AstraZeneca’s manufacturing error raises doubts about the results of vaccine studies

Surprisingly, the group of volunteers who were given a lower dose appeared to be much more protected than the volunteers who received two full doses. In the low-dose group, AstraZeneca said, the vaccine appeared to be 90 percent effective. In the group that received two full doses, the vaccine appeared to be 62% effective. Together, the drug makers said the vaccine appeared to be 70 percent effective. But the way in which the results were achieved and reported by the companies led to serious questions from the experts.

The partial results announced on Monday come from large ongoing studies in the UK and Brazil aimed at determining the optimal dose of the vaccine, as well as examining safety and efficacy. Multiple combinations and doses were tried in the volunteers. They were compared with others who were given a meningitis vaccine or a saline injection.

Before starting the research, the scientists explain all the steps they are taking and how they will analyze the results. Any deviation from that protocol can question the results.

True or strange?

In a statement Wednesday, the University of Oxford said some of the vials used in the study did not have the right concentration of the vaccine, so some volunteers received half a dose. The university said it had discussed the issue with regulators and agreed to complete the process at a late stage with two groups. The production problem has been corrected, according to the statement.

Experts say the relatively small number of people in the low-dose group makes it difficult to know whether the observed efficacy in the group is real or a statistical oddity. About 2,741 people received half a dose of the vaccine followed by a full dose, AstraZeneca said. A total of 8,895 people received two full doses.

Another factor: None of the people in the low-dose group were older than 55. Younger people tend to mount a stronger immune response than older people, so it could be that the youth of the low-dose group participants is why they seemed more effective, not the dose size.

Another point of confusion stems from the decision to combine results from two groups of participants who received different dosage levels to achieve an average efficacy of 70%, said David Salisbury, and associate member of the global health program at the think tank. by Chatham House.

“You took two studies for which different doses were used and you found a composite that represents neither dose,” he said of the figure. “I think a lot of people have problems with this.”

The Oxford researchers say they are unsure and are working to find out why.

‘The amount of Goldilocks’

Sarah Gilbert, one of the Oxford scientists leading the research, said the response is likely related to providing the right amount of vaccine to trigger the best immune response.

“It’s the amount of Goldilocks you want, I think, not too little and not too much. Too much might give you a poor quality response,” he said. “So you want the right amount and it’s a little hit and miss when you try to go fast to get that perfect first time.”

Details of the trial results will be published in medical journals and provided to UK regulatory authorities so they can decide whether to authorize the vaccine to be distributed. These reports will include a detailed breakdown that includes demographics and other information on who got sick in each group and will provide a more complete picture of how effective the vaccine is.

Moncef Slaoui, who leads U.S. coronavirus vaccination program Operation Warp Speed, said in a call with reporters on Tuesday that U.S. officials are trying to determine what immune response produced the vaccine and may decide to modify the study. AstraZeneca in the United States to include half of it. dose.

“But we want it to be based on data and science,” he said.