Intro. [Recording date: May 8, 2024.]
Russ Roberts: Today is May 8, 2024, and my guest is oncologist and Professor of Epidemiology, Vinay Prasad, of the University of California, San Francisco.
This is Vinay’s fifth appearance on EconTalk. He was last here in August of 2023 talking about cancer screening. Both of his 2023 appearances made the top 10 of your favorite episodes of last year. Vinay, welcome back to EconTalk.
Vinay Prasad: Russ, thank you for having me, and it’s such a treat to hear that, that the listeners liked those episodes.
Russ Roberts: Yeah, they were awesome.
1:08
Russ Roberts: Our topic for today is the COVID vaccine, and in particular recent paper of yours in the Monash Bioethical Review co-written with Alyson Haslam that we will link to. The title of the paper is “COVID-19 Vaccines: History of the Pandemic’s Great Scientific Success and Flawed Policy Implementation.”
Before we dive in, I want to observe that it remains surreal to me that the very issue of vaccines has somehow become a huge area of discussion, a lightning rod. Much of it seems to be, if not fact-free, cherry-picked by lots of average people–not experts–but some experts, too. Somehow it’s become such a big issue. Does this seem strange to you? Could you have imagined this drama in advance of how it has played out? If someone said to you, ‘Well, you know, it’s going to be really controversial and people are going to lie and exaggerate and ignore key facts,’ is that strange to you?
Vinay Prasad: It is strange to me, Russ. You know, there’s something about vaccines that has captured people’s attention and interest and perhaps even ire for–in the last 30, 40 years.
There’s long been a movement, I think, in America and globally skeptical of vaccines, particularly childhood immunization, and maybe that has something to do with the fact that it’s injected. If they were all tablets, that might have been different, you know. Maybe it has something to do with the fact of the age with which these vaccines are typically administered. For whatever reason, I think it has captured some small group of people’s interest for a long time.
But, the COVID-19 pandemic, I think, naturally expanded that group. I mean, naturally, we were making policy decisions and scientific decisions–which we are going to talk about today–some good, some not so good; some self-inflicted wounds, I think, by policymakers. Some mistakes were made. And I think that naturally was just pouring kerosene on something that had been smoldering for a while, which is a skeptical anti-vaccine sentiment.
But, you’re totally right. There’s so many things we do in medicine that don’t capture people’s interest, like giving kids Tylenol or acetominophen, giving kids ibuprofen or something–that when they are sick–or all the things we do, pediatrics. But for some reason, vaccines has always gotten people’s attention.
Russ Roberts: I think you’re right about the injection part. And, I think it’s important to point out, or at least clarify–tell me if I have this right–traditionally, vaccines are an example of the dose makes the poison. Right? You get a little bit of the disease, and it mobilizes your body’s natural immune system to fight the recurrence.
And yet, this vaccine–there are different variations of it for COVID–but the most important ones were not of that nature. Correct? And therefore, you weren’t giving yourself a dose of the disease. You were doing something else, it turned out, that may have been challenging. But it didn’t have that emotional, I think, unintuitive, for maybe people, idea that, ‘Hey, give yourself some disease for your own good.’
Vinay Prasad: Yeah. It’s a really interesting observation. I think you’re right that, you know, as far back as the days of Edward Jenner, vaccines have always been either a weakened version of the virus, a weakened cousin of the virus, a weakened viral strain or a lower dose–something to expose you to what was potentially harmful without the harm, so that you would build immunity so that when you came across it in everyday life you would have some resilience against it.
This vaccine, in a number of ways, is different, of course. I mean we’ll talk about–there’s a couple different platforms. Johnson & Johnson and AstraZeneca, which actually was withdrawn from global market yesterday, are both adenoviral vector vaccines using DNA [Deoxyribonucleic acid].
And then the novel–the most novel–formulations were the mRNA vaccines of Moderna and Pfizer, and those are probably the ones that have maybe created the most, I think, discussion, perhaps because they are new. But, also, there are some concerning safety signals across all these products. Oh, and I used that jargon again, so maybe you are going to want to unpack that.
Russ Roberts: Right. No: You unpack it.
Vinay Prasad: Safety signal. Russ and I were just talking before, and he said, ‘In your guys’ line of work, when you say safety signal, what you mean is there’s something concerning there. It’s a harm.’ And actually, yes, that’s what we mean.
I think typically, we refer to these things as safety signals when you discover some untoward adverse event, something you didn’t expect, you didn’t want linked to these vaccines.
And those really do play an important role in policy. And I think the big policy blunders around COVID-19 vaccination were not taking those signals serious enough, fast enough, and not acting upon them. So, we can get into that.
6:14
Russ Roberts: Let’s start with the opening line of your paper, quote,
The COVID-19 vaccine has been a miraculous, life-saving advance, offering staggering efficacy in adults, and was developed with astonishing speed.
That is the good news, and it is certainly is an opening–close quote; before that, before I said, ‘That’s the good news.’
That certainly is an answer to anyone who might say, ‘Well, Vinay Prasad is anti-vaccine.’ You’re not anti-vaccine. And so, talk about what was impressive and good about this rollout.
Vinay Prasad: Yeah. And I think that this is something that–I frame it intentionally this way because I think it’s the truth. I think this is something that people don’t fully admit. One, President Donald Trump launched Operation Warp Speed, which was a sort of economic [?incentive?] program to expedite these vaccines to market. And what the government did was offered to essentially incur the risk of all the pharmaceutical firms: ‘We will aid you. We will provide guidance, and we will sustain any losses you take if these vaccines are unsuccessful.’
That coordination, I think, was remarkably successful. Even the optimists weren’t bullish enough at the speed with which the vaccine could be developed and deployed. We had a positive press release for the Pfizer and Moderna vaccines in November of 2021. And keep in mind: In January, we were barely starting to sequence the virus itself. So, all within one calendar year. I think that’s a remarkable story about vaccine development.
And the next point I want to make is–and this is something that I think is really sort of clear from the evidence–is that if you were a 70-year-old person, an 80-year-old person, a 60-year-old person with medical problems, if you had not already had COVID-19 and you got that vaccine in January of 2021 where millions of people globally did, that vaccine remarkably lowered your risk of severe disease and death from COVID-19.
And we know that because the randomized controlled trials [RCTs], particularly the one by Moderna, showed a huge reduction in severe disease from COVID-19 from having received the vaccine.
So, I think there’s some extreme skeptics out there who say, ‘The vaccine did more harm than good in all age groups. The vaccine was a scientific bungle.’
It saved many lives. Some of the estimates, I think, are maybe misleading. Maybe there are estimates that are kind of speculation.
But, there’s no doubt about it: If you were an older un-immune person and you got that vaccine in first quarter of 2021, you had a remarkable reduction in severe disease and death as a result. Certainly, randomized trials have shown the severe disease part, and some observational data has shown the death part. That’s a very good thing.
And it did aid in ending the pandemic. By that I mean, COVID-19 will continue to spread. It didn’t stop the spread. We can talk about that. There’s some policy errors around the messaging around that. However, it remarkably reduced the death toll, and there are many people alive as a result of these vaccines who otherwise would not be had we not developed them.
9:20
Russ Roberts: We interviewed Gregory Zuckerman on his book about the creation of the vaccine, which we’ll link to. I’ve talked about how–I think I was 65 when the vaccine came out, or maybe 66. I think 66. And of course, I was over 65. Which meant I had a higher risk of COVID! Which, it’s one of those weird things where it’s really not discrete. It’s a continuous effect, and it also depended a lot on your general health. I was generally healthy. While, as listeners know, a little more heavy than I wish I otherwise were, I don’t have the worst kind of comorbidities that COVID-19 wreaked havoc with.
Despite that, at that point, most of us were living in what felt like the Middle Ages and the bubonic plague. We felt danger all around us. I remember vividly going to the grocery store and putting my hands in Ziploc bags that I brought from home, touching on the handle of the cart, going through the groceries. I remember with horror when the cashier helped me bag the groceries with unwashed, unknown hands touching my cans, and probably washing them in the early days.
And when I got that first dose, as I’ve said here before, I felt like Superman. I felt like–other than kryptonite, which I didn’t think was around–I had suddenly beaten the demon of COVID. I did occasionally remember I was still mortal. But I felt immortal there even with only one dose.
So, it was a remarkable and I think generally a wonderful thing. So, what’s wrong? That’s all great. What went wrong?
Vinay Prasad: Well, many things went wrong. I think that’s all the good stuff, and I think it’s important to acknowledge the good stuff as we get into the things that we did wrong. Because I think there are some people who are quick to dismiss criticism of the vaccine in any form as a blanket sort of anti-vaccine sentiment, as you articulated.
Now, what are the things we got wrong? I mean just a short list.
One, the rhetoric around whether or not the vaccine could halt transmission was incorrect and misleading.
Number Two, in the randomized control trials that led to vaccine approval, we could have explicitly tested whether or not the vaccine slowed or halted transmission. We did not do so.
Number Three, we started really well with older, un-immune people, but we quickly made the mistake of extrapolating our vaccine advice to people who had already had and recovered from COVID-19, an extrapolation that lacked evidence. An extrapolation that ran counter to a longstanding medical tradition of thinking that having had and recovered from a disease does confer some sort of durable immunity, particularly against the severe manifestations of that disease. So, we extrapolated that advice incorrectly.
Number Four, we pushed this in younger and younger populations, often using the brute force of the state and the schools to mandate this. Even into populations where the risk and benefit balance were more tenuous and uncertain.
What am I–Number Five, we started to discover safety signals. In other words, there were harms of this vaccine. We–the governments–were reluctant to admit those harms. They delayed interrogating those harms. And they failed to act upon those harms. And those harms did not fall equally across the age distribution. In many cases, those harms fell disproportionately among the people with the least to gain, the youngest people.
One of those harms is inflammation of the heart, myocarditis. That’s a harm that particularly affects young men between the ages of 16 and 22. The risk of that was massive. The Israeli experience–which we can talk about–where the first estimates were 1 in 3,000, in the second dose of the mRNA vaccines, that risk of myocarditis far exceeded the potential benefit of those doses on severe disease.
So, in other words, that’s a roundabout way of saying I’m fairly confident, for some populations, we actually started to inflict a net harm on these groups of people by recommending and mandating dose after dose after dose.
And then, the last thing is children. I think the evidence is quite weak, particularly children who have had COVID-19.
And then, finally, the benefits of an annual or biannual, perpetual vaccine policy, which is in the United States right now–we have essentially an at least once a year, possibly two times a year in certain age groups, vaccination for COVID-19 in perpetuity till the end of time. What’s the evidence for that?
And so, this paper, which is a very lengthy policy paper, about 22 pages, talks about all of this stuff.
And then, one last point I want to make: It talks about all that stuff. But, the last point I want to make is we should talk about the initial vaccine approval. It came out after the election. Why did it come out after the election, not before the election, when Trump was saying it was going to come out before the election? Was that based on science or was that based on politics? And I think that’s the first, most provocative part of this paper. And I think that’s a very–your listeners might find that interesting.
14:47
Russ Roberts: Yeah. Let’s go back to the first thing you mentioned, the transmission. It’s a classic argument in economics. The technical term is externalities, the idea being that if you don’t vaccinate, you’re imposing costs on people who might have very high costs of getting vaccinated themselves relative to yourself; and therefore, even though it’s your risk and your life, you might be exposing others to the dangers of the disease–others who cannot protect themselves or who the cost of protecting them is very high for health reasons.
And this argument was made over and over again, in the early days of the COVID-19 vaccine: That a mandate was, as you argue, the argument was it was ethical. It was justified. Because, you needed to help old people–and potentially children, although here in this case it wasn’t true. But, the argument, say, in other vaccines would be: Well, you might think, well, it’s just up to you. But, no, if you don’t vaccinate, you’re risking[?]–you’re putting elderly and children at risk who–where it’s very costly to vaccinate them, health-wise cost.
And, you argue that’s not true. Was that true at the beginning, or just when the Omicrom variant came out?
Vinay Prasad: So, I think the Omicrom variant, which really sort of came out by the fourth quarter of 2021, clearly had vaccine escape–i.e., that no matter how many doses you’d gotten in the past, you could get Omicrom through that and you could spread Omicrom through that.
However, it was known as early as the summer of 2021 in the United States, from places like Provincetown, Massachusetts, where they had a sort of annual gathering of many men, 97% of whom had been vaccinated, but many of whom came down with COVID-19, that even some of the earlier strains could spread despite vaccination.
So in other words, I think we knew pretty early on that vaccinated people could get COVID-19 even after being vaccinated. That the vaccine would not be able to halt transmission.
But, I want to make one more point about the trial.
One of the points that I think we don’t talk enough about is that all global economies are put on hold. I mean the pandemic has, as you say, it was like living in the plague. I mean, it has changed the lives of so many people. Governments are spending tens of trillions of dollars globally on pandemic economic relief and on the sequela of having diminished economic productivity. In other words, this is a huge global event.
We run the randomized control trial, and it would not have cost them much more and it would have been infinitely logical to do the following: In this Pfizer study, I think 40,000 people, we divide them in two groups. Half get the vaccine. Half don’t. And we measure how many of those people feel like they have symptoms of COVID-19; we test them for COVID-19. That’s the study design.
The study could have also been powered and designed to look at things–I think some of the critics are correct–to say, ‘How come you didn’t run a study in older people and actually look at all-cause mortality as an endpoint?’ Could have done that. They could have run a different study in just over age of 80, and the endpoint could have been all-cause mortality.
And how come you didn’t take your big study and basically say, ‘Out of these 20,000 people in one arm, we’re going to say we’ll sample 5,000 people and test every one of their family members every week for COVID-19 to see does it actually slow the spread? Not only are they less likely to get COVID, are they less likely to spread it to their family members?’ And you could have analyzed that in a randomized study. And it would have cost a little bit of money. But, in comparison to what we’re spending on this, it’s literally a drop in the ocean.
That, to me, is a missed maneuver. [More to come, 18:29]