38 minutes | Mar 1, 2019

Mark Boguski on Antidotes to Overspecialization in Medicine

Adjusting to a more collaborative style may take doctors some time, says Dr. Mark Boguski, but if they stop confining themselves to disciplinary boundaries, they'll be able to see connections between different areas of medicine that aren't taught in medical schools. Boguski draws on examples from oncology, where he says doctors are gradually being retrained to think in terms of disease pathways instead of discreet organ systems.

Dr. Boguski is the chief medical officer of Liberty Biosecurity and founder of the Precision Medicine Network. He's a member of the U.S. National Academy of Medicine and a fellow of the College of American Pathologists and the American College of Medical Informatics. He's served on the faculties of the U.S. National Institutes of Health, the Johns Hopkins University School of Medicine, and Harvard Medical School, and as an executive in the biotech and pharmaceutical industries. He is the former vice president and global head of genome and protein sciences at Novartis, and a graduate of the medical scientist training program at the University of Washington in St. Louis. He has written a series of books on cancer for the general public, under the series title "Reimagining Cancer."

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Harry Glorikian: Welcome to the Moneyball medicine podcast,

Dr. Boguski: It's a pleasure to be here Harry.

Harry Glorikian: So, Mark I was reading that statement and when I hear a statement like that that I read at the top of the show I step back and I think systems biology, not necessarily disparate pieces. And so, it seems like over time if I go back to doctors, you know they'd look at the patient as a whole and now it looks like we're looking at them in pieces.

Dr. Boguski: It's actually worse than that you know when I was in medical school we actually did physical rounds on the patient - on the patients on our floor, you know we'd go around to the bedside and examine every one of them. Today people do rounds in a conference room sitting in front of their laptops and there's actually less patient interaction, than there used to be.

Harry Glorikian: You also say like it doesn't stop there, by looking at the bigger picture and not confining ourselves to disciplinary boundaries. We'll be able to make connections between different fields of medicine and glean information, that isn't taught yet in medical schools.

Gaining insights that have the potential to transform medicine and when I hear that, I think again systems biology but how data is going to help us reassemble the parts because there's so much detail in each part.

Dr. Boguski: So, let's start with oncology because considering revolutionizing all of healthcare is just too big a bite to take. The example that of interdisciplinary interaction that you mentioned plays out in something called a tumor board or the multidisciplinary tumor board. Where all of the sub specialties are our representative the medical oncologist, the surgical oncologist, the radiation oncologist, cancer genetic counselors, advanced practice nurses, radiologists they all come together to discuss a case and that's where the multidisciplinary input occurs.

The problem is they only happen once a week or maybe twice a month and that's not helping individual patients in real time. So, there's something we've been working on in conjunction with Dr. Mike La Posada at the University of Texas Galveston called the diagnostic management team, and I see this team as an integrator of the various data inputs from different specialties. Where a group comes together and reaches a consensus interpretation of all these data streams coming into effect, one patient at a time.

Harry Glorikian: Well that was going to be one of my comments and I had put together a piece on this on my blog but it is it time to just - when I think about corporate worlds we used to always joke that when there was a reorg, the CEO had read some book or something and now we're reorg-ing around it, but I don't know if I've ever seen a reorg in medicine based on where technology is going and are we at the point where let's take oncology. Do we need to reorganize oncology do we need to forget about the organ per se I mean I don't want to take it away from the surgical oncologist, because they need to understand that organ and actually work on it. But the treating oncologist I mean we're doing basket studies, we're looking at pathways we're understanding how drugs perturb a pathway.

You know that has nothing to do with the where the it is in the body and I feel like if we look at AIDS and we're playing - we played whack-a-mole and now we understand how to beat it back. Oncology is sort of following in the same footsteps of once you perturbed two maybe three pathways, you've sort of cut off the lifeblood of whatever this you know mistake that's happening in the body is going on.

Are we at the point of organizations or institutions need to really rethink how they do this for the benefit of patients?

Dr. Boguski: Absolutely we are, as an aside before I come back to describing the situation more in detail. I'll tell you the biggest problem is change management it's getting people to behave in in ways that they weren't trained to they're not comfortable with and may take some extra time initially for them to learn and this diagnostic management team concept is one of those things that people will have to be motivated to adopt.

So, with respect to the – to oncology but when I was at Novartis back in 2009, 2007. I'm sorry 2005, 2007 there were only a handful less than five targeted therapies. The first one dates back to the late 1990s it was Herceptin the second one was Gleevec which is approved around 2001 2002 but even then we foresaw a day when the FDA would approve drugs, not based on the Oregon system in which the tumor originated but the underlying molecular pathway.

So, let's say that was back in 2006 that we thought that would eventually happen. It's actually taken until 2017 for that actually to happen there was a drug Pember ilysm app that had previously been indicated from melanoma, but was finally indicated for any tumor of any tissue origin that had DNA mismatch repair as its molecular genotype and phenotype.

So, the biggest challenge in oncology and is really educating the up-and-coming oncologists and pathologists to think in a systems way, to think in terms of pathways in that organ systems.

Harry Glorikian: But it I look at it two ways, one is do we need to rethink med school from that perspective because there's data streams coming from everywhere now. The other thing is let's face it if the institution you go into like the corporation is structured a certain way, you file into the structure in it.

So, if you had a computer science group or a data analytics group that was associated with the treating oncologist and you know a tool booth said, you know if you're not using genomics in oncology today it's like driving at night without headlights. Wouldn't that force the specialty to go down a certain road and we I'm assuming we would see a benefit towards patients?

Dr. Boguski: So, here's the deal when I listen to Barrett Rollins podcast which was excellent. I think he kind of left out one thing. And that is when you talk to the head of an NCI Cancer Center they only treat about 10% or 15% of cancer patients in the U.S. so if you really want to have an impact you want to get to that what I call the 80% market. Which is private practice or group practice on college in community hospitals and regional health systems and the reason I bring that up is because I - not long ago I was talking to the president of a major Oncology Group with 1,500 oncologists in you know in a wide group of practices all over the country.

 And according to him about 2/3 of his oncologists never heard of DNA you know don't really want to learn about it and they're thinking of retiring early because they can't understand you know this the subject matter.

Harry Glorikian: But that's crazy - I mean but that's insane I mean - I think about that - I hear that all the time and it absolutely just floors me, because I think to myself the patient is getting the incredible short end of the stick right? We always talk about health care cost going up, well if you're not treating them the right way of you know I would think that of course you're not you know health care costs will go up because you're not getting the best outcome. What do we need to do to turn the ship faster?

Dr. Boguski: So, what you have to realize is that these Doc's who don't really know about DNA we're never trained in it. I mean you know a generation ago or half a generation ago genomics didn't really exist in the typical training of an oncology fellow or even going back to medical school, not everyone was a specialist in genomics or over immunology now the dominant science in oncology is genomics and immune-oncology and the practitioners particularly those outside academic medical centers just simply don't have the background to understand what these tests can provide.

And so, we identified, you know the major gap is really an educational one they need tools and hopefully on a mobile platform that they can consult in real time and not have to take extra time out of their day to go and read you know 25 papers in the literature. They have fingertip access to the latest knowledge about biomarkers and pathways cetera and overtime is they use these essential tools over and over again. You know that will help educate them to take advantage of some of these modern diagnostics.

Harry Glorikian: Well I always think to myself like if we think about the super consolidation that's been happening in medicine over the past say since the Affordable Care Act has come into play we're not talking about the one to little hospitals that are sitting out there, now there - they're big conglomerates for lack of a better term.

 I would think they would be able to create an internal group that would then assist or read out to everybody out there think of it like a central HR group in a sense but I want to step back and so we've known each other for a long time. What are you doing these days? What are you focused on at Liberty and just give us a little bit of background there?

Dr. Boguski: Sure, well Liberty biosecurity is a company that views the biggest threats to human health in the 21st century as biological threats and these can be man-made biological threats or simply the result of shifting ecosystems as a consequence of climate change or they can just be really hard medical problems, that no one else is cracked yet. So, we brought together a multidisciplinary group of people. Who are connected in a way that we're only sort of one node away from anyone that we can live that we need to help solve a problem.

So, we're working on two major things now I'll describe oncology first because one of the reasons that it's hard to innovate in oncology is people try to do it in the United States. Where there's a lot of legacy institutions - you know legacy standard of care. It's very difficult to innovate in a system that's already running a certain way.

So, we're actually happening helping the government of Thailand and one of the largest companies in Thailand kind of reinvent medicine. We call it skipping the lane line and it's pretty obvious what that metaphor means, but we're trying to in conjunction with the government which has this concept of tylium 4.0. That concept involves changing the economy from an industrial economy to a smart economy and skipping the land line in the process.

So, we're helping set up several advanced cancer research centers and existing hospitals and these will be dry runs or trials or pilot projects that will eventually be incorporated into a new physical institution called CP Medical Center, which is due to opening in about four and a half years.

Harry Glorikian: If I gave you a whiteboard right now and you were to redraw oncology, how would you redraw it? How would you incorporate genomics, digital ecology, image analysis? How would you just walk through that quickly?

Dr. Boguski: Well it's interesting because in the design of this new hospital they really have to think about how to juxtapose different departments and divisions and so we have a Greenfield situation here, where we can help them put together things that were separate that belong together and then sort of the transformation of oncology.

So, you want radiology to be right next to pathology because these are the two diagnostic specialties and 60 days 70% of clinical decisions are made on data that comes out of the pathology lab. So, I think Eric Topol is the first person who really called this out explicitly but I would combine radiology and pathology into a new specialty called rad path in which their primary job is to synthesize data streams into a report that can be used by the clinicians. So, that that's one of the things I would do. I would also transform tumor boards into more frequent real-time diagnostic management team meetings that meet more frequently, that meet in time to make a therapeutic decision at the time when one is being made. And those are two of the things that we will be experimenting with in this time and at CP Medical Center.

Harry Glorikian:  I'm always thinking that when you analyze an image and utilize the machine learning or artificial intelligence or all the different methodologies necessarily that are out there today, I think the systems do an amazing job of seeing things that a person might not be able to see. When I was interviewing Massimo blue Cemil, in one of the podcasts. He was saying they've come up with a way of having the pixel sort of look at each neighboring pixel and you can see a blockage in an artery when it's not visible to the naked eye. And the machine can actually look at images that aren't necessarily easily visible to a human eye, so we get a processed image whereas the machine can look at raw data.

Where do you see that sort of capability going and is it going to advance what we're doing in the medical area?

Dr. Boguski: So, I'm a pathologist by training so I'll signal that bias upfront but as you've said in the introduction and I do take a more systems view of Medicine because I've not only been a pathologist in my career but I've been in genomics, bioinformatics I've been in the biotech sector, I've been in the pharma sector and I'm seeing the problem from many different angles. So, getting back to pathology, pathology has been criticised for not adopting digital technologies sooner and they're often compared with radiology who adopted them you know almost overnight.

You know the problem between the two fields is that with pathology you still have to remove something from the body and process it in a laboratory before you can digitize it. So, the savings that you realize from not having in in radiology not having film libraries and chemical tanks to develop x-ray film, that that changed the economy of radiology. It's harder to do in pathology and so as I'll just have been slower to adopt it and also because pathology departments, all those 60 70 % of clinical decisions are made on their output.

They tend to be viewed as cost centers in their health system not nonprofit centers and so everything, you know if you look at the c-suite. They want every test to be as cheap as a complete blood count or urinalysis and with genomics and digital pathology, whole slide imaging you know that's not what it costs. So, people have to retool and recapitalize their equipment in order to fully realize the value of digital pathology.

But as you said once that's done, we can use it to augment humans by pre-processing the slides and pointing out suspicious areas that pathologists need to put their human eye on, we can also use it to spot things that you a pathologist might not spot. Actually, let me let me express that a different way, so one of the diagnostic modalities for predicting the efficacy of immune oncology drugs is of the body's immune response to the tumor.

Now that's done right now with anti PDO antibodies, it's just a brown stain on a regular microscope slide in a DNA setting, it's done with tumor mutational burden. But both of these things are really surrogate markers for lymphocytic infiltrate in the tumor and pathologists don't normally have the time to manually count all the lymphocytes associated with a tumor. A computer can do that in two seconds and but you know just imagine being able to replace expensive time-consuming the long term around time tests with just an AI or machine learning application on a $2.00 HNE microscope slide. So, that's where part of the potential really makes sense.

Harry Glorikian: Yep and I think in some ways it would help standardize the process, right? You and I both know you go from institution to institution you will get a different answer depending on who's looking down the barrel of that scope. So, you know interestingly enough I was also reading sort of you know there was a paper presented at the 2018 machine learning for healthcare conference at Stanford University. Where you know - MIT Media Lab researchers so we're not even talking about you know a university hospital or something like that but MIT Media Lab researchers detailed a model that could change the dosing regimes, to be less toxic specifically in glioblastoma with a self-learning technique where the model sort of literally of just dosages, eventually finding an optimal treatment path with the lowest possible potency and frequency of doses that should still reduce the tumor size to a you know degree comparable with traditional regimes. And you know they showed that this seems to be working quite well. How do you see something like that being incorporated in this practice of oncology? Because it seems that technology when applied across a number of areas, should have a probability of increasing outcomes, yet decreasing cost over time. I understand that there's going to be an initial bite to take all this on but it's just like anything else we do in corporate America. You got to spend it upfront and then you realize the savings on the back end.

Dr. Boguski: Right that's why you have to take a systems view of the healthcare system or you know or an individual - a hospital system. Again, each department is either a profit center or cost center and that's not a holistic view of the value that the diagnostic laboratory supplies. Getting back to more directly answer your question I think one thing that's never mentioned you know people talk about the DNA driven data transformation of oncology but one of the nuances, that is seldom is the common networks of therapy. So, let me give you an example for they're both targeted therapies and immunotherapies for melanoma and lung cancer and many of the solid tumors.

In fact, for melanoma there are there are six different targeted drugs you can try and there are two immunotherapies you can try or you can try some combination. So, where computers are really necessary and figuring out the best common it's a real possibility given an individual patient or a patient avatar that looks like that patient. So, back in the day when there were only six targeted drugs you could figure that out on your head. Right you know today there's about a hundred and fifteen targeted drugs or immunotherapies we're going tissue agnostic.

What the heck do you do with the combinatoric of that kind of pharmaceutical armamentarium you have in front of you now?

Harry Glorikian: Oh, I remember I you know I could almost when it when all this first started you could keep up with the papers.  I can't possibly even try - so if you didn't have a system to help you in some way, I don't know how you would manage between the gene, the drug, all the other details around a patient and how do you keep that straight, I don't know how you would practice what you practice. It would be like you know flying a plane without all the other instrumentation around you.

Dr. Boguski: Yeah so this is the the missing link in oncology and pathology training now, it's training our future oncologists and pathologists to think in systems biology ways to teach them enough about combinatorics. So, they apply those principles to what's coming out of a eyes and machine learning algorithms and have the ability to synthesize them based on at least some understanding of the underlying technologies that lead to these data streams.

Harry Glorikian: So, what do you think the changes are that we need to make and institutions today to get the I don't want to say the biggest bang for the buck but before lack of a better term, it is a business. But at the same time we're need to be looking at patients right? and I always try and tell people that talk to me about oncology issues that they have is always remember that the person on the other end of this yes they want your best interest but it is still a business, so there there's sort of interesting ways to look at that. Where do you believe that this is going?

Dr. Boguski: Well I'll answer that - my first thing that I'm not a businessman but I know enough about business that when young people, who are thinking about are developing new technologies come to me for advice or small companies ask me what they can do to get their methodology or their technology incorporated into the workflow physicians. I said you're aiming at the wrong target, you've got to develop a value proposition for the c-suite and not just think that that Oncologists are going to adopt this because again there's two challenges, it's how to how to support it from a revenue point of view and in the change management it's getting them things to do differently so it's really dual targets for introducing new technologies and new operating systems and new standard of care. It has to make sense to the c-suite it has to make sense to the practitioners and it's that combination, I think that you have to convince to adopt a new way of doing things.

Harry Glorikian: So, just shifting gears for one I'm not actually shifting gears and we're moving it up the pathway in a sense is how do you feel about liquid biopsies? As the next generation of where we're going with this, as opposed to actually looking at the tumor. You know, I know right now it's approved for treatment monitoring, right because we can actually, we knew there was a tumor we right?

But I'm thinking about how do you think about it from a treatment monitoring perspective but then ultimately there's no reason why we couldn't see something before it actually happens.

Dr.Boguski: So, I'm very excited about liquid biopsies. I think there's a lot of work to do yet before they become routine for cancer care, but I think about them this way. The standard of care now in terms of clinical practice and a sort of FDA approval is imaging.

You treat a patient with a drug, you're doing you know some sort of Radiologic study to show that the drug is working and you often monitor response to therapy that shows visually that the tumor is shrinking. You know what if you could replace all of that expensive technology and logistics with a simple blood draw and get the answer in in a couple of days, rather than have you know your radiology exam scheduled you know a month or three weeks in advance? So, that's one thing there - there's a cost-benefit ratio to the conceiving of replacing radiologic imaging with liquid biopsy.

The other thing it could be it could be much cheaper it's not yet but cost turnaround time and the ability to detect the presence of a tumor before it's even visible by radiology is another big potential advantage. In fact, I know one little company that can actually has technology that you can tell from the DNA sample collected from the blood, which tissue the mutations are likely to be coming from that's exciting technology too because it can direct your attention to where you might want to concentrate the imaging resources.

Harry Glorikian: Well I keep thinking about you know these technologies will also - can also cause a complete shift in the business model in other words I could go to CVS, and you know with one of these non-phlebotomist oriented technologies, draw blood ship it off, have it done and now instead of the patient driving fifty to a hundred miles in some cases to an institution. Everybody could be sort of monitored on a regular basis.

Dr. Boguski: That's particularly intriguing you know given the work that we're doing in Thailand because the CP group owns the 7-eleven brand for Asia, and you know they're thinking holistically about this monitoring patients in the community without having them coming to the hospital, you know and have an expensive time-consuming radiology scan. When they might be able to just drop into their local retail pharmacy and have the test done there.

Harry Glorikian: Well that's when I think about CVS and Aetna I mean if if you go into the hospital, they sort of lose right because now they have to pay. Whereas if they're able to sort of monitor you or keep you healthier at their local CVS. They change the economics of this and so you know telemedicine is the other area, where something happens as they see something in the CVS. Well the doc can technically be right there. They don't need to be at an institution, so it's interesting how this whole shift is happening from technology enabled medicine. And I know that's heresy and the worlds were used to without where we come from but you see it how technology has affected everything else and so I think you know we're at the cusp of a revolutionary shift, now whether the institutions can shift as quickly is the part that worries me the most.

Dr. Boguski: Well again it gets back to innovating in in the U.S. so many things are ingrained in our healthcare system that it's very difficult to innovate in any one step of the process when it affects upstream and downstream activities as well as the economics of it. and again that's why this opportunity to work with the government and major a major company and Thailand gives us a better shot at changing things over the next four to five years, because they're motivated to become a smart economy, skip the landline and go right into some of these new clinical and business models that you're describing.

Harry Glorikian: It's interesting I wish we could do that here but I don't think that's gonna happen anytime soon except from external forces like Aetna CVS, Walgreens and you know maybe Humana or any of these other groups that are coming together or maybe Apple, Amazon or these other different groups that are out there. I know you had listened to a couple of the earlier podcasts on precision medicine and you had said to me a few things were missing or what's burning, what did we what did we leave out that we should have put in there?

Dr. Boguski: Well there there's a lack of organized training the neck for the next generation of oncologists and pathologists into this new way of thinking. Now eventually by generational turnover and things like that the you know oncologists will begin thinking in more of a systems biology, tissue, agnostic manner. Again, Anatomy will always be important for surgical oncologist and radiation oncologists, so we don't want to we don't want to ignore them because their therapies are anatomically directed but more and more of medical oncology is going to be tissue agnostic and we're simply not training our residents and fellows in this way of thinking.

They're still being trained in a in a fairly traditional manner.

Harry Glorikian: It's interesting well I mean I always think when Kaiser announced they were going to open their own medical system, now this was post Affordable Care Act because they could see that things were moving to a value-based as opposed to fee-for-service. Do you think we need more medical schools along those lines to really get us to where we're going?

Dr. Boguski: Yes, I do and the reason is, is that again even in medical schools that want to do this there was a lot of tradition. You know it's the professor of teaching you know his or her subspecialty and there's not as much opportunity to integrate in a systems biology mindset in those traditional teaching models. I know Harvard Medical School teaches their curriculum based on system biology now, but not up not every Medical School has adopted that yet.

So, I think it will take some new medical schools that train and in some rudiments of computer science and in statistics in order for the practitioners not to become you know the AI specialists but simply to understand where those data come from. So, they can they they're they can trust the data coming from human augmented machines.

Harry Glorikian: Well it's interesting right if you think that physicians will also be measured based on performance and outcome, just like regular corporate America, right? That they're gonna want to go to institutions that give them the tools to be the best not just go to school per se but become even more choosy then maybe then they already are about where they attend school to be able to be the best at what they do.

Dr. Boguski: So. how do you how do you do that marketing and communication you know that that's another challenge you know it's change management and marketing and communication. These two things are often ignored or downplayed when you're trying to change your system people tend to focus on the technology and the bleeding edge science but they don't consider the mundane aspects of how do you get the message out and how do you how do you manage change among established practitioners.

Harry Glorikian: Well it's interesting, right when I look at a company and think about strategy the first thing I look at is the age of the management team and I don't mean to generalize, but it as a as a rule of thumb you know I think are they over 55 or under 55. And if they're over 55 it's generally what you see is a mentality of TTR, time to retirement alright and do I shift or do I just make sure that nothing screws up along the way.

And if it's under 50 right then I actually almost have to do something because I'm gonna be around for a while. So, I have to actually make some fundamental shift or put my mark on it and so again not to generalize because I know you know people like you and others that are on the bleeding edge of change, but I think that those you guys might be the exception as opposed to the norm.

Dr. Boguski: Well I'm a big believer in neuroplasticity and I think anyone at any stage and age in their career can learn this stuff but they haven't had the tools to teach themselves, and I think that's been one of the missing links or big gaps in the way people think about this. They never think about how you're gonna market communicate and provide tools in order for the people who better learn to be able to readily learn.

Harry Glorikian: Well some people are very comfortable with change right and some people are not comfortable to change at all, as we all know. So is there anything else that you thought was a missing portion in in some of the areas that we talked about?

Dr. Boguski: No, I think we've pretty well covered it. I mean again the missing link is education and training both at the early career level but also in terms of continuing medical education and I think the other big challenge is focusing on convincing the c-suite that this is going to either reduce costs or improve patient outcomes or both, and it's convincing the physicians and in the c-suite executives as both groups in order to get changed really enacted.

Harry Glorikian: Mark, thanks so much it was great having you on the show and look forward to hearing how the Thailand experiment works out.

Dr. Boguski: Well let's get together again in six months to a year and I'll let you know.

Harry Glorikian: Okay, excellent thank you.

That's it for this episode hope you enjoyed the insights and discussion for more information, please feel free to go to www.glorycamp.com. Hope you join us next time, until then farewell.

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