While an announcement Monday by Astrazeneca and Oxford showed their shot was 70% effective on average in a late-stage study and as the world celebrated hopes of an effective Covid-19 vaccine to be available soon, it was reported that it was actually a stroke of good luck.
AstraZeneca and Oxford who are among the front-runners in the quest to deliver a Covid-19 vaccine face a lot of questions about their trial results after acknowledging a manufacturing error.
What was the error?
According to the British drug giant AstraZeneca, one dosing regimen showed vaccine efficacy 90% when a half-dose was given, followed by a full dose at least one month apart, and that two full doses showed an efficacy of 62%. The combined analysis from both dosing regimens resulted in an average efficacy of 70 percent.
In a later statement, Oxford said a difference in manufacturing processes led to some participants being given a half dose instead of a full one.
The nearly 3,000 participants in the UK on whom this result was based were never supposed to be given a half dose instead of a full one in the first place.
“The reason we had the half-dose is serendipity,” Mene Pangalos, the head of AstraZeneca’s non-oncology research and development, told Reuters.
The revelation has flagged the lack of transparency in the entire process and added doubts about the way AstraZeneca and Oxford have been conducting these trials.
“With the exception of the US-based trial, I am not aware of details on how these trials are being monitored. Is there a centralized DSMB (Data Safety and Monitoring Board)? Are they combining the accrued data? They seem to have combined events across Brazil and the UK. Why not other countries?” Natalie E Dean, a biostatistician at the University of Florida, tweeted on Wednesday.
With the exception of the US-based trial, I am not aware of details on how these trials are being monitored. Is there a centralized DSMB? Are they combining the accrued data? They seem to have combined events across Brazil and UK. Why not the other countries? 3/5
— Natalie E. Dean, PhD (@nataliexdean) November 24, 2020
“And reporting out a secondary analysis that was not pre-specified (since it seems to be based on a dosing error) is not desirable. If they seek to get the half-dose approved, they should wait until they have a compelling result. Otherwise, we can land in ‘evidence limbo’,” she tweeted.
And reporting out a secondary analysis that was not pre-specified (since it seems to be based on a dosing error) is not desirable. If they seek to get the half-dose approved, they should wait until they have a compelling result. Otherwise, we can land in "evidence limbo." 4/5
— Natalie E. Dean, PhD (@nataliexdean) November 24, 2020
“Any time you have confusion in trials it’s not a good thing because it effectively removes any kind of credibility you had,” said Ketan Patel, a fund manager at EdenTree Investment Management. “I think there will be a lot more scrutiny of Astra’s product due to the manufacturing issue.”
‘Unknown’ Efficacy
“The most likely explanation for the divergent efficacy in its interim analysis is either chance or patient demographics,” Sam Fazeli, a Bloomberg Intelligence analyst, wrote in a note.
“Either way, approval based on current data means people will be inoculated with a vaccine the true efficacy of which is unknown.”
The battle against Covid-19 is at a turning point with encouraging vaccine trial findings coming this month. One vaccine from Pfizer and BioNTech SE and another from Moderna Inc. were both about 95% effective in preliminary analyses of trials of tens of thousands of volunteers.
Fazeli added: “We remain most convinced by the Moderna and Pfizer data for now.”
While researchers have argued that the efficacy of the Oxford-AstraZeneca vaccine is not comparable with the candidates being developed by Pfizer and Moderna as The Oxford-AstraZeneca trials have taken into account both the mildly and seriously ill cases unlike the other two, which considered only serious illnesses.
No need to panic says Serum Institute of India
As AstraZeneca is planning to run additional trials, the Serum Institute of India has said there is yet no reason to worry as far as trials in India are going on.
“The Indian trials are running smoothly with strict adherence to all the necessary processes and protocols. So far, there are no concerns. However, we are going through the data that is available and will make a further statement, if needed,” SII said.
The company CEO, AstraZeneca has also said that the company is likely to run an additional global trial to assess the efficacy of its Covid-19 vaccine using a lower dosage, amid questions over the results of its late-stage study.
“Now that we’ve found what looks like a better efficacy we have to validate this, so we need to do an additional study,” he said, reported Reuters.