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Living in the UK, I've heard lots of triumphalistic announcements regarding AZ approval on the radio so I think it's wise to offer a complete perspective of what happened. Here's a thread. 1/17
AZ's vaccine (AZD1222) is a chimeric viral vaccine: an engineered chimp virus that cannot replicate alone in human cells and produces the Sars-Cov2 spike protein to challenge our immune system. It's cheaper and easier to distribute than mRNA alternatives 2/17
AZ started the trial back in Autumn, with the goal of testing 40k subjects in 3 countries (UK, Brazil, S. Africa). The protocol was meant to be two shots of 5 million viral particles each with a four weeks gap. 3/17 https://clinicaltrials.gov/ct2/show/NCT04516746
You may remember back in October the trial was halted because wan Brazilian subject (a doctor) died after the shot. The trial resumed after a few days when it became clear the subject had actually received the placebo control, not the vaccine. An unlucky coincidence 4/17
In November, AZ revealed the interim data on Lancet. Kudos to AZ for being the only producer who swiftly associated their press release to actual data. That was well-received from us scientists (alas can't say the same about Moderna and Pfizer). 5/17 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32661-1/fulltext
From the data, something awkward and embarrassing emerged. AZ screwed up the dosage in 1/6 of the subjects. 11k were subjected to the expected dosage (SD/SD) but 2.5k received a low dose by mistake (LD/SD). AZ/Oxford came out transparently about it and admitted the mistake. 6/17
However, that led to confusing results. SD/SD had only 62% efficacy; LD/SD had 90% efficacy. @MHRAgovuk could not approve the latter dosage: sample was too small. So AZ decided to drop the first condition and pursue the latter with a second trial. 7/17
Today the announcement is that the SD/SD dosage was approved in an emergency, based (as far as we understand) on the data released back in November. No new data were communicated regarding that condition. Moreover: the approved SD/SD dosage has a gap of 12 weeks, not 4. Why? 8/17
The 12 weeks gap came from the Brazilian branch of the trial. Even though the target was set at 4, some subjects experienced a 12 weeks gap (things happen). Those numbers (how large?) apparently led MHRA to revise the protocol in the interest of a broader coverage 9/17
Now, the questions. What happened to the more promising dosage? MHRA claims data did not bourne out so we don't know if that 90% was a statistical fluke due to a small sample. Possible. Given the current situation with the new variant, probably wise to revert to plan A 11/17
Is the vaccine safe? Of course. Despite the very embarrassing screw up with dosages and missed trials, no reason to think it should not be safe to start with. 12/17
Is it going to work? God knows. Given its alleged genesis, the new variant can very possibly change everything. There is no evidence whatsoever vaccines will have the same efficacy on this new variant. AZ's dosage has a lower starting point (62%) so things are not brilliant 15/17
Why did MHRA approve before EMA? As far as we know, EMA was not even asked to be involved in all this. I suspect the very special UK situation played a role in this decision and I agree that B.1.1.7 leaves no time to waste. 14/17
What is the right course of action? Well, tricky. There are two vaccines in the UK now. One with 90%+ efficacy and one with 62% efficacy. For both, efficacy could turn out to be much lower anyway because of the variant. Tricky situation. 15/17
@IndependentSage recommended today that the country should enter a national lockdown AND to use a proper isolate & support system, alike to what Asian countries did. I personally think this is a sensible course of action. 16/17 https://twitter.com/IndependentSage/status/1344222227961548800
Overall, important to say one thing: in dire straits, transparency is paramount. @MHRAgovuk should come out crystal clear about the data they reviewed to approve and about what prompted them to approve the same data that were available back in November. 17/17
