Alright, next up AstraZeneca…
AstraZeneca has four ongoing trials. Late in November, they reported interim results from two of the four trials (UK and Brazil) with approximately 4 months of follow-up data among 11,636 people. AstraZeneca initially reported that the vaccine had 70% efficacy.
Shortly after the report was released, a big mistake was revealed. Researchers in the UK had been meaning to give volunteers the initial dose at full strength, but they made a miscalculation and accidentally gave it at half strength. About 3,000 participants were given the half dose and then a full dose four weeks later; nearly 9,000 volunteer were given two full doses four weeks apart.
This may have been a lucky mistake. The half-dose regimen had 90% efficacy; the full-dose regimen had 62% efficacy.
No one knows why the half dose regimen worked better. There are two hypotheses: 1) The lower first dose did a better job of mimicking the experience of an infection, promoting a stronger immune response; 2) It isn’t truly better. Participants who received the half-dose regimen had been exclusively <55 years old. It’s possible that volunteers who got the half doses are different (ie healthy) compared to those who got the full dose regimens, making it seem like efficacy is higher. Since age is the biggest risk factor for getting seriously ill with COVID19, this is an extremely important consideration.
This error and a series of other irregularities are causing scientists to lose confidence in the reliability of the results. It’s not clear, at least to me, whether AstraZeneca is making rookie mistakes or if they are blatantly nontransparent. For example,
1. They initially pooled data and reported 70% efficacy. When, in fact, efficacy was 62% and 90%. This was just wrong.
2. They also initially pooled Brazil and UK data even though the trials were designed differently (ie different dose intervals). Pooling different clinical trials is a break from standard practice.
3. They halted the trial because of an unexplained illness. This IS completely normal. However, AstraZeneca didn’t promptly announce the decision publicly. Instead, they provided details about the nature of the illness on a private conference call with investors hosted by the investment bank J.P. Morgan. This is just…weird?
The US trial is still underway and results should come in late January. There is no indication the the US has made the half dose error, so we should get some solid data. And, although the efficacy may be lower than other vaccines, FDA is requiring 50% efficacy benchmark, so it could pass. I’m looking forward to the FDA external advisory board meeting, as it should be a VERY interesting discussion about AstraZeneca’s errors and whether they cloud confidence.
The UK external advisory board is meeting TODAY to discuss the AstraZeneca vaccine and whether to grant emergency approval. This should also be interesting; stay tuned.
In the meantime, AstraZeneca has said it is considering a new global trial based on the half dose first regimen.
AstraZeneca published results:https://www.thelancet.com/…/PIIS0140-6736(20…/fulltext