The results of the first peer review describing the clinical trial of the COVID-19 vaccine, jointly 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: “Most assumptions are that we have been trying to select data to find good results.” “But this is not the case. We have reached an agreement with regulators in advance that we will adopt this approach.”
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, this number is still difficult to explain.”
“It’s a mess,” John Moore, a virologist at Weill Cornell College of Medicine in New York, who is working to develop 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 derivative company Vaccitech, and launched it to the market 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 after modification, it can produce “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 is 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 other vaccines will cost about US$20-25, while rival drug giants Pfizer and Moderna have conducted large-scale Clinical Trials. Is a biotechnology company located in Cambridge, Massachusetts.
In addition, 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.
However, since the release of AstraZeneca on November 23 Confusing The press release describes the combined results of trials conducted by Oxford University in the United Kingdom and Brazil, involving approximately 23,000 volunteers. Based on 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 have shown that they are more than 90% effective.
But there is a turning point. AstraZeneca and Oxford claim that if they give participants a half-dose and then full-dose vaccine, their vaccine is also 90% effective. At the same time, the two full doses produced only 62% efficacy. The more successful results are particularly prominent in their promotional activities.
“What’s exciting is that we found that one of our dosing regimens may be about 90% effective. If this dosing regimen is used, more people can be vaccinated according to the planned vaccine supply,” Pollard in the news Said in the draft.
Initially, scientists were puzzled by these findings. “I found the presented results difficult to explain,” Dean told BuzzFeed News last week.
As more details emerged, experts became increasingly skeptical of the 90% claim. First Mene Pangalos, Head of Non-Tumor 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 gave half of the initial dose to volunteers were all under 55, so they could not 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, resulting in a confusing 12 experimental groups and 25 subgroups receiving 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 carried out 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 is no data on the elderly most vulnerable to COVID-19.
“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, when a British participant suspected a serious adverse reaction, the trial of the vaccine was shelved, and concerns about transparency increased.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 had 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/higher doses and higher/higher doses, allowing us to include this at the same time Two methods. “
The new document states that the agreement was revised on June 5, approximately one week after the trial started. 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. It is expected that US regulators will 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 Warp Speed operation, told reporters at a press conference on December 2. Based on the facts and data about 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 said in a briefing at the Science Media Center that he expects the FDA to request the results of 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 involved was slightly different from the placebo group. After the Oxford research team realized that the UK’s success in reducing 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 definitive results, it was necessary to reconcile these two trials. Combine the data.
The Oxford team was Initially bullish Information about its chance to be the first to prove an effective COVID-19 vaccine. “Our current location may be one of the highest levels of COVID transmission anywhere in the world, of course in Europe, so we have a good chance of getting efficacy results in the next three months,” Adrian Hill Director Oxford Jenner College, 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 against time. At present, we have a 50% chance that there will be no results at all.”
Since the Oxford-AstraZeneca vaccine has great hopes, the stakes are high.In the UK, this is especially true of Prime Minister Boris Johnson in the UK Praise this work “Our Distinguished Scientist”, according to reports, a unit in his office was promoting 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. The US Department of Health’s advisory group met on 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 worry 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.