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At-Home Paper Influenza Test Differentiates Strains, Gives Hope for Improved Screening and Surveillance of Viral Outbreaks

Researchers used CRISPR-based assays to develop new clinical laboratory point-of-care blood test which boasts accuracy, affordability, and accessibility

Here’s a novel use of paper as clinical laboratory test media. Researchers at Princeton University in New Jersey, the Massachusetts Institute of Technology’s Broad Institute, and Harvard University have developed an at-home paper-strip test that can not only identify the presence of influenza, but it can also differentiate between different strains of the flu bug.

According to UPI, the test can “distinguish between influenza A and influenza B—the two main types of seasonal flu—as well as identifying more virulent strains like H1N1 and H3N2.”

Many research teams are working to develop paper-based diagnostic screening tests because of their lower cost to produce and usefulness in remote locations. Should this near-patient point-of-care test become clinically viable, it could mean shorter times to answer, enabling speedier diagnoses and earlier start of treatment.

It also means patient specimens do not have to be transported to a clinical laboratory for testing. And reduced cost per test makes it possible to test more people. This serves the public health aspect of monitoring outbreaks of influenza and other diseases and gives hope for improved treatment outcomes.

“Being able to tease apart what strain or subtype of influenza is infecting a patient has repercussions both for treating them and public health interventions, said Jon Arizti Sanz, PhD, co-lead study author and postdoctoral researcher at the Broad Institute of Harvard and MIT, in a Broad Institute news release.

The researchers published their findings in The Journal of Molecular Diagnostics titled, “CRISPR-Based Assays for Point-of-Need Detection and Subtyping of Influenza.”

“Ultimately, we hope these tests will be as simple as rapid antigen tests, and they’ll still have the specificity and performance of a nucleic acid test that would normally be done in a laboratory setting,” Cameron A. Myhrvold, PhD (above), Assistant Professor of Molecular Biology at Princeton University in New Jersey, told CIDRAP. Influenza tests that can be performed at the point of care and in remote locations may reduce the number of screening tests performed by clinical laboratories. (Photo copyright: Michael James Butts/Hertz Foundation.)

Inspiration from Prior COVID-19 Test

According to an article published by the Center for Infectious Disease Research and Policy Research and Innovation Office (CIDRAP) at the University of Minnesota, the original test was developed in 2020 in a Harvard laboratory led by computational geneticist Pardis Christine Sabeti, MD, PhD, professor, Department of Organismic and Evolutionary Biology, and co-senior author of the study.

Her team developed their tests using Streamlined Highlighting of Infections to Navigate Epidemics (SHINE), “a clustered regularly interspaced short palindromic repeats (CRISPR)-based RNA detection platform,” the researchers wrote in their Journal of Molecular Diagnostics paper.

“SHINE has a runtime of 90 minutes, can be used at room temperature and only requires an inexpensive heat block to heat the reaction. The SHINE technology has previously been used to identify SARS-CoV-2 and later to distinguish between the Delta and Omicron variants,” Bioanalysis Zone reported.

“The test uses genetically engineered enzymes to identify specific sequences of viral RNA in samples,” the researchers told UPI. Originally designed to detect COVID-19, the team adapted the technology to detect influenza in 2022 “with the aim of creating a screening tool that could be used in the field or in clinics rather than hospitals or high-tech diagnostic labs,” they said.

Influenza A and B as well as H1N1 and H3N2 subtypes were the targets of the four SHINE assays. “When tested on clinical samples, these optimized assays achieved 100% concordance with quantitative RT-PCR. Duplex Cas12a/Cas13a SHINE assays were also developed to detect two targets simultaneously,” the researchers wrote in their paper.

The team used “20 nasal swabs from people with flu-like symptoms during the 2020-2021 flu season, nasal fluid from healthy people as the control, and 2016-2021 influenza sequences downloaded from the National Center for Biotechnology Information Influenza (NICB) database. They compared the results with those from quantitative reverse transcription-polymerase chain reaction (RT-PCR) tests,” CIDRAP reported.

The original 2020 test (shown above) takes 90 minutes to develop at room temperature. The test developers aim to drop this down to 15 minutes. In comparison, typical polymerase chain reaction (PCR) testing requires medical laboratories to have specialized equipment, trained staff, and prolonged processing times, the Broad Institute news release notes. (Photo copyright: Broad Institute.)

Implications of the New Tests

The ease of the new tests is an important development since approximately only 1% of individuals who come down with the flu see doctors for testing, according to the news release. And researchers had this in mind, looking at speed, accuracy, and affordability as a means to “improve outbreak response and infection care around the world,” UPI reported.

There are great benefits to strain differentiation that be achieved with the new test. Doctors are hopeful the test will help dial in the best treatment plans for patients since some strains are resistant to the antiviral medication oseltamivir (Tamiflu), UPI noted. This is significant since Tamiflu “is a common antiviral,” said Sanz in the Broad Institute news release.

“These assays have the potential to expand influenza detection outside of clinical laboratories for enhanced influenza diagnosis and surveillance,” the Journal of Molecular Diagnostics paper noted. This allows for more strategic treatment planning.

“Using a paper strip readout instead of expensive fluorescence machinery is a big advancement, not only in terms of clinical care but also for epidemiological surveillance purposes,” said Ben Zhang, an MD candidate in the Health Sciences and Technology at Harvard and co-first author of the study, in the Broad Institute news release.

Future Plans for Tests

“With further development, the test strip could be reprogrammed to distinguish between SARS-CoV-2 and flu and recognize swine flu and avian flu, including the H5N1 subtype currently causing an outbreak in US dairy cattle,” the study authors told CIDRAP.

The team is also looking at ways to help prevent H5N1 from crossing into human contamination, Sanz told UPI.

The new Princeton/MIT/Harvard tests echo the trend to bring in affordability and ease-of-use with accurate results as an end goal. Faster results mean the best treatments for each person can start sooner and may render the transport of specimens to a clinical laboratory as a second step unnecessary.

As research teams work to develop paper-based viral tests for their plethora of benefits, clinical laboratories will want to pay close attention to this development as it can have a big implication on assisting with future outbreaks.

Additional research is needed before these tests are going to be commonplace in homes worldwide, but this first step brings inspiration and hope of what’s to come. 

—Kristin Althea O’Connor

Related Information:

Simple Test for Flu Could Improve Diagnosis and Surveillance

Simple Paper-Strip Test Might Spot Flu, Identify Strain

CRISPR-Based Assays for Point-of-Need Detection and Subtyping of Influenza

Paper Strip Test Can Identify Flu Subtypes, May Have Other Applications, Scientists Say

Streamlined Inactivation, Amplification, and Cas13-based Detection of SARS-Cov-2

Paper Strip Test Using CRISPR and SHINE Technology Has Been Developed for Rapid Influenza Diagnosis

Salary Rates for Travel Nurses Remain Strikingly High, Spurring States to Lobby Against Alleged Price Gouging by Staffing Agencies

Proposed regulation to limit rate increases during health crises gets pushback from staffing agencies and travel nurses who disagree with salary restrictions

Hospitals across the nation are seeking relief from skyrocketing costs due to increased demand for temporary workers—especially travel nurses. This has led organizations like the American Hospital Association (AHA) to step in and call for legislators to cap spiking salary rates. Many clinical laboratories report similar increases in salaries following the outbreak of SARS-CoV-2 for medical technologists (MTs), clinical laboratory scientists (CLSs), histologists, and other skilled positions. This increase in salaries of lab scientists was mirrored by an even greater increase in the cost of travel MTs.

According to analysis conducted by Becker’s Hospital Review of hiring data from Vivian Health, an online job placement website for healthcare professionals, “Average weekly travel nurse pay climbed from $1,896 in January 2020 to $3,782 in December 2021, a 99.47% increase.”

A prior study by Kaufman Hall and Associates, LLC., found rates for temporary workers almost 500% higher than pre-pandemic times. While numbers are trending downward, it’s clear that rates are still high enough to cause alarm, KFF Health News reported.

Dave Dillon

“During the pandemic there were staffing companies who were making a lot of promises and not necessarily delivering,” Dave Dillon (above), VP of Public and Media Relations at Missouri Hospital Association, told KFF Health News. “It created an opportunity for both profiteering and for bad actors to be able to play in that space.” (Photo copyright: L.G. Patterson/Missouri Hospital Association.)

AHA Alleges Price Gouging

Demand for temporary healthcare workers surged during the COVID-19 pandemic, and, because supply was limited, salaries for temporary workers—such as travel nurses—soared as well. This dramatic increase in hospitals’ costs prompted the AHA in 2021 to send a letter to the Federal Trade Commission seeking relief for healthcare providers from what the organization called “anticompetitive pricing by nurse-staffing agencies.”

In January 2022, about 200 House members urged then White House COVID-19 Response Team Coordinator Jeffrey Zients “to investigate reports that nurse staffing agencies are taking advantage of the COVID-19 pandemic to increase their profits at the expense of patients and the hospitals that treat them,” an AHA new release noted.

In an AHA House Statement titled, “Pandemic Profiteers: Legislation to Stop Corporate Price Gouging,” the AHA wrote “Our concerns range from potential collusion to increased prices way beyond competitive levels and/or egregious price gouging and the impact these behaviors could have on efforts to care for patients and communities.”

Temporary nurses make up a large portion of staff nationwide with 1,760,111 employed nationally as of September, according to Zippia research. With some nurses commandeering $40,000 signing bonuses and pay rates up to $10,000 a week for ICU nurses during the height of the COVID-19 pandemic, the significant impact of these rate hikes cannot be ignored.

“We have received reports that the nurse staffing agencies are vastly inflating price by two, three, or more times pre-pandemic rates, and then taking 40% or more of the amount being charged to the hospitals for themselves as profits. This situation is urgent and reliance on temporary workers caused normal staffing costs to balloon in all areas of the country,” Representatives Peter Welch, D-VT, and Morgan Griffith, R-VA, wrote in the letter submitted by the AHA to House members.

States Take a Stand

But nothing was done at the federal level to cap rates for travel nurses, so hospital organizations in 14 states lobbied legislators to cap rates at the local level. However, this has proven to be problematic.

At this time, at least 14 states have proposed legislation that impose limits on what temp nursing services can charge and what stipulations they must follow during a crisis. Navigating this patchwork of state laws could be challenging for both hospitals and temporary nurses.

Some states are taking sterner measures, KFF Health News reported:

  • Missouri regulators proposed legislation that would allow felony charges to be brought against healthcare staffing agencies that raise prices during emergencies.
  • Texas lawmakers proposed legislation that would administer civil penalties against agency price-gouging—laws which the state does not have on the books at all—and also would allow fees up to $10,000 to be assessed per violation of the proposed law.
  • New York proposed amendments to legislation that would cap the amount temporary staffing agencies could charge.

Nurses, Staffing Agencies Tell Their Side

The implementation of new laws to protect hospitals from alleged temp agency price gouging presents new challenges. One issue is state-to-state competition.

“It might become difficult to hire travel nurses, and some states could face a lower-quality hiring pool during a national crises if the neighboring state doesn’t have strict measures,” Hannah Neprash, PhD, Assistant Professor, Division of Health Policy and Management at the University of Minnesota, told KFF Health News.

And financial handcuffs may not sit well with staffing agencies that feel misunderstood by hospital organizations pushing for regulation. According to KFF Health News, “Typically about 75% of the price charged by a staffing agency to a healthcare facility goes to costs such as salary, payroll taxes, workers’ compensation programs, unemployment insurance, recruiting, training, certification, and credential verification, said Toby Malara, a Vice President at the American Staffing Association trade group.”

Malara added, “hospital executives have, ‘without understanding how a staffing firm works,’ wrongly assumed price gouging has been occurring. In fact, he said many of his trade group’s members reported decreased profits during the pandemic because of the high compensation nurses were able to command,” KFF Health News reported.

Not surprisingly, many nurses have also come out against government regulation of their wages.

“Imagine the government attempting to dictate how much a lawyer, electrician, or plumber would make in Missouri. This would never be allowed, yet this is exactly what’s happening right now to nurses,” Theresa Newbanks, FNP, a nurse practitioner who is affiliated with several hospitals in multiple states.

Creative Responses Required

Increases in both rates and legislation continue to spur creativity among hospitals needing to fill shifts, support staff, and prevent worker burnout.

The American Hospital Association December 2022 Task Force noted this in their “Creative Staffing Models” paper. The AHA cited telehealth visits, technical support, and working with non-traditional partners as beneficial ideas. These were also noted as meaningful ways to recruit and retain staff.

Other hospital systems have even created their own staffing agencies. Allegheny Health Network (AHN) developed a variety of systems where nurses can work a single weeklong assignment, multiple-week assignments, or transfer to other facilities, Kaiser Health News reported. While these staffing scenarios make up a small percentage of the hospital staff, it’s a worthwhile addition to increase options for nurses.

Staff turnover for RNs increased from 8.4% to 27.1% last year, as reported by the 2022 NSI National Healthcare Retention and RN Staffing Report. Finding solutions to staffing shortages—and consequently increased temporary nursing cost—is crucial because burnout is still a problem, just as it is in clinical laboratories and pathology groups.

—Kristin Althea O’Connor

Related Information:

Temp Nursing Cost Hospitals Big During Pandemic, Now Hospitals Mulling Limits

White House Urged to Investigate Price Gouging by Nursing Staffing Agencies

AHA House Statement: Pandemic Profiteers: Legislation to Stop Corporate Price Gouging

AG Campbell Issues Advisory on Maximum Rates for Temporary Staffing in Nursing Homes

Attorney General’s Advisory: Rates for Temporary Nursing Services Charged to Long- Term Care Facilities

Agency Nurse Demographics and Statistics in the US

University of Washington Researchers Use Genomic Analysis to Track Shigella Infections as Decreased Cost of Gene Sequencing Aids Public Health Research

Another study in the United Kingdom that also used genomic analysis to understand drug-resistant Shigella produced findings that may be useful for microbiologists and medical laboratory scientists

From the onset of an infectious disease outbreak, public health officials, microbiologists, and clinical laboratory managers find it valuable to trace the origin of the spread back to the “index case” or “patient zero”—the first documented patient in the disease epidemic. Given the decreased cost of genomic analysis and improved accuracy of gene sequencing, infectious disease researchers are finding that task easier and faster than ever.

One recent example is a genomic study conducted at University of Washington (UW) in Seattle that enabled researchers to “retrace” the origin and spread of a “multidrug-resistant Shigellosis outbreak” from 2017 to 2022. “The aim of the study was to better understand the community transmission of Shigella and spread of antimicrobial resistance in our population, and to treat these multi-drug resistant infections more effectively,” the UW scientists stated in a new release.

Shigellosis (aka, bacillary dysentery) is a highly contagious disease of the intestines that can lead to hospitalization. Symptoms include fever, stomach cramps, diarrhea, dysentery, and dehydration.

“Additional analysis of the gut pathogen and its transmission patterns helped direct approaches to testing, treatment, and public health responses,” the UW news release states.

Usually prevalent in countries with public health and sanitation limitations, the “opportunistic” Shigella pathogen is now being seen in high-income countries as well, UW reported.

The researchers published their findings in Lancet Infectious Diseases, titled, “Genomic Reconstruction and Directed Interventions in a Multidrug-Resistant Shigellosis Outbreak in Seattle, WA, USA: A Genomic Surveillance Study.”

Ferric Fang, MD

“You can’t really expect an infectious disease to remain confined to a specific at-risk population. [Shigella infections are] very much an emerging threat and something where our public health tools and therapeutic tools have significant limitations,” infectious disease specialist Ferric Fang, MD (above) told CIDRAP News. Fang is a UW professor of Microbiology and Clinical Laboratory Medicine and a corresponding author of the UW study. (Photo copyright: University of Washington.)

Why are Shigella Cases Increasing?

The US Centers for Disease Control and Prevention (CDC) records more than 450,000 shigellosis infections each year in the US. The most common species in the US, according to CDC statistics, is Shigellaa sonnei.

Other members of the genus include:

Generally, Shigella infects children, travelers, and men who have sex with men (MSM), the CDC noted.

The UW researchers were motivated to study Shigella when they noticed an uptick in drug-resistant shigellosis cases in Seattle’s homeless population in 2020 at the beginning of the COVID-19 pandemic, Center for Infectious Disease Research and Policy News (CIDRAP News) reported.

“Especially during the pandemic, a lot of public facilities were closed that homeless people were used to using,” infectious disease specialist Ferric Fang, MD, told CIDRAP News. Fang is Professor of Microbiology and Laboratory Medicine at University of Washington and corresponding author of the UW study.

The researchers studied 171 cases of Shigella identified from 2017 to 2022 by clinical laboratories at Harborview Medical Center and UW Medical Center in Seattle. According to CIDRAP News, the UW researchers found that:

  • 46% were men who have sex with men (MSM).
  • 51% were people experiencing homelessness (PEH).
  • Fifty-six patients were admitted to the hospital, with eight to an intensive care unit.
  • 51% of isolates were multi-drug resistant (MDR).

Whole-Genome Sequencing Reveals Origin

The UW scientists characterized the stool samples of Shigella isolates by species identification, phenotypic susceptibility testing, and whole-genome sequencing, according to their Lancet Infectious Diseases paper. The paper also noted that 143 patients received antimicrobial therapy, and 70% of them benefited from the treatment for the Shigella infection.

Whole-genome sequencing revealed that two strains of Shigella (S. flexneri and S. sonnei) appeared first in Seattle’s MSM population before infecting the PEM population.

The genomic analysis found the outbreak of drug-resistant Shigella had international links as well, according to CIDRAP News:

  • One S. flexneri isolate was associated with a multi-drug resistant (MDR) strain from China, and
  • S. sonnei isolates resembled a strain characteristic of a current outbreak of MDR Shigella in England.

“The most prevalent lineage in Seattle was probably introduced to Washington State via international travel, with subsequent domestic transmission between at-risk groups,” the researchers wrote.

“Genomic analysis elucidated not only outbreak origin, but directed optimal approaches to testing, treatment, and public health response. Rapid diagnostics combined with detailed knowledge of local epidemiology can enable high rates of appropriate empirical therapy even in multidrug-resistant infection,” they continued.

UK Shigella Study Also Uses Genomics

Another study based in the United Kingdom (UK) used genomic analysis to investigate a Shigella outbreak as well.

Motivated by a UK Health Security Agency report of an increase in drug-resistance to common strains since 2021, the UK researchers studied Shigella cases from September 2015 to June 2022.

According to a paper they published in Lancet Infectious Diseases, the UK researchers “reported an increase in cases of sexually transmitted S. flexneri harboring blaCTX-M-27 (an antibiotic-resistant gene) in England, which is known to confer resistance to third-generation cephalosporins (antibiotics),” the researchers wrote.

Their analysis of plasmids (DNA with genes having antibiotic resistance) revealed a link in two drug-resistant Shigella strains at the same time, CIDRAP News explained.

“Our study reveals a worsening outlook regarding antimicrobial-resistant Shigella strains among MSM and highlights the value of continued integration of genomic analysis into surveillance and research,” the UK-based scientists wrote.

Current challenges associated with Shigella, especially as it evades treatment, may continue to demand attention from microbiologists, clinical laboratory scientists, and infectious disease specialists. Fortunately, use of genomic analysis—due to its ongoing improvements that have lowered cost and improved accuracy—has made it possible for public health researchers to better track the origins of disease outbreak and spread.    

Donna Marie Pocius

Related Information:

Genomic Reconstruction and Directed Interventions in a Multidrug-Resistant Shigellosis Outbreak in Seattle, Washington, USA: a Genomic Surveillance Study.

Genomics Aids Study of Seattle 2017-22 Shigella Outbreak

Q/A: Shigella—Shigellosis

A Spotlight on Growing Threat of Drug-Resistant Shigella

Emergence of Extensively Drug-Resistant and Multidrug-Resistant Shigella flexneri serotype 2a Associated with Sexual Transmission Among Gay, Bisexual, and Other Men Who Have Sex with Men, in England: A Descriptive Epidemiological Study

Large Dutch Survey Shines Light on Fraud and Questionable Research Practices in Medical Studies Published in Scientific Journals

About half of nearly 7,000 respondents admitted to sloppy practices, which suggests that pathologists and clinical lab professionals may want to be skeptical about the findings of many papers published in medical journals

It may surprise pathologists and medical laboratory professionals to learn that as many as 10% of surveyed authors of published scientific papers admitted to regularly falsifying or fabricating data! This was one finding in a study conducted by researchers to determine the quality and accuracy of scientific papers that are published in journals.

The National Survey on Research Integrity (NSRI), an organization based in The Netherlands, conducted the research.

In its coverage of the NSRI’s findings, Nature wrote, “Between October and December 2020, study authors contacted nearly 64,000 researchers at 22 universities in the Netherlands, 6,813 of whom completed the survey.”

According to Nature, “An estimated 8% of scientists who participated in an anonymous survey of research practices at Dutch universities confessed to falsifying and/or fabricating data at least once between 2017 and 2020. More than 10% of medical and life-science researchers admitted to committing this type of fraud, the survey found.”

Gowri Gopalakrishna, PhD, an epidemiologist and public health policy scientist with the Amsterdam University Medical Center (AUMC) who helped lead the NSRI study “thinks that the percentage of researchers who confessed to falsifying or fabricating data could be an underestimate,” Nature reported.

Thousands of Researchers Admit to ‘Questionable Research Practices’

Conducted online, the NSRI received responses from nearly 7,000 academics and researchers across a wide range of disciplines. About half admitted to engaging in “questionable research practices” (QRPs), 4.3% admitted to fabrication of data, and 4.2% admitted to falsification of data.

The NSRI presented its survey results in two preprints:

The NSRI study authors wrote that QRPs included “subtle trespasses such as not submitting valid negative results for publication, not reporting flaws in study design or execution, selective citation to enhance one’s own findings and so forth.”

An article in Science, titled, “Landmark Research Integrity Survey Finds Questionable Practices Are Surprisingly Common,” notes that the NSRI survey organizers took steps to ensure anonymity of respondents. “So, we have good reason to believe that our outcome is closer to reality than that of previous studies,” Gopalakrishna said.

Publish or Perish

Survey organizers originally sought responses from more than 60,000 researchers, but “many institutions refused to cooperate for fear of negative publicity,” Science reported.

The authors cited “publication pressure,” otherwise known as the “publish or perish” reward system, as the top factor driving questionable research practices. Respondents were “less likely” to engage in questionable research practices, data falsification, or fabrication if they subscribed to scientific norms and perceived a high likelihood of being detected.

According the NSRI findings, within academic ranks, PhD candidates and junior researchers were “most likely” to engage in QRPs, as well as males and people involved in empirical research.

Gowri Gopalakrishna, PhD

Epidemiologist Gowri Gopalakrishna, PhD (above), a post-doctoral researcher and the project secretary for the NSRI, told Science that advocates for research integrity should pay more attention to “sloppy research practices” as opposed to outright misconduct. “We need to have a positive environment where mistakes can happen, and where there is more focus on responsible conduct, slower science, and taking time for good quality research,” she said. Clinical laboratory professionals would likely agree with Gopalakrishna’s assessment.  (Photo copyright: University of Amsterdam Medical Center.)

Tracking Retractions

Retraction Watch, a blog founded in 2010 by medical journalists Ivan Oransky, MD, and Adam Marcus, offers a day-to-day barometer on research integrity. As the name indicates, the blog tracks research studies that have been retracted due to scientific misconduct or other reasons. In 2018, the bloggers launched a searchable database with more than 18,000 papers or conference abstracts that had been retracted.

An analysis by Science, titled, “What a Massive Database of Retracted Papers Reveals about Science Publishing’s ‘Death Penalty’,” looked at about 10,500 retracted journal articles in the database. It found that about half of those retractions involved scientific misconduct, including fabrication, falsification, and plagiarism. Nearly 40% were withdrawn “because of errors, problems with reproducibility, and other issues,” the analysis noted.

The data also indicates that a relatively small number of authors—about 500—accounted for about 25% of the retractions in journals.

In addition to the blog, Oransky and Marcus penned a column for STAT, titled, “The Watchdogs” in which they called attention to scientific misconduct and suggested solutions. Some solutions included:

Tips From a Media Watchdog

Gary Schwitzer, founder and Publisher of HealthNewsReview.org, a media watchdog website, offers additional insights. Schwitzer is a longtime medical journalist who also taught health journalism and media ethics at the University of Minnesota.

“Not all studies are the same and no study should necessarily be equated with the truth,” Schwitzer said in a video embedded on the website. People “often lose sight of the fact that journals were meant to be forums for discussions among scientists, not a source of daily news.”

The website includes the following Tips for Analyzing Studies, Medical Evidence, and Health Care Claims:

The website also includes a tip sheet for evaluating claims about medical tests.

The NSRI’s research is the latest in a long line of studies into so-called “scientific research,” some of which found “cooked” data and outright fraud. This suggests that pathologists and clinical laboratory professionals should follow the saying caveat emptor (“Let the buyer beware”) when absorbing research published in scientific journals or presented at meetings.

Stephen Beale

Related Information

Prevalence of Questionable Research Practices, Research Misconduct and Their Potential Explanatory Factors: A Survey Among Academic Researchers in the Netherlands

Prevalence of Responsible Research Practices and Their Potential Explanatory Factors: A Survey Among Academic Researchers in the Netherlands

Largest Study Ever on Research Integrity Launches, Aimed at All Researchers in the Netherlands

Prevalence of Research Misconduct and Questionable Research Practices: A Systematic Review and Meta-Analysis

A Huge Database of Scientific Retractions Is Live. That’s Great for Science

The Real Plague Affecting Science? It Isn’t Fraud

Academic Journals, Journalists Perpetuate Misinformation in Their Handling of Research Retractions, a New Study Finds

What a Massive Database of Retracted Papers Reveals about Science Publishing’s ‘Death Penalty’

Why Our Peer Review System Is a Toothless Watchdog

Science Isn’t Broken. It’s Just a Hell of a Lot Harder Than We Give It Credit For

Q/A with Dr. Ivan Oransky from Retraction Watch

The Science of This Pandemic Is Moving at Dangerous Speeds

Op-ed: Covering Science at Dangerous Speeds

The Watchdogs: We’ll Sniff Out Scientific Misconduct

Why Most Published Research Findings Are False

Tips for Analyzing Studies, Medical Evidence and Health Care Claims

There’s a Way to Spot Data Fakery. All Journals Should Be Using It

Does Science Self-Correct? What We’ve Learned at Retraction Watch

Retractions, Post-Publication Peer Review and Fraud

Ivan Oransky Co-Founder of Retraction Watch Discusses Scientific Research Integrity

Boston Globe Investigation Finds Many Boston Hospital CEOs Also Sit on Healthcare Company Boards

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.”

One of the hospital chief executives The Globe’s investigation highlighted was former-Boston Children’s Hospital CEO Sandra Fenwick. While there, The Globe noted, she also held a seat on the board of for-profit telehealth company Teledoc Health, and during her tenure as Children’s CEO, she lobbied Massachusetts legislators for telehealth funding at the start of the COVID-19 pandemic.

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.

carl-elliott-md-phd-at-podium
“It does seem like buying influence and it’s hard to imagine what else it would be,” Carl Elliott, MD, PhD (above), Professor in the Center for Bioethics and the Department of Pediatrics at the University of Minnesota told BioPharma Dive. “If you’re actually trying to buy scientific knowledge, then you wouldn’t really be going after CEOs. What they have is power.” (Photo copyright: Boston University.)

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.

Andrea Downing Peck

Related Information:

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Elizabeth Nabel Steps Down as President of Brigham and Women’s Hospital to Team Up with Husband’s Biotech Joint–Report

Betsy Nabel, MD, to Step Down as President of Brigham Health

Dr. Elizabeth Nabel Rejoins Moderna’s Board of Directors

Hospital CEOs, Med School Leaders Shouldn’t Sit on For-Profit Health Care Company Boards

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