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Clinical Laboratories and Pathology Groups

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What Key Laboratory Leaders Will Learn at This Week’s 2023 Executive War College on Diagnostics, Clinical Laboratory, and Pathology Management

Executives and pathologists from many of the nation’s most prominent clinical laboratories are on their way to the Crescent City today to share best practices, hear case studies from innovative labs, and network

NEW ORLEANS—This afternoon, more than 900 lab CEOs, administrators, and pathologists will convene for the 28th Annual Executive War College on Diagnostics, Clinical Laboratory, and Pathology Management conference. Three topics of great interest will center around adequate lab staffing, effective cost management, and developing new sources of lab testing revenue.

Important sessions will also address the explosion in next-generation sequencing and genetic testing, proposed FDA regulation of laboratory-developed tests (LDTs), and innovative ways that clinical laboratories and pathology groups can add value and be paid for that additional value.

All this is happening amidst important changes to healthcare and medicine in the United States. “Today, the US healthcare system is transforming itself at a steady pace,” explained Robert L. Michel, Editor-in-Chief of The Dark Report and Founder of the Executive War College. “Big multi-hospital health systems are merging with each other, and payers are slashing reimbursement for many medical lab tests, even as healthcare consumers want direct access to clinical laboratory tests and the full record of their lab test history.

“Each of these developments has major implications in how clinical laboratories serve their parent organizations, offer services directly to consumers, and negotiate with payers for fair reimbursement as in-network providers,” Michel added. “Attending the Executive War College on Diagnostics, Clinical Laboratory, and Pathology Management equips lab leaders with the tools they’ll need to make smart decisions during these challenging times.”

Executive War College

Now in its 28th year, the Executive War College on Diagnostics, Clinical Laboratory, and Pathology Management convenes April 25-26 in New Orleans. Executive War College extends to a third day with three full-day workshops: LEAN fundamentals for lab leaders, a genetic testing program track, and a digital pathology track. Learn more at www.ExecutiveWarCollege.com. (Photo copyright: The Dark Intelligence Group.)

Challenges and Opportunities for Clinical Laboratories

With major changes unfolding in the delivery and reimbursement of clinical services, clinical laboratory and pathology practice leaders need effective ways to respond to the evolving needs of physicians, patients, and payers. As The Dark Report has often covered, three overlapping areas are a source of tension and financial pressure for labs:

  • Day-to-day pressures to manage costs in the clinical laboratory or pathology practice.
  • The growing demand for genetic testing, accompanied by reimbursement challenges.
  • Evolving consumer expectations in how they receive medical care and interact with providers.

Addressing all three issues and much more, the 2023 Executive War College on Diagnostics, Clinical Laboratory, and Pathology Management features more than 80 sessions with up to 125 lab managers, consultants, vendors, and in vitro diagnostic (IVD) experts as speakers and panelists.

Old-School Lab Rules Have Evolved into New-School Lab Rules

Tuesday’s keynote general sessions (to be reported exclusively in Wednesday’s Dark Daily ebriefing) will include four points of interest for clinical laboratory and pathology leaders who are managing change and pursuing new opportunities:

  • Positioning the lab to prosper by serving healthcare’s new consumers, new care models, new payment models, and more, with Michel at the podium.
  • How old-school lab rules have evolved into new-school lab rules and ways to transition the lab through today’s disrupters in healthcare and the clinical laboratory marketplace, with Stan Schofield, Managing Principal of the Compass Group.
  • The growing trend of clinical laboratory-pharmacy relationships with David Pope, PharmD, CDE, Chief Pharmacy Officer at OmniSYS, XIFIN Pharmacy Solutions.
  • Generating value by identifying risk signals in longitudinal lab data and opportunities in big data from payers, physicians, pharma, and bioresearch, with Brad Bostic, Chairman and CEO of hc1.

Wednesday’s keynote sessions (see exclusive insights in Friday’s Dark Daily ebriefing) explore:

Wednesday’s keynotes conclude with a panel discussion on delivering value to physicians, patients, and payers with lab testing services.

Clinical Labs, Payers, and Health Plans Swamped by Genetic Test Claims

Attendees of the 2023 Executive War College on Diagnostics, Clinical Laboratory, and Pathology Management may notice a greater emphasis on whole genome sequencing and genetic testing this year.

As regular coverage and analysis in The Dark Report has pointed out, clinical laboratories, payers, and health plans face challenges with the explosion of genetic testing. Several Executive War College Master Classes will explore critical management issues of genetic and genomic testing, including laboratory benefit management programs, coverage decisions, payer relations, and best coding practices, as well as genetic test stewardship.

This year’s Executive War College also devotes a one-day intensive session on how community hospitals and local labs can set up and offer genetic tests and next-generation sequencing services. This third-day track features more than a dozen experts including:

During these sessions, attendees will be introduced to “dry labs” and “virtual CLIA labs.” These new terms differentiate the two organizations that process genetic data generated by “wet labs,” annotate it, and provide analysis and interpretation for referring physicians.

State of the Industry: Clinical Lab, Private Practice Pathology, Genetic Testing, IVD, and More

For lab consultants, executives, and directors interested in state-of-the-industry Q/A and discussions concerning commercial laboratories, private-practice pathology, and in vitro diagnostics companies, a range of breakout sessions, panels, and roundtables will cover:

  • Action steps to protect pathologists’ income and boost practice revenue.
  • Important developments in laboratory legal, regulatory, and compliance requirements.
  • New developments in clinical laboratory certification and accreditation, including the most common deficiencies and how to reach “assessment ready” status.
  • An update on the IVD industry and what’s working in today’s post-pandemic market for lab vendors and their customers.
  • Federal government updates on issues of concern to clinical laboratories, including PAMA, the VALID Act, and more.

Long-time attendees will notice the inclusion of “Diagnostics” into the Executive War College moniker. It’s an important addition, Michel explained for Dark Daily.

“In the recent past, ‘clinical laboratory’ and ‘anatomic pathology’ were terms that sufficiently described the profession of laboratory medicine,” he noted. “However, a subtle but significant change has occurred in recent years. The term ‘diagnostics’ has become a common description for medical testing, along with other diagnostic areas such as radiology and imaging.”

Key managers of medical laboratories, pathology groups, and in vitro diagnostics have much to gain from attending the Executive War College on Diagnostics, Clinical Laboratory, and Pathology Management, now in its 28th year. Look for continued coverage through social media channels, at Dark Daily, and in The Dark Report.

Clinical laboratories are invited to continue the conversations by joining the Executive War College Discussion Group and The Dark Report Discussion Group on LinkedIn.

Liz Carey

Related Information:

Executive War College on Diagnostics, Clinical Laboratory, and Pathology Management Agenda

Six Important Themes to Help Labs Succeed

Executive War College Press

The Dark Report

Dark Daily eBriefings

The Dark Report Discussion Group

Executive War College Discussion Group

PwC Survey Finds 50% of Companies Plan Layoffs and 83% Intend to Move Forward with Streamlined Workforces

Amid cost pressures, healthcare providers also plan to cut staff though some jobs are plentiful; adequate staffing at medical laboratories continues to be a challenge

Thanks to the COVID-19 pandemic and subsequent “Great Resignation,” masses of people have left the workforce and companies large and small in all industries are struggling to retain employees. Clinical laboratories have been particularly hard hit with no relief in sight.

Now comes the results of a PricewaterhouseCoopers (PwC) survey which shows 50% of US companies in various industries—including major healthcare providers—plan to lay off employees. And 83% of organizations intend to move forward with a “streamlined workforce,” according to the latest PwC Pulse: Managing Business Risks in 2022 report.

How this will affect the workload on remaining hospital and medical laboratory staff is clear. And healthcare consumers may not take well to healthcare provides running leaner and with fewer staff than they currently do.

Nevertheless, the PwC survey results “illustrate the contradictory nature of today’s labor market, where skilled workers can still largely name their terms amid talent shortages even as companies look to let people go elsewhere,” Bloomberg wrote on the  CPA Practice Advisor website.

Bhushan Sethi

“Organizations are still walking a tightrope when it comes to talent as we begin to see the longer-term impacts of the ‘Great Resignation.’ Finding the proper balance between investing in specialized talent, managing headcount costs, and driving productivity and morale will remain a top focus,” said Bhushan Sethi (above), People and Organization Joint Global Leader at PwC and an adjunct professor at NYU Stern School of Business in a PwC news release. Clinical laboratories are finding it particularly challenging to fill staff positions across all areas of lab operations. (Photo copyright: PwC.)

Healthcare Has Biggest Challenges, says PwC

Clinical laboratory leaders and pathologist groups are well aware of the unique financial pressures on healthcare systems and medical labs, as well as shortages of pathologists, medical technologists, clinical laboratory scientists, information technology (IT) professionals, and other healthcare workers.

“Healthcare is seeing bigger talent challenges than other industries and is more focused on rehiring employees who have recently left,” the PwC report acknowledged. This is the second Pulse survey PwC conducted in 2022. The 722 respondents included leaders working in human capital and finance.  

Finding Right Talent, Focusing on Growth, Automation

Finding the right employees is so important to companies that PwC ranks “talent acquisition” as the second highest risk (38%) behind cyber-attacks (40%).

“Finding the right talent continues to be a challenge for business leaders,” PwC said. “After a frenzy of hiring and a tight labor market over the past few years, executives see the distinction between having people and having people with the right skills.”

Unlike the high-touch and personal nature of healthcare, industries such as consumer technology, media, and telecommunications can turn to automation to alleviate staffing struggles. And that is what nearly two-thirds, or 63%, of companies in those sectors, aim to do, PwC said.

Other survey talent findings:

  • 50% of companies plan layoffs.
  • 46% are dropping or eliminating sign-on bonuses.
  • 44% are rescinding job offers.

Conversely, the surveyed executives also told PwC they are “cautiously optimistic” and plan on growing and investing even as the economy gives mixed signals:

  • 83% of companies are focused on growth.
  • 70% plan an acquisition.
  • 53% aim to invest in digital transformation, 52% in IT, 49% in cybersecurity and privacy, and 48% in customer experience.

“After more than two years dealing with uncertainty related to the pandemic, business leaders recognize the urgent need to focus on growth in order to compete, and they’re zeroing in on what they can control,” PwC said.

New Remote Work Programs, Reduction in Real Estate Investing, Big Tech

Although companies report having more than enough physical office space, many (42%) have launched remote work programs:

  • 70% have expanded or plan to increase “permanent” remote work options as jobs permit.
  • 22% are reducing real estate investment (financial services and healthcare industries lead the way with 30% and 29%, respectively, saying real estate buys are cooling off).

“While companies continue to invest in many areas of the business, they’re scaling back the most in real estate and capex ex [capital expenditure]. After two years of remote work, many companies simply need less space, and they’re allocating capital accordingly,” the PwC report noted.

In a somewhat parallel release to PwC’s findings, news sources are reporting reductions in real estate and staff at high-profile Big Tech companies.

Meta Platforms, Inc. in Menlo Park, Calif. (formerly Facebook Inc.), is closing one of its New York offices and cutting back on plans to expand two other locations in the city, the Observer reported.

Business Insider reported, “More than 32,000 tech workers have been laid off in the US till July, including at Big Tech companies like Microsoft and Meta (formerly Facebook), and the worst has not been over yet for the tech sector that has seen massive stock sell-off.”

According to Forbes, “San Francisco-based electronic signature company DocuSign will lay off 9% of its more than 7,400 employees (roughly 670 employees), the company announced in a Securities and Exchange filing Wednesday, saying the cuts are ‘necessary to ensure we are capitalizing on our long-term opportunity and setting up the company for future success.’”

And Bloomberg recently reported that Intel is planning to layoff thousands of people “around the same time as its third-quarter earnings report on Oct. 27.”

Healthcare Providers Plan Layoffs, Seek IT Pros

Meanwhile, major healthcare provider networks also are planning staff cuts amid service closures, rising costs, and other issues, according to Becker’s Hospital Review:

“Our health system, like others around the nation, is facing significant financial pressures from historic inflation, rising pharmaceutical and labor costs, COVID-19, expiration of CARES Act funding, and reimbursement not proportional with expenses,” BHSH said in a statement shared with Becker’s.

Amidst these layoffs, however, IT jobs in healthcare seem to be growing. According to Becker’s Health IT, some healthcare providers have posted information technology openings:

So, though it appears IT positions continue to expand, clinical laboratory leaders and pathology practice managers may want to prepare now for dealing with customers’ response to leaner healthcare systems overall.

Donna Marie Pocius

Related Information:

PwC Pulse: Managing Business Risks in 2022

Layoffs are Being Planned at Half of US Companies, PwC Survey Shows

Business Executives Remain Bullish about Their Ability to Manage Turbulent Conditions, according to New PwC Survey

Meta Is Closing a Manhattan Office as It Consolidates Its New York City Presence

50% of Companies Planning Job Cuts Amid Economic Downturn: Report

Ascension to Close Hospital, Lay Off 133 Workers

Microsoft Reportedly Cuts Nearly 1,000 Employees—Here Are the Biggest US Layoffs This Year

Intel Is Planning Thousands of Job Cuts in Face of PC Slump

Hospitals Cut Jobs to Resuscitate Finances

IT Job Openings at Mayo, Northwell, CommonSpirit, and Providence

Do New Strains of SARS-CoV-2 Coronavirus and Inconsistent Distribution of COVID-19 Vaccines Threaten a Return to Normalcy in 2021? McKinsey Weighs In

The latest McKinsey report addresses when the COVID-19 pandemic is “most likely” to end and what needs to happen to get there

Clinical laboratory leaders, pathologists, and diagnostics professionals everywhere want to know when the SARS-CoV-2 coronavirus will burn itself out. When can we expect to return to normal? Since there is no such thing as a crystal ball, it might be helpful to review the latest report from international management consulting firm McKinsey and Company, titled, appropriately, “When Will the COVID-19 Pandemic End?

It’s a good question, and McKinsey is not certain of the answer. Barring other factors, McKinsey predicts “Transition toward normalcy in the United States remains most likely in the second quarter of 2021 and herd immunity in the third and fourth quarters, but the emergence of new strains and a slow start to vaccine rollout raise real risks to both timelines.” The report also states, “the emergence of more-infectious variants of SARS-CoV-2 increases the risk that this milestone will not be achieved until later.

“More-infectious viruses,” McKinsey continued, “require that a higher percentage of people be simultaneously immune to reach herd immunity. While a more infectious variant likely means more people are acquiring natural immunity through infection (despite ongoing efforts to minimize new cases), the net impact of more-infectious strains is likely to be that a higher portion of the population needs to be vaccinated, which may take more time.”

Challenges That May Slow Herd Immunity to COVID-19

“It is now harder to imagine the United States or United Kingdom transitioning to normalcy before second quarter 2021 or reaching herd immunity before third quarter 2021,” McKinsey added. “Herd immunity to a pathogen is achieved when a sufficient portion of a population is simultaneously immune to prevent sustained transmission.”

But problems in [COVID-19] vaccine distribution, supply shortages, and intermittent participation by the population could push the pandemic endpoint to 2022, cautioned McKinsey.

“We believe herd immunity in the United States is still most likely in third or fourth quarter 2021, but that the chance of delay until first quarter 2022 or beyond has increased,” the report states, “Even later herd immunity remains possible if other challenges arise, especially vaccine safety concerns or ambivalence to vaccination following a transition toward normalcy.”

Other factors that went into the firm’s “most likely” set of possible timelines include:

  • “Unexpected safety issues emerging with early vaccines,
  • “Significant manufacturing or supply-chain delays,
  • “Continued slow adoption,
  • “Further mutation [of the virus],
  • “A shorter-than-anticipated duration of vaccine-conferred immunity.”
Graph from McKinsey and Co. report about covid-19 herd immunity projections into year 2023
The graph above, taken from the McKinsey and Co. report, illustrates how “the probability of reaching COVID-19 herd immunity in the United States is highest in the third or fourth quarter, but could shift.” (Graphic copyright: McKinsey and Company.)

A ‘Transition Toward Normalcy’

In its report, McKinsey notes that “During this transition, controlling the spread of SARS-CoV-2 will still require public-health measures (such as continued COVID-19 testing and mask use in many settings), but mortality will fall significantly, allowing greater normalization of business and social activities.”

In apparent agreement, according to data from the COVID Tracking Project, as of Jan. 27, 2021, 107,444 people were hospitalized in the US with COVID-19, as compared to 130,000 hospital cases on Jan. 13, 2021. Numbers of new cases appear to be dropping, however, McKinsey predicts that “COVID-19 will not disappear during this transition but will become a more normal part of the baseline disease burden in society (like flu, for example), rather than a special threat requiring exceptional societal response.”

It may help that more people are taking one of the vaccines. A recent survey conducted by London-based research and analytics firm YouGov, found that people worldwide are becoming more willing to take the COVID-19 vaccine. For example, in the UK, 80% of those surveyed gave a thumbs-up to getting vaccinated, compared to 61% in November. In the US, however, still only about 45% said they will get the vaccine, up slightly from 42% who said so in July, YouGov reported.

However, McKinsey points out that “vaccine rollout has not yet proceeded far enough to protect much of the population.”

How Should Medical Laboratories and Other Healthcare Providers Proceed?

In “No One Said it Would Be Easy,” Jan. 22, 2021, Becker’s Hospital Review, Michael Dowling, President and CEO of Northwell Health, wrote, “We will be living in a world preoccupied by COVID-19 and vaccination for many months to come … And the stark reality is that the vaccination rollout will continue well into the summer, if not longer, while at the same time we continue to care for hundreds of thousands of Americans sickened by the virus. Despite the challenges we face now and in the coming months in treating the disease and vaccinating a US population of 330 million, none of us should doubt that we will prevail.”

“To achieve that,” McKinsey notes, “we will need to see significant progress on the epidemiological end point … Favorable findings on natural and cross-immunity would help accelerate timelines.

“Five additional criteria will also contribute to the transition to a form of normalcy—the more of these that are achieved, the faster the milestone is likely to be reached:

  • “Continued improvement by governments in the application of public-health interventions (such as test and trace) that don’t significantly limit economic and social activities.
  • “Compliance with public-health measures until we achieve herd immunity.
  • “Accurate, widely available, rapid testing that effectively enables specific activities.
  • “Continued advancements in therapeutics (including pre- and post-exposure prophylactics) for and clinical management of COVID-19, leading to lower infection-fatality ratios—substantial progress has already been made through a combination of effective drugs, such as Dexamethasone and Remdesivir, and changes in clinical management.
  • “Public confidence that there aren’t significant long-term health consequences for those who recover from COVID-19.”

Finally, McKinsey notes that “Both the epidemiological and normalcy ends to the COVID-19 pandemic are important. The transition to the next normal will mark an important social and economic milestone, and herd immunity will be a more definitive end to the pandemic. In the United States, while the transition to normal might be accomplished sooner, the epidemiological end point looks most likely to be reached in the second half of 2021.”

It is not clear when clinical laboratories and pathologists will know for certain when the pandemic’s end point has been reached. Predictions coming from sources such as McKinsey’s latest report may be as close as we get to a crystal ball view of the pandemic’s future.

—Donna Marie Pocius

Related Information:

When Will the COVID-19 Pandemic End?

International Study How Many People Will Take COVID-19 Vaccine

Pandemic Will Not End for Anyone Until it Ends for Everyone

No One Said It Would Be Easy

Autopsies Clearly Help Pathologists Understand COVID-19 and How It Affects the Body, So Why Are More Not Being Performed?

Payers are unwilling to reimburse for autopsies despite the fact that autopsies are a proven way to learn more about new diseases and how they attack the human body

Each year, less money is spent by Medicare and private health insurers on autopsies. However, autopsies regularly provide pathologists with relevant, clinically useful information about exact causes of death and other elements of disease in the deceased. Some diseases cannot be identified any other way but by autopsy. And data from autopsies have helped developers bring critical new medical laboratory tests, therapeutic drugs, and vaccines to market.

Thus, the healthcare system is losing valuable research that would bring a better understanding of diseases and processes in the body that contribute to poor health and death. This is true with COVID-19. Autopsy results have already provided revelations into how the SARS-CoV-2 coronavirus affects the body, and yielded clues that are helping pathologists combat the illness.

Looking Closely at Death from COVID-19

“You can’t treat what you don’t know about,” Alex Williamson, MD, an anatomic/clinical/pediatric/forensic pathologist at Northwell Health in New York and Associate Professor of Pathology at Zucker School of Medicine at Hofstra/Northwell, told the Associated Press (AP), ABC News reported in “The Autopsy, a Fading Practice, Revealed Secrets of COVID-19.”

“Many lives have been saved by looking closely at someone’s death,” he added.

Autopsies performed on deceased patients could help clarify why there is such a wide array of symptoms for those affected by COVID-19 and provide details that cannot be detected in living patients.

For example, autopsies completed early in the pandemic confirmed that the SARS-CoV-2 coronavirus causes respiratory disease, and that extended use of ventilators could cause considerable damage to the lungs, the AP article noted. This discovery led physicians to re-evaluate how ventilators should be used on COVID-19 patients.

The AP story also stated that pathologists learned the SARS-CoV-2 coronavirus may spread the illness to other organs such as the heart, brain, liver, kidneys, and colon.

Through autopsies, COVID-19 patients also were discovered to have dramatic blood clotting issues in almost every organ of the body and micro-clotting in the lungs.

“The clotting was not only in the large vessels but also in the smaller vessels,” said Amy Rapkiewicz, MD, an anatomic and forensic pathologist, Chair of the Department of Pathology at NYU Langone Medical Center and Associate Professor, Department of Pathology at NYU Long Island School of Medicine, in an Advisory Board Daily Briefing. “And this was dramatic, because though we might have expected it in the lungs, we found it in almost every organ that we looked at in our autopsy study.”

Doctors are now exploring whether blood thinners should be utilized to prevent blood clots from forming in COVID-19 patients.

Lab samples and Amy Rapkiewicz, MD, Chair of the Department of Pathology at NYU Langone Medical Center and Associate Professor, Department of Pathology at NYU Long Island School of Medicine
“When you’re able to see what’s happening at the level of the cells, you just have a broader picture of the potential mechanism by which the disease is happening,” Amy Rapkiewicz, MD (above), Chair of the Department of Pathology at NYU Langone Medical Center and Associate Professor, Department of Pathology at NYU Long Island School of Medicine, told Undark. (Photo copyright: Associated Press.)

Autopsies Identify Secondary Causes of Death

Autopsies also have shown that some COVID-19 patients are dying from secondary bacterial infections that appear alongside the disease. This discovery may help doctors understand lingering symptoms that plague some coronavirus patients.

“What you see at autopsy represents an effective catalogue of the injury that occurs in patients who have COVID,” pathologist Stephen Hewitt, MD, PhD, associate research physician, Laboratory of Pathology, and head of the Experimental Pathology Laboratory at the National Cancer Institute Center for Cancer Research, told Undark. “And it gives you an understanding and a basis to try and forecast forward what we’re going to see in post-COVID syndrome.”

Shortage in Funding and Forensic Pathologists

With advances in technology, clinical laboratory testing, and imaging scans, autopsies are performed much less than they were in the past. In the 1950s, autopsies were performed on about half of the patients who passed away in hospital situations, but now that number is somewhere between only five and 11%, ABC News reported.

At this time, hospitals are not required to provide autopsy services and the costs to perform autopsies are often not covered by private or government insurance.

“As medicine has become closer to the bottom line, community hospitals don’t want to perform the autopsies because they’re not getting any functional reimbursement for them,” Hewitt told Undark.

Hospitals usually have to cover costs associated with autopsies themselves or pass those expenditures along to the deceased patient’s family. Autopsies typically cost anywhere from $1,000 to $5,000 per patient, Undark reported.

“When you consider there’s no reimbursement for this, it’s almost an altruistic practice,” Billie Fyfe-Kirschner, MD, a pathologist with Rutgers University, told the Associated Press. “It’s vitally important, but we don’t have to fund it.”

According to the AP, the US faces a critical shortage of forensic pathologists who are trained to perform autopsies. It is estimated, AP reported, that “the US has only a few hundred forensic pathologists but could use several thousand—and less than one in 100 graduating medical school students enters the profession each year.”

Clearly, pathologists have much to offer in the field of autopsies. Autopsying patients who died from COVID-19 may provide data that could greatly affect treatment for those diagnosed with the disease and improve patient outcomes overall.

—JP Schlingman

Related Information:

The Autopsy, a Fading Practice, Revealed Secrets of COVID-19

Collection and Submission of Postmortem Specimens from Deceased Persons with Confirmed or Suspected COVID-19

Autopsy Rates Were Falling for Years. Then COVID-19 Came Along

What Dozens of COVID-19 Patient Autopsies Have Revealed About the Disease

Autopsies in Maryland Show Much Higher Rate of COVID-19 than Expected

Dirty, Smelly, Raw: The Future of Forensic Pathology

Multiple Studies Raise Questions About Reliability of Clinical Laboratory COVID-19 Diagnostic Tests

In the absence of a “gold standard,” researchers are finding a high frequency of false negatives among SARS-CoV-2 RT-PCR tests

Serology tests designed to detect antibodies to the SARS-CoV-2 coronavirus that causes the COVID-19 illness have been dogged by well-publicized questions about accuracy. However, researchers also are raising concerns about the accuracy of molecular diagnostics which claim to detect the actual presence of the coronavirus itself.

“Diagnostic tests, typically involving a nasopharyngeal swab, can be inaccurate in two ways,” said Steven Woloshin, MD, MS, in a news release announcing a new report that “examines challenges and implications of false-negative COVID-19 tests.” Woloshin is an internist, a professor at Dartmouth Institute, and co-director of the Geisel School of Medicine at Dartmouth.

“A false-positive result mistakenly labels a person infected, with consequences including unnecessary quarantine and contact tracing,” he stated in the news release. “False-negative results are far more consequential, because infected persons who might be asymptomatic may not be isolated and can infect others.”

Woloshin led a team of Dartmouth researchers who analyzed two studies from Wuhan, China, and a literature review by researchers in Europe and South America that indicated diagnostic tests for COVID-19 are frequently generating false negatives. The team published their results in the June 5 New England Journal of Medicine (NEJM).

For example, one research team in Wuhan collected samples from 213 hospitalized COVID-19 patients and found that an approved RT-PCR test produced false negatives in 11% of sputum samples, 27% of nasal samples, and 40% of throat samples. Their research was published on the medRxiv preprint server and has not been peer-reviewed.

The literature review Woloshin’s team studied was also published on medRxiv, titled, “False-Negative Results of Initial Rt-PCR Assays for COVID-19: A Systematic Review.” It indicated that the rate of false negatives could be as high as 29%. The authors of the review looked at five studies that had enrolled a total of 957 patients. “The collected evidence has several limitations, including risk of bias issues, high heterogeneity, and concerns about its applicability,” they wrote. “Nonetheless, our findings reinforce the need for repeated testing in patients with suspicion of SARS-Cov-2 infection.”

Another literature review, published in the Annals of Internal Medicine, titled, “Variation in False-Negative Rate of Reverse Transcriptase Polymerase Chain Reaction–Based SARS-CoV-2 Tests by Time Since Exposure,” estimated the probability of false negatives in RT-PCR tests at varying intervals from the time of exposure and symptom onset. For example, the authors found that the median false-negative rate was 38% if a test was performed on the day of symptom onset, versus 20% three days after onset. Their analysis was based on seven studies, five of which were peer-reviewed, with a total of 1330 test samples.

Doctors also are seeing anecdotal evidence of false negatives. For example, clinicians at UC San Diego Health medical center treated a patient with obvious symptoms of COVID-19, but two tests performed on throat samples were negative. However, a third test, using a sample from a bronchial wash, identified the virus, reported Medscape.

The lesson for clinicians is that they can’t rely solely on test results but must also consider their own observations of the patient, Joshua Metlay, MD, PhD, of Massachusetts General Hospital told Medscape.

Sensitivity and Specificity of COVID-19 Clinical Laboratory Tests

The key measures of test accuracy are sensitivity, which refers to the ability to detect the presence of the virus, and specificity, the ability to determine that the targeted pathogen is not present. “So, a sensitive test is less likely to provide a false-negative result and a specific test is less likely to provide a false-positive result,” wrote Kirsten Meek, PhD, medical writer and editor, in an article for ARUP Laboratories.

“Analytic” sensitivity and specificity “represent the accuracy of a test under ideal conditions in which specimens have been collected from patients with either high viral loads or a complete absence of exposure,” she wrote. However, “sensitivity and specificity under real-world conditions, in which patients are more variable and specimen collection may not be ideal, can often be lower than reported numbers.”

In a statement defending its ID Now molecular point-of-care test, which came under scrutiny during a study of COVID-19 molecular tests by NYU Langone Health, Northwell Health, and Cleveland Clinic, according to MedTech Dive, Abbott Laboratories blamed improper sample collection and handling for highly-publicized false negatives produced by its rapid test. An FDA issued alert about the test on May 14 noted that Abbott had agreed to conduct post-market studies to identify the cause of the false negatives and suggest remedial actions.

Issues with Emergency Use Authorizations

In their NEJM analysis, Woloshin et al point to issues with the FDA’s process for issuing Emergency Use Authorizations (EUAs). For example, they noted variations in how manufacturers are conducting clinical evaluations to determine test performance. “The FDA prefers the use of ‘natural clinical specimens’ but has permitted the use of ‘contrived specimens’ produced by adding viral RNA or inactivated virus to leftover clinical material,” they wrote.

When evaluating clinical performance, manufacturers ordinarily conduct an index test of patients and compare the results with reference-standard test, according to the Dartmouth researchers. For people showing symptoms, the reference standard should be a clinical diagnosis performed by an independent adjudication panel. However, they wrote, “it is unclear whether the sensitivity of any FDA-authorized commercial test has been assessed in this way.” Additionally, a reference standard for determining sensitivity in asymptomatic people “is an unsolved problem that needs urgent attention to increase confidence in test results for contact-tracing or screening purposes.”

Stephen Rawlings, MD, PhD
“To truly determine false negatives, you need a gold standard test, which is essentially as close to perfect as we can get,” Stephen Rawlings, MD, PhD, (above), a resident physician of internal medicine and infectious diseases fellow at UC San Diego’s Center for AIDS Research (CFAR), who has been working on SARS-CoV-2 test validation since March. “But there just isn’t one yet for coronavirus,” he told Medscape. (Photo copyright: University of California, San Diego.)

In a perspective for Mayo Clinic Proceedings, Colin P. West, MD, PhD; Victor M. Montori, MD, MSc; and Priya Sampathkumar, MD, offered four recommendations for addressing concerns about testing accuracy:

  • Continued adherence to current measures, such as physical distancing and surface disinfection.
  • Development of highly sensitive and specific tests or combinations of tests to minimize the risk of false-negative results and ongoing transmission based on a false sense of security.
  • Improved RT-PCR tests and serological assays.
  • Development and communication of clear risk-stratified protocols for management of negative COVID-19 test results.

“These protocols must evolve as diagnostic test, transmission, and outcome statistics become more available,” they wrote.

Meanwhile, clinical laboratories remain somewhat on their own at selecting which COVID-19 molecular and serology tests they want to purchase and run in their labs. Complicating such decisions is the fact that many of the nation’s most reputable in vitro diagnostics manufacturers cannot produce enough of their COVID-19 tests to meet demand.

Consequently, when looking to purchase tests for SARS-CoV-2, smaller medical laboratory organizations find themselves evaluating COVID-19 kits developed by little-known or even brand-new companies.

—Stephen Beale

Related Information:

New Report Examines Challenges and Implications of False-Negative COVID-19 Tests

Questions about COVID-19 Test Accuracy Raised Across the Testing Spectrum

COVID-19 Test Results: Don’t Discount Clinical Intuition

FDA Provides New Tool to Aid Development and Evaluation of Diagnostic Tests That Detect SARS-CoV-2 Infection

EUA Authorized Serology Test Performance

Emergency Use Authorization (EUA) Information and List of All Current EUAs 

Coronavirus (COVID-19) Update: FDA Provides Promised Transparency for Antibody Tests

Understanding Medical Tests: Sensitivity, Specificity, and Positive Predictive Value

Webinar Part 1: Quality Issues Your Clinical Laboratory Should Know Before You Buy or Select COVID-19 Serology Tests

Webinar Part 2: Achieving High Confidence Levels in the Quality and Accuracy of Your Clinical Lab’s Chosen COVID-19 Serology Tests, featuring James Westgard, PhD

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