Ali Rahimi: A Cardiologist in Your Pocket

Transcript

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, and we’re trying to get closer to the truth about health and healthcare. Our guest today is Dr. Ali Rahimi, but first we like to check in on current hot topics in health and healthcare. Harlan, you’re promising me it’s going to be exciting for me today—tell me.

Harlan Krumholz: There’s so much going on, there’s so much to choose from.

Howard Forman: There is, yeah.

Harlan Krumholz: I don’t know whether our listeners have GLP-1 receptor agonist fatigue, but I can’t resist talking about it again this week.

Howard Forman: Oh my God, there’s so much news just this week. And remind our listeners what we’re talking about.

Harlan Krumholz: Three really important and interesting storylines happening at the same time around these anti-obesity medications. And look, it started getting me to think I wanted to talk about it this week, because I’m watching TV... Should I admit that I watch TV? Well, I’m watching TV.

Howard Forman: I watch a lot of TV.

Harlan Krumholz: And there are all these commercials out of nowhere that are pushing this microdosing—

Howard Forman: Oh, really?

Harlan Krumholz: ...for tirzepatide. And so, I started saying like, “Oh my gosh, this is their new strategy,” and it’s just a growing number of telehealth companies, Hims and Hers, Nu, Found, Ageless Rx, marketing these microdosed compounding versions—

Howard Forman: So, explain what that means. Explain what that means.

Harlan Krumholz: Exactly. So, the microdosing is taking the lowest possible dose of these, and what they’re saying is ease yourself into weight loss with compounded GLP-1 microdose treatment plans, going for about $199 a month. And these are really, I think a lot of us would think about this as sub-therapeutic doses of these medications, that would be sort of weekly injections with the same active ingredient as Ozempic or Wegovy, but not about escalating to therapeutic doses, but just giving you just a taste, just a taste of this stuff.

Howard Forman: But can we just clarify for our listeners, one thing is that by compounding them, by selling them at doses below what Lilly and Nova Nordisk sell it at, they get around some of the legality of FDA regulation because—

Harlan Krumholz: So, the fine print here says “compounded drug products.” So they’re not taking the approved drugs, they’re making it themselves. They’re outside of the purview of the regulatory guidance.

Howard Forman: Yeah.

Harlan Krumholz: And the fine print says “compounded drug products are not approved or evaluated for safety, effectiveness, or quality by the FDA.” This still blows my mind, Howie—

Howard Forman: I know.

Harlan Krumholz: ... that we can be having this group of companies making medications on their own, not being overseen by the FDA, promoting them on the media, on TV, on commercials as if... I mean, I don’t think the average person really differentiates this from other drug advertisements they see on TV, which are about approved drugs. And this started when we had the shortages in 2023 and 2024 with Wegovy and Zepbound, and so these came in to sort of fill that gap, they were making it themselves, they were selling it. There was no real oversight, we’ve talked about it on the podcast before. And so, this is this regulatory loophole, this section 503A and 503B of the FDA Act, which allows compounding for individual prescriptions when there’s a drug shortage, but the FDA never approved these compounded drugs and has warned firms against mass-manufacturing them. But I think the FDA is also overwhelmed right now; this hasn’t really been intervened on. And here’s the key that you should know: there are no clinical studies that have tested microdose GLP-1 receptor agonists for safety or effect or efficacy.

Howard Forman: Right. It literally is going back to what we’ve talked about so many times, this is snake oil, like potentially snake oil. Maybe it works, but how do you know?

Harlan Krumholz: Well, it could work really well; somebody would have to study it. Dan Drucker, who sits on the mountaintop, he was the one who helped develop these drugs, he’s international leader in this area, he says uncertain whether such doses would actually combat, for example, inflammation. Because people who are microdosing aren’t necessarily people with obesity; in fact, they’re probably not people with obesity, they’re people who are looking for longevity.

Howard Forman: Right.

Harlan Krumholz: And so, people just think, well, maybe just a taste of this stuff, just injecting a little bit will help me. But the Cleveland Clinic has made it very clear on their website that these are untested, this isn’t the same as a physician adjusting a legitimate prescription, and have warned against it. So, anyway, what they’re trying to, these companies are seeing this as an entirely new stream. So, that’s one story, and I just wanted to say it’s a little crazy. Because it’s a legal gray zone, a medical vacuum, a consumer experiment wrapped in clinical branding, and I think a vivid example of how fast innovation can outpace regulation and evidence, and that these people are doing. So, that’s the one thing. The second thing I wanted to talk about was just how hot the area is here.

So, you may have been following this, and we mentioned it on the podcast, remember I told you about my friend, Clive Meanwell, who started this company, Metsera, that had acquired some really interesting assets for anti-obesity drugs that were going to be kind of the next generation of was going to happen. They did some very early testing, it was very intriguing, favorable, but very early. They didn’t get to the large-scale pivotal trials that you would need for regulatory approval, but they were moving in that direction. Pfizer agreed in September 2025 to buy Metsera for up to 7.3 billion if all of the things lined up in the right way, with regard to the evidence.

Then Novo Nordisk, who makes Ozempic, Pfizer doesn’t have an anti-obesity drug, they came in with the initial offer, Novo Nordisk, which has Ozempic, countered with a $9 billion, and then raised it to $10 billion on November 4th, 159% premium over Metsera’s pre-announcement stock price. And Pfizer’s response was to offer, now go back and say, well, we’ll raise ours from seven three to eight one, and then they put two lawsuits to block Metsera from leaving its deal with Pfizer and to join the one with Novo Nordisk, talking that, saying this was anticompetitive. And the judge is declining right now to block the bidding, and the bidding keeps going up. And so, Pfizer’s motive, it needs an anti-obesity drug because it doesn’t have one, it wants to get into this, Novo wants to prevent Pfizer from getting a potentially disruptive competitor, and they want to regain ground that they lost to Lilly, and all I can say is “God bless” to Clive, because it’s great for him. And nothing better than having two major pharmas fight over you.

Howard Forman: It’s a fascinating time in this market, not to mention that by the time this comes out, the Trump administration may announce a negotiated rate for Medicare for the obesity drugs.

Harlan Krumholz: That’s my third story. So, there is this Trump administration, as you said, negotiating deal... We talk about what’s going on with CDC, we talk about what’s going on with Kennedy and MAHA and vaccines, some stuff, I don’t know, whatever side you’re on, you got to be thinking that if they can negotiate with the drug manufacturers.... These others have people on both sides, this is one where everyone should line up together. If they can negotiate $149 per month, and by the way, for a lot of Americans, that’s still too much, but it’s a lot less than what it’s been by a huge amount, $149 per month through this government platform, believe it or not, called Trump Rx... we’ve talked about this before, too. This deal would open Medicare and Medicaid coverage for obesity treatment, and that’s got to be a good thing. Now, I think that they’re pricing it based on the dose.

So, many people have to go up in dose, the question is, what will it be eventually? But if this gets based on Most Favored Nation pricing authority, linking the U.S. prices to those in Europe, and it gets run as a pilot through Medicare’s innovation center, which can cap drug prices for specific groups without new legislation, then that could be quite interesting. Drug makers would receive priority FDA review vouchers for future drugs, so they do get something in exchange. And in particular, Lilly’s interested because they’ve got something teed up, an oral non-peptide GLP-1 receptor agonist. So, rather than people having to inject themselves once a week, there’ll be a pill that people will be able to take. They want to be able to move this quickly through the FDA; that’s an incentive for them to lower the cost on the injectable, and then they’re going to, if all goes well, they’ll have an oral drug that mimics the natural GLP-1 hormone that people have been using to—

Howard Forman: There’s still a lot of moving parts there. And it’s not clear they’ll make the announcements more because we’re still... remember that Medicare does forbid, at the moment, paying for a drugs-for-obesity treatment, and so that’s something that has to—

Harlan Krumholz: I don’t think that’s going to stop this administration. But yeah, you’re absolutely right. If you followed all the rules, you’d say there’s a lot more things that you have to go through. But it’s interesting, it’s interesting. So, this space is so hot right now. Like I said, you got this microdosing coming with no evidence, and being promoted like crazy in the teladoc things, you’ve got this bidding war that’s escalating around these new assets that are anti-obesity, that are different than the current ones, and then you’ve got this drive down in price, potentially, from the administration. And I got to say, I believe obesity should be considered a disease, we should be treating it like we treat hypertension. Of course, we should be focusing on lifestyle and nonpharmacologic interventions, but we’ve got drugs that can really help people, and we know that they can improve outcomes.

We need to continue to accumulate evidence, but now we’ve got to figure out ways to make them affordable and give people the option without bankrupting them, or without precluding them because of their financial resources. As more drugs become available, as more options become available, as the government leans on companies, we may get a day where we can treat obesity like we’re treating hypertension, and God bless, we need to do better than we’re doing with hypertension with regard to giving those options, because in the next segment we’ll talk to our guest about hypertension treatment. But it’s... lots happening here.

Howard Forman: I will say, though, that the Novo Nordisk is down 60 or 65% from its all-time high, it’s underperformed the market over about a five-year window. So, as hot as this is, it’s still a very competitive space, just to keep that in mind.

Harlan Krumholz: Well, that’s why Lilly has been kicking their butt for a bit, and they got a new CEO, you know that, Novo got a new CEO because people’s dissatisfaction, and I think this bidding war is part of them saying, “We got to really get moving.”

Howard Forman: No question, but just for our listeners to understand, just because you have a great drug doesn’t mean that you’re necessarily hitting it out of the park. A lot of these companies still struggle, so we’ll see.

Harlan Krumholz: Yeah, but they generate a lot of revenue, and they’re in a much better position than they were before they had this drug. They were mostly selling insulin before. All right, let’s get on to our guest, Ali Rahimi, former student of mine. I’m so glad to have him on.

Howard Forman: Dr. Ali Rahimi is the CEO and founder of ALYKA Health, a digital heart health app that uses personalized data-driven insights to support patients between clinic visits and improve health outcomes. A practicing cardiologist and longtime advocate for quality improvement in patient empowerment, he previously served as physician director for performance improvement in cardiovascular quality at Kaiser Permanente Georgia, where he continues to see patients. He’s also an adjunct professor at Emory University’s Rollins School of Public Health. He received his MD from the Medical College of Georgia and an MPH in health policy and management from Emory. He completed his residency in internal medicine at Yale New Haven Hospital, Yale University, followed by a cardiovascular medicine fellowship at the Beth Israel Deaconess Medical Center at Harvard.

And so, first I just want to welcome you to the podcast. This is a topic that is of great interest to all of us, and I did my own little due diligence studying a little bit about the app and trying to understand it better, and it really does seek to engage patients actively in their own care. That is obviously something that Harlan and I both embrace fully and hope that it can make a meaningful difference with patients. Can you tell us about what is the traction that you have with patients once you get them to use the app one time, and how do you keep them coming back for more?

Ali Rahimi: Well, first off, thank you, Howie and Harlan, for this opportunity, it’s a delight to be with both of you today. Generally, taking a step back, as to our why, you speak about engagement, and after many years of being in public health and practicing medicine, you come to recognize quick and fast that we do not have a diagnostic dilemma in medicine—we can make diagnoses of hypertension, heart disease, and whatnot—nor do we have much of a treatment dilemma. We have treatment algorithms and pathways, but what lies before us is a patient engagement empowerment opportunity, and that is the journey that we’re on. And to answer your question, we have been working steadily to create an interface, a user experience, that is super engaging, a form of digital health entertainment. So, when folks come in on our application, we try to personalize the experience, and we started early on as low as 45% engagement, where folks were logging in, watching content or whatnot, we’ve driven that as high as 71% today after many iterations of looking at the content and the interface.

Harlan Krumholz: What a pleasure to have you on the podcast. I’ve had so many students over the years, I love all of them. You among my students has always distinguished yourself by your commitment to mission, your willingness to do the work, your aspiration to touch people. The paper that we did together really was on financial barriers, how people couldn’t quite get what they needed, not because of anything more than what their financial circumstances were. You just have bloomed, you’re a great clinician, you’re on this journey with this company... I wonder if you could just give people a little bit of perspective about what that’s been like for you personally and how you actually ended up deciding to take this on, because you’re still a practicing cardiologist, and yet you’ve taken on this enormous opportunity to try to help shift the curve of how well we care for our patients, how well they do. So I know people listening might want to know a little bit more about your own personal journey here. You go to cardiology fellowship at BI [Beth Israel Deaconess Medical Center at Harvard], you end up going to Kaiser, can you just pick up a little bit on that? Why did you decide to go to Kaiser? What did you do, and how did it bring you to where you are?

Ali Rahimi: Yeah, thank you, Harlan. Again, it’s a pleasure to be with you. It’s so nice to see you and be together. Our journey is guided by those experiences and mentors that we have along our way. My first passion started back when I was at Emory getting my MPH in health policy, that was a time when we were trying to get health insurance reform, very much interested in access to care, and then, as I continued my education, had the opportunity to fortunately be mentored by you during my three years in New Haven, and seeing the good work that you were doing and leading quality outcomes research. And trying to identify that gap in knowledge, we’d always ask, “What is that gap in knowledge that we can answer?” And the education continued onward to Boston, to look at cardiology. I was always, as the guidelines were coming out and the papers were being published, was always puzzled by how can we operationalize the knowledge that we’re generating. How do we scale and spread best practices? And I remember we had a conversation, I was very much going into academia to teach and do research, but then the opportunity came available in Georgia, where Kaiser was internalizing cardiology, creating a new division, and to be their director of cardiovascular quality at a population level. We had a heart-to-heart, it was a very difficult decision to not do pure academics, but here was an opportunity to operationalize best practices and look at a population level of how we can do better. And that’s the journey I was on for eight or nine years, oversaw all sorts of different quality measures and programs, also led performance improvement—

Harlan Krumholz: I just want to interrupt to say one thing, because I think it’s really interesting for people to hear. One of the hardest nuts to crack is this issue about getting people with high blood pressure under control. When we say “under control,” what we mean is that the levels of their blood pressure are at normal or near normal levels, being able to use the medications we have. I have never encountered anyone who achieved what you achieved in Kaiser, that was only one of your remits, you had lots of different responsibilities. But at least, can you brag for a second about what you were able to achieve with Kaiser? Because I have never seen, even to today, anyone be able to do what you did with a population like that.

Ali Rahimi: Yeah. It goes down to our training in looking at engineering principles, I always thought we need more engineers in medicine and healthcare. So, my training in Lean and Six Sigma looking at process management. So, we looked down at processes. What are the processes at the high level that we need to implement and spread? One, it was getting an organizational commitment for that blood pressure is a vital sign; there’s a reason we call it a vital sign. And wherever that is taken outside of acute care or pain management clinics, you have to own it. So, whether it was dermatology or internal medicine, it’s not just primary care, all the specialists, if you get an abnormal blood pressure, we have to do something with it. And we focused on process measures and managed it throughout the entire region, and then we spread and scaled those best practices.

Harlan Krumholz: And what did you achieve?

Ali Rahimi: We went from 68% hypertension control to 90%. It took us about two and a half years, but we got there.

Harlan Krumholz: Ninety percent. So, just keep going now with your story. So you’re at Kaiser, you’re doing this kind of stuff, that’s, by the way, is just a mind-blowing number, that you were able to get 90% of the people in Kaiser with high blood pressure down to levels that were considered to be acceptable—that’s crazy. But keep going, keep going with the story.

Ali Rahimi: Yeah. So, we got to 90%, notably we still had a 10% disparity gap between whites and African-Americans, and that didn’t settle well, but we were able to achieve that. Again, lots of in the way of change management, organizational operational commitment to open up nurse visits for follow-up blood pressure readings.

We looked at the guidelines. We did not micromanage our clinicians to say “These are the treat-to-target medicines,” and this is a stepwise therapy, but went a couple steps higher at an operational level. And then, we continue to do that across statin adherence, all sorts of other, if you will, HEDIS and quality measures, focused on readmission rates, again, process measures, make sure everyone has a seven-day follow-up, because that’s the early work that you led. And again, it’s about deployment and scaling best practices across a system that is challenging but achievable.

Howard Forman: I want to go back to the app because I really want people to understand this and understand why it’s important, but why it’s also so challenging as a business. You are importing data from the medical record with the patient’s consent to be able to track real-time things, both from the medical environment as well as wearables or other data that they’re able to acquire, and I think one of your pitches is that patients might see their cardiologist four times a year, but they still have 360-plus days of the year beyond that. And I get the fact that you’re trying to engage with them and make it very interesting for them to work with that, and that the goal is, as Harlan was alluding to also, to try to get them to be more compliant with their regimen so that they achieve better outcomes ultimately with process measures and ultimate outcomes.

I’m trying to understand, though, how do you compete in a world where there’s so many companies out there now that are offering quick ways to make your life better, where you input data and they’ll tell you everything you’re supposed to know about you, using biometrics, if they claim biometrics, or simple things. How do you compete with that when what you are selling is sort of the real deal and everybody else is selling Christmas?

Ali Rahimi: Yeah, that’s a great question, and I believe the principles of science, of data, of outcomes will always be the next best thing, or the stories or ads people tell. And those are from the teachings I learned by Harlan’s side, and where I trained. We focused when we took a step back and said we need to be smart by data, and in 2019, that was when the ONC Cures Act with the data interoperability and FHIR, we wanted to create a smart application, and we needed to have data. We wanted to curate that data from the EHR, so we knew that data was important, so we really worked on that data piece.

Second, self-reported outcomes data from patients, their behaviors, that piece of data is important too, where we can understand their challenges and their opportunities from primordial behavior prevention to some of the conditions that they may have. And then lastly, with the era of more devices and wearables, those data pieces were important as well. So, how do we integrate three layers or multiple layers of data that then we can connect to the latest science and evidence that is proven to help both behavior change and improve outcomes? And I think that is our North Star or guiding light to be evidence-based and to be data-centric.

Harlan Krumholz: So, give us a sense of where you are with the company. Where do you stand? How do you stand with fundraising? What have been the principal challenges? What do you see as the next milestones? Give us a little bit of an entrepreneur’s journey of this. You’ve been at this for a bit, where are you?

Ali Rahimi: Yeah. Yeah, first of all, I think everyone will tell you, you never know what you’re completely getting yourself into, having a great idea is not even half of it. But certainly it starts with going in it for the right reason because it’s a long journey, it’s an arduous journey. So, you have to be mission-driven. Our mission really centered on the great opportunity around prevention, around the impact we can make worldwide across geographies and cardiovascular care, prevention and management. Next, it comes down to surrounding yourself with an amazing team. So, once we had the idea started, going to my closest friends, folks that I trained with and my mentors and whatnot and said, “This is what we’d like to do. Would you like to help us?” So, we brought together an amazing team. And the part that they don’t tell you is it costs a lot of money to bring an idea from zero and to get it somewhere, and that each stage, because you’re zero-revenue and then one day pre-revenue, then early revenue, your costs always exceed that, and you’re having to raise funds.

So in the beginning we raised capital from friends and family, our advisors, our team members all invested, and then we went through two rounds, if you will, of seed and an extended seed round where we were able to raise over about five and a half million dollars in capital, and of that capital we were able to devote the first probably 90% of it to pure product research and development. And we’ve gotten the company to the stage of commercialization after about four and a half years of really iterative development, the nice part of software, and what we did is we made it available direct to consumer on purpose so we can get our first 10,000 user downloads and to help graduate those folks so that we can learn and continue refining the solution.

Howard Forman: And you already mentioned that you have as much as a 71% traction rate with return visits from individuals. What has been the experience with the payers or providers that you’ve been contracting with? Do they seem sticky? Where are they excited and where are they directing you maybe to change the product?

Ali Rahimi: Yeah, so where we’re at in our stages, we provided the application available in the App Store and Google Play so that now it’s available worldwide. We have users in the U.K. and Australia and Canada, where we have a patient advisory or member advisory group, where we’re continuing to refine the application, understand the user interface. Initially we would have 900-word blogs. They were not reading it. We dropped it to 500 words, they were still not reading it. Not until we got to 300 to 325 words at a sixth-grade reading level, that was empathetic in a warm tone, with pictures, were people reading those blogs. So, really the first four years of the product journey has been really bleeding insights from our users to get it ready for this, if you will, this B2B commercialization stage. We had our first client that had close to 10,000 members, a self-employed insurer, and from them we learned onboarding.

Just because you have a great product does not mean people will download and use it. So, going to your question, we really have refined those processes. We use process management, if you will, to measure and monitor, if you will, adherence and what parts of the app people like, what areas they don’t, and make iterative changes. So, now we’re going to the B2B market, meeting with payers. Our ideal customers, if you will, are those that are accountable care organizations or value-based care, they see this as a must-have, not a nice-to-have, where we need to improve patient engagement to improve health outcomes, that’s lean and scalable.

Harlan Krumholz: One of the things I’ve found is that making the pitch about better outcomes is sometimes harder than making the pitch that you’re actually going to save money. So, when you’re encountering potential customers, you’re trying to figure out how to position this. Do people respond to the idea that you might improve outcomes, or are they looking for you to help them understand how you might decrease healthcare utilization, improve productivity, and so forth? What are the levers here that you find most important in this area to try to get traction?

Ali Rahimi: Yeah, that’s a great question. We first always lead with the patient. We say that we have an opportunity in healthcare to elevate the care experience, and we’ve taken our patients for granted, sending them home with a black and white after visit summary is not working. So, number one, we have to elevate that care experience. And then second, looking at how we’re going about doing that, their current state where we’re hiring more care managers and extenders of care, nutrition, pharmacists, complex case managers, transitional case managers... There was an article recently in The Lancet that showed that the number of providers over the past 40, 50 years has been relatively flat, but the number of adjunct care providers has been increasing significantly, and that’s not sustainable. So, we lead by asking a question as to how are you closing care gaps? How are you moving care gap closure upstream, and how much is that costing you? And a lot of times they don’t have an answer because it’s such a human-touch-heavy component of providing care. And then we offer, what if we could provide a pure-software touchless solution that can move care gap closure upstream in between those visits, whereby not only are you improving outcomes and quality so you can realize greater revenue because your Stars or HEDIS ratings are going up, but from an operational standpoint, you now have a lean, scalable solution that requires less human intervention.

Harlan Krumholz: All right, well, we’re getting, first of all, this is great to hear, we’re getting more toward the end, we’ve got lots of people who are listening here who may even be investors, and people who are looking to pair with groups that are doing exciting interesting things. Which, I’m going to give you a chance to give your final pitch. Where are you? Are you in a raise now? What are you doing, and what would you like? If there’s somebody on the line listening who’s an investor, what’s your pitch?

Ali Rahimi: Right now, we’re going to change the world. Our goal is to affect 10 million hearts in 10 years worldwide, we’re working and building a platform of virtual care management that’s data-smart. We are speaking with a number of healthcare systems and healthcare plans that see the value that we’re providing. Once we sign the next couple of contracts, where we meet our annual revenue targets, likely in the next six to eight months we’ll be looking to go to our next round of raising capital, but mindful that we’re looking for the right partners that understand our mission and would like to see this in the long run and see this spread globally.

Howard Forman: Well, we wish you the best of luck. It’s exciting to see what progress you’ve made and also to see you following your passion. So, thanks very much for joining us on the podcast.

Harlan Krumholz: Yeah, thank you and good luck.

Howard Forman: Thank you very much, gentleman.

Harlan Krumholz: It’s great to see you.

Ali Rahimi: It’s been a pleasure.

Howard Forman: It was great.

Harlan Krumholz: Well, that was a terrific interview. That’s an example of somebody who’s got an entrepreneurial spirit, has been working in the trenches, trying to get something to work, trying to feed his family at the same time, trying to make the world better. Anyway, I admire his effort and what he’s accomplished so far.

Howard Forman: Absolutely.

Harlan Krumholz: I wish him the best. Well, let’s get to your segment. What’s on your mind this week?

Howard Forman: Yeah. I spend an awful lot of time in class talking about how little we actually know about medicine, like we think we know a lot, but there’s a lot that we’re just not confident about. I use lots of examples, we’ve talked about some of them on the podcast, and our listeners know by now, certainly, between the two of us, that science is iterative and frequently gets things wrong, even while attempting to do the most good based on the best evidence of the time. Sometimes facts just change. I thought this week I would reflect on two major diseases where new evidence might be pointing us in new directions. And first, prostate cancer. Reminding our listeners, 300,000 men each year are diagnosed with prostate cancer, about 35,000 will die from it, so a little more than 10%, and the challenge of prostate cancer is how do you diagnose and treat it when you know that most men will actually die with prostate cancer, whether they know it or not, and not from prostate cancer.

How do we treat the ones that actually can be helped? And for many years, prostate-specific antigen screening, we call it PSA screening, was part of the recommended approach for men under the age of 70. And we could spend a lot of time even talking about why 70 was a fair number to use. And over that same time, there were many who were practically evangelical in the belief that PSA screening was the best way to reduce deaths and morbidity from prostate cancer. And then there were others in the other direction who would point to research that said, the risks from both the workup and the surgeries on the less lethal forms of prostate cancer far outweighed the benefits to those who might have died from it. And in the meantime, clinicians and policy analysts have mostly been neutral to negative about using screening in more recent years.

In fact, the U.S. Public Services Task Force rates PSA screening a C on a typical A-to-D-and-Fail rating level, and they specifically recommend that screening only be undertaken after explicit discussion of risks and benefits to the patient and only after affirmative consent is given by the patient for screening. And I’m pointing this out because it’s really easy to just add on a lab test to blood that you’ve already drawn on a patient. So, last week, an enormous prospective study out of Europe that included 160,000 men demonstrated a 13% reduction in mortality in the group that was randomized to get a screening. The follow-up period was a median of 23 years, and the study initiated enrollment 32 years ago, which is just amazing. Both the article and the accompanying editorial highlight the need to also consider the immense progress made in identifying high-risk patients and using MRI to better determine risk to patients.

This certainly made me reconsider my own preference to not be screened, I have not engaged in screening to this point, and I do think more progress may yet be made in this space. So, I think people need to think more, I’m going to come back to that at the end. Pivoting to the second related topic, over 100,000 women have a mastectomy for breast cancer each year in the United States, and many of them have what is considered intermediate-risk breast cancer, meaning that they have more localized disease with risk of progression, but no immediate further spread, at least that’s how I’m going to simplify it for our purposes here. In these patients, it has been the general standard of care, or at least recommendation, to use radiation therapy to the chest wall after mastectomy to reduce the risk of chest wall recurrence, which is a significant risk in these patients, or at least was a significant risk in these patients.

There had been considerable evidence to support this approach, but thankfully, over the years, other advances including earlier detection and systemic therapy after detection have changed the calculus. In a newly released randomized trial from the United Kingdom, investigators found no significant difference in survival between those receiving radiation and those who did not, at a median follow-up of 9.6 years, another very long study, this one began enrollment 19 years ago. I’m highlighting the times of each study because these studies are longer than some careers, and it is a true credit to these teams that they carry out this essential work. I don’t believe that either of these investigations by themselves are going to dramatically change practice in the near term, but they should definitely encourage patients and our listeners in particular to always ask their clinicians for as much recent data and evidence as possible to make an informed decision.

Harlan Krumholz: Great recaps, Howie, both of them actually, probably really relevant to some people who are listening. I just want to get to the one about the PSA, so no PSA for you, no way no how?

Howard Forman: Well, in the past, no way no how, now I’m going to really rethink it because it really does start to raise the possibility that you have a real survival benefit.

Harlan Krumholz: But it’s small, still.

Howard Forman: It’s small, but it’s not—it’s like out of every 13 people that would have prostate cancer, one life is now being saved, that’s not as small, considering how many people I know that have died of prostate cancer just in my lifetime, it’s starting to get into a number, and the harm is dramatically lower than it was 10 or 20 years ago.

Harlan Krumholz: Just say the way I’ve thought about it, some of it’s about avoidance of regret, the reason I have agreed to have PSA screening is because how would I feel if I end up with disseminated disease that I... I don’t know. It’s just like, it’s all psychological.

Howard Forman: I agree.

Harlan Krumholz: It’s like, what side of this do you want to be on? What do you want to know? Are you willing to put yourself in a position—

Howard Forman: And where’s the tipping point?

Harlan Krumholz: ... what’s the tipping point? How big does it matter to you?

Howard Forman: Yeah.

Harlan Krumholz: But anyway, great information. 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, email us at health.veritas@yale.edu or follow us on any of social media, and now we have even an Instagram account, so it’s going to be at HealthandVeritas with “and” spelled out. So we look forward to seeing you on Instagram.

Harlan Krumholz: And we always love hearing from you, give us feedback, helps people find us, and we do our best to respond.

Howard Forman: Health & Veritas is produced with the Yale School of Management and the Yale School of Public Health. To learn about the Yale SOM’s MBA for Executives program, visit som.yale.edu/emba, and to learn about the Yale School of Public Health’s Executive Master of Public Health program, visit sph.yale.edu/emph.

Harlan Krumholz: We always like to give a shout-out to our superstar undergrads, Tobias Liu, Gloria Beck, to our fabulous producer Miranda Shafer, and to my, I like to talk about how great it is for me to be with the best in the business, Howie Forman.

Howard Forman: Best in the business. I appreciate you Harlan, very much.

Harlan Krumholz: Talk to you soon, Howard.

Howard Forman: Thanks Harlan, talk to you soon.