Oncology Unscripted With John Marshall

No Evidence of Disease—No Need for the Knife?

John Marshall, MD: John Marshall for Oncology Unscripted. Let's talk a little science and cancer medicine. I’m gonna come at you from a little bit of a different angle. Yep. A GI cancer angle, but a little bit different.

We have long felt in order to cure GI cancers, we had to do surgery, that it was the only way to ultimately cure people. But we all know that when we do neoadjuvant something could be chemo chemoradiation. we operate. A certain sub portion of the patients have no evidence of disease in their pathology specimen, and we sort of say, we just put somebody through a big operation gastrectomy, esophagectomy, could be a Whipple, could be a rectal surgery that they actually didn't probably need or benefit from, but we had no way of determining that until we did surgery. And so, as you know as well, there's increasingly neoadjuvant therapies for a bunch of different cancers. People are having good clinical responses where after the neoadjuvant treatment, by scope or by scan, and now by new blood testing, we can't find evidence of disease. We're torn about whether we can simply watch and wait that patient and see their cancer comes back, or do we have to operate anyway.

And there's a new paper that just came out, that I used actually in last week's tumor board here at Georgetown about watchful waiting in esophageal cancer versus surgery. So basic story, neoadjuvant treatment, everybody got it. If you had a complete clinical response, you were randomized, so not done in the United States. We'd never pull it off here, were observed for clinical recurrence and not operated on unless they had a recurrence. The other half were operated on, and then they looked for survival. And believe it or not, there was no difference survival outcome. So, some of those people avoided a surgery that they didn't need in the end and no impact on the survival. Now we still need to do better because it's still pretty crummy survival in this group of patients whether you had surgery or not, but still no difference.

In rectal cancers, we are increasingly not doing surgery. I've got a 35-year-old woman who had a very good initial response, a very good response to chemoradiation, no clinical evidence of disease. Doesn't want a colon surgery and a permanent ostomy, as you might imagine, at 35 years of age. And we've been doing watchful waiting, including doing MRD testing, and so far, nine months with no evidence of disease. And I'm sure all of you have patients like that. 

We are also, of course, doing this in pancreatic cancer. And the reason for obvious reasons is that it's a difficult operation. A lot of people don't want the operation. More often, it's because of where the tumor is. It might be grabbing onto a blood vessel that the surgeon doesn't really think they can get around. Or it might be that the risk of the surgery is just too great for that individual patient. So, we are doing neoadjuvant treatment. We are doing radiation, sometimes maintenance after, sometimes not, and observing. And you, like me, have had over your career some patients whose tumors never regrew and maybe just maybe got out of the need for surgery. So, this then brings up. What are the right treatments? How do you pick which patients should have surgery, which you're not. The current neoadjuvant study that's in the cooperative groups here in the United States is surgery first versus chemoradiation first, followed by surgery. Should we begin thinking about a no surgical arm in this group of patients? As our drugs are getting better, as we are learning more about targeting RAS and BRCA and the other molecular targets that we have. Will we get to a place where we can actually increasingly avoid what is fairly morbid surgery? Let's particularly think about pancreas cancer, in this regard, because remember. It's very good at sowing early seeds. It's very good at metastasizing early, and in fact, only one out of 10 is found with resectable pancreatic cancer at initial diagnosis most have already spread. So, the value of that resection, don't get me wrong, it is the way we cure people, but the relative value of that resection in the global scope of pancreatic cancer is increasingly in question. So, as we pick therapies, highest response rate, three drug combinations, 5-FU, irinotecan, liposomal irinotecan, and oxaliplatin. Highest response rate, highest survival in the books for metastatic disease. As we use regimens like that in the neoadjuvant setting, as we add to those regimens with new targeted therapies, I do think what we will see is more and more opportunities for observation in that patient population.

We held a think tank here at Georgetown back in the fall where we invited people from all over the country who were experts in this field to think about this issue and the consensus among, what I think are some of the smartest people in the world around this subject was, that yes, indeed, the improvement of chemotherapy, the advent of precision medicine, the increasing role of immunotherapy in this space will get us to a place where, in fact, we are curing more and more people with pancreatic cancer. We need to get there. We need to make the progress. We need enrollment in clinical trials, but I believe we are going to see it. I believe we're going to see progress in 2025 and 2026. So, stay tuned for more positive papers, more positive data in the world of GI cancers and in pancreatic cancer, specifically.

John Marshall for Oncology Unscripted.

MedBuzz: This Isn’t Just About Harvard—It’s About All of Us

It has indeed been a busy couple of weeks here in Washington and around our country. Specifically, the relationship between our new federal government and academic institutions. I mentioned this previously about the issues between the government and Columbia University. And as everyone knows who's listening in, the most recent confrontation is between the federal government and Harvard University. You know that recently Harvard has refused to comply with the government's demands. There's been a countersuit back from Harvard to the federal government, so I guess discussions are ongoing, Harvard did release the letter that was sent to them lead signator of this letter, I have it here in my hand, is a guy named Josh Gruenbaum, who is a government appointee by the new administration. He's the commissioner of the Federal Acquisition Service. He's co-signed by a couple of other people, I wanted to just make sure that our audience out there knows about this document can read some of the language that is in it because as a professor at an academic institution, as a member of a, a medical community out there trying to advance science, trying to be inclusive and not only who we take care of, but also who is doing the care taking. This I thought was worth bringing in short, but some high level discussion. It's a multi-page letter. You can find it online yourself first from the government. An investment, their grants, is not an entitlement, it requires that you uphold the civil rights laws, whatever those are. And they get to be the judge of whether you're holding those, upholding those civil rights laws. So, the first point they come forward with is government and leadership reforms. They want to reduce the power held by faculty, whether tenured or untenured, and administrators who are more committed to activism than scholarship. It's all it says. So how do you decide, how do you judge a faculty member's commitment to, you know, in their words, activism versus scholarship? Aren't those two in some ways connected? That was the first paragraph no longer can you hire based on race, color, religion, sex, or national origin. They're gonna contradict themselves here in a minute. No longer can you admit students based on that. No longer can you admit students, and here's the contradiction, from countries hostile to the American values, institutions inscribed in the Constitution and the Declaration of Independence, including students who are supportive of terrorism or antisemitism. So how are you gonna not do sort of biopsies of who people are, but at the same time not allow students who represent terrorism or antisemitism? They bring out this thing called viewpoint diversity. Which again seems to me to be contradictory. They were asking Harvard, not asking, telling Harvard to audit their student body, faculty and staff and leadership for viewpoint diversity. They're supposed to produce quarterly reports.

It's supposed to be by an outside group that the federal government approves. So, they're gonna have to hold up standards quarterly so that they're meeting this rule. there could be no program. with Records of antisemitism or any other bias. Pretty broad. One that's we are all struggling with is discontinuation of DEI. So, it can't be part of anything. And that students must be disciplined are not complying with all of this. So, it then puts the role of the leadership of the institution, the academic institution of overseeing and monitoring their students for compliance with all of these rules. And Mr. Gruenbaum signed that along with some others.

Can you imagine being the academic administrator who opened this letter and began to read it? You know that there are billions of dollars at stake with this relationship between just Harvard and the Federal government, and we as institutions are struggling with, do you just comply with these things? Because that's the new law of the land. Do you push back and say, that isn't the law of the land? Do you have to prove that? What really is the truth here and what do we have to do? But you can understand why this is threatening to what is truly been special about United States education, and that is the freedom of speech, the freedom of thought, the challenging of each other, and our thoughts. Acknowledging what we know, acknowledging what we don't know, whether that's around science or other fields, and investing in improving our knowledge and our understanding in that we make the world a better place for us all. 

I worry about this letter a lot and I'm pretty sure you do too. For Oncology Unscripted, this is John Marshall. Let's keep our heads up. Let's keep figuring out the truth and let's make sure we share that with others. Every day makes the today a little bit better for someone nearby. That one little rock you throw in the puddle that makes the ripple, you never know how far that ripple will reach. And I'm convinced that if we keep our heads up, and, if we keep tossing those rocks in and keep making those positive ripples, that we will keep the world headed in a better direction.

John Marshall Oncology Unscripted.

Truth, Science, and the Next Big Leap: A Conversation with Dr. Mace Rothenberg

Welcome back everybody out there and wherever you are, might be video, might be audio, might be both. This is John Marshall for Oncology Unscripted. And it's been a busy week, as they say on the John Oliver Show. There's been a whole lot going on out there in the world of oncology, healthcare, relationships between the government and healthcare providers, et cetera. So, there's tons to talk about, but I want to focus right now on keeping truth and science alive. And so, I am lucky enough to know one of the world's experts. In both truth and science. Not only the creation of truth and science, but the maintenance of truth and science.

And this is a longtime friend. We won't say how long, but a longtime friend and I would actually go as far as. I refer to him as my Obi-Wan Kenobi, one of those people who had a major influence in my decision making early on in my career around GI cancers and clinical research, et cetera. And this is Dr. Mace Rothenberg. And Mace thank you first so much for being willing to be interviewed and join us on Oncology Unscripted. Welcome.

Mace Rothenberg, MD: Thank you, John. Thank you for the very kind introduction.

John Marshall, MD: I am not done because at first you started. As sort of a dumb GI oncologist, a little bit like me, but you were into drug development. You were into caring about the patient. You were into connecting your academic institution with the state of the art science, and, you were one of those folks who coached me and mentored me, as I said. But then, you surprised me, you surprised many of us, when you made a decision, back before it was something that was done regularly, of joining the industry. And I was wondering if you could just start a little bit of talking about that decision, however many years ago that was about leaving academic, medicine and cancer and going over to industry.

Tell us a little bit about that process.

Mace Rothenberg, MD: Well, it actually starts when I was training at the National Cancer Institute. So, the first part of my oncology career was actually spent in government. I did my three-year fellowship there, and then I stayed on as a junior faculty member the NCI. And then I developed some great skills, great interest in drug development, and then I got a call, one day from Dan Von Hoff at San Antonio who invited me to join academia at the university in phase one drug development. I didn't really anticipate this, but it was a call that I received, and I said, you know what, given my interests, this is the next natural step in my career. So, I moved from government to academia for seven years we were in San Antonio. The next 10 years were in Nashville at Vanderbilt. During that time, it was an opportunity to evolve as the field, as opportunities presented themselves. So, when some of the drugs we had worked with in San Antonio, like gemcitabine and irinotecan ended up having applications in GI cancer, that became my area of focus. As I developed skill in designing and running clinical trials. Had a chance then to run the phase one drug development program at Vanderbilt, and then as translational research, linking the laboratory in clinic came along, and things like SPORE grants were designed to really encourage that. I branched out into that and became co-principal investigator of the GI SPORE grant at Vanderbilt. So, I think throughout my career there was always a recognition of what I liked doing and what I was good at. But also, recognition when the new opportunity came along and I was ready for, and that happened again through a call in 2008 when I was at Vanderbilt about a new opportunity at Pfizer. Now, we've all gotten calls throughout our career from industry, and we usually say thanks, but no thanks.

John Marshall, MD: I'm too much trouble. They never call me Mace, just so you know. They're like, no, not that one. 

Mace Rothenberg, MD: And, and so they were reorganizing one of the business units to be focused on oncology. They had a really great pipeline, nor known as an oncology company at the time, but they were making a real commitment. So, I decided that even though that was unanticipated, that I felt that this would be a next opportunity for me to contribute in a way I hadn't been able to before, so I decided to take that big plunge and I, I had a, a tremendous experience at Pfizer for the first 10 years, running clinical development, for the

John Marshall, MD: Let me, let me interrupt you there. Because you, because you, that, that's that decision. There are a lot of clinicians who do get that phone call.

Mace Rothenberg, MD: Yeah.

John Marshall, MD: And they think, okay, I'm gonna, this is gonna be a very different world. 

Mace Rothenberg, MD: Mm-hmm.

John Marshall, MD: You're trained, you've done your whole life about seeing patients delivering care to patients. That's your world. That's your culture. Give me a little flashback on how unsettled that was, or were you excited? Was the excitement more than the unsettled part of that?

Mace Rothenberg, MD: I think with, with all big decisions, we have to think about what we're getting and what we're giving up, and I had to go through that whole thought process because what I love doing, seeing patients, being able to bring ideas from the laboratory to the clinic, being able to design the clinical trials, having the opportunity to, grand rounds to be the discussant at professional meetings like ASCO. I had to think about whether I was ready to give up those things in order to take on new responsibilities of running a large global program. Being able to prioritize the drugs within the portfolio to be able to identify where the opportunities were for us to make a big difference with the drugs we brought forward. I really had to think about that, that trade off. But as I, I've been fortunate in the big decisions I've had in my life, both personally and professionally when I sat down and thought about it, all the indicators pointed in one direction. And that was for me to move from academia to industry because I realized.

John Marshall, MD: Let me poke at one that, because when I thought about this in all sincerity over, over career. You know me, I'm a big mouth. one of my biggest worries was I was losing my ability to write my own script and was now being given a script. And you've, you've, you have, you're different in that you, you're like, you say you're my Obi-Wan. You have this sort of good, deep rudder. You're centered; you're focused. So, when you had to take on a company script, if you will. Did you feel that way? Or coach me a little bit on that experience.

Mace Rothenberg, MD: You know, I didn't feel that way. I felt that they were recruiting me because they needed my critical thinking abilities, my ability to be able to, to take the information that was available to sift through it, to analyze it, and then to be able to come up with a recommendation.

John Marshall, MD: Let me go, let me go a little deeper then. So, what, what if I was younger, you got a really cool high-level position too,

Mace Rothenberg, MD: Mm-hmm. Mm-hmm.

John Marshall, MD: have some junior people listening to us today. So, what if your job is at a lower level, you're given one drug, you're to develop that one drug or whatnot. It is a very narrow focus that you now have. I thought of that as both a positive and a negative as an individual, as you've seen other folks come along. And as the culture has shifted that more and more, industry is hiring physicians, do you see that as a, a distinction or not?

Mace Rothenberg, MD: Even though you may be assigned to one project or one drug, you are not defined by that one drug. Your career does not depend on that one drug. In fact, when there were failures in our portfolio during my tenure at Pfizer, no one lost their position because the drug they're working on failed. In fact, we needed to be very honest and recognize what the drugs we thought they could do and what they actually could deliver and then be able to re-deploy those assets to areas where they're more likely to be successful and to help patients. And so, what I would tell people in my team is that your skills are too valuable to spend it on toiling on a drug that's never gonna help a patient. We need to redeploy you in drugs that will help patients. And that's, that's the way we're able to operate. So, I don't want anyone to ever feel that they're defined by the success or failure of one drug. Your career is more than that. You are more than that.

John Marshall, MD: So, you had a remarkable first career developing new medicines that have had an impact on patients around the world. You had a remarkable second career where you then were able to deploy this and develop even more pipeline, with your commitment to Pfizer. And now, I recently figured out that you got a third career cooking now as someone who's going to be a keeper of the truth or helping to provide others with the truth and this concept of building an essentially a science or medical or biotech museum.

And our audience would really love to hear about this. So, I'm gonna shut up and you tell us what your newest career is all about.

Mace Rothenberg, MD: So, something I'd been thinking about for, for a while even though there were some tremendous advances in science and medicine in the course of our careers and our lives, all the places and venues that you go and see these things. Museums of medicine, for instance, were very static. Basically, displaying artifacts behind glass that you read about. And we know how exciting and wonderful and wondrous and joyful medical research can be. Scientific discoveries can enable us to gain insight into health and disease and from those insights come new medicines and interventions that change our lives and change the world. Yet there was no place that captured that excitement, that wonder. So, I began talking to people about it. And for several years people said, interesting idea. Good luck. It was only in late 2021 that in the conversation I was having with Larry Marett over dinner, he was at that time, Dean of Basic Sciences at Vanderbilt. Someone I had known for 25 years whose response was different.

After I told him about this idea, he looked at me and said, great idea. Let's do it. So that's also something that's been critical in my career is having people who believed in me, believed in the idea and were willing to help along the way. So, this was one of those moments, and thanks to his belief and the resources, he was able to garner the, the people he was able to bring to the table. We took this nebulous idea and began to refine it to identify what the problem was we were trying to address. What the vision was, what the mission would be, because we needed something that could be able to convey this not just to other professionals, but to the general public whose belief and trust in science and medicine have been eroding for the last five years. Despite all the things that we've done, all the great renowned researchers and scientists and government officials who speak to the public. That has not gained the trust and respect and traction that we should have. So, I began thinking about other ways we could do this, and out of that, sprung the Museum of Medicine and biomedical discovery.

John Marshall, MD: Do you think that the trust imbalance, right as you, as you allude to, is that we are learning more and more about how things work? and the public is increasingly skeptical about what, what we know and what we don't know. True.

Mace Rothenberg, MD: Yeah.

John Marshall, MD: do you think that's because it's more complicated? Do you think there's counter voices that are being heard more strongly? The idea around this museum, around this information, resource is to try and level that field a little bit. And when we first talked. I was thinking about how I learned. I learned once I can see it in my head, once I can create a visual, once I saw in my head DNA spinning around, or once I saw a protein docking, then I got it and, and I could under, I could read it and see it at the same time and believe it. Whereas many people don't have that skillset or never really don't learn that way, for example. So, give me a sense from your angle. The problem of why the distrust, and why you think this strategy will help bridge that.

Mace Rothenberg, MD: I think for far too long we as professionals have spoken to the public as if there were other scientists and researchers and medical professionals, and that they were purely fact-based. That's what we like to think of ourselves, we're evidence-based. But the public. Isn't wired that way. They take the facts that we provide and put them into context of their own lives, their community, their political affiliate affiliations. lots of different factors that come into how much, how they process that information. And we've not been responsive to that. And one thing that I've known about myself is that I don't learn just when I'm presented with a list of facts. That's why I really wasn't very good medical student for the first two years where it was just rote memorization. It was only in the second two years of my training when we actually got into the clinic and got into the hospital and I could see patients who had those symptoms, and those symptoms put together into diagnosis that it began to stick with me. And so I think the same approach is needed in trying to convey the progress we've made in science and medicine by telling stories that engage the visitors and to do it in a way that uses 21st century technology, like immersive interactive platforms, to be able to take them on the arc from that scientific discovery in the laboratory all the way through how a medicine or intervention was developed and the impact that that's had on, on, on people.

John Marshall, MD: I really love you.

Mace Rothenberg, MD: that'll

John Marshall, MD: You know, I get you. I'd really love your opinion on, on, on this or reflect on this. We, in healthcare and science in general are quite proud of what we know, but it's only as we get older, you and me are actually comfortable in saying what we don't know. And so, I wonder on some level is that if, if we, if we came clean on what we don't know. Better. Would it also help legitimize those things? We do know, and I, I was thinking about, you know, putting together exhibits. Obviously, you're gonna put together things of what we know, of what we've learned of new, of, of knowledge, but isn't it also equally important to understand the list of things that we are curious about, or we don't know.

Mace Rothenberg, MD: Yeah. that is perfectly described from the perspective of a researcher. But when you, you, you take away that and look at it from a lay person's perspective, they want to know what is it, what's true? What should I do? And, and I'll do it, because they trust you. The problem is what they, what, what's often not conveyed is that you know this to be true as of today. Yet because of science and research, we're gonna know more tomorrow. And the next day. And the next day. And some of the things that we believe to be true today, may be proven to be not as true as we think they are tomorrow, or next year, or in five years. That's the nature of discovery. Whether you're talking about medicine or space exploration, we are constantly learning more, and that's something that we haven't conveyed to the public very well.

Think about the COVID pandemic when we talked about social distancing, cleaning services because we are concerned that COVID could be spread in that way and how later on we said, no, actually it's more spread through aerosol root. And people were confused. They said, wait a second. You told me one thing yesterday, another thing today, what, what makes me certain that if I do this today, it won't be reversed tomorrow? So, we didn't really get through to the lay public that this is, this is the nature we're giving the best advice we have based on the information we have today.

John Marshall, MD: I want you to, I want to spend the closing moments that we have together of telling us where are you with this idea? I know you're pretty far along. How can we as a scientific and medical community help accelerate your progress? Obviously, very important project that could benefit all of us, all of humanity.

Tell us where you are. How can we help you?

Mace Rothenberg, MD: Well, we've been in existence for about two and a half years. We have had receptions in major cities. We have launched a website. We have engaged with museum design and planning firms, and we actually have a three-phase plan for development. So, the first phase is going to be creation of an exhibit. In fact, the topic for the first exhibit is gonna be cancer, and it’s tentatively titled Cancer, from Despair to Discovery to Triumph. And it'll actually take visitors on a journey, not just throwing facts at them, but by drawing them into the story. So just as, as an example, when a visitor enters the exhibit, they're gonna be met by people, people of all ages and ethnicities and backgrounds, talking about what their lives are like as a truck driver, as a third grader, as a business person. And then, their lives were changed by one word, cancer. That brings people into the story, putting a human face on this, not just throwing facts at people. And then going into the exhibit, what is cancer? And the, the 12 essential characteristics that Hanahan and Weinberg described, which will allow people to explore and delve into that deeply. And in fact, understand why cancer detection is better because the cancers haven't developed all those characteristics yet, so they're caught early stages when they're treatable and curable. what? What we do to help the body fight cancer beyond just chemotherapy and radiation and surgery, but things like immunotherapy, cellular therapies, protein degradation, and again, imagine being able not just to read about what a CAR T cell does, but to actually climb in one. See how it's created. See how it's trained to recognize the cancer and travel along through the bloodstream. To see it find and kill that cancer cell. Those are the kinds of immersive experiences that that aren't available elsewhere and that we need to tell in order to engage people. Another thing is that we're not going to be trying to convince people of anything. What we're gonna try and do is open up what's currently a black box to the public to say, this is how science is, is performed. This is how discoveries are made, and this is how it's translated. We're gonna be very open about the fact that we're not always right. We make mistakes. There's a role of serendipity. There's the ethical aspect as well where we have, we have made mistakes over time. What were those mistakes? How were they detected and what steps were taken to correct them and prevent them from happening in the future? So, these are the things we plan for the museum, and I'm just, I can't wait. We're able to bring that forward and show people what we can do and tell these stories.

John Marshall, MD: I know you didn't ask, but I just can't resist. I think the CAR T thing needs to be bumper cars. You actually get in one and you bump into other cells, if you will, and you, you.

Mace Rothenberg, MD: right.

John Marshall, MD: There you go. I, you, you can just have that one for free. You, you,

Mace Rothenberg, MD: That would be great.

John Marshall, MD: We need to help you do this, and we'll certainly help promote the activity. We know it's both a fundraising effort, but also an awareness effort, that's out there to make this be a reality. And I,

Mace Rothenberg, MD: Yeah.

John Marshall, MD: know that all of our listeners hear the need and hear how your strategy and your project and all your past successes are funneling into a new one that'll be left for generations to come.

So, Dr. Mace Rothenberg, I cannot thank you enough for taking the time today to join us, and we really, really appreciate your time and we only wish you success in your third career as a museum developer. Mace. Thank you.

Mace Rothenberg, MD: Thank Really appreciate.

John Marshall, MD:

 I cannot thank Dr. Mace Rothenberg enough. First at NCI, San Antonio, Vanderbilt, and Pfizer now in the next phase of his career is going to build out a museum that's gonna change the lives of all of us in our understanding of science and help keep truth alive. So, Mace, again, thank you very much for joining us.

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We Funded the Cure—Now We're Pulling the Plug?

John Marshall: Welcome to Washington DC. My name is John Marshall. This is Oncology Unscripted. There is a whole lot of stuff going on out there, seemingly unscripted, seemingly without much in the way of a sense of motivation, really a plan. It's just blow it up. Let's see what'll happen after the fact. 

But let's stop for just a second and think about what science, federally funded science, has accomplished over the last many decades here. Because a lot of us, including a lot of the population as well as the government, feels like, it was really business that did everything, not the government. So, we should shift all of this money over to business and take it away from the government. So, they're firing all sorts of people here in Washington and around the country with the science community.

But let's start by acknowledging what science has done for our health. So first, we know that cancer mortality has fallen dramatically. If you think about when I first started as a fellow a thousand years ago, really the only investment in clinical translational research was through the National Cancer Institute, occasional company here and there, and all of this improvement that we're seeing today comes really from that beginning, and so we've had a clear, positive influence. But let's look at some of the details here. The concept of, I don't know, rituximab, immunotherapy, and multi chemotherapy treatments, and the cures for lymphomas comes out of government invested research, bone marrow transplant comes out of government investment research.

How about understanding HPV and using vaccines? I know. Vaccines are crazy things that we shouldn't be giving because they're terrible things, right? According to the current government. But let's talk about the discovery of HPV and vaccines, which is going to get rid of HPV-mediated tumors. 

What about imatinib? Remember that drug that was really out of the beginnings, of government research? But you know what? One of the ones that's my favorite is actually HER2. HER2 was discovered with government funded research, the therapies for treating HER2-targeting, transforming it from just a bad target, prognostically bad target, to something that actually is good news nowadays because we know how to treat it well. That was all done with government research, right? And so then here comes swooping in a pharmaceutical company under the name of Genentech that took it and made it into a billion-dollar profit that helped to fund other research.

And so, we have failed to value the innovation that comes from the government world, and there's just so much of it out there. And over the last month or so, there's been this dramatic downsizing of grants, grant applications, payment for grants that are funded, downsizing the number of people who are at the National Cancer Institute and other places around the world where there is federal funding for these with the, with the idea being that that's just wasteful, I guess that's the thought. 

We know that the NIH investment has fueled a great deal of economy in all of the places that it's ongoing. So, not only is it producing science and our understanding of the biology of cancer and other diseases, it is also helping the local economy. Then what really got me going on, this was an ad. I'm pretty sure you're probably seeing them too, at your home for our new president and our new, folks that have taken over, ruling our country in a completely different way. And in fact, this team had the boldness to put out an advertisement that in four years they will cure cancer. You should watch it. It's just unbelievable. If they're going to fire all of these people who are the brains and the brain trust and the innovators and they're not going to fund the science that's teaching us what we need to know in order to actually cure cancer. We're going to get rid of all of those people and somehow through some other mechanism, they are going to have cured cancer in four years. So, what have we got to worry about? Right? This is going to be all fine because don't you worry our boss is going to cure cancer.

Speaking of cancer that we need to cure. We've been talking a lot lately about pancreatic cancer and what a difficult disease it is, and despite great deal of investment and positive input around it, we've made some strides, but not the kind of strides we need to make. But I do want to reinforce the progress that we have made. I've been thinking a lot about pancreas cancer comparing to colon cancer. I'm still giving the same adjuvant therapy I've been giving in colon cancer for 21 years. That's an embarrassing statement. On pancreas cancer, we have made progress. We know the drugs that are working there better. We are curing more people with pancreas cancer. One of those innovations is liposomal irinotecan, and the idea that you could take existing drugs and improve their performance by modifying their delivery and the formulation, and that's what liposomal irinotecan is all about. So, we now have pretty clean data that frontline incorporation of liposomal irinotecan in a FOLFIRINOX recipe is in fact better than other options in frontline.

And so, it really begins to fall on us more and more to make individual decisions about which drugs we're going to use and when. And so, this pushes down onto each of us. A sort of plan or a strategy of what regimen do you give in frontline? What do you give in second line? Which of the drugs do you combine? I think the best data we have is with NALIRIFOX, if you will, in frontline. 

How much of this is going to be under our control? We are all feeling the pressure. How many peer-to-peer reviews are you having to do every week for what is essentially standard of care? I'm doing too many of them I have to tell you. So, we are clearly feeling an outside pressure in healthcare today about incorporating what we see as best of care for our patients, and so I want us to make sure that we are connecting, that the experts in your area and the generalists in your area are talking. And that we're sharing advice and optimizing individual patient care for all patients throughout our communities, because we know that if you do that, you get better outcomes. It's not necessarily about being more aggressive. That's often the term we use. It's honestly about being more effective. 

As you know, we've been interviewing some of the leaders in the world of pancreatic cancer and we thought it would be appropriate to reshow some of these key comments that leaders have made, such as Julie Fleshman, who started and runs the biggest advocacy group for pancreas cancer, PanCan.

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Pancreatic Progress: Revisiting our Discussion with PanCan CEO Julie Fleshman 

John Marshall, MD: Welcome everybody back to Oncology Unscripted. No script at all on this one and the person who's joining me right now, really, doesn't need a script because she wrote it. She was the one who really defined, in my opinion, what advocacy is all about. Taking maybe one of the most difficult, if not the most difficult, cancer, inspired by a personal story to change the outcome for people with pancreatic cancer. And I'm proud to say she's my friend, but she's also one of my mentors, as she has shown the way for so many as to how to really move the bar in advocacy. And this is Julie Fleshman, who is coming to us live and we're so grateful, Julie, for your joining us. So, first, welcome to Oncology Unscripted.

Julie Fleshman: Thank you so much for having me. 

John Marshall, MD: You are so awesome. And you know, I think that, but let me start from the beginning, because a lot of people were coming up on a change in our world. And we know that advocacy is a critical component to our success in making advances in healthcare. It's not just handed to us. We have to push the forces around us to make it happen. Maybe give us your Quick version of, you know, what inspired you and the value of advocacy in the world of pancreatic cancer. 

Julie Fleshman: I have a personal story. 25 years ago now, my dad was diagnosed with pancreatic cancer. 52 years old. Died four months after diagnosis. And I was devastated, and I didn't understand why there was nothing offered for him. Why were there no options? At the same time PanCan was founded and I was lucky and privileged to be hired as the first employee almost 25 years ago.

And I've really just watched, you know, the field, the pancreatic cancer field back then, there was nothing. There was no federal funding. There was no philanthropy. There were no, there's nobody studying the disease. There were no resources for patients and families. And you know, I really believe PanCan has been a catalyst for changing that. And today there is a robust pancreatic cancer research community. And I think a lot of exciting things on the horizon for patients. And so, you know, I believe advocacy being the voice of the patient, not backing down when everyone tells you this isn't the way that we get things done, but it makes the most logical sense for overcoming a hard disease and you keep at it and you keep chipping at it. And I believe advocacy is what gets us to where we're going and accelerates the rate of progress. And in this case, I think it has really helped to build a field that just didn't exist before.

John Marshall, MD: You did all that stuff. Let's talk about the important stuff. Why did you pick purple for the ribbon?

Julie Fleshman: So actually, our founder who lost her mom to pancreatic cancer, her mom's favorite color was purple. That is the story.

John Marshall, MD: I love, I love that.

Julie Fleshman: So yes, so you know, and it was one of the colors not taken, right? You can't, you need to have something different than the other cancers, but it is a great color.

John Marshall, MD: But all kidding aside, yeah, I actually have several purple ties now because of the of the purple ribbon. But all kidding aside, I mean, you have you and your team have built an incredible infrastructure, not just a Hill presence and an advocacy there. Not only a clinical research infrastructure that we'll talk about in a minute, but also operators standing by patients can call in, and get advice about what they should do with your team members. And in fact, I think that feeds back to the practicing clinician, because there's a lot that we don't know that's going on out there, particularly the general oncologist in the world of pancreatic cancer. I'm assuming each one of those was a decision and you needed to have the bandwidth to do it. Like how, how much struggle was that to get all of those resources together?

Julie Fleshman: Yeah, I mean, you looked at and said, okay, where are the gaps, and 25 years ago, there were a lot of gaps. One of the first and most obvious areas was, you know, when someone is diagnosed with this disease, there's no place to go for information or resources. So building that patient services program in the early days, you know, was so critically, I believe, important for helping patients be informed so that they can make the right decisions about their care and go in and be an advocate with their, you know, doctor. Just as you said, many physicians don't see hardly any pancreatic cancer patients. And so, to have someone come in and ask you questions about clinical trials, about testing, about these different things, and hopefully it is also helping to educate the health care professionals.

John Marshall, MD: Yeah. And you've given these folks a home, a club, if you will, where they can share thoughts. And I think with our, you know, the bad cancers, there isn't that sort of survivorship that you see in some other cancers. So you've, you've provided that place where people can interact and teach each other, which to me is just critical.

Julie Fleshman: Everybody needs a cheerleader, right? Whether you're a researcher, a doctor focusing on this tough disease, patients and family, someone who's lost someone. And I think that's what PanCan does. We rally the troops. We make people feel good about the work that they're doing and that there is hope and that we're going to get there. We just all have to work together to do it.

John Marshall, MD: Let me, let me kind of drill down on something you and your team were clearly setting those standards when you develop the concept around precision promise. This was an understanding that molecular abnormalities occur. There are different ones in different patients. We have targeted therapies. Could we drive progress in pancreatic cancer through that? And you, a lot of work, a lot of investment, a lot of science went into this, but it didn't turn out the way you want to maybe reflect a little bit about that and that experience for others, because, you know, for me personally, I think it's exactly the right way to go. And lessons we could share for others trying to do this and other diseases.

Julie Fleshman: Yeah. Yeah. So Precision Promise was an adaptive clinical trial platform. And so, you know, basically the goal behind it was that you could develop a drug with fewer patients, less cost, less time, a way to accelerate new treatments for patients. All of that's true. And I think we learned a lot about sort of that process, and does this platform concept work? And I think the answer is yes. However, in order to make it financially work, you have to constantly have new drugs coming into the pipeline on the platform. And that was the part that turned out to be the, the challenge. Part of that was, you know you were convincing a pharmaceutical company or a biotech company to develop their drug, that PanCan was going to develop their drug, they were going to lose control. So that proved to be an obstacle. The pharma and biotech companies, you know, changed their priorities and their strategies. And so maybe at one point they were developing this drug in pancreatic cancer and six months later they were deprioritizing the asset. And so all of those things became challenging.

 The trial will go on. another organization that is going to launch a new, you know, basically Precision Promise version 2.0 and learn from all the things that that PanCan learned over the last, you know, four years. And, you know, Some people have said it was before its time, you know, now with there's so much excitement around drug development and targeting KRAS and all of these things that maybe, you know, if we were launching it today, it would be a different story. We launched it in 2020 in the middle of COVID. It was, you know, couldn't have been a worse time to be launching a, a big, you know, basically phase three clinical trial for an organization like us that had never operated one before. So, you know, we, we didn't have all everything working with us, we did this, but we certainly learned a lot.

And I think, you know, the, the investigators that were a part of the network and the sites that were running Precision Promise, really, that part ended up being pretty amazing. That network, and the camaraderie and the sharing and the learnings. and you know, I think that those things will continue far beyond.

John Marshall, MD: Yeah, no, I totally agree with you. You know, we, held here at Georgetown at the Ruesh Center, a think tank around pancreatic cancer. And we, we invited a bunch of very smart people. some of the smartest people in our country around this disease who've made a lot of progress. And the whole point of the think tank was to say, why haven't we cracked this nut? Why have we had a few new medicines? They've helped. Yeah. But we really haven't cracked the nut the way we want to. And it was interesting. One of the participants got up and said, but wait, we have done it or we have about to do it and all we really need to do is give it time and ongoing investment. But we're about to reap these rewards in pancreatic cancer, whether it's targeting or new understanding of immune therapies, understanding, how to control. cancers and the like I went into that meeting discouraged thinking there wasn't going to be much in our summary document of what we were going to be able to share, but I left that meeting maybe as excited as I've ever been, and I'm an old GI oncologist, as excited as ever been about the future of where we're going in pancreatic cancer reflect a bit where you all are on that and that stance and The one concern I had again is how do we make sure that that investments there to your previous point? How do we make sure that patients have access to these trials and new medicines around the country? So that all can move this faster. What are your what are your thoughts on that?

Julie Fleshman: I've heard multiple physicians and researchers say that they feel we're at a tipping point, and I've never heard, you know, that kind of talk, before. I mean, 25 years, I've been told KRAS, RAS and KRAS, super important. but it's undruggable. And suddenly, it's druggable. And so that's pretty amazing and exciting. you know, there are multiple, multiple companies with targets for KRAS for pancreatic cancer. The first phase three trial just launched last month. and then lots of phase two, phase one trials that are in development. So, I mean, this is exciting. This is really important.

John Marshall, MD: Yeah, I was going to say that we saw I saw a bunch of waterfall plots. Everybody knows what those are, where I'm used to seeing one patient and being excited about that. This was half the patients were below the line. We were seeing lots of, responders in those patients.

Julie Fleshman: Absolutely. And, and most likely it won't be the silver bullet. I think we've learned that in this disease. So the next step is what do we need to combine it with? What is that going to look like so there's durability, and, and we get, you know, even we extend patients lives even longer. I think that'll be the sort of immediate next step that we need to begin working on. But I was really heartened, at the AACR pancreatic cancer meeting That already it feels like the field is thinking about that, and they're working together across institutions. They're getting together in groups and trying to solve the problem based on different expertise. And so, I do feel like we have a very special community that knows this is hard. That this isn't just going to be the answer, and we're going to have to continue to work together. And PanCan wants to play that role. Whether we're funding, advocating, educating, you know, whatever that looks like to ensure this moves, moves forward for.

John Marshall, MD: I would go one step further, Julie. I don't think we would be where we are today with that progress without your work and PanCan's work, and we are all looking forward to the future in large part, thanks to you. So, I very much thank you for taking the time to talk with us today and, and wish you well as now we watch that survival curve improve.

Julie Fleshman: Thank you so much. I always appreciate your passion and enthusiasm, and, and all you do for patients. So, thank you.

MedBuzz: Who’s Next? Cancer Research in the Crosshairs

John Marshall, MD: If your world is like mine, you're spending a lot of time thinking each day about the impact of governmental changes, administration changes, and their impact on us as healthcare providers, us as humans. Us as educators, us as researchers in the world of cancer care today, and we know there are dramatic events occurring every day that we are sort of figuring out what's the impact, how do we preserve what it is we wanna do?

So, for example, as little as one week ago. Some of the fellows that matched in our area here in Washington DC weren't sure that they were going to be able to start in July because their positions were those kinds of positions that were under the current hiring freeze that just was thrown out there and it took until last Thursday for the leadership to realize that oh, uh, we didn't mean them. They could come on and join in July. But those same fellows we're given an option to say, well, if you don't believe that, that's gonna be there for very long. In which case I'm talking about the NCI. You can go and maybe get a job for some other place, but there aren't gonna be other jobs. Right? So, these are people who their entire lives have dedicated to this prospect, have thought that they have just matched and what might be the most stable organization around the country, the National Cancer Institute, to only find out it might be one of the least stable.

And I was reflecting, as many have been reflecting on these just callous, huge government cuts that have been made just over the last week or so at the FDA. Some of the best minds there gone at the NCI, at the NIH, some of the best minds there gone. Let's think about that a second. So the director of the Institute of Nursing Research gone, the head of the National Institute of Minority Health, health Disparities gone. The director of the Institute of Child Health and Human Development gone along with many others just on a dime, right? 

They're using a model of a game show, a TV evening show, where the answer is you're fired. So we just fire people because we don't like what shirt they're wearing or where they park their car or some stupid answer like that. And I know it's so disruptive to everybody figuring out what does tomorrow hold? When's somebody gonna come and knock at your door? et cetera. So we are all in shock as an academic institution. 

Who's the next Columbia? Apparently, it might be Harvard. They're going after them. How do we work together? NCI designated cancer centers to make sure that the administration and the house, et cetera. Understand the importance of our collaborative research and how we have contributed and will continue to contribute to the cures for cancer and other diseases.

Now the last piece of this is that, you know, as we talked about before, don't worry because Donald Trump and his administration is gonna cure cancer. Now, if you believe that, then sit back and let all of this just go. Leave them in charge. Let 'em do what they wanna do, because don't worry. Trust me, they're gonna cure cancer in four years. My argument is that that's unlikely at best, right? The kind of investment, the kind of people that have been fired, the kind of things that are going on is gonna reverse this process. If anything, and don't get me wrong, I would love to be wrong about this, but I don't think I am. And so how are we as a community, a medical healthcare community? How are we as a research community, how are we, are we as a drug development industry? To ensure that we keep the bar moving forward, that we provide care for our patients, that we innovate, and that we indeed do reach the same goal that our administration is seeking, and that is to cure cancer, but actually do it in as fast a timeline as we can.

We're gonna have to step out of our foxholes. We're going to have to look down the street, talk to each other, collaborate. Scream out loud when it's important. Stand up in front of Congress for 25 hours in a row and make sure they know that we're not happy with what's going on. The rest of the world is extremely unsettled. We are extremely unsettled. I think we should not just sit back and let it be. I think we should figure out how to work together, how to make larger voices, push back and say, there are some things that you are doing that are just not right, and we want it fixed. 

John Marshall for Oncology Unscripted. ​

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Published, Performed, Passed Over—Because Science Still Has a Gender Problem

[00:00:05]

John Marshall, MD: John Marshall, Oncology Unscripted. It's unscripted because you can't make this stuff up. I don't know if your week or the last two has been anything like mine, but our country and our science and healthcare, and all of that stuff, is really undergoing an incredible number of changes so quickly that we can't even catch up with what the impact will be. And maybe It's only because we're in health care, but I gotta believe that the impact that all of these changes these edicts that are coming out on Friday afternoons are going to have are going to have on science on the future of discovery on curing cancer we're really feeling that threat. And so, what I wanted to do is talk a little bit about that uh, today in our current episode. 

Now, our main theme today is about the imbalance of credit in the scientific community. And we've really drilled down on the topic around women in science. And how they, over the decades, century, has not really been able to get the same credit as men. 

But we have to talk about all that's been going on just in the last one to two weeks. You know, we went from the freeze that we've already talked about to now this cutting of people, just firing a bunch of people. A bunch of people at the FDA. A bunch of people at the NIH. A bunch of people at the National Cancer Institute. And these are essentially all levels. Some of them leadership levels, some of them mid, some of them are the earliest hires, those within their first couple of years were fired on a dime, no matter what role they were playing. 

One person that I know, I used to coach her in basketball when she was a young woman. Now she's a grown woman and she's an epidemiologist working at the FDA. And because she's only a year and a half into her career, she was fired on Friday afternoon. And what she was doing was reviewing medical devices to make people better able to get around. Accessibility was what she was all about, and now no one's doing that job. So, I don't know, will there be no improvements in accessibility because those people are not there?

We then had the cap on indirects applied. All the cancer center directors got an email around that. All the medical center leaders and academic center leaders got the email. And so, we're all scurrying around to see what can we still do moving forward. What do we have to stop on a dime in order to keep the books open and to keep everything going the best we can. What will be the future of research and science in the current world without all of this infrastructure?

Diversity, equity, inclusion, and accessibility. Gone. Right? So, if we can't have that, how will we acknowledge and credit those folks whose role it is to make sure that we are hiring the best person, not the person who looks like the last person, right? So, quality and qualifications are what DEIA was all about. Not about what others seem to think it's all about. So how are we going to maintain that and will the quality of those folks that are in these positions therefore fall because we're not hiring the best people.

MedBuzz: Welcome to the Healthcare Hunger Games

John Marshall, MD: In our world here in Washington, we've been on this wild swing back and forth where, one Friday, we think that our fellows are no longer going to be hired, that they're going to all be fired. All trainees within the NIH are going to be fired. That was the word. Then it was like, no, we think they can stay, but then, later on this week, it's back on the table. So, we're being called to immediate meetings to say, well, are we going to have fellows from the NIH or not going forward? And if you think about what that would do, not only to them as individuals, but how about all the people that they are taking care of, all the people that are on clinical trials that are getting lifesaving care for cancers and other illnesses that those fellows are critical in providing their care and learning as for the next generation, and so I don't really know. where we are. I've been in cancer center meetings all week long about what we can keep, what we're not going to be able to keep. What sorts of progress can we make? Is it worth writing grants anymore? Should we just give up on this for the moment, tread water and wait, and see? 

My wife went down to one of the protests, and I know they happened all across the country and there were a lot of people there, who came out all across the country to say, none of this makes sense. This is not good for each other. This is not good for us. And most of us are sitting around thinking, well, who is it good for? 

Why is this being done? Is there a methodology? Is it just random? Is it just random rich people who are playing with us? Is it random rich people who are reducing government so that they can reduce taxes so they can have even more money? We don't know. We don't know if there's a strategy here versus just a bitterness and a randomness to it. But it's something that none of us has ever lived through before, at least I know of or anybody I have met. And so, we don't know what to do. I don't know what to do. I can't make light of it. I try to make light of everything. I'm really good at making light of cancer, by the way. But this I can't make light of.

And so, I want you to write to us. I want you to comment to us what you think is going on. What you feel is the right language we should be using. What is the right way to make sure our positions are heard and that our other government leaders are helping to influence in a positive way how we move forward, because for most of us day in and day out, we don't know what to do.

And as leaders, there's nothing more awkward than not knowing what to do. So, for Oncology Unscripted, I want you to help provide some of our script for the future, because if you're like me, you're worried. You're worried about what's next. You're worried about those people who are being fired on a dime. You're worried about those people who come from different backgrounds or have different barriers to enter the workplace or to succeed themselves. We're worried about a new medical head, RFK Jr., who's saying that nobody can be on certain antidepressant medicines, etc. just wide sweeping statements that threaten people's existence and productivity, on a dime like that. And so, how do we defend against this? How do we maintain those things that are good so that we can move forward together? Share your thoughts on Oncology Unscripted, John Marshall. 

I hope you have some good answers. 

One area that we have made clear success in is progress for women in science. Most of my medical school class, I think more than half of my medical school class were women. More than half of my residency program were women. More than half of my faculty here at Georgetown are women. When you look at leadership positions though, when you look at credit for academic productivity, there's still work to be done. And we need to make sure we're hearing all the right voices and those that have been successful and those that have struggled so that we can better balance, make even, our world today so that women have the same opportunities and credit that we do as men. 

So, our focus today with incredibly smart people is to drill down on the issue of women in science and how to ensure balance and parity for all. 

Candid Conversations: Science, Struggle, and the State We’re In—My Interview with Dr. Lucile Adams-Campbell

John Marshall, MD: We have been talking about how disrupted the world is. And in particular, we've been focusing on women in science and how not only is the world disrupted, but women in science have all had a long history of disruption, of steeper climbs, of more difficult challenges ahead and I am so pleased to introduce and welcome, another incredible voice, another incredible person who has had dramatic impact on cancer and cancer outcomes for us here in the D.C. area, but frankly, on a global scale. Dr. Lucille Adams-Campbell and I have been working together for a long time now, and neither she or I will say exactly how long. We first met when she joined us here at Georgetown having come from Howard University where she directed the Cancer Center here in Washington D.C. We had some partnerships even before she joined Georgetown, but since coming to Georgetown she has continued her work and dedication to serving those who are not equally served, if I could just put it that way. But she's also, as you can see, a woman. She's also a woman. I don't know, what does one say as a white man of color? She's a Black woman, and she has had a strong, mature, consistent voice. about what it is to be a woman in science, what it is to be a black woman in science, and we're just honored that she's joining us today for some of her thoughts. So Lucille, with all of that preamble, welcome, but give us a sense of your take on all of this. Is this real? Women have a steeper climb? Is it worse for Black women? What are your initial thoughts out there about this topic?

Lucile Adams-Campbell, PhD: Thank you for having me, John. And I will say that women in science, and women of color in science have an incredibly steep climb in this world. And the reason being is they often are looking for mentors and role models. You don't find many role models of color. And the role models that I have sought out even in my latter days in my job recently, have died. So, we have a dearth of mentors, role models that we can look up to. So, we have to really do a lot our own. We also have to do a lot with society, which means I have had white male mentors throughout my career. I started in engineering, which was a male dominated field. I spent four years in chemical engineering. 

John Marshall, MD: This mean you actually know how to use a slide rule? Do you know how to use a slide rule?

Lucile Adams-Campbell, PhD: Yes, but those days have changed. But I did use a slide rule for many years. But at the same time, I've had phenomenal male mentors. Including someone named Baruch Blumberg who won the Nobel Prize in 1976. That spurred me on to become an epidemiologist. I've also had people during my training predominantly male and White institutions at University of Pittsburgh, for example. The only Black female in the program at a point in time for a PhD. So, for me the curve is very steep, but at the same time, you have to ground yourself. You have to really study. I felt like I worked ten times harder than all of my classmates. I feel that even today, I work harder than many people are working.

John Marshall, MD: Can you tell me a little bit about what that is, why that is? Is that because white men aren't listening? Is it because there's additional barriers? Give me a little sense of why you are working harder.

Lucile Adams-Campbell, PhD: Well, I'll tell you, coming through my training, one of the faculty members said I should be dismissed. I should not be allowed to get a PhD. Only because of the color of my skin.

John Marshall, MD: Seriously?

Lucile Adams-Campbell, PhD: Seriously.

John Marshall, MD: Did they say that out loud to you?

Lucile Adams-Campbell, PhD: They said that out loud, and my chairman, who was my staunch supporter, said, ignore this person. You don't work for this person. You don't take classes with this person. You will get your PhD. You are staying in the program. But I always had to make certain I worked much harder than everybody else. I'm an epidemiologist. We did a lot of biostatistics. We did a lot of computer programming. People would run computer programs. What was I doing? I was writing the programs that people were running. I always had to go to another level, just to fit in, just to fit in.

John Marshall, MD: Let me, let me drill down on that a little bit more because, you know, I think about today. And diversity, equity, inclusion, and all of the vulnerability that that's there. Because you went from a world where someone could say out loud to you, a mentor or a boss could say, you can't do this because you're a Black woman.

To now, to for a while there, that was no way anyone would be able to say that. To now, I think it's okay to say again.

Lucile Adams-Campbell, PhD: Now it's okay to say, and I can tell you that I have witnessed white medical students, I'm not calling any places, that say Black people are just taking up space. We can do better without them. So, these things are now made very easy to say. There's no punishment, nothing. You just said it. And so that's a, that's a really big change. And right now, Black and Brown people are almost invisible. And we watch the administration just wipe it out. Wipe it out. Anything that even is remotely linked to minorities. It's taken away, and that's very demoralizing feeling. They know that. So all you can do is stay pigeonholed, do your work, don't go out of your little square domain because of what's going on.   

People don't understand what DEI is. It's supposed to be enhancing diversity, equity, and inclusion in the workforce. Did you see the Super Bowl? Did you hear the comments after the Super Bowl? The halftime show performed by All Blacks what did the white women complain about? There were no whites in it.

But you don't want diversity, equity, or inclusion. So, an all-Black performance should be applauded because that's what you are asking for. Blacks and Browns are really being removed at an alarming pace. Without any rationale. 

John Marshall, MD: Let's talk a little bit more about mentorship. Is it different today? Are there specific, mentors that are bringing forward women? And women of color and people of color. You know, I was thinking about my own medical school class, my own faculty here. It's about half and half men and women, many more people of color than certainly we had 10 years ago.

Do you see that trajectory of mentorship changing?

Lucile Adams-Campbell, PhD: I think we will strive to continue in the same vein that we're going now. I think we have external forces that might try to slow us down, but at least mentally, I think we are there to see. Increases in women, increase in minorities, in the whole arena for oncology, for medicine, I think that would be the norm.

John Marshall, MD: Let me ask a very biting question. If you put training grant money out for specific subgroups, let's say women, or let's say people of color, one argument is that that's making the hill less steep and that you're identifying the right person and overcoming them. The discrimination, if you will. The counter argument is that you're setting aside money for maybe people who are less qualified and my argument has always been the former and that you're allowing people through that would not have gotten through otherwise.

But do you think there's any legitimacy to the qualification issue?

Lucile Adams-Campbell, PhD: You know, I've heard this discussion about qualifications, saying, can't remember who said it, but on national TV, if I get a Black surgeon, I know that they're less qualified. Standards have not changed. So my, my take on that is, We have a training grant. We do want to make certain that we bring on minorities. But guess what? If they do not come up to the bar, we do not bring them on. So we believe that people of color, they excel just as their white counterparts. There are people that aren't of color that don't do well. But we put all the pressure and emphasis on minorities are always at the bottom of the, of the, of the poll. So I believe in targeted recruitments. But not just as a handout. People that deserve to be in. Now, do we ever make exceptions? Not really when it comes in terms of what they can do. If there's no way this person can do this job, not hiring. Not hiring them. So, I think I've been true to that. People that come on and they can't do the work, they have to be let go. I think it has to be fair system across the board. 

John Marshall, MD: I was just in a country, New Zealand, believe it or not, where it was the first Western country where women were given the vote, quote unquote Western country. And then I was thinking about that women in this country have only frankly recently been given the vote. Black women, you know, the last of the group.

And then, but then now this swing back the other way, that basically, as you say, to make them invisible again, 

What's your advice to our folks out there who are listening in to me as a white man? What's your advice to us to how do we push back against this?

Lucile Adams-Campbell, PhD: Well, I think there will be a revolution one day. I think it will be televised. We always say a revolution will not be televised, but it will be televised.

John Marshall, MD: Or it'll all be, you know, filmed with this, right? Yeah.

Lucile Adams-Campbell, PhD: Filmed with your phones. 

I think it's really important that we stay the course. We cannot back up. We cannot back up and back away. We have to stay the course, and we have to start fighting more for what is right. We know what's happening is wrong. Now, my mother, as you know, who died, was 101 years old. She said to me one week before she died, ‘I am sorry that you're getting ready to live the life I lived when I was growing up.’

I think we have to fight, but we're in a very awkward position right now. We have the oligarchs, we have the, the, the authoritarian approach, and in that type of system, it's very dangerous as well. So, we have to stay the course with our science. We have to keep doing as much as we can to promote ourselves, but we still have to collaborate and work, and we have to be inclusive. This not work in silos, it's not just about Blacks or Brown people, it's everybody. And the difference now, and I'll say this out loud, the difference nowadays is the fact that oppression has been felt by Blacks. I have felt oppression, racism, discrimination all my life. I have had different people over time, even here, say comments that they don't realize are really offensive and racist. But you understand all of this racism going on, you still have to function. You still have to keep working. You still have to do what you do. But you hope that the people in power will not just sit back and let it happen to our institutions, to our universities. Don't take away our academic freedom. We have to be certain that we're fighting for the right things. And what's right is not what's happening in this world.

John Marshall, MD: I see you as one of my mentors. I know we're peers as well, but I also see you as an important mentor to me. And you've taught me many things over the years, and you continue to even with our discussion right now. Still keeping the job going. I get that. You know, try to keep your head up, keep looking forward, but it feels to me, I feel like, as, as a voice, you're a voice in this world, that it needs to, in fact, at our level, be even a little higher at the leadership level of a tone setting or, not just show up and do the job, but to somehow not accept what's going on at the same time, and that's a fine balance, right? Because we work for institutions that need to keep existing. Is there any advice that you would give me or share with others about pushing that envelope further than just showing up and being inclusive and being accepting? Is there something more that we should be doing in your opinion?

Lucile Adams-Campbell, PhD: We need to stop labeling. We need to just do the work. We label DEI, and it gets struck down. But we need to get rid of the labels and do the work. If you're going to build your community, build your scientific world, build your labs, whatever you're going to build, it being inclusive of people. And that's really not what's happening. People say it, they say those words, but it's not happening. I think we need to be involved and engaged at every level. So, you're in leadership roles, I'm in leadership roles, but who's really in leadership in academia? It's the lawyers, not us! We want to fight for it. I just had a grant that was taken from me, but it wasn't because of DEI.

John Marshall, MD: Well, it had the word woman in it, didn't it?

Lucile Adams-Campbell, PhD: Women, Women's Health Initiative.

John Marshall, MD: That's out!

Lucile Adams-Campbell, PhD: It's out. But also it was with Columbia University. And they are a hot target right now. So, I really don't have a solution. Because we have to keep fighting. 

But you know, I look at the farmers as an example, and it's really intriguing and very sad. We have been oppressed for so long as people of color. Now, what's different? The difference is, now, everybody is feeling it. Before, you've never felt this before. And I think that's the difference that's happening right now. That White people are feeling that they are being oppressed. Even those that voted for this administration never thought it would come back and hurt them. So, for me, I do sit back at some point and say this what we've always gone through. Now, there's a change in mentality across the board, across all races and genders. You know, it is a change. So, that's, that's different. That's different. Have you ever felt like this before? 

John Marshall, MD: No, I keep saying that too. I've never lived at a time. I mean, we keep equating ourselves with the Jewish people in 1937, right? And the Black people in, you know, slavery and post slavery. and, and now white guy, Presbyterian White guy from, you frigging Mayflower is now feeling it, right?

Lucile Adams-Campbell, PhD: That’s the difference.

John Marshall, MD: Yeah.

Lucile Adams-Campbell, PhD: And that, and that different feeling, I think, is going to help us regain what we need, because it is now oppressing everybody. And when I go back to the farmers, the white farmers are outraged because they are not getting the money that was promised to them. But they never cared. The Black farmers never got a penny of the money. So now, the Blacks have always struggled in farming. But they made it. Now the Whites are struggling, and they don't know what to do. 

John Marshall, MD: Will we ever stop scoring people based on their skin color? And do you think this is an opportunity for us to get there? Do you think that's ever going to happen?

Lucile Adams-Campbell, PhD: In this administration?

John Marshall, MD: No. In our lifetime, how about that?

Lucile Adams-Campbell, PhD: A lifetime. Well, I think there's beauty in skin color.

John Marshall, MD: Me too.

Lucile Adams-Campbell, PhD: I think that there are so many hues that we have to look at. I don't think it would be really a nice fit for everybody to look the same. So, I think the diversity in color tones and hues is so important. So, for me, we win. with the score with all the different shades of gray, literally. I think we really win.

John Marshall, MD: I'll tell our audience, I'm hoping you watched all of this. Dr. Lucille Adams Campbell, an amazing voice, an amazing mentor to me, and I hope now to you, Lucille, thank you very much for joining us today on Oncology Unscripted.

Lucile Adams-Campbell, PhD: Thank you.

Candid Conversations: From Lab Coats to Leadership—My Interview with Dr. Caryn Lerman and Dr. Deborah Schrag

John Marshall, MD: Hello, everybody. I promise you famous people to interview. And I'm lucky enough to know, they won't admit that they know me, these two people, but they are incredibly famous, successful people in the world of cancer. Dr. Caryn Lerman on the other coast out there, where it's probably warm and sunny out in Southern California. Dr. Deb Schrag, who is just up 95, somewhere up there, who is up curing cancer, GI cancer person from up there. These are leaders in the cancer world and they have agreed to join us for Oncology Unscripted today to talk about something we've been dancing around in the last few episodes, and that is women in science, women in professions, and the fact that over time, since sort of modern science, I guess we'd say, the DNA and things like that discovery is that women have not consistently been credited with their contribution with their success with their leadership in this world.

And so, they were nice enough as successful leaders in this world to join me today to share a little bit about their perspectives. Caryn let me Let me pick on you first, if you will. I mean, you've made it to leadership role in an NCI designated comprehensive cancer center in the biggest city in America, right? That's still the biggest city in America. So, tell us a little bit about your perspectives and your thinking about women in science. 

Caryn Lerman, PhD:Well, first of all, thanks for having me, John. I totally admit that I've known you for decades and I'm really excited to be here.

I started, In the mid-80s. So just to give some context, and I was fortunate to have an absolutely exceptional female mentor Barbara Rimer, who ultimately became Dean at UNC, Dean in the school public health. And so, I was fortunate to have a wonderful female leader, role model who took me under her wing and helped me. And I will say that as my career advanced and I had the opportunity to work at other institutions, it became very obvious to me that there are very few women in leadership roles as role models as mentors, and I've had great male mentors as well, but I think it's very important because there are unique perspectives and it is more challenging as a woman. 

If you look in the cancer center leadership space, you know, and in the research space, this is where I live. Even now, there's just a small minority of cancer center directors who are women. Okay. And, and then you look at the next level down, you know, associate directors and deputy directors, and it's still like 80, 85 percent are men still at that level. So, 10, 15 percent are women. 

John Marshall, MD: Can I, can I drill down on this mentorship thing?

So, when you have a good mentor, I, I, this is white man looking from the outside in. Okay. So, I want you to mansplain back to me what the reality is. Are there some women mentors that just say, tough it out. You're not. You're not strong enough or so or are you all actually is the mentorship of recognizing that this is an unfair world and here's some strategies for getting there or is it both?

Caryn Lerman, PhD:Well, like anything, there's a lot of variability, right? And I think there is some folklore and there's probably a kernel of truth in the fact that the farther you go back. The harder it was so there's a little bit of I had a battle my way through with all my male colleagues, who treated me differently, didn't let me into the old boys’ network, who felt that I had to always be charming and not push back and had different expectations. So, you do have sometimes women coming, you know, moving up the ranks, feeling like you do just tough it out, tough it out, tough it out. And I think as I mentor people for me, it's really about how do you be authentic to who you are? It's not about trying to be one of the, the, the guys, it's about, you know, being authentic, being authentic to your personality, showing compassion, being nurturing and being tough when you need to be tough. So, I think there's some great female mentors out there, but there are also some who are pick yourself up by your bootstraps because it's tough out there, and I had a tough. So just deal with it. 

John Marshall, MD: Yeah, Deb, let me get to you, because I think about, you know, I'm a member of the GI old boys club, right, and I think part of the reason why I'm still giving the same adjuvant therapy for the last 20 years, and no other cancer is that true, but colon cancer, is because of it some old boys that didn't want to move things. But you have in fact changed standards of care and in the backdrop of an old boy’s club through innovative clinical research and taking a stance that, you know, was impressive and you stuck to it and succeeded. So maybe reflect a little bit at that research level and, you know, disease orientation and clinical leadership roles. You know, some of the struggles or feedback you would have in this space.

Deborah Schrag, MD, MPH: Yeah. So let me start by saying that, you know, Caryn and I have different roles, and we have different jobs and have had somewhat different trajectories, but I agree with everything she said. I think it applies to people who are focused on wet lab research, dry lab research, you know, basic biology, behavioral, clinical trials. It spans the gamut because these are fundamental human sort of issues about how we work together and what people's expectations and biases are. I think as women leaders, we have to get comfortable with ourselves. 

I completely agree with what Caryn said about authenticity. Women lead differently. We just have different styles. There are certainly women who lead like men and men who lead like women, but as a generalization, and this is a generalization, you can find many exceptions. Many women have a more male style, and men have a more female style. It is really hard for us when everyone is angry with us when we feel like everyone is hating us for making difficult decisions, not to staff, not to grant, not to fund to say no, that is really hard. And those are hard skills to learn. And women struggle with that. Some of it's very cultural. 

For us to learn how to be comfortable with power, to navigate conflict, to communicate clearly, to sit with the discomfort, and again, that is with people who are above us in positions of power, people who are our peers with similar levels of, as well as with trainees and mentees and team members because science is so these days to do anything really impactful and involves a team. And you have to inspire and lead a team, and you have to make tough calls. You know, we were going to do this project, the budget was cut by X, and we got to chop off an aim or we submitted this grant. And it had four components, and this part scored really badly. And so now we are cutting your project loose. That is something that women leaders, I think, that's something that women really struggle with. I think men have the same struggles, but I think they sometimes experience them differently or feel the pain, a little bit less. 

Would Caryn agree? I'm curious if she agrees with me or not. 

Caryn Lerman, PhD:I agree 100 percent and I'll just add that I think that still in this day and age. And there's research to back this up. Women are more likely to experience the imposter syndrome, more likely to downplay what they have to offer. And I would just tell you, I've run a lot of searches, and you have women, you know, reaching out to people say, are you interested in being chair of department X? I don't know if I'm qualified for that. Yes, you are, come on. I don't know. And then. It's just a very, it's very different for people to even consider their candidacy or whether they are worthy of roles like that. The system has created some of that and I 100 percent that. 

John Marshall, MD: Let me lean in on that, because on the other end of Pennsylvania Avenue, just down that way, this is only going to get worse, right?

I mean, right now the public tone is very male driven, women minimizing, almost dehumanizing tone. So do you feel like that the gains that have been made in science and medicine are even more vulnerable now than ever before?

Deborah Schrag, MD, MPH: So, so John, I want to just quickly respond to that question, Caryn I don't mean to interrupt. Women should not interrupt each other, but you know, are we all terrified and worried and distraught about the immediate future? Yes, sure we are. We are. Noone in biomedicine is happy, whether, no matter male, female, junior, senior, east coast, west coast, blue state, red state, we're all concerned, alarmed even. But when you look at the long game and look at the arc of history and how much progress has been made, women are too central. We are too critical to the biomedical research enterprise. It cannot function or run without us. If you look at PhD graduates, medical schools, yes, at the top echelons, I completely agree with Caryn about it still hasn't penetrated up to the top-level C suite. But I believe that in the long run, that is going to happen because the talent is there, the training is there, the motivation is there, the skills are there, and we are in it for the long game.

So yes, we're in a bad patch, but long game? We're going to prevail. I know. I believe nothing can prevent that from happening because it's so powerful. 

Caryn Lerman, PhD:I have to agree. And I love your optimism. I agree. But I do at the same time, these the efforts to dismantle programs, you know, in the name of efficiency, reducing staff at NIH, reducing indirect costs. This is going to affect all of us. And that means that this is the time where we have to band together as scientists of all of all genders and all backgrounds, because we're going to lose the tremendous breakthroughs and scientific gains that we've made over the decades. And, and that to me is the biggest threat that's out there right now. 

John Marshall, MD: But let me lean in on that just a minute for the last few comments from you guys. And that is, when we went back and looked at literature around women in science, one of the very strong themes that came forward was the lack of credit. Those people who had done the work were not on the papers or were tucked in the middle or, and the like. And I, there was part of me that didn't understand that there, is this right, even today that if you that as a woman, you might not get the proper credit because of your gender. 

Caryn Lerman, PhD:I don't feel that I've experienced that personally. Obviously, I feel it's wrong. I feel people should get credit and there should be transparency about individuals’ contributions and agreements up front about authorship and who's going to be PI, and so forth. I guess I've been fortunate to not experience that. 

Deborah Schrag, MD, MPH: I wish I could say the same as Caryn. I have experienced that, and I think it continues to be an issue, but it relates to the comment I made earlier, which is that women are more likely to be conciliatory. We have that hardwired in us from pre-kindergarten. So, when there's a discussion about authorship, sure. Let's have two first authors and two last authors and you can be, I'll be second. In other words, I'll be the one, I'll be the co first author, but you can go first, I'll go second.

But women are also wily and strategic. We're in it for the long game. We're not going away. I think we have to support and coach each other. 

but I think that we are really making great strides. I've seen it, and I think that when there are more women who are directing cancer centers, and who were sitting on panels, whether study sections or other things. That is a really important corrective because they help ensure that awards. Resources grant funding is allocated according to merit, which is what we all want, right?

That's what we all want. We want merit-based systems. We really do. 

John Marshall, MD: You guys have been awesome. I know you both have lots to do, and I've interrupted your busy day and the world's gone to hell. We all know that we're trying to hold on to what we can. So let me, on behalf of everyone, thank you guys for sharing your thoughts and your feedback on this.

And I know that your comments and your success, personal success and collaborative success will have an impact on women in the future.

Caryn Lerman, PhD: Thank you very much. 

Deborah Schrag, MD, MPH: Thank you, John. 

John Marshall, MD: It's just amazing to talk to such smart people who have made so much progress, not only for cancer and cancer medicine, but for women in science. And so, I'm very grateful to them for joining us. And to all of you out there for sharing and thinking about these issues in front of us, not only the, the parity in individuals, women versus men, diversity, equity, inclusion, accessibility, but also in the increasing threat day in day out threat that is to science from our current administration and how we will keep innovation going forward. We all have to work together to ensure that success. 

​[00:24:32]

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THE WEIGHT OF THE WHITE COAT: BATTLING BURNOUT

How Do Middlemen Impact Our Practices? [00:00:00]

John Marshall, MD: Welcome back everybody to Oncology Unscripted. It is August and if you're lucky like I am, August is vacation time for me. I am at this beautiful place somewhere in the south, somewhere near a golf course and an ocean; a little river flowing right over there, some egrets and an occasional pelican flying by. There are fruity rum drinks, most evenings, which makes for a very pleasant time away from work. So, I'm on vacation, and I hope you guys have gotten some time away.

We're going to focus on in the second part of our series of three programs on the middlemen in our lives. The last episode, which many of you have commented on and have watched, is around pharmacy benefits managers; their role in our healthcare system and how they've inserted themselves and made a bunch of money and not necessarily adding value. 

Today, we're going to riff a little bit along the electronic medical records, certainly a middle thing in our lives that many of us are sort of frustrated by. And then our next episode will focus on clinical research organizations that I know many of you can be frustrated about, as well. 

Silent Crisis: Can You Admit You're Burned Out? [00:01:27]

But, to set up this EMR vacation setting. I think we ought to talk a little bit about the concept of burnout. Now I'm on record as having officially burned out. It was in, really, 2018, 2019. I didn't really know it. I just thought I was grumpy because I had good reason to be grumpy. But it was actually my wife and my daughter who noticed that I just wasn't my same old self. I had lost my sparkle. And I thought a lot at that time about my own personal burnout: therapy, I ended up taking a sabbatical, my wife and I wrote a book. We had to get away for a while in order to deal with that. 30 years of being an oncologist is a big deal. 

And then I started to look into this issue of burnout and realized that lots of us in our space have a lot of burnout. There's some studies that have been done and basically looks at, sort of, not only our burnout, but how are we dealing with burnout. And given that I'm on vacation, I thought it would be kind of useful to look at some of the data for us around vacation. And we don't take very much vacation. And when we do, we actually work. Like this morning, I actually have already seen four patients in tele visits. God help us. So even though I'm on vacation, I'm still working. And I bet many of you do that the same way. 

So, in this survey. 60 percent of us as physicians, we're only taking 15 days or fewer per year. That's terrible. With 20 percent of us, one in five, taking only five vacation days a year. And most of us, when we're on vacation, like me right now, 70 percent of us work every day of a typical vacation. We do something. We check email; we do something while we are on vacation. And a third of us will spend more than 30 minutes a day on work while on vacation. 

Now, looking at subspecialties, oncologists are a little bit better because 60 percent of us were taking about three to four weeks of vacation. But you get more vacation than that!

Is Relaxation Worth Sacrificing RVUs? [00:03:46]

I know as well as you know that we're disincentivized to take vacation, right? Because we are RVU-driven, and every week I'm not getting RVU's, I'm actually getting less money. So, if I take vacation, I'm actually making less money.

Now, the other thing that sort of started happening more recently is this concept of paid time off PTO, right? Didn't used to be called that. It used to be called vacation. If you're in a business where when you're on vacation, you're paid, you're supposed to call it PTO. For those of us who don't have that sort of tracking system, we call it vacation. but it still makes me feel guilty, I guess.

Are Your Patients and Staff Mad When You Go on Vacation? [00:04:32]

Now, one other perspective that I learned the hard way when I took my sabbatical is just how angry patients get when we're on vacation. Our staff also is angry at us when we're on vacation because we're not immediately available and they depend on us in order to, you know, do the day-to-day stuff we have to make decisions here and there. And our patients, particularly when we take a longer vacation, do get kind of fussy at us. Well, you know, as soon as you get back, let me get in to see you, or I need to see you right away. So right before and right after vacation, we clearly pay the price, by, you know, all the catching up that we have to do when we are away.

PROMISES UNFULFILLED: THE EMR PARADOX

Do You Love or Hate Your EMR? [00:05:17]

Now, the new one that I think is the most kind of creepy of all is that of course our patients have access to their electronic medical record, right? Our topic for today. And so, they can look up their results or they can wait on, you know, they can find what their CT scan showed or their CEA level or whatever it is. They can see and now they know this result. You're on vacation. You don't really want to get into the discussion. They've got to wait until you get back. And of course, that just generates more anxiety for everybody. You have to decide whether to stop everything, pick up the phone and call Mrs. Smith and tell her about her scan and talk it through. Wait till you get back or do as I did this morning and schedule four tele visits with your patients while you're on vacation in order to catch them up and make sure they're okay. Which for me in the end was a good trade off. I feel better about what I did. I'm happy for the patient. I won't have to get creamed when I get back, but I had to eat vacation time in order to do it.

Now, I'm old enough, maybe some of you out there are old enough, to remember charts. They could get really thick in some patients, and you would carry them around if a patient was inpatient. Often in our shops, you could find the chart up on the floor, which is not where it was supposed to be, or they couldn't quite find it. Or the last person just stuck something in the chart, and you didn't know whether the result was going to be there or not. So, we didn't really like our charts either. They were inefficient and we were hoping that the electronic medical record was going to be this, this great savior. But in many ways, it has become the primary thing that we do is enter data into the EMR. 

More EMR Screen Time Than Patient Time—Is This Your Reality? [00:07:12]

It's very, very common—I catch myself all the time, really common with the younger physicians, is that they stare at the EMR the whole time. The patients over there, they're staring at the EMR. And they're just typing right and entering in data and not really paying attention to the patient over here. 

We've seen a clear fall off on physical examination because it's all there. You don't need to examine the patient. Everything is right there. We collect money, we bill, based on how much we documented in this EMR. And, you know, what's interesting is the EMR is not really that great at being able to find the data, right? So, I think about genetic tests, for example. they could be scanned in somewhere, and they could be in the right portal where I could find it, or they could be under, like, outside records, page 37 of 130 of somebody's outside records. So, I can't find the genetic data. So even though it may be supposed to be in there, I can't find the data that's in there. So, we've separated ourselves from our patient. We're totally driven to entering data. And the world is really excited about this data that we're creating.

Who Owns the Valuable EMR Data? —Certainly Not Us or Our Patients… [00:08:27]

The reason I think of the EMR as a middle person, a middleman, is that the data that we are entering has value, worth something, because it's clinical outcomes, it's behavior and usage and money spent and, opportunities for improvement in healthcare. So, I have been jokingly calling us physicians, you know, highly paid data entry specialists because that's kind of who we are. What we enter into the EMR has value to someone else. We're being paid to enter the data. Someone else can mine that data in order to make money off of it, to watch us, to oversee us. You know, it becomes a new way of tracking our own metrics, our own benchmarking, how good are we, how fast are we, what's our charge lag, all the different things that we have to do so. It’s an oversight of us. It's how we get paid. It's how we interface with the patients. It’s someone else's value in the end. 

So, the EMR is a big deal. We spend tons of time entering data focusing on it. We spend tons of time trying to find information for our patients. Our health care systems value that data very much, and third parties value it very much. But, in essence, we have to recognize that we're in this awkward ménage à trois between our patient, the physician health care team, and this computer system that runs our lives. So, we need to think about how to make a better world around the EMR. To make it more efficient, to make it more clinically friendly, to make it shareable across all health care systems. I think we'd go a long way to improving our health care out there.

EMRs AND BURNOUT: A CRITICAL INTERSECTION

How Much of Our Burnout Can We Really Blame on the EMR? [00:10:27]

So, we're focusing on burnout. We're also focusing on the middleman, the electronic medical record. Why are we focusing on these two? Because clearly they are linked. 

We did a quick literature search and found a bunch of articles that focus on burnout and the electronic medical record. I'm going to put my readers on to share with you one conclusion from one of these papers. it says, "the volume and organization of data, along with alerts and complex interfaces requires substantial cognitive load and results in cognitive fatigue. Patient interactions and work life balances are negatively affected by the time requirements of the EHR tasks during, and, of course, after clinic hours patient portals and, EHR messaging have created a separate source of patient care outside of our face-to-face visits. It is often unaccounted productivity and not reimbursable." It's no wonder that we're burning out. 

As I told you, I am a burnout victim, if you will. Maybe a recovering burnout person. I'm always on the verge of it at this point, but I've learned a little bit better how to manage it. Vacation can help, by the way. 

But, 59 percent of respondents in a survey that was taken did report some symptoms of burnout, and this was compared to only 34 percent back in 2013. So, essentially a doubling of those who are complaining of some symptoms of burnout. Now we are burning out with high levels of emotional exhaustion. And if you think about oncologists, we bring a lot of emotion into our patients. Patients are very emotional themselves. We deal with very high-end kinds of critical moments for patients’ lives that we're walking along with them. So we there's no way we can't not feel that day in and day out. And we feel burned out regularly, right? And that's really up, quite a lot from even just 10 years ago. So, we're getting more and more burned out, more and more, influence of that burnout on our emotional well-being ourselves. 

My health care system just did its annual and maybe it's every other year survey saying they care about my well-being. And so, they've sent out a survey. They set a deadline, September 9th, to fill out this health care form, and they basically claim that what we're going to give them is going to give them a better idea about how to support our well-being and professional fulfillment. Now, this is the same group that's also monitoring me and tracking each of our performance levels and our Press Ganey scores and all of the different components that we are judged by in today's electronic world are. You know, they're going to have this other data that says that that's stressful. So, I'll be very interested to see this. I'm sure your health care systems have done the same thing. How do you bring those two things together. How do you take what stressing us out is the monitoring that you're doing but continuing to monitor us in a way that balances that out so that we get to a place where we can maintain our careers long term, avoid burnout, or at least manage the burnout in a way that's healthy and positive, and mentoring those that are, behind us, if you will. And, and making for a better overall product for our patients and for our teams around us. 

Closing Out Your Vacation—Is it the End or the Beginning? [00:14:17]

As you might have already figured out, the problem with vacations is that they do end. You have to get on that thing back there and fly home. I already looked at my week ahead, it's very, very full, with patients, of course, and meetings, and catching up. That stuff I didn't do over the last week, and it is a stressful week as you look ahead. But I have to say that the tradeoff for the break from all the action and doing what we do as oncologists, administrators, researchers, all the things we do, the break from that was so totally worth it. So, I encourage you out there to make sure and take all of your vacation. Your partners will cover for you. The RVUs, in the end, you won't remember, the vacations, you will. So, make sure, don't trade off those RVUs for those days away. Take those days away. Enjoy your family. Make your life better. Avoid that burnout. 

And by the way, our lack of burnout and our progress and our innovation, maybe some of which comes during a vacation, will one day make it so you got cancer cured. 

Until next time. See you later.

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John Marshall, MD: Hey, everybody. John Marshall with Oncology Update. Welcome back. This is episode 5. 

We now have a really cool function called ask a question. Click on that. Send us something. We hope to get back with you with an answer.

Most of the time, you know, you see these things and it's all nailed down, and you know exactly what you're about to get. Not so much with this. We’re really trying to bring to you the current days news. What's going on in our world in the world of cancer, both in the science world, the social world, and the business world. And you know what? You just can't script that kind of stuff. It just happens as it happens—so a little bit of Oncology Unscripted. 

OncoBuzz

First, the news of the day. U.S. News and World Report just came out again. Guess which one was the number 1? Of course, it's MD Anderson. Number 1 again. The top tier teams, it's like the Yankees going against the Dodgers. It's always the same teams year after year. But congratulations to that fabulous group down in Houston, Texas.

We here at Georgetown are just pumped that we got our NCI renewal; our comprehensive status for a fresh five years. Always a good moment for NCI Cancer Centers, either to get it or to maintain it. So, thank you for all the hard work that went into that. 

Big news out there. Friends of Cancer Research gave out annual leadership awards—Monica Bertagnolli, our new head out at the NCI doing a fabulous job, as well as Brett Guthrie. So great people who well deserve the Friends of Cancer Research Leadership Award. So, kudos to them. 

Just some business news out there. 

Lei Zheng, MD, PhD, who was a UT San Antonio person all along, just named the Executive Director of their fabulous Mays Cancer Center.

Mark Burkard, MD, PhD, he's a good human as well. University of Iowa, just named him their new cancer center director. He was at University of Wisconsin. So, he moved kind of, I don't know, south a little bit. Still will not be such great weather, although it was probably a little better weather than Wisconsin. We'll see how it goes there. So, congratulations to him. 

On the clinical research front, some news that maybe doesn't really make it here to the U.S. so much, is that the E.U., which has been doing a lot of our major clinical research lately, making up for some of the gaps that we certainly haven't been filling as well. They've had a sort of sudden halt to clinical research because of some new regulations around devices and things one uses to test and measure stuff. So, you can imagine scans and other things like that. So, there's some new regulations there that is sort of thrown a monkey wrench into E.U. clinical research. And my guess is, it may take them a bit of time to figure that out, but hopefully they will figure that out fast. 

The one piece of news that really caught my eye this cycle was not something you would see in the journals that hit your door. Maybe not something you'd see in any of your feed, and this is from the Federal Trade Commission. So, there was a Federal Trade Commission report that had to be voted on, and it's all about the anti-competitive harms of pharmacy benefit management industry, PBMs, pharmacy benefit managers, PBMs, and we know in the cancer world, these things have become huge. But on July 9th, not too long ago, the FTC voted 4 to 1, I'm reading this to not get it wrong, to release an interim staff report around pharmacy benefit managers, the powerful middlemen, inflating drug costs, and squeezing Main Street pharmacies.

You and I know this is going on out there. We're feeling it. Our patients. Maybe not. Interestingly, they're a little bit on the sideline about this because in the United States, we don't judge value around here. 

PBMS: THE POWERFUL MIDDLEMEN

John Marshall, MD: This is going to kick off one in a series of the middlemen in our world. We are going to talk about CROs, clinical research organizations, certainly going to talk about electronic medical records. They're sort of our data middlemen. But for this episode, we're going to talk about pharmacy benefit managers. 

Now benefit. I love that word. I get benefits for my job here at the university. It's in my benefits package. What these pharmacy benefit managers are taking advantage of is that that's money that I don't really feel. I don't really see. It's going to pay for things and they're getting, of course, their cut. So, we're going to try and drill down on this. 

Now, as we usually do, we did a pretty extensive literature run, and there are some papers here and there. There's a JCO paper. It was a little while ago. Lancet had one, but nothing really recent about the impact of PBMs on our medical world.

So, what we did, because we went out and found a couple of really good experts that we're going to be interviewing. 

But let me talk a little bit about just these PBMs and the impact that they are having. So, for example, a couple of or three PBMs or at least these are now big companies that are of course vertically integrated, but they've gotten so big that they're thinking about buying practices.

And one of the practices that's out there being considered is Florida Cancer Specialists and Research Institute. Now, I know a lot of the people at Florida Cancer. It's a great health care system. The cancer community is outstanding, McKesson, Cencora, and Cardinal Health, not commenting, but there are suggestions that they're out trying to buy this organization, and they're worth about 3 billion out there in the open marketplace. And then what you could see is you've not only got, you know, pharmacies and hospitals and all of that. But now you own the physicians as well in this. So that's going to be an interesting thing to watch out for is that. 

But let me show you another sort of side mark of this. And this is this thing that I recently heard about called Lilly Direct. Now, Eli Lilly, right? They are solid company. They've been doing a lot. They've got a lot of innovative drugs that are out there. But they had something called Lilly Direct, so I went on to their website. You should do this too. And what it is, is a website for patients who might not have a doctor, or whose doctor might not be willing to prescribe a medicine at Lilly sells. There's some weight loss drugs in there, by the way. And you can click and it says, do you have a doctor or don't you? And if you don't, they give you one and you have a visit, I assume, with that doctor. But then Lilly mails you the drug. There is no in between pharmacy. So now you're even being sidelined as a physician to where Lilly will be providing the physician through some mechanism and then will be mailing you the drug directly to remove this middleman. A different kind of strategy to cut out that PBM and now your own pharmacy or your local pharmacy from that pathway as well. It'll be just coming direct from Lilly. 

Now the big ones, of course, are CVS Caremark, Express Scripts, and OptumRx, and those three companies have nearly 80 percent of the market share. And of course, this is a subject of a recent House Oversight Committee review to look at that and see if there is any, you know, is that clean? Is that what are the rules in there? Are we getting the best for our buck there? 

On the other end of the country, Blue Shield of California actually kicks out CVS Caremark as a PBM, and they basically are starting up their own new pharmacy model.

So, there's a lot of big, moving parts in this space. Some of you out there are familiar with PBMs and all of this world, I was not when I started to get into this world a little bit more in my roles. And so, there's a lot to learn a lot to know. And I do think we represent an important voice in this process, not just victims of it, but part of it that we can influence some change.

I encourage you to listen to it. A couple of interviews that we did with people who are really smart about this subject, so you too can be a little smarter about it and maybe have some influence on this in your own way.

THE PBM IMPACT: INTERVIEW WITH STACEY MCCULLOUGH, PHARMD

The first of our two interviews is Stacey McCullough, PharmD, and Stacey's just amazing. She is the Chief Pharmacy Officer at NCODA. 

As I promised, I have got a world expert on PBMs to come and join us. Now, I didn't know this person until pretty recently when I started working with a group called NCODA. They were silly enough to invite me to be part of the group. Of their oversight group, and it's been an incredible eye-opening experience for me to understand so much more about this important aspect of the business of oncology.

So, with me, shutting up, let me introduce Stacey McCullough. She is the chief pharmacy officer of NCODA, and she is our sort of guru, if you will, of understanding what's going on out there in our oncology world and the impact specifically on access to drugs and the impact of PBMs. So, Stacy, first, let me thank you very much for, as usual on short notice, being willing to jump in and share your thoughts on this important topic.

Stacey McCullough, PharmD: Dr. Marshall, happy to be here and thank you for serving with us and bringing all your expertise to NCODA. It's a pleasure. 

John Marshall, MD: As I said, I've learned more from you than I've taught back the other direction, so I'm keeping going that direction. But, you know, here at our hospital system in Washington D.C., I had no real PBM awareness until really more recently, I used to think of PBMs as maybe a good thing, as a maybe a cost savings thing, a way to manage prescriptions on a higher level for patients who needed chronic prescriptions. But more recently, I've had  actually now, I think, up to 4 episodes where I tried to order a medicine for colorectal cancer for a patient on label, a perfectly straight indication where I was told I couldn't. I was trying to figure out who, in fact, told me I couldn't, and I couldn't get a peer-to-peer review. None of that, but I was told I had to order a different drug 1st before I could order the drug that I wanted to order so now my recommendations were being dictated by some really, I don't know who, out there, telling me what I could do. And so, my PBM awareness. Changed on a dime. So maybe if you could give us a little bit of background on all of this and how that could have gone from something that we thought of as good to something, maybe not so good.

Stacey McCullough, PharmD: Absolutely. So, I think what you reference is, is maybe the experience of a lot of people and probably started a decade or so plus ago when as you know, being a giant with an oncology space, we started going from infused products to oral products.

So instead of, you know, a buy and bill model, we introduced the pharmacy benefit. And what we saw in kind of that deluge of specialty products coming out, Oncology led the way, in that growth of specialty products. And so, we saw pharmacies and PBMs start to compete, not just within specialty pharmacy, but with an eye on oncology specifically because it was a leader among the field.

So, PBMs, integrated in 2018 or so, where the payer and the PBM had their own specialty pharmacy. And so probably that would have been the entree into your world more specifically, all of these new oral oncology drugs. And then in addition to that, specialty pharmacies, maybe within your institution, as well as specialty pharmacies that are owned by the plan and the PBMs now competing for the control of your patient from a pharmacy, dispensing the drug perspective.

John Marshall, MD: We've been talking about being a middle person, middleman, but you know, it's today. So, it's a middle person in the chain of events. Often middle people add value. To the chain, if you will, and I think that was the initial intention is that this was going to be value added, maybe save some of our staff some time and effort, maybe speed the delivery of medicines. What's your take on the value added of the middleman of the PBM.

Stacey McCullough, PharmD: Yes, I think the value added is services offered. So, ideally the definition of a specialty pharmacy would be that you do prior authorization to help the patient find copay assistance. You utilize manufacturer copay cards, but really every step in the process. You know, your teams, you have an internal pharmacy there. And so, your teams are set up to do that. They have access to the EMR. They can go in and get the patient’s information. So, you've created your own efficiencies, I guess. The benefit would be if you're asking for a benefit versus if you've already established the process, and then it's an intrusion basically, on your current workflows.

And that latter case is probably what has happened with the PBMs in that they then insert themselves between the physician and the patient. Oftentimes, the services that they offer may be difficult to offer without access to the EMR. So, they're kind of offering, I guess, education as well as benefits that maybe are outside what you're aware of, often confusing to the patient because you introduce another party into their care. And then, you know, your oversight really is lost a little bit. You don't know when the patient is getting their refills, if the patient calls the pharmacy to report a side effect or an issue with the medication, how does that get back to you? So, all well intended potentially. But now, the complexity of oncology care is definitely an impediment a lot of times to the care versus a benefit.

John Marshall, MD: Yeah, I mean, there's a lot of money involved. I mean, here in Washington, we get ads about PBMs on bus stops and on the morning news. So, it's obviously an important political. issue as well about how this is going to go.

What's your take or maybe what's in NCODA's take on, you know, how this should evolve or what the recommendations are to improve this process further? Because the orals are not going to go away. They're going to only increase. So, we need to figure this out. 

Stacey McCullough, PharmD: Sure. I mean, the complexity of oncology care, in itself is enough. So, fragmentation of care should be avoided. You know, the pharmacies that are in your institution, the medically integrated pharmacies.

There's accreditations for specialty pharmacies out there and NCODA has an accreditation as well. These accreditations are intended to ensure operational as well as patient care. So, with those accreditations, that is the establishment, if you will, of good sound practices that should buy a pharmacy access to dispense these medications.

Basically, what you're showing is that you're helping patients get access, you're making it affordable, and you're able to manage the patient from a side effect educational profile. So outside of, of having that in every pharmacy, kind of showing those competencies. Specialty pharmacies mandating that it go to their mail order pharmacy, or it go to their specialty pharmacy is really without validation. There's no reason other than the economic benefit, as you mentioned in that. So, you know, we support the continuity of care. We support the physician being the overseer of all of the care and the medically integrated team so that when you prescribe a medication, you have expectations of what your pharmacy team is going to do. You know that that patient is going to get access to the medication. It's going to be affordable. It's going to be dispensed. They're going to be educated in it. They're going to have tools that are going to empower them to be adherent with the medication. And any glitches in any of those steps in the process, you're going to get a notification back through your EMR to let you know that. Outside pharmacies aren't able to do that. And so, what goes on the outside of that, not only are they not able to promote optimal care, but some of the actions that they take may actually derail the care. As you mentioned in that, you know, you chose a product for a patient, and an outside entity tells you that you need to choose a different product.

Typically, we all know these are very expensive products. As you mentioned, list prices are about the same. And so why the choice of one agent over another? I think, you know, even within a class of medication, distinct side effect profiles and your experience and your conversation with the patient to understand what's going to be the better choice. Anybody coming in and inserting themselves without knowing that conversation is really outside the benefit of the patient.

John Marshall, MD: Yeah, and dictating a therapy based on a price they got not on the medical recommendation you're giving.

Stacey McCullough, PharmD: Well, and you know, you bring up one point that we hadn't talked about, and that is the difference in buy and bill and the pharmacy side buy and bill you, you get the, the bill on the backside at the pharmacy, you pay at the register before you get your prescriptions.

So, any of these price concessions that are on the back end, the patient is often paying a higher price because they're paying it off that list price, not off the net price sans any of the rebates or discounts that are in that. So that bubble pricing effect really does impact the patient often as well.

John Marshall, MD: And of course, no transparency to that. You would never know what actually happened behind the scenes on all of that. Right. 

Stacey McCullough, PharmD: Absolutely. And that's where, you know, the resources that manufacturers often put out to help the patients, the copay, the patient assistance programs, we've seen, you know, copay maximizers and copay accumulators that redirect that benefit from the patient, you know, back to the PBM. We've seen alternative funding models and that, you know, patients are effectively uninsured because the preferred drug list is nonexistent. And so that actually qualifies them for manufacturer copay assistance or patient assistance programs, even though they're paying for insurance. So, there's no transparency, but the level of deception is very high within that too, and so patients are often caught in the middle of that, and you as their prescriber trying to get them medication, that's the downside.

John Marshall, MD: Stacey McCullough, Chief Pharmacy Officer at NCODA. As I promised you all out there, she knows what the heck she's talking about and the vision going forward of what we need to do, what we need to make sure and emphasize as practicing physicians and all of us in this business of oncology, we need to figure out and evolve this PBM process further so it's in the best interest of our patients. So, Stacy, again, thank you so much for joining us. 

Stacey McCullough, PharmD: Dr Marshall. Oh, it's a pleasure to see you. 

John Marshall, MD: That was amazing. I hope you agree that Stacy's insights and thoughts about how we need to move this stuff forward is really useful to us. 

THE PBM MONEY TRAIL: INTERVIEW WITH ANTONIO CIACCIA 

But we actually got also a 2nd interview in a 2nd take on this. I do want to introduce you to Antonio Ciaccia. Antonio founded several things along the way, as he'll share with us, but he works at a place called Three Axis Advisors which spends their day thinking about this issue of pharmaceuticals in the United States and ways that we could evolve it so that not only is there more transparency, there's more access and improved market system in place for all of us. So, I am pleased to introduce Antonio Ciaccia. Antonio, welcome. 

Antonio Ciaccia: I study drug prices for a living. We track manufacturer price changes. We track Medicare expenditures, Medicaid expenditures. We look at publicly available data sets that demonstrate utilization and pricing trends and what we have learned over time is that, between those moments of money going in and money squeezing out, there is a lot being lost in translation.

John Marshall, MD: Okay if that's the problem, where do we go? 

Antonio Ciaccia: Well, in a number of directions. First and foremost, I think everybody believes that we should move toward a system of value-based medicine. I'm a big believer in the philosophy of value-based payments and value-based medicine. Problem is, is that the architecture of our system today is not aligned in that direction. We buy medicines based on volume, not value. The bigger you are, the bigger discounts you achieve. Thus, typically, the greater financial rewards you will yield. Everything I said there has nothing to do with the quality of the service rendered, the outcome to the patient, et cetera.

The key driver of volume-based payments and volume-based reimbursement, starts with our exemptions to federal anti-kickback laws that allows PBMs, and health insurance companies to collect big kickbacks. from drug companies in exchange for preferential treatment on the formularies. Those exemptions create an arms race, to become larger and larger, thus, to extract larger and larger kickbacks, which results in significant market concentration and also insulates drug companies from the traditional competitive forces of lowering prices. Instead, incompetent competitive environments, they compete to raise prices. To create more bandwidth for kickbacks, which increases our reliance on the intermediaries to negotiate our way out of the problem. 

John Marshall, MD: Do you see us ever getting to value-based? I always, I've spoken for years on this subject because I've lived for 32 years as an oncologist. I've watched this business evolve. And I regularly say like, would you swipe your own visa card? Maybe I should say now tap your own visa card for it. And then because that would say, all right, well, let's connect the magnitude of benefit with the cost. And I can decide value-based medicine as a consumer, but because the consumer is in essence removed from the formula, they're not able to judge value ever.

Antonio Ciaccia: The consumer has no meaningful impact on the business practices of the health care delivery system as it stands today. In general, decisions are made for them. And as a result, those who provide goods and services in our health care delivery system calibrate their business model and their offerings in the direction of the desires of the payers. Not necessarily the origin of the payment, which is the individual patient. And a good example. And you could see in pharmacy pharmacies don't compete to lower prices. Pharmacies don't often compete to increase their staffing, to attract a patient to come there instead. The PBM decides where you'll go.

Right. And if they don't have complete carte blanche to decide where you'll go, they can heavily influence through cost sharing pressure, you name it, where you ultimately go. I know pharmacies that have very low prices. And here in Columbus, Ohio, we have a pharmacy called Freedom Pharmacy.

They don't accept insurance. Their prices are a fraction of what any other pharmacy offers. Mark Cuban's Cost Plus drug company. His list prices, his sticker prices, meaning the prices that are offered to everybody are a fraction of what you'll find in other pharmacies. It begs the question that if the people that we hired to get us out of this drug pricing mess really had our interest at heart, they would be crawling over one another to get those pharmacies to be not only a network, but preferred.

The opposite happens, right? They don't want them in network because they mess up the math. Instead, PBMs incentivize higher and higher usual and customary prices charged by pharmacies, and they negotiate big discounts off of those bogus inflated prices. The challenge though is, is that because of the way that PBMs contracted pharmacies, they actually incentivize them to charge higher and higher prices over time because of the disparate way that they pay them in the most favored nations clauses in their contracts, et cetera, which I don't need to bore you with, but trust my shorthand that PBMs incentivize pharmacies. To charge higher and higher sticker prices. And so what that leaves us with is greater necessity To use the PBM to put out the very fire that they're partially responsible for creating And so what is our way out of it? Well our way out of it is having a system that actually incentivizes drug companies and pharmacies to lower their actual prices to increase the quality of their goods and services rather than the opposite. Which is getting bigger and bigger discounts off of increasingly inflated prices without any sort of quantification of value for the actual service that's being rendered by the provider or the quality of the product that is being offered by competing drug companies. 

John Marshall, MD: So, let me ask one more angle on this is that from the work that you are doing, one of the principles that we've been talking about is lack of transparency. So, if you're going to then report to a government or to whatever that's asking for this information, how do you find it? Where is it? 

Antonio Ciaccia: I often complain about the lack of transparency in this marketplace, and to be clear, there is not enough. However, relative to other forms of other types of things that we buy in healthcare, pharmacy is relatively very transparent. My introduction into this world, in a formal drug pricing research capacity was in my home state of Ohio, pharmacies in our state were complaining about underpayments within our Medicaid managed care program.

PBMs were driving lower and lower rates of reimbursement that was causing a lot of pharmacies to go out of business. Meanwhile, on the other end of the transaction, the state of Ohio said we're spending more for medicines. Those two things didn't make sense. How could pharmacies be getting paid less? How could the state be getting charged more when they're ultimately involved in the same transactions?

Well, what we started doing was downloading very boring Excel files off of CMS's website. One being the National Average Drug Acquisition Cost, which for those that don't know, is a benchmark that is provided by the Centers for Medicare and Medicaid Services where they survey pharmacies on a month-by-month basis and they simply ask them the question, what did you pay to put the drugs on the shelf?

And so we took that data set and combined it with another data set called state drug utilization data, which is a quarter by quarter, state by state, drug by drug accounting of how much every Medicaid program is buying and for how much they pay for those drugs. And so we were able to stitch those two data sets together.

One being the real cost of the drug as purchased by pharmacies. The second being what Ohio Medicaid and every other Medicaid program across the country was being charged. And what you saw was this divergent experience over time. Well, we took all that information and gave it to state officials at the time, who I felt didn’t do what I thought they should do with that information. And so, I turned it over to local reporters. I sat down with reporters at the Columbus Dispatch. I flew out to New York to meet with folks at Bloomberg News. And I gave them all this data and they said, we think there's a big story here. The state of Ohio eventually followed the trail. Our state auditor, Dave Yost, decided to open the books and, voila, they found that there were $245 million worth of hidden PBM spreads where they were buying low, paying the pharmacies very low, billing the state high and pocketing the difference.

All of that was started thanks to the accessibility and availability of limited, imperfect, but very valuable drug pricing data. What we have learned since then is that there's even more data out there. Medicare Part D has a ton of pricing information available on its site. You have folks like Mark Cuban that are publishing their prices. Costco publishes their prices, and, before, you know it, yeah, we have a black box in drug pricing, right? But the beauty of a black box is that it's multi-sided and there's a lot of things that you could find around it. Right. And, and so in answer to your question, there's not enough transparency, certainly. And I would argue that when we do work on behalf of state agencies or employers. They're not given the itemized receipt that they deserve. However, the limited amounts of transparency into the system we do have often helps us uncover the latest and greatest drug pricing schemes that are being cooked up by the various intermediaries in the drug supply chain.

John Marshall, MD: You've done a great job of pulling this together and really serving the community at large, because the money that we're talking about. Is not really, I mean, whether it's government money or insurance company money or whatever, it's our money, right? This was money that we paid into these banks, these quote unquote banks for them to then distribute and cover this. And so, there couldn't be honestly, a more important way to try and make our health care system more efficient and find the fat in it so that we can deliver more services.

I mean, it's just crazy how much we spend and still how much we're limited by what we can do. 

Antonio Ciaccia: Let me let me depress you just one little bit more. 

John Marshall, MD: Go for it. 

Antonio Ciaccia: It's an oncologist. Our story is very relevant to your line of work. So, the very first report that we ever issued was in August of 2018, when we launched 46Brooklyn Research as a nonprofit dedicated to what I would call drug pricing journalism.

The very first report we released was called The Cancerous Design of the U.S. Drug Pricing System. And it was all about generic Gleevec, okay? Which I would argue is the poster child for drug pricing dysfunction. It was a huge part of the Federal Trade Commission's report that was released within the last month.

But basically what we found was that Medicaid programs across the country were getting charged thousands of dollars for something that had been declining in its underlying cost significantly over the last few years. Fast forward the tape and again, this shows you the value of drug pricing transparency.

We still see to this day Medicaid programs being charged thousands of dollars per prescription for generic Gleevec. We see employers being charged thousands of dollars per prescription. Patients in those commercial programs having cost sharing based upon those bloated prices. We just released a report in July, where we were looking at pricing information for generic Gleevec in the Medicare Part D program and the beauty of the Medicare program is that they will show you the prices of every single Medicare Part D plan. And within those Medicare formulary and pricing files you can see it within every plan the parent organization of those plans as you well know PBMs aren't really PBMs anymore. They're part of large vertically integrated companies that are often health insurers. Well, if you take all the prescriptions for generic Gleevec across all the different Medicare plans and roll them up to their parent organization, what you'll see is a company like CVS Health, which has hundreds of Medicare Part D plans, despite the fact that this drug has been generic for a long time and is very cheap. Still to this day, you will find CVS Health Medicare plans setting 597 different prices across all of its plans. The lowest price is around $2,600 per claim. The highest price is $8,200 for prescription. Okay. Now to give context here, not only do you have 597 prices, not only do you have about a $5,500 difference between the lowest price that they offer and the highest that drug can be bought from Costco or Mark Cuban for less than $40.

Okay. So the games that we find, right, are not limited to that drug, but it is a demonstration of I think how much risk there is When there is not an aligned approach for how the prices of medicines are set at the pharmacy counter and when there are raging conflicts of interest within the companies that are setting those prices.

John Marshall, MD: Are we the only country that does this? 

Antonio Ciaccia: We are the only country that does this. Other countries have a much more heavy-handed approach to drug availability and pricing. They say, look, these are the drugs we're going to have in, and these are the prices they're going to be. Sometimes that means that they cut off a lot of the inefficiencies that our system has.

In other ways, they disincentivize manufacturers from bringing certain products into those marketplaces. That's a double-edged sword, and those are policy tradeoffs that I think everybody has to, has to consider. I personally am not as much of a fan of that heavy-handed approach, because I think sometimes it can, throw cold water on the access to medicines in the in the innovative churn that we rely upon to get access to those medicines but regardless I think the U.S. System hasn't been given a chance to flourish the way that a traditional market based approach could Because we have all of these special rules for Medicaid rebates, 340B rebates. We have these GPOs and exemptions to kickback laws. We have all these things that make the U.S. marketplace special. Aside from the price controls that separate, you know us on paper I think that the U.S. marketplace can be materially different than what it is today without having to go all the way and say hey, we just need to take this over as at a government level.

John Marshall, MD: So the free market could handle it if really it was a free market and when I hear in the spectrum of sort of, you know, government heavy, quote-unquote, socialized medicine. You're not really there because of the level of restriction. But, you know, I think about the British health care system and the nice committees that oversee new drugs or new therapies, and they put a value proposition to it. So, they say, okay, here's what you're going to charge for it. Here's the magnitude of benefit. Medical people make a judgment. They have a certain fixed amount of taxes they can spend on health care, and they make a decision in or out. So they actually, and then publish the data, the decision in Lancet, for example, but, but that's often criticized because they, you know, there's a lot you can't get in Great Britain, because of that public health service system, we can get it all, but it's a very disrupted system, as you say.

Antonio Ciaccia: I think it's important to remember that there was a, there was a market-based system before PBMs, right? And certainly, it was not nearly as robust as it is today, but it is important to remember that there was a time where our wallets and purses are what guided this, this marketplace. And if a medicine was too expensive, we sought alternatives. If a pharmacy was too expensive, we sought alternatives. The second, that third party payment governed the marketplace. All right. That's when things really started to get out of whack. And that's not me saying we don't need third party payment at all. It's not me saying that we should go back to a system where people can't afford their medicines. But I think it's important to understand the traditional forces that we rely upon in a free market are not present in the environment we have today for medicine. 

John Marshall, MD: This has been perfect. 

Antonio Ciaccia: Have a good one.

PUTTING PBMS IN PERSPECTIVE  

John Marshall, MD: I hope you all watched both of those interviews. I learned so much from both of those people about our world. Every time I click on an order in my EMR and send that prescription off into the ether somewhere, you know, how many people are touching it? How many people are skimming a little money off of it?

How many people are valuable in the process? How many people are unnecessary to the process and just making a dime off of this game that we play? It is so important that we fix this. Our patients are literally dying for better treatments and new treatments. Our industry partners are spending great resources on developing new therapies, most of which are today are going to be oral therapies. And so we have to fix this. We have to fix it. For progress. We have to fix it for our national, frankly, security. We have to make this cost less. We have to make it have the value that it really has so that the money we're spending is going to the appropriate cures for cancer. And, you know, the reason we want to do this is that the next time you see a patient with, you know, say, metastatic cancer, you say stage 4 metastatic cancer. Don't worry about that. Because we can cure that. 

This transcript has been edited for clarity. 

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[00:00:00]

John Marshall, MD: Hey everybody, this is, believe it or not, episode four of Oncology Update, where we're really trying to get to, God should we say it, the truth in oncology. There's so much going on out there. It's a complex business. There's a lot of really cool science. There's a lot of progress going on. We're affecting a lot of people's lives, including our own. 

So, let's jump right in and see what's going on out there this week. 

Remembering the Father of Tamoxifen

[00:00:31] I don't know if you saw this, but a guy named V. Craig Jordan, PhD died. If you don't know who Craig Jordan is, he actually worked here at Georgetown briefly. He invented tamoxifen. You think about the impact of understanding the estrogen receptor and being able to intervene on it and have an impact on people. Talk about somebody who's had an impact on a whole lot of lives. That is Craig Jordan, and his impact will always be felt. But as a human, we will miss having him around. 

DOD Gives Colon Cancer Research Thumbs Down

[00:00:58] Up here on Capitol Hill, kind of a bad day for colon cancer. We've been lobbying to try and get colon cancer as a set aside in the DOD budget. Remember that breast cancer stuff that's in there? A couple of other cancers are in the DOD budget as a set aside, but colon is not. A set aside. It's in the pot. You can do colon research with DOD funding, but we didn't get our set aside. Even though we are among the top five in terms of common and seriousness and cost and all of that. We think we should be in the DOD budget, but we didn't make it. 

NCI Budget Challenges

[00:01:33] Dr. Kim Rathmell, new director of the NCI, she's got a lot of work in front of her. Budget being slashed up there on the hill. But there's this ARPA-H thing, which is this new kind of designated money for more, I don't know, inspirational research might be the right way to put it. Whereas NIH is kind of incremental research that gets funded, ARPA-H is looking for that leap of research. 

Time to Unionize Oncology Practices? 

[00:01:59] And then, I don't know if you saw this. This is kind of interesting. We'll have a little bit of a theme on this today is that out in California, there are 400 residents who work for a Kaiser organization there, and they actually formally filed to unionize, and I want to think a little bit about unionization and practice and the like. 

Merging Oncology Practices: More Guidelines, Fewer Choices

And let's talk a little bit about the business of oncology. So there was a recent paper by Mike Milligan, it was actually one of the ASCO pubs, and it was looking at U.S. oncology practice patterns. And, just very briefly, what they showed is that there was an increase in number of oncologists by 14 percent over, say, 2015 to 2022, but a decrease in number of practices by 18%. Well, you can do the math on that one. What it means is, is that more and more practices are getting bigger and bigger. And in fact, here in Washington, D.C. I work for a 7000-physician practice here in Washington, D.C. And our oncology team is all 1 big team, if you will, and work together. So, we're working more and more for someone and we're working in larger and larger groups. And what it sort of suggests to me is. Maybe we need to start thinking about unionizing. 

[00:03:28] Now, I'm not trying to be some socialist, although I was in England when the Labour won their vote over there. Now, they know how to have an election. That was way cool. We should take a tune from them. They know how to have an election, but we still don't. But, you know, we are being asked more and more to follow guidelines, to basically be on the assembly line doing what we're expected to do and less and less freedom. And I think the way that we will regain some of that independence is through collaborative sort of bargaining, if you will. And so, I do think I see that trend increasing, as more and more of us work for one individual. Or one company, if you will. 

Dr. Ferris Heads to Lineberger After UPMC Layoffs

[00:04:10] Other news on the headlines is that a guy named Robert L. Ferris, MD, PhD, a very prominent runner of the UPMC Cancer Center has just moved down to, a great cancer center as well, down at UNC and North Carolina at Lineberger Cancer Center. He's a great guy and, and he's going to do very, very well wherever he is. But then it made me sort of think, well, what's happening up at UPMC? Because I think about that as being a great place. They turned out to have lost over the last year, 200 million bucks in, unbalanced budget, if you will. And they had to let go 1000 people. And so, we understand that our business is indeed fragile. Makes me wonder if Dr. Ferris made the trip out of there knowing that things weren't going to be very good at UPMC for the while, but we do need to take care of each other, in our business of oncology.

Science of the Week: Risk Reduction vs Absolute Change

[00:05:01] What we're going to really drill down on today scientifically is a single paper. This is a breast cancer adjuvant paper published in JCO not too long ago. And the drug that was added to hormone therapy in a big, randomized trial was abemaciclib. So, Priya Rastogi was the principal investigator. The full manuscript is out there. And what this was, was the five-year survival, the five-year update of this group. So, half got traditional hormone therapy for ER/PR-positive, HER2-negative, breast cancer, quote, unquote, high-risk. Breast cancer. I'm going to come back to that. Versus the same group getting the same treatment plus two years of the CDK 4/6 inhibitor abemaciclib. 5600 patients.

Let's think about what they call high-risk over there in the breast cancer world. Well, the control arm of this patient population had a 90 percent 5-year progression free. So, I mean, it's just a huge number, right? They're all doing very, very well, even though high risk. And it was, it's node positive. It's bad features on the tumor. So, as we, it is bad cancer, but they've already figured out so much now that the many of most of those people are cured. And certainly in 5 years, it's a very high number of people who are doing well, but to try and make that even better, they added 2 years of abemaciclib. And this drug comes with diarrhea and neutropenia, sometimes severe, sometimes requiring dose modifications. 

Would you take it or not? Well, let's look at the data. Well, the data, um, and the curves do show an improvement in distant relapse. Okay, of about 7 percent with a hazard ratio of 0.67, right around there, and, by any study in my world, this would be a home run. And I think it was pretty positive in the breast cancer world too, but you could think of it a couple of different ways. Remember, Already, the vast majority of these patients were cured or certainly disease free, with just the hormone therapy that they were on, and so to add on this, you know, you could say, well, you reduced the risk by a certain amount. You know, the risk was already small, 7%. You know, such a small number. So, if you treat 100 women for 2 years, you pick up a few. 

But then what this paper was all about was overall survival. And I'm going to try and show you that. You see that curve? That's the bottom curve there. That's overall survival. And of course, at five years, there was no difference in overall survival. And even though this paper does, sort of engender changing the standard of care, you treat a hundred women with this situation. You give a bunch of them side effects, there's cost. And in fact, you haven't changed the overall survival. And most of them were already okay. And you did bump it a little bit. 

How do you present that data to a patient? Do you use hazard ratios? Do you use treat 100 people? It only helps one. Do you present overall survival and say it's not worth it? Or do you have sort of a risk avoidance for yourself where you don't want to have been wrong. You have a patient on the other side who's afraid and will do almost anything to get out of this. Right? So, they're willing to risk toxicity, even for a very low percentage, or at least most people are. And so, it’s all aligned. The stars are aligned. to add this medicine for everyone. And so, we are really dramatically overtreating most of these people. If we were to add this drug to everyone, because most of them didn't benefit, most of them don't need it. It's only a small proportion of the patients who really get benefits. So, I think as we are presenting new science or as we are presenting options to patients, we need to be aware of this.

Patient Perspective on Risk vs QOL: Interview with Zach David

[00:09:24] So what we did is we found a patient. I happened to be walking around a golf course with him. He wanted to share his story of his decision making, where he actually decided not to do it—to take additional treatment, risk a higher risk of relapse, in order to keep his taste, to keep his saliva, and to keep his quality of life.

So, let’s hear from him now.

Just a few days ago, Zach David, who, as we were walking and talking and comparing life stories on a golf course, was telling me about his recent experience with his own cancer, head and neck cancer with radiation and chemo.

And what he told me was a fascinating story. So, I want Zach to do a brief introduction of himself and really tell us about the process and the decision making. And in particular, this one decision towards the end of his treatment, that was a tradeoff between quality of life and maybe survival. So, Zach, thank you on such short notice for being willing to join us, but take it away Give us a little blurb on who you are and what you've been through and maybe a little bit more about that decision 

Zach David: Sure, Dr. Marshall. Thank you very much for the opportunity to help in any way that I can. Zach David. I was diagnosed with squamous cell cancer in my neck when I was 48 years old. Three children, obviously a big, big shock to us. Otherwise, I seemed very healthy. And then, you know, the decision trees that you talked about, you know, which process. I started off with a surgical removal of the tumor in my tonsil. And then they did a radical, um, where they took out, I forget the name of it Dr. Marshall, 

John Marshall, MD: Radical neck dissection, I think they call it.

Zach David: Yeah, that's right. 

They took out all my lymph nodes where they thought I'd gone on the side of my neck. I had to decide whether to get a feeding tube before, we went through this process because the radiation was going to impact my swallowing.

We ended up doing that. Seven weeks of radiation and three courses of cisplatin, which was a, you know, an all day event. of hydration, cisplatin, hydration. And by the end of my second cisplatin, I think it was about week five and a half, six of the radiation, I was fully dependent on the feeding tube, was being admitted into the emergency room because the cisplatin was wreaking so much havoc. No taste. High fever. And I went to Dr. Deekin, who was my oncologist. And I said, do I have to take this last dose of cisplatin? He said, well, you don't have to. And actually, a lot of people don't get to that last dose. I said, what are my percentages of survival? He said, your survival rate goes from 96 percent to about 90%.

My next question was my quality of life will have a chance of more saliva. Well, I have a chance to regain more taste and all the side effects that go with that chemo, and we decided after he told me that my chances were 90 percent versus 96 percent to not go with that. Today. I, you know, I do again, taste a good wine, taste a cheeseburger versus, uh, no cheese, et cetera, et cetera. 

John Marshall, MD: that's a really great story and very helpful to our discussion today. So, thank you for sharing. But when you think back on that, obviously you're in good shape, right? There's no evidence of the cancer returning. Do you sometimes have sort of chills or what goes through your mind about that 6 percent that you were sort of willing to give up, for the tradeoffs that you mentioned. 

Zach David: The biggest thing that I think about was that I had advocates. And I asked the question. And you're faced with so many different questions through this process without advocates and lots of people to speak to and ask about the decision points really, you won't know until you ask or are faced with these decisions. Obviously, you know, everybody's a little bit different, and everybody has a little different decision tree that they need to make.

John Marshall, MD: If you hadn't asked Dr. Deeken about that, you would have gotten that last dose, right? He wasn't going to come forward. It's not natural. I'm not picking on John. I know him very well, but we don't naturally come forward and say, do you want this trade off from the patient?

Zach David: Yeah. I mean, this was, this treatment was recommended, by lots of doctors, you know, nationally, worldwide. So, this was the prescribed treatment for my particular cancer.

John Marshall, MD: Maybe one last thing, because you, you know, a lot of docs, a lot of oncologists around the country and really around the world are watching this right now. So, what would you tell us as a patient? You know, what advice would you give us about communicating these kinds of issues to patients, these kinds of tradeoffs to our patients who may be not quite as good a self-advocate as you were? 

Zach David: That's a really hard question. But one thing that my doctor, Dr. Deekin did, he, he took a lot of time with me and just taking the time to slow down in your decision-making process and educate, which not everybody has that luxury. and talk to people, I think that's, that would be my, my number one thing. 

John Marshall, MD: I love it. I love it. Zach, David, thank you so much for joining us as we discuss this really tricky subject of these tradeoffs, decision making, shared decision making to optimize patient outcomes.

Zach, thanks a lot. 

Zach David: Thank you for having me, doctor. 

John Marshall, MD: Zach certainly has an interesting story where he made the decision to not do a dose of cisplatin in order to try and optimize his quality of life, even though he knew that there was about 6 percent delta. Just like our women in our breast cancer study had of having a relapse. He made that decision and so far he is happy with it. 

Talking Truth with Patients: Interview with Mark Lewis, MD

[00:15:42] But what I think we need to do is drill down with one of the world's experts on decision-making. And so right now we're going to cut to an interview with Dr. Mark Lewis 

We are very, very lucky today to be joined by Dr. Mark Lewis. He is the Director of GI Oncology at Intermountain Healthcare in Murray, Utah, which is, I'm assuming, a place somewhere in Utah. He does a lot more out there, but he's really one of the key thought leaders in the world of decision making and oncology and he comes at it from a couple of very important angles, both sides of the exam room, if you will. And it really takes that perspective to, I think, make us all better at what we do. And so with that, let me welcome Dr. Mark Lewis, and we're going to drill down on this concept of decision-making.

So, Mark, thank you so much for joining us and maybe just open this up a bit. What's your take on how we're communicating with patients? These complex decisions, these complex pro and cons for adding drugs, length of therapy, toxicity versus benefit. Where are we with that in your head?

Mark Lewis, MD: Yeah. Thank you so much, John, for having me. And this is a topic that's near and dear to my heart, both in professional practice. And as we might discuss a little bit, even in how I've made decisions about my own care as a patient. So, I'll start by using an analogy. I love figurative language. And one of the things we're talking about here is how to communicate with patients. So, one of my tools is analogies. So, I think a pendulum has been swinging where on one extreme we have sort of the old paradigm of paternalism. You or I would walk into a room with a white coat on and we would sort of try to project confidence. I think sometimes that maybe became almost kind of overbearing or imposing. And, you know, the, you know, idea there was that you and I have done this long enough that we know what we're doing, and we basically just prescribed to the patient what they were going to do. 

And then I think the pendulum has swung potentially a little bit too far all the way across the other pole, which I call a la carte oncology. Which is the patient comes in to consult with you or me, and we basically give them a menu. And we say, would you like option A, B, or C? And I think the problem with that, while it does respect autonomy, to be very honest with you, it kind of abdicates our responsibility. Again, there's a reason people come to us. And I think somewhere between, you know, sort of, uh, bravado and, you know, complete abdication, I think there's a place where the patient wants to know our opinion, or our recommendations.

So, what I do is, I do like to present options, but I also feel like I'm not doing my due diligence for any given patient if I don't tell them at the end of the visit, Hey, listen, this is, this is what I'm going to recommend that you do. One tool I found really helpful is sort of trying to take the patient's pulse on an individual level as to their, not just their scientific literacy, and I don't mean that in a condescending way. You and I both know how easily we lapse into jargon and the alphabet soup of oncology. But even how they view risk, because I think a lot of what you and I do actually is we're trying to mitigate risk for people. And what I've learned over the years is just percentages, might not, especially if we just say them verbally, might not have the same impact as, again, trying to figure out, you know, what do numbers mean to a given person, or do they prefer visuals? And it's interesting, John, we're all products of our training. I trained; I did my fellowship at the Mayo Clinic. At the time I was training, there was a huge emphasis, as you might imagine, on how to counsel patients on adjuvant therapy. And You know, the two diseases that I think made the most impact on me, were breast cancer, and colon cancer. Now, breast cancer was interesting at a time, there was a software tool available, not just at Mayo, but elsewhere called Adjuvant! Online. You may be familiar with it. And it was beautiful, especially for a fellow, because you could essentially sort of plug and play with a given patient's data and you could show them in, in visual format, the added benefit that they would get from say endocrine therapy. And I know you're talking about, about abemaciclib which is, you know, a little bit different. But then, endocrine therapy plus chemo, like if you maximize your odds of risk reduction. And what was it worth? And I guess what struck me, John, was with those patients I was counseling, and again, it was at the very sort of outset of my oncology career, there were some patients who would incur literally any toxicity that you consented them for. If it resulted even theoretically in a 1 percent greater chance of being alive at five years. 

And so I had that perspective from my breast cancer population, and then I developed actually a completely different perspective from treating patients with colon cancer. So, you know, again, I trained under some really wonderful GI oncologists, and the first day of my entire fellowship, one of them who was a true expert in colon cancer said to me, Mark, if you do nothing else as a practicing oncologist, whether you're going to GI or you're doing general practice, I want you to respect oxaliplatin, and I know that you know why, why he said that, and I've certainly learned it over the years. 

So, I think one of the great advances of the last several years in our field, John, meaning GI oncology, was the IDEA trial. I don't know if we'll ever see its like again. Almost immediately as I was sitting at ASCO hearing about it, I think it was the plenary session in 2018, if memory serves, I remember thinking, I can use this the day I get back to clinic. The question is, how am I going to relay these findings to, my patients in a manner that really matters to them? 

So again, without getting too much in the weeds of that study, but you know, you and I both know, and I'll just repeat for the audience here, really a fascinating trial. Again, really looking, I think, at the risk benefit of oxaliplatin in particular. So, Looking at this huge, internationally pooled group of about 12,000 patients with stage three colon cancer. Looking essentially at what was the tradeoff between three or six months of oxaliplatin containing chemo. And there was a lot more nuance to it, but what I came away with was, okay, the disease-free survival of three years, which was the primary endpoint, was actually roughly equivalent, depending on some risk stratification. And what I came away with was to tell patients, listen for perhaps a 1 percent greater chance of being alive at three years without your colon cancer coming back, you're incurring triple the risk of neuropathy that I probably am not going to be able to reverse for you. When I, when I put it that way, rather than just, you know, saying, oh, the three-year DFS was 74 versus 75%. And especially when I put it into visual form. So, I've started using pictograms rather than seeing percentages, actually printing out a picture of a hundred theoretical patients usually, and usually coloring them and showing, okay. It's almost like a spot the difference. I literally just spot the difference. So, on one side I had. like all the colors of the people if they did three months of oxide applied containing chemo. On the other graph, I had the one with six months, and I said, hey, spot the difference. And I had, you know, colored it pretty subtly, but if you looked carefully enough, you see that there was one extra person alive without their cancer having recurred at the three-year mark on the six months.

John Marshall, MD: But even with all of that, we still see our colleagues feeling like, you know, if the cancer came back, what if I had given you three more months, right? You the 1%. And so, this sort of regret avoidance pushes us, I think, to do more than and many of us. I mean, you take the time, which is valuable. You show in a clearer way. What it is to a patient, but a lot of us don't either have that skill set or have that level of knowledge on an individual decision. And so, they say, well, the NCCN guidelines say this, that's what I'm going to do. Right? Because you have to, it's the playbook. Right? And so, you know, we have to figure out a way for us as healthcare providers to increasingly be comfortable with the de-escalation concept and the traits that come with it.

Mark Lewis, MD: Yes. So, two things there, John. Thank you. And you're giving me so much credit and I'm really flattered. One is that the concept you are, important notion you raised about time. So, I agree with you. Uh, the greatest premium needs to be placed on the time that we have, especially face to face with our patients. I don't know how your practice works. I get an hour with new patients. I get 30 minutes with follow ups. And that first hour, as you know, there's like, you want to be present, but there's a to do list in your head, right? As the oncologist, you know, you have to do X, Y, Z. And by the end of the visit, you're supposed to, you know, lay out a treatment plan and explain the intent. And I think one of the things that's really tricky about say adjuvant therapy in particular is it's all risk reduction. There, there is no 100 percent foolproof guarantee that the cancer is not coming back. So, in regard to the time aspect, I am actually a huge fan of, and I'm just throwing this out as a practical tip for our colleagues. I really like One aspect of the EMR, okay. The electronic medical record is largely a billing and compliance tool. I’m well aware of that, but the part I like, and I think it's available in most systems now is the patient portal where I can exchange information with them, almost like a secure email. And it's nice because it's asynchronous. Like they can send me a message at midnight, and I can answer at five in the morning when I'm prepping the next day's clinic. So, we can have that almost immediate interaction. We can exchange information and I can send them resources. I can send them pictures or articles that I think are helpful, whatever issue they're grappling with, especially if it's this one.

And then the other thing I would tell you about, you know, decision or regret. It is a hundred percent real. There have been times in my career where the weight of decision regret has been so crushing that frankly, I've had a crisis of confidence and said, oh my gosh, like, am I really cut out to do this? And, you know, I think if any of us are honest with ourselves, like it's appropriate from time to time to sort of. step back and sort of survey your own acumen. But frankly, John, and this is gonna sound strange, to me that that one percent who recurred because I gave them three months versus six months, I see that a lot less often than the people I see who are struggling with, and I'll use the word very carefully, crippling grade three or above neuropathy because I gave them, quote, too much oxaliplatin.

I have had so many of those people in my career, especially pre 2018 and pre-IDEA, that all those things that my attendings told me the first day of fellowship, they have absolutely, you know, rung true in my head. I probably give, I have given thousands of patients oxaliplatin, and I've given a substantial number of them, and it weighs on my conscience considerably, neuropathy that I sometimes wonder, I sometimes lay awake at night thinking, gosh, did I need to do that? So, you're absolutely right. The decision to regret it. sort of very black and white is, okay, did I, did I affect mortality risk reduction? But the other decision to regret is, you know, first do no harm is a very difficult principle for an oncologist to follow. Like primum non nocere with the drugs that you and I are dispensing is very, very tricky.

John Marshall, MD: Now, those surgeons cut people open and let's give it, you know, they have to do that. Listen, we could go on all afternoon, but I want to really thank you for coming in and sharing your thoughts on this decision making and the complexity and some of the strategies that you've used to make it better for your patients.

I couldn't agree more with that. We need to be voting on what we would recommend to our patients more than we are today. And just put up with that decision regret because it's us that know more in many ways than our patients. So, Dr. Lewis, thank you so much for joining our program if we want to go quite so fancy as that.

And I can't wait to see you in person soon.

Mark Lewis, MD:

Likewise, John. Thank you so much for having me. 

John Marshall, MD:

That's a wrap on episode four. I hope together we are working to find not just the news and oncology, but deeper than that. What's the reality of what we do? What's the truth in our world? And once we get the truth, we'll all be better at what we do.

See you next time. 

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Oncology Update: Introduction [00:00:00]

John Marshall, MD: Welcome back to Oncology Update. My name is John Marshall here from Georgetown University, Washington, D. C., the land of freedom. I don't know what it is the land of anymore, but welcome back to Episode 3 of Oncology Update. 

Our theme for this session is going to be, how do you stay up to date? How do your patients stay up to date with all that's going on in the world of oncology? And are you, in fact, delivering state-of-the-art treatment? Or are you, in fact, maybe delivering something, some recommendation that maybe AI created? So, we do want to, you know, Be careful about that. 

Oncology Update: New and Noteworthy [00:00:40]

But before we do, let's kind of start with some of the news of the week. You know, everyone knows who Dennis Slamon is, an amazing scientist and clinician who, really, his group really defines the whole HER2 targeted pathway, defined the use for trastuzumab in more than one disease and turned HER2 into something that you didn't want, to, now, something it is you want, in certainly in breast cancer. And he, of course, rightfully receives another, major award from the National Foundation for Cancer Research, so a big shout out to Dennis Slamon for the incredible progress that he has made and the impact he's had on so many people. You think about how many lives that man and that science has saved just through that research that he's done. It really is impactful.

On the other side. I want to give acknowledgement to Dr. Harpreet Singh, who worked at the FDA in drug approvals, right? So, the whole idea of giving back to the government, working for not very much money to try and establish the metrics, et cetera, for FDA approval for medicines. But just recently, Dr. Singh took a job as the CMO for Precision for Medicine, which is a, basically a research CRO. And that's very much similar to what we see here in Washington of that kind of revolving door between working for the government and then working for industry. Taking the skills and the inner inside knowledge and the like that's important out to the rest of the world to try and improve the process there. So that's a little bit of what's going on in the world of drug development.

But, maybe most importantly, this is Juneteenth. Actually, we are recording session 3 here, episode 3 here. And it's also part of Pride Month. And so, we have a lot of folks who are out there, who really are underrepresented in our research, underrepresented for access to the treatments we have, for a variety of reasons. Not just here in the United States, but everywhere around the world. And I know many of us are working to try and level that playing field. I always think about this as a really difficult subject, is health care a right or is it a privilege? And we try to dance both of those here in the United States with the private health insurance and other government health insurances underneath that  are clearly not providing the same level of care. And these kinds of months that we think about those who are less fortunate or those who have struggled with their own personal world in a world that's not necessarily built to—ready to receive them. And so, I do think we have to make sure we're taking care of everyone and acknowledging all of that that goes on. So, it's an important month, the month of June for us all to stop and reflect a bit on all of this, particularly in health care.

Oncology Update: Vetting Medical Information [00:03:47]

But let's look at the science of the week. Now, you're going to think, this is, you're waiting for a Nature paper or some major JCO paper. I'm actually going to show you a minor JCO paper. It was written by a very good friend and a person who I really go to for my sort of ethics checks. And this is Dr. Paul Helft out in Indiana, and his team put forward a survey paper that was published in JCO looking at what patients are doing on the Internet, what they're going to see on the Internet, and then what they're bringing into us as information they have found on the Internet. Again, sometimes it's supportive care things, but often it's therapies that someone has posted somewhere on the internet that might be helpful for their cancer. They're looking for a better answer than the ones we are giving them. And it comes to mind is how many times a week does somebody come in with, you know, I've heard that ivermectin can really help cure my cancer. Or, you know, if we just allowed more medical marijuana. This would solve the whole problem. People wouldn't have cancer. Maybe they wouldn't care about having cancer, but they wouldn't have cancer is what they think. Or turmeric is my favorite one. You would think that whole, you know, populations would never get cancer because of the turmeric that is in the diet in certain populations. But no, that seems to be a popular one. Acupuncture and other sorts of mind-body approaches are of course very popular. But many times, you know, we in the healthcare industry aren't really qualified to comment on the things that are being brought in, or they irritate us, or they just take time, and we spent time then waving off the things that patients have found on the Internet. And there's an entire, you know, burgeoning literature around this, and we clearly see that social media and the Internet are actually promoting this sort of alternative oncology all the way to what we would call quackery. And the publishers want this. You know, in my position in academia, it's very common that I'll get emails from some new journal that's just coming out that they need new reviewers, and they want an editorial board or something. And I see that mostly as spam email myself. But, you know, somebody’s saying yes to that. And somebody then is publishing stuff that may not be up to the same scientific rigor that we're used to. And we might come across some of those things on the Internet searches and not really be able to judge what it is we're seeing. And this has created these so-called predatory journals that are out there to just make a living having medical information, no matter what quality of medical information is out there. And a nice recent paper did summarize a lot of this that's out there to be careful. Because when we're going online ourselves, we really need to figure this out. 

Now, where do you go for your information to stay most up to date? Well, I bet you go to UpToDate sometimes. And that's obviously a much fuller annotated version of things. It requires you to do some reading and thinking in order to apply the knowledge there. But most of us are going to NCCN. It used to be that around here, at least, that we would not allow our fellows to cite NCCN as the reason to do a treatment. That was not the source document. The source document was the study on which the NCCN guidelines were based. So, you had to know where the NCCN guidelines came from so that you could interpret that. But somewhere along the way, we sort of slipped off of that. Don't you think that if it's on there, then it's legit. And the payer on the other side is like, well, if it's on there at the right level of evidence, we'll cover it. So, it's almost more important to be on NCCN than it is on FDA. Once you're on the market, NCCN will get you covered. So, it creates a sort of new target that's separate from the FDA, different levels of evidence. 

Did you look down in six-point at the very bottom of the NCCN guidelines on every one, it has the disclaimer and I'm going to read it just so you guys can read, hear this out. NCCN explicitly disclaims the appropriateness or applicability Of the NCCN content, the guidelines and any derivative resources or the use of or application of the NCCN content, the guidelines or any such derivative resources to any specific patients care or treatment. 

That's exactly how we use it. Right. We look up a patient who. You know, we're not quite sure what the rules are. We're not quite sure if that drug's got approval or you covered. We're not quite sure what to do next. So, we open up NCCN and make an individual patient decision based on what's on that, even though they in fact, say that that's not what we built it for in the baseline. So, I just want us to remember that that's where that sits. 

Now, in the old days. I used to be able to know pretty much everything I needed to know to be a practicing oncologist. I could study it; I could remember it. Nowadays, I can't. And there's so many new drugs, they have so many new names and funky names that I can't remember, that in fact, I'm constantly, even in my own space in GI cancer, needing to reconfirm or look back up in the internet of some place—NCCN, UpToDate, or even just Google, to figure out where the answer in fact is. 

Oncology Update: Tracking FDA Decisions  [00:09:45]

And so, I just did a little looking myself about, new drugs that were approved, but now have been withdrawn. It came through my inbox that a, a drug infigratinib (Truseltiq), which you may know as an FGFR fusion molecule for cholangiocarcinoma, was withdrawn. The approval was withdrawn. Originally approved in '21, just in May 2024 was withdrawn. And so, if I had one of those FGFR fusions, even though this drugs on the market, I can't use it for cholangiocarcinoma. But if I looked that up, and I didn't see that it was withdrawn, I might not. I may only see the FDA, the positive FDA approval, but there are a bunch of them here. And in fact, there were 29 drugs withdrawn that had initial approvals within cancer medicine.

Some of the others that we noticed was belantamab mafodotin-blmf (Blenrep). Okay, so Blenrep is a drug for multiple myeloma. It's been withdrawn. It was withdrawn back in 23, but new data, we think it may be coming back on. So, it depends on when you looked up what your reference pops up in your search of whether that drugs in or whether that drug is out. In my world, pembrolizumab (Keytruda) was originally approved for gastric/GE junction cancers. Now that's been withdrawn, depending on what your PD-L1 status is, etc. And then also a really interesting one that maybe, you know, you younger people don't even know the arc of, but gemtuzumab ozogamicin (Mylotarg), was originally approved in 2000, withdrawn in 2011, but then back on the market in 2017. So, you get my idea of what really is out there, what really is FDA approved, and these accelerated approvals give us access to medicines, importantly, but then sometimes they are pulled back. 

Now, just in June. There were a bunch of approvals. There are six new approvals. I want to read you a couple of them because they're pretty pedantic, if you will. One of them is a drug called blinatumomab (Blincyto). You've probably heard of that one. But the approval is for adult and pediatric patients one month and older, CD19 positive, Philadelphia chromosome negative, B cell precursor, ALL. How about this one? repotrectinib (Augtyro)? This is for 12 years and older for patients who have NTRK gene fusions. Now, I've only found one of those in my entire career, but you need to know that there are drugs that that just got added to the list of other drugs that are out there. Another one is a drug called lisocabtagene maraleucel (Breyanzi), I believe it's how you pronounce that. And this one is for adult patients with relapsed and refractory mantle cell lymphoma, who have received at least 2 prior lines of systemic therapy, including a BTKi drug. 

So, you have got to really know what's going on. If you're a general oncologist, how would you know what's going on? So, you're dependent on looking stuff up. You're dependent on our education resources and other online resources to keep up. 

So how about this one? This is real or not real? This is a paper that a search found and it's for entrectinib (Rozlytrek), you remember I talked about repotrectinib, this is for entrectinib, for NTRK fusion positive solid tumors after a larotrectinib (Vitrakvi) or repotrectinib, so as third line, if you will, for entrectinib. Now, this paper is from the Journal of Clinical Oncology, says it was published in 2021. And in fact, one of the authors is one of my partners here at Georgetown, named Mike Atkins, and Rick Pazdur is listed as an author on this paper, Michael Slayman, Jeff Weber, a lot of prominent people are authors on this paper. And you would think if this came up in your inbox that this is real, right? And so, you might even take this paper and send it to the insurance company, to the guy at Aetna, and say, look, I got a JCO paper here that says I got a response rate that's very high in this patient population. It's already an approved drug. Let me give it to my patient in front of me. Except, it's not real. This paper was created. By an AI search engine, and it says it's a JCO paper. It was completely the right format, the right color scheme, the right font, the right references. But what made us all suspicious was the author list. Why would Rick Pazdur, from the FDA, be on a paper such as this? Mike Atkins doesn't do this kind of research, technically. And then we went one further step. And in fact, showed that the page numbers from this JCO paper didn't line up correctly with the journal. And so, this really suggested that we were getting a bum paper. This was a made up what they call hallucinated paper. So, we also have to be careful at that level.

Oncology Update: Maintaining Certification in Today’s World [00:15:03]

All right, so how do you keep up? And I want to kind of shift gears a little bit to our maintenance of certification, or MOC. Now, I'm in internal medicine. It's originally boarded in medicine, then oncology, and I've only maintained my oncology after a while, my 4th go-around, and this 4th go-around, because I do it every 10 years, this go-around, I decided not to sit for the exam and to take the maintenance of certification, questions. Those of you who are doing this out there know what this is all about. But maybe most some of you do. Some of you don't. So, every quarter I get 30 questions in a portal. And these questions are heme/onc questions, onc questions, med onc questions. And the way I do it is that I put 2 hours on my calendar each quarter. 1 hour I do 15 questions. Next hour. I do another 15 questions just so I make sure and get it done. But you also know that when you go on to this, you have 4 minutes to answer the question. And there's a clock running up in the corner there. And you can use any online resource that you want, but you can't talk to somebody. So, when I originally started this, I thought, Division Chief, we've got a big fellowship program here, maybe I should do this in front of the fellows. And they're like, nope, you can't do that because this has to be just you and whatever internet resources you have. So, they're giving us the internet. to do this. So, what I do is I have two screens. I put the question over here, my little clock running over there, and open here, I've got, what do I have open? I have NCCN Guidelines, and I have UpToDate open on my computer screen, and I read the question. It's always a leukemia question or one more breast question and the like, and I don't know a lot about that, so I really need to understand what my answers are. So, I look it up, and I'm doing pretty well. Every 30 questions, I might miss three or four. But that's with all of these resources, and I get nervous about the clock running down, and I am pressed for time. And so, in the end, I just hit one and say, I hope I'm right. And most of the time so far, I'm right. Except the GI questions. I'm getting killed on the GI questions because I really know the medical literature in GI cancers. And one of them recently was a case where a patient had liver mets that was resected, had not had adjuvant therapy a couple years before, and there's no literature on what to do with that patient. None at all. And so, I put, you know, you observe the patient, which is to me, what would be a standard of care. If you had an isolated liver met, it was removed, you don't know what to do. But then I missed the question. Missed it because it said I should give chemotherapy. There's no data for this. In fact, the data does suggest maybe progression free, but no overall survival benefit, no true adjuvant effect. So, I go on to their reference, which was the NCCN guidelines and down in the small print, some branch point way down here. It basically said, look, if you've never given adjuvant, consider giving adjuvant. That was the correct answer by the ABIM version of the process, which, in my opinion, is a very controversial answer. And, yeah, I could see the argument for, but there's no literature to support that. And so, you know, this is why I'm kind of frustrated. Now I'm getting nervous every time there's a GI question that comes up because, you know, do I know too much? Do I not know enough? What's going on here? Why am I missing the GI question?

So, it is clear that we can't know everything anymore. There's too much coming at us. There's too many funky words. There's too many subtleties to genetics and the drugs, etc. So, we need to get better. I need to get better at online access. I need to have trusted sources. Sure, UpToDate and NCCN are very good sources. I don't hear anything different than that, but we also need to have that sort of inside baseball knowledge about what the right way to do it is. What's the right way to dose things? This sort of thing. Right? So, we need good, over our shoulder help that the Internet can provide to make sure that we're providing state of the art care for the patient in front of us with all of its complexities and all of this changing that's going on so that we're dependent on it just as much as everybody else is. So, we need to get better at it. 

And so, with this, I just challenge all of us to think a second time when you're going on a search, and you find a paper that supports what you want to do for a patient. Do some cross referencing. Think a second. Was it created? Real? Is it on guidelines? Is it cross referenced with other sources before you then go forward? If it's a therapy you've never given before, try and find somebody who has, and talk to them about what is the right dose, what is the right way to monitor for side effects, et cetera. Because those kinds of subtleties are awfully hard to get off of the internet and find, phone a friend and figure it out. Because I think with that, we'll all be better doctors and using this great tool, this great knowledge base that's in front of us, using it wiser for the patient.

So, to really try and dig down deeper on this issue of the ABIM and MOCs, there's a lot of confusion about that. We are lucky enough to have a guest visit us for a brief interview. From the inside, one of the leaders at the ABIM 

MOC Ins and Outs: Interview with ABIM Chair Suresh Nair, MD [00:20:53]

So as promised, I have a world's expert on how we get board certified in oncology, and we're lucky enough that Dr. Suresh Nair has agreed to spend a little bit of time with us. Now, if you don't know who he is, you should. He's an important guy. He was the physician in chief at the Lehigh Valley Health Network and Pennsylvania, just north of where I'm sitting. When I look through his resume, the guy likes Pennsylvania for sure. He's been from the east side to the west side with all of his training, and he's trained in some of the best places in the world, and he has dedicated himself to building just an incredible practice there. Part of his busy life as well has been to be involved in the ABIM. The process and certifying us all for our licensure. He's an oncologist, and in 2022, if my numbers are right, he actually took on the leadership role in the ABIM structure over medical oncology and having somebody like that to give us a few minutes is really special.

So, Suresh, let me first say thank you and welcome. 

Suresh G. Nair, MD: John, I feel honored. Thank you so much. And to be, as I said, being with a legendary oncologist who I respect highly. Thank you. 

John Marshall, MD: Well, I get in trouble a lot, as you know, so hopefully we'll keep each other out of trouble on this one. Because for the first time, this was number 4 for me on going around on, on a, on a getting recertified and I thought I had been doing it right. But it was December 15th of 2023 that I realized that I wasn't doing it right. My CMEs weren't MOCs, for example. And so, I had to very quickly figure out how I was going to do everything by the deadline so that I maintain my board certification. So, I had a panic moment here as a senior doc.

I wanted to talk a little bit about my choice, for example, to take the test. Sitting down formally number two pencils, no longer, versus the orderly tests as a way to maintain and just to get your high level that those of us in oncology are doing this. Who's doing what? Everybody, or is it a gemish all over the place? 

Suresh G. Nair, MD: I've been on the ABIM med onc board for the last five years, and as you said, the last two years as the chair. So, I was there as the board responded to diplomats that sometimes the 10-year exam took time out of practice to go to courses, and it was very stressful. And especially I feel like in oncology where things are changing, you know, by the week, by the day for some of the questions. I know you probably had the same experience, the areas that I spent a lot of time in like melanoma, kidney, I was getting some of the questions wrong because the test questions were written five years ago. And they have to go through verification and standardization and all of that. So, the longitudinal knowledge assessment (LKA) was launched. We have about 14,000 board certified oncologists, 85 percent of them are engaged in the LKA, once they become eligible for it, and about 15 percent are choosing to do the 10-year. I also did the 10-year exam about two years ago. I've decided to do the 10-year in oncology and I'm doing the LKA in hematology and in internal medicine. I don't practice much hematology anymore, but I was originally boarded in that at the University of Pittsburgh, and I thought I would try it out, and it's been a bit humbling, but I'm gradually—I have a barely passing score and continue to improve in that. We are finding that, we're continuing to listen to the diplomats and we're looking at making some changes because, I too, the week of Christmas and the new year was reading a lot of up to date to get my MOC credits because I too had a deficit and, you know, I didn't have the hundred that was needed and So at the board level, we're looking at giving—there is credit for the LKA. You do get MOC credits for that, which I think more and more a lot of diplomats are going to, but we're working with ASCO, working with thought leaders in all facets of CME and maintenance of certification credits. 

John Marshall, MD: Yeah, no, I think that's really great. And it's, it's, you're having to live it yourself. You know what it feels like when all of us are out there, because you and I are pretty specialized. A lot of generalists might do better on some things, but still need the props you know, resources and source things to help with the questions. When I first started, I did really badly on the first 30.

I have to share with you that the four minutes was stressful to me. I kept watching. I wasn't. very good actually at looking things up. And as I've done this now for a year or more, I actually realized that I've gotten better at looking things up. Now what I'm not sure of is, is that making me a better doctor or not? I mean, I can find the answer what's being asked, but I don't necessarily have any familiarity with What I'm talking about so I can match the words up to get the right answer But how much feedback have you had in that way that people because I do feel smarter I actually used to dread the time when I was doing The questions to now sort of looking forward to it because I do leave knowing more than I did before. What's been the feedback so far to you at your end?

Suresh G. Nair, MD: The feedback's been very similar to you John in that the four minutes is stressful. There is a time bank that you can click on for extra time for certain questions. I, I too, on, on the hematology, which I don't practice as much and I'm doing it for pure learning I didn't do that well in the first two, and now I've been engaged in about two years and keep getting better.

One of the things it's made me do is areas that I feel weak, and I do when I have some time read up on that area a little bit. And I'm noticing my scores going up and getting expertise. We are, you know, kind of wrestling with certification versus education. So, it's not a pure education tool. When we go to ASCO and we sit at the education sessions, that's a pure education tool. This is also a summative assessment, and there's a lot of science at ABIM. I've been very impressed with the test gurus there. There's a lot of science that basically about 96 percent of us end up being certified, but it is stressful to some degree. But I think all of us believe in lifelong learning. And there is, there is some science that when, when the test has some stakes. We actually learn at a higher pace.

John Marshall, MD: No question. My juices go up on when I'm doing those questions. No, no, I totally they do. And, and I believe I take away things that I wouldn't normally have ever learned if I hadn't come across the question.

Let me come back to the, you know, you miss questions, I miss questions, but in our own field, right? So, I'm getting the leukemia questions right, but I missed, there was a question the other day, where it was a resection of a colon met in the liver, and the question was, do you give chemo afterwards? Well, I happen to know there is zero literature to tell you what to do one way or the other. And when I got the answer wrong because I said to observe the patient and done in the subtext was the reference was NCCN guidelines. So, I went to the NCCN guidelines and saw that said, well, consider this. And so of course, you know, you know too much, right? And so, it's a frustrating moment. How do I miss that question? When I know the literature there and you and I talked a little bit before about How does the ABIM keep up to date? Where are the sources of the questions and that sort of thing? 

Suresh G. Nair, MD: So, so we have a test writing committee and a test approval committee, and our board has given feedback for instance in the LKA, okay, there's 30 questions. There's usually at least one or two that the standard of care has changed, even if the question was written, you know, two years ago. I think a clear case would be in melanoma at the plenary, the neoadjuvant change from pembro to, you know, ipi/nivo now the two doses and our, our, we have a, you know, there, there's been test questions that, that If you do what we heard at ASCO, what's in the New England Journal, you probably could get it wrong. So, so one of the, one of the suggestions at our last board meeting was to have a group of experts. Literally, the, the, the week of go live of LKA go through with it with the fine-tooth comb, because it is very frustrating to diplomats. 

John Marshall, MD: But I was thinking to us in my head was like, could you put the date up there? Because I remember we were talking about. You know, if I go on a Google search for something, and if I find an answer I like, but it's an older answer, it might not still be correct, but it's what I was looking for. And so, I don't keep looking. I'm done. I validated what I thought I knew, and then I move on. And, and so, as you say, we're, this is assessing a moving target. So, there is a time, but I think your strategy is perfect. It's just making sure that folks, Have a good look.

That still wouldn't have solved my problem. 

Suresh G. Nair, MD: No, and we acknowledge that there's just some bad questions. That that question you were you were right, you know, based on the literature based on studies. And NCCN sometimes it's just more opinion rather than studies. And so, unfortunately, there are on the board, you know, so they are looking continuing to look for more test writers. We are starting to get a good number of applicants. And then what one other important direction that the board is going and based on listening to the ASCO survey of the diplomats is to tailor the exam so that 70 percent of the exam will be general content, 30%. We can't hit every narrow specialty, but the major specialties that we have that physicians in the future could say, I specialize in GI, or I specialize in lung, and so, so it can be more tailored to them. Because this is a summative assessment and the science has to be intact, right now we're working on what's called practice profiles and kind of focused assessment and we'll be having the fall meeting where our committee will present a lot of stuff to us.

We have Furman McDonald is the new CEO and president of ABIM. You know, had a distinguished career at Mayo Clinic was at Penn and really is, is a strong listener and I heard his vision at the ABIM Council last week. There was always this feeling the board was a bit tone-deaf to the diplomats and I, I see that changing. I'm a practicing community oncologist who has been lucky enough to have partnerships and stay involved in NCI trials. I'm supposed to be 40 percent clinical, but I ended up being 80 percent clinical in my 40 percent time. So, so I hope I bring the practicing physician perspective to the board. The board has been receptive and sometimes it does seem like it’s turning a plane around. Because they have to keep the science and the validity that the board certification means, you know, that that it means something to the public. One of the things we want to do is to celebrate maintenance of certification but continue to evolve. 

And one of the areas we're grappling with now is the, you know, quick adoption of AI. Now Siri soon going to have AI on our phones you know, pretty much any, any Google search, you know, there's an AI running in the background. We know we can't run away from societal innovation. So, we just need to continue to see, you know, what's the most important thing to try to test. And more and more we're actually finding, it goes back to John, how you started, I think trust and being able to trust your physician because patients are going to be confused, there's going to be misinformation, there's going to be a lot of things. So how do, how do we test for, you know you know, trust and, and, and the things that makes a human physician different from a, from a robot. 

John Marshall, MD: Totally right. I'll be quick, but the AI thing you mentioned, there was some complicated gene in one of the questions and I, instead of typing it, I tried to swipe and copy it and this alarm went off and it basically says, if you do that one more time, we're going to do something bad to you. So, I haven't done it again. Okay. But anyway, you have put some checks and balances on the ability to just cut and paste that question over and put it in AI and see what the answer is. But listen, I know you've had a busy day already. And you're giving us extra time on short notice to talk about a really important question about how do we keep up to speed and you are the sort of overseer of truth in many ways. And, like you. I am proud of my certification, and I am proud to be part of that club. We were all worked very hard to get the 1st one, and so we should continue to maintain that. And I think it's great to hear how both receptive you are, but at the same time, holding our feet to the fire to make sure that we're providing the public with a trusted human on the other side who knows what they're talking about and knows when they don't know what they're talking about. Maybe more importantly and knows how to figure it out for the patient in front of us. 

So, Suresh, thank you so much for this. And good luck as you continue in your leadership role.

Suresh G. Nair, MD: John, I really appreciate it thank you so much. All right. Thank you. 

John Marshall, MD: Thank you all for joining us for episode three of Oncology Update, where we focused on the whole concept of how do we stay up to date. I'll see you in a couple of weeks for episode four. 

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John Marshall, MD: Hey everybody, John Marshall for Oncology Update. Believe it or not, second episode. They let me do a second one. There's bad judgment on their part.

ASCO Buzz

[00:00:13]

We're just back from ASCO, so you know how everybody's doing. You're still trying to pile out of your emails and figure out if you're actually going to get reimbursed for that dinner or not try for it. You never know. It might work out. 

Let's start and kind of reflect a bit on this meeting, that is ASCO. You know, is it really a medical meeting, or is it really a celebration? Let's think about this. You walk into that place, there's signs everywhere. You get out at O'Hare Airport, there's signs everywhere. They're welcoming you to ASCO. You get a bunch of cancer centers marketing their cancer centers that aren't in Chicago, in the Chicago airport. And then you get to the meeting itself, it's like a celebration. You go in to where the booths are now. This makes it look like we have won, that we have cured cancer! The lights are going off, everything is all shiny and sparkly, the carpets are extra cushiony when you get onto one of the drug company booths.

I asked people while we were there which booth was by far the over-the-top booth and there is a clear winner here. We're going to give it to AstraZeneca. Amazing booth. Also, the most likely to cause a seizure was this booth, the lights and everything going on; most likely to cause a seizure for sure.

But there was also a really fun booth. I'm not going to name the company where it came from, but they had the most funky lights. There were these huge tubes that were bigger than a human. And all the lights were hanging from the ceiling from these huge tubes. All I could think about as I was walking by is that, somehow, those things must be really for erectile dysfunction, right? I mean, that's kind of what it looked like—it solved that problem. I went to the booth, turned out, no, they were just decorative. Not any erectile dysfunction problem at all. But, you know, go figure. It's what it seemed like to me.

It was clearly a super spreader event. We pretty much figured out that the best COVID comes from Western Europe, the sort of romance language part of Europe. The Germanic language part not so good, their COVID is more serious, the romance language COVID is the best. 

There weren't many community oncologists there because they had to make a decision to go there, lose RVUs to gain CME. And that trade off just wasn't there for them. If you remember from the first episode, when we really drilled down on the RVU and its value, it's going to be a disincentive for somebody to go to a medical meeting like this to try and learn the state of the art of cancer care. So, clearly that's not who was at this meeting. 

Probably the wildest thing I heard somebody say was that when I was asking about the booth, and a typical booth, even a small, modest booth might cost half a million dollars, is that they came back and said, ‘you know what, this is a good use of our money.’ Wait a second, half a million dollars, that could fund a phase 2, small phase 2, clinical trial for goodness sake. So, you know, is that the best use of your money is to have this big booth, and then the other part is who's paying for those booths? That's our health care dollar at work, whether it's the National Cancer Institute's booth, which is our tax dollars at work, or the pharmaceutical industry and all the money that they have because of the health care industry. So, that's our money they're spending in there on these celebratory booths that we need to kind of come back and think about why is that the right way to go.

Our theme today is going to be all about costs and expense, and why is it so expensive? Why is cancer care so expensive? And we're going to really drill down on a few main areas around that, the cost of drugs and the cost of clinical research.

ASCO Wins

[00:04:17] Let's start with looking at the success, amazing success, of the clinical research that was presented at ASCO. There were three standing ovations among the five plenary abstracts that were presented, and the one that probably deserved it was a drug called osimertinib. You know, this is for EGFR-targeted non-small cell lung cancer. And the benefit was dramatic. A huge delta between the curves. And all of a sudden, everybody said, this is the way to go. I think probably yeah, there's a terrible disease. It's a therapy that works very, very well. Huge improvement in outcome for patients in the curative setting. All in, right? We're all in in that group. Worth standing up and clapping for. 

But, did you know that the rumor is, a little gossip, that, uh, that the other two standing ovations also, drug therapy studies were actually started by plants from the companies who wanted everybody to stand up for their therapies as well. I hope that's not true. I really hope that's not true, but it might be. You never know. Could be true that they're trying to get more standing ovations to applaud this victory that everyone is claiming that we have in cancer. 

[00:05:40] I can't resist telling you about one other study was done in colon cancer. My baby. A study that could only be done, where they have the best COVID, in France. This was a study led by a brilliant surgeon who has set so many standards for us all around the world, a guy named Rene Adam. And believe it or not, liver only metastatic colon cancer, half the patients got standard chemotherapy, The other half got a liver transplant. Do you think you could ever do that study here in the United States? No way. There is no way you could ever do that study here. What patient would allow you to randomize them to a transplant over there or continued chemotherapy over there? If you were eligible, I want that transplant, baby. I'm American, I can have whatever I want. They pulled it off over in Paris, and what they were able to show is again a dramatic difference for the transplant. Something like 70% versus 15%, a huge delta between the two groups. And even though it was a small study, it was very well done, very well, conceived and followed correctly. So, setting a new standard for in the right patient liver transplantation for metastatic colorectal cancer. 

Clinical Research Reality Check

[00:06:55] This has made me reflect a bit about clinical research in general. What is the value of clinical research? Well, one of our lines has always been that if you're on a clinical trial, you live longer; that somehow patients who participate in clinical research live longer.

There was a recent paper that was in JAMA that actually did this. They took a bunch of studies, and they pulled it apart and they actually did show that there was some benefit to being on a clinical trial. So, you're okay in saying that, but then the authors went a little bit deeper and actually compared it to what if you were on standard therapy, and, if they pulled out those clinical trials where the control arm or whatnot was a standard therapy that was in place right now, there wasn't any survival advantage. So, it was only when you compared it against other kinds of approaches that people showed that survival advantage. So, it was a little bit of a mixed message of, yeah, there's a survival, but maybe not so much as we thought before. That was a little bit of water on our flame. 

[00:08:03] And then a second approach that was, was presented in Cancer Medicine actually looked at how we've done not a very good job of increasing accrual to clinical trials. There are all sorts of strategies and studies and education and all of this that we've done to try and increase awareness of clinical trials; increase participation in clinical trials. And, yet we really haven't made too much out of that. 

So, on the backdrop of all of that, we’ve still got a lot of work to do. I don't think we have a victory just yet. 

Drug Price Negotiations

[00:08:41] Let's get back to this value question. You may not know that there's a law in the United States that says, I can't judge value. I can't put together the cost of something and the magnitude of benefit. We're the only country in the world that has this law. And so, to begin to undo that law. A year ago, the folks from the government said, we're going to put out 10 drugs. We're going to give you a list of 10 drugs that we would like to negotiate price on. And we want to start this discussion. Well, lots of people said, this is never going to go. It wasn't just cancer drugs, but some of them are cancer drugs. People said, this is never going to happen. We're not going to have that discussion. It's just going to go away. There's too much going on that’s good with the way the current system works. So, we're not going to mess with that. 

The reason this has come back to mind is that it didn't go away. Just about a month ago here near me, in Maryland, the state legislature had a meeting. They put together a committee and had a meeting. And in this case, they picked eight of those ten drugs, and they began to talk about how are we going to think about this. Now, I worry a little bit because who's on this committee? Who's making this decision? Well, we do have people from the pharmaceutical industry, we have insurers on that, we have medical communities, and unions, and patient representatives, etc. So, you know, probably pretty good representation to discuss the impact of should we or shouldn't we. And you must remember that Maryland is quite, I don't know if you want to call it progressive, but it's out there with regard to government healthcare, has completely different laws around Medicare than any other state in the country. They might just take this on and think about it in more detail.

You know who I really find missing in all of this discussion is the payer. So where is Medicare on a huge pot of money over there? Where are the Blue Crosses and Blue Shields in all of this discussion? Because the way I think about it, we are each paying into those banks, whether it's Medicare or your own health insurance company. Each month coming out of your paycheck, taxes going into those banks, and you haven't gotten a raise in a while because companies are putting in more and more on our behalf. So, the bank's getting filled up, and then they guard it. The insurance companies guard the bank, but distribute it to people as they need it. And that's the model of insurance, of course. We hate our insurance companies because they're always fighting. We don't like the way they guard that bank. We want them to let everything out of there if they can. But on the flip side, we don't want our individual costs to rise. So, we kind of talk out of both sides of our mouths. 

I've been thinking like a crazy idea. Go with me on this. What if you just got diagnosed with, I don't know, say metastatic colon cancer? And your insurance company calls and says, sorry, you've got metastatic colon cancer. We'll offer you today half a million dollars, five hundred thousand dollars cash, to not take treatment. Would you take the money? Who out there would take the money? I see you. Who out there would not? Turn it down and take treatment? Because in fact, we're about to spend more than half a million dollars on you. And so, I never understood why insurance companies don't offer you a buyout to get out of all of this and just pay some cash and go, but that's never going to happen. We know that. 

So, we are in fact having the discussion. We probably will over time begin to whittle away at this concept of negotiating drug prices so that that component of our over-expensive health care system can at least fall into line. That yes might make for less fancy booths at ASCO. We're going to have to realize that you won't be able to get quite as good a cappuccino at that favorite drug company booth that you got when you were in Chicago this past weekend. But I think we'd be willing to make the trade for, some sort of better pricing, better access to drugs, in our country and around the world. 

I want to shift gears to a really, I think, even bigger problem than the expense of new drugs. Because one of the arguments that the companies make is that clinical research has gotten really, really expensive.

And there's a law that you might know about sort of a theoretical law called Moore's law, that I think, came around building computer chips, that with every year, with every five years, it not only got cheaper to build the chips, the chips got dramatically better. They could hold more data, they were faster, etc. So, that Moore's Law of it gets cheaper and faster, is how much most things work in the development world. Well, in drug development, jokingly, they call it Eroom's Law, it's Moore's Law backwards. And essentially this says that with each passing year, it is getting more expensive and less efficient to do clinical research. And this has been going on, as an old guy, this has been going on for gosh, 10, 20 years.

We thought we'd do is deep dive into this subject, and we have invited maybe one of the brightest people on the planet with regard to clinical research. And not only smart about it, but is determined to do something about it. We will meet Dr. Laura Esserman right now.

Smarter Clinical Research: Interview with Dr. Laura Esserman

[14:40] As I just promised you, I have found maybe. the smartest person on the planet about how clinical research has to evolve in order to actually cure cancer. Because remember, that's what we're here to do. And Dr. Laura Esserman is a professor of surgery at the beautiful UCSF out in San Francisco. And for the last while she has built this incredible program around breast cancer research, and now other cancers are starting to follow suit. And she's nice enough to take a bit of a break out of her own clinic day to come and join us and talk about this. 

Dr. Esserman ,Laura, thank you first for joining, but right away, what the heck happened to clinical research? What happened over the evolution of the last 10, 20 years that's got us in this bad state? 

Laura Esserman, MD, MBA: In an effort to try and make it more consistent, I think we took a wrong turn. I have two words to sum it up, misplaced precision. We have two systems, one for clinical research and one for clinical medicine. They're both terrible, and, what we need to do is improve both with one better approach. People say clinical data isn't good enough for research. Really? So, it's really only good enough for patient care?

What is that? Right? You know, who would accept that? There are a certain set of facts that you would not forego if you're taking care of a patient with colon cancer. Same way for me with breast cancer. The surgeons want a little bit more detail on this, and the medical oncologists want a little more detail on this, the radiation oncologists might want something else, but all of us know what it is that we need to collect. We need to get to the business of collecting the right data once. And just having a commitment to high-fidelity, high-quality data as we go. And then you've got all the data you need for clinical research. Now we've got these CROs who are coming in and combing through the data, and they make money every time you find a discrepancy. So, our incentives are completely misaligned to make things better. And everything's gotten so bureaucratic that no one wants to do any of this stuff. This is crazy. 

John Marshall, MD: I kept thinking that we become highly paid data entry specialists, right? And even then we don't do it correctly, as you say, and they in the CRO thing. I remember the day when a clinical trial might be $2500, $5000 a patient and you could abstract out from the data, and cooperative groups accepted this, the FDA accepted this, this was good enough. And then this CRO thing came in, and what is it, one-third of the total budget of most trials is this data discipline over top of us that's paid, as you say, to find us making mistakes. If we don't make any mistakes, then they don't have a job. 

Laura Esserman, MD, MBA: That model, I think needs to go, I've dispensed with it. And you don't need it. And the thing is, there's already data you can extract. We've developed these tools called OneSource. You can pull the data out. I mean, why, why are we having data coordinators extract lab values from one electronic system to another?

One of the things that isn’t going to break the bank is the patient reported outcomes because the patient's only going to report them once. And we only need them once, and, again, the patient should report what they know best. You don't need the clinician or the study coordinator to report what the patient's going to know. They know if they are having aches and pains. And then, the clinicians should focus on grade three and grade four adverse events, adverse events of special interest, and immune related events. And anything that causes a dose delay, reduction, or discontinuation, and that is it. Are we collecting adverse events so we can report them to the FDA? Okay? Are we collecting information so we can get them to the clinician to manage, improve and minimize toxicity? Again, a complete lack of focus on what matters, what's important to patients. 

Imagine if you had a trial where you were constantly learning and evolving and figuring out the best sequence of therapies, trying to learn and manage and optimize the management of toxicities as they arrive. Everyone would want to participate in such a trial. And that's what I-SPY is. That's what we've done.

John Marshall, MD: you brought it up, the I-SPY, and I have watched you. I was your IRB reviewer here at Georgetown for many years, so I know it well. and as you know, I'm really interested in it for us in the GI cancer space. I think it is a great model for us all to follow. Getting back that control over decision-making, simplifying, expediting; all the things you talk about. So maybe, those of us who know, know, but there are a lot of us who don't know about your solutions for this, and so maybe some highlights of that for our audience. 

Laura Esserman, MD, MBA: Let me just sort of give you a quick summary. And again, I think there's plenty of complexity in the trial, but it's focused on clinical decision-making, not on, you know, the nitty gritty detail of every last event.

All disease is heterogeneous. And all of us really know that, and we'll say, oh, well, it's a heterogeneous disease, but then we go ahead and treat everybody the same. That makes no sense. And then people are like, oh, well, you can't do subset analysis. I'm like, okay, fine. So let's start. We started, actually, I started in the cooperative groups, and I left the cooperative groups because they weren't moving at a pace that I felt was appropriate. I mean, the cost of drugs and the cost of development is astronomic because we've allowed it to be so.

John Marshall, MD: And time is a factor in that 

Laura Esserman, MD, MBA: Time is a factor, and If you think about it, the person sitting across the table from you does not have 10 years for you to get your act together. So, what we started with first was, let's take the fast-growing, molecularly high risk, stage two, three breast cancers, where we showed in I-SPY 1 in the cooperative groups that, you know, if you could actually start with the therapy first, and you could make that tumor go away, you've got your intact biomarker. By the time you operate, you're getting in the course of care. The important information that tells you what to do next. So, if the tumor's gone away, that is strongly associated with event free survival and distant recurrence free survival, which is what kills people, right? So that with a hazard rate of 0.2, that is an amazing early surrogate marker.

So, your goal should be to try and figure out what are the different disease subtypes? How do you start figuring out what the right drugs are for the right patient at the right time and constantly learn and evolve and improve the algorithm so that you can optimize everybody's chance at getting that good outcome. In the first 10 years of the trial, we studied 23 drugs in control and 10 of the arms graduated. And some of them are on the market today or were superseded by other drugs. We had Taxol (paclitaxel) with a novel therapy, plus or minus any one of a number of therapies, followed by ACE, adriamycin, which is a terribly toxic drug, then followed by surgery. The next person coming into the trial would get the benefit of what we learned from that. That's actually not what patients want. They want to know that they're going to be on a trial that is smart, and that will actually give them some agency and some learning.

At the beginning, we couldn't do that because we didn't have the drugs, but now we're running the trial the way I'd envisioned in the first place, which is three blocks of therapy, three shots on goal. Again, everybody starts with the systemic therapy first. I'm a surgeon. I'd love to be here, but you know what? You know, everybody would love to do much less surgery. I can do less if the tumor is gone but if the tumor isn't gone, my surgery isn't going to fix them. So, you've got to figure out the next drug. I think everyone's like, ‘oh my God, you're putting them at risk.’ You're not putting anybody at risk. I think we've learned that. Right. And that's how you found, you know, in colon cancer to some remarkable treatments for immune drugs in the right patients, but you don't bring them to the wrong patients because they have a lot of side effects. So, the idea is you give them the first set of drugs, but you make that a non-standard chemo. It can be, you know, bispecific antibodies. It can be anybody drug conjugates, you know, any number of things. 

John Marshall, MD: What's so crazy about that from most of our traditional thinking is that this is curative. In this neoadjuvant, I mean, think about the old days that it would take 10 years to find an adjuvant therapy because you had to wait forever—you've developed a system where you can change the standard of care within a year or two based on neoadjuvant pathologic complete responses, right?

Laura Esserman, MD, MBA: Right. So, here's the thing, patients care about efficacy and toxicity. 

John Marshall, MD: Exactly. 

Laura Esserman, MD, MBA: Right? Not just efficacy, you know, and I think a lot of clinicians are like, I just don't want to be blamed for making a mistake. You know, 

John Marshall, MD: Regret avoidance, 

Laura Esserman, MD, MBA: You’ve got to come up with a strategy that makes people feel comfortable. So, what we did was we've been using MRI and quantitative imaging, not RESIST criteria, that it's like doing some two dimensional thing when you've got really, you know, rich data.

John Marshall, MD: You created a new endpoint of essentially pathologic complete response that ultimately gets regulatory approval, right? So, you changed the rules on, you know, the old established rules that weren't doing us any good.

Laura Esserman, MD, MBA: Right. As you know, we have to let go of some of the rules stuck in our heads because you can't improve without that. The thing is, we need to not be afraid to do some safe experiments. You know, it's true, you might make a decision that you might find that something's wrong. Okay, just set it up in a way that you've got your safeguards built in, but you're giving everybody the chance for benefit. These new drugs, you don't know if they're going to work, but six weeks, no one's going to die in six weeks. And there's a huge upside if they work in avoiding future therapy. And, if by 12 weeks it really works, you can skip the toxic chemotherapy and go to the OR. Same thing for going on to block B. So, you've got some agency in the middle, and we have good algorithms, and we keep working on making them better. If you want these companies to build these new exciting therapies, you've got to give them a place to test them and to do it much more quickly. You know, the whole Silicon Valley, the whole dot tech tech revolution is about systems-based learning and, you know, rapid learning. You know if it's not going to work, learn fast, fail fast. If it's going to work, great, build on that and move on. 

John Marshall, MD: You've done it, right? Got it. And the way I think about…

Laura Esserman, MD, MBA: People are following it. 

John Marshall, MD: Yeah, we're coming after you.

Laura Esserman, MD, MBA: And now we're working with the FDA on developing a regulatory strategy around it. We haven't finished we haven't gotten there quite yet, but we will. 

John Marshall, MD: It really is Innovation and individualization are the two priorities, that you want to make sure that that patient in front of you, their individual tumor characteristics are recognized and optimized, the therapy for them learned from that through innovation. And you bring those two things together and then you create a new way of practicing medicine and cancer.

Laura Esserman, MD, MBA: So, the basis of this new trial is a smart, sequential, multiple, Assignment randomized trials, 

John Marshall, MD: You certainly sold me as a GI oncologist of how we might partner with your team for similar things you have learned. You've already done it. You're doing it with COVID vaccines as well 

Laura Esserman, MD, MBA: During the COVID trial, you know, the, one of the agencies that was sponsoring us was concerned. I said, look, we do not need to have, every time there's an adverse event, someone doesn't have to fill out an adverse event report because when people are dying of COVID, they have ARDS, they're dying. They have multi system organ failure. I mean, you could be filling these forms in all day. Here's a checklist of 10 things that happens to every patient. Do it the same on every single patient. It'll take you two minutes. That's a much smarter way of going about it. But they were concerned that we were hiding things or not collecting information. And they made us do this full audit. And you know, we spent six and a half million dollars doing this audit. And we didn't find one adverse event. 

John Marshall, MD: You know, you say that that would have bought a kick ass booth at ASCO, six and a half million dollars. That would have been money well spent, is to take that money on your audit and spend it on a fancy booth.

Laura Esserman, MD, MBA: I'm trying, I'm trying to get this published, but, you know, it's going to be very threatening to the industry, but it should. But, to us, it's like we need to take back control of our profession. We need to, like, develop better systems for clinical care that actually help us with research because the goal of clinical medicine, what are we practicing for? We should be practicing to improve, but if you don't know what you're doing, you can't improve it. So that's my story and I'm sticking to it. 

John Marshall, MD: I think we should just leave it right there. Dr. Laura Esserman taking a break out of her clinic from UCSF Department of Surgery there and the leader of the I-SPY program, transformative. Dr. Esserman, thank you for joining us. 

Laura Esserman, MD, MBA: Oh, you're welcome. Thanks for having me. 

John Marshall, MD: I hope everybody enjoyed this episode of Oncology Update. My name is Dr. John Marshall and maybe while you're out there, think a little bit about why is cancer so expensive?

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[00:00:00] John Marshall, MD: Hey, everybody out there. This is John Marshall live from my office at Georgetown University. And this is oncology update for May 22, 2024. We're about one week out from ASCO. There's a lot going on, but first let's talk a little bit about what's going on out there in our business world in oncology today.

Shifts & Shocks: Layoffs, Dose Reductions, and Drug Withdrawals

[00:00:27] There’s been a crazy lot of stuff happening. First, I don't know if you saw this, but Bayer laid off a thousand plus people or will do that over this year. And it's going to be at the management level, pretty high level. They say they need to thin down, become more lean and mean. They got a bit top heavy, but this is not the only company doing it. Biogen and Novartis are also in the process of downsizing their sort of corporate offices. So, look out for, I don't know, people looking for jobs as these folks get laid off and need to move on to something else.  

https://www.fiercepharma.com/pharma/bayer-reduced-1500-roles-new-organization-takes-shape   

[00:01:01] Another fascinating thing that's going on is that there's this recognition around dosing of new medicines; that we're using too high of a dose of medicine. That's the ones that were tested. We didn't want to miss any effect, but that means we're giving too much of a dose. New studies are looking to see if we can we use significantly lower doses of a lot of our cancer medicines and still have our best bang from the buck? And so, this is critically important as we become better physicians. So watch out for that research. 

https://www.washingtonpost.com/health/2024/05/04/cancer-chemo-drug-dosage-fda/

[00:01:32] The next, and I don't know if you saw that just this last couple of days, FDA announced that, infigratinib, now this is one of those fusion molecules for FGFR2 that was seeking to get approval at the FDA level. It got initial approval based on early clinical trial data, but you know why they withdrew the request for approval. They couldn't get it because they couldn't get patients to go on the study. And that means we're not doing good molecular profiling and we're not enrolling patients into clinical trials. This is a shame that this has happened. So, we need to be better about this because now we've lost a drug that could have been useful for our patients with FGFR fusions.

https://www.fda.gov/drugs/resources-information-approved-drugs/withdrawn-fda-grants-accelerated-approval-infigratinib-metastatic-cholangiocarcinoma  

Redefining Cancer Center Operations: Strategic Mergers and Leadership Changes 

[00:02:19] On the big medical corporate front, the news that's out there is that Rush, up in Chicago, has become the seventh internal in the U. S. partner with MD Anderson's network. And this is quite a network. You've got Banner Health in Phoenix, you've got Baptist in Jacksonville, you've got Community Health in Indianapolis, in Camden, New Jersey, a site, Ochsner, Down in New Orleans, Rush in Chicago, and, of course, UT San Antonio, and you think about just the size of this. I happened to be down in Houston to do grand rounds. Actually, only four people showed up live for that. Everybody is virtual. Will grand rounds ever be live again? But nonetheless, I was down at MD Anderson, my wife and I giving grand rounds and lo and behold, it is huge. It's shiny. It's beautiful. And now they've got even more size to go after. 

[00:03:13] So why would you do this? Well, of course, from MD Anderson's perspective, this is a great thing for them. This is connections to cancer centers around the country. They can do more studies, for example. They probably get paid for this brand.

[00:03:26] Why would you want to be this? If you were in New Orleans or in Phoenix? Well, you're trying to compete in the marketplace, and the MD Anderson brand carries a lot of weight for people out there as they're seeking cancer care. So, it seems like it's a win win for both of these groups or all of these groups to get together. But it also means we're getting bigger and bigger conglomerations of cancer care providing, and so, you know, there'll be less variability, less innovation is what I worry about in that space. 

https://www.bizjournals.com/houston/news/2024/04/29/md-anderson-cancer-center-rush-university-chicago.html  

[00:03:58] One last point around the business of oncology, if you will, is that for NCI designated comprehensive cancer centers like ours here at Georgetown, it is increasingly really impossible for one individual to run that shop because cancer medicine, particularly at the NCI level, has two, at least, major components.

[00:04:22] One is a research component, and one is the business side of this. And the latest to join this splitting of the leadership is out in Oregon. You know, Brian Drucker has been running that shop for a thousand years, and he's just the greatest cancer center director there ever was. But he basically said, look, I need corporate help to run this, and he brought in Tom Sellers, and they split the head office into these two different sections, and it really speaks to the times that we have. You need that research, mentor leader on one side, the scientists coupled to the business side of things. Moffitt did it. Huntsman did it, and they've now done it. So, a lot of action out there in our business world today. 

https://news.ohsu.edu/2024/03/14/ohsu-knight-cancer-institute-announces-leadership-transition   

ASCO's Pinnacle Presentations: The Path to Plenary Recognition

[00:05:08] Let's shift gears and talk a little bit about what's going on in the research world. Well, it's May 22nd today. And so all of us are getting ready for the big show in Chicago. 45,000 of your closest friends will be assembled in Chicago. There isn't a hotel room to be found, so don't even try.

[00:05:28] And, we'll present a bunch of data. I mean, a lot of what the meeting is about is other meetings to try and move some balls along, if you will. Let's hope it's not a super spreader event. I think hopefully we're done with that kind of thing. But, you know, there's big data that gets presented. And I've been on the review committee for ASCO for many years over in the past, and I was fascinated at how the abstracts get chosen. You know, the disease teams get a dump of 300, 400 abstracts per working group. They review, they prioritize, and up bubbles the top 50, the top 100, the top 25, top 10, the top 10 of the orals that get presented by colon or non-colon or breast or whatever, and then from all of that, the subcommittees nominate an abstract to be in the plenary session. We now have five abstracts in the plenary session. We don't know what they're going to show yet because they haven't released those abstracts yet. They're all called late break abstracts. 

https://meetings.asco.org/2024-asco-annual-meeting/15848?presentation=234899#234899

[00:06:33] So, I took a look, see what we're about to see coming forward at ASCO this year. And of the five, three of them have to do with lung cancer. One small cell clinical trial using IO, one non-small cell using osimertinib. And interestingly, one that's palliative care, whether you should give palliative care remotely or in person, who knows what that's going to show, but it's a positive either way. There is no placebo arm on that. There's nobody not getting palliative care. It's just how it was delivered. How that made it to the plenary session, I don't know. It better be a big impact. 

[00:07:08] There's an immunotherapy study for melanoma, adjuvant. Got to be positive, right, got to be practice changing. 

[00:07:15] And, then the GI one, my world, was actually two not very good treatments. No new fancy drugs compared head-to-head. FLOT, which is a three-drug regimen for upper GI cancers versus the CROSS regimen, which is chemoradiation for esophageal, and this was looking at adeno. And, how this became the top abstract of the year. I don't know, not a new drug, not anything, not even that common of a cancer. But what we're going to see is a head-to-head of two competing standards, where I'm assuming one of these wins. Now, If the FLOT regimen wins, that's one less place where we're giving standard radiation to people. And, we have to recognize that as chemo and other systemic treatments have gotten better, radiation certainly gets less impactful. But if the other way wins, it means that some of our systemic chemos that we're using in gastric and other cancers may not be optimum treatment either. So, I'm interested to see what happens. I don't really see a standing ovation like we've had in previous years around breast cancer ahead of us, but you never know. Maybe the data will be that transformative that we'll get that standing ovation at ASCO. But I hope to see you, many of you, there, and, of course, on our next episode in a couple of weeks, we'll reflect a bit on what data actually did cause the stir, what bubbles up to be the most impactful out there for us.

The RVU Rundown: Interview with Kashyap Patel, MD

[00:08:48] Now, as our final section, I really wanted to talk about something that is near and dear to my world as an administrator. So, I'm director of a division, and I work in a big healthcare system, and the metric that we use nowadays to incentivize, credit physicians, and other providers, is the RVU, relative value unit. I sort of think of it as our cryptocurrency. And how do we really understand how that came about, and how we're going to use it? Should we be using it? Should we be tailoring it in some way? And I don't know enough about this. So what I have done is invite somebody who does.

[00:09:34] I promised you all a world expert in the world of RVUs and there is no one smarter or more experienced about it than Dr. Kashyap Patel. He is the CEO of the Carolina Blood and Cancer Care Associates. He's the chair elect for clinical affairs and the trustee of the Association of Community Cancer Centers, ACCC. Huge organization is the immediate past president of COA. And, more important to me as a coauthor, he has written a brilliant book that I think everybody out there should get called between life and death. It's a beautiful set of stories about his relationship with patients, and all oncology teams should, should read this. Great book club book for that. But that's not why we're here today. We're here for a much more important topic than patient doctor interaction. We're here to talk about money and in specific, the RVU. He and I are both giving up maybe one or two RVUs right now to be here with you guys. 

  https://betweenlifeanddeath.org/

[00:10:31] Dr. Patel, let me first welcome you, but jump right in. You know, what is an RVU? Why was it created? Let's get into the weeds of this a bit. 

[00:10:43] Kashyap Patel, MD: First of all, it's my honor to be Speaking with you, John, I think you're a big personality.

[00:10:48] You have name all over the world. And my first memory goes back to when we meet at the Ballantyne Hotel back in 2002, when you came and spoke on colorectal cancer as an expert. I remember that. So, I'm so honored to be here with you. 

[00:11:01] And coming back to our core point here, the RVU, Relative Value Unit, It's actually one of the methods that CMS has organized to identify a way to compensate physicians, and it looks into the training time. For example, if you're oncologist in primary care, it also looks into something called GPCI, which is geographical practice cost index. It has a lot of inbuilt adjustments within that. And so, it's a way to define the time that a doctor spends, the overhead cost for the practice, and other logistical expenses. And then what would be that cost plus physician time be combined together, and how does the American Medical Association CPT Committee and CMS decide together. And it also applies to not just the patient, it also applies to procedure as well.

[00:11:58] John Marshall, MD: So, would you and I actually get different RVUs? I'm in Washington, you’re in the Carolinas. Would you, would we have differences or we're the same? 

[00:12:07] Kashyap Patel, MD: No, we are different. So, so they, they adjusted with something called GIPC, which is Geographical Practice Costing Index. And they make adjustments based on the cost of living, based on the cost of hiring employees, and the cost of the rent . So, it's adjusted based on where you practice. You may be having highest RVU when you're in New York, and the lowest when you're in Alabama, like South Carolina, because CMS perceives that the cost of running business is low there. 

[00:12:33] John Marshall, MD: And so, but then we've got the differences between like, orthopedic surgeons who are making 10,000 RVUs a year, and we oncologists who average somewhere around, you know, 4,000, 5,000, depending on what kind of practice you have, some more, some less. Is that because we're different busyness or we get different credit for what we do? 

[00:12:55] Kashyap Patel, MD: So, it's very interesting. The RVUs forcing patients is one thing, but if an orthopedic surgeon does a procedure where they do surgical procedure, there's an RVU tied to that as well. Now the big limitation is that going back to like 20 years back, when technology was not so much evolved, we didn't have robotic surgery.

[00:13:15] If you had a procedure that, you know, somebody did surgery and spent four hours, technology evolved, time become very efficient. The same thing could be done in one hour, but RVUs still four times. So that's a discrepancy there itself, that with the evolution of the time and technology, the RVUs lag behind adjustment. That's why you're somebody said this may be getting paid 10,000 hours for the RVU versus us probably 4,000. 

[00:13:43] John Marshall, MD: So, you think that it's a good system? Do you think in general, it's a fair way of giving credit where credit is due? Because I remember the good old days when you got a salary. Right. You just got this much money. You might get bonused if you were really busy or there was some sort of extra way to make money here or there, but this really does credit you for the individual part of your role in the health care system, you know, one patient, one doctor encounter versus your role as a sort of leader and organizer of a practice. Do you think it's a pretty fair way to do things?

[00:14:22] Kashyap Patel, MD: I think at the beginning of the career, it may be pretty fair way to do that, but then people like me and you, we spend a lot of time outside seeing patients. For example, you teach so many students, you do so much research, you publish so many papers, and it doesn't come free.

[00:14:38] I mean, you give up something. time that you can never reproduce. Unfortunately, the CMS as well as AMA committee that looks at RVU has not factored in the length of experience, the type of experience, and the administrative time. So to a certain extent, people who go beyond their call of duty of seeing patients, doing research, bring new technology in particularly into the medicines, elective specialties.

[00:15:08] We may be treated unfairly because the time spent in teaching research or experience is not factored in into the compensation. So it's almost like if you started your career with a fresh MD from the same school at the same hospital, John Marshall will still be within the same money that he started making, but your MBA colleague becomes CEO and he probably will get 50 times more than what you get. 

[00:15:32] John Marshall, MD: Well, we went through this, right? So, we went from this salaried, you know, differed by rank here at the medical center, you know, different rank, you made different money, um, to where everybody essentially got the same pay, whether you were right out of residency, or if you were a 30-year senior physician, and so it normalized that. And there was a lot of initial pushback on that, of course, is that you don't get any credit for your seniority, as you mentioned, your experience. But also, as you get older, you have more duties, and, so, our docs are now pushing back and saying, well, if this is how you're going to pay me, then that committee I'm on or whatever else I need to be doing to keep a practice and a hospital going, you need to credit me for that. And I think that part of our compensation hasn't caught up. Do you think that's right? 

[00:16:24] Kashyap Patel, MD: That's absolutely right. I think they need to factor in the extra clinical duties that you do other being a part of the committee or part of the NCCN coming to write guidelines for part of the ASCO committees. All of this should be factored in within the legitimate kind of time frame to ensure that people who want to give back in a different way are not disincentivized.

[00:16:46] And let me tell you one more thing here, John, that, for example, seeing a patient after 20 years’ experience and make a clinical decision is a lot different than seeing a patient right out of college. So, there's definitely a wisdom to aging and maybe, you know, people like us with gray hair and wrinkles. But I do feel that RVUs should factor in that element, even in the clinical side as well, in addition to the extra clinical duties. 

[00:17:12] John Marshall, MD: Yeah, I think there are a lot of places around the world that do acknowledge that expertise. And, you know, there might be a base healthcare system for everybody and then kind of a premium healthcare system for those with more experience out there.

[00:17:27] And so, again, we don't, right now, we don't, everybody's treated the same, uh, in most of our healthcare systems. And I do think RVUs seem to be the dominant way it is done, although there are still Those that have kind of a more traditional thing, let's look at it from the health care system because I know you're big into that too on that side.

[00:17:48] You understand that part of it. Is it fair from the health care system? There's some people come to me and say they're making money on us. Because what they're paying us, they're making more money in revenue than what we're doing. So in fact, we're not being credited for that back in the day when people owned their practices, they could pay themselves what their practice could make.

[00:18:11] And so do you think that's fair under an RVU model? 

[00:18:16] Kashyap Patel, MD: No, I think you're right. Because once again, I think, you know, the RVU probably ends up in people work hard to earn some bonuses based on RVU, but then RVU produces more and more revenue for the health systems, which unfortunately ends up going into the administrative costs without having a lot of other kind of rewards to the person who does it. So, I feel that it's important to have a base as an RVU, but then they should, they should evolve. From my perspective, RVU space has failed to evolve to keep up with the changes of the time. And if you don't change with time, you may become like a dinosaur. 

[00:18:57] John Marshall, MD: Last sort of point about this that I want to bring out and then whatever you want to share is that, you know, when you're driven by these RVUs, you don't take a Friday afternoon off anymore to go to a meeting or to go to a CME event or, um, or frankly go play nine holes of golf and clear your head because you're driven to see more patients.

[00:19:20] And so I worry a lot about our sort of mental health, both emotional, social health, but also our education and keeping up because we're so driven by these RVUs. Are you feeling that happening? 

[00:19:35] Kashyap Patel, MD: I do feel because, you know, we experience compassion fatigue when you deal with the patient over and over again. And if you don't have time to take a break, to attend a meeting, shake hands with people who know something may be better than what I know, or maybe, you know, take some time off to unwind. It's only going to make mental health crisis worse. I think we are in the perfect storm between the post COVID recovery phase, between the RVU world, and between the push to do more and more and more without getting time. I think we are entering into a whole different era of healthcare delivery systems.

[00:20:10] John Marshall, MD: I can't thank you enough for joining me today. I hope everybody listening appreciates it. I think it's you and me and people like us that need to keep this conversation going so that we allow this system to evolve to take care of some of the issues that you and I brought together. So, thanks very much for joining. 

[00:20:29] Kashyap Patel, MD: Thank you very much, my friend. I look forward to learning more from you, my brother.

[00:20:33] John Marshall, MD: And both of us back to clinic so we can stay down for the long haul. 

[00:20:36] Kashyap Patel, MD: Get some RVUs. 

[00:20:38] John Marshall, MD: So that's a wrap. Oncology update, John Marshall, May 22, 2024, a week ahead of ASCO. I hope this has been useful and I hope these insights and our world of oncology will make us all better so one day we indeed will find the cure for all cancers.

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[00:00:05]

John Marshall, MD:

Hey, everybody, John Marshall back for oncology unscripted. If you've been silly enough to further away your time with me, we're now on the 7th episode, believe it or not. Goodness gracious, the sponsors of this are crazy to let me keep going. 

But we do have some really cool stuff to talk about today, and I hope you'll listen in as I review not only sort of what's going on in our world, a little bit of gossip, a little bit of business, we're going to talk about the latest science, but as you remember, this is the third in three parts about the middle men, the middle people in oncology. And so, we've done pharmacy benefit managers. We've done the EMR. Now, the next one is Clinical Research Organization, CROs. So, stick around for some discussion about the impact of CROs on us, on clinical research, and maybe, are they helpful or not? You'll have to decide after you listen in. 

[00:01:11]

Vermont Sues PBMs

But let's start with a little bit of gossip. So, if you remember, we talked about PBMs before, and just so happened that the state of Vermont, their attorney general has sued the pharmacy benefit managers for illegally driving up drug costs. You thought that was just me saying that? No, the Attorney General of Vermont also thinks that. 

[00:01:29]

ACS CEO Steps Down

Sort of on a business note too, Karen Knutson, who's a really very prominent member of our cancer community, was or still is briefly the CEO for the American Cancer Society and the American Cancer Society Action Network. She has decided to step down, she's going to do a lot more work in that space. So, we will be seeing a new ACS leader. I always want to think about the ACS. It is the largest private nonprofit funder of cancer research in the United States. And, so, we do want to make sure and hold them accountable for their product beyond their journals and the like and what comes out of their science, but I think they've had a great impact over time. So, congratulations to Karen and we look forward to the transitions ahead.

[00:02:16]

NCI Puts Millions into AI Efforts in Breast Cancer

Sort of a crazy thing we came across is that, you know, there's a lot more AI in health care today. But the NCI just dropped 3. 7 million in an effort for AI to predict breast cancer risk and also sort of to try and wrap in health disparities to try and level that up a bit. But there's another one looking at AI outperforming conventional methods for prostate cancer. management. So, we're increasingly seeing AI being used, just like every time you drop something in your Google browser, AI being used to try and help us be better at what we do.

[00:02:59]

Honoring Dr. Jeff Weber

I do want to give us a bit of an update. There's a really important obit that I'm sure you saw a guy named Jeff Weber. Jeff Weber was 72 and he died. He actually. died of pancreas cancer, but we will know him forever as one of those people who's made a major impact in the world of cancer. His work in melanoma, his work in immunotherapy, frankly, his work as a mentor and making sure that for generations to come, we are going to see that kind of high quality clinical translational researcher, educator, the whole bit. We lost a big one when Jeff Weber died of one of my diseases, sadly, pancreatic cancer. I wish he was working on this one, because maybe he would've solved that one. I feel like we let him down, but here's to him and all that he has done and all the lives that he has touched.

[00:03:48]

McKesson Wins Bid for Florida Cancer Specialists

Just one little bit of business news. You may remember a few episodes back, we talked about sort of the interface about the You know, our industry and how groups are buying other groups, etc. Well, I mentioned Florida cancer specialists was being looked at by a bunch of different parties. Well, we now know McKesson, I guess, won the bidding for a low 2. 5 billion. McKesson bought Florida Cancer Specialists. And then if you think about everything from patient care all the way up the business chain is owned and organized by one group. And so, I do think we need to watch this space carefully because are things going to improve? Are they going to get more expensive? Are they going to get more efficient? We really need to see how this kind of structure works, because we know more and more of that is going to happen. In fact, I've heard some people predict that not too long from now, the entire United States might be covered by just 10 different health systems that there'll be mergers and acquisitions up and down the chain. so that will be just about 10 of us nationwide. We'll see if that comes too fast. But there's the 1st pass at it with Florida cancer specialist and McKesson working together. 

[00:05:06]​

John Marshall, MD: 

What Did We Learn From the 2024 ESMO Congress?

So, let's look at a little science at this point. As you may not know, 34,000 of our closest friends gathered in Barcelona. Have you ever been to Barcelona? It's one of the greatest cities on the planet. The food is fabulous. The weather is fabulous. The views are spectacular. So, if you ever have a chance to go there, go to Barcelona. 

Well, 34,000 heme/onc docs descended for the annual ESMO meeting. It moves around, unlike ASCO, which is always Chicago. ESMO moves around this year to Barcelona, and I thought it would be useful just to take a look.

I'm going to show you a few high-level abstracts and make sure you guys have seen these. You probably did. Because both the New England Journal of Medicine and Lancet Oncology had featured publications with the full articles that reviewed some major new science that was out there. So, I encourage you to browse both of those editions because there's a lot of practice changing stuff that went in there. But I thought I would actually feature a couple that maybe didn't make it; were still high value papers, 

[00:06:15]

Enzalutamide + Ra223 in mCRPC with Bone Mets

So, one is a prostate cancer study, and this is where enzalutamide was given either alone or with radium 223. As you know, radium 223 is good for painful bony mets and things like that. So here was the question of what if you put the two together on initial treatment and the punchline was. It worked. So, you got a progression free survival of 19.4 versus 16. So, you got a three-month bump by combining these therapies. And I think the conclusions of the authors are probably accurate to what we will see in guidelines and the like is that this will become certainly a new standard option to patients with hormone refractory, metastatic prostate cancer. 

[00:07:00]

Retifanlimab + Carboplatin-Paclitaxel in Anal SCC

Now, you don't see a lot of stuff around anal cancer, do you? We haven't made much progress in this space in a long time, and we've tried all sorts of different things. Well, we did get one clinical trial, and I'm going to screw the name of this drug up. It's retifanlimab basically another checkpoint inhibitor in combination with platinum and carbo taxol in patients with metastatic or inoperable squamous cell cancer, the anus and has not been treated with prior chemo. So, these are not common. This is a cancer I take care of. So fortunately, we take care of them most of the time, but this study actually demonstrated an improvement in outcome.

[00:7:43] 

Pembrolizumab Plus Chemoradiotherapy for High-Risk Locally Advanced Cervical Cancer

And related to this a little bit further north, I don't know, is pembrolizumab plus chemo radiotherapy in cervical cancer, similar biology, similar risk, chemo radiation treatment, similar this kind of thing. Well, this study did show an improvement, but here the delta, it was not so great. So, if you added the pembro to the chemo radiation, you got 82.5%. Whereas if you just did the chemo radiation, it was 75%. A bump. Most people were cured. The bump was small. Giving everybody pembro for that small bump will be the decision we have to make going forward in cervical cancer patients. Big study, statistically significant. Got to think about the magnitude of the benefit. Is that worth it in these patients? 

[00:08:23]

TACE + Lenvatinib and Pembrolizumab in Intermediate-Stage HCC

Another one back in the GI space, which I thought was important. We're seeing more and more HCC around the world. We know about lenvatinib. We know about IO therapy here. Well, what about if you gave TACE? So, you injected the liver lesions and gave the lenvatinib and some pembro. So, some TKI and IO concomitantly. This was the LEAP 012 clinical trial. And guess what? It was positive. It was positive by 4 months. So, 10 months versus 14 and a half months. So, I expect that we will see that moving very quickly to the front line setting as well when you're doing TACE early on in diagnosis. Current standard would be TACE alone. Now it's going to be TACE with combo therapy. So that's a good study. That's moving the bar forward in HCC. 

[00:09:21]

Neoadjuvant Pembro Plus Chemotherapy and Adjuvant Pembro for High-Risk Early-Stage TNBC

Breast cancer cannot be left out. Triple negative breast cancer. You give Pembro to chemo in patients in the neoadjuvant setting with triple negative breast cancer. Overall survival. Of course it was positive, but here again 82% of patients were cured with the old standard. Adding the pembro to this, bumped it to 86%. So, you got five percentage points more. You gave a hundred women pembro for those five extra points, but it's a bad disease. My wife had it. I'm glad she didn't die; 5 percent may be my wife next time. So, we do understand the importance of adding that to treatment. 

[00:10:04]

Neoadjuvant Durvalumab in Muscle-Invasive Bladder Cancer

And then the last one I want to talk about is again, an IO clinical trial. They featured it as well, plus chemotherapy, and in the adjuvant setting, neoadjuvant setting for bladder cancer. So, do you give it before or only after the treatment? And so, basically, the answer was by giving it before you did have an improved event-free and overall survival. So again, I'm expecting that we're going to see more and more neoadjuvant therapy coming in bladder cancer, clearly a trend and almost every cancer there is out there. 

So, I sadly did not make it to ESMO, but I wanted to bring just a little bite of ESMO to you. I got no beautiful Barcelonan food to offer you, and you know, to make you feel more at home, but I hope you one day will go. And maybe not when ESMO is there, maybe just go with your family and have some fun.

[00:11:03]​

Main Topic - Complexity Overload: CROs and the Rising Cost of Clinical Research

John Marshall, MD:

Let's shift gears now to our middlemen series. And the next area we really want to focus on, as I've mentioned, is clinical research organizations. And I have two outstanding folks that we're going to interview to talk about this sort of from all angles, but I want to just set the stage with a very brief history of what all happened. I've been around since before CROs were really much of a thing. They only came into play in the 1980s. And this was because of the worries that clinical trials were getting to be more common and that we needed to have our data cleaner. The FDA was, in fact, tightening up in some way. The way packages would be submitted to them for approval or not. It wasn't just the trial, yes or no, on a curve. You needed to have all of the data in there together. It needed to be highly qualified data, good quality data. 

You know, I always joke that even the National Cancer Institute, you would think they could handle this. They went out and got a CRO, and they partnered with Theradex. And they have for many years. What the issue here is, is that the sponsor, somebody who wants to do the trial, needs to get access to that patient who fits their trial. And traditionally, they just needed us, the clinician, who did clinical research, to identify and enroll that patient on the clinical trial. But, we apparently didn't do a good enough job of maybe managing the data, is really where we got in trouble. We're good at finding the patient, not good at managing the data, maybe, or at least to the quality that we need. And that's what CRO's who now get inserted into all of this will do. They came in as the savior for all of this problem. They said, don’t worry, sponsor, we'll find you the best sites. We'll make sure their data is the best. We'll train them and we'll make sure your package is great, and we will, by the way, add a whole lot of money to the overall cost of the clinical trial. Some say as high as one third of the per patient costs goes to the CRO to manage this. 

These are for-profit companies. We need to remember this. These trials are going through the roof in terms of numbers of trials, complexity of trials, so that as a result of this too, the number, the value of per patient accrual. So, what it costs to put a patient on study is going through the roof and it's a competitive marketplace.

Back in the day when I was young, you know, you could put a patient on a study for, I don't know, 2,500 bucks a, a head. And that was enough to do all the data analysis. Of course, that was old money. New money, you need to add at least one zero, maybe two zeros per patient. and so, the cost of one patient on a clinical trial has gone through the roof in large part due to this additional administrative oversight. So, we get analyzed. We get trained. We have to hire up all the people. They hire up all the people to cross check one another. That actually, made it incredibly expensive so that, it's actually made it not very much fun.

So, I was the associate director for clinical research here at Georgetown for a long, long time. And I just got to the point where this got to be crazy. Even I as a clinician didn't like it very much. I was signing forms that said I had to sign a form. Just the burden of documentation was so much. Today, I saw 4 patients on clinical trials, and I was noting that with each 1 of those, it cost me about 10 extra minutes of documentation to make sure that I had all the data that was needed for the audit and, our own people to enter the data, et cetera. And remember, back when we were talking about EMRs last week, they're not really built for clinical research, are they? So, we have to hand do and then hand enter a lot of the data from clinical trials into some other EMR for the CRO to give to the sponsor.

So very, very inefficient. So, what do we do? Like everything else? We offshore it. One of the consequences of CROs has been that the U. S. market can't handle this. And so, lots of clinical research is done in parts of the world where they're dying to get on clinical trials, right? We're a rich country. We have access to everything. Lots of places don't. So, if they do trials, they actually get that investment there locally and their patients can have access to newer therapies. So, we enjoy FDA approvals on the backs of studies done in other countries where the price differential is better for those sponsoring and managing the clinical trial. We need to think about that as we move on to the next FDA approval. A lot of the work was done by other patients who probably in the end won't have access to the drug that we will have access to. 

And then the last piece of this is that. You know, the specificness of a patient to enroll into a clinical trial. We already have the precision medicine piece, so they have to have the right gene test, but they also have to have a very good, what we call, performance status. Their labs have to be perfect, so much so that the patients who are on trials don't actually represent the patients that we will end up using the drug on. So, to get these pristine results, we have to test pristine patients, then apply the drug to the less pristine. And so, we have a disconnect there in all of this.

And then the last part of this, of course, is, is the patient interested in participating? some are, yep, we know that, but we are still well below where we need to be as a nation, as a world, in clinical research. Because let's face it, we haven't figured out cancer. We could argue that almost every patient should be on a clinical trial. And yet patients are not really incentivized to participate in clinical trials. And I think actually, there needs to be some change in that space too, but not from my perspective, an old grumpy guy whose kind of a little burned out on the clinical research world. Let's talk to some experts.

[17:23]

Do the Complexities of Clinical Trials Demand CRO Support? 

Interview with Dr. Gwyn Bebb

John Marshall, MD: As we promise for Oncology Unscripted we bring the best voices, the brightest minds on all of our subjects. And so, we are very, very lucky to have Dr. Gwyn Bebb join us today. He's the Senior Vice President and Franchise Head and Global Therapeutic Area Head for Oncology from Parexel International, one of our world's greatest organizations CRO institutions. And he's nice enough to join us early in the morning from the West Coast to talk a bit about CROs today. So, Dr. Bebb, welcome and thank you for joining. 

Let me start right in by. So, you're saying, where are we today with CROs? You know, a little bit about the evolution of that, and maybe even wax poetic a little bit about where we go in the future. I know I've just asked a lot, but. Fire away. Tell us what you're thinking. Okay.

Gwyn Bebb, MD, BM, BCh, PhD: Well, John, first of all, I want to say thank you very much for inviting me to this forum. 

I was just chatting to one of my colleagues recently, and we were commenting on how protocols for clinical trials have evolved from being fairly simple, you know, maybe three or four page documents to being the kind of encyclopedic tomes that we see today with many hundreds of pages, and I think that sums up some of the aspects of the evolution of clinical trials in general. Which essentially, is an increase in the need to be precise about the endpoints, to be precise about the design of the clinical trial, to understand the regulatory bodies perspective, to understand the nuances of the endpoints and the measurements that we take in trying to prove that these new treatments are better than what we have. And as a result, I think, however innovative and exciting your new molecule or your new therapeutic approach is, and however motivated we are to get these promising new things into the clinic for our patients, there is a very, very important need of maintaining the rigor required to demonstrate that what we are proposing is safe and is going to be better than what we have. And in there, I think, lies all the complexities. And for, say, a small team from an academic institution that has promising data who now want to bring it to the clinic. It is a very daunting prospect to try to conduct a clinical trial in today's environment. So therein, there is an immediate need, if you see, for somebody who has the expertise to run clinical trials, and that in some ways is where the clinical research organizations come in. 

John Marshall, MD: Let me jump in there. You know, you and I have watched this evolution occur. So, I remember one of my first protocols is, as you say, maybe a four-page document. And, and now they're, they're incredibly long. I'm thinking about the escalation of that complexity. It’s multifactorial.

The way I think about it is that cancer has gotten more complicated. There's more and more subtypes of patients and the like. Okay. The drugs have gotten more specific, so I get an element of complexity there. But we've also started to measure more and more things in order to prove that safety that you talk about. You have that you have the sponsor wanting to get to the patient. Before that was just through the physician, and now the CRO, because this is this middleman kind of discussion we've been having, the CRO has joined in on this to identify and train and oversee the clinical site. Can you talk a little bit about that piece of it, and the importance of that in in the overall flow of things?

Gwyn Bebb, MD, BM, BCh, PhD: So, that kind of sums up a lot of the challenges we have. There's many paradoxes in here. I think. The world of clinical trials is so exciting and so promising, seeing the new ideas that are coming through. Gosh, you know, everybody gets very excited and very motivated to bring these to the patient as quickly as possible. But as you say, cancer as an example has evolved very much. We have a very specific slivers of classification of patients with, for example, lung cancer. It wasn't just used to be maybe just lung cancer. We have small cell, non-small cell, and then we have all these molecularly defined categories of lung cancer, each with a potential molecular marker that can be targeted for benefit. Now, if you have an agent that, it targets one agent. But if those patients don't have a, that marker in their tumor, then we're not going to have an effect. And so, including too many patients in the clinical trial that are unlikely to benefit will mask the positive effect. On the other hand, trying to get too specific, maybe it limits your, the number of patients that you have accruing the right number of the required for the statistical design may be challenging. And so, these are all components where it is very important. to invoke the help of a body of expertise that can help you through the clinical trial trajectory. And that's essentially what clinical research organizations are. When I was a physician, when I ran my own lab, my expertise was very limited to those particular areas. And if I had been lucky enough to bring something to the clinic from my own lab, I would not have been able to do everything that was required to conduct that clinical trial. And that need, you know, I’ve said it's particularly required for small Innovative teams from academia, but the same applies for innovation anywhere and the same applies for big pharma they have a lot of internal capabilities, but sometimes, whether they're overloaded with their current, requirements, whether they're pivoting to a new area, where they're doing something completely different. Sometimes the expertise provided by a clinical research organization, such as Parexel, is exactly the expertise they need to invoke to move things forward. Everything included in that package, from the identification of the biomarker, all the testing that's required to do that, the clear delineation of which patients is the investigator in the trial going to bring into the trial. How do we meet the regulatory body requirements to make sure that the test we use to identify the patients is a valid and reliable and reproducible one? How can we help design a trial in such a way that it can run uniformly across many countries? How can we make sure that the statistical design is going to meet the criteria required of the regulatory bodies to demonstrate that what we have is better than what we had? And so, these are not, this is not a range of expertise that you can just pluck out of the air. And, you know, I think that's one of the things that makes me very excited about working for Parexel is that we have this expertise that can slot into this critical area to drive innovation forward while maintaining the academic rigor required, and of course, most importantly, protecting the interests of the patients who are kind enough to volunteer their time and their bodies in a way to take part in what is a scientific experiment.

John Marshall, MD: I think that's great. I was going to ask, and you just answered was sort of your perspective on the value of what the CRO brings to the table. And I think you did a great job of describing that. As you were going to, I want to kind of go to the patient side of things. So one of the worries we have in the clinical side is that the patient who now is eligible for that trial in the end is so perfect is so squared off at the corners to fit, that that doesn't end up representing the ultimate patient who will be treated with this therapy because there's, you know, patients are not that clean in general, if you will, so, you know, softening the edges around eligibility for us would be good to increase accrual and also therefore represent that patient at the end. 

And one other angle on this is, you know, the patient is volunteering. A lot of clinical trials, that are not so cancer therapeutic, we've actually ethically understood it's okay to incentivize a patient to go into a clinical trial. We do ask a lot of them. It is extra visits. It is extra time, extra biopsies, sometimes, things like that. So, they are volunteering their bodies at a sacrifice of some quality-of-life component. And I wonder what your thoughts are. Ultimately, could we get to a place where we are incentivizing that patient? So, softening the edges of eligibility, is there a role for incentivization of patients?

Gwyn Bebb, MD, BM, BCh, PhD: Well, thank you very much for bringing that up because the patient centricity of clinical trials is a very important theme. It is something that we at Parexel are very, very aware of. We have a patient officer who is part of our company whose task is to maintain a focus on the patient as we look at the design of clinical trial. And as you say, these patients are volunteers. A very important part of clinical trials is the moral and ethical framework for essentially conducting experiments on our fellow human beings. And this is, this is a very, very important area. I have a lot of passion for that. And, you know, the history of experimentation of fellow humans is a terrible one. And so that's just why we have international agreements, we have ethical review. An awful lot of regulatory input on how to go about attracting patients to clinical trials. 

Let's address the inclusivity to start with. I think this is an important point. One of the things I like about clinical trials is the tension that we get when we, when we have slightly opposing forces trying to drive us forward.

So, as you say, on the one hand, we do want to create the biggest possible chance of deriving the positive signal that we're looking for and so we have to be very rigorous about the patients that we put in a clinical trial. Otherwise, we will lose the positive signal that may be there in a very, very important, new, therapeutic, agent. On the other hand, as you say, we don't want to be too restrictive. There's many, many examples of this, you know, performance status, for example, clinical trials have always honed in on performance status 0 or 1. Because the outcome that we associate with performance status 2 and 3 can actually compromise the signal that we're looking for. So, trying to soften those edges is something that many of the regulatory bodies are trying to drive us forward in doing. Another example, for example, is the inclusion of brain metastases in our clinical trials. Very often it has been the case that patients with brain metastases from their primary cancer were excluded from clinical trials and we know that that is a very unfortunate paradigm, and I think that too is now evolving and changing. But as we said at the beginning, you know If you're looking at a new agent that targets a particular therapeutic target including patients in whom that therapeutic target is not present is not going to be useful for anybody. It's not going to be useful for that patient and it's not going to be useful for that clinical trial. 

Now let's turn to the incentivization of patients. I think this is a very difficult area to navigate very often, and, as you say, incentivizing patients is not the main theme of our approach to clinical trials. Many patients, when I was in clinical practice would ask me, you know, why would I, why would I join this clinical trial? And I would say, broadly speaking, there are three reasons for a patient to take part in a clinical trial. One of them is for the opportunity of getting new, exciting, innovative therapy. That is very, very good motivation. Another one I think is overall, there is a body of literature that suggests that patients participate in a clinical trial. Generally, do better than those who don't. And there's lots of reasons for that. And that is possibly, as you said, the more intense follow up, the more supervision of their whole clinical experience probably helps drive those, those data of survival forward. And then the third reason, this is very altruistic indeed, there are some patients who just want to contribute to the general body of knowledge about their disease for those who, as I say, come after them. 

Now you know a very important part of this having made having looked into their heart and realized what motivates them, the next thing is if we are patient centric, we have to make the burden of the clinical trial as minimal as possible. And I think one of the major things that we see happening is that the increased visits the increased procedures they Don't make your quality of life better, right? They take a lot of time and a lot of energy for the patients. And when it gets to the point where you're missing work, you're missing the opportunity of giving care to those who depend on you, then that is a significant detriment. And so, making sure that there is what we have termed fiscal neutrality, for example, participating in a clinical trial is very important. So, there is a drive to make sure that the costs incurred by patients, whether it's food, travel, care costs, those such things are very much part of, of what we provide to, to make sure that it is not too much of a detriment to the quality of life. I think those things are probably slightly different from actually incentivizing patients to take part in a cancer clinical trial.

John Marshall, MD: Thank you very much, Dr Gwen Bebb for sharing all of your experience and knowledge around the world of clinical research and in the role of a clinical research organization in making sure that we do it right. And we do see the clearer value, but as we've talked about, there are still lots of issues that we need to address as we evolve this relationship further.

So, again, thank you very, very much for joining us on Oncology Unscripted.

Gwyn Bebb, MD, BM, BCh, PhD: Absolute pleasure, John. Thank you for hosting so gracefully.​

[31:11]

Are There Alternatives to Traditional CROs? Interview with James Palazzolo

John Marshall, MD: As I promised you, I have experts in the world of CRO and clinical research, and not just experts, really visionaries about the problem and about how we can move forward. And I'm honored to be joined today by what is becoming a pretty good acquaintance in this world of clinical research. So, James, James Palazzolo, is out on the West Coast right now and he has joined us from Quantum Leap Healthcare Collaborative, and I'm going to really leave it to James to describe, to us, the CRO, in a sense, that he and his team has created in large part response to the problems we have been talking about with CROs. So, James, welcome.

So, you get to tell us whatever you want to say about CROs. Tell us a story in the background of what you've created.

James Palazzolo: Yeah, thank you, John. So, it's an interesting world, right? We all want our medical decisions to be made based on data. And the ultimate way to do that is with a randomized control clinical trial, an RCT. And as the practice of medicine became more and more data driven, of course, more and more trials are needed to be conducted. RCTs by themselves are the pinnacle of how this data is collected and the results are generated, but there are some downsides. The downside is it requires extreme precision. Data collection needs to be done in a way that's meticulous. And it creates also a form of a Hide-Bound system where we can only do things one way. And frankly, I think there are alternatives. Alternatives can include things like using game theory, Bayesian statistics, platform trials, master protocols, and the list goes on...decentralized trials. We can make a long list. Of innovations, but these new innovations haven't always penetrated the traditional world of the RCT. The RCT is driven heavily by government regulation, but also by the routine of practice. So, the people or organizations that conduct these are usually called CROs. They're professional data collectors and can put that data together for people who wish to have an R C. T. conducted. The downside, though, is that it really doesn't benefit us to have all these innovations over and above what we can provide to RCTs. And so maybe we need a new form of an organization to make that happen. And that's what we've done at quantum.

John Marshall, MD: Yeah, tell us a little bit about that. I mean, you know, part of what the concern is, is that there's this ever-ending escalation of precision. If we can look for more data. If a CRO came and audited us here and found no problems, then that would put them out of a job. Right? So, part of their essence has to be to find some problems to justify their existence. So maybe tell us a little bit about how you've evolved this for your team.

James Palazzolo: There's no doubt that misplaced precision is everywhere, right? We could focus on all the wrong things, but we tried to apply a bunch of newer tools to make this better. So, one is we set up a platform clinical trial that once it starts continues to run. So, it'd be like if you brought the Olympics to the same city, every 4 years, you wouldn't need to build more stadiums. And some people would love that because the public would have access to these things. Other people would hate it. Like if you're in the stadium building job, it would be bad for you. So, it's going to depend on where you sit on this issue. In our case, with a platform clinical trial, we can run cancer trials over and over again with the same infrastructure, but that's not all we can do. Right? We're also going to listen to veteran clinicians like yourself, who guide us into what is the most important. We no longer use misplaced precision. Parameters that are most important, but we're also going to provide these results to patients in in plain English in digestible form. So, whether you participate in the trial, or you're curious about the results, we're going to make them available to everyone. 

Another thing we've done is put this in not in a not-for-profit company, so that the company itself isn't doing this. We don't have a vested stake and who wins or loses. We're not looking for the next contract from the next pharmaceutical company. Frankly, we're working with groups of very curious, but also very experienced investigators who want to learn more about it. their particular, area of oncology, and then we're going to grind on that, not just for two or three years in a trial, but maybe decades until we find real lasting solutions that make the problem better for the patients who suffer from it.

John Marshall, MD: I want to kind of come back to a couple of things you said so this idea of having experts be part of the decision-making. So, I remember back when we were involved in decision-making and design of clinical trials and running them. And then something happened where Industry actually hired the physicians.

So now instead of borrowing us when it was time to design a trial, everybody went in house. And so, they had their internal experts. And so, we no longer were really being asked what our opinion was about a trial or a trial design. But we were being asked just would we do the trial that's being handed to us? Are we okay with that? I do think that's driven a further wedge between the reality of patient care and this sort of mystical   of precision, you know, data from the randomized controlled trial. So that's one. The second, and I can't help but have this vision of the London underground and this platform clinical trial, like, you know, you could be on the London underground sitting next to Paul McCartney, right?

So, Paul McCartney would ride the London underground, everybody uses the public transportation there in order to get around. It's the most efficient way to do it. You've built, in essence, the, you know, the Piccadilly line for clinical research that everybody can get on and use if they want to try and lower costs and to improve speed of accrual. Is that a fair analogy?

James Palazzolo: I think that's absolutely fair. And, you know, if we're going to improve things like racial disparities and medicine, we need a more uniform tool platform trial where everyone can participate that, of course, includes the high-end academic centers. We're going to provide very useful information, but also safety net and community hospitals where everyone has a chance to participate. Of course, it's up there choosing. But, if they choose to participate, their data will be included, and we'll get more information that allows us to do a better job for everybody.

John Marshall, MD: And so, it's just so our audience knows your basic group is supporting as a CRO in a way for this platform trial and its relatives. Right? 

James Palazzolo: That's right. So, our organization provides the same functions to conduct a clinical trial that a CRO would have. If an industry company, a medical device company, a pharma company did some of their trials in house. They would have these same functions. We have them. But rather than going out and seeking new projects to work on, we built the project with people like you to make sure that it was relevant in reflective current clinical practice and then continuously improved it over time, so that we could enroll patients in trials that more closely reflected their actual routine care and didn't get hidebound in the routine or the tradition of an RCT. It is an RCT. But it is more flexible. And then it collects the appropriate information at the right time.

John Marshall, MD: And we know you guys have been at it a while, and you guys have produced FDA approvals and innovation in how we treat patients in general. You've broken the mold in a way that's allowed us to accelerate our innovation instead of sort of plodding along as we've been doing. So, James, I can't thank you enough for joining us. I know everyone will be interested in hearing more about your success, so be careful. You might get some phone calls after this. James, thanks for joining us.

James Palazzolo: Thank you, John.

John Marshall, MD: I can't thank our experts enough for sharing their thoughts about clinical research, CROs, and maybe some thoughts about how we move forward going ahead, because we need to move forward, and we need to make it more efficient so that we can provide better cancer care for people all around the world.

And I hope you have found this episode seven of Oncology Unscripted useful, maybe a little enjoyable, but certainly thought-provoking as you go forward in your week ahead. John Marshall, thanks for joining.

This transcript has been edited for clarity.

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