Since the results of the Oxford vaccine trial were announced yesterday, I have been trying to understand how the efficacy rates for the different vaccine dosage regimens were calculated.
This is the year that some of us became amateur epidemiologists and virologists, talking about terms such as the “R number”, “asymptomatic” and “exponential growth”, as if virology and epidemiology have always been our national pastime. As the race for a vaccine to protect us from covid-19 gathers pace, we are entering the next stage of our education in the terminology of vaccines.
So what do scientists really mean when they talk about “vaccine efficacy” during the development of a vaccine ? For those of us who aren’t part of the scientific community, “vaccine efficacy” probably isn’t a term we’ve come across much in the past. Vaccine efficacy is a measure of how much a trial participant’s risk of getting a disease drops if they have had the vaccine, compared with those given a placebo jab.
“The greater the percentage reduction of illness in the vaccinated group, the greater the vaccine efficacy,” according to the US Centers for Disease Control and Prevention (CDC). The CDC sets out one way of calculating vaccine efficacy on its website.
Scientists testing a vaccine establish the number of trial participants who caught the disease even though they’d been given the vaccine. In the Oxford trial, that was 30. They then subtract this figure from the number of unvaccinated trial participants (those who got a placebo) who were infected. On the Oxford trial, that was 101. Then, they divide the result – that’s 71 for the Oxford trial – by the number of unvaccinated participants who developed the disease, which as we just said was 101 in the Oxford vaccine example. Finally, to get a percentage, multiply that by 100. click for source.
Oxford Vaccine Efficacy (VE) = (101 – 30)/101 = 70.3%
Apparently, there were 3,000 people in the vaccine arm who had the half dose followed by the full dose and 9,000 people who had the two full doses. Assuming the placebo group who tested positive for covid-19 (101) are distributed in the same proportion (25%/75%) means that there would be 26 in the low dose arm and 75 in the high dosage arm. The only split of cases who tested positive in the vaccine arm (30) to give the reported efficacy rates are 2 low dose cases and 28 high dose cases :
Half dose/Full dose Oxford Vaccine Efficacy (VE) = (26-2)/26 = 92.3%
Full dose/Full dose Oxford Vaccine Efficacy (VE) = (75-28)/75 = 62.7%
Clearly, these efficacy rates are based on very small numbers and must be subject to a very wide margin of error. They assume that the people in both arms of the vaccine trials had the same chance of exposure to coronavirus and contracting covid-19, which to me is questionable, given that recruits in the trial were in different countries such as the UK, Brazil and South Africa.
I find it hard to believe that such simplistic formulae and assumptions have been used to determine efficacy rates in a multi-billion vaccine programme, but what do i know. Time will tell.
Interestingly, the Oxford University and AstraZeneca vaccine trials reached 90% efficacy by accident thanks to the “serendipity **” of an error that led to some participants receiving half doses, it has emerged. Yesterday, scientists revealed that the Oxford vaccine had an overall efficacy of 70%, but could be around 90% effective when administered as a half dose followed by a full dose a month later. (**the occurrence and development of events by chance in a happy or beneficial way: “a fortunate stroke of serendipity“).
When university researchers were distributing the vaccine at the end of April, around the start of Oxford and AstraZeneca’s partnership, they noticed expected side effects such as fatigue, headaches or arm aches were milder than expected. They went back and checked and found they had underpredicted the dose of the vaccine by half,. Instead of restarting the trial, he said researchers decided to continue with the half dose and administer the full dose booster shot at the scheduled time.
About 3,000 people were given the half dose and then a full dose four weeks later, with data showing 90% were protected. In the larger group of 9,000 people, who were given two full doses also four weeks apart, efficacy was 62%. Scientists said they still could not fully explain why the half dose gave better protection, but said it may be that it triggers the immune system differently. Click full article
Update = it turns out that I was not alone in understanding the “dose error” of the trial and the subsequent calculations. It turns out there were 3 people rather than 2 people in the half dose/full dose arm of the vaccine trial. Here is the full explanation BBC article.
Further update – Damning article in the Guardian inc “One analyst in the US wrote in an investor note that “we believe that this product will never be licensed in the US” and alleged the company had tried to “embellish” the results”.
Mene Pangalos, AstraZeneca’s head of biopharmaceuticals R&D, confirmed that the trial included no one over the age of 55. ………..so much for protecting the elderly.