Oxford vaccine: experts question data on efficacy of medium dose and transparency in testing Vaccine

• Oxford vaccine needs to undergo ‘further study’ to re-evaluate efficacy at half dose
• The Ministry of Health signs an association for the development and production of the Oxford vaccine

The first panorama with doubts about the transparency of the studies was published in a report in the newspaper “The New York Times” on Wednesday (25). The vaccine called ChAdOx1 Distribution in Brazil is already planned: the federal government will invest R $ 1.9 billion to produce 100 million doses.

The data provided by the developers has not yet been published in a scientific journal. The company reported that the immunizing agent has an average effectiveness of 70.4%, considering both the 90% obtained in the group that received half a dose in the first stage of vaccination and the 62% obtained in those who took both full doses.

After applying the half dose, now valued as a methodological error, the researchers raised, among other points, the following questions about the Oxford vaccine:

• Despite having three different levels of effectiveness, what is the true effectiveness of the vaccine?
• How many people in the 90% effective group had Covid-19?
• How many severe cases of Covid-19 occurred in the placebo group?
• Only the young volunteers took half the dose. How does this dose behave in other age groups?
• What is the difference in efficacy between the full dose and half the dose?
• Why doesn’t clinical vaccine research in different countries follow a single protocol?

In a note, AstraZeneca informed the G1 that the half-dose regimen was reviewed by the Independent Safety and Data Monitoring Committee and the UK regulatory agency (MHRA), indicating continuity of the study.

• The greater efficacy of the half dose of the Oxford vaccine against Covid still does not have a definitive explanation

In addition, the pharmacist reported that “given the high efficacy that we now see with different dosing regimens, (…) there is strong evidence to continue researching and understanding these findings in order to establish the most effective dosing regimen for the vaccine”.

In an interview with the Bloomberg news agency on Thursday (26), Pascal Soriot, director of the pharmaceutical company AstraZeneca, said that the Oxford vaccine against Covid-19 should undergo an “additional study” to re-evaluate the effectiveness of the medium application. dose combined with a full immunization dose.

“Now that we have discovered what appears to be better effectiveness, we have to validate it, so we need to do an additional study” – Pascal Soriot, director of pharmaceutical AstraZeneca, in an interview with Bloomberg

Experts collect data

In an interview with Reuters, Peter Openshaw, professor of experimental medicine at Imperial College London, said that all the scientific community currently knows is a “limited amount of data” about the vaccine.

“We have to wait for the full data and see how the regulatory agencies view the results,” Openshaw said, adding that the US and European agencies “possibly have a different opinion” of each other.

At the core of the concerns is that the most promising result of the 90% test comes from subgroup analysis, a technique that many scientists say can lead to incorrect readings.

According to the Reuters news agency, Moncef Slaoui, senior scientific advisor to the US government’s vaccine program Operation Warp Speed, no one in the subgroup that received half the initial dose was over 55, suggesting that the effectiveness of the regimen in crucial age groups has not been tested in these interim data.

Older people were included in the group that received a correct full dose followed by a full dose, according to Slaoui.

“There are a number of variables that we need to understand and what the role of each of them has been in making the difference in effectiveness,” Slaoui said at a news conference Tuesday. “It is still possible that the difference (in effectiveness) is a random difference,” he added. “It is unlikely, but it is still possible.”

Subgroup details and data

Professor of Medicine at the University of East Anglia in the UK, Paul Hunter said that “subgroup analyzes in randomized controlled trials are always very difficult” and increase the risk of “type 1 errors”, which are of the type What happens when an intervention is considered effective when it is not.

This is partly because the number of participants is very small in a subgroup, which makes it more difficult to be sure that a discovery is not just due to chance differences or similarities between participants.

“To have faith in the results,” Hunter said, any subgroup analysis “must be sufficiently developed” with a large number of volunteers to take the readings.

“The devil is in the details,” said Danny Altmann, professor of immunology at Imperial College London. “We are trying to evaluate really complex test projects based on short press releases.”

“Many questions were left unanswered,” said Morgane Bomsel, an expert at the French National Center for Scientific Research, adding: “We have the impression that they (AstraZeneca) are selectively choosing the data.”

The microbiologist Natália Pasternak questioned the transparency of the studies during the development of the vaccine and highlighted that the half dose was applied only to young volunteers.

“The half dose was a mistake and worse, it was only given to young volunteers. The company tried to cover it up,” Pasternak wrote on social media.

“It is not the case that the vaccine has gone through the roof. It may still be a good vaccine. But it is certainly the case of waiting for the full primary analysis and also studying the half dose in a separate trial with a larger number of volunteers and in a transparent way “- Natália Pasternak, microbiologist

For the epidemiologist Denise Garrett, it is not possible to affirm the real effectiveness of the vaccine, since the application of the half dose was an error and not an expected part of the investigation. Furthermore, Oxford / AstraZeneca did not reveal important parts of the study, such as the number of Covid-19 cases in the group that was 90% effective.

“What we have so far is strong data for a less effective vaccine (62%) and less robust data for a more effective vaccine (90%),” Garrett posted on Twitter.

Vaccine trial specialist Natalie Dean from the University of Florida in the United States posted on her Twitter that vaccine clinical trials conducted in different countries do not follow a unified development protocol.

“AstraZeneca is evaluating its vaccine in several trials around the world, but they are not included in a unified protocol. In fact, the trials appear to be quite different by country, in terms of populations, subgroups, etc.,” Dean said. .

The American expert suggested that the preliminary data presented this week be sent to a scientific journal for peer review.

According to the Oxford / AstraZeneca announcement on Monday (23), the combination of a half dose with a full dose ended up being more effective in protecting against the disease, by 90%. In contrast, the effectiveness in participants who received the two full doses was lower, 62%.

Of the 11,636 people vaccinated, 8,895 received 2 full doses of the vaccine, one month apart, as planned. The other 2,741 volunteers received a half dose, followed by a full dose a month later.

On Monday (23) Mene Pangalos, executive vice president of AstraZeneca, in an interview with the Reuters news agency, said that half the dose applied to part of the vaccinated volunteers was a “fluke”.

“The reason we have a half dose is chance,” Mene Pangalos, head of non-cancer research and development at AstraZeneca, told Reuters.

According to the news agency, at the time the drugmaker began its partnership with Oxford in late April, university researchers were dosing volunteers in Britain.

But they soon realized that anticipated side effects, such as fatigue, headaches or an arm, were milder than expected, Pangalos told the agency.

“So we went back and checked … and found they had halved the dose of the vaccine,” the deputy director said. Pangalos also claimed that the company decided to continue with the half dose and administer the full booster dose as scheduled.