番茄社区

In this video, Jeremy Faust, MD, editor-in-chief of 番茄社区, and Robert Califf, MD, commissioner of the FDA, discuss the end of the U.S. public health emergency and what it will mean for COVID care moving forward. Their conversation covers the continued use of boosters for the immunocompromised and elderly, the mechanisms of emergency use authorization (EUA), and creating equitable technology.

The following is a transcript of their remarks:

Faust: Hello, it's Jeremy Faust, editor-in-chief of 番茄社区. Today, we're joined by Dr. Robert Califf.

Dr. Califf is a cardiologist and a member of the National Academy of Medicine, and this is his second stint as the commissioner of the FDA. Dr. Califf, thanks so much for joining us today.

Califf: Hey, good to be here.

Faust: Let's jump right in on what's top of mind for so many readers and viewers, which is spring boosters for COVID-19. For the immunocompromised, I think increasingly this is the area of importance, and in older populations as well.

Will the FDA reconsider a spring booster, and what would it take to trigger that kind of reassessment? You've got the U.K. and Canada going forward, Israel is studying this very carefully, is it too late?

Califf: Let me just make a couple of points first. I'm glad people are interested, because I've recently had several conversations with people who have been studying the history of pandemics, and there's this thing called "amnesia" that comes into play. It's where people just don't want to hear about it or think about it when they're in [quiescent times] -- thank goodness we're in this relatively quiescent phase, but it's good that people are interested.

It's not too late. We're looking at all the data coming in and as soon as we have the evidence that we need one way or another, we'll make a decision and let people know. We're not quite at that point yet, but you know, we're aware that people are interested. I'm 71 years old myself, and I'm 7 months out from my last updated boost. So, it's very much on our minds here at the FDA.

It's not like we go months without looking at anything, it's for people that work in the Center for Biologics. There's a group that is looking at this every day, and across the administration, of course, Dr. Jha is always very interested in what we're doing.

Faust: How fast can these things move? We just came off this pandemic period where things were moving at a lightning pace, and during the normal times that's not the usual pace. I feel like we're sort of in between here. It's early April right now, how quickly can the FDA come and say, "We did see some new data. Let's go ahead and do an every-6-months booster or even more often for the immunocompromised," [is it] May, June? What kind of timeline are we talking about?

Califf: Everybody always wants to know the timeline, and I appreciate that. I would just say that the machine is well-oiled and when it's time to make the decision, we can make it quickly. I can't really put an exact timeline on it because we never know what new data may come in. Everyone around the world is following the course of both the pandemic and of the impact of vaccination on outcomes.

You know, so far I think it's beat expectations so much more than I ever thought, with this dramatic reduction in death and hospitalization for those that are up-to-date. So it's quick once the decision is made, and we're constantly looking at the information.

Faust: Does the end of the public health emergency, the PHE, affect the lever of the EUA pathway, the emergency use authorization pathway, for these particular vaccines?

Califf: It doesn't. Those go on separate tracks. Obviously they're related in some ways, but we still have the authority for EUAs in place.

Faust: And what about for totally different areas with EUA? For example, if there were to be a new treatment for long COVID that came out and the public health emergency is over, what's the apparatus? Is it still the same apparatus or is it not a PHE anymore, so back to the old way?

Califf: Well, that's an interesting question, and I think the answer to that is it probably all depends.

The authority is still there, but we want to be careful not to use it unless it's needed because we've got a lot of other therapeutics and other diseases that are taking a toll. I'm sure you're aware that the life expectancy in the U.S. is dropping right now, and not just due to COVID.

So I feel like we have all the tools we need if we need to move quickly to do it, but we want to be careful in the use of that authority.

Faust: One more question about the EUA pathway. I think it's been very successful. I mean, there's no argument there. We've seen some really big wins with this pathway during the pandemic.

But one thing that I think is interesting is that these are not FDA-approved drugs, right? So you can't just use them off-label, and academic or investigator-initiated trials aren't really possible, right? If Pfizer doesn't want to give you Paxlovid to study, you can't study it, you can't do a randomized controlled trial because you can't just go to your pharmacy and dispense the drug.

Do you think that the EUA pathway can be refined in a way that can actually allow investigator-driven studies to be done more quickly in the future?

Califf: Well, I think the reauthorization of the Pandemic Preparedness bill is up this year, and I think there'll be a number of fine-tuning efforts with various approaches to the pandemic, including this one.

I do think, though, that it is entirely possible to do trials in this situation. After all, the government with the vaccinations, for example, bought a huge stockpile of vaccines. So it's not that you can't do the trials, it is just the mechanism is a bit different.

You know, Jeremy, you brought up the investigator-initiated studies. I'm all for those. I've spent 35 years in academia, but I think we'd be a lot better off if the investigators worked together and did trials that were large enough and coordinated enough to actually answer the questions.

There's a phrase that Janet Woodcock had coined in an interaction I was involved in with the NIH a few years back: the SCT, the "." There's a real place for small trials when they're well done, but we need more trials that answer the critical therapeutic questions definitively, and that is a major effort that we're thinking a lot about right now.

Faust: STAT News reported that one of the reasons the FDA is less interested in [things] like interferon lambda, this is the done overseas, is because it wasn't an industry-funded U.S. study. Is that true?

Califf: No. We don't care who the sponsor of a study is. What we need is good data, a well-designed study, and someone putting in an application who can actually manufacture the product and distribute it with the kind of quality that's needed.

I think sometimes the academics forget about all the rest of what has to go into getting a drug distributed. It's not just a clinical trial result. You have to have a manufacturing facility, you have to pass inspections, you have to have a distribution mechanism. There are many, many other aspects involved in a drug application other than just the clinical trial.

We have nothing against data coming from foreign countries if the studies are well done. I personally in my career mostly did multinational clinical trials where the U.S. was not the major enroller in most of those trials because we're only 4% of the world's 8 billion people. You wouldn't expect the U.S. to be the major enroller in global studies.

So, no, I think there are a lot of myths out there, but hopefully this will clarify some of it.

Faust: That's very helpful.

I'm also interested in reciprocity in general. We have our own FDA, and it's probably one of the greater regulatory bodies in the world on this question. But when you look at Europe and other parts of the world where they have many, many more rapid tests for COVID, and now even one of my readers talks about the 4-in-1 that they've gotten in Europe, where you have both flus, RSV, and COVID all in one point-of-care test.

Should there be a reciprocity pathway for something like an inexpensive point-of-care test? That seems to me like low-hanging fruit. Why have all this infrastructure devoted to a question when we're already on the 10-yard line, first in goal, let's get it out?

Califf: I really think, Jeremy, that that's a little bit of misdirected thinking. I mean, if someone has developed a test and they've done the studies to demonstrate that the operating characteristics of the test -- sensitivity, specificity, predictive value numbers, and hopefully even the operating characteristics measure beyond that -- and they've submitted it to a regulatory agency in Europe and it's been okay, it's not a hard deal for them to come to the U.S. and just submit their data.

That's all we really are saying. You don't have to redo the studies if they've been well done and they're in a representative population and meet all the quality characteristics.

I'd also say that in general in Europe, it's not that there are a whole bunch of more tests that are actually being used. In fact, I think one of the characteristics of countries that may have done a bit better with testing than we did in the U.S. is that they focused on a smaller number of overall tests, but made sure that they were used by a much larger proportion of the population. I mean, we've ended up with a lot of tests in the U.S. You're probably aware that early on there was a period where it was perhaps too restrictive and then a period where the gates were open and a lot of tests turned out not to be so good and had to be reigned back in.

If you have good data, bring it. We're wide open to look at it.

Faust: Yeah. I think early on the antibody tests were really problematic. For the antigen tests, I think it feels like a lot of companies applied and only a few got it. But there seems to be a big public demand for this moving forward, not just for COVID, but for flu or strep or RSV. Do you see that market expanding?

Califf: I think at-home testing is going to be a huge area. The only part of it I'm really concerned about -- again, if people develop good tests, do good studies, advertise what their operating characteristics are in a way that people can understand it, it's going to be really good -- but I'm worried about equity here.

You said inexpensive. To someone who's in the lower half of incomes in the U.S., buying a test in the drugstore is not a minor decision. So we really have to think about how all this is going to get paid for in a way that leads to equitable availability. Because I would argue that the people that are going to benefit, who should benefit from it the most, are those who are in the working class and have to go to jobs and take kids to school, not those of us who are professors.

There's a from The Atlantic that Ed Yong wrote, "Technological solutions drift into society's penthouses; diseases seep into society's cracks." I'm not worried about the technology, I'm not worried about evaluating or having a market, I'm worried about equity when it comes to the use of this technology.

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