COVID-19 research scandal: Unwanted diversion during pandemic

The first research scandal of the coronavirus pandemic has created unnecessary distraction around the politically divisive drug hydroxychloroquine, scientists say, as questions swirl around the tiny health care company at the center of the affair.

On Thursday, most of the authors of major studies that appeared in The Lancet and the New England Journal of Medicine (NEJM) retracted their work and issued apologies, saying they could no longer vouch for their data after the firm that supplied it—Chicago-based Surgisphere—refused to be audited.
At any other time the matter might have led to hang-wringing within academia, but it has taken on a new dimension as the world grapples with a virus that has claimed some 400,000 lives.
Of particular interest was the paper in The Lancet that claimed to have analyzed the records of 96,032 patients admitted to 671 hospitals across six continents, finding that hydroxychloroquine showed no benefit and even increased the risk of death.
Its withdrawal is seen as a boost to backers of the decades-old anti-malarial drug, who include US President Donald Trump and his Brazilian counterpart Jair Bolsonaro.
“It’s very politicized—there is a group, probably not particularly small, who have learned to mistrust science and scientists, and this just feeds into that narrative,” Gabe Kelen, a professor of emergency medicine at Johns Hopkins University, told AFP.
This is despite the fact that even without The Lancet paper, evidence has been building against hydroxychloroquine’s use against COVID-19.
On Friday, results from a fourth randomized controlled trial—carefully designed human experiments considered the most robust form of clinical investigation—showed it had no impact against the virus.
Mystery company
The Lancet, which first published in 1823, is one of the world’s most trusted medical journals.
As a result, the hydroxychloroquine paper had an outsized impact: the World Health Organization, Britain and France all suspended ongoing clinical trials.
But things soon began unravelling after researchers noticed numerous red flags, from the huge number of patients involved to the unusual level of detail about the doses they had received.
Both The Lancet and the equally prestigious NEJM, which had published a paper on whether blood thinners elevated the risk of COVID-19 that relied on the same company, issued expressions of concern—before the authors themselves pulled both papers.
Surgisphere, founded in 2007 by vascular surgeon Sapan Desai, had refused to share data with third-party reviewers, saying it would violate privacy agreements with hospitals.
However, when science news site The Scientist began reaching out to hospitals throughout the US to ask whether they had participated, it found none.
Surgisphere’s internet profile has also raised numerous questions. Only a handful of employees could be found on LinkedIn, and most have now deactivated their accounts.
According to the Guardian newspaper, its employees included an adult model and until last week the contact page on its website redirected to a WordPress template for a cryptocurrency website, leaving it unclear how hospitals could have reached out to them.
Meanwhile Desai, who according to court records has three outstanding medical malpractice suits against him, has written extensively in the past on research misconduct.
“The most serious cause of fraud in medical publishing is manufactured data that authors use to support high impact conclusions,” he said in a 2013 paper.
Systemic issues
For Ivan Oransky, who founded Retraction Watch in 2010, the affair is far from surprising, serving instead to highlight systemic issues in science publishing and the way science is reported to the public.
“No one took a hard look at the data,” said Oransky. “But we’ve known about these issues for literally decades.”
Policymakers should get away from the idea of using the results of a single study to inform their decisions, he added, as was the case for the WHO—and the media has a responsibility to place papers in context instead of hyping them up.
The problem also stems from the fact that even leading journals rely too heavily on an honor system, but “you never know when a catastrophe is going to happen, if you’re not willing to put into place some reasonable safeguards,” added Oransky.
As to the future, the current episode is unlikely to serve as a wake-up call, he said. If one journal increases its diligence, more blockbuster papers will start appearing in its competitors.
https://medicalxpress.com/news/2020-06-covid-scandal-unwanted-diversion-pandemic.html

Michigan Supreme Court sides with barber who defied coronavirus shutdown

A 77-year-old Michigan barber won a legal battle with Gov. Gretchen Whitmer over her coronavirus shutdown orders — in a stinging unanimous decision of the state Supreme Court.
“It is incumbent on the courts to ensure decisions are made according to the rule of law, not hysteria,” Justice David F. Viviano wrote Friday, MLive.com reported.
The court’s 7-0 decision vacated a lower court’s order upholding the state’s attempt to shutter the barbershop owned and operated by Karl Manke in Owosso, Mich.
Manke reopened his shop May 4 in defiance of Whitmer’s orders keeping salons closed to prevent the spread of coronavirus.
“Either Jesus comes, they cut my hands off or she resigns, one or the other,” he said Wednesday.
Manke has argued that he has a right to work — and kept cutting customers’ hair as the legal fight raged. He has racked up thousands of dollars in fines, and the state has rescinded his licenses.
The ruling returns the case to the appeals court for a full hearing scheduled for Thursday. But the case will soon be moot: under Whitmer’s orders, barbershops will be permitted to reopen fully on June 15.
https://nypost.com/2020/06/06/michigan-supreme-court-sides-with-barber-who-defied-coronavirus-shutdown/

Enrollment in clinical trials for cancer dropped as COVID-19 cases rose

Patient enrollment in clinical trials sponsored by the National Cancer Institute dropped significantly in March when the country experienced a surge in COVID-19 cases, a new study shows.
The study, published in JAMA Network Open, examined enrollment in clinical trials conducted by the SWOG Cancer Research Network, a member of the National Cancer Institute’s Community Oncology Research Program. Researchers studied enrollments between Jan. 1 and April 25. They compared the enrollment numbers to the incidence of confirmed COVID-19 cases in the U.S. in the same time period.
They found that weekly total enrollments ranged from 125 to 150 per week in the period between week one (Jan. 1-4) and week 11 (March 8-14).
The weekly total enrollment dropped to 109 in week 12 (March 15-21), when COVID-19 cases increased from 2,918 to 25,697. From week 13 (March 22-28) until the end of the study period, weekly enrollments remained at 74 patients.
In total, 1,870 patients were enrolled over the study period. Of these patients, 1431 (76.5 percent) were enrolled from weeks one to 11, and 439 (23.5 percent) from weeks 12 to17.
https://www.beckershospitalreview.com/oncology/enrollment-in-clinical-trials-for-cancer-dropped-as-covid-19-cases-rose-study-shows.html

West Virginia sues Walgreens, Rite Aid, claims they flooded state with opioids

West Virginia Attorney General Patrick Morrisey filed two lawsuits against Walgreens and Rite Aid this week, claiming they failed to monitor and report suspicious orders of controlled substances and ordered excessive amounts of opioids to their pharmacies in the state.
In the June 3 lawsuit against Walgreens, Mr. Morrisey claimed that Walgreens distributed 28 million oxycodone pills in West Virginia between 2006 and 2014, though the state has less than 2 million people. The volume of pills should have been a red flag that not all of the prescriptions were for legitimate medical reasons and that many were being diverted, the lawsuit says.
In the lawsuit against Rite Aid, Mr. Morrisey claims that between 2006 and 2014, the company distributed more than 87 million oxycodone pills in West Virginia.
He claimed that both Walgreens and Rite Aid were among the top 10 opioid distributors in West Virginia between 2006 and 2014.
In 2017, more  than 1,000 people in West Virginia died from drug overdoses, and 86 percent of those deaths involved an opioid, the lawsuit claims. That’s three times higher than the national rate of 14.6 deaths per 100,000 people.
Also in 2017, providers wrote 81.3 opioid prescriptions for every 100 people in the state, compared to the national average of 58.76 prescriptions, the lawsuit claims.
Mr. Morrisey claimed both Walgeens and Rite Aid violated West Virginia’s consumer credit and protection act and caused a public nuisance.
A Walgreens spokesperson told Becker’s: “We never manufactured or marketed opioids and never sold opioids to the pain clinics, internet pharmacies and pill mills that fueled the opioid crisis. Prior to 2014, unlike other companies involved in this litigation, we delivered opioids only to our own pharmacies, and the only place we ever sold opioids was at the pharmacy counter, when presented with a prescription written by a prescriber, with a valid DEA license, for a legitimate medical need.”
Becker’s has also reached out to Rite Aid for comment and will update this story accordingly.
https://www.beckershospitalreview.com/opioids/west-virginia-sues-walgreens-rite-aid-claims-they-flooded-state-with-opioids.html

When offices reopen, will Silicon Valley build a health system for its own?

As the first private commuter shuttles return to Silicon Valley, a lesser-known perk at companies like Google, Apple and Facebook is poised to emerge from the coronavirus crisis in a new form: the corporate health clinic.
For years, employer medical providers like Stanford Health Care, Crossover Health and One Medical have been building out custom clinics to offer not only urgent care and routine doctor’s appointments, but also dental work, musculoskeletal assessments, acupuncture and therapy — both physical and mental. The idea is to rein in health care costs while providing another attractive recruiting benefit.
Now, in Silicon Valley’s rarefied version of the company town, the question is how premium health insurance plans and contracted doctors might be used to administer COVID-19 diagnostic tests, virtually screen employees for risk factors or issue some form of “immunity passports” based on so-far-unproven antibody tests. In the process, tech executives and HR departments must grapple with unprecedented questions about worker privacy, corporate liability and the role of employers in a health care system on the brink.

“They are now becoming public health officials,” said Scott Shreeve, an emergency medicine physician-turned-CEO of employer medical provider Crossover Health, which works with Apple, Facebook, LinkedIn and others. “They didn’t realize they had these little cities.”
Public health departments and hospitals are wary of a second wave of COVID-19 cases, especially with police brutality protests roiling cities, so any efforts by employers to stave off virus hospitalizations are likely to be welcomed. And even though offices in the Bay Area are permitted to reopen beginning June 15, big companies including Facebook and Salesforce have said their nonessential employees will not be forced to come back in 2020, reducing the number of people circulating in the area.
But as with previous social flash points driven by the tech boom, like policy fights over the commuter shuttles and affordable housing, a retrenchment to isolation to set up blue-chip employee health services could add fuel to the “techlash” that has defined recent years in Silicon Valley.
“Companies that define their role narrowly in these crises do so at their own peril,” said Mark Muro, a senior fellow and policy director of the Brookings Institution’s Metropolitan Policy Program. “We’ve been seeing a drift toward a broader definition of the company’s responsibility in the United States.”
It could be read as “grotesquely tone deaf” for tech employers to wall themselves off, he said, when companies like drugmaker Eli Lilly in Indianapolis have “turned themselves inside-out” to offer free testing to medical workers. Some tech executives have made large donations to groups working on vaccines or to social programs in recent months, but more hands-on relief efforts like a tech task force convened by Apple, Google, Amazon and Microsoft have largely “failed to materialize,” The Wall Street Journal reported.

The details of tech companies’ in-house plans are still in flux for COVID-19 testing, antibody testing and the process of helping infected employees navigate the treatment process while retaining their privacy. Given the virus’ lethality among less-protected workers, though, the stakes are high.
“The disparities in impact of COVID could be paralleled by the disparities in safety in returning to work,” said Robert Harrison, a clinical professor of medicine who specializes in occupational health and safety at the University of California San Francisco.

‘Totally uncharted’

Where should employees get tested for COVID-19? How often should they get tested? What happens if it turns out there’s a “super-spreader” in the office? These are the kinds of questions that Harrison and others well-versed in the world of employer medical care are getting.
Ultimately, the responsibility for public health during a pandemic “rests primarily with the local county health departments,” Harrison said. So he’s urging employers to report all positive coronavirus test results to health officials and ensure that any on-site symptom screening is integrated with isolation procedures and HR privacy protections.
“A company like Google or Tesla, I mean, they should be doing that also,” Harrison said. “But they can probably act like their own local, mini health department on site.”

At One Medical, which operates clinics that serve employees of Airbnb, Instacart and Google, Chief Quality Officer Raj Behal and his team are working with tech employers considering a wide range of screening measures. Some lean toward lower-cost, less-invasive temperature checks and apps that ask employees to self-certify that they are symptom-free.
One Medical is among a growing number of vendors that have devised a new platform to dole out employee “boarding passes” to go back to work after they’ve been screened for risk factors like travel and preexisting conditions. Class 1 workers are lowest-risk and have tested negative for the virus, Class 2 haven’t had symptoms, exposure or testing, and Class 3 have symptoms or have tested positive.
Some employers concerned about privacy have told One Medical, “We don’t want any of that information. Just tell us which risk class they’re in,” Behal said. “But there are a handful that would like the detailed data. They want to know if somebody tested positive and what their antibody status would be.”
One Medical, however, cannot share that information unless employees sign an explicit waiver. Experts like Harrison say companies should create a new “firewall” between any on-staff or hired medical providers and HR to protect confidential medical data.
“This is totally uncharted,” Behal said. “There’s legal rights on both sides, and pandemic exceptions kind of loosen things up.”

All of these issues are magnified for employers who choose to set up hands-on virus or antibody testing programs. On-site clinics, outdoor tents or drive-throughs are all options, but Shreeve favors at-home diagnostic tests — that is, assuming companies can get access to enough of them.
“You can imagine an employer, you have 5,000 workers, you’re going to send 5,000 tests to everyone’s home,” Shreeve said. “Employers have never had to do anything like this, and then the science is like, well, I don’t even know if this is the right thing to do, but it’s something to do.”
The murkiest area — and the most intriguing, in Shreeve’s opinion — is antibody testing, done through serologic tests already on the market. They carry the caveat, at least so far, that they should not be interpreted as a guarantee of immunity. But there’s already interest in Silicon Valley in adopting that approach as antibody tests 2.0 emerge.
“Immunity status is going to be a really big deal,” he said. “No one’s going to want you back on campus unless you have immunity.”

The 21st-century company doctor

The concept of companies offering employees subsidized medical service at work is not new. It started with railroad companies in the 1930s and expanded to manufacturers and other industrial bosses looking to reduce workplace injuries that drove up employer costs in emergency rooms and through worker’s compensation claims.
But in the last decade, amid the erosion of U.S. primary care and skyrocketing health costs, health clinics have been absorbed into Silicon Valley’s perks economy, with a range of services geared toward desk-dwellers rather than the factory workers for whom occupational medicine was created to serve.

“Technology, for lack of a better word, is very loosely goosey,” said Katelyn Johnson, integrated health manager for Cisco’s four global employee health clinics. “There are no drug screens. There’s no preemployment physical. There’s no occupational health center you go to, and that’s because our work is sedentary.”
Johnson, a long-distance runner and veteran of the fitness and hospital industries, was hired by Cisco in 2007 to create the company’s first clinic at its San Jose headquarters. The company wanted to rein in health care costs that were steadily increasing thanks to chronic conditions like obesity and heart disease by offering primary care visits with high-quality doctors hired through a contract with Stanford Medical Center, instead of the nurse practitioners and other “midlevels” increasingly staffing ordinary doctor’s offices.
The 25-person San Jose clinic that opened in 2009 was designed to better integrate employee health care and encourage usage by tacking on popular wellness services like physical therapy and acupuncture. Though such clinics can cost millions of dollars to build out, the resulting decrease in health care costs has proven so valuable that Cisco’s operation has since grown to 40 full-time staffers and three additional clinics in North Carolina, Bangalore and Mexico City.
“Every time somebody uses the health center versus a community center, Cisco saves money,” Johnson said. And if employees are referred out to specialists, she said, the clinic helps ensure that they’re encouraged to go to “value-based providers.”

The financial advantages have pushed the field beyond tech. Goldman Sachs advertises access to specialists like dermatologists. One 2018 survey found that one-third of U.S. companies with more than 5,000 employees offered “general medical clinics” at work, up nearly 10% from a similar survey in 2012.
But most companies aren’t trying to get into the health care business themselves. While Amazon and Apple have posted job listings for medical personnel to staff employee clinics, almost three-quarters of the companies surveyed in 2018 outsourced the work of running on-site clinics.
That demand has bolstered growth for companies like Crossover and One Medical, which position themselves somewhere between mass-market medicine and white-glove “concierge” services
For employers still nervous about the up-front investment in a clinic, there are also shared “near-site” clinics located between several employers who split the costs, said Larry Boress, executive director of the National Association of Worksite Health Centers. He expects the pandemic to boost demand for such services.
“Employers, even though it’s not their core business, will find that it’s going to be a necessity,” Boress said, “just as many of them offer child care and other kinds of support.”

A third way?

At Dropbox, which does not have an employee health clinic, Chief Legal Officer Bart Volkmer said he and the rest of the company’s crisis response team are now evaluating whether — and how — to bring medical personnel to its Silicon Valley campus.

“I don’t know on the on-site health clinics if we’re going to go down that road,” Volkmer said. But he added, “We don’t want to say, ‘Hey, just go deal with the health care system.'”
From a policy perspective, employer-provided health care is at a complicated crossroads. Gig companies like Uber, under fire for providing no health insurance, are seeking to align themselves with left-leaning workers rights groups in calling for state or national action on “portable benefits” that decouple insurance from individual jobs. Meanwhile, employers including Amazon and Apple are pushing further toward creating their own insurance pools and severing traditional fee-for-service health care models.
Lisa Yee of the Silicon Valley Employers Forum, a tech membership group that works on issues related to employment benefits, is among those who wonder if COVID-19 will unleash political changes that could leave even tech companies on the vanguard of generous benefit packages scrambling to react.
“Given that so many people are unemployed now, the question of the viability of self-insured employer plans is sort of in question,” said Yee, who is the group’s executive director. “It raises the question of, is there going to be a move toward a one-payer system for this country?”
In the meantime, Boress of the National Association of Worksite Health Centers said the value of a centralized employer medical system that can refer workers out to any number of providers is magnified in a high-stakes situation like COVID-19. “In a perfect setting, you have an on-site center, and most have electronic records,” Boress said. “They can be the hub of the wheel.”

At Crossover Health, Shreeve sees another path forward — that third-party membership medical programs like his or One Medical’s will expand beyond the realm of Silicon Valley to be the norm. Like a gym membership, but for health care, and borrowing heavily from the Medicare Advantage model in which patients are also offered related services like meal programs or prescription deliveries.
“What is the same concept for the modern employer?” he said. “I don’t think it exists today.”
https://www.protocol.com/tech-coronavirus-private-health-clinics

New synthetic red blood cells are even better than the real thing

Researchers have created synthetic red blood cells (RBCs) that have all of the useful properties of the real thing, plus a few new tricks. These new cells could be put to work carrying oxygen or drugs through the body, sensing toxins, and other tasks.

It goes without saying that red blood cells perform a vital function – namely, they carry oxygen from the lungs to all tissues in the body. They do this by way of molecules called hemoglobin, which use proteins containing iron that bind to oxygen. RBCs also have a range of safety features that allow them to do their jobs properly. They can squeeze and stretch to get through tiny capillaries, and can circulate for a long time.
In trying to create synthetic versions of red blood cells, scientists have had some trouble mimicking all of these properties. Now, researchers from the University of New Mexico, Sandia National Laboratories and South China University of Technology have created synthetic RBCs that can do all that – and more.
To make the synthetic cells, the researchers start with real ones. These donated human RBCs were first covered with a thin layer of silica, followed by layers of polymers with positive and negative charges. The silica is then etched away, and finally the surface is coated in natural RBC membranes.

 

The end result is artificial red blood cells that have similar size, shape, charge and surface proteins to the real thing. The team showed that these synthetic RBCs were able to deform enough to squeeze through tiny gaps in model capillaries. In tests in mice, the cells circulated for over 48 hours, and the team detected no toxic side effects.
In other tests, the team showed off the various other abilities that these synthetic RBCs could perform. They successfully carried different cargoes of hemoglobin, anticancer drugs, toxin sensors, and magnetic nanoparticles. Each of these could represent a different potential use for the cells – transporting oxygen, delivering drugs, sensing toxins, and allowing for outside manipulation, respectively.

The team plans to continue investigating and testing the cells, with the hopes of eventually getting them ready for human tests.
The research was published in the journal ACS Nano.
https://newatlas.com/medical/synthetic-red-blood-cells-oxygen-drugs-toxin-sensors/

Novavax Analyst: DoD Funds Reflect Conviction In Platform, Ability To Deliver

Novavax, Inc. NVAX 3.67% is landing financing deals that could help to successfully develop a vaccine for SARS-CoV, the virus that causes COVID-19.

Novavax’s Defense Department Funding

The Gaithersburg, Maryland-based biotech said late Thursday that it has been granted funding of up to $60 million by the Department of Defense for manufacturing several components of the vaccine codenamed NVX-CoV2373 in the U.S.Novavax Analyst: Positive NanoFlu Readout Could Have Driven Increased Conviction
The accent on domestic manufacturing is probably due to security reasons, Cantor Fitzgerald analyst Charles Duncan said in a note.
Novavax’s vaccine consists of stable, prefusion protein antigen made using its proprietary nanoparticle technology and includes its proprietary Matrix M adjuvant.
The analyst said he expected funding from government organizations, although Novavax was not part of the “unofficial” list of five finalists for the White House’s “Operation Warp Speed.”
The agreement signals conviction in Novavax’s recombinant nanoparticle platform and its potential to deliver an efficacious vaccine for COVID-19, probably due to the recent positive Phase 3 readout for its NanoFlu vaccine, he said.
Cantor has an Overweight rating and $45 price target for Novavax shares.
In mid-May, the company received an incremental $384 million in funding from the Coalition for Epidemic Preparedness Innovations for its vaccine program.
“We are genuinely honored at the opportunity to protect our military personnel and their families who have devoted themselves to the needs of U.S. citizens and others worldwide,” Novavax CEO Stanley Erck said in a statement.

What’s Next For Novavax

Novavax said as part of the contract it will work with a U.S.-based biologics CDMO to manufacture the antigen component of NVX-CoV2373 for at least 10 million doses of vaccine to be used in Phase 2/3 studies and/or under an Emergency Use Authorization if one is approved by the FDA.
It will also work with U.S.-based CDMOs to scale up production and manufacture of the Matrix-M adjuvant component of the vaccine.
The company is conducting a Phase 1 study in healthy volunteers, with preliminary immunogenicity and safety data due in July.
“Forthcoming data this summer should provide a gauge of possibilities and probabilities for moving forward,” said Cantor’s Duncan.
https://www.benzinga.com/analyst-ratings/analyst-color/20/06/16188708/novavax-analyst-says-dod-funding-reflects-conviction-in-platform-ability-to-deliver