The first peer-reviewed results describing clinical trials of a COVID-19 vaccine developed by Oxford University and pharmaceutical company AstraZeneca were released on Tuesday, following a preliminary announcement done in late November caused confusion and criticism among scientists.
He paper, published in the medical journal Lancet, described trials of the Oxford-directed vaccine 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 symptomatic COVID-19. No serious security issues were reported in all three countries.
The results announced in a press release in November had highlighted that the vaccine could be up to 90% effective if given in half a dose for the first shot. But the group did not disclose that the data were obtained as a result of a dosing error, and scientists later criticized the process leaders for lack of transparency and rigor.
Andrew Pollard, head of the Oxford team, told BuzzFeed News that he hoped the newspaper would drop concerns about the trial. “Most of it has been assumed that we have been trying to collect data to find good results,” he said. “It simply came to our notice then. We have agreed in advance with the regulators on the approach to be taken. “
“When it comes to policy making, the number of 70% remains difficult to interpret,” Natalie Dean, a biostatistician at the University of Florida who specializes in designing strategies to test vaccines, told BuzzFeed News. emerging diseases.
“It’s a disaster,” John Moore, a virologist at Weill Cornell Medical College in New York who works on the development of HIV vaccines, told BuzzFeed News. “The vaccine clearly ‘works,’ but we still don’t know to what extent.”
The vaccine, developed by Oxford University and its derivative company Vaccitech, is marketed in collaboration with the British-Swedish pharmaceutical company AstraZeneca. It consists of a chimpanzee adenovirus – a group of viruses that can cause colds common to humans – designed to make the “spike” protein of SARS-CoV-2, the virus that causes COVID-19.
Scientists and public health officials have been anxiously awaiting these results because the Oxford-AstraZeneca vaccine is the most pre-ordered of the COVID-19 vaccines that governments hope will eventually control the pandemic.
The appeal lies in the low cost and ease of delivery of the vaccine. Supply agreements announced so far indicate that the Oxford-AstraZeneca vaccine will be marketed at less than $ 4 per dose, compared to $ 20-25 for the rest of the vaccines with results of large-scale clinical trials, conducted by rival drug giant Pfizer and by Moderna, a biotechnology company based in Cambridge, Massachusetts.
In addition, the Oxford-AstraZeneca vaccine can be stored at normal refrigeration temperatures, unlike those of Pfizer and Moderna, which must be frozen until shortly before use, in the case of the Pfizer vaccine. around -70 degrees Celcius.
But claims about the vaccine’s effectiveness have been under a cloud since Nov. 23, when AstraZeneca issued a confused press release describing the combined results of trials conducted by Oxford University in the UK and Brazil in which some 23,000 volunteers participated. Based on the distribution of 131 cases of COVID-19 between the vaccine and placebo arms of the trial, AstraZeneca stated an “average efficiency of 70%.”
This suggested that the vaccine was less effective than its main rivals, since Pfizer i Modern each had previously announced in November that trials for their vaccines indicated they were more than 90% effective.
But, in one twist, AstraZeneca and Oxford claimed that their vaccine was also 90% effective if participants were given an average dose followed by a full dose. Meanwhile, two complete doses resulted in 62% efficacy. The most successful result stood out in its advertising.
“Excitingly, we have discovered that one of our dosing regimens can be around 90% effective and, if this dosing regimen is used, more people could be vaccinated with a planned supply of vaccines,” he said. said Pollard in the press release.
Scientists were initially confused by these findings. “I found the results presented difficult to interpret,” Dean told BuzzFeed News last week.
And as more details emerged than happened, experts became increasingly skeptical about the 90% claim. First Mene Pangalos, head of non-cancer research and development at AstraZeneca, admitted to Reuters that the half dose was the result of an error, first revealed by the newspaper Mirror in June.
Then, on November 24, Moncef Slaoui, chief scientist of Operation Warp Speed, the U.S. federal government’s association to accelerate the development of the COVID-19 vaccine, they told reporters that the volunteers who mistakenly received the initial half dose were all under the age of 55, so they were not representative of the age of the volunteers throughout the trial.
The fact that the dosing error affected a non-representative group reflects another confusing aspect of the UK trial: since it was the first listed on ClinicalTrials.gov by the end of May, the number of trial-specific patient groups had steadily increased, resulting in a bewildering range of 12 experimental groups and 25 subgroups with subtly different treatments each.
“What do these tests mean? We don’t know, ”Moore told BuzzFeed News last week.
In the new Lancet paper, the Oxford team statistically monitored age differences between groups given the different doses, finding that improved efficacy for full-dose and medium-dose treatment was maintained. But other scientists remain concerned that so far there is no data on how it works in the elderly, who are more vulnerable to COVID-19.
“It needs additional evaluation,” Dean said.
Unlike Pfizer and Modern, Oxford University and AstraZeneca did not publish a complete breakdown of their test protocols so that other researchers could examine them from the start of the large-scale trials, which made it difficult to understand the results presented in press releases. previous. More transparency concerns arose in September when vaccine trials were suspended following a suspicion of a serious adverse reaction in a UK participant. The break was only made public after being informed in the biomedical news place Estad.
In a statement sent to BuzzFeed News last week, the Oxford group downplayed the significance of the dosing error and said the plan to proceed with the analysis had been drafted with UK regulators: “[W]when it was evident that a lower dose was used, we discussed it with the regulator and agreed on a plan to test both the lowest / highest dose and the highest / highest dose, which allowed us to include both approaches. “.
The new document notes that the protocol was amended on June 5, about a week after the trial began. And Pollard told reporters today at a news conference organized by the Science Media Center in London that this change was made before the trial’s “database lock”, meaning it was part of the officially approved plan.
Still, it seems unlikely that the confusing results will be acceptable to the FDA. The US regulator is expected to await the results of another ongoing AstraZeneca trial in the United States, led by AstraZeneca instead of Oxford, before deciding whether to approve the emergency vaccine.
“All I can say is that there is a lot to tell,” Paul Offit, director of the Philadelphia Children’s Hospital Vaccine Education Center and a member of the Vaccine Advisory Committee, told BuzzFeed News last week. and FDA Organic Products. .
“It is not obvious to conclude why there appear to have been substantially different efficiency results, 90% versus 62%,” Slaoui, chief scientist at Operation Warp Speed, told reporters during a press conference. press on December 2nd. 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 is not enough for approval ”.
Speaking at the Science Media Center briefing, AstraZeneca CEO Pascal Soriot said he anticipated the FDA would ask for results from the U.S. trial.
Another concern is that the results have been combined from the UK and the UK Brazil trials that were originally conceived as separate tests of vaccine efficacy, involving slightly different treatment and placebo arms. The combination of data from the two trials became necessary after the Oxford group realized that Britain’s success in cutting COVID-19 transmission to lightning in late spring meant that his trial in the UK did not see enough cases to yield definitive results.
The Oxford team was initially bullish on their chances of being the first to demonstrate an effective vaccine against COVID-19. “We are probably in a place that has one of the highest levels of COVID transmission anywhere, probably in Europe right now, so we have a good chance of getting an efficiency 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 he told the Telegraph daily: “It is a race against the disappearance of the virus and against time. At the moment, there is a 50% chance that we will not get any results. “
The stakes are high due to the huge hopes of the Oxford-AstraZeneca vaccine. This is especially true in the UK, where Prime Minister Boris Johnson is present praised the work of “our brilliant scientists,” and where it was reported that a unit in his office pressed for vaccine vials to be labeled with a jack junction, according to the Huffington Post.
Obstacles to vaccine emergency approval in the UK are expected to be lower than in the US. In fact, the Nation’s Medicines and Health Products Regulatory Agency has already approved the Pfizer vaccine, which still continues to be considered by the FDA. The U.S. health agency’s advisory panel meets Thursday to evaluate the results of the Pfizer vaccine, which is expected to be the first vaccine to receive emergency authorization in the U.S.
UK approval of the Oxford-AstraZeneca vaccine could lead to a run-up of orders, given the cost and ease of delivery of the vaccine. According to one data analysis of the life sciences analytics company Airfinity, of the scientific journal Nature, is already in high demand, with some 2.7 billion doses already pre-ordered, significantly more than any other candidate vaccine.
Scientists are concerned about questions revolving around the effectiveness of the vaccine, because any problems that arise later could undermine confidence in COVID-19 vaccines more generally.
“Our biggest collective fear is that things will go wrong that compromise public confidence,” Moore said. “We wanted a process as clean as possible.”
Stephanie M. Lee contributed by reporting this story.