The first peer-reviewed results describing clinical trials of the COVID-19 vaccine developed by the University of Oxford and pharmaceutical company AstraZeneca were published on Tuesday, after Initial announcement In late November, it caused confusion and criticism among scholars.
The paperPublished in the medical journal The Lancet, it described vaccine trials that Oxford had conducted in the United Kingdom, Brazil and South Africa. Overall, data from the United Kingdom and Brazil indicate that the vaccine was 70% effective in preventing symptoms of COVID-19. No serious safety issues were reported in the three countries.
Results announced in a November press release showed that the vaccine could be up to 90% effective if given half a dose in the first shot. But the group did not disclose that the data was obtained as a result of a dose error, and the scientists later criticized the trial leaders for their lack of transparency and rigor.
Oxford Team Leader Andrew Bullard told BuzzFeed News that he hopes the newspaper will allay concerns about the trial. “Most of it was the assumption that we’re trying to carefully curate the data to find good results,” he said. “But this is not the case. We have agreed in advance with the regulators on the approach to be taken.”
“In terms of policymaking, it’s still hard to interpret the 70% figure,” Natalie Dean, a biostatistician at the University of Florida who specializes in designing strategies to test vaccines against emerging diseases, told BuzzFeed News.
“It’s a mess,” John Moore, a virologist at Weill Cornell Medical College in New York who is working to develop vaccines against HIV, told BuzzFeed News. It is clear that the vaccine “works”, but we still do not know how good the vaccine is. “
The vaccine, developed by Oxford University and its subsidiary Vaccitech, is being put on the market in cooperation with the British-Swedish pharmaceutical company AstraZeneca. It consists of a chimpanzee adenovirus – a group of viruses that can cause the common cold in people – and is designed to manufacture a “spike” protein from SARS-CoV-2, the virus that causes COVID-19.
Scientists and public health officials are eagerly awaiting these results because the Oxford-AstraZeneca vaccine is the most widely required COVID-19 vaccine that governments hope to eventually bring the epidemic under control.
The attraction is the vaccine’s low cost and ease of delivery. The supply deals announced so far indicate that the Oxford-AstraZeneca vaccine will be marketed for less than $ 4 a dose, compared to about $ 20 to $ 25 for other vaccines with results from large-scale clinical trials, conducted by rival pharmaceutical company Pfizer and Moderna. , A biotechnology company headquartered in Cambridge, Massachusetts.
Moreover, the Oxford-AstraZeneca vaccine can be stored at normal cooling temperatures, unlike those in Pfizer and Moderna, which must be deeply frozen up to a short time before use – in the case of the Pfizer vaccine. At around -70 ° C.
But claims about the vaccine’s efficacy have been blocked since November 23, when AstraZeneca released confusing A press release describing the combined results from experiments conducted by the University of Oxford in the United Kingdom and Brazil in which around 23,000 volunteers participated. Based on how 131 cases of COVID-19 were distributed across the vaccine and placebo arms of the trial, AstraZeneca claimed “Average efficiency is 70%.”
This indicates that the vaccine was less effective than its major competitors, such as Pfizer And Modern Both had announced earlier in November that trials with their vaccines had indicated that they were more than 90% effective.
But in a twist, AstraZeneca and Oxford claim their vaccine is 90% effective as well, if participants are given a half dose followed by a full dose. Meanwhile, two full doses resulted in only 62% efficacy. The most successful result was featured prominently in their advertising campaign.
“It is exciting that we found that one of our dosing regimens could be approximately 90% effective,” Pollard said in the press release. “If this dosing regimen is used, more people can be vaccinated with the planned vaccine supply.”
Scientists were initially confused by these results. “I found the results, as presented, difficult to interpret,” Dean told BuzzFeed News last week.
As more details emerged about what happened, experts became increasingly skeptical of the 90% claim. First Mene Pangalos, Head of AstraZeneca’s non-specialized R&D department in Oncology, He admitted to Reuters That half of the dose was actually wrong, first Revealed by the Mirror newspaper Back in June.
Then, on November 24, Moncef El-Salawi, chief scientist at Operation Warp Speed, a partnership of the US federal government to accelerate development of a COVID-19 vaccine, Reporters The volunteers who accidentally administered half of the initial dose were all under the age of 55 – so they do not represent the ages of the volunteers across the entire trial.
The fact that the dose error affected a non-representative group reflects another baffling aspect of the UK experience: since it was the first Listed on ClinicalTrials.gov In late May, the number of patient groups identified in the trial increased steadily, resulting in a bewildering group of 12 experimental groups and 25 subgroups each subtly given different treatments.
“What do these experiences mean? We just don’t know,” Moore told BuzzFeed News last week.
In the new Lancet paper, the Oxford team statistically controlled the age differences between groups given the different doses, and found that the improved efficacy of the full treatment half dose was still in place. But other scientists remain concerned that there is still no data on how well it works in the elderly – who are most vulnerable to COVID-19.
“It needs more evaluation,” Dean said.
Unlike Pfizer and ModernaThe University of Oxford and AstraZeneca have not released a complete breakdown of their experimental protocols for other researchers to scrutinize the start of their large-scale trials, making it difficult to understand the findings presented in previous press releases. Further transparency concerns arose in September when vaccine trials were suspended after a suspected serious adverse reaction in a UK participant. The stop was not announced until after it was published in the biomedical news Stat website.
In a statement sent to BuzzFeed News last week, the Oxford Group downplayed the dosing error and said the plan to proceed with the analysis had been approved by the UK regulatory authorities:[W]When it was evident that a lower dose was used, we discussed this with the regulator, and agreed to a plan to test both lower dose / higher dose and higher dose / higher dose, allowing us to include both approaches. ‘
The new paper indicates that the protocol was revised on June 5, about a week after the trial began. Today, Pollard told reporters in a press briefing organized by the Science Media Center in London that this change was made before the “database closure” for the trial, which means that it is part of the officially approved plan.
However, the confounding results seem unlikely to be acceptable to the Food and Drug Administration. The US regulator is expected to await the results of another trial of AstraZeneca currently underway in the US, run by AstraZeneca instead of Oxford, before deciding whether to approve the vaccine for emergency use.
“All I can say is there’s a lot of explanation that needs to be done,” Paul Offitt, director of the Vaccine Education Center at Children’s Hospital of Philadelphia and a member of the FDA’s Vaccine and Related Biological Products Advisory Committee, told BuzzFeed News last week. .
“It is not clear that we come to a conclusion why there appear to be very different efficacy results, 90% versus 62%,” Slaoui, the chief scientist for Operation Warp Speed, told reporters during a press conference on December 2. It is a very clear explanation based on facts and data about what is behind these two numbers, it is very likely that the package will not be sufficient to agree with it. “
AstraZeneca CEO Pascal Suriott, speaking in a briefing to Science Media, said he expects the FDA to request the results of the US trial.
Another concern is that results from the UK have been combined Brazilian The trials, originally envisioned as separate tests of vaccine efficacy, involve slightly different treatment and placebo arms. Combining data from the two trials became essential after the Oxford group realized that Britain’s success in minimizing transmission of COVID-19 by late spring meant its UK experience had not seen enough cases to produce definitive results.
The Oxford team was I got up at the start About her chances of being the first to demonstrate an effective COVID-19 vaccine. “We are probably in a location with one of the highest levels of COVID transmission anywhere, and certainly in Europe at this time, so we have a good chance of getting an effective result over the next three months,” said Adrian Hill, director of the Jenner Institute in Oxford, He told CNN In late April.
But less than a month later, Hill The Telegraph said Newspaper: It is a race against the virus that is disappearing, and with time. At the moment, there is a 50% chance that we will never get a result. “
The stakes are high because of the high hopes for the Oxford AstraZeneca vaccine. This is especially true in the United Kingdom, where it was Prime Minister Boris Johnson Praised work From “Our Genius Scientists”, and where it was said that a unit in his office paid for the marking of vaccine vials with a union socket, According to the Huffington Post.
It is expected that the obstacles to emergency approval of the vaccine will be fewer in the United Kingdom than in the United States. In fact, the nation’s Medicines and Healthcare products Regulatory Agency has it It has already been approved Pfizer vaccine that is still Still under consideration By the FDA. The Advisory Committee of the American Health Agency is meeting this Thursday to evaluate the results of the Pfizer vaccine, which is expected to become the first vaccine to obtain emergency clearance in the United States.
The UK’s approval of the Oxford-AstraZeneca vaccine could lead to a rush of requests, given the vaccine’s cost and ease of delivery. According to A. data analysis From the life sciences analytics company Airfinity by the scientific journal Nature, demand is already high, with about 2.7 billion doses already ordered, far more than any other vaccine candidate.
Scientists are concerned about questions about the effectiveness of the vaccine, because any problems that emerge later could destroy confidence in COVID-19 vaccines in general.
“Our biggest collective fear is that things will go wrong and threaten the public’s trust,” Moore said. “We wanted the process as clean as possible.”
Stephanie M Lee contributed reporting for this story.