Rebekah Gee: Improving Health, One Family at a Time

Harlan Krumholz: Welcome to Health & Veritas. I’m Harlan Krumholz.‌

Howard Forman: And I’m Howie Forman. We’re physicians and professors at Yale University. We’re trying to get closer to the truth about health and healthcare. Our guest today is Dr. Rebekah Gee. But first we like to check in on current or hot topics in health and healthcare. What do you got, Harlan?‌

Harlan Krumholz: Well, Howie, how could I not talk about the biggest story in medicine over the last week? Probably the biggest story in medicine in a long time, and that’s saying a lot because things are happening every week that blow my mind. And I really think it might mark the beginning of a whole new era. It’s about a baby named KJ, born with a devastating and often deadly genetic disease, who became the first person in the world to be treated with a personalized, CRISPR-based gene editing therapy. And here was a kicker. This is what really I thought amazed me was that the treatment was developed in just six months. So if you don’t mind, let me just walk through this a little bit and then we can talk about what—‌

Howard Forman: And do spell out CRISPR for people, ’cause I think a lot of our listeners probably even hear “CRISPR”... I hear “CRISPR,” and I forget what it stands for. Just remind them what it even stands for.‌

Harlan Krumholz: Yeah, yeah, yeah. So let me get into this. So first of all, this baby was born with a rare and severe disorder that basically meant that his body couldn’t properly eliminate ammonia, a byproduct of protein metabolism, and ammonia, the reason that we’ve got, most of us, almost all of us I guess, except for people with this problem, can eliminate ammonia, really get rid of it, is because it’s toxic to the brain. And without treatment, babies with this condition can suffer severe brain damage. And often these people die within weeks after birth. And even with current treatments, which involve extreme dietary restrictions and modifications with medications, about half of the affected infants die very early in life.‌

So in this case, this baby’s doctors, they were researchers at Penn Medicine and CHOP, Children’s Hospital of Pennsylvania, one of the leading children’s hospitals in the world, led by a really remarkable physician, Kiran Musunuru, and Dr. Rebecca Ahrens-Nicklas, they really decided to try something radical, ’cause the alternative was just awful. They used this CRISPR tool, which is really an editor for the DNA to fix the mutation in this baby’s liver cells that were causing the problem. And this wasn’t a one-size-fits-all therapy. It was custom-built for this one child. They identified the mutation, which was a nonsense mutation, which means within a string of DNA that was supposed to produce a protein, there was something which caused the protein not to be produced properly and it’s called a nonsense mutation, ’cause it really ends up producing nothing useful. And they developed a personalized base editor that was designed to correct that exact error in the DNA.‌

So here’s the thing. You can have this problem because of many different mutations that cause the proteins, which will end up metabolizing the ammonia not to function. So they went and found the exact thing that was causing the problem and they basically put together something that was going to go in and fix that exact problem. And then to deliver it, they used what are called lipid nanoparticles. Think of them as microscopic delivery vehicles loaded with mRNA encoding this editor and a guide to the specific place of that mutation. So they’re basically transporting this thing that’s going to go in, this is all occurring at molecular levels, but it’s a fix-it kit and they’re delivering it to the DNA and then they’re basically fixing that one single mutation that’s a problem, first at a low dose at seven months of age and then a higher dose three weeks later.‌

And then, what was the result? In the seven weeks after the treatment, the condition stabilized. Baby was able to eat more protein and needed less medication to control the ammonia levels. And despite going through multiple viral infections during that period, the kid was doing so much better.‌

Howard Forman: The point about the viral infections is important, ’cause I think they point out that it’s when you have these viral infections that your ammonia levels would usually shoot up and you’re heading down the wrong path.‌

Harlan Krumholz: That’s right. So these infections are usually catastrophic and they cause a crisis, just as you said. And because he’d been treated in this way, he was able to manage them and there were no serious adverse effects of this thing. Liver enzymes rose temporarily but then normalized, and they didn’t do a liver biopsy. It’d be kind of risky for the baby, but all the biochemical signs showed that the gene editing had worked. It’s not exactly a cure yet, and he still needs monitoring, but they did what seemed to be impossible, that this kid is gaining weight, hitting developmental milestones, and eating foods that would have been unimaginable for him to be able to eat if he had this condition.‌

Howard Forman: Now, two other things about this story that I just think are really exciting are it’s not just about this one disease, because there are literally millions and millions of people with rare, rare diseases, some of which we may not even understand right now, that potentially could be cured in the not-too-distant future using the exact same paradigm. And then the other thing is that the FDA is much more amenable to using a single case like this and of one study to advance the approval process. So we’re moving, as you said, so much more rapidly right now toward cures for diseases that would seem impossible even 10 years ago.‌

Harlan Krumholz: Right, so people are going to remember stuff from this particular episode, this historic moment was one, first, the speed that they were able to do it. Second, they used a platform approach, which meant that the base editor and the delivery system stayed constant. Only the actual fix-it kit changed so that they could use it, as you said, for a wide variety of other mutations. And it’s a proof of concept of this, what we call “N of 1” medicine—truly personalized interventions for individuals with ultra-rare diseases. And there are more than 7,000 rare diseases affecting hundreds of millions of people that are caused by mutations that in principle could be fixed by this sort of gene editing. Of course, there’s lots of challenges ahead, cost, scalability, regulatory hurdles, safety, and durability, all these things.‌

Howard Forman: But this is huge.‌

Harlan Krumholz: But I think people will remember this as being a really critical juncture where things kind of changed.‌

Howard Forman: We’ve talked about CRISPR for over 10 years now, and the first version of CRISPR was really bombing in a few different ways, and people were playing it down. Now, the sky’s the limit in the opportunity.‌

Harlan Krumholz: Yeah. Well, how great for this family. But again, yeah, lots of things still to go. But little fix-it kit and a little molecular package went in and seemed to have done what it was supposed to do. The kid’s doing much better. Amazing, just amazing.‌

Howard Forman: Yep.‌

Harlan Krumholz: It’s a great time to be living, Howie. It’s a great time to be living.‌

Howard Forman: I agree. There are good stories.‌

Harlan Krumholz: Okay, let’s get to Rebekah, who’s also a great story. She’s doing great work, and this is going to be an interesting segment.‌

Howard Forman: Dr. Rebekah Gee is an obstetrician-gynecologist, OB/GYN and the founder and CEO of Nest Health, a value-based healthcare company that delivers in-home and virtual care to whole families. She served as Secretary of the Louisiana Department of Health from 2016 to 2020 where she led the expansion of the state’s Medicaid program and developed a subscription drug payment model for hepatitis C medication that enabled Louisiana to provide unlimited access to the treatment for its Medicaid and incarcerated populations. From 2020 to 2022, she served as CEO of Healthcare Services for Louisiana State University, where she continues to serve as a professor of public health and medicine and is an elected member of the National Academy of Medicine. She obtained her bachelor’s degree in American History and her MPH in Healthcare Policy and Management from Columbia University before obtaining her MD from Cornell. She then completed her residency in OB/GYN at the Brigham and Women’s Hospital at Harvard before completing her Robert Wood Johnson Clinical Scholars Program at the University of Pennsylvania, where she also obtained her master’s in Health Policy Research.‌

I will say for those of you that have listened to her on our last podcast, Harlan and I have pointed out that we came very close to getting her to Yale, but not quite close enough.‌

Harlan Krumholz: So close, Howie. So close.‌

Howard Forman: But she does have most of the Ivy League within her grasp.‌

Harlan Krumholz: She knows how much we admire her and how much we believe in her.‌

Howard Forman: Absolutely. And as a second-time guest, we get to really follow up on so many of the topics that you brought to us three years ago. It’s been three years and that is the journey of Nest Health. So I want to start off by giving you an opportunity to talk about what that journey’s been like. You are a true, not just an entrepreneur, but now you have a full enterprise. I looked at your website today. It’s an extremely well-developed website. You have real offerings, you have real contracts. Tell us about Nest Health.‌

Rebekah Gee: Well, Howie, the only thing that background tells you is I couldn’t get a job. Who would get four Ivy League degrees? Just because I was unemployable, so I had to keep getting degrees. No, but thank you for that lovely introduction. So it’s great to be with you. I love you and Harlan, I long admired you both and your work, and you’ve mentored countless of my colleagues and others. So thanks for having me. And it’s great to be virtually at Yale. I love Yale. I am excited to maybe come in person soon and enjoy meeting some of your students.‌

So the Nest story is a really exciting story. You’ve heard a little bit. I’m a practicing physician, in fact, I have clinic this afternoon. So I see women and take care of them. I have been in a variety of roles to improve and advance women’s health as a health services researcher, as a policymaker, and running an academic health center’s health system, all of that. But I really coming out of all of that had an opportunity to start a new company and I looked around to the right and left and said, “Where is there anything that I admire that I want to work at?” And I frankly just didn’t see it, and I had an opportunity to start my own thing. And so I did. And it was kind of a harrowing journey.‌

So the last time I talked to you, I think we may not have even launched clinically yet. It was really an idea in gestation and as an entrepreneur, it is kind of like having a baby. So it’s your idea, you birth it and then you hope it survives and you get all the kinds of things, talent, financing, all of that, that are needed to grow this baby. We are now an adolescent, I would say, at Nest. We’ve grown now into a company that is caring for 29,000 people across two states, and we are very proud of what we’ve accomplished.‌

So I’ll just say, what is Nest Health? Nest Health is the first company in the United States to be able to provide care at home to children on Medicaid, primary care to children on Medicaid and their families. So that we’re very intentionally a family health company. The reason for that, and I know this so well as a mother of five kids, our health of infants, of children is intimately connected to the health and well-being of caregivers, and we cannot pretend that we can advance childhood well-being without caring for the caregiver. And so Nest really does that, care for the caregiver, their mental health, their physical health, their social needs as a family unit.‌

And we launched this in Louisiana in 2023 by doing what I learned as a clinical scholar, community-based participatory research. We spoke with community members, we talked to moms, we got their ideas, kind of the Don Berwick, “Nothing about me without me.” So we did all that and then we launched in 2024 and now we are in our second year and growing to Arizona. So it’s been an amazing journey, and I’m excited to talk to you about it today.‌

Howard Forman: Just one quick follow-up. When you think back to the inception point to where it is now, almost every company changes something from what they first think about to what they’re doing now. Can you just tell us about if there are any major things in your mind that you look back and you’re like, “Yeah, we’re doing this differently now than three years ago?”‌

Rebekah Gee: Great question, Howie. So I thought we were solving a problem, which is the following. I thought we were solving this early childhood neglect, zero to five, not being, we’re not doing developmental screening. Only a third of children get developmentally screened. I knew that we didn’t do the postpartum visit to the level we should. What I did not know at the time I started Nest is that 46% of American children on Medicaid last year did not get a well visit, which is abysmal—‌

Howard Forman: It’s incredible, yeah.‌

Rebekah Gee: ... and unacceptable. So we’re actually solving a much, much bigger problem than I thought we were solving. It’s a problem that impacts millions of children. I also didn’t know how hard it would be to make money in Medicaid. I thought, well, I guess I did know not many people are trying and no one’s ever IPO’d a company that’s a Medicaid-focused company. So I guess I should have known that. And then I also didn’t realize, and I’m very pleasantly surprised, all this work we’ve done on quality improvement in Medicaid has paid off. These managed care companies who are our customer really, really care about quality ,and it’s meaningful dollars for them.‌

And I think finally, I had started off thinking, “Let’s really focus on birth to five,” and now we are birth to when kiddos leave the house—21. And so we’re really, the thought was this problem isn’t only early childhood, it endures, and the health of adolescents and the health of other children is so important and so neglected. So we’ve morphed into more of this whole family company from a concept of dyadic care, maternal and child health. And it’s been really an amazing set of learnings.‌

Harlan Krumholz: It’s so great to have you on the show. For people who are listening, you should know that from the moment I met Rebekah, I thought like, “Wow, this person is so extraordinarily mission-driven and will just not be denied.” I just want to focus on Nest, just continue Howie’s momentum here on Nest. The approach is family-based and doesn’t really conceptualize it as patient-based. And I was going to say, what convinced you that healthcare needs to pivot towards caring for nests of people, not just the individuals? And when you started pitching this to investors, who may care a bit about the mission but mostly care about the return, how are you able to pitch the idea that this isn’t just the right thing to do, but it’s actually the good business thing to do?‌

Rebekah Gee: Yeah, well, and first of all, I have a lot of kids. So I think as a mother of these children, I intrinsically understand that we’re all connected. And as a parent, and I have to say, no offense to men, but I think the reason Nest hasn’t been created is ’cause men normally don’t have to deal with all of these details, the scheduling, the follow-up. We know all the data show that women tend to have the burden of managing healthcare for their family. And it is burdensome for me. It’s been hard for me to get behavioral health for my own children. It’s been hard for me to get myself into primary care. In fact, I haven’t been to a PCP in three years, so I mean that tells you anything, but I’m pushing my husband to go. So that’s the kind of thing that we do as women.‌

And it’s even worse for people on Medicaid. And I think it comes from, frankly, probably I have to go back in my mind to my early work at, I went to Cornell Med School, I rotated through Lincoln Hospital in the Bronx and saw just abysmal child neglect, child sexual abuse. There were, at that time, kind of crack baby and AIDS wards where these children were neglected. And I thought, “Wow, what if someone had actually helped the parent? Where would this child have ended up? What if there had been mental health support or addiction support for the parent? Where would this child have ended up?” And the other piece is that I know as a practicing physician that I can deal with a mother or a woman, and I may see this often, often I see this, but if her partner is abusive or giving her chlamydia or whatever it is, I’m not going to solve that by taking care of her. And so the model just makes sense. I also can’t solve for childhood health and well-being if I’m just taking care of a kid if I’m not caring for the issues in that home.‌

So the model makes sense. And the nice thing is, the finances make sense. So the other piece of this and why it’s financially extremely interesting to investors, and we’ve had multiple successful fundraisers, is because the biggest difficulty in home visiting is the driving and preparation. But when we go to a home, we don’t just go and see one person, leave, and go see another, as you would with a Landmark [Health] or Medicare-focused company. We’re going and seeing 2 to 12 people at a time, and so the cost for us is lower and also the income is greater. So our model starts to then look like a Medicare Advantage from a revenue standpoint because we are so much more efficient and effective.‌

And further, the family, and this is one thing again we’ve learned, the family is the key to engagement. So the hardest part about value-based care is engaging people in clinical activities that will lower their costs and improve their outcomes. We are exceptional at engagement. In fact, we’ve engaged 82% of the people that we have been assigned. Why? Because when I find, let’s say you had five kids, Howie, and I’m looking for you, but one of your kids goes into an emergency room and puts in a new phone number, but I haven’t been able to reach you. All of a sudden, I can reach you, I can reach every child. So using a family, it allows us orders of magnitude more data on where do you live? And as we know, with Medicaid, there’s a lot of loss of housing, there’s a lot of loss of phone number. So this real secret sauce around Nest is the family. It’s financially secret sauce is engagement.‌

Harlan Krumholz: And just when you say the word “engagement,” how do you define engagement?‌

Rebekah Gee: Multiple ways, and many payers define it differently. When I say 82%, I mean, we’ve reached, contacted, scheduled, or seen. In terms of who we have completed initial visits on, it’s 42% of the families.‌

Harlan Krumholz: So just so listeners understand how this works. You’re assigned people, like people don’t pick you; you’re assigned to people. And when you say engagement, it means ’cause you’re going out and saying, “Hey, guess what? We were here to help.” And what happens typically is somebody is calling up this group of people who don’t have a lot of trust necessarily in the system, are worried that somebody is trying to scam them or worse, something bad is going to happen. And when you call up and say, “Hi, I’m here to help you,” that’s the last thing they believe is really true. And what you’re saying is, by the way that you’re doing this, they actually will pick up the phone and start talking to you and engage and give you a chance to be worthy of their trust, which is a big deal, right? Because normally it’s like, yeah, you’re assigned people, but it doesn’t mean they’ll engage with you. I mean, I’m just trying to help—‌

Rebekah Gee: And so how do we find, let’s just go quickly back to how do we find people. So we have a proprietary algorithm that looks at (a.) how do we identify a family? Because a lot of payers don’t approach their population in a family way, in a family manner. I think we also, then we also look at “Where are there folks who have addressable spend?” So where are the families where there’s ER use and hospital use, any kind of chronic disease that will lead to high spend. And then most importantly, we find all of the children and parents who did not get primary care last year. So they have zero claims for well visits, vaccination, well care, for kiddos under four at six months or more, and then above that it’s a year or more.‌

So that’s our cohort, and we pull between 9% and 22% of a Medicaid book of business with that. Then what happens is the payer attributes those to us. Either they assign us on day one to be the primary care clinician for that entire list or they share data with us and say, “This is your population. As soon as you engage, go find them and visit them in the house. You will be assigned as PCP and get paid for these folks.” So that’s the model.‌

Howard Forman: So your first point of contact are the patients. You’re not contracting with the payers first, you’re contracting with the patients? You’re finding the patients first?‌

Rebekah Gee: Well, the contract is with the payer. Most Medicaid programs have managed care entities that put their—and that’s our customer. But the patient’s first contract, it might be that the health plan sends them a letter and says, “Nest is going to....” We usually do co-branding with the health plan and ours, so they may expect us to call. We do door hangers, we’ll go door-to-door, but then the onus is on us to go, find, engage. It’s not the health plan calling them, it’s us. Because often, actually just real quick, 50% of the people we got last year had no working number. So the health plan hadn’t been able to contact them.‌

Howard Forman: You have worked, I don’t think we mentioned, even—we did on the prior episode, but you’ve worked in the White House and obviously, you’ve worked in the state government in Louisiana. What do you wish people in those positions knew what you know now? What could you help them do differently to make your job better and to make people’s lives better?‌

Rebekah Gee: I wish they could go on one ride-along with us, and I wish they could see the lack in America. I wish they could see how many homes have no toys, how many homes have no food, how many homes have.... There’s a lot of judgment about low-income women. How many women have no support. This afternoon, I’ll probably have some no-shows, but just imagine you’ve got five children and no car and you’re trying to take a bus with a baby and the other four, and there’s no childcare for them. So I just wish that they could walk in the shoes of these folks before judging. We talk about a country that, we live in a state that’s pro-life, that has ended the ability for abortion access and there’s this big focus on birth, but how about we think about what happens after that? And it’s been shocking to me, frankly, doing some of these home visits, what we’re living with here in America and how much of a need for something like Nest there is.‌

Howard Forman: You also, you mentioned sort of Louisiana being pro-life and the abortion issues, and we are now coming up on, I think, three years after the repeal of Roe v. Wade. You’re dealing with families, but you’re dealing also with mothers at this point. Do you find any tension with that where you are right now? How do you manage issues around reproductive health?‌

Rebekah Gee: No, look, I think we’ve always been able to align. When I ran what was called the Birth Outcomes Initiative for Governor Bobby Jindal, who’s a Republican, I then worked with Bruce Greenstein, who’s now the Secretary, so I’ve never met a politician who doesn’t want a healthy mother or a healthy baby. And so I think we can all align on that. Nothing we are doing is controversial. There might be for a very select few, but we’re getting women birth control, we’re making sure they have postpartum care. We’re going to start a prenatal care at home module soon. We’re doing all of this work for children. We’re making sure we get vaccines in arms. We’re making sure that they get hearing and vision, that their labs are done. So all of this is kind of bread-and-butter table stakes for society. So I think we haven’t encountered that.‌

I think the other piece of it is we’re saving money, Howie. We save substantial money. We saved double our fees last year, and I just wrote a memo about this. We could save the state over $100 million just in urban areas if all the health plans would contract with Nest. So we are saving money, so Republicans like that. We are improving the care and we are engaging the unengaged, ’cause the other problem is that states are paying these managed care companies per member, per month fees to care for people and if they’re not doing any care, that’s a big waste of money. So we’re also solving that problem.‌

Howard Forman: And just to let our listeners know, you mentioned two states and you said you’re expanding into Arizona. Is it Arizona and Louisiana, or is there one more state that I’m missing?‌

Rebekah Gee: Arizona and Louisiana.‌

Howard Forman: Gotcha, okay. We’re getting to the end, but I want to make sure I ask this. You had a recent post on LinkedIn that was sort of calming to those of us that are really worried about the Medicaid negotiations going on right now. And for our listeners, as we speak, the House is navigating, negotiating their bill. It still has to go to the Senate, it’s a lot that still has to happen. So nobody knows what the outcome’s going to be, but you’re at least a little bit calm by the current state as opposed to the more aggressive efforts that might’ve been taken. Can you just speak a little bit about what you’re thinking and what you’re hearing as somebody who is very much in the know?‌

Rebekah Gee: Sure. Well, Medicaid matters because Medicaid covers half of our children in America and 40% of our moms. So fundamentally, this is the program that supports our most vulnerable and, in my view, important people. And so I think one of the things that could have happened is they would have said, “We’re going to change the CHIP program. We’re going to dramatically reduce maternity care. We’re going to do this and that.” What they have come out to say is they’re interested in work requirements. Now, I don’t believe in those, having had to implement them after my governor went on a radio show and said, “We’re doing them.” They don’t work, right? You have to be healthy to work. It’s a stupid concept, in my opinion, but our folks, our children I don’t think are going to be required to work, nor are single mothers. So those don’t affect us. Some of these actually, they’re going after some of the creative match schema that have been executed by states like Texas and Louisiana that frankly are money grabs, mostly for hospitals, and are not benefiting Medicaid patients. So some of it I’m excited about.‌

There’s also some really great talent at CMS. Abe [Sutton], who leads CMMI, is one of them. I like how he’s thinking. (a.) The budget doesn’t identify cuts that would really dramatically impact our children or moms. (b.) The policy direction of the administration is not towards cutting Medicaid. And (c.) We are in a great position to weather all of this because we (a.) save money and (b.) improve quality. So who better to weather something like this than a company that’s actually been able to do that?‌

Howard Forman: Well, look, I’ll speak for me, and Harlan can say, I think it is incredibly important that people continue to try to innovate, and nobody is more prepared to be able to innovate in this space than you. It is so rare to find an entrepreneur who is also sort of a subject matter expert as you are. So it’s always a privilege to have you come back and I am excited about having you come back in the fall to see us in person. So thank you very much.‌

Harlan Krumholz: It continues to be inspiring to hear the story and it’s great to see you and we wish you the best. We all need for you to succeed.‌

Rebekah Gee: Thank you. Thanks. Great to be with you.‌

Howard Forman: Harlan, that was terrific.‌

Harlan Krumholz: I really enjoyed Rebekah, and I’m so glad she was able to share this with us. But now let’s get to the Howie Forman part of the show. What have you got for us this week?‌

Howard Forman: Yeah, so I’m very curious to get your feedback on this. So you and I have gotten COVID boosters in the past, and in general I’ve been a proponent of boosters for most people, though, so I’m certainly less certain about the benefit-to-risk relationship for healthy young adults and children. But if I had to choose for me, my children, who are now adults, I’m in favor of boosters, in general. The evidence of reduced hospitalization risk alone has seemingly supported this contention, and safety concerns around boosters have been near nil. We really don’t hear concerns about the boosters.‌

But now, with the new administration, we do have our first big challenge to vaccines in general, and it comes in the form of a press release, a live public announcement, and a New England Journal of Medicine article by the head of the FDA and the head of the division that approves vaccines. It lays out the case for boosters to only be approved for those over the age of 65 and also for those below that age, as long as they have one or more high-risk condition. And this is where it starts to get squirrely.‌

But before I get to that, I just want to raise their arguments for making this change. Number one, they indicate there is insufficient evidence for the younger groups in terms of both benefit and risk, and they also argue that our broad application of COVID policy is hurting other vaccine take-up. And then last, they further argue that we are out of line with the mainstream of other countries’ policies around COVID vaccination. And they make some really important points that I think do get lost. COVID today and the benefit of vaccination today is probably very different than in December of 2020 when we first approved vaccinations and then about a year later, when we first started using boosters. It would be valuable to reassess the benefit. It would be better to know more about such benefit for very different groups, subgroups within that.‌

As to vaccine uptake, it is true that vaccine uptake has declined in the post-COVID period and also true that red states—those are Republican-led states—have seen more kindergarten exemptions since that time. But if they were truly committed to childhood vaccination uptake, they would be doing a lot of different things. And so I’m not sure that that’s the biggest motivation, but I think it’s a worthy thing to be discussing, at least. And as to the other countries, they are correct that no other country has as an expansive policy as our own. But it should also be noted that their new policy is now narrower than most of our peer nations that they actually cite in the article.‌

But finally, on to the logistical nightmare that they seem ready to unleash, according to their own figures, 100 to 200 million people will qualify for getting the booster while being below the age of 65, but how? Will they require a prescription from a physician? Will their own acknowledgment of asthma be enough? Will insurance cover anyone or just those that are referred? It’s true that COVID booster uptake has been low, but do we really want to create hoops for people to go through if they are getting the booster?‌

And as this episode is released today, on Thursday, the vaccine and related biologics products advisory committee of the FDA is meeting and will be making recommendations. It is of note that their briefing document actually speaks very favorably about COVID vaccinations for all ages, although it doesn’t specifically address boosters. It’s also worth noting that this entire panel is made up of prior appointees, none to my knowledge from the current RFK era. So how are they going to vote? How will their recommendations be received by the FDA or by the CDC and the separate vaccine advisory committee there?‌

The thought process laid out in the New England Journal of Medicine article is not something I’m going to quarrel with. They actually make a lot of good points, but it does fly in the face of how our regulatory processes work and the risks that this precedent could set for a host of other drugs, devices, or vaccines. This is heavy-handed. It forces a reversal, effectively, of approval on the public without even going through the usual review process, and it will not offer the boost in confidence that they’re looking for. In fact, it might dampen confidence of blue state residents to match what we’ve seen with red state residents. So what are your thoughts? I know, Harlan, this is hitting you with new news in the last 24 hours, but I know that you know a lot about this topic. What are you thinking?‌

Harlan Krumholz: I was just a little confused about what their role is in this case. So for example, they seem to be making these decisions based on who’s going to be most likely to benefit from a vaccine. That’s a very reasonable approach, to say we should definitely be focusing on those at highest risk, they have the most to gain. And yet, is the FDA really the one to be making that call? The evidence for people over 65, we lack trials now in this next iteration of vaccine for everyone because that’s the way it usually works in vaccine trials. They try to update every year. We don’t redo the randomized trials.‌

Howard Forman: It’s very hard to do it in a timely manner.‌

Harlan Krumholz: This isn’t the group that has disproportionately greatest evidence, necessarily. They’re making a judgment call. I thought that that kind of promulgation of policy comes out of the CDC where the CDC says, “Here’s what we recommend who should get what.” The FDA, I thought, should be looking at this and saying, “We should be approving the vaccine because this seems like a legitimate next-generation vaccine. And people can make their own choices about whether or not they want to be taking these.” But by making this choice at the FDA level, like you said, it’s going to make it so that you’re getting it off-label if you’re not within the group. You’re creating the need to be able to determine who qualifies for this, what kind of evidence is going to be needed for qualification, and it’s going to complicate likely who’s going to pay for this in ways that are very different than the public health agency coming out and convening a group and saying, “What are our recommendations about now who should be taking something that’s available?”‌

Because ultimately, the decision about taking it has to do with your own preferences, values, and goals, and whether you are risk-avid or risk-averse, how you feel about vaccines, how you feel about your own risk. Two people with the same risk may feel very differently about staying the course without the vaccine and letting nature take its course versus availing themselves of a vaccine that they think may have some chance of reducing their risk. We encounter this every year with flu.‌

Howard Forman: Right.‌

Harlan Krumholz: It’s made available to everyone, and people make different choices based on what their value system is. I’m a big proponent of putting ourselves in that position, accepting cases where vaccines are just so dominantly beneficial and they’re being given to people who can’t make decisions for themselves. So when we say measles for kids, they essentially were saying this is a decision that it should be very rare to get an exemption out of this because it should be a default in general.‌

Howard Forman: And they’re approving the vaccine or the drug. It is the CDC that makes recommendations as to how it should be used and how public policy can be set around it. And then, it’s basically voluntary nationally except to the extent that the states have certain mandates around education and so on.‌

Harlan Krumholz: But their approval is predicated on having these conditions. And now, so they’ve created an indication at the FDA level—‌

Howard Forman: That’s right, exactly right.‌

Harlan Krumholz: ... based on this, which isn’t really based as much on evidence as meaning the relative risk reduction, but they’re basically saying, “We’re going to start making decisions on absolute benefits and we’re going to start cutting it off that way.” As I understand it, like you said, it just came out.‌

Howard Forman: And again, it’s nice to say that we should approve things when there is evidence of this, this, and this. They’re actually taking away approval in a way from something without such evidence. There’s no evidence that should take it away. There may be less evidence than they would like to have approved it the first time, but it does create a lot of problems. And by the way, it is a very slippery slope. There are a lot of other drugs out there that one could re-look at in the same way when they change a formulation in a slight way that the FDA could then say, “You know what—”‌

Harlan Krumholz: And I thought this administration would be more pro-choice for individuals. And in that way to say, we should get rid of mandates, but we should inform people about the level of evidence and be pro-individual-choice about what you want to do with vaccines, as opposed to cutting off a large number of people and saying, “We really don’t think you should take this.” And if you do, like you said, there’s going to be a confusing set of criteria about who qualifies.‌

Howard Forman: It’s frustrating.‌

Harlan Krumholz: Well, it’ll be interesting. This is the first foray into this. There’s more to come. We’ll have to see what’s going to happen.‌

Howard Forman: Stay tuned.‌

Harlan Krumholz: You’ve been listening to Health & Veritas with Harlan Krumholz and Howie Forman.‌

Howard Forman: So how did we do? To give us your feedback or to keep the conversation going, e-mail us at health.veritas@yale.edu or follow us on LinkedIn, Threads, or Twitter.‌

Harlan Krumholz: And give us feedback. We love feedback from you. It helps people find us when you rate us, but also it helps us become better every week.‌

Howard Forman: We really do look forward to the feedback. If you have questions about the MBA for Executives program at the Yale School of Management, reach out via e-mail for more information or check out our website at som.yale.edu/emba.‌

Next week, Health & Veritas will be at the Yale Innovation Summit on May 29th with special guest host Dean Megan Ranney of the Yale School of Public Health, subbing in for Harlan, who will sadly be on another continent that day.‌

Harlan Krumholz: I’ll be in Shanghai, Howie, I’ll be missing you.‌

Howard Forman: I know I’ll be missing you. It’s only the second time without you, Harlan. We’ll be having surprise guests—‌

Harlan Krumholz: That’s hard to believe. How have we kept this streak going?‌

Howard Forman: We’ll be having surprise guests and a live audience.‌

Harlan Krumholz: Health & Veritas is sponsored by the Yale School of Public Health and the Yale School of Management. We are assisted by the terrific Yale undergraduates that Howie’s been able to recruit and bring on board, Tobias Liu and Gloria Beck, and by our marvelous producer, Miranda Shafer.‌

Howie, it’s great to see you. I’m sorry to miss you next week.‌

Howard Forman: I’ll talk to you soon, and I appreciate all of you. So thanks very much, Harlan. Talk to you soon.‌