Josh Geballe: Turning Yale Innovation into Startups
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Howie and Harlan are joined by Josh Geballe, a Yale SOM graduate who serves as managing director of Yale Ventures, Yale’s initiative overseeing the translation of research into impactful new companies. Harlan reports from the debate on AI in medicine; Howie reflects on the FDA’s approval process for an over-the-counter birth control pill.
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Harlan Krumholz: Welcome to Health & Veritas. I’m Harlan Krumholz.
Howard Forman: And I’m Howie Forman. We are physicians and professors at Yale University. We’re trying to get closer to the truth about health and healthcare. This week, we’ll be speaking with Josh Geballe. But first, we’d like to check in on current or hot topics in health and healthcare. And Harlan, what’s got your attention this week?
Harlan Krumholz: One quick thing before we get started. I just want to do a shout-out to Akiko Iwasaki, my friend, colleague, your friend, colleague, who just won the Else Kröner-Fresenius, I don’t know, Prize for medical research, but it’s one of the most prestigious honors of its kind. She was awarded for her groundbreaking contributions in the areas of diseases of worldwide significance, and it comes with, really, funding to help her continue her great work. But anyway, I just want to take a moment. Former guest and very good friend of ours and it’s just was terrific. We’re so happy.
Howard Forman: Yeah, throw back to episode 19, about fifteen months ago, when we had her on. We’ll have to have her come on again soon.
Harlan Krumholz: We’ll have to have her come back. But this just a terrific acknowledgment of the wonderful work she’s done.
Howard Forman: She’s amazing.
Harlan Krumholz: Well, Howard, remember when we used to get on every weekend, all we would talk about is COVID, COVID, COVID, while we’re—
Howard Forman: Yes, I do.
Harlan Krumholz: Can you believe that we’re ... I don’t want to say we’re at the end of the pandemic. I actually don’t think we’re at the end of the pandemic! But for all politicians and for all intents and purposes, we are calling it the end of ... let me call it the end of this phase of the pandemic. And for us locally, what’s the big thing? The hospital is allowing people to take off the masks in the clinical care area.
Howard Forman: Yep, exactly.
Harlan Krumholz: Yeah. That’s like, a huge deal. We may have been one of the last to maintain that restriction, and I think everyone’s celebrating, that they feel like it’s a little bit back to normal.
Howard Forman: In fact, I will tell you, Harlan, I just came from an event where the governor spoke at our hospital with ... and I know you were invited to it, but you’re out of town today. But I just came from that event.
Harlan Krumholz: Didn’t get an invitation.
Howard Forman: That is not true.
Harlan Krumholz: Didn’t get an invitation.
Howard Forman: That is not true. And they literally mentioned your name as being one of the leaders for the reopen in Connecticut.
Harlan Krumholz: Then they should have sent me an invitation.
Howard Forman: Harlan, they invited you! But anyway, it really was so—
Harlan Krumholz: Anyone listening who was in charge of the invites.
Howard Forman: It was a huge event.
Harlan Krumholz: Go ahead, go ahead, go ahead.
Howard Forman: It was a huge event, and they did celebrate you as well as the end of this phase of the pandemic.
Harlan Krumholz: Well, that’s nice. That really is nice. And as you know, I’m in London right now, so if I had been invited, I would not have been able to attend. But anyway, I wanted to start off by this by saying, I remember we were talking about every week it seemed like, the major thing going on, it was the major thing going on in the world. So what are we talking about? What am I engaged in discussions with now every week? It’s these LLMs, these large language models, the ChatGPT 4. I was just in some discussions today. It’s fascinating. People are trying to figure out where does this exactly fit into medicine? The topic of this podcast, where does exactly fit? People are thinking more broadly, of course, but for us, where’s a fit in medicine?
Do you need to build models that are built specifically on medical data, or can you use these broad-based models that are built on all sorts of different inputs, that seemingly are able to produce answers that that are quite sophisticated in the medical realm? So for example, the testing of it with regard to medical boards. When the ChatGPT 4 can pass the medical boards, it wasn’t trained ... and just for people listening, these artificial intelligence models begin by being trained. And in other words, you take a whole bunch of data and you teach it and then it learns.
I’m saying it in a way as if they’re humans, but they learn, and the question is, what do they learn on? And without being specifically trained on medical data, they seem to do very well. But other people think if you want to optimize them, you need to really reinforce the amount of medical information. And then even other people think if you start feeding it EHR data, the electronic health record data, they’re actually going to do worse because there’s so much misbehavior and misinformation within the electronic health record, that it actually could teach it bad habits, the kind of habits that we see sometimes.
Here’s what I wanted to ask you, Howie. So I’m here for a British Medical Journal editorial advisory meeting. I’m privileged enough to be on this advisory committee for them and to be able to hear what they think are the issues they’re facing in medical publishing and in scholarship. But we’re debating a topic. The topic is that medical journals should ban the use of ChatGPT. Of course I’m on the side of that’s impossible and I’m against that—
Howard Forman: It’s impossible.
Harlan Krumholz: ... resolution. But it’s just interesting that they’re—and by the way, part of this is for entertainment value, just getting a conversational topic.
Howard Forman: Sure, provoking, yeah. Yeah.
Harlan Krumholz: But I do think that that in academia and in medical journals, I just, a person you and I both respect told me this week that he had some data. He primed the ChatGPT, and he said, “Write me an article.” And bam. He said it was—
Howard Forman: Wow.
Harlan Krumholz: ... 80% to where he wanted it to be based on just feeding it in.
Howard Forman: Wow.
Harlan Krumholz: And of course, it was the methods and results and didn’t make up anything, but it was just, produce the article. And so, what responsibility do we have to acknowledge that, talk about that? Anyway, it’s a fascinating world that way.
Howard Forman: No, and I’ve heard just last week that there is a company called Chegg. I’m just looking it up right now, but there’s a company called Chegg that had its stock plunge 48% last week. That company helps children do their homework. It assists them, it tutors them. It’s got lots of uses apparently. I have no knowledge of it outside of what I read. But these things will change the world, whether we want to or not. The question is, how do we help create guidelines and how do we help people use it for good, not evil?
Harlan Krumholz: Yeah, yeah. And you know about these hallucinations, right, Howie?
Howard Forman: Oh, in ChatGPT?
Harlan Krumholz: Yeah, so that’s what people are calling this when ChatGPT makes up stuff.
Howard Forman: Yeah, it makes things up.
Harlan Krumholz: Makes things up.
Howard Forman: Yeah, crazy.
Harlan Krumholz: So, sometimes you’ll see a fact in ChatGPT and you’ll say, “Give me some references.” They will give you what appeared to be legitimate references. I mean they’re formatted correctly, they make sense. You would think they’re real, but when you look, they don’t exist. It’s a hallucination by the—
Howard Forman: Exactly.
Harlan Krumholz: ... AI machine.
Howard Forman: Exactly.
Harlan Krumholz: I’ll just tell you one last thing real quick, which is that somebody told me that they were just querying it and said—you know that Rutherford had this very famous lab in physics that spawned many Nobel laureates afterwards. Richard Siever was telling me this and that what was asked, how many laureates came out of Rutherford’s lab? This was early, of course, in the 20th century. And it said, “Eight.” Then so back said, and they were queried back, said, “No, no, the correct answer is six.” ChatGPT said, “Yeah, but it should have been eight. The two who didn’t get it, deserved it.”
Howard Forman: It’s learned how humans confabulate when they have to. Yep, it’s true.
Harlan Krumholz: Anyway, it’s a new world. It’s a new world, and this is likely to be a hot topic for a long time. I’ll try not to take all of our space on this. And a teaser for next week, we have paper coming out that that’s one of my most important papers. I’m eager to share it with you next week. So I promise to get off this topic at least for a week. But let’s get onto our guest, a terrific guest today.
Howard Forman: Josh Geballe is Yale’s senior associate provost for entrepreneurship and innovation. In this position, he has worked to connect Yale’s research to entrepreneurial partners in the community and industry. Prior to joining Yale Ventures in 2022, he served as the chief operating officer from 2020 and the commissioner of the Department of Administrative Services from 2019 for the great state of Connecticut. In this position, Geballe led Connecticut’s response to the COVID-19 pandemic and was responsible for 25 state agencies encompassing 30,000 employees.
Prior to his public service, Geballe worked for IBM and served as the CEO of Core Informatics. Core Informatics provided data management services to pharmaceutical and other scientific industries before it was acquired by Thermo Fisher Scientific, a Fortune 500 company.
Geballe holds a bachelor’s degree from Yale College from ’97 and an MBA from the Yale School of Management in 2002. So, first of all, I want to just welcome you to the podcast, but it’s really unusual that we’re doing a podcast with someone that I just saw an hour ago. And the reason why I saw you is because our governor met with the senior leadership of our hospital and the senior leadership of the state, including your successors, to talk about the response to the pandemic and announcing how much we’re at the point of ending the pandemic emergency right now. And he called you out specifically because you had such a central role to play in that. And I just wonder if you could give our listeners a little bit of a taste of what it was like.
Harlan Krumholz: And you know Josh, I wasn’t invited to this thing. I just want to tell you.
Howard Forman: We have discussed this ad nauseam, he was invited. He doesn’t read all his emails. But I want to hear you tell us a little more about what it was like from beginning to end, to play that key role at such a stressful time? And there were a lot of moments that were stressful.
Josh Geballe: There were. Well, first of all, I just want to say, Howie, Harlan, thank you for the invitation. I’m a regular listener to the pod. It’s a great program, so I’m honored to be on. I think to your point about the COVID response, it was an experience like, hopefully, none will ever go through again.
But it was a time where I think we got to see obviously so much struggle, so many challenges, but also in that position to be able to see the state come together actually, in ways to solve problems that we’d never faced before. And to work together to try to do the best we could with what we had at the time. And in particular, Governor Lamont and his leadership and his willingness to make tough calls and tough decisions that ultimately, I think now, with the benefit of hindsight look even better than they did at the time. It was an honor to be part of that team.
Harlan Krumholz: I wanted to just pivot here to Yale Ventures and so, can you tell us a little more about Yale Ventures and how it supports Yale innovators and what really sets apart what we’re doing here with regard to entrepreneurship and innovation, from things that may be going on in other places?
Josh Geballe: Sure. So, as you mentioned, Yale Ventures, now just over a year old, is Yale’s home for all things entrepreneurship and innovation. So, we run a variety of programs and centers and services that support both faculty as well as students who are looking to solve the big challenges that we’re facing in the world today.
And so, those programs typically take the form of what we call accelerators. So, programs that bring in either faculty or as students who have an idea, who in the case of faculty are doing research and have discovered something and they could have potential to have a real-world impact on solving the problem that they’re working on. And we work with them to help develop that technology, get it licensed out, from oftentimes a startup company around it, that can scale it up and develop it or find a corporate partner in the private sector who can take the technology and run with it.
But it’s really about trying to take that next step from the lab out into the world, where technologies can be scaled and can have as much of an impact, positive impact in the world, as possible. And then of course, with our students, we run an entrepreneurship center called Tsai CITY [Tsai Center for Innovative Thinking at Yale] that helps them think about how to solve problems in innovative ways, in some cases start companies as well.
So, it’s an incredibly fun role. We get to meet new people every day, working on some of the most cutting-edge research. So it’s incredibly fun, but it’s timely too. There’s such demand for what we’re doing as well.
Howard Forman: And Yale ends up becoming the promoter in some ways of real product. It’s not just the research that comes out of this, it’s the products. I know I’m looking over your shoulder, our listeners obviously won’t see this, but you have products lined up on your shelf over there. I wonder if you give us a little sense, because Harlan and I think much more about biomedical innovation and life sciences, medicine, and so on, but it’s not just that, it’s a lot more. Can you give us a little sense of some of the products that have come out of Yale?
Josh Geballe: Yeah, absolutely. As you point out, I think Yale’s incredibly large and very strong medical school has produced an enormous number of new innovations that often become new therapeutics, new vaccines, new medical devices, diagnostics. But as you point out, Howie, were seeing an enormous amount of growth in other domains across the university as well.
So, for example, our School of Engineering & Applied Science is growing very rapidly right now, and we’re seeing a lot of really incredible research there around artificial intelligence, quantum computing, areas that are going to transform the world fundamentally in the very near future. And there’s a lot of exciting technology spinning out of there.
We’re also seeing a lot of growth related to climate technologies as well. Research that’s going to help decarbonize our economy and help protect the planet, help address global warming. And so we’re really excited about a lot of the projects.
And then the products you’re pointing to over my shoulders are often consumer products. Those most commonly are being developed by students or graduates, but there’s a wide range of new ideas and innovations coming out of Yale that we get to help support.
Harlan Krumholz: Josh, some of the faculty, I’m not going to name them, could be me, the other people, who actually get very enthusiastic about our work and we actually think they have wide-ranging potential for impact. We have dreams of being able to scale them in ways that can help many people, but we’re not always right about our own judgments about our work. How does Yale Ventures go about evaluating this? Because I would think that you get many more people coming to you saying, “Hey, I’ve got something. I’ve got cold fusion here, you want to take a look?” And you’re trying to figure out ... because you’ve got fixed resources, you can’t get behind everybody. So, how do you on one hand encourage everyone to be thinking this way, on the other hand, make choices about where you’re going to spend your time, where your team’s going to spend their time?
Josh Geballe: Yeah, it’s a really great question, Harlan, and it is one of the most challenging things. I think our approach, and we’ve been evolving this over the years, our approach today is really to try to be as supportive as we can to as many ideas as possible. I think it’s important that we’re very humble in terms of our assessment of our ability to predict what’s ultimately going to work or not work or have an impact or not at this very early stage.
I mean, even the best venture capitalists in the world are wrong 9 times out of 10, and so we’re even upstream of them. So, I think our job is to be as supportive as we can to as many people and technologies as possible and then let the science work or not work and let the market decide if it wants to invest or not.
But you’re right, we do have some programs that have limited resources in terms of some grant funding and so forth. And so, what we do there is we have a number of boards where we bring in independent experts. They’re often alumni who work at venture capital firms or work in industry, and we bring in their expertise to help judge so that we’re not in the position of picking winners and losers amongst our faculty or students but try to leverage the best thinking from the people out in industry today. But generally speaking, our philosophy is that we want to be as supportive and open as we possibly can.
Howard Forman: And you’ve already mentioned this, but I want you to explain it a little more broadly. The university actually does quite a lot both in the silos of the schools as well as in Tsai CITY and through your office to promote and encourage our own students at the undergraduate and graduate level to get involved in innovation very early on. Do you want to give us some examples and maybe also explain how much you do with social enterprise, in addition to the more commercial enterprises?
Josh Geballe: Absolutely. So, at Tsai CITY, we’ve got an incredibly wide range of programs from very starter, entry-level types of intensives that help people think about how to be innovators, how to solve problems, all the way up to supporting students who are starting companies in their dorm rooms and have raised venture capital and are generating revenue. And we have a number of those.
We are also really excited when ... we run a number of programs and fellowships where we hire students to work on faculty-led ventures as well. Oftentimes there’s a need to do market research or to help with analysis or other work that’s helping to get the business off the ground. And we hire a wide variety of students, both during the summer we really swell up, but during the academic year as well, who engage in those programs. The students get incredible experiential learning and we get enormous value out of the support they provide.
And as you said, it really covers the spectrum of different new ventures. When we talk about ventures, we’re not just talking about scalable venture, investible startups, we’re talking about any type of new venture that’s looking to do something innovative or solve a problem. And oftentimes, that takes the form of nonprofits, or arts organizations, or community organizations and we’re excited to support all of those.
Harlan Krumholz: You have such a broad mandate. I’m only just trying to imagine when you interviewed for this job, it’s sort of like, you want me to do this and this and this and this and this? It’s such a wide range of things. Now you’re a year in, does Yale Ventures measure the success of its programs and source? Because it’s not, I would think, just simply on return on investment, it’s more culture and so forth. So, do you have examples of the kind of metrics you’re using that at the end of a year you’re trying to see to evaluate the impact of the program and both on Yale innovators as well as the broader community?
Josh Geballe: Absolutely. So, Yalies will know we have this saying, “For God, for country, and for Yale.” It’s usually on banners that go on people’s dorm room walls and stuff. It’s the last line in the fight song, I think. But it’s really about that. I’ll go in reverse order. So, for Yale, the impact is really, when we do a good job, we make Yale an incredible place that faculty want to come and they want to stay because they know they’re going to be supported. If they want to innovate, they want to see their research translated for the benefit of society, and same for students.
So increasingly, students want to go to a place that will support innovation, entrepreneurship. So, it’s a very important service to Yale as a university. For country, maybe it’s a little less for country, maybe more for the state, for the state of Connecticut. There’s a really important economic development aspect to this. As we spin out companies, those companies increasingly are based here in New Haven. They grow, they create jobs, they import capital from all around the world that gets reinvested back out into the community. It fuels real estate development and just generally helps support the local ecosystem. So, there’s huge benefits there.
And then for God, I don’t know about God, but you think about some of the problems that our researchers are working on solving. I mean, we are improving human health, we’re curing diseases, we’re creating new ways to pull carbon dioxide out of the atmosphere. I mean, things that seem a little bit out there oftentimes, but our incredible faculty are hot on the trail of some incredible breakthroughs and have already delivered so many in ways that will profoundly impact the world we live in such a positive way. So, it’s a wide variety of metrics that we measure, but they all come together to help those different components.
Howard Forman: So, as I mentioned in the intro, you’re a twice-graduated Yale student. You came here for Yale College and you then went to the School of Management. And the School of Management is foundationally built on this idea of serving business and society, which is very much what you just described as part of what your mission is here.
But I wonder if you would give us a little reflection on, when you look back to what you did in those two years at the School of Management, what coursework, what teachers got you enthusiastic about the types of work that you’ve done during your career and now?
Josh Geballe: Oh my gosh, there’s so many. Yeah, the School of Management’s such an incredible place, and there’s so many, I shouldn’t start naming them because—
Howard Forman: Yeah, no, that’s ...
Josh Geballe: ... I’ll leave out things that were incredibly impactful. The irony, I think, and I know from a lot of my classmates feel the same way, is that actually some of the classes that we felt were the least exciting, that were the mandated curriculum, have turned out to be some of the most useful, like accounting and microeconomics. Things that are incredibly important, languages of business, and that are fundamental to so much of what we’ve done. But I think what you’re alluding to also, Howie, is the core values of the Yale School of Management, which are about solving problems in business and society. And I am proud to be one of the many alums who’ve pivoted back in growth across different sectors over my career and hopefully made a difference across many areas.
Harlan Krumholz: There’s some people who bemoan the introduction of business into academia, but I really see it as an ability to scale. I mean, to actually see the impact of the ideas get all the way, because unless you’re working together with a sustainable enterprise, you’re not going to see the end product and value of the work that’s done. And to me, it is a very important potential part of a portfolio of work that someone could do. I wonder if we should start thinking about this in the promotion process, which is, I’m just now thinking about medical school, which is as people show their portfolio of work, part of it is what have you done to ensure its ultimate translation. And I mean, are you working in ways to see it obviously manifesting itself? Do you think we could get to a place where people actually got credit in the promotion process for working with Yale Ventures and ensuring that good ideas that they’ve had actually get a chance to get all the way to the marketplace?
Josh Geballe: Yeah, I think the trends are moving in that direction, Harlan. I mean, I think it’s all within balance. I mean, I think the core mission of the university around research and teaching always has to be paramount.
But I do think at the department level, at the school level, where those types of decisions are made about what’s evaluated in the promotion process, I think we are starting to see those types of factors included. Maybe not over-weighting other things but starting to be part of the discussion and assessed in a positive way.
I think we’re seeing some of our peers start to do that in a more systematic way. And I hope that’s true because I think the things you’ve said are very true. I mean, I think we have an incredible opportunity and maybe responsibility to take the discoveries that are being generated in the billion dollars a year in research that’s being invested here and try to make sure we’re doing everything we possibly can to see those discoveries have as big an impact in the world as possible.
Harlan Krumholz: Yeah, and just guard against the conflicts of interest and be able to ensure that integrity of the science. But that last step is important, yeah.
Josh Geballe: Absolutely.
Howard Forman: So, I wanted to touch on that actually, what Harlan just brought up. And that is, you and I sit on the Conflict of Interest Committee for the university, and you play a very special role working within the provost’s office to help manage this level of complexity, the legitimate conflicts that exist and even the perceived conflicts that exist.
Can you give our listeners a little bit of an idea about why this is a big challenge for a university to make sure that we’re able to protect the science that goes on here from the potential of capitalism, but at the same time help innovate and ensure commercialization of useful products?
Josh Geballe: Yeah, it is a very important topic, for many reasons. You just touched on a number of them. But I do think as we think about managing those conflicts, the good news is that there’s very established policies. As you said, there’s committees that review the edge cases that needed some special attention.
But I think the most important thing is that in the end, all the whole system works largely on trust and on people who want to do the right thing. And my experience, being on the committee for a year now, is that our faculty want to do the right thing and they don’t want to create a real or even perceived conflict and they want to bend over backwards to make sure that doesn’t happen so that the partnership in that process is very strong. I’m sure you see that all the time. And I think it’s an area where it’s ... often you deal with some pretty challenging circumstances, but I think most of our peers I think figured out how to do it and do it well.
Howard Forman: Yeah, no, I will just add that that committee is a rigorous committee. I mean, it’s a time-consuming enterprise, but I wouldn’t participate in it if I didn’t think it was meaningful. And what you said is right, the university takes this very seriously.
Harlan Krumholz: As we get to the end of this part of the podcast, I just wanted to end, Josh, with saying one thing I’ve noticed about you that is really great is you’ve become a person lots of people are coming to advice for, and then you’re able to handle that in ways that are encouraging but realistic. You’re able to help, like you said, balance people’s expectations about what’s possible, but also to inspire them to think about what they can accomplish. I’ve heard that from people who come and talk to you, and I think it’s an important role that you’re playing here.
Now, I just wonder if you could give people who are listening kind of a glimpse of what a conversation like that might go? Where somebody comes to you, they’ve got an idea, it’s not a clear, slam-dunk idea, it’s an idea that’s fledgling, but could potentially ... you’re not sure. And that person’s a little tentative and just doesn’t really quite know whether it’s even worth or would it be embarrassing to push this through? Or is it possible to spend some time on this? What would they hear from you? Would they sit down with you and say, “What do you think of the I’m talking about and what should I do?”
Josh Geballe: Yeah, thank you for the comments, first of all. I do feel like I have the best job at the university. I’m sure there’s a lot of people that feel that way, but the fact that I get to meet all these incredible scholars and students and try to be helpful in some small way is such an honor and so much fun.
I think Harlan, most commonly, it’s just asking questions. It’s probing at the idea from the perspective of maybe somebody from who spent most of my career in industry, or in the private sector and thinking about how it would be evaluated by an investor. And ultimately, that comes down to what problem are we trying to solve and is there going to be demand for helping to invest in a solution that’s solving that problem? Or is it too small or too niche?
And if it is, that means we ... doesn’t necessarily mean we shouldn’t work on it, because it still could be a very important thing to solve, but it just maybe needs to go a different route because it’s not gearing up for venture capital financing at that point. So, it’s really just trying to flesh out and help the entrepreneur understand the types of questions that they’ll likely face so that we can work together on the answers to those questions that give them the best position to see their life’s work, which is often this discovery that they’re bringing forward, have its full potential in the world.
Harlan Krumholz: Yeah, I love that. What problem are you trying to solve, as a starting point for that conversation? Sorry, Howard, go ahead.
Howard Forman: No, no, I was just going to echo what Harlan said and just thank you for what you’ve done. And to also add that I’ve sent several people to you, and I know you meet with an awful lot of people who are just looking for career advice, that are just looking to see what their place in the world is. And you’ve just been a very generous mentor, role model, advisor to so many people. And it is what makes Yale great, to have people like you, and I personally appreciate you a lot.
Harlan Krumholz: Yeah, thanks Josh.
Josh Geballe: Well, listen, right back at you guys. There’s very few people who are more sought-after mentors and more generous with their time than Howie and Harlan. So, you guys set the example that many of the rest of us try to emulate.
Howard Forman: Thanks very much Josh for joining us today, and we look forward to having you back soon because honestly, this field of innovation is always innovating.
Harlan Krumholz: Yeah, thanks, Josh.
Josh Geballe: Anytime.
Harlan Krumholz: Well, Howie, that was a really terrific interview with Josh. I can’t tell you how fortunate we are to have him here and really how many good things he’s done to spark the intellectual aspects of Yale, thinking about how we can bridge from theory and discovery, all the way to application and benefit for large-scale populations and do it through this mechanism. But let’s get to this part of the podcast, part I really like, which is to hear your thoughts. What’s on your mind this week?
Howard Forman: So, while we’re actually taping this segment, the FDA, Nonprescription Drugs Advisory Committee and the Obstetrics, Reproductive, and Urologic Drugs Advisory Committee are in their second day of meeting, to consider the approval for nonprescription use, meaning over-the-counter use of a progestin oral contraceptive pill in the form of norgestrel, which is being marketed as Opill. So, I’ll call it Opill going forward because that’s what the company wants to call it.
I could not do justice to the issues that are being discussed. I assure our listeners there’s a lot to talk about. It’s a full, two-day meeting, an enormous amount of data is being shared, 130-page document from the FDA alone and 10 other lengthy documents are posted publicly on the FDA website that addresses the major issues that the committee is considering, and we’ll link that to our website. But what I want is help our listeners understand why and when a drug moves to nonprescription status and because it’s probably, in my opinion, at least not that obvious to most people.
So, first is background. It’s worth pointing out that ibuprofen and cetirizine, which is Zyrtec, and a host of other drugs that we’ve just come to accept as being over-the-counter, started out as prescription-only drugs. You could only get them when a doctor wrote a prescription for you. Ibuprofen was originally approved in the U.S. in 1974 and then converted to over-the-counter use in 1984. So 10 years later. In the case we’re talking about now, this drug is being reviewed 50 years after its original approval as a prescription drug.
The point being that moving to nonprescription status is rarely as news-making as this one seems to be. So, what are the characteristics of over-the-counter drugs? So quickly, one, their benefits outweigh their risks. Two, potential for misuse and abuse are low. Three, consumers can use them for self-diagnosed conditions. Four, they can be adequately labeled. And five, health practitioners are not needed for the safe and effective use of the product. So, “safe and effective” is a common theme when we’re talking about review by the FDA.
And we could spend a lot of time talking about why drug companies often have had strong incentives to prevent branded, patent-protected drugs from moving over-the-counter. But the biggest one that people should be aware of is that insurance will generally cover a prescription drug and generally will not cover over-the-counter products, right? In my own course, I like to prompt our students to consider why we even have prescriptions at all. Because in my extreme opinion, and this is mostly for provocation, but in my extreme opinion, with the exception of controlled substances and antibiotics, I can make a pretty good case for allowing patients to have much freer access to drugs without requiring continued visits to doctors or other providers.
I certainly don’t think the extreme case is feasible, even though I provoke people with that idea, for reasons that include the shock to consumers in terms of payments out of pocket and so on. But we should think more about why we require patients to have to visit or otherwise reach out to clinicians at some interval for drugs that in many cases, they’ve safely taken for years or decades, or even when they begin a new drug, when they have carefully considered their personal health and the risks and benefits of treatment.
So, in the Opill oral contraceptive case, there’s a lot of attention that comes from many different groups. There’s concern that individuals will not heed the warnings about safety, that they will not fully understand the effectiveness in how to use these medications. And that we don’t have enough real-world data on the use in adolescents, in obese populations, and in those with other comorbid conditions. We also might not have optimized the labeling of the current product to minimize harm and maximize effectiveness.
I think it goes without saying that there are some, I think it’s a small group, who are opposed to the approval merely because they don’t want women to have broader access to contraceptives. But it’s worth knowing that we already have a host of over-the-counter medications that are considered safe by so many and yet have rather serious risks. Tylenol, acetaminophen, is the most common cause of liver transplantation in the U.S. and the cause of over 500 deaths annually due to overdose. Only half of these being intentional. And over-dosage with Tylenol happens inadvertently in many individuals because it’s an ingredient in multiple products.
Nonsteroidal anti-inflammatory drugs, including ibuprofen, have been repeatedly shown to increase risk of acute and ongoing kidney injury in those who take it even in the normal daily dosing recommendations, generally due to other physiologic or medical conditions or for those who take it chronically. So, in summary, I think Opill will eventually be approved. Sometimes people are saying by the summer, and I hope that we can learn more and then revise the labeling and help consumers understand the best use of this and other products.
But just as importantly, I think we should be reconsidering how we manage the over-the-counter drug approval process and continued access. Because there are millions of individuals who don’t have easy access to clinicians. And being able to gain access to drugs or continue to be able to fill prescriptions is vitally important.
Harlan Krumholz: That’s really good. Good points, Howie, you’re such a good teacher. You really draw an analogy to other situations. By the way, in the acetaminophen, do you mean drug caused liver transplantation? Because I would’ve thought alcohol was the number one cause.
Howard Forman: I thought so too, Harlan. I looked this up twice, apparently for ... maybe it’s in the acute phase, but it’s liver transplantation. We do 500 for acetaminophen alone every year.
Harlan Krumholz: That’s wild. I didn’t realize that. And I’ll tell you something else. Well, I’m a big advocate for patient empowerment, people being able to make their choice. I think we infantilize our patients, we make it seem like they’re unable to make choices. But another example is we give broad access to other drugs, like alcohol. I mean, people drink for recreational purposes, but this has risk. People have to make decisions. Sometimes they make good decisions, sometimes they may not make good decisions, but we allow people to make decisions. Nicotine—we allow people to make decisions.
I mean really, where do you draw the line about it is unsafe, sufficiently unsafe, that we are going to require people to have someone else to give them permission to take it? And this thing about the insurance company covering it is huge. Now, what will that mean? Are we actually going to have insurance companies backing this? Because now they want to have women be responsible for purchasing their own oral contraceptive?
Howard Forman: People are concerned about that. So, this is a concern.
Harlan Krumholz: This is a very important area. It’s very important. And I’ve told you before, why not make statins something that anybody can go get if they want to reduce their risk of heart disease. If it seems appropriate, they should be doing it in consultation with doctors. But to have that be the gatekeeping, I’m not sure, anyway.
Howard Forman: If I’m not mistaken, you may be able to remind me better, but I think our colleague, Mary Tinetti wrote a paper in The New England Journal of Medicine maybe 10 or more years ago advocating for simvastatin or maybe one of the other statins going over-the-counter. I’m shocked that it hasn’t happened over time.
Harlan Krumholz: No, I don’t remember that particularly, maybe, but I do remember we came to the brink of the FDA making a decision in that direction and then they backed off. But yeah, no, this may be a really good case to see, set precedent for the future for these kind of meds. Well anyway, thanks very much for raising it. I think it’s a really, really important point. 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, you can find us on Twitter.
Harlan Krumholz: I’m @hmkyale, that’s H-M-K Yale.
Howard Forman: And I’m @thehowie. That’s @T-H-E-H-O-W-I-E. You can also email us at email@example.com. Aside from Twitter and our podcast, I’m fortunate to be the faculty director of the healthcare track and founder of the MBA for Executives program at the Yale School of Management. Feel free to reach out via email from more information on our innovative programs, or you can check out our website at som.yale.edu/emba.
Harlan Krumholz: Health & Veritas is produced with the Yale School of Management and now the Yale School of Public Health. And I’m going to stop saying “now” because they’re just another sponsor of ours now, so it’s not even new. Thanks to our researcher, Ines Gilles, and to our producer, Miranda Shafer. They are absolutely amazing. They make this podcast what it is. Talk to you soon, Howie.
Howard Forman: Thanks very much, Harlan, talk to you soon.