Coronavirus drugmakers’ latest tactics: Science by press release

https://www.politico.com/news/2020/06/05/drugmakers-media-coronavirus-303895

Coronavirus drugmakers' latest tactics: Science by press release ...

Pharmaceutical companies are using the media to tout treatments that are still under review.

Vaccine maker Moderna attracted glowing headlines and bullish investors when it revealed that eight participants in a preliminary clinical trial of its coronavirus vaccine had developed antibodies to the virus. The company’s share price jumped nearly 20 percent that day as it released a massive stock offering.

But the full results of the 45-person safety study haven’t been published, even though Moderna began a second, larger trial in late May aimed at determining whether the vaccine works. Several vaccine researchers say the scant public information on the earlier safety study is hard to evaluate because it addresses less than 20 percent of participants.

Call it science by press release — a tactic that pharmaceutical companies are increasingly relying upon to set their experimental coronavirus drugs and vaccines apart in a crowded field, shape public opinion and court regulators. Public health experts say the approach could increase political pressure on federal health officials to green-light drugs and vaccines before it is clear they are safe or effective, with potentially dangerous consequences.

“There’s a long history of pharmaceutical manufacturers putting out self-serving press releases related to clinical trial data that they’re developing that present an overly rosy picture of the data, usually with a boilerplate disclaimer at the end, which is fairly useless,” said Aaron Kesselheim, a professor of medicine at Harvard Medical School who studies drug regulation and pricing.

There are already signs of hype and political pressure influencing the U.S.’ coronavirus response. The Food and Drug Administration authorized emergency use of the malaria drug hydroxychloroquine in March without any proof that it was safe or effective for coronavirus patients — but with the backing of President Donald Trump, who had begun touting the treatment during daily White House briefings.

Subsequent studies have found that hydroxychloroquine doesn’t help those with Covid-19 and can cause potentially fatal side effects. And a top government scientist, Rick Bright, filed a whistleblower complaint in May alleging that he was ousted from his job leading the Biomedical Advanced Research Authority after he resisted political pressure to greenlight widespread use of the drug.

“The FDA has remained an unwavering, science-based voice helping to guide the all-of-government response,” agency Commissioner Stephen Hahn said in a statement. “I have never felt any pressure to make decisions, other than the urgency of the situation around COVID-19.”

But observers aren’t so sure. “From the outside looking in, there seems to be more political pressure than ever,” said Marc Scheineson, a former associate commissioner at the FDA and head of the FDA group at Alston & Bird. “The example in the White House is trickling down and there is a lot of pressure on the FDA … to color information on the optimistic side for political purposes and that is a hugely disturbing trend.”

A spokesperson for Moderna, which has received nearly a half billion dollars from the U.S. government and praise from Trump, said the company previewed its vaccine trial results by press release because it was concerned that the data might leak. The National Institutes of Health’s top infectious disease expert, Anthony Fauci, had hinted at the results in an interview with National Geographic, and data from a trial of the experimental drug remdesivir had leaked in April.

“You had this data moving widely around NIH and the remdesivir leak was also in our minds,” the Moderna spokesperson said.

But Peter Bach, director of Memorial Sloan-Kettering’s Center for Health Policy and Outcomes, said Moderna’s effort to preview its findings in the press “could be construed as an effort to make sure they are part of the conversation — and it worked on that front.”

Other groups have also previewed their hotly anticipated vaccine studies in the press. In late April, The New York Times revealed that six monkeys given a vaccine developed by researchers at the U.K.’s University of Oxford had stayed healthy for 28 days despite sustained exposure to the coronavirus. The article quoted Vincent Munster, a researcher at the NIH’s Rocky Mountain Laboratory, which conducted the monkey study at the British scientists’ behest.

The Oxford researchers, who signed a deal with AstraZeneca two days later to develop the experimental vaccine, did not publish a formal scientific analysis of the monkey data until mid-May. The study revealed that the noses of vaccinated monkeys and unvaccinated monkeys contained similar levels of coronavirus particles, suggesting that the vaccinated animals could still spread the disease — and the vaccine might not be as effective as the earlier data had hinted.

AstraZeneca has since inked a $1.2 billion deal with the U.S. government to provide 300 million vaccine doses, and a £65.5 million ($80 million) agreement with the U.K. government to supply 30 million doses.

Liz Derow, a spokesperson for Oxford’s Jenner Institute, where the vaccine researchers are based, said they did not give the monkey data to The New York Times. The NIH’s National Institute of Allergy and Infectious Disease, which operates the Rocky Mountain Laboratory, said it did not provide the data to the newspaper — but one of its researchers, Vincent Munster, spoke to a Times reporter about the monkey findings at the request of the Jenner Institute.

“I was really disturbed by not just Moderna, but the Oxford group as well, presenting a press release without data, without a scientific review, without knowing what the press release was based on,” said Barry Bloom, an immunologist at the Harvard School of Public Health. “And very positively enough to raise the stock price so two days later officials within the company sold their stock and made a whole lot of money, whether or not the vaccine works.”

Four of the pharmaceutical firm’s top executives together saw gains of $29 million from prescheduled sales of shares in the company in the two days following the vaccine announcement. The company has not yet responded to a request for comment on the stock sales.

Neither the Oxford nor Moderna vaccines are available to the public. But some drugs whose safety and efficacy are now being studied have already been repurposed or authorized for emergency use during the pandemic. The rush to release snippets of information on drug trials to the press ahead of full results has left some doctors wondering how to best treat their patients.

After leaked data from a trial of Gilead’s experimental antiviral remdesivir suggested the drug might be the first shown to help coronavirus patients, the company put out a press release in late April teasing results from a larger, government-run study. Hours later, Fauci revealed some findings of the study during an Oval Office press spray.

But the full analysis of the NIAID trial results was not published until three weeks later. Until that point, frontline physicians had no way to know that patients on ventilators did not benefit from remdesivir treatment — meaning that doctors may have inadvertently wasted some of the United States’ limited stock of the drug.

This lack of understanding on how to use remdesivir was evident in a recent survey more than 250 hospitals by the American Society of Health-System Pharmacists, which found that just 15 percent planned to use their remdesivir doses as described in the FDA’s emergency authorization for the drug.

Andre Kalil, an infectious disease doctor at the University of Nebraska Medical Center who led the NIAID trial, told POLITICO that physicians could have patterned their use of remdesivir on the dosages given during the trial.

Others say doctors using experimental treatments should have as much information as possible.

“If we want doctors to make rational medical decisions based on data, then before an authorized product reaches patients, the data should be available to review in some way, not just a press release,” said Walid Gellad, director of the University of Pittsburgh’s Center for Pharmaceutical Policy and Prescribing.

Kesselheim, too, said that clinical trial data should be made public alongside any emergency authorizations to give physicians “the maximum amount of help they need in figuring out how to prescribe the drug.”

Gilead did not respond to a request for comment. But NIAID said that the urgency of the coronavirus prompted Fauci to share initial results before a full analysis was ready for publication.

Ivan Oransky, a professor of medical journalism at New York University and co-founder of the blog Retraction Watch, which monitors errors and misconduct in scientific research, told POLITICO he fears that the temptation to conduct science by press release will get “worse before it gets better.”

The world is growing more desperate for drugs and vaccines that could bring the coronavirus to heel. And many members of the public and politicians are treating every scrap of scientific information about the pandemic equally, he said — whether data comes from a peer-reviewed study or a company press release.

“There have been mechanisms to review science critically that, given the speed of Covid, have gone out the window,” said Bloom.

And interpreting results of clinical trial data can be difficult under the best of circumstances — especially when that data concerns a virus that was unknown to science until December of last year. When to end a trial and which conclusions to highlight are in many cases a matter of discretion, said Scheineson.

“It’s an art, not a science, in that respect,” he said. “I, for one, will not be the first in line to the new Moderna vaccine.”

 

 

 

 

Cartoon – Sheep at a Crossroads

Florida needs an executive order requiring wearing of face masks

FDA ends emergency use authorization for hydroxychloroquine

https://www.axios.com/hydroxychloroquine-fda-ends-emergency-use-authorization-f5353a2c-115a-4a57-b8e2-360b735b4937.html?stream=health-care&utm_source=alert&utm_medium=email&utm_campaign=alerts_healthcare

FDA withdraws emergency use authorization for hydroxychloroquine ...

The FDA ended Monday its emergency use authorizations for two controversial drugs, hydroxychloroquine and chloroquine, as a potential coronavirus treatment.

Why it matters: Despite gaining President Trump’s adamant support and use, the drugs have failed in several clinical trials and have been found to possibly cause serious heart problems.

What they’re saying: The FDA said it believes the drugs “are unlikely to be effective in treating COVID-19” under the emergency use authorization.

  • It also said that “in light of ongoing serious cardiac adverse events and other serious side effects, the known and potential benefits of [the drugs] no longer outweigh the known and potential risks for the authorized use.”

Read the letter and memo regarding the revocation:

 

 

 

“What is it that America has failed to hear?”

https://mailchi.mp/9f24c0f1da9a/the-weekly-gist-june-5-2020?e=d1e747d2d8

The Peace Alliance's tweet - ""A riot is the language of the ...

“What is it that America has failed to hear?” asked Dr. Martin Luther King, Jr. in March of 1968, calling riots the “language of the unheard”. “It has failed to hear that the promises of freedom and justice have not been met.” Stubbornly, shamefully, we continue to turn a deaf ear: to structural racism; to institutionalized inequality; to a pandemic of police brutality and bigotry that chokes off the breath of black Americans as surely as a virus in the lungs or a boot on the neck. But the sound in the streets is thunderous.

We in healthcare must listen. We must hear that what killed George Floyd, and Breonna Taylor, and Eric Garner, and Tamir Rice, and Philando Castile, and Trayvon Martin, and Ahmaud Arbery, and countless others, as surely as the terrible actions of any single person, was the pervasive, insidious virus of racism, long since grown endemic in our country.

This week’s protests are a kind of ventilator, providing emergency breath for a national body in crisis. We must work—urgently—on the therapeutics of structural change and the vaccines of education and understanding.

At Gist Healthcare we are listening, and learning. As a team, we’ve committed to each other to be attentive, invested, empathetic allies, and to dedicate our individual and collective time, talents and treasure to antiracist work, in healthcare and beyond. Our contribution may not be large, and it will never be enough, but at least we hope it will be positive. We’d like to hear your thoughts and suggestions as well. For the moment, and for our colleagues, friends, and families, we stand with the protestors.

Black Lives Matter.

 

 

 

Trump: U.S. will terminate relationship with the World Health Organization in wake of Covid-19 pandemic

Trump: U.S. will terminate relationship with the World Health Organization in wake of Covid-19 pandemic

Coronavirus Fears Grind International Diplomacy to a Halt

President Trump said Friday the U.S. would halt its funding of the World Health Organization and pull out of the agency, accusing it of protecting China as the coronavirus pandemic took off. The move has alarmed health experts, who say the decision will undermine efforts to improve the health of people around the world.

In an address in the Rose Garden, Trump said the WHO had not made reforms that he said would have helped the global health agency stop the coronavirus from spreading around the world.

“We will be today terminating our relationship with the World Health Organization and redirecting those funds to other worldwide and deserving urgent global public health needs,” Trump said. “The world needs answers from China on the virus.”

It’s not immediately clear whether the president can fully withdraw U.S. funding for the WHO without an act of Congress, which typically controls all federal government spending. Democratic lawmakers have argued that doing so would be illegal, and House Speaker Nancy Pelosi threatened last month that such a move would be “swiftly challenged.”

The United States has provided roughly 15% of the WHO’s total funding over its current two-year budget period.

The WHO has repeatedly said it was committed to a review of its response, but after the pandemic had ebbed. Last month, Robert Redfield, the director of the Centers for Disease Control and Prevention, also said the “postmortem” on the pandemic should wait until the emergency was over.

As the Trump administration’s response to pandemic has come under greater scrutiny, with testing problems and a lack of coordination in deploying necessary supplies, Trump has sought to cast further blame on China and the WHO for failing to snuff out the spread when the virus was centered in China.

During his remarks, Trump alleged, without evidence, that China pressured WHO to mislead the world about the virus. Experts say that if the U.S. leaves the WHO, the influence of China will only grow.

“The world is now suffering as a result of the malfeasance of the Chinese government,” Trump said. “China’s coverup of the Wuhan virus allowed the disease to spread all over the world, instigating a global pandemic that has cost more than 100,000 American lives, and over a million lives worldwide.” (That last claim is not true; globally, there have been about 360,000 confirmed deaths from Covid-19, the disease caused by the coronavirus.)

When Trump earlier this month threatened to yank U.S. funding in a letter, Tedros Adhanom Ghebreyesus, the WHO director-general, would only say during a media briefing that the agency was reviewing it. But he and other officials stressed that the agency had a small budget — about $2.3 billion every year — relative to the impact the agency had and what it was expected to do.

Mike Ryan, head of the WHO’s emergencies program, said the U.S. funding provided the largest proportion of that program’s budget.

“So my concerns today are both for our program and … working on how we improve our funding base for WHO’s core budget,” Ryan said. “Replacing those life-saving funds for front-line health services to some of the most difficult places in the world — we’ll obviously have to work with other partners to ensure those funds can still flow. So this is going to have major implications for delivering essential health services to some of the most vulnerable people in the world and we trust that other donors will if necessary step in to fill that gap.”

 

Further confusion on the coronavirus testing front

https://mailchi.mp/f2774a4ad1ea/the-weekly-gist-may-22-2020?e=d1e747d2d8

Coronavirus test: confusion over availability and criteria is ...

With all 50 states now in the process of reopening, data reported by public health agencies on coronavirus testing is under increased scrutiny. The issue is not how many tests are being conducted—that number has dramatically increased nationwide (although experts still caution that total testing should be about three times higher than the current 300,000 per day).

Rather, as reported this week, the issue is what kind of tests are being included in public reporting. It emerged this week that several states—including GeorgiaTexasPennsylvaniaVermont, and Virginia—have been combining statistics on polymerase chain reaction (PCR) tests, used to diagnose current infection, with antibody blood tests, used to detect past infection.

More troublingly, The Atlantic reported on Wednesday that the Centers for Disease Control and Prevention (CDC) has been doing the same thing, which artificially inflates the number of tests conducted, and makes the numbers difficult to interpret. Among other experts, Dr. Ashish Jha, director of Harvard’s Global Public Health Institute, was stunned: “You’ve got to be kidding me. How could the CDC make that mistake? This is a mess.”

Accurate testing data is critical to determine the pace and scope of reopening, and to monitor for resurgences of the virus that might necessitate future restrictions. It’s important to know who’s infected now for clinical reasons, and it’s essential to understand who’s already been sick for public health purposes. Combining the two datasets is positively unhelpful, and likely only serves a political purpose.

Testing problems have proven to be this country’s original sin in the way the coronavirus pandemic has evolved, but it’s not too late to make sure that we have ample, accurate, and well-reported testing to guide critical public health decisions.

US coronavirus update: 1.62M cases, 95K+ confirmed deaths, 12.9M tests conducted (of some type).

 

 

 

Huge Study Throws Cold Water on Antimalarials for COVID-19

https://www.medpagetoday.com/infectiousdisease/covid19/86642?xid=nl_mpt_DHE_2020-05-23&eun=g885344d0r&utm_source=Sailthru&utm_medium=email&utm_campaign=Daily%20Headlines%20Top%20Cat%20HeC%20%202020-05-23&utm_term=NL_Daily_DHE_dual-gmail-definition

Huge Study Throws Cold Water on Antimalarials for COVID-19 ...

— No support for continued use seen in analysis of 15,000 patients who got controversial drugs

Chloroquine or hydroxychloroquine (HCQ), with or without an antibiotic, in hospitalized COVID-19 patients were associated with increased risk of death in the hospital and higher rates of arrhythmias, analysis of outcomes in nearly 100,000 patients indicated.

The 15,000 patients who received HCQ or chloroquine were about twice as likely to die compared to controls who did not receive these agents after adjusting for covariates (18.o% for hydroxychloroquine and 16% for chloroquine versus 9.3% for controls), reported Mandeep Mehra, MD, of Brigham and Women’s Hospital in Boston, and colleagues.

The drug was also associated with a higher risk of ventricular arrhythmia during hospitalization (6.1% for hydroxychloroquine, 4.3% for chloroquine versus 0.3% for controls), the authors wrote in The Lancet.

Moreover, risks for both in-hospital mortality and ventricular arrhythmia were even higher compared to controls when either drug was combined with a macrolide antibiotic, they noted.

Mehra said in a statement these drugs should not be used as treatments for COVID-19 outside of clinical trials.

“This is the first large scale study to find statistically robust evidence that treatment with chloroquine or hydroxychloroquine does not benefit patients with COVID-19,” he said. “Instead, our findings suggest it may be associated with an increased risk of serious heart problems and increased risk of death. Randomised clinical trials are essential to confirm any harms or benefits associated with these agents.”

Mehra’s group analyzed some 96,000 patients from 671 hospitals on six continents with COVID-19 infection, from Dec. 20 to April 14, all of whom had either died or been discharged from the hospital by April 21.

Overall, 14,888 patients were treated with hydroxychloroquine, chloroquine, hydroxychloroquine with a macrolide antibiotic or chloroquine with an antibiotic, and their results were compared to 81,144 controls who did not receive these drugs.

Authors adjusted for demographic factors, as well as cardiovascular disease, diabetes, lung disease, smoking, immunosuppressed conditions and baseline disease severity.

The estimated excess risk attributable to the drug regimen rather than other factors, such as comorbidities, ranged from 34% to 35%.

Arrhythmia’s greatest risk was in the group who received hydroxychloroquine and a macrolide antibiotic such as azithromycin (8% versus 0.3% of controls), and this regimen was associated with a more than five-fold risk of developing an arrhythmia while hospitalized, though cause and effect cannot be inferred, the group noted.

“Previous small-scale studies have failed to identify robust evidence of a benefit and larger, randomised controlled trials are not yet completed,” said co-author Frank Ruschitzka, MD, Director of the Heart Center at University Hospital Zurich in a statement. “However, we now know from our study that the chance that these medications improve outcomes in COVID-19 is quite low.”

An accompanying editorial by Christian Funck-Brentano, MD, PhD, and Joe-Elie Salem, MD, PhD, of Sorbonne Université in Paris, noted limitations of the observational data, but said the authors “should be commended for providing results from a well designed and controlled study … in a very large sample of hospitalized patients.”

They also cautioned against attributing the increased risk of hospital deaths to the higher incidence of arrhythmias, noting that “the relationship between death and ventricular tachycardia was not studied and causes of deaths (i.e., arrhythmic vs non-arrhythmic) were not adjudicated.”

The editorialists nevertheless concluded both hydroxychloroquine and chloroquine, with or without azithromycin, “are not useful and could be harmful in hospitalized patients with COVID-19,” and stressed the importance of clinical trials for these drugs.

“The global community awaits the results of ongoing, well powered randomized controlled trials showing the effects of chloroquine and hydroxychloroquine on COVID-19 clinical outcomes,” they wrote.

 

 

 

 

Cartoon – Blinded by Science

A Politician Delivers A Campaign Speech Acrylic Print by Paul Noth

Cartoon – Coronavirus Recovery Plan

Then a Miracle Occurs | HENRY KOTULA