The first peer-reviewed results describing a clinical trial of a COVID-19 vaccine developed by the University of Oxford and AstraZeneca Pharmaceuticals were released on Tuesday. Preliminary announcement The research in late November caused confusion and criticism from scientists.
This paperAn article published in the medical journal The Lancet describes vaccine trials run by the University of Oxford in the UK, Brazil and South Africa. Overall, data from the United Kingdom and Brazil indicate that the vaccine is 70% effective in preventing symptomatic COVID-19. Three countries have not reported serious security problems.
The results announced in the November press release highlight that if the first half dose is injected, the vaccine’s effectiveness can reach up to 90%. However, the research team did not disclose that the data was obtained due to a dose error, and the scientists subsequently criticized the trial leader for lack of transparency and rigor.
The head of the Oxford team, Andrew Pollard, told BuzzFeed News that he hopes the newspaper will alleviate concerns about the trial. He said: “In most cases, we have been trying to select data to find good results.” “But this is not the case. We have reached an agreement with the regulators in advance.”
Still, scientists are right Earlier Press Releases I do not believe that their concerns have been fully resolved.
Natalie Dean, a biostatistician at the University of Florida, who specializes in designing vaccine testing strategies for emerging diseases, said: “As far as policy development is concerned, 70% of the numbers are still difficult to explain.”
“It’s a mess,” John Moore, a virologist at the Cornell Medical College in New York, who is working on an anti-HIV vaccine, told BuzzFeed News. “The vaccine is clearly working, but we still don’t know how effective it is.”
The vaccine was developed by the University of Oxford and its subsidiary Vaccitech, and is being marketed in cooperation with the British-Swedish pharmaceutical company AstraZeneca. It is composed of chimpanzee adenovirus (a group of viruses that can cause the common cold in humans) and is designed to produce a “spike” protein from SARS-CoV-2 (a virus that can cause COVID-19).
Scientists and public health officials have been waiting for these results because the Oxford-AstraZeneca vaccine is the most widely ordered vaccine among COVID-19 vaccines, and governments hope that these vaccines will eventually bring the epidemic under control.
The attraction lies in the low cost and easy transportation of the vaccine. The supply deals announced so far indicate that the price per dose of Oxford AstraZeneca vaccine will be less than US$4, while the market price of other vaccines is about US$20-25. The large-scale clinical trials conducted by rival drug giants Pfizer and Moderna The result of the test is a biotechnology company located in Cambridge, Massachusetts.
Moreover, unlike Pfizer and Moderna vaccines, Oxford-AstraZeneca vaccines can be stored at normal refrigeration temperatures, while Pfizer and Moderna vaccines must be deep-frozen shortly before use-in the case of Pfizer vaccines Around -70 degrees Celsius.
But since AstraZeneca released on November 23 Confusing The press release describes the combined results of trials conducted at Oxford University in the UK and Brazil, involving approximately 23,000 volunteers. According to how the trial’s vaccine and placebo groups allocated 131 COVID-19 cases, AstraZeneca claims “The average efficacy is 70%.”
This shows that the vaccine is not as effective as the main competitor because Pfizer with Modern Each announced in early November that their vaccine trials showed that they are more than 90% effective.
But there was a turning point. AstraZeneca and Oxford claimed that if participants were given a half-dose and then full-dose vaccine, their vaccine would also be 90% effective. At the same time, two full doses produced only 62% efficacy. The more successful results are particularly prominent in their promotional activities.
Pollard said in the press release: “The exciting thing is that we found that one of our dosing regimens may be about 90% effective. If this dosing regimen is adopted, more people can be vaccinated with the planned vaccine. “
Initially, scientists were puzzled by these findings. “I found the presented results difficult to explain,” Dean told BuzzFeed News last week.
As more details about the incident emerged, experts became increasingly suspicious of 90% of the claims. First Mene Pangalos, Head of Non-Oncology Research and Development, AstraZeneca Enter Reuters Half the dose is actually the wrong result, first of all The Mirror revealed As early as June.
Then on November 24, Moncef Slaoui, the chief scientist of Warp Speed, a partnership established by the U.S. federal government to accelerate the development of COVID-19 vaccines, Tell reporter Those who mistakenly administered half of the initial dose to volunteers were all under 55 years old, so they cannot represent the age of the volunteers in the entire trial.
The fact that the dose error affected an unrepresented population reflects another confusing aspect of the British trial: since the first trial Listed on ClinicalTrials.gov In late May, the number of specific patient groups in the trial steadily increased, and 12 experimental groups and 25 subgroups with puzzling results received different treatments.
“What do these trials mean? We don’t know,” Moore told BuzzFeed News last week.
In the new “Lancet” magazine, the Oxford research team conducted statistical control on the age difference between the two groups given different doses, and found that the efficacy of half-dose and full-dose treatment was still improved. But other scientists still worry that, so far, there are no data on the best effects of COUPID-19 among the elderly.
“It needs further evaluation,” Dean said.
Not like Pfizer and ModernaThe University of Oxford and AstraZeneca did not publish the full details of their trial protocols at the beginning of all large-scale trials for other researchers to scrutinize, which made it difficult to understand the results in the earlier press releases. In September, after suspected serious adverse reactions from British participants, trials of the vaccine were shelved, and there were further concerns about transparency.The suspension will only be made public after it is reported in the biomedical news Website Statistics.
In a statement sent to BuzzFeed News last week, the Oxford research team downplayed the importance of feeding errors and stated that the plan to conduct the analysis has been approved by the UK regulator:[W]When it became clear that a lower dose was used, we discussed with the regulatory agency and agreed on a plan to test both lower doses/higher doses and higher doses/higher doses, allowing us to use both at the same time Two methods. “
The new document states that the agreement was revised on June 5, about a week after the trial began. Pollard told reporters at a press conference organized by the London Science Media Centre today that this change was made before the “database lock”, which means that the change was part of an officially approved plan.
Nevertheless, the confusing results seem unlikely to be accepted by the FDA. The US regulator is expected to wait for the results of another AstraZeneca trial conducted in the United States by AstraZeneca instead of Oxford before deciding whether to approve the vaccine for emergency use.
Paul Offit, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia and member of the FDA Advisory Committee on Vaccines and Related Biological Products, told BuzzFeed News last week: “I can only say that there is a lot of explanation.”
“It is not possible to conclude why the efficacy results seem to be significantly different, 90% and 62%, respectively,” Slaoui, chief scientist of the Warp Speed ??operation, told reporters at a press conference on December 2. Based on the facts and data on the data behind these two numbers, this is a very clear explanation, and it is likely that the package is not sufficient for approval. “
AstraZeneca CEO Pascal Soriot (Pascal Soriot) said in a briefing at the Science Media Center that he expects the FDA to request results from the U.S. trial.
Another concern is that the United Kingdom and Brazilian It was originally thought to be a trial to test the efficacy of the vaccine separately, and the treatment method involved was slightly different from that of the placebo group. After the Oxford research team realized that the UK’s successful reduction of the spread of COVID-19 to a mean trickle at the end of the spring meant that the UK did not see enough cases in the UK trial to produce definite results, it was necessary to compare the data from these two trials Combined.
The Oxford team Initially bullish Information about it being the first opportunity to demonstrate an effective COVID-19 vaccine. “At the moment, we are definitely in Europe. This may be the place where the level of COVID transmission is the highest anywhere in Europe. Therefore, we have ample opportunity to achieve curative effects in the next three months,” Jenner College in Oxford, Tell CNN In late April.
But less than a month later, Hill Tell the telegraph Newspaper: “This is a race against the disappearance of the virus and a race against time. At present, we have a 50% chance that there will be no results at all.”
Because the Oxford-AstraZeneca vaccine has great hopes, the stakes are high.In the UK, Prime Minister Boris Johnson has Praise this work “Our Distinguished Scientist” reported that a unit in his office was selling vaccines marked with the Union Jack flag on vials. According to the Huffington Post.
In the UK, the barriers to emergency approval of the vaccine are expected to be lower than in the US.Indeed, the State Administration of Medicines and Health Products has Approved Pfizer vaccine Still under consideration By the FDA. An advisory group from the US Department of Health met this Thursday to evaluate the results of Pfizer’s vaccine, which is expected to be the first emergency authorized vaccine in the United States.
Considering the cost and ease of transportation of the vaccine, the approval of the Oxford-AstraZeneca vaccine in the UK may lead to a surge in orders.According to one data analysis The scientific journal “Natural” from the life science analysis company Airfinity is in great demand. About 2.7 billion doses have been pre-ordered, much more than any other single vaccine candidate.
Scientists are worried about the efficacy of the vaccine, because any problems that arise in the future may damage people’s confidence in the COVID-19 vaccine more generally.
Moore said: “Our biggest collective concern is that things that will go wrong undermine the trust of the public.” “We want a process that is as clean as possible.”
Stephanie M. Lee provided coverage for this story.
