But even though the College of American Pathologists (CAP) and nine other organizations signed a December 12 stakeholder letter to leaders of key House and Senate committees urging passage of legislation that would enable some regulation of LDTs, the VALID Act was ultimately omitted from the year-end omnibus spending bill (H.R. 2617).
That may be due to pressure from organizations representing clinical laboratories and pathologists which lobbied hard against the bill.
Responding to criticism of its stance on FDA oversight of LDTs, in a May 2022 open letter posted on the organization’s website, anatomic pathologist and CAP president Emily Volk, MD, said “we at the CAP have an honest difference of opinion with some other respected laboratory organizations. … We believe the VALID Act is the only viable piece of legislation addressing the LDT issue. … the VALID Act contains many provisions that are similar to policy the CAP has advocated for regarding the regulation of laboratory tests since 2009. Importantly, the current version includes explicit protections for pathologists and our ability to practice medicine without infringement from the Food and Drug Administration (FDA).” (Photo copyright: College of American Pathologists.)
Organizations on Both Sides Brought Pressure to Bear on Legislators
The AAMC and AMP were especially influential, Bucshon told ProPublica. In addition to spending hefty sums on lobbying, AMP urged its members to contact legislators directly and provided talking points, ProPublica reported.
“The academic medical centers and big medical centers are in every state,” Bucshon said. As major employers in many locales, they have “a pretty big voice,” he added.
Discussing CAP’s reasoning behind its support of the VALID Act in a May 26 open letter and podcast, CAP president Emily Volk, MD, said the Valid Act “creates a risk-based system of oversight utilizing three tiers—low, moderate and high risk—in order to target the attention of the FDA oversight.”
While acknowledging that it had room for improvement, she lauded the bill’s three-tier risk-based system, in which tests deemed to have the greatest risks would receive the highest level of scrutiny.
She also noted that the bill exempts existing LDTs from an FDA premarket review “unless there is a safety concern for patients.” It would also exempt “low-volume tests, modified tests, manual interpretation tests, and humanitarian tests,” she wrote.
In addition, the bill would “direct the FDA not to create regulations that are duplicative of regulation under CLIA,” she noted, and “would require the FDA to conduct public hearings on LDT oversight.”
Pros and Cons of the VALID Act
One concern raised by opponents relates to how the VALID Act addressed user fees paid by clinical laboratories to fund FDA compliance activities. But Volk wrote that any specific fees “would need to be approved by Congress in a future FDA user fee authorization bill after years of public input.”
During the May 2022 podcast, Volk also cast CAP’s support as a matter of recognizing political realities.
“We understand that support for FDA oversight of laboratory-developed tests or IVCTs is present on both sides of the aisle and in both houses of Congress,” she said. “In fact, it enjoys wide support among very influential patient advocacy groups.” These groups “are very sophisticated in their understanding of the issues with laboratory-developed tests, and they do have the ear of Congress. There are many in the laboratory community that believe the VALID Act goes too far, but I can tell you that many of these patient groups don’t believe it goes far enough and are actively pushing for even more restrictive paradigms.”
Also urging passage of the bill were former FDA commissioners Scott Gottlieb, MD, and Mark B. McClellan, MD, PhD. In a Dec. 5 opinion piece for STAT, they noted that “diagnostic technologies have undergone considerable advances in recent decades, owing to innovation in fields like genomics, proteomics, and data science.” However, they wrote, laws governing FDA oversight “have not kept pace,” placing the agency in a position of regulating tests based on where they are made—in a medical laboratory or by a manufacturer—instead of their “distinctive complexity or potential risks.”
In their May 22 letter, opponents of the legislation outlined broad areas of concern. They contended that it would create “an onerous and complex system that would radically alter the way that laboratory testing is regulated to the detriment of patient care.” And even though existing tests would be largely exempted from oversight, “the utility of these tests would diminish over time as the VALID Act puts overly restrictive constraints on how they can be modified.”
CLIA Regulation of LDTs also Under Scrutiny
The provision to avoid duplication with the Clinical Laboratory Improvement Amendments (CLIA) program—which currently has some regulatory oversight of LDTs and IVCTs—is “insufficient,” opponents added, “especially when other aspects of the legislation call for requirements and activities that lead to duplicative and unnecessary regulatory burden.”
Opponents to the VALID Act also argued that the definitions of high-, medium-, and low-risk test categories lacked clarity, stating that “the newly created definition of moderate risk appears to overlap with the definition of high risk.”
The opponents also took issue with the degree of discretion that the bill grants to the US Secretary of Health and Human Services. This will create “an unpredictable regulatory process and ambiguities in the significance of the policy,” they wrote, while urging the Senate committee to “narrow the discretion so that stakeholders may better evaluate and understand the implications of this legislation.”
Decades ago, clinical laboratory researchers were allowed to develop assays in tandem with clinicians that were intended to provide accurate diagnoses, earlier detection of disease, and help guide selection of therapies. Since the 1990s, however, an industry of investor-funded laboratory companies have brought proprietary LDTs to the national market. Many recognize that this falls outside the government’s original intent for encouragement of laboratory-developed tests to begin with.
Researchers at the university suggested their findings could lead to new genetic tests that could be offered by medical laboratories
New research conducted at the University of Utah suggests that clinical laboratories may someday be able to deploy genetic tests to indicate whether a couple has a higher-than-average risk of stillbirth.
This is yet another example of how researchers are cracking DNA’s code to understand how certain gene variants may affect the healthcare of offspring. The knowledge produced by this research, as confirmed by additional studies, may lead to genetic markers that medical laboratories can use to diagnose the risk of stillbirth using the parent’s DNA.
“Stillbirth is one of those problems that is so tragic and life-changing,” said study co-author Jessica Page, MD (above). “It is especially frustrating when you don’t have a good answer for why it happens. This knowledge may give us the opportunity to change how we risk stratify people and reduce their risk through prevention.” Should this research be validated, clinical laboratories may soon have new genetics tests to help doctors identify risk for stillbirth. (Photo copyright: Intermountain Healthcare.)
“Stillbirth rate reduction has been slow in the US and we think many stillbirths may be potentially preventable,” she said in a university press release. “This is motivating us to look for those genetic factors so we can achieve more dramatic rate reduction.”
According to the press release, the University of Utah researchers found that stillbirth “can be inherited and tends to be passed down through male members of the family. That risk preferentially comes from the mother’s or father’s male relatives—their brothers, fathers, grandfathers, uncles, or male cousins. But the odds of a couple losing a baby to stillbirth are even greater when the condition comes from the father’s side of the family.”
The researchers made this discovery by analyzing data from the Utah Population Database (UPDB), which contains information on eight million people who were born in the state or have other connections there. The database is maintained by the Huntsman Cancer Institute at the University of Utah. It includes genealogical information and health records that allowed the researchers to trace incidence of stillbirths across multiple generations of families.
The researchers examined 9,404 stillbirth cases between 1978 and 2019, along with 18,808 live births that served as controls. They identified 390 multi-generational families with high numbers of stillbirths. Within that group, they looked at incidence of stillbirth among first-, second-, and third-degree relatives of stillborn babies. They then compared those numbers with data from unaffected families.
“We were able to evaluate multigenerational trends in fetal death as well as maternal and paternal lineages to increase our ability to detect a familial aggregation of stillbirth,” said genetic epidemiologist Tsegaselassie Workalemahu, PhD, lead author of the study. “Not many studies have examined inherited genetic risk for stillbirth because of a lack of data. The Utah Population Database allows for a more rigorous evaluation than has been possible in the past.”
Workalemahu described the research as “an important step toward identifying specific genes that increase the risk of stillbirth, which could one day lead to better diagnosis and prevention,” according to the university press release.
One caveat, the press release notes, is that Utah’s population is disproportionately of northern European descent. “Future studies will need to determine whether the trends hold true among people of different races and ethnicities,” it stated.
Call for More Testing
The University of Utah study is part of a larger effort to gain a greater understanding of the causes of stillbirths.
The story notes that “more than 20,000 pregnancies in the US end in stillbirth,” and in one in three of those cases, the cause is not determined.
Drucilla Roberts, MD, an obstetric and perinatal pathologist at Massachusetts General Hospital (MGH), told ProPublica that at a minimum, “the placenta should definitely be evaluated in every stillbirth.” But citing CDC data, the story notes that this is done in only 65% of stillbirths, and autopsies are performed in less than 20%.
“Experts blame the low rates on several factors,” the story states. “Because an autopsy often is performed in the days following a stillbirth, doctors and nurses have to ask families soon after they receive news of the death if they would like one. Many families can’t process the loss, let alone imagine their baby’s body being cut open. What’s more, many doctors aren’t trained in the advantages of an autopsy, or in communicating with parents about the exam.”
One consequence, ProPublica notes, is that clinicians are ill-equipped to advise patients on how to reduce risk in future pregnancies. The story describes the case of Karen Gibbins, MD, a maternal-fetal medicine specialist and an assistant professor of obstetrics and gynecology at the Oregon Health and Science University (OHSU) in Portland.
An Opportunity for Pathologists
Gibbins’ son was stillborn in 2018. She asked for an autopsy and learned that her son “had a rare disease caused by her antibodies attacking the cells in his liver,” the story states. When she became pregnant again, her doctor prescribed antibody infusions and she later gave birth to a healthy son. “If we had not had that autopsy, my third child would have died as well,” she told ProPublica.
This parent’s comment about the value of the autopsy done after her son’s stillbirth identifies an opportunity for the pathology profession. For several decades, health plans have become ever more reluctant to pay for autopsies. Yet, pathologists know the value that autopsies can provide.
The immediate value comes from revealing useful insights about all the health conditions of the deceased. The long-term value comes from the ability to gather the findings across a large number of autopsies that can contribute to new knowledge about health conditions that physicians use to improve the diagnoses of different health conditions.
Thus, with the publication of this peer-reviewed study about the connection between genetic variations and stillbirth, there is the opportunity for some of the nation’s pathology societies to advocate for funding a pilot program to fund more autopsies of stillborn babies, specifically to add more knowledge about the role of gene mutations as a causative factor in stillbirths.
The fledgling test-kit company sent plastic preforms that were intended for use in the manufacturing of soda bottles, not clinical laboratory specimen tubes
When is a specimen tube not a specimen tube? When it is a plastic tube made for creating soda bottles. And that may be exactly what the Federal Emergency Management Agency (FEMA) received after paying $7.3 million to a fledgling Florida-based company that won a multi-million-dollar no-bid contract from the federal government for COVID-19 clinical laboratory testing supplies, which FEMA then shipped nationwide to states that had requested the supplies.
FEMA signed the deal with Fillakit, LLC, on May 7, 2020, “just six days after the company was formed,” reported ProPublica, which went on to state that the shipment of unusable Fillakit specimen tubes contributed to delays in rolling out widespread COVID-19 testing in the US.
According to ProPublica, Fillakit supplied “preforms” that are designed to be expanded with heat and pressure into 2-liter soda bottles, not laboratory specimen tubes.
Michelle Forman, a spokesperson for the Association of Public Health Laboratories, told ProPublica one major flaw of the Fillakit tubes is their size. “They are an unusual shape, so they don’t fit racks,” she said, “and we are getting lots of pushback about how difficult it is to work with them from our clinical partners.”
Fillakit Employees Describe ‘Unsanitary’ Working Conditions
Ex-employees of Fillakit told the Wall Street Journal (WSJ) the specimen tubes were being handled in unsanitary open-air conditions in a warehouse outside of Houston where the test kits were being assembled.
“There were up to 250 workers crowded in a small warehouse room, shoulder to shoulder … working off of fold-up tables with supplies placed on the floor and handled without gloves,” Teresa Bosworth Green told Community Impact (CI), which reported that Green worked at Fillakit from May 11-20.
“We were told that we would be filling and capping tubes that would be used for COVID testing,” Green told CI.
However, according to CI, Green “expressed concern about the lack of cleanliness and facemasks. Green brought her own mask, but workers were not initially provided any.”
Green told CI, “People were breathing and coughing right over the solution.”
In a letter to FEMA and the Department of Health and Human Services (HHS) after Michigan received more than 322,000 tubes of transport media manufactured by Fillakit, Democrat Senators Debbie Stabenow and Gary Peters wrote, “Even if the tubes themselves were not unsuitable for testing purposes, the contamination risks inherent in such careless handling would cause serious concerns about the reliability of any tests conducted using these materials.”
On July 7, 2020, the Wall Street Journal reported that Fillakit had notified the Florida Secretary of State on June 26 that the company had been dissolved.
Under Pressure, Feds Award Contracts for COVID-19 Test Supplies to Inexperienced Suppliers
Fillakit as just one example out of “more than 250 companies that got contracts worth more than $1 million without going through a fully competitive bidding process,” NPR reported.
“Government procurement experts say federal officials were trying to move quickly to deliver desperately needed personal protective equipment,” NPR continued. “But they question the need to turn to contractors who have never worked with the government before and lacked experience making or delivering the protective gear.”
Among those receiving contracts were companies with little to no experience in manufacturing clinical laboratory testing supplies, personal protective equipment (PPE), as well as others that had never worked in the medical field. One company imported vodka, while another was a school security consultant. Many of the contractors served as middlemen, securing PPE from Chinese manufacturers, which meant they often were “competing with federal agencies, state governments, and local health systems,” all of which were attempting to buy the same equipment in the global marketplace, NPR reported.
A ProPublica analysis of coronavirus contracts found that about 13% of total federal government pandemic spending went to first-time vendors. And in a follow-up article, ProPublica claimed, “many of the new contractors have no experience acquiring medical products.”
FEMA, however, maintains it pays for purchases only after they have been delivered to minimize potential for waste of taxpayer dollars. “FEMA does not enter into contracts unless it has reason to believe they will be successfully executed,” the agency told ProPublica.
The US’ lack of preparedness for the COVID-19 pandemic has resulted in missteps and misspending as federal agencies struggle to provide hospitals, clinical laboratories, and healthcare providers with personal protective gear and test supplies, and to ramp up COVID-19 testing nationwide.
This is yet another instance where federal agencies appear to lack the competencies required to fulfill healthcare requirements with proven products that meet critical specifications. Meanwhile, in every community throughout the United States, independent medical laboratories and hospital-based laboratories are clamoring for adequate supplies of everything from collect swabs and viral transport media to reagents and cuvettes.
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.
‘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.
Previously unreported email messages and documents paint vivid picture of public health laboratory officials’ dismay and frustration over testing delays
Between late January and early March, Clinical laboratory leaders watched with dismay as federal government missteps crippled the Centers for Disease Control and Prevention’s (CDC) rollout of its COVID-19 diagnostic testing in the early days of the pandemic. The resulting lack of testing capacity enabled the novel coronavirus’ spread across the United States.
This first part of Dark Daily’s two-part e-briefing covers how investigators at the Washington Post (WP) have produced a timeline describing the CDC initial failure to produce a reliable laboratory test for COVID-19 and the regulatory hurdles that blocked medical laboratories from developing their own tests for the virus. The WP’s report is based on previously unreleased email messages and other documents reviewed by the WP, as well as the newspaper’s exclusive interviews with medical laboratory scientists and officials involved.
A New York Times report on the federal government’s initial review of the testing kit failure pinned the blame on sloppy practices at CDC laboratories in Atlanta and a lack of expertise in commercial manufacturing. However, the WP reported that COVID-19 testing kits were delayed due to a “glaring scientific breakdown” at the central lab, created when the CDC facilities that assembled the kits “violated sound manufacturing practices” that resulted in cross contamination of testing compounds.
The US and other countries have criticized China for a lack of transparency about the virus’ emergence, which came to light on December 31, 2019, when China reported a cluster of pneumonia cases in Wuhan, according to a World Health Organization (WHO) timeline. A week later, Chinese authorities identified the pneumonia-like illness as being caused by a new novel coronavirus.
In the US, the first case of COVID-19 was found January 21 in a Washington State man who had traveled to Wuhan. But in the weeks that followed, the US government’s inability to establish a systematic testing policy became the catalyst for the virus’ ultimate spread to more than two million people, notes the CDC website.
ProPublica, which conducted its own investigation into the early stages of the government’s coronavirus response, blamed the failures on “chaos” at the CDC and “an antiquated public health system trying to adapt on the fly.”
The CDC’s first mistake may have been underestimating the danger COVID-19 posed to public health in this country. During a January 15 conference call, CDC scientists assured state and county public health officials that the agency was developing a COVID-19 diagnostic test which soon would be available, but which may not be needed “unless the scope gets much larger than we anticipate right now,” reported the WP.
A week later, an interview with CNBC, President Trump said, “We have it under control. It’s going to be just fine.”
CDC scientists designed their test in seven days, which, according to the WP investigators, is “a stunningly short period of time for a healthcare system built around the principles of medical quality and patient safety, not speed.” But when those initial CDC-made tests arrived at a New York City public health laboratory on February 8, lab technicians discovered the COVID-19 assays often indicated the presence of the coronavirus in samples that the lab’s scientists knew did not contain the virus.
When the scientists informed Lab Director Jennifer Rakeman, PhD, Assistant Commissioner, New York City Department of Health and Mental Hygiene, her response, according to the WP, was “Oh, s—. What are we going to do now?”
That night, Director Jill Taylor, PhD, Director of New York State’s Wadsworth Center public health reference laboratory, emailed state health officials, stating, “There is a technical problem in one of the reagents which invalidates the assay and will not allow us to perform the assay,” reported the WP. “I’m sorry not to have better news.”
By the end of February, the Associated Press (AP) reported that only 472 patients had been tested for COVID-19 nationwide. By comparison, South Korea, which identified its first case of COVID-19 on the same day as the US, was testing 1,000 people per day.
A WHO spokesperson told the WP that, “… no discussions occurred between WHO and CDC (or other US government agencies) about WHO providing COVID-19 tests to the US.” When the CDC’s original COVID-19 test kit failed, there may not have been a Plan B. This may explain why the opportunity to contain COVID-19 through surveillance testing was lost during the weeks it took to design a fix for the CDC test and loosen regulations so clinical laboratories could develop their own tests.
As medical laboratory scientists and clinical laboratory leaders know, the lack of early COVID-19 testing was a public health failure and painted a false picture of the virus’ spread. Nearly five months after the first case of the virus was confirmed in the US, testing capacity may only now be outpacing demand.
Click here to read part two of our coverage of the Washington Post’s investigation.