The first peer-reviewed results describing the COVID-19 vaccine clinical trials developed by the University of Oxford and pharmaceutical company AstraZeneca were announced on Tuesday, after preliminary announcement done in late November caused confusion and criticism among scientists.
The paper, published in the Lancet medical journal, has described vaccine trials run by Oxford in the UK, Brazil and South Africa. Overall, data from the UK and Brazil indicates that the vaccine is 70% effective in preventing symptomatic COVID-19. No serious safety issues were reported in the three countries.
The results, published in a press release in November, emphasized that the vaccine could be up to 90% effective if given half a dose for the first shot. But the team did not reveal that the data obtained was due to a dose error, and the scientists later criticized the test leaders for their lack of transparency and rigor.
Andrew Pollard, the head of the Oxford group, told BuzzFeed News he hopes the newspaper will raise concerns about the trial being rested. “Most of it is the assumption that we were trying to gather data to find good results,” he said. “But that is not the case. We have agreed in advance with regulators about the approach to be taken. “
Natalie Dean, a biostatistician at the University of Florida who designs vaccine testing strategies against emerging diseases, told BuzzFeed News: “In terms of policy making, the 70 percent figure remains. still difficult to explain.
“It’s a mess,” John Moore, a virologist at Weill Cornell College of Medicine in New York, who is working on vaccine development against HIV, told BuzzFeed News. “The vaccine is clearly ‘working’, but we don’t yet know how effective it is.”
The vaccine, developed by Oxford University and by Vaccitech, is being marketed in cooperation with the Anglo-Swedish pharmaceutical company, AstraZeneca. It includes chimpanzee adenovirus – a group of viruses that can cause the common cold in humans – designed to produce a “spike” protein from SARS-CoV-2, the virus that causes COVID-19.
Scientists and public health officials have been eagerly awaiting these results as the Oxford-AstraZeneca vaccine is the most widely pre-ordered COVID-19 vaccine that governments ultimately hope to. will control the pandemic.
The appeal lies in the low cost and ease of transport of the vaccine. The supply contracts announced so far show that the Oxford-AstraZeneca vaccine will market for less than $ 4 a dose, compared with around $ 20 to $ 25 for other vaccines with the results. from large-scale clinical trials, conducted by rival pharmaceutical giants Pfizer and Moderna. , a biotechnology company headquartered in Cambridge, Massachusetts.
Furthermore, the Oxford-AstraZeneca vaccine can be stored at normal cold temperatures, unlike the types of Pfizer and Moderna, which must be deeply frozen until use immediately before use – in the case of Pfizer vaccines at about -70 degrees Celsius.
But the vaccine’s efficacy claims have been overshadowed since November 23, when AstraZeneca launched. confuse The press release describes the combined results from trials conducted by Oxford Universities in the UK and Brazil with the participation of about 23,000 volunteers. Based on how 131 cases of COVID-19 were distributed across the vaccine and placebo groups of the trial, AstraZeneca stated “Average efficiency is 70%.”
But in contrast, AstraZeneca and Oxford claim that their vaccine is also 90% effective, if the participants are given a half-dose then a full dose. Meanwhile, the full two doses were only 62% effective. More successful results stand out in their publicity promotion.
“Interestingly, we found that one of our dosing regimens could be as effective as 90%, and if this dosing regimen is used, more people could be vaccinated with supplies. vaccines as planned, ”Pollard said in the press release.
Scientists were initially puzzled by these findings. Dean told BuzzFeed News last week: “I find the results, as presented, difficult to interpret.
And as more details about what happened, experts become increasingly skeptical of the 90% claim. First Mene Pangalos, AstraZeneca’s head of non-cancer research and development, admitted to Reuters that half the dose is actually the result of an error, first of all revealed by Mirror back in june.
Then, on November 24, Moncef Slaoui, chief scientist of Operation Warp Speed, partnerships with the US federal government to accelerate development of the COVID-19 vaccine, told reporters that the volunteers with the wrong initial half dose were all under 55 years of age – thus not representing the ages of the volunteers in the entire trial.
The fact that the dose error affecting an unrepresentative group reflects another confusing aspect of the UK trial: As it is for the first time. listed at ClinicalTrials.gov By the end of May, the number of specific patient groups in the trial had steadily increased, leading to a series of experimental groups and 25 confusing subgroups, each given different treatments. subtly.
What do these tests mean? We don’t know, ”Moore told BuzzFeed News last week.
In the new Lancet paper, the Oxford team statistically controlled for age differences between groups using different dosages, finding an improved effect on half-dose, full-dose treatment. dose is maintained. But other scientists remain concerned that so far there are no data on its activity levels in the elderly, who are most vulnerable to COVID-19.
“It needs further evaluation,” said Dean.
Unlike Pfizer and ModernaThe University of Oxford and AstraZeneca did not publish full details of their testing procedures for other researchers to scrutinize at the outset of their large-scale trials, making it difficult to understand. Results are presented in previous press releases. Further concerns about transparency emerged in September when vaccine trials were halted after a UK participant was suspected of a serious adverse reaction. The suspension is only publicly available after it has been reported on the biomedical bulletin site statistics.
In a statement to BuzzFeed News last week, the Oxford team downplayed the importance of the error of medication and said the plan to conduct the analysis has been approved with UK regulators: “[W]When it was clear that a lower dose had been used, we discussed this with the regulator and agreed on a plan to test both the lower / higher dose and the higher dose / higher dose, for allow us to include both approaches. “
The new paper notes that the protocol was revised on June 5, about a week after testing began. And Pollard today told reporters during a press conference hosted by the Science Communications Center in London that this change was made before “locking the database” for the test, which means it is part of an officially approved plan.
However, the confusing results do not appear to be approved by the FDA. The U.S. regulator is expected to wait for results from another AstraZeneca trial currently underway in the US, run by AstraZeneca instead of Oxford, before deciding whether to approve the vaccine. in an emergency or not.
“All I can say is that there is a lot more to explain,” said Paul Offit, director of the Center for Vaccine Education at Children’s Hospital Philadelphia and a member of the Advisory Committee on Vaccines and FDA’s bio-related products, told BuzzFeed News last week.
Slaoui, the chief scientist of Operation Warp Speed, told reporters during a press conference on December 2: “It’s not clear why the effect is significantly different, 90% from 62%. is a very clear fact-based explanation and data about what’s behind those two numbers, most likely the package won’t be enough for approval. ”
Speaking at the Science Communications Center’s press conference, AstraZeneca’s CEO Pascal Soriot said he predicted the FDA would request results from the test in the US.
Another concern is the combined results from UK and Brazilian nationals The trials initially formed were separate trials of the efficacy of the vaccine, consisting of slightly different placebo and treatment methods. Combining data from the two trials became necessary after the Oxford group realized that Britain’s success in cutting COVID-19 transmission to a drip level in late spring meant their trial was in He is in insufficient circumstances to yield accurate results.
The Oxford team is initial price increase on the chance of being the first to demonstrate that COVID-19 is effective. “We could be in a location with one of the highest levels of COVID transmission anywhere, certainly in Europe at this point, so we have a chance to have an effective result. over the next three months, ”said Adrian Hill, director of the Jenner Institute of Oxford, told CNN at the end of April.
But less than a month later, Hill told the Telegraph newspaper: “It is a race against the disappearing virus and against time. At this point, there is a 50% chance that we won’t get any results ”.
Stakes are very high because great hope is placed on the Oxford-AstraZeneca vaccine. That’s especially true in Britain, where Prime Minister Boris Johnson was praise the work of “our eminent scientists” and where a unit in his office reportedly promoted vials of vaccines labeled with coalition jacks, according to Huffington Post.
Barriers to emergency vaccine approval in the UK are expected to be lower than in the US. Indeed, the nation’s Health Care Products and Drug Administration did has been approved Pfizer vaccines remain is still under review by FDA. The US health agency’s advisory board will meet this Thursday to evaluate the results of the Pfizer vaccine, which is expected to become the first vaccine to receive emergency approval in the US.
UK approval of the Oxford-AstraZeneca vaccine could lead to a shuffling of orders, due to the cost of the vaccine and ease of delivery. According to one analysis of the data from Nature, it is already in high demand, with about 2.7 billion pre-ordered doses, significantly more than any single vaccine candidate, from the life sciences analysis firm Airfinity of Nature. other odd.
Scientists are concerned about questions surrounding the vaccine’s effectiveness, because any problems that emerge later could damage confidence in the COVID-19 vaccine in general.
“Our greatest collective fear is that things will go wrong and affect public trust,” Moore said. “We want a process as clean as possible.”
Stephanie M. Lee contributed reports to this story.