AstraZeneca and Oxford University, who recently released results of the clinical trials for their COVID-19 vaccine candidate, on Wednesday, 25 November, acknowledged that there had been a manufacturing error that led to the 90 percent effectiveness of the shot, news agency AP reported.
This statement reportedly admitting the error comes days after the company and the university released their results claiming a high degree of effectiveness, but chose to leave out mention of why some trial volunteers did not receive as much vaccine as expected.
Oxford Announces 70% Effectiveness of Shot
On 23 November, it was announced that the COVID-19 vaccine developed by the University of Oxford and AstraZeneca had proved to be 70 percent effective after a large-scale trial.
The Oxford University said that the interim analysis from its phase three vaccine trial shows that the 70 percent effectiveness comes from combining two doses. The participants were given two high doses, which showed 62 percent efficiency, but it rose to 90 percent when they were given a half dose, followed by a high one, reports said.
However, the manner in which the results were achieved as well as reported by the makers has led to experts raising questions about the vaccine and its effectiveness.
According to The New York Times, the confidence in the vaccine among experts in the US has eroded firstly because of the error and also because of irregularities such as the fact that the error was revealed not by the company but by its head later, as well as the omission of the detail that there were no older people in the trial group concerned.
A Happy Accident?
Soon after the announcement, it was reported that the vaccine trials reached 90 percent efficacy by accident when some of the participants were given half a dose.
Mene Pangalos, executive vice-president of biopharmaceuticals research and development at AstraZeneca, said that the “trials reached 90 percent efficacy by accident thanks to the ‘serendipity’ of an error that led to some participants receiving half doses.”
When the researchers at Oxford University were distributing vaccines at the end of April, they noticed that expected side effects such as fatigue, headaches or arm aches were milder than expected.
“So we went back and checked, and we found out that they had underpredicted the dose of the vaccine by half,” said Pangalos.
What Problems Are Experts Raising?
AP reported that Oxford University’s statement on Wednesday said that some of the vials used in the trial did not have the right concentration of vaccine, leading to the half dose being administered. However, the manufacturing problem has been corrected, it said.
Reportedly, Oxford said that it discussed the problem with regulators, and decided to complete the late stage trial with two groups.
Further, AP said that experts feel that the relatively small number of people in the low dose group could make it difficult to know if the effectiveness is statistical anomaly or not. AstraZeneca reportedly said that approximately 2,741 people received a half dose followed by a full dose, while 8,895 people received two full doses.
Moreover, all the participants in the low-dose group were reportedly under the age of 55 years. Why is this a problem? Because younger people tend to show a stronger immune response than older people, so this does not shed accurate light on the effectiveness of the dose.
“The press release raised more questions than it answered,” John Moore, a professor of microbiology and immunology at Weill Cornell Medical College told NYT.
Another problem experts seem to be having is the decision to combine the effectiveness of both the groups and achieve a composite result, which is representative of neither group.
David Salisbury, an associate fellow of the global health program at the Chatham House think tank told AP, “You’ve taken two studies for which different doses were used and come up with a composite that doesn’t represent either of the doses... I think many people are having trouble with that.″
According to NYT, experts said that the chances of regulators in the United States and elsewhere authorising emergency use of the shot are low.
“I think that they have really damaged confidence in their whole development program,” Geoffrey Porges, an analyst for the investment bank SVB Leerink told NYT.
Lack of Certainty From Oxford
Oxford researchers themselves are unclear about why the low first dosage turned out to be more effective.
According to Sarah Gilbert, one of the Oxford scientists leading the research, it could be related to the right amount of vaccine which will trigger the best immune response.
“It’s the Goldilocks amount that you want, I think, not too little and not too much. Too much could give you a poor quality response as well,” she told AP.
“So you want just the right amount and it’s a bit hit and miss when you’re trying to go quickly to get that perfect first time.”Sarah Gilbert
AP reports that the details of the results will be published in medical journals and provided to regulators in the UK. These will include a detailed breakdown which will have demographic and other information such as who got sick in each group, providing a better picture of the effectiveness of the vaccine.
(With inputs from The Associated Press and The New York Times.)
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