During that time, consumer demand for all COVID-19 at-home tests quickly depleted the already dwindling supply. However, the 2012 SCOTUS ruling in Mayo Collaborative Services v. Prometheus—which rewrote patent law in the biotech industry—effectively blocked patent protections for many medical laboratory diagnostic tests and procedures, wrote Paul R. Michel in a column he penned for STAT.
Michel served on the United States Court of Appeals for the Federal Circuit from 1988 to his retirement in 2010, and formerly was its chief judge from 2004 to 2010.
Shortage of COVID-19 Home Tests Due to ‘Tsunami of Demand’
The diagnostic test shortage that continued throughout the second year of the pandemic has been blamed on a “tsunami of demand,” as vaccine and testing mandates went into effect, according to CNBC. Other causes of the shortages were linked to shortages of raw materials and the US Food and Drug Administration’s slow review process, The Wall Street Journal reported.
However, as Michel noted in STAT, Mayo v. Prometheus “was a legal bombshell that upended the prior law on patent eligibility. And it has had disastrous real-world consequences for Americans.”
San Diego-based Prometheus Laboratories had developed a diagnostic test that measured how well patients metabolized medicines to treat autoimmune diseases. When Mayo Collective Services, which does business as Mayo Clinic Laboratories, developed its own test based on the Prometheus design, Prometheus sued for patent infringement. But it lost when the case reached the Supreme Court.
Michel points out that developing new clinical laboratory diagnostic tests and methods is “slow and expensive” work that becomes financially unsustainable for biotech companies when patent protections are removed.
In the “wake of the Mayo decision,” he wrote, many small biotech companies that had been focused on developing new diagnostics went out of business. Simultaneously, some major research centers, such as the Cleveland Clinic, ended programs aimed at discovering new diagnostic methods.
“However,” she added, “it is important to note that the yearly investment totals for disease diagnostic technologies have generally increased in the years following Mayo—but it has increased at a lower rate compared to all other industries.”
Shahrokh Falati, PhD, JD, director of the Patent Law Clinic at New York Law School, maintains that the Supreme Court-created exceptions to existing patent law have damaged America’s standing as a leader in new technology development and commercialization.
“The US Supreme Court effectively redefined the scope of patent eligible subject matter when it decided Mayo. This decision focused on medical diagnostic technology and has had a profound effect on the biotechnology and personalized medicine industries in the United States …,” he wrote in the North Carolina Journal of Law and Technology.
Precision Medicine at Risk without Intellectual Property Protection
Elizabeth O’Day, PhD, CEO and founder of Olaris, Inc., a precision medicine company, has advocated for reform of Section 101. In an Olaris blog post, she argues that reform should provide intellectual property protection for therapeutic companies that develop biomarkers and algorithms used in precision medicine.
“We have the omic technologies (genomic, proteomic, metabolomic, etc.) and analytical tools needed to uncover biomarkers that could dramatically enhance our ability to detect and treat disease,” O’Day wrote. “Let’s reform Section 101 so that these breakthrough products have the opportunity to reach the people that need them.”
“It is past time that Congress act to address this issue,” they wrote. “To assist us as we consider what legislative action should be taken to reform our eligibility laws, we ask that you publish a request for information on the current state of patent eligibility jurisprudence in the United States, evaluate the responses, and provide us with a detailed summary of your findings.” That letter went to Hirshfeld on March 5, 2021, with a request for findings no later than March 5, 2022.
For now, patent reform appears to be locked in uncertainty, which means SCOTUS’ decision that altered patent law affecting the biotech industry may continue to hamper development of new diagnostic tests as well as the current supply of at-home COVID-19 tests. Clinical laboratory leaders involved with diagnostic test developers will want to closely monitor for any changes to the Supreme Court’s ruling.
Decision is part of UK effort to diagnose 75% of all cancers at stage I or stage II by 2028 and demonstrates to pathologists that the technology used in liquid biopsy tests is improving at a fast pace
Pathologists and medical laboratory scientists know that when it comes to liquid biopsy tests to detect cancer, there is plenty of both hope and hype. Nevertheless, following a successful pilot study at the Christie NHS Foundation Trust in Manchester, England, which ran from 2015-2021, the UK’s National Health Service (NHS) is pushing forward with the use of liquid biopsy tests for certain cancer patients, The Guardian reported.
NHS’ decision to roll out the widespread use of liquid biopsies—a screening tool used to search for cancer cells or pieces of DNA from tumor cells in a blood sample—across the UK is a hopeful sign that ongoing improvements in this diagnostic technology are reaching a point where it may be consistently reliable when used in clinical settings.
The national program provides personalized drug therapies based on the genetic markers found in the blood tests of cancer patients who have solid tumors and are otherwise out of treatment options. The liquid biopsy creates, in essence, a match-making service for patients and clinical trials.
Liquid Biopsy Genetic Testing for Cancer Patients
“The learnings from our original ‘Target’ study in Manchester were that genetic testing needs to be done on a large scale to identify rare genetic mutations and that broader access to medicines through clinical trials being undertaken across the country rather than just one site are required,” Matthew Krebs, PhD, Clinical Senior Lecturer in Experimental Cancer Medicine at the University of Manchester, told The Guardian.
Krebs, an honorary consultant in medical oncology at the Christie NHS Foundation Trust, led the Target National pilot study.
“This study will allow thousands of cancer patients in the UK to access genetic testing via a liquid biopsy. This will enable us to identify rare genetic mutations that in some patients could mean access to life-changing experimental medicines that can provide great treatment responses, where there are otherwise limited or no other treatment options available.”
Detecting cancers at earlier stages of disease—when treatment is more likely to result in improved survival—has become a strategic cancer planning priority in the UK, theBMJ noted.
“The NHS is committed to diagnosing 75% of all cancers at stage I or II by 2028, from around 50% currently,” the BMJ wrote. “Achieving such progress in less than a decade would be highly ambitious, even without disruption caused by the COVID-19 pandemic. In this context, considerable hope has been expressed that blood tests for circulating free DNA—sometimes known as liquid biopsy—could help achieve earlier detection of cancers.”
The Guardian noted that the UK’s initiative will use a liquid biopsy test made by Swiss-healthcare giant Roche.
In her article “The Promise of Liquid Biopsies for Cancer Diagnosis,” published in the American Journal of Managed Care (AJMC) Evidence-based Oncology, serial healthcare entrepreneur and faculty lecturer at Harvard Medical School Liz Kwo, MD, detailed the optimism surrounding the “revolutionary screening tool,” including its potential for:
Welch compared the investor hype surrounding liquid biopsies to that of the now-defunct blood testing company Theranos, which lured high-profile investors to pour millions into its unproven diagnostic technology.
“Effective cancer screening requires more than early detection. It also requires that starting therapy earlier helps people live to older ages than they would if they started treatment later,” he wrote. “If that doesn’t happen, liquid biopsies will only lead to people living longer with the knowledge they have a potentially incurable disease without extending their lives. These people would be subjected to cancer therapies and their toxicities earlier, but at a time when they would otherwise be experiencing no cancer-related signs or symptoms.”
And so, while there’s much excitement about the possibility of a minimally invasive way to detect cancer, anatomic pathology groups and clinical laboratories will have to wait and see if the hype and hope surrounding liquid biopsies is substantiated by further research.
CDC advises clinical laboratories and microbiologists encountering C. auris to follow their own protocols before adopting federal agency guidelines
In July, the Centers for Disease Control and Prevention (CDC) warned healthcare facilities and clinical laboratories to be on the alert for Candida auris (C. auris) infections in their patients. An outbreak of the drug resistant and potentially deadly fungus had appeared in two Dallas hospitals and a Washington D.C. nursing home.
Since those outbreaks, researchers have studied with urgency the “superbug’s” emergence in various types of healthcare facilities around the nation, not just hospitals. Their goal was to discover how it was successfully identified and contained.
“Seeing what was happening in New York, New Jersey, and Illinois [was] pretty alarming for a lot of the health officials in California [who] know that LTACHs are high-risk facilities because they take care of [very] sick people. Some of those people are there for a very long time,” the study’s lead author Ellora Karmarkar, MD, MSc, told Medscape. Karmarkar is an infectious disease fellow with the University of Washington and formerly an epidemic intelligence service officer with the CDC.
“One of the challenges was that people were so focused on COVID that they forgot about the MDROs (multi-drug resistant organisms] … Some of the things that we recommend to help control Candida auris are also excellent practices for every other organism including COVID care,” she added.
According to Medscape, “The OCHD researchers screened LTACH and vSNF patients with composite cultures from the axilla-groin or nasal swabs. Screening was undertaken because 5%–10% of colonized patients later develop invasive infections, and 30%–60% die.
Medscape also reported that the first bloodstream infection was detected in May 2019, and that, according to the Annals of Internal Medicine study, as of January 1, 2020, of 182 patients:
22 (12%) died within 30 days of C. auris identification,
Be More Proactive than Reactive in Identifying C. Auris, CDC Says
C. auris is a type of yeast infection that can enter the bloodstream, spread throughout the body, and cause serious complications. People who appear to have the highest risk of contracting the infection are those:
Who have had a lengthy stay in a healthcare facility,
Individuals connected to a central venous catheter or other medical tubes, such as breathing or feeding tubes, or
Have previously received antibiotics or antifungal medications.
It tends to be resistant to the antifungal drugs that are commonly used to treat Candida infections.
It can be difficult to identify via standard laboratory testing and is easily misidentified in labs without specific technology.
It can quickly lead to outbreaks in healthcare settings.
“With all this spread that we’ve been seeing across the country we’re really encouraging health departments and facilities to be more proactive instead of reactive to identifying Candida auris in general,” Lyman told STAT. “Because we’ve found that controlling the situation and containing spread is really easiest when it’s identified early before there’s widespread transmission.”
Candia Auris versus Other Candida Infections
C. auris can cause dangerous infections in the bloodstream and spread to the central nervous system, kidneys, liver, spleen, bones, muscles, and joints. It spreads mostly in long-term healthcare facilities among patients with other medical conditions.
The symptoms of having a Candida auris infection include:
Redness and swelling
Fluid drainage (if an incision or wound is present)
General feeling of tiredness and malaise
C. auris infections are typically diagnosed via cultures of blood or other bodily fluids, but they are difficult to distinguish from more common types of Candida infections, and special clinical laboratory tests are needed to definitively diagnose C. auris.
Whole-genome Sequencing of C. Auris and Drug Resistance
The CDC conducted whole-genome sequencing of C. auris specimens gathered in Asia, Africa, and South America and discovered four different strains of the potentially life-threatening Candida species. All four detected strains have been found in the United States.
There are only three classes of antifungal drugs used to treat Candida auris infections:
However, 85% of the infections in the US have proven to be resistant to azoles and 38% are resistant to polyenes. Patients respond well to echinocandins, but more effective therapies are needed especially as some isolates may become resistant while a patient is on drug therapy, STAT reported.
Although relatively rare, C. auris infections are on the rise. The good news is that there may be further pharmaceutical help available soon. New antifungal agents, such as Ibrexafungerp (Brexafemme) show promise in fighting C. auris infections, but more research is needed to prove their efficacy.
What Should Clinical Laboratories Do?
The CDC stresses that clinical laboratories and microbiologists working with known or suspected cases of Candida auris should first adhere to their own safety procedures. The CDC issued guidelines, but they are not meant to supersede the policies of individual labs.
The CDC also recommends that healthcare facilities and clinical laboratories that suspect they have a patient with a Candida auris infection immediately contact the CDC and state or local public health authorities for guidance.
Cozy relationships between hospital chief executives and healthcare companies they do business with may raise ethical questions
If hospital employees, including pathologists, wonder why their hospital uses a certain company’s products and services it may be because their Chief Executive Officer (CEO) sits on the Board of Directors of the same companies from which the hospital buys products and services. That’s the suggestion in a recent Boston Globe investigative report.
In “Boston’s Hospital Chiefs Moonlight on Corporate Boards at Rates Far Beyond the National Level,” The Boston Globe reported that, in Boston, hospital CEOs at the city’s academic medical centers frequently sit on the boards of healthcare companies with which their hospitals do business. However, because the investigative reporters did not list the healthcare companies which had Boston hospital CEOs as board members, clinical laboratory managers and pathologists cannot determine from the article if their medical laboratories are using products from those same companies.
According to The Globe, five of seven CEOs and Presidents of Boston’s major teaching hospitals also receive compensation for serving as directors of publicly traded companies. And in their roles as corporate board members, hospital CEOs often receive stock in these companies, making the value of their remuneration potentially worth millions of dollars, The Globe reported.
Not Illegal, But Is It Ethical?
The Boston Globe’s investigation noted that such moonlighting, while not unheard of elsewhere in the country, is commonplace in Boston, raising ethical concerns despite conflict-of-interest policies aimed at limiting outside relationships.
“Hospitals in Boston and elsewhere that allow this outside corporate work do so under the terms of conflict-of-interest policies,” The Globe reported. “A Globe review of more than a dozen hospital conflict-of-interest policies across the country found more similarities than differences. Almost all require hospital trustees to approve a hospital chief’s outside board work and consider certain factors, such as the amount of business a company does with the hospital and time required.
“But the policies offer limited evidence about actual practices,” The Globe added. “Trustees typically retain significant discretion over what is permitted or barred, and their deliberations are generally hidden from the public. It is hard to tell if the relative rarity of hospital chiefs in other cities holding outside directorships is because of a lack of interest or opportunity, or is the result of trustees saying no.”
Though no laws were broken, some questioned the ethics of such actions. Nevertheless, The Boston Globe wrote that “Debra O’Malley, a spokesperson for Secretary of State William Galvin’s office, said Fenwick’s actions did not appear to violate the law: She is required to disclose in writing to the state that she is a lobbyist for the hospital and the bills she lobbied on, which she did, O’Malley said. That information is publicly available.”
And though The Globe reported that Boston Children’s Hospital had “declined to answer detailed questions about [Fenwick’s] lobbying efforts,” the paper wrote that a hospital spokesperson said, “[Fenwick’s] directorships are publicly disclosed in filings with the Securities and Exchange Commission.”
Fenwick retired from Boston Children’s Hospital in March 2021. The Globe noted that at that time her Teledoc Health stock, which was compensation for her board work, was worth $8.8 million. Additionally, she had been paid $2.7 million annually as CEO of Boston Children’s Hospital.
Avoiding Conflicts of Interest
Bad optics created by a Boston hospital CEO receiving seven-figure compensation for serving on the board of directors of a publicly traded company is not new. In July 2020, former Brigham and Women’s Hospital President Elizabeth Nabel, MD, resigned from the board of biotech company Moderna (NASDAQ:MRNA) “to alleviate any potential concern about the conduct or the outcome of the COVID-19 vaccine trial when Brigham and Women’s Hospital was identified by NIH as one of the clinical sites for the Phase 3 trial,” a Moderna press release states.
On March 1, 2021, Nabel also stepped down as Brigham and Women’s Hospital president. She then rejoined the Moderna board of directors on March 10, 2021, the press release noted.
In a STAT editorial, titled, “Hospital CEOs, Med School Leaders Shouldn’t Sit on For-Profit Health Care Company Boards,” endocrinologist and former Dean of Harvard Medical School Jeffrey Flier, MD, wrote, “As dean, I vigorously supported the value of robust interactions between faculty and industry to advance innovation and human health, and still do. In my current status as a professor of medicine at Harvard, I serve on several for-profit and not-for-profit boards. I learn from this work, and I believe I am making useful contributions as a board member. But I also believe that the considerations governing such relationships should be judged differently for institutional leaders.”
Flier maintains there are multiple reasons why hospital and medical school leaders should not sit on for-profit boards despite the expertise they bring to the table, including:
The time commitment required,
The “extraordinary compensation packages” they receive in their full-time jobs,
The potential for complicated “business intersections,” and
The risks to an “institution’s reputation for integrity.”
“I recommend that hospital CEOs and academic leaders at the level of Deans and Presidents devote their full attention to their well-compensated day jobs and defer positions on the boards of for-profit companies—and the unavoidable conflicts they raise—to the post-leadership phase of their careers,” Flier wrote.
While cozy relationships between hospital and academic medical center leaders and for-profit healthcare companies may not directly impact hospital pathologists and staff, it is worth staying aware of potential conflicts of interest.
Though some experts claim widespread antibody testing is key to effective public health safety, the WHO warns positive serological tests may not indicate immunity from reinfection or transmission of SARS-CoV-2
It may be the largest program of clinical laboratory testing ever conducted in the United States. Health officials are preparing to undertake large-scale serological surveys (serosurveys) to detect and track previously undetected cases of SARS-CoV-2, the novel coronavirus, that causes the COVID-19 illness.
Microbiologists, epidemiologists, and medical laboratory leaders will be interested in these studies, which are aimed at determining how many adults in the US with no confirmed history of SARS-CoV-2 infection actually possess antibodies to the coronavirus.
Serological screening testing may also enable employers to identify employees who can safely return to their job. And researchers may be able to identify communities and populations that have been most affected by the virus.
Serological Study of COVID-19 Taking Place in Five States
In an interview with Science, Michael Busch, MD, PhD, Senior Vice President, Research and Scientific Affairs of Vitalant (formerly Blood Systems), one of the nation’s oldest and largest nonprofit community blood service providers, and Director of the Vitalant Research Institute, discussed several serological studies in which he is involved. The first study, which he said is being funded by the National Institutes of Health (NIH), is taking place in six metropolitan regions in the US: Seattle, New York City, San Francisco, Los Angeles, Boston, and Minneapolis.
The interesting twist in these studies is that they will test blood samples from people donating blood. In March, participating blood centers in each region started saving 1,000 donor samples per month. Six thousand samples will be assessed monthly for a six-month period using an antibody testing algorithm that enables researchers to monitor how people develop SARS-CoV-2 antibodies over time.
Busch told Science this regional study will evolve into three “national, fully representative serosurveys of the US population using blood donors.” This particular national serosurvey will study 50,000 donations in September and December of 2020 and in November 2021.
“We’re going to be estimating overall antibody prevalence to SARS-CoV-2 within each state, but also map it down within the states to regions and metropolitan urban areas, and look at the differences,” Busch told Science, which called the serosurvey “unprecedented.”
“It’s certainly the largest serosurvey I’ve ever been involved with,” Busch said.
Some of the SARS-CoV-2 serological surveys underway include:
The National Institutes of Health serosurvey involving as many as 10,000 adults in the US who have no confirmed history of infection with SARS-CoV-2, which will analyze blood samples for two types of antibodies—anti-SARS-CoV-2 protein IgG and IgM. Researchers also may perform additional tests to evaluate volunteers’ immune responses to the virus.
A World Health Organization (WHO) coordinated follow-up study to its Solidarity Trial named Solidarity 2, which will “pool data from research groups in different countries to compare rates of infection,” which WHO officials say is ‘critical’ to understanding the true extent of the pandemic and to inform policy, Research Professionals News reported.
In Germany, the Robert Koch Institute, the country’s disease control and prevention agency, is tackling Europe’s first large-scale COVID-19 antibody testing. Its three-phase study will include serological testing on blood from donation centers, followed by testing on blood samples from coronavirus regional hotspots and then the country’s broader population.
But Can Serological Testing Prove Immunity to COVID-19?
The Times of Sweden reported the WHO warned in mid-April that there is no proof recovering from COVID-19 provides immunity.
“There are a lot of countries that are suggesting using rapid diagnostic serological tests to be able to capture what they think will be a measure of immunity,” said Maria Van Kerkhove, PhD, the WHO’s Technical Lead for COVID-19, at a news conference in Geneva, Switzerland, the Times of Sweden reported.
“Right now, we have no evidence that the use of a serological test can show that an individual has immunity or is protected from reinfection,” she said, adding, “These antibody tests will be able to measure that level of seroprevalence—that level of antibodies—but that does not mean that somebody with antibodies [is] immune.”
In addition, the reliability and quality of some serological tests produced in China, as well as some being manufactured in the US, have come into question, the Financial Times reported.
Nevertheless, as serological testing for COVID-19 becomes more widespread, clinical laboratories should plan to play an ever-increasing role in the battle to stop a second wave of the epidemic in this country.