From the Lab to Big Pharma

Well, you know, the timing I think of the announcement of Their engagement is awesome because it coincides perfectly with like the NFL season starting, too. >> Well, it it was a it was a big story in our household. >> Yeah. Yeah. Big time T Swift fan. >> A big deal. My my wife is a big time Taylor Swift fan, but the engagement story, I actually broke it to her. You know, I saw it on my phone through the NFL ticker. I got an NFL alert that Taylor Swift and Travis Kelce are married.

And then I ran over to her office, uh, you know, next to me and I was like, "Hey, guess what?" And she was like, "What?" >> And I was like, showed her the the the picture and then she did freak out that I found out first before her. >> Hey, but you know, I'll give it that whatever, you know, some people hate on her, some people love her, but I went to her concert uh with with Mariam uh, you know, last year and it's just spectacle, man. It's it's something. >> She's an awesome awesome performer.

Yeah, it's impressive. And you know, there's quite a bit of concerts I went to last year. The other concert that I really loved is uh Ed Sheeran. He he came to Houston. Oh >> yeah. >> And we went to his concert uh just few months or earlier this year and it was amazing. We also went to Justin Timberlake's concert a few a few few months ago. But Ed Sheeran's concert was memorable. It was amazing. And you know, my son is obsessed with that uh Sapphire song. >> Yeah, he is.

>> Hey, can you play the Indian Sapphire, please? There's an Indian version, too. apparent, you know, and he he loves that song. It's funny when kids get to the age where they like start requesting the music. Like Rayan has two go-to songs whenever we're riding in the car. At least he does with me. He has actually different songs with Samia because her music choice is a little different. Um, he really likes this one song by Masked Wolf called Speedraer. It's got a sick beat.

He'll straight up say like, "Aba, play Speedraer." It may not be the most child appropriate song. And then he likes this one desi song which is it's just a hilarious song. It's called Brown Monday. Um great song, dude. I just I love hearing him say, "Aba, play Brown Monday." >> This song called Daisy Boys. >> Yeah, I've heard it. I've heard it. >> Yeah. So, and but he has this thing.

He's like, "Play this song, play Sapphire first, then play DY Boys, then play this song, and we go through this whole thing." I don't I don't like short rides because short rides we can't listen to music. >> He's got a vibe, bro. >> Yeah. But Cat Lab, I mean, you know, Cat Lab, we some of the cases are so short that some of the music that we play in there, you know, I'm I don't care much for the music, but your cases are much longer.

You >> They can be, you know, we we have we like one song cases, you know, sometimes quick cases like a trigger finger or a carpal tunnel release. Um, but yeah, like especially if you're doing a shoulder replacement or something, longer cases, you can get a pretty good playlist going. Uh, my my go-to in the O usually is like Tropical House, EDM, anything upbeat. Um, usually that jabs with everybody. Um, those are probably my two go-tos.

Yeah, you can you can really just get into the zone, you know, with the >> Yeah. And honestly, it's so easy, too, cuz you just go to YouTube and type in like EDM long mix or tropical house long mix and you have like a 2hour thing playing constantly on YouTube so you don't have to mess with it. No one has to change it and it's not on someone's phone cuz then when they get a text or a phone call it shuts off like totally kills the mood. >> Yeah. No, no.

It has to be a radio that's inside the in the in the cat lab or the >> they just play. A lot of times they just play the radio. But I just I love my music is more like singer songwriter. I pay a lot of attention to lyrics as well. And just having a good singer songwriter that uh writes his own songs and produces or his or her sorry uh you know those those are my favorite. You know some of these artists like I mentioned Etier earlier. >> Yeah. uh Taylor.

So back in the day, back in college, John Mayer used to be, you know, I don't know if you remember that guy. >> I do. I do. >> Um but but that's it's you know, and I think in medicine, you have to kind of everyone has their own sense of music and you know, in cat lab, I just let the nurses play whatever they want to hear because my cases last probably 15 to 20 minutes max. >> Yeah, I hear you. And the nurses staying there all day. >> Yeah.

But, you know, talking about medicine and cat lab, I mean, we I was just kind of reflecting on our discussion about um the GLP ones we had a few weeks back and um it's crazy. I was just reflecting on the Hila monster story about how this this venomous uh lizard or monster or animal that has this J molecule in saliva and somehow they extracted that and made it into a medication.

I mean, I think a lot of people don't realize what goes on behind drug development from discovery to um, you know, uh, it being available to mass populations. I mean, it's crazy, right? >> Yeah. I mean, the, you know, the discovery and innovation can come from sometimes the most random places like the saliva of that lizard, you know, um, just like how penicellin came about or insulin.

I mean, it just honestly the stories it's like history of medicine is tied to these stories of often these chance encounters. I mean like we we kind of talked a little bit in a past episode about insulin related to the GLP1s, but I think the story of how insulin was discovered is is really fascinating. I mean, you know, one of the surgeons in Toronto, Frederick Banting, and a medical student, Charles Best, who actually discovered it and eventually ended up sharing the Nobel Prize for it.

But like even years years before that, they knew there was something in dogs. There's a lot of study in dogs with the pancreas that there was something they didn't know what it was. They called it some substance of the pancreas that led to when it was removed it led to diabetes and then the dogs died because they found that out by just removing the pancreas from dogs and watching what happened and eventually they withered away and died.

And you know, they started isolating more and more stuff and they got this extract, this like murky brown stuff that was coming out of the pancreas, which was obviously an unrefined version of insulin in addition to other pancreatic stuff. They would inject it back into the dogs and they were able to keep the dogs alive for longer and longer until you know they eventually passed away. Um, and that is what eventually became insulin.

Um, and so >> before before 1921, that discovery, people who had type 1 diabetes, it was a death sentence, right? It was just >> you were born with type 1, you developed type 1 diabetes in your teens or 20s and all you could do was just starve, otherwise you would die soon. >> Yeah, it was game over. I mean, it like literally that was the medical practice put someone on like a sub 500 calorie a day restriction. I mean, you're basically starving to death. Um, it was the only way.

That's all they had. And so when they finally isolated this, I mean, I think it's it's also crazy the perseverance to discover some things like this, like all this research and study from dogs to translate it into humans. And the first patient they ever injected what they thought was the cure was insulin into this kid, he was a 14-year-old kid in Toronto. They injected him and he almost died from an allergic reaction to the medication.

And you know, obviously he didn't die and they refined it again. They purified it. some something in there. Um and they injected him again and remarkably I mean and so rapid he improved his his blood glucose everything improved. Um and he he lived years after that and eventually died of pneumonia not from his diabetes and that was revolutionary. I mean it changed the game like so many kids they would have wards of just kid after kid after kid in these diabetic comas and they it saved their lives.

I mean it totally changed the lives of those children and the families and you know the rest is history. I mean it gets commercialized and and becomes one of the most gamechanging medications. >> Imagine if they had stopped after the allergic reaction or if >> imagine they were like oh man this doesn't work. This guy died. I mean let's not let's go somewhere for something else. We would have never discovered insulin.

>> But that that's like the belief in your science you know when you've really put your thought your heart and soul and real research.

I mean they did so many leadup experiments the rigorous real scientific process and you don't get stalled and crippled by fear by one mistake one error one miscalculation I mean you have this body of evidence you've built up you know logically it should work you just push through I mean it's the perseverance in science is remarkable sometimes to make these discoveries happen >> yeah I mean you know science is truly a beautiful thing and there's been unfortunately a lot of distrust of science I mean you know there's a lot of people that love doing their own research.

Uh, and for a lot of people, doing their own research means going on Google or Chad GPT and just looking something up, right? Uh, but what research truly is is the perseverance having a hypothesis, doing experiments, failing multiple times, uh, and at some point successfully uh, conducting an experiment that has a positive result and that positive result sometimes leads to a game-changing discovery. I mean, there's countless drugs, right? There's things like insulin, there's penicellin.

I mean in cardiology there's you know statins or uh you know medications like in Tresto that have completely revolutionized uh the treatment of heart failure or lipid management. Uh you know these the science is not efficient. Science is not a business. You don't you don't do science to make money. Yeah some people can make a lot of money from the right discovery.

But you know unfortunately in in our society now there's been this anti-science or um >> distrust >> distrust of science which is you know sometimes I don't blame people. I mean you know there was a lot of >> uh anxiety after co uh a lot of misinformation from all sides and from everywhere. People were told certain things that turned out to be false later on uh and they lost a lot of trust.

But in the end we have to realize as physicians that science and the scientific process is truly um you know vetted out. It's very important to go through the scientific process to have a hypothesis to have a null hypothesis conducting experiments finding out uh and see if your hypothesis is met. You know that kind of rigorous um you know perseverance towards a goal uh leads to the discoveries we have.

And unfortunately now we have this um you know cutting of funding towards science that's not uh you know efficient. A lot of labs are losing money. A lot of big institution NIH is uh has is getting their funding cut because uh somehow our government thinks that their research and the work they're doing is not efficient which science is not supposed to be efficient which >> yeah it's being looked at in the totally wrong way unfortunately.

I mean I mean academics and like some of my partners like in my group uh they've had their funding cut they've had their grants rescended um it's led to like institutionwide changes um and funding cuts which which affects everything and it's it's across the board in academia um and that's the training grounds for the next generation of doctors for the country and when the funding is cut education suffers. >> Yeah.

And just imagine that one lab that gets shut down that eventually had the cure for Alzheimer's.

I mean you know >> it just takes one person one or two people that have a small lab they're conducting experiments and they can discover something groundbreaking and people do not realize that they think that you know just uh you know there's a lot of money being wasted at these academic institutions and you know they would rather have their money go to um wars or you know violence or you know taking countries. >> No no kidding.

I mean and that's the thing like real science like you were saying earlier it has to be inefficient because it has to be repeated and validated again and again and trial and error and it has to be consistent and you have to not just do it one time and be like oh voila there we go we did it. You got to do it again and again and again and make sure that you can reliably execute it again and again and it stays true.

That's never going to be an efficient method to create something and it doesn't need to be. >> Yeah. And you know there's a there's this huge idea of big pharma is is all out to get us and fool us into uh you know giving giving up their money and taking all these drugs and making all their focus is is on profits. I mean pharmaceutical companies are corporations in the end. Their goal is to maximize the bottom line.

But I mean, a lot of the funding comes through them and a lot of groundbreaking medications receive the funding from a lot of these uh big pharmaceuticals that end up becoming the life-saving treatments that we have. I mean, me and you both use these medications on a daily basis or or procedures or or devices that we use on a daily basis that went through clinical trials. You know, there's so many different phases of clinical trials, so many ways that these medications get approved.

Sometimes from discovery to it being available in the market for people can take up to 10 to 15 years. >> Yeah, it takes a long time. A lot of R&D cost to recoup too. Talk about that a little bit. I mean there's there's a lot of colloquial stuff. Oh, this is phase one, this is phase two. What do those really mean? What are the phases of a clinical trial?

Like how does a drug pass through these phases, get so-called FDA approved before it can go from an idea in some scientist's mind and a lab into a pill in a patient's mouth? >> Yeah. I mean there's technically like you know say let's say five stages to uh drug development, right? There's a pre-clinical stage. Preclinical stages before it ever reaches human beings.

Uh most of these pre-clinical studies are done in labs with animals with mice through techniques not not like how we discovered insulin which is squeezing the pancreas and insulin out of it but more specific more sophisticated techniques of extracting different >> like a lemon you just squeeze the juice. >> Yeah. A little bit more sophisticated techniques to extract the medications uh or uh test maybe in rats or animals or mice uh how these medications are working.

It looks for things like toxicity or safety or the biological activity. They're able to measure the pharmacocinetics of the medication. Uh and if it shows some kind of promise in animal studies, it moves on to u phase one clinical trials which is where um humans come into play where these are very small groups. Uh you know these phase one studies are very small sometimes hundred few hundred people right.

Um, usually the focus is on safety and figuring out the dosage, making sure it's safe, making sure the dosage is right. A lot of time these phase one trials are inatient trials. I mean, they're they're not I mean there's phase one centers where patients get admitted, they get the medications, they're monitored for a few days live and there's a lot of um close monitoring, a lot of blood sampling going on.

So these this is a very involved process u you know comprise a very small amount of volunteers um you know and then first once we determine if it's safe for consumptions for human beings and making sure that it's safe for the dosage that they're using then they then move on to phase two clinical trials and the phase two clinical trials are pretty much determining you know where the you know the the if if if it's effective if it's truly effective based compared to placebo and are there any side effects and what exact dosages are effective.

So is it the 10 milligs versus the 20 milligs versus the 50 milligs? So when we do phase 2 clinical trials, there's many legs and arms and phase 2 clinical trials um are not as easy to do. I I I have done some uh um but they're very complicated. Patients get randomized into multiple arms. They can get multip you know randomized into six or seven different arms. uh and each arm has its own dosage, its own um length and own processes.

So it could be very um uh you know complicated trial to do for a lot of people. Uh but that's where we kind of refine the dosages. We see if the drug is inherently safe. There's you know there's no other side effects. And once that all that safety and the dosage is established, that's where the large scale trials come in. And these are the phase three clinical trials. That's what mainly a lot of the phase three clinical trials is where I participate in.

I've done some phase two, but phase three is uh mostly bread and butter and phase three is pretty much confirming the efficacy versus placebo or some other competitor. You know, you're they're large groups. There's thousands of people in there. Uh they're multi-enter global trials. Uh you know, they you you look at robust evidence of effectiveness.

You see if there's years and you know you you'll you do these trials over two three four years and after these trials all the data that's collected based on what the endpoint are uh then it gets submitted to the FDA.

Now you know one drug, one med one compound uh from from its discovery to now it can go through uh trials for multiple indications right so it can be for uh cardiovascular outcomes it can be for a specific end goal for example like how much does it lower the LDL or the question could be does it make you know does it cause a decrease in cardiac events or decrease >> so the same drug basically can concurrently be running in different trials for different purposes of use.

>> Yeah, it's a whole program, right? So that one drug is going through multiple trials. It could be the same drug could be uh being tested for kidney disease and liver disease and for obesity and for cardiovascular disease. You know, there's multiple trials and multiple different types of physicians are involved, right?

And then once they go through the phase three trials where we know the dosage, where we know its efficacy against placebo or another competitor, uh we know the kind of effects it causes. At this time, we already know it's very safe. Then it it gets FDA approved. It goes through FDA for the review um based on all the data that's collected. And then once it gets FDA approved, then the phase four trials come in, which are post marketing trials usually.

You know, they're postmarketing surveillance when the drug is already on the market. uh a lot of uh data is being collected on what kind of side effects it's causing, what kind of effects it's causing.

Uh some of the long-term effects come into play like for example, you know, the weight loss from a lot of the GLP ones kind of start showing phase and those in that phase where it's in large populations, you start seeing a lot of people are losing weight over long term and maybe they're having an an improvement in their heart failure or cardiovascular outcomes. Again, I'm talking a lot from the cardio cardiology perspective because that's what I do. But it can mean any indication, right?

All these treatments. >> Yeah. Yeah. But no, but it's good to have like a a basic understanding, you know, like essentially phase one, you're looking at safety profile. Phase two, next level up, you're looking at efficacy and dosing in a little more detail. Phase three, much bigger trial, much broader trial, really refining that safe dosage, and now comparing it head-to-head for your specific indication. Does it actually make a difference compared to placebo or some existing gold standard?

And then FDA gets approved, goes to market and now you do post market once real patients are being prescribed this drug by real doctors across the country and now you monitor it longer term. Hence that's phase four. But it's good to hash that out. One interesting thing is the the diversity of the patients that these drugs are tested on during especially these earlier phases even up to phase three. the initial cohort of patients that you use as your sample for these newer medications.

If those patients are not representative of the population, it's hard to really know if the drug is going to have a similar efficacy and similar side effect and safety profile or is it just because you happen to sample just young males in the south. You know what I mean? That that was an issue with a lot of trials, especially back in the day.

I mean, even like the Frammingham Heart Study, one of the most famous series of studies that was done, one of the biggest critiques of that is it was largely young white males from northeastern United States that were followed. And obviously that study went on for generations, generations, but the initial results of that were very much not generalizable to females, non-whites, people different age groups, people that potentially lived elsewhere, had different diets, all that kind of stuff.

So I that's something that I think is interesting and I think it's changed a lot. Would you agree in in modern day trials? >> I mean yeah there's you know I do a lot of work with a lot of different pharmaceuticals.

I'm currently working with all the big pharmaceutical companies doing clinical trials um as well and there's a big push for diversity looking for uh diverse patients and now a lot of these companies are doing trials in different countries right it's not just it's not just uh doing trials in the in the continental United States but also having trials in China in India you know in in in the Middle East uh in Europe and and combining all that data so but that's where the trial design is very important.

Um you know before even the medication gets started, the project gets started and you know a lot of very smart physicians that um some that are practicing, some that have left and are solely working on drug development, they all work together on creating the design of the trial, what kind of patients we'll be recruiting and and you're constantly reviewing the kind of patient you'll be recruiting through as a trial is going on, right?

I mean, you know, they start getting the data and they said, "Okay, we've already uh 60% of the patients so far that are enrolled in a clinical trial are women, so let's try focusing more now on males." 60% of the patients are now Caucasian. So, let's try getting more African-American patients and Asian patients. So, there's a big push right now for having diverse set of populations.

And a lot of sites are being chosen based on the diversity of the population and and and a lot of times the physician that's conducting the trials uh you know their ethnicity kind of leads to uh the ethnicity of the patients that will be enrolling in the trial as well. So that uh a lot of the pharmaceutical companies or um you know the CRO's per se that are conducting the trials or choosing sites have a lot of those ideas in mind.

Are are we going to go in the valley in in South Texas and have a couple of sites there and have one in inner city Houston, maybe have one in San Francisco and have one in Alabama? So depending on uh what kind of population mix they're looking at, the geography uh plays a huge role.

But I think that's awesome though that that's becoming much much more accepted as what should be the standard practice in these trials because you have to have a diverse sample a diverse study population otherwise you have no idea how it's going to behave when it actually gets exposed to a diverse real patient population out in the real world. >> Yeah. I mean we've seen that right.

I mean there's certain medications there's certain anti-hypertensive like you know I treat I treat people with high blood pressure all the time and some medications work really well for some people right and and then that same medication for another person it does not work as well and then you have to try a different medication right no two people are the same and you need to have uh a diverse set of population uh in a clinical trial to have the right amount of data to journalize for the country that we're living in right uh maybe in Sweden uh or in Norway in Scandinavian countries it's a more homogeneous mix of population and you can you can journalize based on smaller data over there but in the in the US uh we're a very diverse country and we need medications and uh that will be journalizable to the rest of the population as well so I I think having diversity is very important um and that's where the the trial recruitment and the sites come into play right so it's a very interesting um established setup that you know there's a pharmaceutical company right a lot of times either the pharmaceutical company develops the compound or they buy a smaller company or a smaller entity that had developed the compound they buy it in that pre-clinical or phase one stage uh and the more of a trend that's becoming now is that there's smaller companies that get funding they they develop something and in the phase one stage is it shows promise and a bigger pharmaceutical then comes in and buys it and then starts moving it into the larger scale trials because those phase 2 phase three clinical trials need a lot of funding a lot of money right uh and without uh the FDA the the complicated FDA regulatory process we have they have to go through that kind of funding those large scale trials so there's the pharmaceutical that creates the compound is responsible for getting that compound to the market and then there's the middleman which is which is the CRO's the clinical research organizations these are uh organizations uh like IQ via or um you know PPD and what their responsibility is to to um conduct that trial, right?

These are the the middlemen between pharmaceutical and the actual patient and the the clinical sites. Uh they they a lot of times are involved in uh creating the procedures of the trial, choosing the vendors. You need the the central lab where all the blood will be sent and the data will be collected. you need monitors to come in and make sure that the data being collected at each site is accurate and uh applicable. Um no site is doing like you know shady activities and collecting false data.

So there's a lot of closed monitoring. So these CRO are middlemen and then below that are uh you know uh physicians and clinical sites and what's in historically a lot of times these CRO would come to academic institutions like University of Texas, Baylor or MD Anderson and they would give them the trials and they would conduct the trials over there. They would you know uh co coordinate with the pharmaceuticals and and collect the data.

But now uh things are moving more towards the private side you know as private practice physicians or bigger practices are also conducting trials in the community because not everyone wants to go to the academic centers.

And when we talk about diversity in clinical trials, you get diverse populations by being in smaller um you know community settings, you know, in the suburbs, in the rural towns in South Texas, uh you know, in Alabama, and a lot of physicians practicing there are uh are community physicians. So that's where the site management or site networks come in place. And site networks is a is a a network of of physicians or clinical sites where research is being conducted.

So CRO's select these sites and these site networks or the physician offices or investigator networks are in charge of conducting the trials, recruiting patients, uh collecting the blood, sending it in, you know, and following all the protocols as they designed. So it's a very complex large scale system that's that's developed over time and used to be more in academics and now has moved on to the private uh uh sector as well. >> Yeah, that's interesting.

I mean it's a full production with so many moving parts, right? Like the pharmaceuticals that have the funding and essentially ownership of the drug. Um the CRO's as you said it's middlemen but more than middlemen. I mean really like trial managers and they handle the logistics of how patients potentially could get recruited, keeping the data, storing the data, remaining compliant with regulation, HIPPA and all of that stuff.

Um, and helping the physicians actually do it because if you're running a really busy practice and you have a high volume of patients, you you want to be involved with research and also help your patients potentially be involved with new drug development. I mean it is almost impossible to do this by yourself that you you need something like the CRO that are professionals at doing it.

Um so it's very interesting this process and what you know what you commented on that it shifted away from academics a bit obviously academic still has a lot of clinical trials going on. Um, but the fact that it doesn't only have to be done in that setting, I mean, for one, it could make it a bit more efficient and less red tape because big institutions in general are slower at things and less efficient at things.

Um, but two, it almost coincides with like the funding cuts that we just mentioned from the governmental level coming on down. Those are putting a lot of downwards pressure on these big institutions, these academic institutions, and their funding and ability to get these kinds of grants. um you're almost hamstrung in a way and it may make the private side a much more not only possible avenue to do this um but one that may not require such huge grants and funding from the government level.

>> Yeah. you know like for example um um we run a big clinical research business uh and uh we have many sites across the United States right in south in in Texas in Dallas in we have sites in Dallas in Houston and South Texas we have sites in California and you know in in uh Philadelphia and a lot of times you know these pharmaceuticals or the CRO cannot find site networks like uh you academic institution to be able to activate sites like that all over the country.

So for private site networks like ours uh they can just come to us and say that hey we will have one contract uh we can uh get access to all these different sites and these diverse populations and activate all site by just talking to one person because we're we function as a more efficient organization.

So there could be one point of contact that can be a point of contact for all these different sites along the around the United States and they cannot do that at academic centers where there's a lot more red tape, a lot more bureaucracy where you have to get permission from multiple different stakeholders before you can move on. Whereas here it's easy to make a decision. One person decides yeah let's finalize this contract.

this is how much uh we will charge per patient or per study and let's sign this and get it through and let's start the trial. So usually the startup times are much faster for private site networks versus uh academic institutions. >> No, that makes sense. I mean the more lean you are, the easier things are that way. I mean in terms of speed but also cost.

And and you know that brings up another interesting topic is a bit on the ethics and finance side right and so many different players in this like the patient themsself who is a patient but also the subject right I mean it's this is research they're a subject a human subject um obviously you know keeping it all as ethical as possible with um with all of the rules um but the ethics of that like are these patients potentially double dipping in multiple different trials because some people become professional trial patients.

That's how they make their income. They gather funding and money and that's how they maintain their livelihood. That's one thing to consider and it's it's hard to really parse that out. Um two is like the incentives now for a doctor or a CRO or anyone involved in this process. The more patients you enroll potentially the more the trial is pushed forward towards eventually drug development. You are incentivized in some way to just do more. it becomes a volume game and a bit of an assembly line.

Um, and obviously the pharmaceutical company at the end of the day is a business. Their main incentive is to their shareholders. So obviously they have to go through this process. There's a lot of check marks like you said with the trial phases and the FDA um and all the regulation um but their whole goal is to get this out to market to recoup their R&D costs and eventually make a profit.

So there's a lot of potential checks checkpoints uh in this whole uh journey of drug development where it could be a little ethically swayed financially. Yeah. You know there's uh incentive for patients to be part of clinical trials. Patients get access to free medications, free labs and also uh compensation for their time and travel. So there are professional patients. Um but I'd say majority of the patients go into clinical trials for the right reasons.

uh most of them you know get recommended by their doctors by their physicians or or a lot of them seek out trials for sometimes medications that are not yet available in in in the market and these medications can possibly help them. So a lot of patients seek out clinical trials through through websites or through um you know online marketing or social media marketing that they see. that they seek out versus some get recommended by the physicians.

But yeah, there's a small component of professional patients that double dip and go to multiple trials and sometimes there's no way to know if they're in multiple trials at the same time and you have to take their word and you don't even know if sometimes if the medication that is part of the you know it's it's at home. Are they even truly taking it? So that's where uh the physician patient relationship comes into play.

you know being a good investigator, principal investigator um it's very important for you to judge every patient uh see if they would be good candidates for the trial and honestly fra have frank conversations up front I mean you know tell them that yes this may potentially help you this may you may get the placebo you know it is the clinical trial so you could either be in the treatment arm versus the placebo arm um you also have to be frank that yes you are uh helping us by being part of this trial.

So you, you know, we provide a lot of more personalized care and service for these patients um because they're doing us a favor. You know, they're they're doing a favor to science, favor doing a favor to society.

But then we also have to remind them that the medications they're on currently that's cured their heart failure or prevented their first heart attack or you know uh the the the medications they're currently on someone participated in clinical trials in the past to uh help them get there you know help them live longer help them get to 60 70 80 year old you know um and now they can maybe repay the favor as well. So there's multiple conversations uh you have to have.

Physicians do get compensated for their work when they're uh you know monitoring a large trial and supervising a large clinical trial like that. Uh you do get compensated for every patient but there are checks from the pharmaceutical side and from the CRO side. They are the ones paying you and they want to make sure that they're not paying you for the wrong reasons and for um you know just for your greed. So there's constant monitoring, right?

I mean, so you there's trials where they're high enrolling trials. You enroll five patients and they put a pause on it. They make sure they come in and they make sure that all the data you've collected is accurate.

uh all the subjects that you've enrolled in the trial truly qualify for the trial and you are not frauding them in any way because these again are larger corporations that want to maximize their profits and minimize their revenue and they want to make sure that they're not paying some site some physicians money for no reason and then them then providing them uh poor quality data right uh so in the end I mean this is part of science right I mean you peach patients we have to do these trials with patient involvement.

They have to be part of those clinical trials. Yes. Uh there's there are there is a lot of evidence that patients who are in clinical trials get a lot more personalized treatment. They end up doing better because they do get close monitoring. Their labs are checked frequently, right? They have interaction with people in the medical community more often. So, they're getting their blood pressure checked. They're getting their labs checked.

And they're potentially getting a life-saving medication versus just a placebo. but still uh having frequent interactions. So there's a lot of benefits. Yes. Uh patients are helping. They are um you know but also they're also benefiting from this. >> No, that's very interesting. And you know it it's also not just like oh a bunch of doctors are recruiting patients. They're getting paid for it. I mean it it adds time.

It takes away time from your otherwise the running of your practice seeing patients that are your other patients the ones that are not related to the trials. having research staff, research coordinators, all of the special regulation involved with safe data storage, whether it's with the cloud in person or whatever, the site visits, extra time to meet with these people, the coordinators and stuff. Um, communication with CRO or the pharmaceutical company themselves.

So, it's a lot of extra stuff, right? So, it's not just, oh man, Dr. X enrolled these five patients this week. Let's cut them a check now, one for each patient. I mean it goes towards a lot of the extra overhead which is separate from your own practice overhead. It's is separate. It's a whole different thing that you're doing. So I think a lot of the initial like naysayers or pessimism about oh these doctors are just getting paid to enroll a bunch of patients.

I mean yeah time has value and they're adding a lot more of their time into this in addition to their real clinical resources. So in some ways it's got to be compensated. It's the same thing when you apply for an NIH grant for research in the lab. I mean you have carveouts within that grant. The budget is very stringent and this much is for materials in the lab, reagents, test tubes. This much is for hiring clinical staff, support staff, research staff. This much is for statistics.

This much is for manuscript preparation. And then you have carbots for indirect cost and your own time that you have now 20% of your allotted time is going to be covered by the funding from this grant. I mean that basically covers some of your salary. So it's no different whether the grant is from a government institution or you're getting funding from a private entity. It still goes to cover a whole litany of different expenses that are just necessary to do this endeavor. >> Yeah.

I mean the amount of paperwork and documentation that goes into clinical trials is just unreal, you know, just just because we have such high regulatory requirements in our country with the FDA. Uh there's there's so so many different forms to be uh filled out to be kept up with. Uh the protocols constantly keep changing and an updated protocol needs to be reviewed all the time. The IRB is constantly uh making corrections or you know there's pauses and the IRB has to review everything constantly.

the in investigational review board. Um, and there's a huge uh a lot of manpower involved, right? I mean, you have multiple coordinators for clinical trials. I mean, just one coordinator per clinical trial sometimes is not enough. You have you we need you need to hire people that are making sure the quality is good, right?

You have to make sure that the datas that being collected u by and and and um written down by the coordinator and entered into the computer is accurate and it it it makes sense you right.

You have to make sure that there's people that are uh chart screening that are going through uh patients and making sure that the patient qualifies or does not qualify and maybe uh you know suggesting patients that could qualify because you have to mine through a lot of data to see what patients could qualify, what patients could not qualify for a clinical trial. Um you know and clinical trials is how we've advanced medicine in the country, right?

I mean, we would not have these life-saving medications, these lifech changing devices, uh, you know, through which now we're doing shoulder replacements and hip replacements and treating heart failure and cholesterol and putting in stance. These had to go through clinical trials. It's I think it's it's one of the most important part of medicine, right? The advancing of medicine through clinical research is as important as practice of medicine and treating patients, right?

So yeah, patients do get a lot of benefits because for example, you know, we're doing a lot of clinical trials with um the GLP1 agonist that we've talked about and some of the patients were able to get on these medications through clinical trials and they truly seek out these medications. It helps them lose weight, improve their metabolism uh and they got the medication for free under supervised care and and they benefited from that.

But then we also benefited because now we're able to bring on these life-saving medications into the market uh and then have larger populations benefit from it too. >> So here's another another question. What happens to these patients? Let's say you know you have a patient that goes through a clinical trial for like you're mentioning like a GLP1 looose or something. They go through it. They get a benefit from it. They lose weight. Their glucose gets better controlled.

They become overall healthier. The trial ends the drug goes to market. What happens to that patient? Do they keep getting that medication at obviously like a subsidized or free cost or now they go kind of back to being just like any other patient and okay now it's time for you to pay for your med or you and your insurance combined pay for your med just like everybody else. What what is that um interplay? >> Very dependent on the trial.

I mean some trials um uh have a open label phase where they tell you okay after 3 years once the medication is approved or the trial ends we'll enter the open label phase where you'll be able to uh know if you were on placebo or you know or sorry you won't know if you're on placebo or not but everyone will get the actual uh investigational product. So, some trials have that, some trials do not have that.

And that's where the physician that's working with the patient has to make a plan of transitioning them on to another medication or the same medication that's now approved by the FDA. It's on the market. Um, so yeah, sometimes it ends and patients don't have a plan or are now off that medication. Um but and sometimes they're extension extended studies uh extension studies uh where patients enter and then those studies are looking for long-term effects of these medications.

So they enter those trials, they get offered those trials first and they enter those and they can continue being on that medication for a longer time. So there's very different things. It's all study specific and especi also um dependent on what was being looked at in the study.

Was it a cardiovascular outcomes trial or was it uh just a short-term trial seeing if this medication within 12 months lowers the cholesterol by this percentage and that was it you know um so very dependent on the trial but you know uh you have to have a plan with your physician and that's why a lot of these trials need to be done with physician supervision and um and and trial physicians play a very important role in you know advancing medicine pretty much. >> Oh totally.

I mean clinical research is huge. You know what's interesting is um like this is all drug development like within orthopedics. Uh a lot of the clinical trials are really like uh surgical outcomes or the outcomes of non-surgical treatment. Right? A lot of that is weighing between for X condition Y condition. Do I do surgery or not do surgery? And what happens to the patient if I have someone that comes in with an elbow fracture? What happens if I just treat it with a splint?

Then they do some therapy and give it some time and see versus I fix it. I go in there, I open it up, put plates and screws and then see. There's not really like a drug there. Um, you're not really comparing something like that. And I guess nonop treatment is not really a placebo. It's just you kind of live life. Um, that a lot of that is is different because it's much less um like private industry involvement.

Obviously with implants you can have industry funded studies that happens a lot but a lot of the studies when in orthopedics in in something like this are a lot of retrospective looking at chart data of a large series of patients that underwent some similar treatment and how they did versus a actual randomized trial where you said okay I'm going to fix this fracture with the standard plate and screw type fixation for the broken bones versus I'll do a joint replacement on it you basically cut out the fracture, do a replacement so they don't have to worry about the broken bones and see which arm did better.

Those are very common um in orthopedics but the the difference being essentially all of those are surgeonled.

there's really no intermediary like we have talked about with drug development that you know it's pharmaceutical company CRO's and then doctors and their patients kind of coalesing together and making this happen with a lot of these trials um and these case series these retrospective reviews um and even prospective trials in orthopedics it's kind of just the surgeons just do it along with their patients and really like an army of residents and fellows who work together to make the research happen.

Um, and a lot of them, a lot of them are not funded. They're just done based off of the time and sheer will to push science forward. Um, because there is no funding coming from anywhere uh for a lot of these trials. >> Yeah, definitely. I mean, >> it's a different game. It's a different game. >> It's a different game. And how how how do you do a placebo trial in the surgical field, right? It's tough.

you can't really do like it like one of the um you know one of the most like landmark orthopedic uh studies which you know was published in the New England Journal of Medicine which is like the most reputable journal in all of medicine. So for an orthopedic trial to be published in there is almost unheard of.

I mean, you would think that someone played an April Fool's joke like the New England Journal of Medicine publishing an orthopedic trial, but it was actually done at Baylor many, many years ago as looking at knee scopes, knee arthroscopy.

Um, and basically seeing like could you do just like a little sham procedure in a in a knee that had arthritis just going in patient didn't know whether they had something done to their meniscus in the knee, the little shock absorbing cartilage disc in the knee or not. And so they did a sham.

They just basically the patient's sleep made little arthoscopic portals and in some of the patients they just stitched it up and patient was like well I got the scars I don't know if I had surgery or not or they just kind of faked it versus the other group they went in and did the scope they did a little shaving debreeding for the torn meniscus and the arthritic knee and they really found that basically like >> there's really no difference that the sham procedure sham I'm calling it um basically did just as well because >> the knee is already arthritic and just doing a little bit of a so-called cleanup job on the knee doesn't really do anything once it's arthritic.

The dye is cast. It's done for. It's kind of like if you have brake pads on your car, they start wearing away. It doesn't matter what kind of fancy lubricant you put on there, you have lost material. You have lost a brake pad. You just need a new brake pad. Uh and I think that study, it was published in New England Journal because it was just so well done.

Um it would be really hard to uh put a patient in the modern day under general anesthesia, make a fake cut on them, and they wake up not knowing if they had a surgery done or not. But um you know that's like the so-called placebo type research um in orthopedics um >> harder harder to do now. >> Yeah.

I mean you know it's things are changing the landscape is changing quite a bit and you know within drug development now >> uh you know it's a it's a it's a data game right you're constantly collecting data and you're constantly looking for patients.

sometime as a physician you know who is a cardiologist I'm seeing a lot of patients that are not on clinical trials and seeing them on a daily basis and then uh seeing patients who who are interested in clinical trials or who uh you know you have to have a conversation you have to take that time out and have discussion with them and you truly have to talk about placebo about blinding and why why it is important to not not see your own labs you know there's a lot of um due diligence you need to do maybe even discussing with their primary care doctors, hey, make sure you don't check their lipids because we're blinding them from their lipids because they're on this medications for the next 12 months.

>> But that's interesting. Yeah. You got to make sure like other doctors don't don't spill the beans, so to speak. >> Yeah. And a lot of times, I mean, these trials are not perfect. Patients do get unblinded, right? they get they do find out if their uh lipoprotein A is uh reduced once they've been on this medication or they they take a GLP-1 and if they're on the placebo they're not losing weight and if they're not on the placebo they start losing weight.

So that's definitely not uh you know blinded clinical trial.

It's none of the trials are the they're the perfect um you know a lot of times the problem with data is that the data can be manipulated right um you can have a certain amount of patients and you know maybe have a smaller experiment you know smaller trial where some data ends up being significant versus you know or non-significant versus if you did the same trial in a lot more population or a lot larger population maybe it would be significant.

So trial design plays a huge role in the beginning and now uh >> yeah it's got to be appropriately powered. >> Yeah it has to be appropriately powered and then powered and now with the advent of AI now uh I think things are becoming a a lot more efficient.

I mean, you know, based on um predictive studies and large large data models, um you know, they're able to predict better of where to go for these patients, uh where to look for patients, how many patients should be enrolled in this clinical trial.

and even from the site network site or from a physician side um uh AI can play a huge role in data mining and collecting information suggesting patients that would be eligible for clinical trials cuz that's the the hardest part of the game and you don't want to you don't want to sound like a salesman where you're trying to sell different clinical trials to the patients but you it's also important to recruit good eligible patients for a clinical trial because you know that can in the end advance medicine and where is that balance of not sounding like a salesman and and then actually recruiting good patients for the clinical trials and that's where uh it's it can be you know a lot of the AI softwares or uh data mining capabilities can be used to suggest to you good eligible patients that you can then have a conversation with.

Um, so there's already a lot of different companies that are working on this where they can have like different plugins to the EMR where as you're seeing the patients, you start getting suggested patients that could be eligible for the multiple clinical trials you're doing. And then um, you know, you can based on those suggestions have that true honest discussion with the patient. Hey, I think you'll be a good candidate for this clinical trials.

You have all the different eligibility requirements. Um, you know, this is how you will benefit.

this is how we will benefit uh and these are the services we will provide you while you're on the clinical trial and you know if you participate you're truly helping us advance uh clinical medicine uh and then after having that conversation you know um uh hopefully you hope that the patient would agree if they don't agree you still treat them the same way you still make sure you continue treating them um but I think AI will play a huge role in in conducting these clinical trials >> yeah for Sure.

I mean, that's very interesting. I'm using it as a tool to identify patients cuz it can I mean it can comb over more data instantly than any human eyes can. Um, another interesting one of my buddies, he works for a a company out of Dallas actually that um they also use AI for the clinical trial space, but on the other side of it actually looking at potential targets for drug development. They basically use these giant institutional databases like that these huge cancer centers have for example.

I mean they're taking biopsies of every tumor. They have DNA and genomics on every single tumor that is resected at that location. I mean, they have huge I mean, remarkable repositories of these DNA libraries. Um, and basically just combing through that data and identifying potential areas that you could target a new chemotherapy drug, a new imunom modulating drug, a new biologic target, um, all these kind of things.

I mean, that's something that there there's no human there's no army of humans that can look through that data and make sense of it. But these AI algorithms, I mean, they are nothing but pattern recognition to the best possible degree. And that's what they're using. And a lot of these companies are now using that as their initial uh baseline of how to identify target for drug development and then take that into this whole process we've just talked about.

Start going through the phases of the trials, identify patients to, you know, test it on your your study cohort and go on. It's very remarkable where where this AI stuff can take us. >> Yeah, I mean, I'm very excited about that.

I mean I think uh we're going to have a lot more progress into a lot of these rare diseases, a lot of these rare type of cancers uh where you know um a lot of gene therapies where we have not been able to kind of make progress right these these rare diseases only very few patients have them. It's very hard to recruit patients.

Um and sometimes maybe the financial incentives are not there but with these AI pattern recognitions with all already present data that we have we can really develop therapies for a lot of these rare diseases and a lot of people can go through life-changing um treatments. Um and kind of that's where uh the other other place where AI is also playing a huge role and technology is playing a huge role is decentralized clinical trials.

So instead of uh being monitored in the physician's office now with the with the with the use of like you know different wearables or different uh tablets uh patients can be at their home have nurse visits collect data there um have blood draws at their homes and uh you know um the clinical trials are decentralized. You don't have to wait for the patient to come into your office.

um the clinical trials and the data collection can go to their um where they are and make make things easier for them because a lot of patients that participate in the clinical trials may not have time to leave their jobs and come for trial visits.

they might not have uh the transportation to come to the research sites but if the research uh capabilities can go to them through a lot of technology wearables, tablets, um you know video chats and things like that um you know we can we can solve a big problem in patient recruitment in clinical trials. >> Oh yeah, it would increase access a ton >> for sure. >> You increase access. So I mean you know and then like clinical trials are very messy. Um clinical trials are not always perfect.

You know, there's a lot of uh good patients that are part of it, but then there's a lot of professional patients like we talked about, right? There's a lot of uh downfalls and um collection of the data. You know, there's good sites where patient, you know, where physicians are truly working on get collecting good data, working with integrity, but then there's sites that are not working with integrity. They're focused on maximizing the profits.

uh they are working through their greed and trying to maximize the amount of money they're making from the clinical trials, right? And that messes up the data. Sometimes sites can uh uh enroll patients or random patients that truly did not needed to be randomized and there's a lot of patients end up being lost to follow-ups. They can recruit there's there's stories of people recruiting homeless patients to come in and be part of clinical trials and then after that lost to followup, you know.

So those are bad clinical trials. So clinical trials are messy. They're expensive. But I think they're they're necessity in advancement of you know medicine and advancement of our world pretty much because we need to keep finding new therapies and you know improve clinical outcomes. >> For sure man. I mean it's how it's going to push forward. I mean it both of us every single person listening to this we've all taken medications that have come about through this whole process.

So it's already affected all of our lives and it's only going to continue to. >> Yeah. >> Interesting stuff man. Yeah, I hope I hope we keep uh you know our government continues to keep funding the right things and you know a lot of government support is needed for these trials. So I hope um the politicians come to their senses to stop thinking selfless uh you know selfishly instead of focusing on accumulating their own wealth through these unnecessary wars.

They they focus on uh advancing of humanity and focus on science and advancing science. >> Totally real science. It needs funding. Well, >> all right, guys. Two docs, one mic. We'll see you next time. See you.