The United States could be within a month of a turning point in the country’s fight against coronavirus: the first working vaccine.
Demonstrating that a new vaccine is safe and effective in less than a year, a seven-day work week for scientists and billions of dollars in government investment will break the record for speed. If enough people could get one, the vaccine could slow the epidemic that has already killed one million people worldwide.
It’s amazing to see the first vaccine like President Trump: a switch-no-switch f-switch will bring life back to what we know it to be. “As soon as he is told to move on, we will get him out, we will defeat the virus,” he told a news conference in September. But vaccine experts say we should instead prepare for an unsettling, frustrating year.
The first vaccine can only provide moderate protection, which makes it prudent to continue wearing the mask. By next spring or summer, there may be many of these vaccines, without a clear understanding of how to choose them. Because of the array of these options, the best vaccine makers at an early stage of development may struggle to finish a clinical trial. And some vaccines may suddenly be withdrawn from the market, as it turns out not to be safe.
The director of the Mayo Clinic’s Vaccine Research Group, Dr. “So far no one was able to send in the perfect solution, which is not strange,” said Gregory Poland.
Some of this confusion is inevitable, but some of the results are how coronavirus vaccine tests were designed: each company is running its own trial, comparing it to its own placebo. But it shouldn’t be this way.
In the spring, when government scientists began discussing how to invest in vaccine research, some wanted to test multiple vaccines simultaneously against each other – known as the master protocol.
Dr. Director of National Allergy and Infectious Diseases. Anthony S. Fauci, was in favor of this idea. But these mega-trials pose a business risk to any given vaccine manufacturer because they reveal how the vaccine survives against its competitors.
Instead, companies offer to bankroll large vaccine trials if they agree to some common land rules and share some data. Companies were still allowed to run the trials themselves.
“You have to have the full cooperation of pharmaceutical companies to get involved in the master protocol,” said Dr. Fawcett said. “That – I don’t know what the correct word is – didn’t happen.”
A vaccine testing system was not set up for this logjam. In particular, it takes many years for scientists to develop a vaccine before testing it on humans. Early safety tests, known as phases 1 and 2, can take many years.
If all goes well – and it doesn’t normally do – then Phase 3, the final phase, could begin, comparing the thousands of people who get vaccinated to the thousands who are given placebo. It may take another three years to get these results. Only then – a decade or more after research begins – will a vaccine manufacturer build a factory to make products.
When coronavirus began to spread earlier this year, vaccine researchers around the world knew we could not afford to wait that long. The World Health Organization organized a group of experts to launch what is known as the Solidarity Vaccination Trial. A large group of volunteers will receive a random number of vaccines, while a small group will receive a placebo.
All vaccines will be tested against the same placebo group, and all volunteers will be living under the same circumstances. “You have a perfectly valid comparison, not just one of those vaccines against placebo, but against each other,” said Thomas Fleming, a member of the University of Washington’s Biost at Tistian and Sid Leadership Vaccines Trial group.
It took nine months to get off the field, but that hearing will begin in October with a small study of Latin America.
At the same time that the WHO was planning for its mega-trial, U.S. Government officials were discussing how they could – and accelerate – invest best in vaccine tests. Some researchers, including Dr. Fausi, advocated design similar to WHO.
But Monsef Sloi, chief adviser to Operation Vorp Speed, said in a statement that such a trial would be “impractical”. “If the OWSA had tested all the vaccines under one master protocol, it would have had to wait months before the operation began and recruit 200,000 volunteers at the same time.”
In the end, the government chose what it described as a “harmonious approach.” It will allow vaccine manufacturers to run their own tests, but only if they use a protocol that follows certain guidelines and allows the National Institutes of Health to test all of their volunteers in the same way. In return for complying with these rules, companies will gain access to NIH’s large network of clinical testing sites, and receive large financial support for their trials. Through this program, the government has so far pledged 10 10 billion to vaccine manufacturers.
So far, AstraZeneca, Johnson & Johnson and Moderna have begun trials in the network. Novavax and Sanofi are expected to begin their Phase 3 study in the next two months. But Pfizer, one of the front runners, never joined the network, preferring to run trials entirely on its own.
If Pfizer’s results are good, many experts expect the company to ask the Food and Drug Administration for immediate authorization of its vaccine, possibly just for a group of people at risk. The company can then quickly proceed to apply for a license, so that it becomes widely available.
The validity of the vaccine will depend on how much protection the vaccine provides in the trial of Fake 3, which global scientists refer to as its effectiveness. In June, the FDA set a 50 percent efficacy target for the coronavirus vaccine.
But the effectiveness of the trial does not match its effectiveness in the real world. This is because, like any statistical study, there is a margin of error in the Phase 3 trial. A vaccine that meets the FDA guidelines may actually be more than 50 percent effective, or less so. It can only be 35 percent effective.
Then whether it goes to Pfizer or another company, that first vaccine authorization could prevent its competitors from running an ongoing trial. Some volunteers, unsure about whether they have been given an experimental vaccine or a placebo, may opt out of an ongoing trial to obtain an authorized vaccine, slowing research. John Shiver, global head of vaccine research and development at Sanofi, agreed that the scenario could play a role in the company’s vaccine trial.
Things may get worse for the vaccine in the first phase of testing. Those products have to prove that they are better than the newly approved vaccine. The difference between the two vaccines will be less than the vaccine and the placebo. As a result, the trial may be longer and last longer. The cost may be higher than many small start-ups working on innovative vaccines.
“It basically prevents the development of a better vaccine,” said Dr. John Hopkins, a vaccine specialist at the Johns Hopkins University School of Medicine. Said Naor Bar-Zive. “Given the large taxpayer investment, the public should demand better.”
The FDA’s guidelines increase the likelihood of future vaccine testing against an authorized person, but it is not clear whether they will change the requirements for agency testing. “We cannot predict what will happen in the future,” an FDA spokesman said.
“Once the vaccine is authorized, tests for volunteers who have not yet started or have started will be limited to groups that were not approved to receive an authorized vaccine,” said Dr. Sloan of Operation Operation Speed Speed. . Because the first wave of vaccines goes to health care workers or other high-risk groups, this policy means these groups will not be allowed to be part of new clinical trials.
By spring or summer, there may be several coronavirus vaccines for American consumers to choose from. But that choice will be tough. A vaccine that has been shown to be 100 percent effective in one trial, for example, may actually be more protective than one that has been shown to be 100 percent effective in another trial.
“I read a lot of people, even in small differences that can only be a statistical opportunity,” said Natalie Dean, a biostatist at the University of Florida.
In a phone call with reporters Friday, Health and Human Services Officer Paul Carey said the operation was on track to receive 70,000 million doses of various vaccines by March or April, he said. , “All Americans who want to get it.” On who will get which vaccine, he said the vaccine for disease control and prevention would be left to the advisory committee. “They will guide us to which class of Americans the vaccine is most appropriate for.”
But the advisory committee does not yet have a plan, and a Stanford University School of Medicine professor of pediatrics and a member of that committee, Dr. Grace Lee has warned that it will be a difficult time to come up with. “It’s hard to do, given all the uncertainty with the covid vaccine,” she said.
Even moderately effective vaccines will go a long way in reducing the incidence of covid-19 – but only if enough people take them, and they realize they may still be sick. De Poland of the Mayo Clinic. “We have to continue to use masks for some of these vaccines,” Poland said.
NIH’s harmonious approach to all Phase 3 trials receiving Operation Operation Speed Funding is likely to bring some scientific insights. It is possible, for example, that in all tests, some molecular signatures in the vaccinated person’s blood show that they are safe. Future trials, people can search for those signatures instead of waiting to get sick.
However, there is no clear guarantee that such a clear signature will come out. There will be more uncertainty as regulators continue to find rare but dangerous side effects in authorized vaccines.
“You will have random events,” Dr. Bar-Zive said. For example, a group of older people can all have a stroke immediately after being vaccinated, raising the question of whether the vaccine is the culprit. “It is very likely that some vaccines will be withdrawn.”
Dr. Poland said the only way to manage this chaotic year is for scientists to talk honestly about how vaccines are tested and for people to learn what lies ahead. “People do better with it as long as you frame something in advance,” he said.
Sharon Lafrenier contributed to the report.