Genomics experts say this is a sign that clinical laboratory genetics testing is maturing into a powerful tool for population health
Faced with lagging sales and employee layoffs, genomics companies in the genealogy DNA testing market are shifting their focus to the healthcare aspects of the consumer genomics data they’ve compiled and aggregated.
Recent analysis of the sales of genetic tests from Ancestry and 23andMe show the market is definitely cooling, and the analysts speculate that—independent of the consequences of the COVID-19 pandemic on consumer behavior—the two clinical laboratory genetic testing companies may already have done testing for the majority of consumers who want to buy these tests.
“I think the consumer market is going to become more integrated into the healthcare experience,” Joe Grzymski, PhD, told GenomeWeb. “Whether that occurs through your primary care doctor, your large integrated health network, or your payor, I think there will be profound changes in society’s tolerance for using genetics for prevention.”
In February, Ancestry, the largest company in the home DNA testing space, announced it was laying off 6% of its workforce or approximately 100 people, across different departments due to a decline in sales, CNBC reported. Several weeks earlier, 23andMe, the second largest company in this market, also announced it was laying off about 100 people or 14% of its workforce due to declining sales.
“I wasn’t surprised by the news,” said Linda Avey, a 23andMe co-founder who is now co-founder and Chief Executive Officer at Precisely Inc., a genomics company headquartered in San Francisco. She was commenting to GenomeWeb on the recent restructuring at her former company. “The level of expensive advertising has been insane here in the US. Those [customer acquisition costs] are not a sustainable model.”
CNBC surmised that the lull in at-home genetic testing is due mainly to:
A drought of early adopters. Individuals who were interested in the testing for genealogical and health reasons, and who believed in the value of the tests, have already purchased the product.
Privacy concerns. Some potential customers may have reservations about having their DNA information collected and stored in a database due to concerns about how that data is safeguarded and its potential uses by outside companies, law enforcement, and governments.
COVID-19 May or May Not Be a Factor in Declining DNA Testing Sales
The COVID-19 pandemic may be playing a role in the decline in sales of at-home DNA testing kits. However, there are indications that the market was cooling before the virus occurred.
An article in MIT Technology Review reported that 26 million people had purchased at-home DNA testing kits by the beginning of 2019. The article also estimated that if the market continued at that pace, 100 million people were expected to purchase the tests by the end of 2020.
However, data released by research firm Second Measure, a company that analyzes credit and debit card purchases, may show a different story, reported Vox. The data showed a general decline in test kit sales in 2019. Ancestry’s sales were down 38% and 23andMe’s sales were down 54% in November 2019 compared to November 2018. The downward trend continued in December with Ancestry sales declining 15% and 23andMe sales declining 48% when compared to December 2018.
Second Measure, however, compiled data from the two companies’ websites only. They did not include testing kits that may have been purchased through other sources such as Amazon, or at brick and mortar locations.
Nevertheless, the measures being taken by genomics companies to shore up their market indicates the Second Measure data is accurate or very close.
Rise of Population-level Genomics
This decline in genealogical sales seems to be behind DNA-testing companies shifting focus to the healthcare aspects of consumer genomics. Companies like 23andMe and Ancestry are looking into developing health reports based on their customers’ data that can ascertain an individual’s risk for certain health conditions, or how they may react to prescription medications.
“We are seeing the next wave of maturity of the genetics market,” Othman Laraki, co-founder and CEO of Color Genomics, told CNBC. “If expensive diagnostic testing was genomics’ equivalent of mainframe computers, direct to consumer ancestry genetics was the hobbyist use. While the early adopter wave is petering out, we are seeing the real market (the equivalent of a PC in every home and a phone in every pocket), which is population-level use of genetics, taking hold.” (Photo copyright: San Francisco Business Times.)
For some genomics companies like 23andMe, the at-home DNA testing market was never specifically about selling testing kits. Rather, these companies envisioned a market where consumers would pay to have their DNA analyzed to obtain data on their ancestry and health, and in turn the testing companies would sell the aggregated consumer data to other organizations, such as pharmaceutical companies.
“Remember that 23andMe was never in the consumer genomics business, they were in the data aggregation business,” Spencer Wells, PhD, founder and Executive Director of the Insitome Institute, a US-based 501(c)3 nonprofit think tank focused on key areas in the field of personal genomics, told GenomeWeb. “They created a database that should in principle allow them to do what they promised, which is to improve people’s health through genomic testing.”
Even with clinical laboratory testing currently focused on COVID-19 testing, there remains an opportunity to sequence large numbers of people through at-home DNA testing and then incorporate those findings into the practice of medicine. The hope is that sales will again accelerate once consumers feel there is a compelling need for the tests.
Pathologists and clinical laboratory managers will want to watch to see if the companies that grew big by selling ancestry and genealogy tests to consumers will start to send sales reps into physicians’ offices to offer genetic tests that would be useful in diagnosing and treating patients.
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.
Australian government heralded April purchase of 10 million clinical laboratory diagnostics tests from BGI, but most of the nation’s states and territories say kits are unneeded or unable to be used by their health departments
While the United States and other nations attempt to bring the COVID-19 outbreak under control, many countries have turned to China to offset shortages of clinical laboratory SARS-CoV-2 test kits needed to diagnose the coronavirus. This did not work out well for the United Kingdom and Spain, each which purchased large volumes of COVID-19 test kits from Chinese companies in April.
Now comes news that Australia spent roughly $130 million US ($200 million AUD) in late April for COVID-19 RT-PCR tests from BGI Genomics. However, those kits are mainly going unused as Australian state governments say they are unneeded or incompatible with existing testing equipment.
This is the latest example of the problems plaguing governments worldwide as they scramble to boost SARS-CoV-2 testing capacity during the evolving pandemic.
The new problem is that COVID-19 testing capacity has increased so much it now exceeds demand for testing. This is true for portions of Australia and in some states in the US.
Demand for Testing in Australia Far Lower than Expected
With a population of roughly 25 million, Australia has a smaller population than Texas, which in 2020 stood at about 28 million. According to the Johns Hopkins COVID-19 Dashboard, Australia had 7,139 confirmed cases of COVID-19 as of May 27 and 103 deaths.
Australian billionaire Andrew “Twiggy” Forrest, former CEO of Fortescue Metals Group, orchestrated the purchase of 10 million COVID-19 RT-PCR testing kits for Australia from BGI. He did so through his philanthropic organization, the Minderoo Foundation, with the understanding that the purchase cost would be refunded by the Australian government.
On April 28, the Australian government heralded Forrest’s purchase as a commercial coup, because it occurred in the midst of sparring between the two countries over China’s handling of the coronavirus outbreak and fierce international competition for COVID-19 diagnostic testing kits.
“Today we are securing perhaps the most critical step in our testing capability,” Australia’s Minister for Health Greg Hunt, MP (above) stated during a press conference, reported ABC News. “What these 10 million tests will do is allow our state and territory public health units to be able to test right through 2020. [They] provide us with the capacity to contain, suppress and defeat the virus, but also if a case were to emerge, to find it and to find everybody around.” However, demand for testing has not been as great as Australia’s leaders had anticipated. (Photo copyright: ABC News.)
Forrest credited his personal relationship with BGI for his ability to secure the kits for Australia. “Chairman Wang [Jian] and BGI kept to their word and resisted that very clear temptation of a businessman to make a much bigger profit and maintain the integrity of my relationship, and I’m very grateful for that,” Forrest told ABC News.
However, less than a month later, The Guardian Australia reported the taxpayer-funded coronavirus testing kits Forrest brought to Australia were not being used. Instead, the test kits have been added to the country’s strategic reserve. Three of five Australian states and both territories—Queensland, New South Wales, Western Australia, the Northern Territory, and the Australian Capital Territory—all told the newspaper they were not using the BGI tests. Only Victoria reported it was using the BGI tests.
“PathWest, Western Australia’s leading pathology laboratory, is not using the BGI-manufactured COVID-19 PCR testing kits,” the Western Australia Department of Health told The Guardian. “PathWest has capacity and sufficient reagent to provide testing throughout the state without the need to use these tests.”
“Queensland Health does not use the BGI COVID-19 test or its operating platform,” a spokeswoman told The Guardian. “Queensland already has ample testing capacity, illustrated by the world leading figures of 137,000 COVID-19 tests since January.”
According to ABC News, Minderoo also purchased 11 testing machines, which were installed around the country. Six Chinese experts flew to Australia to help oversee the testing machines’ installation.
Testing Capacity Also Exceeds Demand in US
Increased COVID-19 testing capacity has been considered a cornerstone to fully lifting stay-at-home orders and reopening businesses, schools, and entertainment venues. But Australia is not alone in ramping up testing capacity only to have public demand not keep pace. The Washington Post reported in mid-May that in at least a dozen states COVID-19 testing capacity exceeded the number of patients lining up for testing.
Utah Department of Health spokesperson Tom Hudachko is among those questioning why people aren’t getting tested in his state, which has a 9,000-test capacity, but was conducting only 3,500 tests a day.
“Well, that’s the million-dollar question,” Hudachko told the Washington Post. “It could be simply that people don’t want to be tested. It could be that people feel like they don’t need to be tested. It could be that people are so mildly symptomatic that they’re just not concerned that having a positive lab result would actually change their course in any meaningful way.”
Meanwhile, Australia’s federal government has the interesting problem of having purchased $130 million (US) of COVID-19 test kits from a Chinese company—test kits that most of the nation’s states and territories have yet to use. Could this be a sign that many clinical laboratory scientists in Australia have their doubts about the accuracy and reliability of these Chinese-manufactured COVID-19 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.
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.”
“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.)
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.
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.
Washington Post investigation outlines scientists’ frustrations in the early days of the pandemic, as they worked to deploy laboratory-developed tests for the novel coronavirus
In the wake of the failed rollout of the Centers for Disease Control and Prevention’s (CDC) COVID-19 diagnostic test last February, many CLIA-certified academic and public health laboratories were ready, and had the necessary resources, to develop their own coronavirus molecular diagnostic tests to help meet the nationwide demand for clinical laboratory testing. However, the response from the US Food and Drug Administration (FDA) was, in essence, “not so fast.”
In this second part of Dark Daily’s two-part e-briefing, we continue our coverage of the Washington Post (WP) investigation that detailed the regulatory hurdles which blocked private laboratories from deploying their own laboratory-developed tests (LDTs) for COVID-19. The report is based on previously unreported email messages and other documents reviewed by the WP, as well as the newspaper’s exclusive interviews with scientists and officials involved.
The CDC’s COVID-19 test kits began arriving at public health laboratories on February 8, just 18 days after the first case of the novel coronavirus was confirmed in the US. As the WP noted in an earlier analysis, titled, “What Went Wrong with Coronavirus Testing in the US,” the CDC’s decision to develop its own test was not surprising. “The CDC will develop [its] own test that is suited to an American healthcare context and the regulations that exist here,” explained Jeremy Konyndyk, Senior Policy Fellow at the Center for Global Development. “That’s how we normally would do things.”
But state and local public health laboratories quickly discovered that the CDC test kits were flawed due to problems with one of the reagents. While numerous academic, research, and commercial labs had the capability to produce their own COVID-19 PCR tests, FDA rules initially prevented them from doing so without a federal Emergency Use Authorization (EUA).
The bureaucratic hurdles arose due to Health and Human Services Secretary Alex Azar’s January 31 declaration that COVID-19 was a “health emergency” in the US. By doing so, HHS triggered a mandate that requires CLIA-certified labs at universities, research centers, and hospitals to seek an EUA from the FDA before deploying any laboratory-developed tests.
Scientists, Clinical Laboratories Frustrated by Bureaucratic Delays and Red Tape
To make matters worse, the EUA process was neither simple nor fast, which exasperated lab scientists and clinical laboratory administrators. “In their private communications, scientists at academic, hospital, and public health labs—one layer removed from federal agency operations—expressed dismay at the failure to move more quickly, and frustration at bureaucratic demands that delayed their attempts to develop alternatives to the CDC test,” wrote the WP investigators.
In a Feb. 27 email to other microbiologists, Marc Couturier, PhD, Medical Director at ARUP Laboratories, a national reference laboratory network located in Utah, voiced his irritation with the red tape that stymied private laboratory development of COVID-19 tests. He wrote, “We have the skills and resources as a community, but we are collectively paralyzed by a bloated bureaucratic/administrative process,” reported the WP.
Keith Jerome, MD, PhD (above), Head of the Virology Division at the Fred Hutchinson Cancer Research Center in Seattle, maintains federal regulations muted one of the nation’s greatest assets in the fight against COVID-19. “The great strength the US has always had, not just in virology, is that we’ve always had a wide variety of people and groups working on any given problem,” he told MIT Technology Review. “When we decided all coronavirus testing had to be done by a single entity, even one as outstanding as CDC, we basically gave away our greatest strength.” (Photo copyright: Jonathan Hamilton/NPR.)
‘FDA Should Not Treat Labs Like They Are Creating Commercial Products’
According to Kaiser Health News (KHN), Greninger was able to identify one of the nation’s first cases of community-acquired COVID-19 by taking “advantage of a regulatory loophole that allowed the lab to test samples obtained for research purposes from UW’s hospitals.”
But navigating the EUA process was a different story, Greninger told the WP. He spent more than 100 hours filling out forms and collecting information needed for the EUA application. After emailing the application to the FDA, Greninger received a reply containing eCopy Guidance telling him he needed to resubmit the information to the Document Control Center (DCC) at the Center for Devices and Radiological Health (CDRH), a federal agency Greninger knew nothing about. Another FDA rule required that the submission be copied to a hard disk and mailed to the DCC.
In an interview with ProPublica, Greninger stated that after he submitted his COVID-19 test—which copies the CDC protocol—an FDA reviewer told him he would need to prove the test would not show a positive result for someone infected with either a SARS or MERS coronavirus. The first SARS coronavirus disappeared in mid-2003 and the only two cases of MERS in the US were diagnosed in 2014. Greninger told ProPublica it took him two days to locate a clinical laboratory that could provide the materials he needed.
Greninger maintains the FDA should not treat all clinical laboratories as though they are making a commercial product. “I think it makes sense to have this regulation when you’re going to sell 100,000 widgets across the US. That’s not who we are,” he told ProPublica.
FDA Changes Course
Under pressure from clinical laboratory scientists and medical doctors, by the end of February the FDA had issued new policy that enabled CLIA-certified laboratories to immediately use their validated COVID-19 diagnostics while awaiting an EUA. “This policy change was an unprecedented action to expand access to testing,” said the FDA in a statement.
Since then, the FDA has continued to respond—albeit slowly—to scientists’ complaints about regulations that hampered the nation’s COVID-19 testing capacity.
Clinical laboratory leaders and pathologists involved in testing for the SARS-CoV-2 coronavirus should monitor the FDA’s actions and be aware of when and if certain temporary changes the agency implemented during the early days of the COVID-19 pandemic become permanent.
To read part one of our two-part coverage of the Washington Post’s investigation, click here.
