What to make of the AstraZeneca vaccine data — and the surrounding controversy

AstraZeneca’s up-and-down quest to develop a vaccine for Covid-19 stands out from what has otherwise been a remarkably straightforward process in the U.S. And the latest twist for AstraZeneca’s vaccine, involving a contentious back-and-forth with federal authorities, only adds confusion to an already muddled process.

STAT’s Helen Branswell recently joined the “Readout Loud” podcast to talk about AstraZeneca’s current predicament, the implications for vaccine confidence, and how this affects the global effort to beat back the pandemic by getting doses into arms.

Excerpts from the conversation have been lightly edited and condensed for clarity.

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When discussing the AstraZeneca situation, experts consistently reach for the word “unprecedented.” Is that accurate? And how shocking was this back-and-forth compared to the normal process of developing a vaccine? 

I think it was quite shocking. I don’t know that I could go as far as unprecedented. I haven’t looked for, you know, precedents.

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But typically, when a sponsor of an experimental product, whether that’s a vaccine or a drug, and a DSMB [data and safety monitoring board] are going back and forth, that happens behind the curtain. We don’t see that. And if there’s a disagreement between the two on how to read the data, they resolve that before anybody goes public with the data. So to have this situation where AstraZeneca made their statement and then the DSMB made it known that they had they disagreed with the analysis, or the way that AstraZeneca had done its analysis by focusing on earlier cases only, that was quite a stunning rebuke. This kind of stuff doesn’t normally happen in the public eye.

It’s been a bit of a rollercoaster this week. As of Thursday morning, it appears that all the alarm was over a 3 percentage point relative difference in vaccine efficacy — 79% in AstraZeneca’s interim data announced Monday, versus 76% from the more up-to-date analysis we got more recently. Who do you think will get the blame for this bizarre news cycle taking place: AstraZeneca for releasing outdated data or the NIH for putting this all on the public record?

I don’t think it looks good on either party, to be honest. Given that it’s only 3 percentage points, you would be tempted to say, oh, the NIH looks worse from this. But there’s been so much drama around this vaccine, so much uncertainty about the the data, that the company and Oxford University have generated … they had a lot of baggage coming into this fight. So I don’t think anybody walks away from this looking particularly great.

We knew that within 48 hours we are going to get an updated set of results. When you saw that the results were only 3 percentage points different from the original results, did that make you feel better about what might have happened, or did it make you scratch your head even more about why it happened? 

I think I would say both, in a way. At the end of the day, we’re all fascinated by this fight, the drama. But the reality is this is a really important vaccine and the world needs it and needs it to work. And what the data show is that it does work. And so 76% is quite a bit better than the 62% the Oxford group originally reported out of their three Phase 3s, the ones that they did in the U.K. and Brazil and South Africa. So this trial has given us information we really need and it’s really good news. So in that respect, that’s great.

“This vaccine project has had more plot twists and turns than an Agatha Christie novel.”

Helen Branswell, STAT senior writer on infectious disease

But I would love to know more about why the DSMB two days ago thought that the more accurate figure should have been somewhere between 69 and 74. And why now? I mean, you know, there’s there’s part of this story that we just don’t know yet. And I’m really curious about what it is.

The stateside controversy over the vaccine comes just days after a host of European countries briefly paused its distribution to investigate some rare potential side effects. Because this vaccine is being made at a not-for-profit price and it’s easier to store than many of the others, its inventors at Oxford University have called it a “vaccine for the world.” So from the world’s perspective, is this recent news damaging confidence in the vaccine?

Certainly it is damaging confidence in the vaccine in North America, potentially in Europe.

A lot of countries have given emergency authorizations to this vaccine. Whether they are all following this to the same degree that we are, I don’t know. But certainly a lot of people, friends of mine who are not journalists and who are not reporting on this, have been asking me about this vaccine. A lot of my family and friends are in Canada and a lot of them anticipate that this will be the vaccine they’re going to be offered and they feel like they don’t really know what to believe about it, to be honest.

What should AstraZeneca do to rebuild some of the trust and confidence? Or I guess more accurately, what can they do at this stage? 

No more drama. This vaccine project has had more plot twists and turns than an Agatha Christie novel. What they need to do is just generate and disseminate good, reliable data. That’s obviously been done. Going forward, they’re going to be putting in an application for an emergency use authorization. And the FDA is going to be crunching their raw data and it will tell the world what it thinks of how well this vaccine works. And that will be an extraordinarily important step in the process for this vaccine.

Speaking of which, the trial that we’re talking about was meant to support this application to the FDA, but the vaccine likely won’t go before the regulator until a month or two from now, by which point the U.S. might have enough supply of other Covid-19 vaccines to meet its needs. So what do you think the odds are that despite all this contentious debate, AstraZeneca is vaccine never actually gets distributed in the U.S.?

You know, I think that’s a possibility. I guess I’m not sure that we know at this point. One of the things we have to see is, at some point in time, people are going to have to start to vaccinate children and trials are going to need to be done to test the various vaccines and kids. And there is a strong likelihood, I think, that one or two of the vaccines might be more useful in children than others. If they’re less reactogenic, for instance. Parents don’t like to see their kids having a rough go of it after getting a vaccine. So if you can find a vaccine, one of the vaccines, or two of the vaccines that are less reactogenic in children, then those will probably be the ones that would be used.

So would I shut the door on the possibility that this vaccine might have some use in the United States? No. Do I think it’s a possibility that it won’t be used or won’t be used much in the United States? Yeah, I do think that’s a possibility. Just from the point of view of what you just what you said yourself, the U.S. may not need much of this vaccine or any of this vaccine by the time it’s available for use here.

Source: STAT