Oxford Vaccine Red Flags

Hilda Bastian in Wired has looked in detail at the AstraZeneca trial and is extremely unimpressed, arguing the vaccine “isn’t up to snuff”.

Presumably, neither of the two trials from which they combined data could have provided a clear answer on the vaccine’s efficacy on its own. To make things worse, Oxford-AstraZeneca reported only the results for certain subgroups of people within each one. (For perspective on this: The two subgroups chosen leave out perhaps half the people in the Brazilian trial.) Meanwhile, one of their key claims is that giving half a dose of the vaccine on the first injection, followed by a standard dose on the second one, led to better outcomes – but neither of these trials had been designed to test this hypothesis. In fact, it’s since emerged that the half-dose/full-dose option started out as a mistake, and one that was only caught when some people in the study didn’t have the usual high rate of adverse effects.

The problems are legion.

There are other problems, too. In the press release, Oxford-AstraZeneca reports that two of the dosing regimens “demonstrated efficacy.” Presumably, none of the others did, but they didn’t give specifics. Of the only two regimens they reported, one (the mistaken first half-dose, followed by a full dose at least a month later) came in at 90%, and the other (two standard doses at least a month apart) achieved only 62% efficacy. You’ll see reports that the vaccine had 70% efficacy, on average; but that’s un-knowable, because we only have numbers on these two regimens, as opposed to everyone in the trials – and how they arrived at those percentages isn’t explained. As far as we know, some of this analysis could hinge on data from just a few sick people. That means the findings could be a coincidence, or they could be biased by other factors. For example, it has since been revealed that the people who received an initial half-dose – and for whom the vaccine was said to have 90% efficacy – included no one over the age of 55. That was not the case for the standard-dosing group, however, where the reported efficacy was 62%. This demographic difference could be more important than the change to the size of the first dose.

That’s not the end of the problems. Overall, the Oxford-AstraZeneca trials appear to include relatively few participants over the age of 55, even though this group is especially vulnerable to COVID-19. (People over 55 were not originally eligible to join the Brazilian trial at all.) Compare that to BNT-Pfizer’s trial, where 41% of the volunteers were over 55. The Oxford-AstraZeneca vaccine also seems to produce relatively high rates of adverse events. If you want to dig further into this vaccine’s story and issues, I’ve laid out a more detailed rundown of the Oxford-AstraZeneca trials and sources here.

The Oxford vaccine is a more traditional type of vaccine so the lower efficacy and stronger side-effects are more in line with what was originally expected. The concerns do call into question though how political any UK decision to approve the vaccine will be, as well as how many will agree to have it and how far the Government will deem it sufficiently protective to bring the emergency to a close. The Pfizer and Moderna RNA vaccines appear to be more effective (if more expensive and logistically challenging), but we don’t yet know for how long or if they will prevent serious illness or transmission. There are also questions of long-term safety.

Even if a vaccine does enable this crisis to come to an end in the next six months, there is still the problem of what happens next time. We can’t go through this every time a new flu-like pandemic gets going.

Stop Press: A new peer-reviewed article has appeared in Annals of Internal Medicine, “Ethical and Scientific Considerations Regarding the Early Approval and Deployment of a COVID-19 Vaccine“, questioning the ethical basis of the current Covid vaccine trials. Is this the kind of anti-vaxx messaging that Keir Starmer wants banned?