"Don't Use This Thing in Pregnant Women!” - NIH Director Dr. Jay Bhattacharya

There's a clannishness, a closed-mindedness at the center of government that has as its premise that the government knows best and the plebs don't. It's a very anti-democratic thing, especially in public health. I think that there is a legitimate role for government to play in the context of pandemics. But if there's not some capacity to criticize the government from the outside, to identify government failure when it does exist, then the government's going to fail and fail badly, which is exactly what we had during the pandemic.

You know, it's funny, because pivot into vaccines from here.

In I think it was like 2016, 2015, right before the Obama administration expired, there was a bipartisan approved law called the 21st Century Cures Act that actually made it easier to get drugs approved inside the FDA. Rather than show efficacy, meaning I have to show that my drug saves lives, I can show that it just produces antibodies or something. It can have intermediate endpoints and gain approval. Faster track approval for drugs that have a big, big use. I think that's not an unreasonable thing to ask for. But there has to be a flip side to that, which is that if you have approved a drug relatively quickly and you're actively looking for side effects and warnings, you very rapidly say, 'Look, don't use this thing in pregnant women. Take this drug off the market because it's killing people in ways that we can't control.' You have to have both parts of the equation for the public to actually be protected by this agency. Ultimately there's uncertainty. Neither the regulator nor the drug company nor the public knows exactly what this drug is going to do. You learn by people taking it. And if you can take it in systematic ways like in randomized trials, you're liable to learn quicker than if you don't. After you've approved it, you need to be looking. There's never going to be a perfect solution because at the heart of it is we're not God. We don't know exactly what this drug is going to do for every single human being. Doctors practice an art because whatever you give somebody, there may be some harms and some benefits and you're hoping that the benefits outweigh the harms. And the knowledge a doctor has for a patient allows them to tailor the message so that it's a combination of the science around the thing you're telling the patient to do and the reality, the story of the patient themselves. It's a complicated thing. There's no omnipotent God sitting in the room of Tony Fauci that allows him to know the difference between a good safe product and an unsafe product, or the FDA. So, you have a difficult problem.

What's happened with the capture of the agencies, and I didn't really understand the capture until the pandemic, is that the pharmaceutical companies first, they pay for a lot of the activities of the FDA. That's legal. There's a law called the Prescription Drug User Fee Act that allows drug companies to pay for the activities of the FDA. The 21st Century Cures Act and other regulatory reforms have made it much easier to get drugs approved. And I worked with the FDA for a decade on safety before the pandemic. It's very difficult. The FDA scientists are very conservative to call a drug unsafe, to issue a black box warning. It takes a lot of evidence, a long time before they're willing to do that. Much more conservative than I think they ought to be. And so, it's just very, very unbalanced. And you saw this during the pandemic. With the vaccines, I think it was a reasonable case to make that the vaccines ought to have been recommended for older people, even though the randomized trials themselves did not check to see if it prevented you from dying. That was not the primary endpoint of the trials. It was reasonable to say, 'Look, it prevents you from getting symptomatic illness. And for older people, getting symptomatic illness is a really high risk of dying.' And so therefore, the benefits of this, even though we don't know all the full set of side effects, are likely to offset whatever potential harms there are to older people from taking it.

Yes, that's correct.

The key thing is that it's not that deadly a disease. Point two percent, two out of a thousand. So, you would have had to enroll a million people in order to address the question, what does it actually prevent you from dying? Because you need to have in a randomized trial, you have one arm that gets the vaccine or whatever the drug and one other arm that doesn't.

Exactly. And so, if you have a very rare event, you need a very large number of people to get a sufficient number of those rare events. I'll just give you an example. The trial to demonstrate the effectiveness of the polio vaccine that Jonas Salk ran in the '50s, it enrolled something like 1.8 million children. Because paralysis after polio infection was a rare outcome. So, you needed a very large sample size. The trials as they were constructed, instead of having mortality, which is a rare outcome, it had prevention of symptomatic infection, which was not a rare outcome. You could then get away with enrolling only 40,000 people for the trial rather than a million or two million people. So, we knew in December 2020 that it would prevent you from getting symptomatic infection for two months. Why only two months? Because we're in the middle of a pandemic, people really want the vaccine. I would love to have had a much longer trial, but you can understand why they would do it for a relatively short period of time.

Okay. So, 40,000 people sounds like a lot of people, but then when you recommend that 300 million people take it or 2 billion people take it, you're going to find side effects that were not in the trial of 40,000 people. Because 2 billion is so many more people than 40,000. And you're going to find things.

It is. It's an incredibly complicated problem, especially since people are different from each other. On genetics, yes, but in terms of the way they've lived their lives, a million different ways. This is why medicine will always be an art. There's always the question of is the person that you're seeing as a doctor different than the person that was enrolled in the randomized trials? You have to apply the result of the studies, which is an average for a population that's typical for randomized trials, to the person that the doctor is seeing. It has to be tailored, and there's always going to be uncertainty, and there is no way around that fact. Nothing AI, nothing will ever get around that fact. It's just propaganda of medicine to pretend like we've solved that problem. It's an unsolvable problem. It's always going to be an art.

That's a tough question. Let's just stick for right now with the COVID vaccines. If there had been an open discussion allowed around it, it would have been very clear, I think, to most doctors and most parents that the benefit of the COVID vaccine for young people, especially children, was very, very small. Why? Because the mortality risk of dying from COVID for children was very, very small. You reduce a small mortality risk to an even smaller mortality risk, you're not getting very much benefit. That is enough to say that any possibility of side effects in that group would lead you to say don't use that product in that group.

In fact, Martin Kulldorff and I wrote an op-ed in The Hill, I think, in April 2021, recommending against younger people taking the vaccine with exactly that reasoning. There was evidence coming out already around then that young men especially got high rates of myocarditis and heart inflammation when they took the COVID vaccine. And so the question then is what benefit is there to my child from taking it? That's the first question. If it's potentially large, then you want to consider it. If it's not potentially large, then you want to be more careful about it.

The flip side for the older population, there's a much higher risk of dying and you're reducing the risk of getting sick with the disease, you're probably going to have a much wider range of how much benefit there could be and you're going to be willing to allow there to be, I should speak for myself personally. If I'm going to gain a lot of benefit in expectation, I'm going to be willing to take some risk. I'm going to allow there to be some potential harms, especially if they're low probability, and I'll still take the thing because I expect to have more benefit than harm. So that's the basis of the recommendation for older people to take the vaccine. If somebody tells you that there's a uniform risk, you know there's not a uniform risk. If somebody exaggerates to you the nature of the risk on either side, the taking the vaccine or not taking the vaccine, and you can get a sense of are they alarmist? Are they reasonable? Are they balanced? Are they accounting for other people disagreeing with them? What do they have to say about the people that disagree with them? Then you should be very careful about believing them about the nature of the risk that they're trying to evaluate for you.

So let's just stick with myocarditis and then we'll talk about long COVID. The calculus around myocarditis is really interesting. COVID can cause myocarditis. It did cause myocarditis in people, absolutely. The question though isn't the relative risk of myocarditis for COVID versus the vaccine. The question is if I take the vaccine, what's the marginal impact on my likelihood of getting COVID? And what's the marginal impact on the likelihood of getting myocarditis if I get COVID? Marginal meaning if I take it versus if I don't, what's the change in the likelihood of getting COVID? It turns out that it prevents you from getting symptomatic infection for two months, but that declines very sharply after just two or three months. So it doesn't really prevent you from getting COVID. You're very likely to get COVID afterwards.