Front Burner - AstraZeneca's self-inflicted wounds

Episode Date: March 25, 2021

The Oxford-AstraZeneca is hailed as a cheap and easy jab to fight COVID-19. But a series of corporate stumbles have clouded it's promise, and science backed results.

In the Dragon's Den, a simple pitch can lead to a life-changing connection. Watch new episodes of Dragon's Den free on CBC Gem. Brought to you in part by National Angel Capital Organization, empowering Canada's entrepreneurs through angel investment and industry connections. This is a CBC Podcast. Hello, I'm Jamie Poisson. These are just the kinds of communication mishaps that just don't bode well for a vaccine in a public health program like this. It's a real head-scratcher. I've not seen something like this. So earlier this week, Oxford AstraZeneca released the results from its U.S. trials, and it was great news.

They said the vaccine was 79% effective at preventing COVID-19, higher than previous trials. Then U.S. health officials sent this scolding letter to the company for releasing data that was, quote, outdated and potentially misleading. This news has to do with the efficacy of the vaccine, which is currently approved and being administered in Canada, not its safety. But it's also the latest in a real saga related to this vaccine, developments and mishaps that have sowed confusion and undermined trust in the company. To make sense of all of this, I'm joined by Helen Branswell. She's a Canadian infectious disease journalist with Stat News.

Hi, Helen. Thank you so much for making the time today. Hi, Jamie. It's nice to talk with you. So you sent out a tweet this week about this letter to AstraZeneca from U.S. health officials, basically telling the company that they were using misleading efficacy data. And you said it left you speechless. And can you talk to me a little bit about why?

Well, you know, this vaccine is a really important vaccine for the fight against COVID-19, for the effort to control the pandemic worldwide. A lot of countries are relying on this vaccine, which is cheap to make and doesn't require ultra-cold chain, so easy to use. And we've been very clear about the fact from the beginning that this was always going to be a vaccine for the world. But this vaccine has been plagued by communications missteps and strange decisions. AstraZeneca is hitting bumps in the road once more.

What they have done time and time again is continue to shoot themselves in the foot. And so there's been a lot of interest in seeing the results of the U.S. trial because it's a big trial, bigger than any of the others that have been done with this vaccine. And the thinking was that this was really going to be the trial that shows how well this vaccine works. And then to see the company come out with a number, make a claim, only to be rebuked by the scientists who are overseeing the data. I mean, that's really very extraordinary. That typically doesn't happen. And can you explain to me a little bit about what actually happened here? So I know that on Monday, AstraZeneca's U.S. clinical trial is over, and the interim results are better than many expected. AstraZeneca said that the vaccine was 79% effective

and 100% effective at reducing severe illness and hospitalization. Paving the way for the company to apply for U.S. approval. And so is that not the case then? What happened was they issued results from an interim analysis with data collected up until February 17th. But there have been weeks since February 17th, about five at this point. And there's also been more data that has accrued since that point. And when they looked at the whole packet of data that has been accrued, they did an analysis and they told the Data and Safety

Monitoring Board, the independent panel of scientists who reviews the data on an ongoing basis, that they intended to say that, you know, the interim analysis showed that the vaccine was 79% effective. The DSMB apparently told them that they should include the more recent data as well, which clearly has drawn down the efficacy estimate to somewhere between 69% and 74%. And yet the company did not follow the advice of the DSMB. They put out this 79% figure, you know, in my mind, I kind of think of it as using an old picture on your dating profile, on, you know, a dating app, you know, it's like, I look, I look like this in February, I don't look like this now, but I'm going to tell you what I look like in February. And what the DSMB did was say,

And what the DSMB did was say, whoa, this is misleading because the data that have come in since, which is a fuller picture, suggests that the vaccine's efficacy is a little lower. Not a ton, but enough to make a difference. I just want to mention the DSMB. It's this group in the United States that looks at the data and analyzes the data. But this idea, as you just mentioned, that this isn't a very big difference, 69% to 74% versus 79%. Why do that then? That's a really good question for which there isn't a really good answer at this point. You know, as Dr. Anthony Fauci, the head of the National Institute for Allergy and Infectious Diseases, said, you know, this was an unforced error on the part of the company. This is really what you call an unforced error, because the fact

is, this is very likely a very good vaccine. And this kind of thing does, as you say, do nothing, but really cast some doubt. They chose to use a figure that made their vaccine look better and got about, you know, 18 hours of great publicity out of it. That was quickly followed by a lot more bad publicity. AstraZeneca, you can see down there the stock more than 3%. It's not that the vaccine doesn't work. It's that people's trust in, you know, the credibility of the company's assessment of the vaccine gets called into question as a consequence. Right. And of course, as you mentioned before, there have been some other mishaps or miscommunications that I want to get into in just a moment with you. But first,

you know, speaking of that bad publicity, one US federal official told the Washington Post that this was like, quote, telling your mother, you got an A in a course when you actually got an A in the first quiz, but a C in the overall course. And I have to say, I like your dating profile analogy better. But is that a fair way of looking at it? Yeah, I think it is. I mean, I would quibble with the A and the C because the distance between 79 and 69 to 74 is probably not the difference between an A and a C, but it might be the difference between an A and a B minus or a C plus. And I'm certain the company's officials would say they didn't do anything wrong. They showed what the snapshot to that time was. But given that they

knew that there was a fuller picture available, it kind of makes it look like they were fudging the data. Okay. And I just want to be clear about one more thing before we move on. You know, we're talking about the efficacy. We're talking about preventing symptoms, symptomatic COVID. But you know, there's also the number that this vaccine is 100% effective at reducing severe illness and hospitalization. And do we have any data or evidence at this time that would suggest that that is not the case? To my knowledge, no, I don't think the DSMB challenged that figure. But it is also true. It's very early days. I mean, that's based on a very small number of severe illnesses in the placebo arm of the trial. Over time, as the vaccine is used broadly,

and it is being used very broadly, both in the UK and in other countries in the world, you know, it's not going to remain at 100%. That's pretty much impossible. But, you know, right now, it looks like the vaccine works quite well to prevent any symptomatic illness and very well to prevent people from getting severely sick, which is what we need a vaccine to do. Yes, yes, absolutely. I should say my parents got this vaccine yesterday, the AstraZeneca vaccine. It's being widely administered in Canada. It's being widely administered in Canada.

The bottom line is that it doesn't change the recommendations with respect to the AstraZeneca vaccine in Canada at this point in time. In the Dragon's Den, a simple pitch can lead to a life-changing connection. Watch new episodes of Dragon's Den free on CBC Gem. Brought to you in part by National Angel Capital Organization, empowering Canada's entrepreneurs through angel investment and industry connections. to hear. You may have seen my money show on Netflix. I've been talking about money for 20 years. I've talked to millions of people and I have some startling numbers to share with you. Did you know that of the people I speak to, 50% of them do not know their own household income? That's not a typo. 50%. That's because money is confusing. In my new book and podcast, Money for Couples, I help you and your partner create a financial vision together. To listen to this podcast, just search for Money for Couples. Going back to this issue of trust, there was some confusion here in Canada recently when the

vaccine was initially only available for those under 65. We talked about this on the show before. This is because there just wasn't enough data for people over 65. We talked about this on the show before. This is because there just wasn't enough data for people over 65 from initial trials. And now there's more data, and that advice has changed. So that's certainly one example here. But can you talk to me about some of the other issues, other examples that this company has come up against? What's the first one that comes to mind to you? Well, they had a problem early on in a trial that they were conducting in the UK. They accidentally underestimated how much vaccine was in some vials. There were two groups of volunteers who took part. The first group received two identical doses of the vaccine, but because of a manufacturing

error, the second group received half a dose and then a full dose of the vaccine. In some of the people who got, who were in the clinical trial in the UK, instead of getting a full dose of vaccine as their first of two doses, they got half a dose of vaccine. That didn't come to light for quite a long time. And the reason for it still is not 100% clear. The company says it was a mistake. The Oxford group, the researchers who devised the vaccine in the first place, they sort of didn't like calling it a mistake. They shied away from that and sort of implied that it was not a mistake, that they were trying to figure out different dosing schedules to see what might work. For whatever reason, it happened. And when it came to light later,

it became a real issue because, bizarrely, when they started to analyze data from three different trials, they found that this small subset of people, about 2,800 people, in an arm of the trial where people got a half dose followed by a full dose, the vaccine worked better in that group. And so, you know, people were scrambling to try to figure out why. And that has led to all sorts of questions. The fact that they had that accident led to some questions. The fact that they didn't disclose that accident for a while has led to more questions, you know. All along the way, there have been missteps, and a number of them have only come to light after the fact, and that hasn't worked well. And that is, this morning, raising and credibility when, you know, things come to

light afterwards. There was another incident, the company temporarily paused the UK trial because somebody who'd gotten the vaccine got quite sick. And regulators didn't know about it until they read about it in the news. And that's a real no-no. Right, that was in the fall. I remember, Helen, you know, people who are listening right now, what do you think they should make of all of these mishaps and issues? Like, you know, should they be concerned about the vaccine itself? Or does this really speak more to the company's handling of sort of the messaging around the vaccine? It speaks to the latter. You know, it is clear the vaccine works. How well whether it's 70% or 74%, we'll have a better picture in the next few weeks when all of the

data from the US trial comes out. But regardless of what number it finally hits on, this is a vaccine that definitely works well enough to be put into use and will prevent a lot of people from getting sick. And the fact that, you know, for example, like the trials had to be paused, could you not also see this as a good thing? You know, maybe it's not a good thing that that information wasn't communicated well, but is this not an indication of the system working too? It's absolutely an indication of the system working. Well, I think it's important to point out that that's the reason why you have various phases of trials. And then you proceed cautiously as you go forward. But it's really one of the safety valves that you have on clinical trials such as this. Vaccines are given to people who are healthy, so the bar has to be really high in terms of safety.

Sometimes drugs that are kind of toxic can be used in circumstances where people are very sick and the risk-benefit ratio points to use of a toxic drug. But when you're using something in effectively hundreds of millions, if not billions of people who are not sick, you really have to be certain that it's as safe as is possible. Doesn't mean that, you know, there won't be some rare side effects. But so far with this vaccine, millions, maybe tens of millions of people have received it. And there are some concerns, but at a very, very low rate. And for the vast majority of people, the benefit clearly outweighs any risk. You know, Helen, on that issue of safety, I do want to ask you about one more issue that I think

might be very top of mind for people around this vaccine. You know, it recently made headlines that, you know, several countries in Europe were pulling the vaccine temporarily because they were worried about this issue of blood clots. The vaccine was never pulled in Canada. Our regulator has felt comfortable with it. But can you tell me more about what happened here around the blood clot issue? So earlier in March, authorities in Denmark announced that they'd seen a couple of cases of strange clotting events in some people who had been vaccinated recently with this vaccine. Since then, Germany, Italy, Austria, Norway have also reported some cases.

Four more European nations, Spain, France, Italy and Germany, are suspending use of the AstraZeneca vaccine. The European Medicines Agency, which is the EU's equivalent of Health Canada or the FDA in the United States, has been conducting an investigation. They've urged countries to continue to use the vaccine. At this point, they say they cannot rule out the possibility that there is a link between receipt of the vaccine and these rare events, but the events are very rare. And in the EMA's messaging, what they've made clear is, you know, while there may be a low risk of this happening in somebody who receives the vaccine, the risk of contracting COVID right now in the European countries that are using this vaccine is high.

And in their estimation, the benefits continue to outweigh the risks. This news around the blood clots, does this surprise you? Is this something that you would have expected to see in any of these vaccines as they sort of roll out around the world? So I wouldn't have known necessarily to be looking for blood clots. Looking for blood clots, I certainly knew to anticipate that as a vaccine that's been tested in tens of thousands of people moves out into millions and hundreds of millions of people, you're probably going to see some rare adverse events that hadn't been picked up in the clinical trials. It's just a numbers game, frankly. You know, it's bad luck for the people from AstraZeneca, because they've already had a

number of other problems, and they don't need this on top of that. But it's not the first vaccine among the COVID vaccines to have been linked with a rare health risk. I mean, I think it was the first day, in fact, that the Pfizer vaccine was used in the UK, two nurses experienced anaphylaxis. And that was also seen with the Moderna vaccine. And now it's accepted that with the messenger RNA vaccines, there's a low risk of developing anaphylaxis after the vaccine. All the vaccination clinics have EpiPens at the ready, and they're watching people for 15 minutes after vaccination to, you know, catch any such cases if they occur. Right. So essentially, you're saying that it is possible that if they do find a link between the AstraZeneca vaccine and this very rare blood clot issue, then they could also find a way to identify and treat it. steer those people towards another one of the vaccines. People should really keep in mind that these events are happening at a very, very low rate, which is not true about COVID infections.

COVID infections are happening at a far too higher rate. And, you know, the risk benefit analysis still points to use of the vaccine. Okay. And, you know, like I said before, my parents got this vaccine yesterday. I will take whichever vaccine anybody could give me whenever it's available. So, Helen, thank you so much in the conversation. More tough headlines for AstraZeneca this week. The EU announcing tighter controls over vaccine exports with reports. The EU announcing tighter controls over vaccine exports with reports India... The company has been in the middle of this fight with the European Union, which said they'll stop the company from exporting doses to other countries

until they get what they were promised. The EU was supposed to get more than 100 million doses of AstraZeneca jabs by now, but they've only gotten 16.6 million so far. In a statement to the CBC on Wednesday, the EU said, quote, This is not an export ban. It is about making sure that Europe gets its due share of vaccines and inviting other countries to open up for exports. Ottawa says this won't affect vaccine shipments to Canada, but we'll keep you posted on that front. I'm Jamie Poisson. Thanks so much for listening to FrontBurner.

We'll talk to you tomorrow. Thank you.