August 24 Update: U. S. Food and Drug AdministrationBut it’s not the first time Issued an emergency use authorization on August 23 for COVID-19 with convalescent plasma.
U. S. President Donald Trump has asked COVID-19 survivors to donate their blood plasma as a remedy for the disease, saying he “has so far had a massive response. “Meanwhile, rumors circulate that U. S. drug regulators wonder if they should administer plasma. more people by allowing it as an emergency remedy. But researchers and physicians around the world are involved in an increase in blood plasma distribution that can undermine the clinical trials needed to determine whether it actually works as opposed to COVID-19.
Although some U. S. hospitals have been able to do so. But it’s not the first time Already offering remedies in urgent cases, an emergency use authorization from the Food and Drug Administration (FDA) would make it easier to obtain and manage convalescent plasma, the yellow liquid left after blood cells are removed.
But so far, there is little evidence that plasma is helping patients, and the resolution can simply tarnish efforts to examine its effects, said former FDA communication Robert Califf, who now runs clinical policy and strategy at Verily and Google Health in southern San Francisco. California. Remdesivir, an antiviral drug and an anti-inflammatory drug dexamethasone, are the only remedies that have been shown to be effective in combating COVID-19 in rigorous clinical trials.
Convalescent plasma has only been tested in small trials without the statistical strength needed to provide company conclusions. The FDA did not respond to Nature’s questions about the existing scenario with its resolve to allow convalescent plasma. But if the FDA issues an authorization, experts say, other people with COVID-19 may simply decide to access the remedy directly, rather than enrolling in a clinical trial and the threat of being assigned to a plasma-free control organization.
“It’s prospective treatment that can work, and I don’t think it’s very unlikely to be available,” Califf said. “But we deserve to emphasize in public policy announcements that participation in randomized trials is a very sensible priority. “
For more than a century, doctors have been using convalescent plasma from convalescent donors to treat others with the same disease, adding Ebola and Middle East Respiratory Syndrome (MERS), also caused by coronavirus. The concept is that plasma comprises antibodies and proteins involved and some of those antibodies could have helped the donor recover from their infection, so giving them to other inflamed people can also simply encourage their recovery. While there is little knowledge about whether convalescent plasma definitely improves the outcomes of For Others with Other Diseases, it made sense to seek a remedy for COVID-19 when the epidemic began, but researchers struggled to discover its effectiveness amid the pandemic, says Michael Joyner, an anesthesiologist at the Mayo Clinic in Rochester, Minnesota. .
On the one hand, other people’s convalescence plasma varies significantly in antibody concentration, making it difficult to test. At first, researchers had no way to measure and standardize the antibody point in a batch. Even now, researchers in some parts of the world cannot check whether plasma contains hard ‘neutralizing antibodies’, which can save you viral replication because verification is expensive and requires some containment procedures, says infectious disease specialist Fazle Chowdhury of Bangabandhu Sheikh Mujib Medical University in Dhaka.
Gathering rigorous knowledge from clinical trials was also complicated, as doctors administered convalescence plasma to critically ill people on a “compassionate” basis. foundation to more than 66,000 people, without operating any group. The program’s researchers, adding Joyner, gathered knowledge and published the effects of another 5,000 people with severe COVID-19, suggesting that treatment is sometimes safe1.
“We don’t know what happens when used with compassion,” Chowdhury says. “If we use convalescent plasma, it deserves clinical testing. ” Researchers have complained that barDA-funded allocation deviated potential participants and plasma donors from randomized clinical trials that would produce more rigorous data.
In the absence of a control group, Joyner and his colleagues benefited from the fact that the concentration of anti-SARS-CoV-2 antibodies was not standardized. The team evaluated more than 35,000 plasma receptors and compared the effects of those who won. plasma with relatively low degrees of antibodies with the effects of other people who received plasma with higher grades. The test, published on the medRxiv prepress server prior to peer review, found2 that participants who gained transfusions in a time after diagnosis and achieved higher degrees of antibodies showed a higher improvement and were less likely to die in the test age than those who gained the following transfusions with reduced antibody concentrations. “It was an incredibly vital discovery,” says Cassandra Josephson, a pediatrician at Emory University in Atlanta, Georgia, who treated young people with COVID-19.
But the lack of randomization makes it difficult to draw a conclusion from the studio’s company, warns Anthony Gordon, an anaesthetist at Imperial College London. health, he said, expanding his chances of a better outcome. ” We only see one association,” he said. “We don’t see a cause and effect. “
Instead of gigantic traditional clinical trials with statistical power, some researchers are looking to collect evidence from smaller evidence. a dozen studies, hoping to edit statistical power. The team found that the remedy reduced mortality from 26% to 13%.
But it is difficult to draw a conclusion from the company from the combined knowledge of disparate studies, Josephson warns. The trials treated others whose severity of the disease varies, using other doses of plasma and following a variety of successful measures. “There’s a lot to do, distinguish”in the analysis,” Josephson says. At the same time, it’s not useless. ” We had nothing before, security knowledge. “
And there’s still knowledge to come. In the UK, epidemiologist Martin Landray and infectious disease researcher Peter Horby, both from Oxford University, are leading the giant RECOVERY trial, which is testing several therapies, adding convalescent plasma, in others hospitalized by COVID-19. and their colleagues are testing convalescent plasma in other people in extensive care, in a foreign trial called REMAP-CAP. But the first wave of pandemic in the UK has passed largely, so Landray says it does not expect to have effect until later in the year, when some epidemiological models expect COVID-19 instances to increase again, meanwhile, he says, the RECOVERY team is storing plasma with donors, to be temporarily deployed if this increase occurs.
Landray warns against speculation that convalescent plasma works until knowledge is available. “We have noticed in this epidemic how false well-intentioned clinical hypotheses can be,” he says, and mentions hydroxychloroquine as an example. COVID-19 in small initial trials and laboratory studies, but in the end it was shown to have no effect on the disease4.
“There is a convalescing plasma of intelligent science and an intelligent explanation of why to think it can be an effective treatment,” Landray says. “But the bottom line is that we don’t have enough knowledge to know. “
Nature 584 and 505 (2020)
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