Category Archives: Clinical Trials

A coronavirus vaccine: Where does it stand?

Posted on by • Posted in 2020 Election Issues, Clinical Research, Clinical Research Funding, Clinical Testing, Clinical Trials, Coronavirus, Crisis, Crisis Management, Scientists, Vaccine, Vaccine RNA, World Health Organization (WHO) • Leave a comment

https://www.politifact.com/article/2020/jul/13/coronavirus-vaccine-where-does-it-stand/?fbclid=IwAR3hk04P0N3AuJXsKCr_JqV8vu0qZ6njsHE3if6xX6E2AxsllV1m81LjtX4

Coronavirus vaccines get a biotech boost

IF YOUR TIME IS SHORT

• Scientists are expressing cautious optimism that a vaccine can be ready to go by the late spring of 2021, although it’s unclear how much longer it would take to distribute the vaccine widely.

• Two possible vaccines are in phase 3 clinical trials; once those trials are completed, they would be candidates for approval. Another eight vaccines have begun phase 2 trials. And more than 100 other vaccines that haven’t begun clinical trials are in the pipeline.

• The Food and Drug Administration recently produced guidelines for the minimum effectiveness of vaccines seeking the agency’s approval. Vaccine officials say these guidelines are important to ensure public confidence in vaccines.

 

More than four months into the coronavirus pandemic, how close is the U.S. and the world to a safe and effective vaccine? Scientists say they see steady progress and are expressing cautious optimism that a vaccine could be ready by spring of 2021.

As of early July, there were roughly 160 vaccine projects under way worldwide, according to the World Health Organization. 

Generally, a vaccine trial has several phases. In an initial phase, the vaccine is given to 20 to 100 healthy volunteers. The focus in this phase is to make sure the vaccine is safe, and to note any side effects.

In the second phase, there are hundreds of volunteers. In addition to monitoring safety, researchers try to determine whether shots produce an immune-system response.

The third phase involves thousands of patients. This phase continues the goals of the first two, but adds a focus on how effective the vaccine is. This phase also collects data on more unusual negative side effects.

In ordinary circumstances, these phases take years to complete. But for coronavirus, the timeline is being shortened. This has spurred more public-private partnerships and significantly increased funding.

Here’s a rundown of the 13 vaccine candidates that are furthest along in the clinical phases:

Coronavirus vaccines that are the furthest along:

A Coronavirus Vaccine: Where Does It Stand? – Corridor News

The three vaccine candidates that are furthest along are both in phase 3. 

One is being developed by researchers at Oxford University in the U.K. It uses a weakened version of a virus that causes common colds in chimpanzees. Researchers then added proteins, known as antigens, from the novel coronavirus, in the hope that these could prime the human immune system to fight the virus once it encounters it.

Another candidate in a phase 3 trial is being developed in China. It uses a killed, and thus safe, version of the novel coronavirus to spur an immune reaction.

And on July 15, the biotech company Moderna, which is partnering with the National Institutes of Health, announced that it would be moving to phase 3 within two weeks.

Two others have made it as far as phase 2, while eight others are finishing their phase 1 trials while also beginning phase 2 trials.

These candidates are being developed by a mix of corporations and institutions in several countries. These efforts seek to leverage a range of different technologies.

One uses RNA material that provides the instructions for a body to produce the needed antigens itself. This is a relatively untested approach to vaccination, but if it works, it has aspects that could make it easier to manufacture. Another approach is similar, but uses DNA instead of RNA.

One U.S. biotech firm, Novavax, is receiving federal funding to produce a vaccine that uses a lab-made protein to inspire an immune response.

Beyond these, another 10 vaccine candidates are in phase 1 clinical trials, while another 140 haven’t reached the clinical phase yet.

Having so many potential vaccines this far along is impressive, experts say, given the short time scientists have known about the novel coronavirus. 

“Overall, the pace of development and advancement to Phase 3 trials is impressive,” said Matthew B. Laurens, associate professor at the University of Maryland School of Medicine’s Center for Vaccine Development and Global Health. “The public-private partnerships have been highly successful and are achieving goals for rapid vaccine development.”

In addition, the fact that several types of vaccine approaches are being tested means we aren’t putting all of our eggs in one basket.

“We will need several candidates should any one of these experience difficulties in manufacturing or show a safety signal when implemented in larger numbers of people,” Laurens said.

Meanwhile, at a time of rising public skepticism of government and vaccines, the Food and Drug Administration recently released additional guidelines on vaccine effectiveness. The new guidance requires vaccines to prevent or decrease the severity of the disease at least 50% of the time if they are to win the agency’s approval.

The FDA guidelines “reaffirmed the very rigorous FDA process for approving any vaccine. That gives a great deal of reassurance that this was going to be handled by the book,” said William Schaffner, a professor of preventive medicine and infectious diseases at Vanderbilt University Medical Center. “The more we talk about doing things fast, the more the public thinks, ‘They’re probably cutting corners.’”

How fast will we have access to a workable vaccine?

In early April, Kathleen M. Neuzil, director of the University of Maryland’s vaccine center, told PolitiFact that if all went well, there might be five or six vaccines in trials within six months. Now, three and a half months later, there are two to three times that number.

Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, and other officials have remained consistent in their estimation of the timeline: 12 to 18 months from the start of the pandemic, or roughly the late spring of 2021.

Schaffner told PolitiFact that he continues to see the first quarter of 2021 as a reasonable target. “I think that’s where the needle is pointing,” he said.

It remains to be seen how fast vaccines can be manufactured and distributed once approved for general use. Officials are also grappling with which Americans will get access first. So it’s unclear how long a person would have to wait to get vaccinated.

Laurens said he is not overly concerned about the distribution, because that is something that officials have long experience with. “Well-established programs exist for vaccine distribution, including for seasonal vaccination of large numbers of individuals,” he said.

Another hopeful sign, Schaffner said, is that the coronavirus itself seems to be relatively stable. There had been concern that the novel coronavirus, like many other viruses, is mutating over time. If the virus changes enough, that could become a problem that bedevils vaccine researchers.

But so far, that hasn’t happened. Even if evidence emerges that mutations are making the virus more transmissible, or that a new variant is making people sicker, that shouldn’t affect the vaccine process. “The central core of the virus would remain the same,” Schaffner said.

During the past month, there has been relatively little news about how much progress is being made on particular vaccines. Schaffner is not worried by the relative quiet.

“In a vaccine trial, if there’s an adverse safety finding, the guillotine comes down and that trial is stopped,” he said. “So quiet is good, because we’d know if something bad happens.”

 

 

 

Op-Ed: We Still Don’t Know the Risk Posed by COVID-19

Posted on by • Posted in 2020 Election Issues, Clinical Research, Clinical Research Funding, Clinical Testing, Clinical Trials, Coronavirus, Crisis, Crisis Management, Economic Crisis, Economic Recovery, Evidence-based Leadership, Evidence-Based Plan, Evidence-Based Policy, Food and Drug Administration (FDA), Infection Control, Infection Control Plan, Infectious Virus, Leadership Decentralized, Misinformation, Misinterpret, Mislead, Misleading, Mistrust, Mixed Message, Mortality, National Strategy, Pandemic, Public Health, Public Safety, Quarantine, Scientists, Social Distancing, Uncertainty • Leave a comment

https://www.medpagetoday.com/infectiousdisease/covid19/87629?xid=fb_o&trw=no&fbclid=IwAR2V6CbOCIXDf2K9sJCcRb0PhbqM4inXixe_poOFYudOcoUFZCmU2JzyrDg

Op-Ed: We Still Don't Know the Risk Posed by COVID-19 | MedPage Today

The need for a coordinated national research strategy

Confused about the risks of dying from the coronavirus or of catching it from someone who seems healthy? We all are, and the dizzying differences in scientific opinion are now linked to political perspectives. Progressives cite evidence that loosening restrictions would cost lives and offer little benefit to the economy, while conservatives embrace evidence that the risks are low. We offer a guide to help navigate the tangle of numbers and suggest a way forward.

Google and many others display the number of cases and deaths (3.6 million and 138,840, respectively, by July 17). This invites a simple calculation for understanding the risk: divide the number who have died by the number who have been diagnosed. So, the chance of dying if infected is about 3.9%. Right? Well, not so fast. Six months into the pandemic, neither the number of deaths nor the number of people infected is known.

Some argue that deaths have been overemphasized since people who die of COVID are mostly older and sicker. Others suggest deaths have been overcounted since if a patient tests positive for COVID-19, it will likely be listed as the cause of death even if the person succumbs to another illness or, in some jurisdictions, dies due to an accident or suicide. Others argue that deaths have been undercounted.

Missing from the tally on any given day are those who died before testing was available, those who died shortly before or after but whose death has not yet been reported, or who died as an indirect result of the epidemic such as failing to seek medical care for fear of going to the hospital.

One carefully designed recent analysis compared deaths this year to the number of people who die during a “normal” year. The analysis concluded that through May, almost 100,000 people died from COVID-19 in addition to 30,000 who died from other causes related to the pandemic.

In short, uncertainty remains about the number of deaths due to COVID-19, which is supposed to be the easy part.

Estimating the number of people who have been infected is harder still. Most infected people are never formally diagnosed and never become one of the “cases” in the news. The limitations of the tests and the difficulty of attracting a representative population to be tested make it hard to estimate the true number of infections. The preferred test (reverse transcription polymerase chain reaction-based tests) uses RNA technology to see if the virus is present in nasal or oral swabs. It is a good test, but still may miss infections in up to 30% of cases.

A second type of test uses blood samples to look for an antibody called immunoglobulin (Ig)G that implies the person was previously infected. Based on IgG test results, the CDC assumes that 5% to 8% of the population has been infected. That would mean 24 million Americans have already had COVID-19 or a very similar illness. That is more than 10 times the number of confirmed cases.

The number is consequential: a higher infection rate for the same number of deaths implies that the virus is less deadly. A review by a prominent epidemiologist considered 23 population studies with sample sizes of at least 500 people and found the percentage who have positive antibodies ranged from 0.1% to 48% — a 480-fold difference. Although the study was robustly criticized and at odds with highly cited, peer-reviewed research, it has appeared in over 30 news outlets, and the range of estimates allows people to pick a number that justifies their political position.

Contributing to this uncertainty is the FDA decision to, in a hurry to catch up for lost time, temporarily relax its standards for approving tests. Among over 300 antibody tests currently on the market, data on only a handful are publicly available, and some are being recalled.

The other number we need to know is how many people are spreading the infection without knowing it. Estimates are all over the place. Some major employers, including Stanford Healthcare, have systematically tested all of their employees and found very few infected people who do not have symptoms. In contrast, a CDC study of young, healthy adults working on an aircraft carrier found that 20% of those infected reported no symptoms.

So here we are, months into the epidemic without consensus on the basic information about how many people are infected, the risk of death for those infected, or the risk of asymptomatic transmission. In contrast to official agencies that use transparent methods to report the weather or the unemployment rate, trust in our official health statistics agencies has broken down as reports continue to emerge form myriad sources with conflicting methodologies and motivations.

The time has come to activate impartial groups, like the National Academy of Medicine, to build consensus on how to monitor the epidemic. We know the risks are serious. As cases have started to rise, whether or not the number of U.S. deaths is higher or lower than 130,000, the risk of inaction is too high.

We are staying near home, wearing masks, and treating COVID-19 as a serious threat to public health.

 

 

What happens if Covid-19 symptoms don’t go away? Doctors are trying to figure it out.

Posted on by • Posted in 2020 Election Issues, Centers for Disease Control & Prevention (CDC), Clinical Testing, Clinical Trials, Contact Tracing, Coronavirus, Coronavirus Long-Term Complications, Coronavirus Treatment, Deconditioning, Delirium, Essential Businesses, Essential Workers, Evidence-Based Care, Health Insurance Coverage Adequacy, Health Policy, Health System, Hospital, Hospital Industry, Infection Control, Infection Control Plan, Infectious Virus, Intensive Care (ICU), Lingering Symptoms, Long-Term Consequences, Mortality, Out of Pocket Expenses, Pandemic, Post-Covid Care, Preexisting Conditions, Public Health, Public Safety, Quarantine, Scientists, Social Distancing, Underinsured, Uninsured • Leave a comment

https://www.vox.com/2020/7/14/21324201/covid-19-long-term-effects-symptoms-treatment

Covid-19 long-term effects: People with persistent symptoms ...

People with long-term Covid-19 complications are meanwhile struggling to get care.

In late March, when Covid-19 was first surging, Jake Suett, a doctor of anesthesiology and intensive care medicine with the National Health Service in Norfolk, England, had seen plenty of patients with the disease — and intubated a few of them.

Then one day, he started to feel unwell, tired, with a sore throat. He pushed through it, continuing to work for five days until he developed a dry cough and fever. “Eventually, I got to the point where I was gasping for air literally doing nothing, lying on my bed.”

At the hospital, his chest X-rays and oxygen levels were normal — except he was gasping for air. After he was sent home, he continued to experience trouble breathing and developed severe cardiac-type chest pain.

Because of a shortage of Covid-19 tests, Suett wasn’t immediately tested; when he was able to get a test, 24 days after he got sick, it came back negative. PCR tests, which are most commonly used, can only detect acute infections, and because of testing shortages, not everyone has been able to get a test when they need one.

It’s now been 14 weeks since Suett’s presumed infection and he still has symptoms, including trouble concentrating, known as brain fog. (One recent study in Spain found that a majority of 841 hospitalized Covid-19 patients had neurological symptoms, including headaches and seizures.) “I don’t know what my future holds anymore,” Suett says.

Some doctors have dismissed some of his ongoing symptoms. One doctor suggested his intense breathing difficulties might be related to anxiety. “I found that really surprising,” Suett says. “As a doctor, I wanted to tell people, ‘Maybe we’re missing something here.’” He’s concerned not just for himself, but that many Covid-19 survivors with long-term symptoms aren’t being acknowledged or treated.

Suett says that even if the proportion of people who don’t eventually fully recover is small, there’s still a significant population who will need long-term care — and they’re having trouble getting it. “It’s a huge, unreported problem, and it’s crazy no one is shouting this from rooftops.”

In the US, a number of specialized centers are popping up at hospitals to help treat — and study — ongoing Covid-19 symptoms. The most successful draw on existing post-ICU protocols and a wide range of experts, from pulmonologists to psychiatrists. Yet even as care improves, patients are also running into familiar challenges in finding treatment: accessing and being able to pay for it.

What’s causing these long-term symptoms?

Scientists are still learning about the many ways the virus that causes Covid-19 impacts the body — both during initial infection and as symptoms persist.

One of the researchers studying them is Michael Peluso, a clinical fellow in infectious diseases at the University of California San Francisco, who is currently enrolling Covid-19 patients in San Francisco in a two-year study to study the disease’s long-term effects. The goal is to better understand what symptoms people are developing, how long they last, and eventually, the mechanisms that cause them. This could help scientists answer questions like how antibodies and immune cells called T-cells respond to the virus, and how different individuals might have different immune responses, leading to longer or shorter recovery times.

At the beginning of the Covid-19 pandemic, “the assumption was that people would get better, and then it was over,” Peluso says. “But we know from lots of other viral infections that there is almost always a subset of people who experience longer-term consequences.” He explains these can be due to damage to the body during the initial illness, the result of lingering viral infection, or because of complex immunological responses that occur after the initial disease.

“People sick enough to be hospitalized are likely to experience prolonged recovery, but with Covid-19, we’re seeing tremendous variability,” he says. It’s not necessarily just the sickest patients who experience long-term symptoms, but often people who weren’t even initially hospitalized.

That’s why long-term studies of large numbers of Covid-19 patients are so important, Peluso says. Once researchers can find what might be causing long-term symptoms, they can start targeting treatments to help people feel better. “I hope that a few months from now, we’ll have a sense if there is a biological target for managing some of these long-term symptoms.”

Lekshmi Santhosh, a physician lead and founder of the new post-Covid OPTIMAL Clinic at UCSF, says many of her patients are reporting the same kinds of problems. “The majority of patients have either persistent shortness of breath and/or fatigue for weeks to months,” she says.

Additionally, Timothy Henrich, a virologist and viral immunologist at UCSF who is also a principal investigator in the study, says that getting better at managing the initial illness may also help. “More effective acute treatments may also help reduce severity and duration of post-infectious symptoms.”

In the meantime, doctors can already help patients by treating some of their lingering symptoms. But the first step, Peluso explains, is not dismissing them. “It is important that patients know — and that doctors send the message — that they can help manage these symptoms, even if they are incompletely understood,” he says. “It sounds like many people may not be being told that.”

Long-term symptoms, long-term consequences

Even though we have a lot to learn about the specific damage Covid-19 can cause, doctors already know quite a bit about recovery from other viruses: namely, how complex and challenging a task long-term recovery from any serious infection can be for many patients.

Generally, it’s common for patients who have been hospitalized, intubated, or ventilated — as is common with severe Covid-19 — to have a long recovery. Being bed-bound can cause muscle weakness, known as deconditioning, which can result in prolonged shortness of breath. After a severe illness, many people also experience anxiety, depression, and PTSD.

A stay in the ICU not uncommonly leads to delirium, a serious mental disorder sometimes resulting in confused thinking, hallucinations, and reduced awareness of surroundings. But Covid-19 has created a “delirium factory,” says Santhosh at UCSF. This is because the illness has meant long hospital stays, interactions only with staff in full PPE, and the absence of family or other visitors.

Theodore Iwashyna, an ICU physician-scientist at the University of Michigan and VA Ann Arbor, is involved with the CAIRO Network, a group of 40 post-intensive care clinics on four continents. In general, after patients are discharged from ICUs, he says, “about half of people have some substantial new disability, and half will never get back to work. Maybe a third of people will have some degree of cognitive impairment. And a third have emotional problems.” And it’s common for them to have difficulty getting care for their ongoing symptoms after being discharged.

In working with Covid-19 patients, says Santhosh, she tells patients, “We believe you … and we are going to work on the mind and body together.”

Yet it’s currently impossible to predict who will have long-lasting symptoms from Covid-19. “People who are older and frailer with more comorbidities are more likely to have longer physical recovery. However, I’ve seen a lot of young people be really, really sick,” Santhosh says. “They will have a long tail of recovery too.”

Who can access care?

At the new OPTIMAL Clinic at UCSF, doctors are seeing patients who were hospitalized for Covid-19 at the UCSF health system, as well as taking referrals of other patients with persistent pulmonary symptoms. For ongoing cough and chest tightness, the clinic is providing inhalers, as well as pulmonary rehabilitation, including gradual aerobic exercise with oxygen monitoring. They’re also connecting patients with mental health resources.

“Normalizing those symptoms, as well as plugging people into mental health care, is really critical,” says Santhosh, who is also the physician lead and founder of the clinic. “I want people to know this is real. It’s not ‘in their heads.’”

Neeta Thakur, a pulmonary specialist at Zuckerberg San Francisco General Hospital and Trauma Center who has been providing care for Covid-19 patients in the ICU, just opened a similar outpatient clinic for post-Covid care. Thakur has also arranged a multidisciplinary approach, including occupational and physical therapy, as well as expedited referrals to neurology colleagues for rehabilitation for the muscles and nerves that can often be compressed when patients are prone for long periods in the ICU. But she’s most concerned by the cognitive impairments she’s seeing, especially as she’s dealing with a lot of younger patients.

These California centers join new post-Covid-19 clinics in major cities across the country, including Mount Sinai in New York and National Jewish Health Hospital in Denver. As more and more hospitals begin to focus on post-Covid care, Iwashyna suggests patients try to seek treatment where they were hospitalized, if possible, because of the difficulty in transferring sufficient medical records.

Santosh recommends that patients with persistent symptoms call their closest hospital, or nearest academic medical center’s pulmonary division, and ask if they can participate in any clinical trials. Many of the new clinics are enrolling patients in studies to try to better understand the long-term consequences of the disease. Fortunately, treatment associated with research is often free, and sometimes also offers financial incentives to participants.

But otherwise, one of the biggest challenges in post-Covid-19 treatment is — like so much of American health care — being able to pay for it.

Outside of clinical trials, cost can be a barrier to treatment. It can be tricky to get insurance to cover long-term care, Iwashyna notes. After being discharged from an ICU, he says, “Recovery depends on [patients’] social support, and how broke they are afterward.” Many struggle to cover the costs of treatment. “Our patient population is all underinsured,” says Thakur, noting that her hospital works with patients to try to help cover costs.

Lasting health impacts can also affect a person’s ability to go back to work. In Iwashyna’s experience, many patients quickly run through their guaranteed 12 weeks of leave under the Family Medical and Leave Act, which isn’t required to be paid. Eve Leckie, a 39-year-old ICU nurse in New Hampshire, came down with Covid-19 on March 15. Since then, Leckie has experienced symptom relapses and still can’t even get a drink of water without help.

“I’m typing this to you from my bed, because I’m too short of breath today to get out,” they say. “This could disable me for the rest of my life, and I have no idea how much that would cost, or at what point I will lose my insurance, since it’s dependent on my employment, and I’m incapable of working.” Leckie was the sole wage earner for their five children, and was facing eviction when their partner “essentially rescued us,” allowing them to move in.

These long-term burdens are not being felt equally. At Thakur’s hospital in San Francisco, “The population [admitted] here is younger and Latinx, a disparity which reflects who gets exposed,” she says. She worries that during the pandemic, “social and structural determinants of health will just widen disparities across the board.” People of color have been disproportionately affected by the virus, in part because they are less likely to be able to work from home.

Black people are also more likely to be hospitalized if they get Covid-19, both because of higher rates of preexisting conditions — which are the result of structural inequality — and because of lack of access to health care.

“If you are more likely to be exposed because of your job, and likely to seek care later because of fear of cost, or needing to work, you’re more likely to have severe disease,” Thakur says. “As a result, you’re more likely to have long-term consequences. Depending on what that looks like, your ability to work and economic opportunities will be hindered. It’s a very striking example of how social determinants of health can really impact someone over their lifetime.”

If policies don’t support people with persistent symptoms in getting the care they need, ongoing Covid-19 challenges will deepen what’s already a clear crisis of inequality.

Iwashyna explains that a lot of extended treatment for Covid-19 patients is “going to be about interactions with health care systems that are not well-designed. The correctable problems often involve helping people navigate a horribly fragmented health care system.

“We can fix that, but we’re not going to fix that tomorrow. These patients need help now.”

 

 

 

Coronavirus drugmakers’ latest tactics: Science by press release

Posted on by • Posted in Clinical Research, Clinical Trials, Coronavirus, Coronavirus Treatment, False Hope, False Narrative, Food and Drug Administration (FDA), Hydroxychloroquine, Marketing, Mislead, Misleading, National Institute of Health (NIH), Partisanship, Pharmaceutical Industry, Political Pressure, Press Release, Remdesivir, Stock Manipulation, Vaccine, Whistleblower, Wishful Thinking • Leave a comment

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.”

 

 

 

 

How Jefferson and Franklin Helped End Smallpox in America

Posted on by • Posted in 2020 Election Issues, Clinical Research, Clinical Trials, Leadership, Physician, Smallpox, Vaccination, Vaccine • Leave a comment

https://www.governing.com/context/How-Jefferson-and-Franklin-Helped-End-Smallpox-in-America.html

Drawing Lessons from a Government Protest in North Dakota

As the world eagerly awaits a vaccine for the coronavirus, 200 years ago a smallpox cure struggled to gain acceptance. This is how our founding fathers helped promote the medical breakthrough that saved countless lives.

The great scourge of Thomas Jefferson’s era (1743-1826) was smallpox. Historians have estimated that perhaps as many as 2 billion people have died of smallpox in recorded history. That’s a pretty arbitrary figure, but it certainly indicates how serious the problem was. Modern epidemiology has not only eliminated smallpox as a threat to civilization but has been engaged in a protracted debate about whether to snuff it out altogether once and for all, or to keep a tiny bit of it alive in a handful of tightly secured vials in case we need to study it in the face of other disease epidemics. It was officially declared eradicated in 1980.

For most of human history, you either got it or you didn’t and then you either survived it or you didn’t. George Washington was infected by smallpox in Barbados in 1751. He survived, and though he was slightly disfigured, he was thereafter immune to the disease. It is possible that this early brush with smallpox saved the American Revolution 20 years later. In 18th-century Europe, 400,000 people died annually of smallpox.

By the time Jefferson was born in 1743, there was an experimental inoculation procedure, but it was quite dangerous and therefore highly controversial. The idea was to give healthy individuals a very tiny amount of actual smallpox under quarantine and very carefully controlled conditions and simply hope that the person’s immune system would be able to fight it off. Survival would immunize that individual for life. The procedure required many weeks of quarantine, fasting, puking, and rest, followed by a very light diet through convalescence. John Adams wrote a fascinating account of his own inoculation in 1764. He was 28 years old.

Young Thomas Jefferson’s first journey out of his native Virginia was to Philadelphia in 1766 to be inoculated. He would have undertaken the procedure in Williamsburg or Norfolk had it been available. He made the long journey (eight to 10 days in either direction) because he wanted to protect himself from the disease and study the procedure at the same time for possible incorporation into his own community at Monticello. With his characteristic taciturnity about personal things, Jefferson did not leave us a detailed account of the medical procedure, which required prolonged isolation, personal discipline and a great deal of patience.

Inoculation was first introduced in Europe 40 years earlier. Lady Mary Wortley Montague (1689-1762) had spent time in Turkey as the wife of the British ambassador to the Ottoman Empire. There she had witnessed inoculation in the zenanas (segregated women’s quarters) she visited. She called the procedure “engrafting,” which she described in an important “Letter to a Friend” on April 1, 1717. Mrs. Montagu’s brother had died of smallpox four years earlier and she herself had survived a bout of smallpox in 1715, but with her famous beauty disfigured. She had her five-year-old son Edward inoculated in the British Embassy in Turkey.

Lady Mary Wortley Montagu in Ottoman Travel Dress. She was the first to introduce smallpox inoculation in Europe.

When she returned with her family to Britain, she became an outspoken advocate for the procedure. The English medical establishment decried inoculation and denounced Mary Montagu. Still, in 1721 when a smallpox epidemic broke out in England, she had her daughter inoculated in London. This was the first recorded use of the procedure in England. The medical establishment was slow to accept the efficacy of inoculation, which it regarded as an “oriental folk remedy.” It seemed counter-intuitive and just wrong-headed to give a healthy person a dose of smallpox to try to prevent her or him from getting it by accident. 

Franklin Learns About Inoculation the Hard Way

New England Puritan minister Cotton Mather (1663-1728) first promoted inoculation in America. In 1706, Reverend Mather purchased a black slave he named Onesimus (from the Epistle to Philemon). Ten years later, Onesimus told Mather he had been made immune to smallpox in Africa by having the pus of an infected person rubbed on an open wound on his arm. This is known as the variolation method. Mather interrogated other slaves to learn more, confirmed the story, and became an advocate for inoculation. He was subjected to the usual criticism and pushback. An explosive device was thrown through the window of his home. In this instance, racism joined fear as a means of discrediting the medical procedure. What possible wisdom could come from a slave?

The smallpox plague that disturbed Britain in 1721 found its way that same year to Boston. Now Mather and Dr. Zabdiel Boylston, the only physician in Boston who supported the technique, offered their inoculation services to anyone who would trust them. Of the 242 people Boylston inoculated, only six died, or one in 40. Of those who did not undergo the procedure, one in seven died.

America’s greatest exemplar of the Enlightenment, Benjamin Franklin, became a passionate advocate of the procedure after his first son Franky died of smallpox on Nov. 21, 1736, at the age of four. Because Franklin was known to be a friend to inoculation, rumors spread in Philadelphia that Franky had died from the procedure. To set the record straight, the grieving father wrote an article in the Pennsylvania Gazette on Dec. 30, 1736: He had “intended to get [Francis] inoculated as soon as he should have recovered sufficient strength from a flux with which he had been long afflicted.” Franklin assured the public that his son “received the distemper in the common way of infection.”

In 1774, Franklin, who was an indefatigable creator of associations, societies, clubs and public institutions, including volunteer fire departments and lending libraries, established the Society for Inoculating the Poor Gratis to help the poor people of Philadelphia have access to inoculation. In his famous autobiography, Franklin wrote: “In 1736 I lost one of my sons, a fine boy of four years old, by the smallpox taken in the common way. I long regretted bitterly and still regret that I had not given it to him by inoculation. This I mention for the sake of the parents who omit that operation, on the supposition that they should never forgive themselves if a child died under it.”

Edward Jenner and the Fight to Vaccinate

As a young man, the future English physician Edward Jenner (1749-1823) overheard an English milkmaid say, “I shall never have smallpox for I have had cowpox. I shall never have an ugly pockmarked face.” Many years later, remembering the incident, Jenner, now a doctor, interrogated other milkmaids and then experienced one of the most important “eureka” moments in history. Without understanding how germs work, with no knowledge of anything called a virus, Dr. Jenner realized that cowpox (also known as kinepox) must be closely related to smallpox, and that surviving it seemed to make individuals immune to the more deadly disease. He reckoned that cowpox and smallpox must share some essential epidemiological element and since cowpox was neither lethal nor usually disfiguring, careful use of cowpox material would represent a superior protection against smallpox than variolation, which was a more dangerous procedure.

On May 14, 1796, Jenner inoculated an eight-year-old boy named James Phipps with kinepox pus. Phipps developed mild fever and discomfort. Ten days later he felt fine. Two months after that, Dr. Jenner inoculated the boy again, but this time with serum from a fresh smallpox sore. No disease developed. The smallpox vaccine had been born. Our term “vaccination” dates from this episode. Vaccination comes from the Latin word for cow, “vacca.” Jenner called the cowpox serum “vaccinia.” The terminology reminds us that all western vaccination stems from this moment in 1796.

No good deed goes unpunished, apparently, not even one that changes the history of the planet. In Britain, Edward Jenner was subjected to the usual harassment and ridicule. The paper he submitted to the Royal Society of England was rejected by none other than Sir Joseph Banks, one of Britain’s premier naturalists, botanists, and patrons of science. It took many years and the vaccination experiments of other physicians and scientists before Jenner’s work was vindicated.

Eventually, Jenner received worldwide recognition for his discovery. Devoted like Jefferson to the philanthropic principles of the Enlightenment, Dr. Jenner not only made no effort to enrich himself but devoted so much of his time and energy to promoting vaccination that he endured periods of real poverty. Finally, in 1802, the British Parliament voted him a reward of £10,000. Five years later he received £20,000 more from Parliament.

The true vaccine found its way to America thanks to Dr. John Haygarth of Bath. He sent some of Jenner’s material to Benjamin Waterhouse, a professor of physics at Harvard University. Waterhouse, in turn sent serum and reports of the vaccine’s efficacy to Thomas Jefferson, now the third president of the United States.

Dr. Edward Jenner discovered the true smallpox vaccine in 1796.

Jefferson’s Scientific Approach to Vaccines

In the new world, inoculation had a very rough reception. When John Dalgleish and Archibald Campbell began inoculating individuals in Norfolk, Virginia, an angry mob burned down Campbell’s house. Similar incidents occurred in Salem and Marblehead, Mass. In Charleston, S.C., an inoculation control law of 1738 imposed a fine of £500 on anyone providing or receiving inoculation within two miles of the city. A similar law was passed in New York City in 1747.

The measures in New England were so draconian that Benjamin Waterhouse noted the paradox: “New England, the most democratical region on the face of the earth voluntarily submitted to more restrictions and abridgements of liberty, to secure themselves against that terrific scourge, than any absolute monarch could have enforced.” (This, strangely prescient, anticipates the current debate about liberty versus public health). It was in the middle colonies — Maryland, Pennsylvania, New Jersey — that inoculation was most tolerated in the second half of the 18th century. That’s why Jefferson made the long journey to Philadelphia to be inoculated in 1766.

Jefferson first became aware of the discovery of a true smallpox vaccine from the newspapers he read in Philadelphia and the new capitol in Washington, D.C. Then, on Dec. 1, 1800, just after Jefferson’s election to the presidency, Benjamin Waterhouse sent him his pamphlet on the vaccine with a lovely cover letter saying that he regarded Jefferson as “one of our most distinguished patriots and philosophers.” Jefferson responded immediately, thanking Waterhouse for the publication and declaring, with his usual grace, that “every friend of humanity must look with pleasure on this discovery, by which one evil the [more] is withdrawn from the condition of man: and contemplating the possibility that future improvements & discoveries, may still more & more lessen the catalogue of evils. in this line of proceeding you deserve well of your [country?] and I pray you to accept my portion of the tribute due you.”

The following June, Waterhouse sent Jefferson a long letter explaining how the vaccine must be administered, how the serum could be preserved over time, and how much the controversial procedure needed the public support of a man of Jefferson’s stature in the “republic of letters.” President Jefferson became known as a defender and promoter of vaccination. In fact, he even arranged for his protégé Meriwether Lewis to carry some of the serum with him up the Missouri River in 1804-05, instructing him to “carry with you some matter of the kine pox, inform those of them with whom you may be, of its efficacy as a preservative from the small pox; and instruct & encourage them in the use of it. This may be especially done wherever you may winter.” Unfortunately, by the time the Lewis and Clark Expedition reached their winter encampment in today’s North Dakota, the serum had become inert. Thus Jefferson’s philanthropic initiative to vaccinate the Native Americans of the American West was stillborn.

Then, on May 14, 1806, now in his second term, Jefferson wrote perhaps the greatest presidential fan letter of all time. He took time from his duties as president to write the following letter to Edward Jenner. I quote it in its entirety:

SIR,— I have received a copy of the evidence at large respecting the discovery of the vaccine inoculation which you have been pleased to send me, and for which I return you my thanks. Having been among the early converts, in this part of the globe, to its efficiency, I took an early part in recommending it to my countrymen. I avail myself of this occasion of rendering you a portion of the tribute of gratitude due to you from the whole human family. Medicine has never before produced any single improvement of such utility. Harvey’s discovery of the circulation of the blood was a beautiful addition to our knowledge of the animal economy, but on a review of the practice of medicine before and since that epoch, I do not see any great amelioration which has been derived from that discovery. You have erased from the calendar of human afflictions one of its greatest. Yours is the comfortable reflection that mankind can never forget that you have lived. Future nations will know by history only that the loathsome small-pox has existed and by you has been extirpated. Accept my fervent wishes for your health and happiness and assurances of the greatest respect and consideration.

Who would not have wished to receive this magnificent, selfless, public-spirited, and enlightened letter? Unfortunately, we do not know how or even if Dr. Jenner responded. Except in medical circles, Edward Jenner has been largely forgotten.

 

 

 

 

 

Huge Study Throws Cold Water on Antimalarials for COVID-19

Posted on by • Posted in 2020 Election Issues, Chloroquine, Clinical Research, Clinical Trials, Coronavirus, Credibility, False Hope, Food and Drug Administration (FDA), Health Policy, Hydroxychloroquine, Mislead, Misleading, Mortality, Pandemic, Public Health, Public Safety, Trust, Truth, Wishful Thinking • Leave a comment

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.

 

 

 

 

Vaccine experts say Moderna didn’t produce data critical to assessing Covid-19 vaccine

Posted on by • Posted in Antibodies, Biotech, Clinical Research, Clinical Trials, Coronavirus, Data, Expectations, National Institute for Allergy and Infectious Diseases (NIAID), Vaccination, Vaccine, Vaccine RNA • Leave a comment

Vaccine experts say Moderna didn’t produce data critical to assessing Covid-19 vaccine

Moderna taps $1.34B stock offering to bankroll its promising COVID ...

Heavy hearts soared Monday with news that Moderna’s Covid-19 vaccine candidate — the frontrunner in the American market — seemed to be generating an immune response in Phase 1 trial subjects. The company’s stock valuation also surged, hitting $29 billion, an astonishing feat for a company that currently sells zero products.

But was there good reason for so much enthusiasm? Several vaccine experts asked by STAT concluded that, based on the information made available by the Cambridge, Mass.-based company, there’s really no way to know how impressive — or not — the vaccine may be.

While Moderna blitzed the media, it revealed very little information — and most of what it did disclose were words, not data. That’s important: If you ask scientists to read a journal article, they will scour data tables, not corporate statements. With science, numbers speak much louder than words.

Even the figures the company did release don’t mean much on their own, because critical information — effectively the key to interpreting them — was withheld.

Experts suggest we ought to take the early readout with a big grain of salt. Here are a few reasons why.

The silence of the NIAID

The National Institute for Allergy and Infectious Diseases has partnered with Moderna on this vaccine. Scientists at NIAID made the vaccine’s construct, or prototype, and the agency is running the Phase 1 trial. This week’s Moderna readout came from the earliest of data from the NIAID-led Phase 1.

NIAID doesn’t hide its light under a bushel. The institute generally trumpets its findings, often offering director Anthony Fauci — who, fair enough, is pretty busy these days — or other senior personnel for interviews.

But NIAID did not put out a press release Monday and declined to provide comment on Moderna’s announcement.

The n = 8 thing

The company’s statement led with the fact that all 45 subjects (in this analysis) who received doses of 25 micrograms (two doses each), 100 micrograms (two doses each), or a 250 micrograms (one dose) developed binding antibodies.

Later, the statement indicated that eight volunteers — four each from the 25-microgram and 100-microgram arms — developed neutralizing antibodies. Of the two types, these are the ones you’d really want to see.

We don’t know results from the other 37 trial participants. This doesn’t mean that they didn’t develop neutralizing antibodies. Testing for neutralizing antibodies is more time-consuming than other antibody tests and must be done in a biosecurity level 3 laboratory. Moderna disclosed the findings from eight subjects because that’s all it had at that point. Still, it’s a reason for caution.

Separately, while the Phase 1 trial included healthy volunteers ages 18 to 55 years, the exact ages of these eight people are unknown. If, by chance, they mostly clustered around the younger end of the age spectrum, you might expect a better response to the vaccine than if they were mostly from the senior end of it. And given who is at highest risk from the SARS-CoV-2 coronavirus, protecting older adults is what Covid-19 vaccines need to do.

There’s no way to know how durable the response will be

The report of neutralizing antibodies in subjects who were vaccinated comes from blood drawn two weeks after they received their second dose of vaccine.

Two weeks.

“That’s very early. We don’t know if those antibodies are durable,” said Anna Durbin, a vaccine researcher at Johns Hopkins University.

There’s no real way to contextualize the findings

Moderna stated that the antibody levels seen were on a par with — or greater than, in the case of the 100-microgram dose — those seen in people who have recovered from Covid-19 infection.

But studies have shown antibody levels among people who have recovered from the illness vary enormously; the range that may be influenced by the severity of a person’s disease. John “Jack” Rose, a vaccine researcher from Yale University, pointed STAT to a study from China that showed that, among 175 recovered Covid-19 patients studied, 10 had no detectable neutralizing antibodies. Recovered patients at the other end of the spectrum had really high antibody levels.

So though the company said the antibody levels induced by vaccine were as good as those generated by infection, there’s no real way to know what that comparison means.

STAT asked Moderna for information on the antibody levels it used as a comparator. The response: That will be disclosed in an eventual journal article from NIAID, which is part of the National Institutes of Health.

“The convalescent sera levels are not being detailed in our data readout, but would be expected in a downstream full data exposition with NIH and its academic collaborators,” Colleen Hussey, the company’s senior manager for corporate communications, said in an email.

Durbin was struck by the wording of the company’s statement, pointing to this sentence: “The levels of neutralizing antibodies at day 43 were at or above levels generally seen in convalescent sera.”

“I thought: Generally? What does that mean?” Durbin said. Her question, for the time being, can’t be answered.

Rose said the company should disclose the information. “When a company like Moderna with such incredibly vast resources says they have generated SARS-2 neutralizing antibodies in a human trial, I would really like to see numbers from whatever assay they are using,” he said.

Moderna’s approach to disclosure

The company has not yet brought a vaccine to market, but it has a variety of vaccines for infectious diseases in its pipeline. It doesn’t publish on its work in scientific journals. What is known has been disclosed through press releases. That’s not enough to generate confidence within the scientific community.

“My guess is that their numbers are marginal or they would say more,” Rose said about the company’s SARS-2 vaccine, echoing a suspicion that others have about some of the company’s other work.

“I do think it’s a bit of a concern that they haven’t published the results of any of their ongoing trials that they mention in their press release. They have not published any of that,” Durbin noted.

Still, she characterized herself as “cautiously optimistic” based on what the company has said so far.

“I would like to see the data to make my own interpretation of the data. But I think it is at least encouraging that we’ve seen immune responses with this RNA vaccine that we haven’t seen with previous RNA vaccines for other pathogens. Whether it’s going to be enough, we don’t know,” Durbin said.

Moderna has been more forthcoming with data on at least one of its other vaccine candidates. In a statement issued in January about a Phase 1 trial for its cytomegalovirus (CMV) vaccine, it quantified how far over baseline measures antibody levels rose in vaccines.

 

 

 

New Coronavirus Vaccine Candidate Shows Promise In Early, Limited Trial

Posted on by • Posted in Clinical Research, Clinical Trials, Coronavirus, Food and Drug Administration (FDA), Pandemic, Vaccination, Vaccine, Vaccine RNA • Leave a comment

https://www.npr.org/sections/coronavirus-live-updates/2020/05/18/857997341/new-coronavirus-vaccine-candidate-shows-promise-in-early-limited-trial

Moderna's coronavirus vaccine shows promise in first human trial ...

A vaccine manufacturer is reporting preliminary data suggesting its COVID-19 vaccine is safe, and appears to be eliciting in test subjects the kind of immune response capable of preventing disease.

Moderna, Inc., of Cambridge, Mass., developed the vaccine in collaboration with the National Institute of Allergy and Infectious Diseases. The results reported Monday come from an initial analysis of a Phase I study primarily designed to see if the vaccine is safe.

The company reports no serious side-effects; however, modest side-effects included redness at the injection site, headache, fever and flu-like symptoms, although none of these lasted more than a day.

The first 45 volunteers for the vaccine trial were divided into three groups, with each group getting a different dose of the vaccine. All groups got an initial shot, followed by a booster shot a month later.

In addition to safety, the company also looked at the vaccine’s ability to induce antibodies to the coronavirus — what’s known as its immunogenicity. It did, for all subjects at all dose levels. In addition, eight of the subjects were tested for the presence of neutralizing antibodies that prevent the virus from infecting cells in the laboratory. All eight did.

The Food and Drug Administration has given Moderna the green light to begin a Phase II study expected to enroll an additional 600 volunteers — half older than 55 — to provide additional immunogenicity data. The company hopes by July to begin a Phase III study, aimed at showing that the vaccine can actually prevent disease.

The Moderna vaccine is made using messenger RNA, or mRNA, a molecule containing the genetic instructions to make a protein on the coronavirus surface that is recognized by our immune systems. Although mRNA vaccines have been studied for several years, so far none has been licensed by the FDA.

The advantage of mRNA vaccines over more traditional vaccines is they can be made quickly. The company says it was just 63 days from the time Chinese scientists revealed the genetic sequence to the time a vaccine was injected into the first volunteer.

Moderna’s is one of about a dozen COVID-19 vaccine candidates that have begun studies in humans.

 

 

 

The coronavirus is a moving target

Posted on by • Posted in 2020 Election Issues, Centers for Disease Control & Prevention (CDC), Clinical Research, Clinical Trials, Coronavirus, Economic Crisis, Economy Reopening, Evidence-Based Plan, Health Policy, Infection Control, Infectious Virus, Mortality, Pandemic, Scientists, Vaccination, Vaccine • Leave a comment

https://www.axios.com/coronavirus-research-treatment-vaccines-aedfbf2c-cf09-4a36-ac99-2afb04298e5d.html

The coronavirus is a moving target for efforts to tackle it - Axios

Solutions for COVID-19 are being developed at the same time as knowledge about the disease evolves, a serious challenge for doctors treating patients and for researchers trying to create vaccines and treatments.

Why it matters: What was first thought of as a respiratory infection now appears much more complex, making efforts to tackle the disease more complicated.

“We’re laying the track as the train is moving and the train is coming very fast,” says Mark Poznansky, director of the Vaccine & Immunotherapy Center at Massachusetts General Hospital. “That is an extraordinary place to be at the global level.”

What’s happening: When the world first encountered COVID-19 four months ago, it was deemed a respiratory infection that hammers the lungs. That’s still the case but in recent weeks, clinicians have been reporting wide-ranging manifestations of the disease in some people.

  • Some of this could be that, with enough cases, there are outliers and anomalies. But that underscores that doctors and researchers are learning as they go.

Details: Renal failure, sepsis, damaged blood vessels, skin lesions, stroke, gastrointestinal problems and blood clots in the lungs and kidneys are being seen in some COVID-19 patients.

  • 20% of hospitalized patients in one study in Wuhan, China had heart damage.
  • 31% of people with the disease studied in a Danish ICU had blood clots.

“It comes across more as a systemic disease exhibited initially as a respiratory disease,” says Poznansky. It’s unclear whether the cause is the virus itself, the immune system’s response to it, or the treatment received.

That has implications for developing vaccines. The goal is to prevent infection but not exacerbate the immune effects in response to the virus.

  • “Is [a vaccine] protective or not in a context where we don’t know what exactly defines a protective immune response to COVID-19?” asks Poznansky.
  • The evolving understanding underscores the need to have multiple vaccines in development. (The current count is 123, per the Milken Institute’s tracker.)

What to watch: The changing percent of the disease will feature in regulatory discussions.

  • “This is the question companies will be discussing with regulators: which surrogate endpoints are acceptable as a proxy for going all the way to the worst possible outcomes in a patient?” says Phyllis Arthur, vice president of infectious diseases and diagnostics policy at biotech trade organization BIO.

The bottom line: Pandemics bring a potent mix of uncertainty and urgency to science that experts say requires both nimbleness and rigor to navigate.

  • “This is what a pandemic is like. It’s uncomfortable,” says Arthur. “You need to move swiftly and do good, solid, evidence-based, risk-benefit ratio assessments and understand what you know and don’t know, and make evidence based policy decisions knowing you don’t have perfect information.”

 

 

 

Whistleblower alleges Trump administration ignored coronavirus warnings

Posted on by • Posted in 2020 Election Issues, Clinical Research, Clinical Research Funding, Clinical Testing, Clinical Trials, Conflicts of Interest, Coronavirus, Credibility, Crisis, Crisis Management, Dept of Health and Human Services (HHS), Food and Drug Administration (FDA), Health Policy, Hydroxychloroquine, Misinformation, Mislead, Misleading, Mistake, Mistrust, Scientists, Transparency, Trust, Truth, U.S. Biomedical Advanced Research and Development Authority (BARDA) • Leave a comment

https://www.axios.com/coronavirus-rick-bright-whistleblower-f48cc9c6-8e6e-4662-a127-03e51f323288.html?stream=health-care&utm_source=alert&utm_medium=email&utm_campaign=alerts_healthcare

Whistleblower alleges Trump administration ignored coronavirus ...

Rick Bright, the former director of the U.S. Biomedical Advanced Research and Development Authority (BARDA), filed a whistleblower complaint Tuesday alleging that the Department of Health and Human Services failed to take early action to mitigate the threat of the novel coronavirus.

Flashback: Bright said last month he believes he was ousted after clashing with HHS leadership over his attempts to limit the use of hydroxychloroquine to treat the coronavirus.

What’s new: In his complaint, Bright claims he was excluded from an HHS meeting on the coronavirus in late January after he “pressed for urgent access to funding, personnel, and clinical specimens, including viruses” to develop treatments for the coronavirus should it spread outside of Asia.

  • Bright alleges it “became increasingly clear” in late January that “HHS leadership was doing nothing to prepare for the imminent mask shortage.”
  • Bright claims he “resisted efforts to fall into line with the Administration’s directive to promote the broad use of chloroquine and hydroxychloroquine and to award lucrative contracts for these and other drugs even though they lacked scientific merit and had not received prior scientific vetting.”
  • He adds that “even as HHS leadership began to acknowledge the imminent shortages in critical medical supplies, they failed to recognize the magnitude of the problem, and they failed to take the necessary urgent action.”

The White House declined to comment. HHS did not immediately respond to a request for comment.

https://www.documentcloud.org/documents/6882494-NEW-R-Bright-OSC-Complaint-Redacted.html