CLIA), which the federal agency issued to laboratory surveyors on March 26, 2020, notes that CMS will exercise “enforcement discretion to ensure pathologists may review pathology slides remotely” if certain defined conditions are met.
CMS’ decision, which “is applicable only during the COVID-19 public health emergency,” is intended to increase capacity by allowing remote site review of clinical laboratory data, results, and pathology slides.
Ordinarily, CLIA regulations for cytology (a branch of study that focuses on the biological structure of cells) state that cytology slide preparations must be evaluated on the premises of a laboratory that is certified to conduct testing in the subspecialty of cytology. However, a fast-acting Congressional letter sent by 37 members of Congress to US Department of Health and Human Services (HHS) Secretary Alex Azar II, MD, states, “it is unwise and unnecessary to overburden the remaining pathologists with excess work due to staffing shortages, thereby increasing the risk of burnout, medical error, and further shortages in staffing due to exposure. The number of COVID-19 cases will increase and peak over the next two months and will stretch existing healthcare systems to their limits.”
Decreasing Number of ‘Active Pathologists’ Drives Adoption of Telepathology, Digital Pathology, and Whole-slide Imaging
The current COVID-19 outbreak is just the latest factor in support of enabling remote review of anatomic pathology images and cases. The trend of using telepathology, whole-slide imaging (WSI), and digital pathology systems has been gathering momentum for several years. Powerful economic forces support this trend.
The Dark Report devoted its June 10, 2019, issue to a deep dive of the challenges currently facing the anatomic pathology profession. In particular, TDR noted a study published May 31, 2019, in the Journal of the American Medical Association (JAMA) Network Open, titled, “Trends in the US and Canadian Pathologist Workforces from 2007 to 2017.” The study’s authors—pathologists in the United States and Canada—reported that between 2007 and 2017 the number of active pathologists in the United States decreased from 15,568 to 12,839—a 17.53% decline.
TDR noted that these findings imply there are fewer pathologists in the United States today in active practice to handle the steady increase in the number of cases requiring diagnostic review. In turn, this situation could lead to delays in diagnoses detrimental to patient care.
In the United States, the COVID-19 pandemic created an “immediate need for remote sign-outs, reviews, and consults,” said Mike Bonham, MD, PhD (above), Chief Medical Officer for Proscia, a digital pathology software developer, in an interview with Dark Daily. “In the context of highly relevant workflow and workforce challenges, it reinforces the opportunity for wider adoption of digital pathology.” Prior to the outbreak of COVID-19, several distinct forces were driving adoption and use of digital pathology in combination with traditional microscopy, he said. (Photo copyright: Proscia.)
Distinct Forces Beginning to Reshape Anatomic Pathology
In recent years, the anatomic pathology profession has faced growing financial pressure, a shrinking workforce, and a surge in the global demand for pathology—issues that come at a time when biopsies and cancer diagnostics require greater expertise.
The UCSF School of Medicine started with frozen slide sections and moved to the broader volume of pathology slides. Since 2015, UCSF’s School of Medicine has moved toward a fully digital pathology operation and has serialized the adoption by specialty, according to Zoltan Laszik, MD, PhD, attending physician at UCSF and Professor of Clinical Pathology in UCSF’s Departments of Pathology and Laboratory Medicine.
Laszik is among a handful of specialists and digital pathology early adopters who collaborated on the new Dark Daily white paper, which is available for free download.
Through the adoption of digital pathology, glass slides are digitized using a whole-slide image scanner, then analyzed through image viewing software. Although the basic viewing functionality is not drastically different than that provided by a microscope, digitization does bring improvements in lab efficiency, diagnostic accuracy, image management, workflows, and revenue enhancements.
Additionally, artificial intelligence (AI)-based computational applications have emerged as an integral part of the digital pathology workflow in some settings, the white paper explains.
“These developments are important to anatomic pathologists because the traditional pathology business model continues to transform at a steady pace,” noted Robert L. Michel, Editor-in-Chief of The Dark Report.
Anthony Magliocco, MD, FRCPC, FCAP, President and CEO of Protean BioDiagnostics and former Professor and Chair of Pathology at Moffitt Cancer Center, is featured in the white paper as well. His new pathology service model provides routine pathology services, precision oncology, second opinions, liquid biopsies, genetics, and genomics to cancer centers from a Florida-based specialty laboratory.
To register for this important learning opportunity, click here or place this URL in your web browser: https://www.darkdaily.com/webinar/streamlined-operations-increased-revenue-higher-quality-of-care-conclusive-evidence-on-the-value-of-adopting-digital-pathology-in-your-lab/.
These digital pathology technologies represent an innovative movement shaping the present and future of pathology services. Pathologists wanting to learn more are encouraged to sign up for the May 13 webinar, which will build on the body of evidence and commentary that is included in the new white paper, and which will be available for free on-demand download following the live broadcast.
Facing a backlog, the state’s public health laboratory turned to the medical laboratory at Dartmouth Hitchcock Medical Center
Much of the attention surrounding the COVID-19
outbreak—the illness caused by the SARS-CoV-2
coronavirus—has focused on large urban areas such as New York City and Los
Angeles. However, the virus is impacting many rural areas as well. This is true
in New Hampshire, where the diagnostic response required close cooperation
between the state’s public health
laboratory and the clinical
laboratory at its lone academic medical center. Their experience offers
lessons for medical
laboratory leaders nationwide.
“When these things happen and you surge beyond what you
could imagine, it’s the relationships with people that matter more than
anything,” said Christine
L. Bean, PhD, Administrator of New
Hampshire Public Health Laboratory Division of Public Health Services , Concord,
N.H., during a recent Dark
Daily webinar, titled, “What Hospital and Health System Labs Need to
Know About Operational Support and Logistics During the COVID-19 Outbreak.”
As Bean explained, during the earliest stages of the
pandemic the “CDC was doing the testing” and the state lab’s role was limited
to submitting samples from patients deemed as “presumptive positives.” Then, on
Feb. 4, the FDA granted an emergency
use authorization (EUA) allowing use of the CDC-developed real-time
reverse transcriptase PCR (RT-PCR) assay by designated labs.
The New Hampshire Public Health Laboratory (NHPHL) received
its first test kit on Feb. 10, Bean said. But the kits were recalled due to
validation problems with one of the reagents. On Feb. 26, the CDC
issued revised test instructions allowing use of the test without the N3
primer and probe set that had caused the early validation issues. The NHPHL
verified the test under the new guidelines and went live on March 2, she said.
However, with a capacity of 150 to 200 tests per day, the
lab wasn’t equipped to handle a large volume. “Much of what we do is really
population-based,” she said. “Most of the time we’re not doing patient
diagnostic testing.”
Christine L. Bean, PhD (left), Administrator of the New Hampshire Public Health Laboratory, and Joel Lefferts, PhD (right), Assistant Professor of Pathology and Laboratory Medicine, and Assistant Director of the Molecular Pathology, at Dartmouth’s Geisel School of Medicine, spoke with Dark Daily’s Editor-in-Chief Robert Michel during a webinar on what hospital and health system labs need to know about operational support and logistics during the COVID-19 outbreak. The webinar can be freely downloaded by clicking here. (Photo copyright: Dark Daily.)
NHPHL Turns to the Medical Laboratory at DHMC-CGHT for
Help
The DHMC-CGHT lab began having its own discussions about
testing in the first week of February, said Joel
A. Lefferts, PhD, HCLD, DABCC, Assistant Professor of Pathology and
Laboratory Medicine and Assistant Director of Molecular Pathology at
Dartmouth’s Geisel School of
Medicine. They were unsure of how much need there would be, but “throughout
the month of February, we started exploring different testing options,” he said
during the Dark Daily webinar.
The Dartmouth-Hitchcock lab team began with the CDC test. However,
Lefferts noted that the initial FDA guidance was “somewhat restrictive” and required
specific RNA extraction
kits and real-time PCR instruments. “If our lab didn’t have the capability to
perform everything exactly as indicated, we would be running it off-label and
would have to possibly submit our own EUA submission to the FDA,” he explained.
Later, though, the FDA and CDC loosened those restrictions and the lab began testing with the CDC assay on March 18, using a Thermo Fisher ABI 7500Dx instrument, Lefferts said. According to Thermo Fisher’s website, the ABI 7500Dx “is a real-time nucleic acid amplification and five-color fluorescence detection system available for in vitro diagnostic use.”
However, Lefferts continued, “we only had one of these
7500Dx instruments, and it was a relatively manual and labor-intensive
process.” It allowed a maximum of 29 samples per run, he said, and took about
five hours to produce results.
Then, the FDA granted an EUA for Abbott’s
m2000 assay, which runs on the company’s m2000rt real-time PCR instrument.
“We were really excited, because we happened to have two of these systems in
our lab,” he said. “We quickly got on the phone and ordered some of these
kits.”
The DHMC-CGHT lab went live with the new system on March 23.
It can handle up to 94 samples per run, said Lefferts, and with two instruments
running from 6 a.m. to 9 p.m., “there’s a potential to do as many as 10 runs
per day.”
This was the system they used to help New Hampshire’s Public
Health Lab with its backlog. “It was unbelievable to see that our backlog could
be really wiped out,” said Bean.
Challenges for Medical Labs
Gearing up for testing in a public health emergency poses
many challenges, Lefferts advised. “You need to look at what instrumentation
you have in your laboratory, what the experience level of your lab team is, how
much space you have, your expected batch size, and your needed turnaround
time.”
The two labs also had to deal with regulatory uncertainty. “This EUA process is something for which we don’t have much experience,” he said. “Trying to juggle CLIA, CAP, the FDA, and possibly state regulations is a bit challenging. You definitely need to do your research and talk to other clinical laboratories that are doing this testing to get advice.”
Lefferts explained that the most significant challenges to
develop and validate a molecular assay for COVID-19 included:
Availability of validation materials.
Obtaining “positive [viral] samples may be a challenge, depending on where you
are and what you have access to,” said Lefferts. However, he credits the FDA
for being “very proactive” in suggesting alternative sources for “viral isolates or genomic RNA that’s been
extracted from some of these viral isolates.”
Availability of collection kits. “We can
do a lot more testing now,” he said, but one bottleneck is the limited
availability of supplies such as nasopharyngeal swabs
and viral transport media. “We’re looking at alternative collection options,”
he said, such as 3D-printed swabs or even Q-tips [household cotton swabs], though
“hopefully it won’t come to that.” The DHMC-CGHT lab also considered producing its
own transport media.
Turnaround times. “Our lab wants to get
those results out as soon as possible,” Lefferts said. “So, we’re looking at
alternative methods to get that testing out sooner.” For example, “do we just
do the SARS-CoV-2 testing on a patient, or do we need to do other influenza and other viral
pathogens,” while also keeping up with other routine testing during the
pandemic?
Staffing issues. “Fatigue is a big issue
with members of our labs who put in lots of extra hours,” he said. The
DHMC-CGHT lab has developed contingency plans in case lab personnel get sick.
This critical information will be highly useful for
Laboratory Directors and Managers, Laboratory Supervisors and Team Leaders,
Integrated Health System Leaders, Hospital Group Leaders, Physicians and
Physician Group Leaders, Phlebotomy Managers, Courier and Logistics Managers,
and Safety and Compliance Managers.
