In this last episode of our six-part series on vaccinations, supported by the National Institute for Health Care Management Foundation, we cover vaccine development – particularly in the context of the current global pandemic. We discuss the timeline of Covid-19 vaccine development and the mRNA vaccine approach.
President Joe Biden proposed an ambitious budget for the next federal fiscal year that includes more money for fighting the opioid epidemic, bolstering public health and several other healthcare items.
The budget request to Congress, released Friday, acts as essentially a wish list of priorities for the administration for the next year.
It is doubtful how much would get approved by Congress but sends a message of what the administration prioritizes.
Here are three healthcare priorities outlined in the request:
- The opioid epidemic: $10.7 billion was requested for fighting the opioid epidemic, $3.9 billion over the 2021 enacted level. The money will help support research, prevention and recovery services. The administration also is calling for targeted investments for “populations with unique needs, including Native Americans, older Americans and rural populations,” according to a release from the Office of Management and Budget on Friday.
- Public health infrastructure: $8.7 billion was requested for the Centers for Disease Control and Prevention to boost public health capacity in states and territories. OMB calls the budget increase the largest in nearly two decades for the agency at the frontlines of combating COVID-19. The Biden administration hopes to use the new money to train new epidemiologists and public health experts and “build international capacity to detect, prepare for and respond to emerging global threats.” A letter sent Friday to congressional leaders from the White House said that CDC funding was 10% lower than the previous decade after adjusting for inflation.
- Research funding boosts: $6.5 billion to launch a new agency called the Advanced Research Projects Agency for Health. The new agency would provide major increases in federal research and development spending on cancer and other diseases such as diabetes and Alzheimer’s. The goal of the investment is to “drive transformational innovation in health research and speed application and implementation of health breakthroughs,” OMB’s letter to Congress said. The funding is rolled into a $51 billion request for funding to the National Institutes of Health.
A new report out later today concludes that basic scientific research plays an essential role in creating companies that later produce thousands of jobs and billions in economic value.
Why it matters: The report uses the pandemic — and especially the rapid development of new mRNA vaccines — to show how basic research funding from the government lays the necessary groundwork for economically valuable companies down the road.
By the numbers: The Science Coalition — a nonprofit group that represents 50 of the nation’s top private and public research universities — identified 53 companies that have spun off from federally funded university research.
- Those companies — which range from pharmaceutical startups to agriculture firms — have contributed more than $1.3 billion to U.S. GDP between 2015 and 2019, while supporting the creation of more than 100,000 jobs.
What they’re saying: “The COVID-19 pandemic has shown that the need for the federal government to continue investing in fundamental research is far from theoretical,” says John Latini, president of the Science Coalition. “Consistent, sustained, robust federal funding is how science evolves.”
Details: Latini praised the Biden administration’s first budget proposal to Congress, released last week, which includes what would be a $9 billion funding boost for the National Institutes of Health (NIH) — the country’s single biggest science research funding agency.
- The National Oceanic and Atmospheric Administration would see its budget rise to a record high of $6.9 billion, including $800 million reserved for climate research.
The catch: The Biden budget proposal is just that, and it will ultimately be up to Congress to decide how much to allocate to research agencies.
Context: Government research funding is vital because private money tends to go to applied research. But without basic research — the lifeblood of science — the U.S. risks missing out on potentially world-changing innovations in the future.
- The long-term value of that funding can be seen in the story of Katalin Kariko, an obscure biomedical researcher who labored for years on mRNA with little reward — until the pandemic, when her work helped provide the foundation for mRNA COVID-19 vaccines.
The bottom line: Because its ultimate payoff might lay years in the future, it’s easy to see basic research funding as a waste — until the day comes when we need it.
The halt shows that safety protections are working, experts say
The hold on human testing of the vaccine candidate being developed by the pharmaceutical company AstraZeneca and the University of Oxford was confirmed by the company in a statement Tuesday evening, calling it a “routine action.”
“The announcement yesterday about the AstraZeneca vaccine is a concrete example of how even a single case of an unexpected illness is sufficient to require a clinical hold for the trial in multiple counties,” said Francis Collins, director of the National Institutes of Health, at a Senate hearing.
The announcement comes as scientists and a growing numbers of Americans express concern about the politicization of the vaccine approval process during a presidential election campaign. President Trump has made approval of a coronavirus vaccine a cornerstone of his campaign and repeatedly said it could be greenlighted before the Nov. 3 election.
But Collins and other scientists pointed to AstraZeneca’s decision as evidence that scientists, rather than politicians, are running the process. The experts said that it was hard to estimate how long the investigation would take, but that the pause was a good sign and not unexpected in trials of this size and scale, where many thousands of people are closely followed.
Collins testified that while minimal information is available about the adverse event, he has heard it described as transverse myelitis, rare inflammation of the spinal cord that has been associated with vaccinations, but has also been documented in a few cases of covid-19 and can occur in immune system disorders such as multiple sclerosis.
A study in the journal Lupus reported that between 1970 and 2009, there were 37 cases of transverse myelitis associated with various vaccines.
“The event is being investigated by an independent committee, and it is too early to conclude the specific diagnosis,” said AstraZeneca spokesman Brendan McEvoy.
Serious adverse events are closely monitored in clinical trials to determine whether they are likely to be linked to the drug or vaccine being administered. In trials with many thousands of people, sicknesses are likely to occur, and they may have no connection to the drug or vaccine being tested.
Collins also said he was not worried that the delay or even possible elimination of the AstraZeneca vaccine candidate would limit the eventual availability of vaccines to Americans.
“The reason we’re investing not in one, but in six different vaccines is because of the expectation that they won’t all work,” he told members of the Senate Health, Education, Labor and Pensions Committee.
“To have a clinical hold as has been placed on AstraZeneca as of yesterday because of a single serious adverse effect is not at all unprecedented,” Collins said.
He said that if after a thorough investigation, the adverse reaction is traced back to the vaccine candidate, then all the doses of that vaccine being manufactured would be thrown away. The United States has committed up to $1.2 billion to AstraZeneca to support development of the vaccine and to purchase 300 million doses.
A hold on a trial is not common, but is also not cause for alarm — it is a sign the system in place to protect participants is working, said Susan Ellenberg, a biostatistician at the University of Pennsylvania who has served on the independent data safety monitoring boards that investigate such incidents.
“The process is when something unusual develops, they might want to put a hold on things — and given the incredible attention that’s being given to these vaccines, and the recognition of how fast we’re trying to go, I think people are bending over backwards to show safety is really the top priority,” Ellenberg said.
This is the second pause for the trial. An information sheet for study participants from July noted that the trial had been put on hold after a participant developed neurological symptoms, but those were determined to be caused by an “unrelated neurological illness.”
“I think the company is being prudent to stop and look and to determine whether this severe adverse event, whatever it is, was a coincidence that followed vaccination, or was caused by the vaccine,” said Paul Offit, director of the Vaccine Education Center at Children’s Hospital of Philadelphia. “The vaccine is designed to prevent covid-19, not everything else” that adults might develop.
The pause came a day after the leaders of nine drug companies signed a highly unusual pledge that they would be guided by science and prioritize safety in their effort to develop a coronavirus vaccine, amid worries that political pressure could lead to an unsafe or ineffective vaccine to be used in millions of healthy people.
“This temporary pause is living proof that we follow those principles while a single event at one of our trial sites is assessed by a committee of independent experts,” Pascal Soriot, the AstraZeneca chief executive, said in a statement. “We will be guided by this committee as to when the trials could restart, so that we can continue our work at the earliest opportunity to provide this vaccine broadly, equitably and at no profit during this pandemic.”
“Even if it turns out this is causally related to the vaccine, that doesn’t automatically mean this is something you might not carry on,” said Naor Bar-Zeev, deputy director of the International Vaccine Access Center at Johns Hopkins Bloomberg School of Public Health. “The benefit versus risk needs to be evaluated with the likelihood of each of these things and is clearly context dependent. If there was no covid in the world, you’d not want to take a vaccine.”
But Collins underscored at the hearing that the safety review and pause was just another reason that the United States was spreading its bets so widely, investing in six different vaccines. The United Kingdom has also made purchasing agreements for six vaccines in the final stages of human testing.
At a news conference at 10 Downing Street on Wednesday, United Kingdom chief scientific adviser Patrick Vallance said it was not unusual for a large Phase 3 trial test of effectiveness and safety of vaccines to be paused.
This is precisely why a Phase 3 trial is undertaken, he said.
“A pause is obviously not good,” Vallance said. “But it is sensible to look closely to see what is going on.”
A new report that aims to prioritize groups to receive Covid-19 vaccine lays out detailed recommendations on who should be at the front of the line, starting with health care workers in high-risk settings, followed by adults of any age who have medical conditions that put them at significantly higher risk of having severe disease.
Also toward the front of the line would be older adults living in long-term care homes or other crowded settings.
The draft report, which runs 114 pages, was released Tuesday by the National Academies of Sciences, Engineering, and Medicine, which was tasked with the work by Francis Collins, director of the National Institutes of Health, and Robert Redfield, director of the Centers for Disease Control and Prevention.
A virtual public meeting on the recommendations will be held Wednesday afternoon, and the committee’s final report will be submitted later in September.
When Covid-19 vaccines are approved for use, initial supplies will be tight — potentially in the tens of millions of doses. Most of the vaccines under development will require two doses per person: a priming dose followed by a booster either three or four weeks later.
The report suggests that a second phase of vaccinations should involve critical risk workers — people in industries essential to the functioning of society — as well as teachers and school staff; people of all ages with an underlying health problem that increases the risk of severe Covid-19; all older adults not vaccinated in the first phase; people in homeless shelters and group homes, and prisons; and staff working in these facilities.
Young adults, children, and workers in essential industries not vaccinated previously would make up the third priority group. Remaining Americans who were not vaccinated in the first three groups would be offered vaccine during a fourth and final phase.
The report is meant to serve as a guide for more detailed prioritization plans on the order in which Americans will be offered vaccine. That more granular work is already being conducted by the Advisory Committee on Immunization Practices, an expert panel that crafts vaccination guidance for the CDC, and by state, local, and tribal health authorities, who must identify the actual people in their regions who fall into the priority groups.
There has been discussion of prioritizing people of color, who have been disproportionately badly hit in this pandemic. But the report does not recommend that Black, Hispanic, Latinx people, or American Indians or Alaskan natives be treated as a distinct priority group.
The committee suggested that there does not appear to be a biological reason for why these communities are more seriously affected by the pandemic. Instead, it argues, the high rates of infections and deaths in these communities are due to systemic racism that leads to higher levels of poor health and socioeconomic factors such as working in jobs that cannot be done from home or living in crowded settings.
The report therefore prioritized other factors — people with underlying medical problems, people living in crowded environments, for instance — rather than creating priority categories for racial or ethnic groups.
The ACIP’s recommendations will go to the CDC. It remains unclear, however, whether the CDC, Operation Warp Speed — the task force set up to fast-track development of Covid-19 vaccines, drugs and diagnostics — or the White House will make the final determinations on who will be vaccinated first.
The task of determining who should be at the front of the vaccines line is not an easy one, and must be made without key pieces of information. It’s not yet known how many vaccines will prove to be successful, when they will be approved for use and in what quantities. Critically, some vaccines may prove to be more effective in key groups — the elderly, for instance — than others. Knowing that in advance could influence the recommendations, but people working on the priority groups cannot wait for that information to become available.
Initial discussions suggest large numbers of Americans would qualify as members of priority groups, a reality that will likely require additional tough decisions to be made.
CDC estimates that there are between 17 million and 20 million health care workers in the country, and roughly 100 million people with medical conditions that put them at increased risk of severe illness if they contract Covid-19. There are roughly 53 million Americans aged 65 and older and 100 million people in jobs designated as essential services. There is some overlap among these groups — health workers, for instance, are also essential workers.
A report released last month by the Johns Hopkins Center for Health Security recommended dividing priority groups into two tiers, with health workers and others essential to the Covid-19 response in the first tier and other health workers in the second.
In that report, people at greatest risk and their caregivers, and workers most essential to maintaining core societal functions would also be designated to be in the first tier.
The good news is that they aren’t partisan, and they’re fixable.
In our response to the Covid-19 pandemic, the United States has all too often been caught flat-footed. Our public officials have tried to avoid or deny problems until they have been right on top of us, and legislative measures have tended to react to major challenges rather than avert them.
That has left policymakers with a lot to react to. And the relief and assistance bill now being worked out in the Senate will need to do that on several fronts. But to do better in the future, that bill should also take on several predictable problems that will face our country over the remainder of the year and which could benefit enormously from some advance attention and action.
Three sets of such predictable problems stand out above all, and in all three cases there are measures that can be taken now that should be able to attract bipartisan support.
First, states are going to face a monumental fiscal crisis.
The pandemic and the ensuing shutdowns of economic activity have left state governments with immense revenue shortages. Balanced-budget amendments in all but one state severely restrict their capacity to run deficits, in many cases even in major emergencies. That means states will have to either find other ways to raise revenue quickly or make major cuts to basic services. Such cuts in spending, jobs and public assistance would exacerbate the deep recession we are in and leave millions who need help in the lurch.
Most state fiscal years begin in July, so in many cases budgets designed or enacted before the severity of the crisis was clear are now starting to take effect, leaving states facing gaps they can easily predict but haven’t formally accounted for. In fact, 16 states are now starting the second year of biennial budgets enacted in 2019, before anyone could have imagined the sort of crisis we now face. Over the coming months, there will be no avoiding the fiscal crunch.
The states have already begun pleading with Congress for help, and sooner or later Congress will need to provide it. Taking steps sooner rather than later would make an enormous difference. The federal government has often been called on to serve as a fiscal backstop for states in extreme emergencies, since its borrowing power vastly exceeds that of the states. And that role is particularly appropriate in a truly national—indeed global—crisis of this magnitude.
But to provide such help responsibly, Congress will need to clearly delineate what kinds of assistance it can offer and on what terms. Congressional Republicans are not wrong to be wary of state efforts to use the emergency to fill fiscal holes dug over decades of irresponsible state policies. Yet that can’t mean that they deny state governments the help they need to contend with this crisis. Rather, it means they must draw some distinctions.
As I’ve argued elsewhere, Congress would do well to divide state needs into three tranches: direct pandemic spending (which should be covered by federal dollars), lost state revenue (which states should be given the opportunity to make up with federally guaranteed loans on favorable terms), and longstanding obligations like pension and retiree health costs made untenable by the recession (for which affected states should be given options only for strictly conditional support, like a new state bankruptcy code or federal support conditioned on major pension reforms).
To be effective, that sort of response would need to take shape now, before states have truly hit the wall. It should be part of the bill the parties are now beginning to negotiate.
Second, this fall’s election is going to be seriously complicated by the pandemic.
There is pretty much no way around that. We’ll be voting while the virus is still spreading, which means that far more people than usual will vote by mail. Only a few states have real experience with voting by mail in large numbers, and the logistics involved are not simple. Primary elections in many states have already made the challenge clear.
To take just one example among many, mailed ballots require signature verification. In states that haven’t spent years building the required infrastructure, such verification will probably need to be done by hand, creating huge risks of confusion and error. States will need to develop new processes to handle this, to train election workers to use unfamiliar equipment, and to take on problems in real time. Signature verification also requires a process for notifying voters whose handwriting is challenged and giving them time to respond. All that, and similar challenges on other election administration fronts, makes it easy to imagine that many races will be impossible to call on election night, and perhaps for quite some time afterward.
Particularly in an era already overflowing with cynical mistrust and conspiracy mongering, such problems raise the prospect of a legitimacy crisis around the election. And policymakers need to take steps now to reduce the risk of such a crisis.
The first step must be to prepare the public. Elected officials, candidates, journalists and others must start speaking plainly about the likelihood of logistical challenges around the election so that voters are not shocked if things don’t go smoothly. People must know in advance that we should not expect every race to be called straight away and that results which take days or even weeks to determine are not therefore illegitimate.
But beyond setting voter expectations, policymakers should also be looking for ways to reduce the strain on the system and to deal with predictable problems. One simple step Congress could take now is to push back the deadlines involved in the work of the Electoral College, to give the states more time to count votes in the presidential race if they need it. A simple change in the federal law governing these dates, which wouldn’t give either party an advantage, could give every state about three more weeks to count. Such a change would be essentially impossible after the election—when partisans looking at partial results would argue over which side it would advantage. But it could easily be done today, it would just take a few sentences of legislative language, and it too should be part of the relief bill now being worked out.
Finally, if we’re lucky, we’re going to need to figure out how to distribute a Covid-19 vaccine early next year. That would be a good problem to have, of course, but a huge problem nonetheless. And getting it wrong could catastrophically undermine the effort to defeat the virus.
Vaccine development itself is one area where our country has not been behind the curve: The federal government has invested heavily in the effort, the National Institutes of Health has played a key coordinating role, and the administration is prepared to pay for “at risk” manufacturing of millions of doses of any vaccine that makes it into Phase III trials, so that if a vaccine is found to be safe and effective there will immediately be doses to provide to high-risk individuals. But who will be first in line to get these early doses? And who will decide?
Here, too, there is an enormous danger of a legitimacy crisis. Both public fear about the safety of a vaccine (building on decades of anti-vaccine conspiracy theories on the right and left alike) and the danger of corruption, or at least perceived corruption, in the distribution of doses could undermine the potential of effective vaccination to end the nightmare of this pandemic.
Widespread uptake is essential to the effectiveness of any vaccine. It is not so much by protecting each vaccinated individual as by vaccinating enough Americans to achieve broad-based communal (or “herd”) immunity that a vaccine could truly change the game. That means public trust in the process and wholesale vaccination across our society will be crucial.
To achieve that, it is essential that both the safety of the vaccine-development process and the basic fairness of the ultimate distribution formula be established in advance, and in a very public way. Congress has a crucial role to play here, too. Hearings should begin very soon to put before the public all available information about the efforts taken by the Food and Drug Administration to ensure the safety of the vaccine-development process, even as that process proceeds with unprecedented speed. And Congress should establish, ideally in this next relief bill, a public commission to develop a formula for equitable distribution of early vaccine doses: setting out tiers of priority (for front-line health workers, vulnerable populations, the elderly, and those with particular preexisting conditions), and seeking out ways to make sure that economic and other disadvantages do not translate into lesser or later access to vaccination.
The work of such a group should be reasonably transparent and would need to begin very soon if it is to bear fruit in time to be useful. Policymakers must not underestimate the danger of a loss of public confidence in a Covid-19 vaccine, and must take steps now to avoid such a foreseeable disaster.
The same is true on all three of these fronts. These may not be the greatest problems we confront in the remainder of this dark and difficult year, but they share some features that ought to make them high priorities: All three are predictable and serious, each would amount to a disaster if left unchecked, but each could be made much easier to handle with some straightforward preparation. The relief bill being negotiated this summer could easily, without sparking a partisan war, take concrete steps on all three fronts.
Leadership in a crisis demands a combination of planning for foreseeable difficulties and responding to the unexpected. Getting the former right can make the latter far more doable. To make the rest of this year less disastrous, our leaders need to look ahead.
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.”
A cheap, readily available steroid drug reduced deaths by a third in patients hospitalized with Covid-19 in a large study, the first time a therapy has been shown to possibly improve the odds of survival with the condition in the sickest patients.
Full data from the study have not been published or subjected to scientific scrutiny. But outside experts on Tuesday immediately embraced the top-line results. The drug, dexamethasone, is widely available and is used to treat conditions including rheumatoid arthritis, asthma, and some cancers.
In a statement, Patrick Vallance, the U.K. government’s chief scientific adviser, called the result “tremendous news” and “a ground-breaking development in our fight against the disease.” Scott Gottlieb, a former commissioner of the U.S. Food and Drug Administration, called it “a very positive finding” in an interview on CNBC. “I think it needs to be validated, but it certainly suggests that this could be beneficial in this setting.”
Atul Gawande, the surgeon, writer and public health researcher, urged caution, tweeting, “after all the retractions and walk backs, it is unacceptable to tout study results by press release without releasing the paper.”
The study randomly assigned 2,104 patients to receive six milligrams of dexamethasone once a day, by mouth or intravenous injection. These were compared to 4,321 patients assigned to receive usual care alone.
In patients who needed to be on a ventilator, dexamethasone reduced the death rate by 35%, meaning that doctors would prevent one death by treating eight ventilated patients. In those who needed oxygen but were not ventilated, the death rate was reduced 20%, meaning doctors would need to treat 25 patients to save one life. Both results were statistically significant.
There was no benefit in patients who didn’t require any oxygen. The researchers running the study, called RECOVERY, decided to stop enrolling patients on dexamethasone on June 8 because they believed they had enough data to get a clear result.
“Dexamethasone is the first drug to be shown to improve survival in COVID-19,” Peter Horby, one of the lead investigators of the study and a professor in the Nuffield Department of Medicine at the University of Oxford, said in a statement. He added that the drug should now become the standard treatment for patients with Covid-19 who need oxygen. “Dexamethasone is inexpensive, on the shelf, and can be used immediately to save lives worldwide.’”
A different arm of the same study showed on June 5 that hydroxychloroquine, widely touted as a potential Covid treatment, had no benefit in hospitalized patients. Yesterday, based in part on those results, the Food and Drug Administration revoked an Emergency Use Authorization for using hydroxychloroquine in those patients.
From the start of the pandemic in March, researchers have focused on two different stages of Covid-19, which will likely require very different interventions. Some drugs are designed to directly combat the novel coronavirus, SARS-CoV-2, that causes the disease. The first medicine shown to have a benefit, remdesivir from the biotech firm Gilead Sciences, falls into this category, even though, because it must be given intravenously, it has been tested in hospitalized patients. Remdesivir shortens the course of infection, but has not been shown to save lives.
After patients have become profoundly sick, the problem starts to become not only the virus but their own immune system, which attacks the lungs, a condition called acute respiratory distress syndrome, or ARDS. For these patients, doctors have believed, they would need to dampen patients’ immune response even as they fought the virus.
Initially, excitement in this area fell on new and expensive drugs, such as Actemra, a rheumatoid arthritis drug from Roche that is used to treat a similar condition caused by some cancer immunotherapies. But a study in patients who needed oxygen showed no benefit from a similar drug, although another arm in sicker patients is continuing. The National Institutes of Health is conducting a study of an Eli Lilly pill targeting rheumatoid arthritis, an extension of the study that showed remdesivir has a benefit.
Dexamethasone, which reached the market 59 years ago, seemed an unlikely candidate to help these patients; it was seen as too crude a way of tamping down the immune system. In guidelines for physicians treating the disease, the NIH doesn’t even mention the therapy.
Studies that are testing other medicines may now need to incorporate the use of the drug, which could complicate analyzing the results. A spokesperson for Regeneron, which is testing Covid-19 drugs focused on both attacking the virus and dampening the immune system, said the company’s studies are written so that when a new medicine becomes the standard of care, it becomes available to patients in the trial.
Some studies have shown a benefit for using dexamethasone in acute respiratory distress syndrome not related to Covid-19, although the benefit was smaller than in RECOVERY.
The result, should it hold up to further scrutiny, shows the benefit of the strategy of Horby and Martin Landray, the Oxford researchers who designed the study, leveraging the U.K. health system to start a study of multiple inexpensive potential Covid-19 therapies — including hydroxychloroquine, dexamethasone, and also some older HIV medicines. Several months into the Covid-19 pandemic, two of the most important results come from this single study.
Neither of those results, however, have been scrutinized or published.