I keep seeing weird news about the Oxford AstroZeneca vaccine trials. First it was that a bunch of people in the initial study got the wrong dose
Many scientists raised concerns on the robustness of results from a sub-group of trial participants who, by error, received a half dose followed by a full dose.
The company also issued a statement admitting the error days after it touted the half doses as highly effective in preventing the disease.
Then it transpired that maybe the more important difference was the timing of the doses, but the timing of the two doses was so highly variable within to their study that it made the data muddy.
The 12-week interval was 81% effective, compared with 55% for the 6-week interval. The researchers also found that a single dose of the vaccine was 76% effective 3–12 weeks after the shot was administered.
And, in line with the interim trial results, the researchers observed that a low dose of the vaccine followed by a normal dose was more effective than two normal doses.
According to Dr. Merryn Voysey, the lead statistician at the Oxford Vaccine Group and a lead author of the study, “This latest analysis confirms our previous findings of the higher efficacy of a low- then standard-dose regimen.”
“However, with additional data available, we have found that the enhanced efficacy and immunity may be partly driven by the longer interval between doses that was common in this trial group,” she adds.
Now they are in the news because their Data Safety Monitoring Board suggests they may have fudged the data they released yesterday, by not including the most recent month of data:
I heard Dr. Fauci on the radio describing it as an “unforced error”. He said (and I paraphrase) “This is probably an excellent vaccine. But they are creating uncertainty by not releasing the most complete data.”
So… Is their management tone-deaf? Incompetent? Are all companies like this, but they just had the bad luck to be in the news for it?
I wouldn’t assume the dosage error was anything to do with AZ management. My first guess would be one of their partner health institutions running the trials messed up. I suppose AZ could have scrapped the data.
And I gotta say, I get a whiff of hit job. The Pfizer vaccine was approved for 16 yr olds despite almost no <18 yr olds in the trials. Did anyone hear about that? But the papers sure picked up on AZ not having enough data on 65 yr olds.
The janssen/j&j vaccine is in many ways the most exciting. Cheap, stores in the fridge, a single jab. They don’t seem to have ramped up production, sadly. I’m hoping it will be licensed to the big vaccine plants in India. And like the mRNA vaccines, it’s “plug&play”, they can easily drop in a slightly different DNA instruction, and are already testing a variant to better protect from the new strains.
There was a lot of press about it, because one of the US regulators voted against approval, saying he wasn’t comfortable approving it for kids under 18.
But since very few kids under 18 are eligible to be vaccinated at all, it hasn’t been a very important issue.
Ohio’s vaccinating 16 and up, right now. Not as a general thing, but as I understand it, they’re in the group that can get the vaccine if a clinic has extra doses left at the end of a session.
Wow, what percent of the population has been vaccinated?
Even so, the over 65 year olds were at the front of the line, and high risk, and it mattered a lot what vaccines they could have. The 16 year olds are at the back of the line, and not at very high risk unvaccinated, and if they (or their parents) are feeling uncertain, they are likely to just wait until more research is done. It’s just not nearly as big a deal.
In addition to saying it was odd for them to be publicly squabbling with the study-monitoring board (when fuller data, released today, says much the same thing as the data released a couple days ago) it also says:
Its rollout has been marred by a series of missteps including how the partners communicated earlier U.K. trial results. They presented a confusing array of dosing sizes and schedules, a wide range of efficacy results and few elderly trial subjects.
In Europe, AstraZeneca has fallen far short of supply targets, prompting fierce condemnation from European officials and threats of bans on exports of vaccines as the bloc tries to secure doses amid rising infections.
In happier news, the latest data shows the AZ vaccine perhaps more effective among those over 65 than in younger recipients.
Here’s a question to mull over. This is a quote form the European Public Assessment Report for the AZ vaccine.
Efficacy could not be demonstrated in subjects older than 55 YOA due to the low number of COVID-19 cases in this age group. In the overall pooled efficacy set there are 8 cases in the AZD1222 group and 9 cases in the control group in subjects 56-65 years, and 2 and 6 cases in the vaccine and control group respectively in subjects older than 65 years of age. This is mostly due to the low number of subjects of this age who were recruited (13% of the pooled efficacy analysis set aged 65 years or older and 2.8% aged 75 or older), in addition to the short time of follow-up for this population – as they were enrolled after safety in adults was confirmed. This is considered a major limitation of the dataset since older adults are at high risk for complications upon SARS-CoV-2 infection.
So: I’m pretty sure that at the time the main AZ study was initiated, there was at least a concern that elderly persons were those at greatest risk from the disease. How, then, is it possible to design a trial where only 2.8% of participants are over 75 years of age?
From this situation we get the pan-European debate about whether this vaccine should be given to one of the highest risk populations.
Don’t get me wrong - I have no doubt that the vaccine works well (and I’m currently awaiting my second shot of it). Everyone was developing their vaccine in unholy haste and there were significant issues in other applications. But there are aspects of the AZ package that I have a hard time getting my head around.
It describes the problems. It doesn’t really answer the question. It approaches an answer, saying
At the start of this year, it looked as though post-Brexit animosity might lie behind the sniping
and
“I think that some of the difficulties were that the trials were being set up by Oxford to answer public health questions, whereas very clearly Pfizer/BioNTech and Moderna’s trials in the US were set up to get FDA approval,”
And mentioning that there are issues around AstraZeneca’s communication. But it doesn’t support any of that (except that it’s clear they’ve had communication issues.) In particular, it doesn’t say how “answering public health questions” leads to the muddy trial design they seem to have used. Nor
The real world data from the jab is looking good. Just by virtue of actually producing a lot of vaccine quickly, they are going to be a major factor in dampening the pandemic. (Sad that j&j seems to be behind in production, as that was my initial hope to save the world, based on price and logistics.) And it’s crazy generous that they are not taking a profit on it.
Having worked in this industry, I can tell you the stories about AZ’s trials are so bizarre they’re hard to believe and we’re getting multitudinous explanations so that doesn’t help.
The levels of administrative QA around a drug trial are so vast and layered that it just cannot be believed. Every element of the process is checked, rechecked, checked some more. This level of ineptitude, if it’s all true, staggers me, even in the rush-rush situation we’re in.
Irrespective of the urgency of this, if all these stories are true, people need to be fired and never work in pharma again. In normal times they’d be shitcanned already.