Scott Webb (Host): There are many ways to unlock medical innovations, and my guests today are here to discuss the role that clinical trials play in unlocking these medical innovations for patients today and in the future. I'm joined today by Dr. Alain Litwin. He's the Chief Scientific Officer at Prisma Health. And I'm also joined today by Dr. Jeffery Edenfield. He's an oncologist with Prisma Health.

 This is Flourish, the podcast brought to you by PRISMA Health. I'm Scott Webb. Doctors, it's nice to have you both here today. We're going to unlock medical innovations and what does that mean exactly. And we're going to learn from you the role of clinical trials. So Dr. Litwin, let's start there. What are clinical trials and why are they important in medical research?

Dr. Alain Litwin: Absolutely. It's great to be here, first of all. Clinical trials are crucial in medicine. They really lead to new treatments and approaches for taking care of our patients. They can lead to cures for diseases and to help us live longer and better lives. Clinical trials transform the way we deliver healthcare. You know, they turn scientific discoveries really into pragmatic treatments. And they connect really the lab research with real-world medical care.

What they are, are carefully designed studies that involve human participants. And they, again, allow us to test drugs, procedures, devices, even models of care. They're critical for advancing our knowledge and developing new ways for prevention, for diagnosing diseases, for treating diseases. It's important, again, with clinical trials that we work with not just one population, but all of our communities, diverse populations, real world settings, so we know how these innovations work in the real world. Again, clinical trials drive innovation and they set new standards. So, the way we practice medicine 20 years ago is not the way we practice today, and it'll be different 20 years from now. And they lead to new medical guidelines and standards in the way that we all receive and deliver healthcare.

And finally, as a Chief Scientific officer here at Prisma Health, really proud to say that we have over 1600 active protocols, 750 new studies. You know, thousands and thousands of patients are actively engaged in clinical trials and research.

Host: Yeah, it's really amazing. You say 20 years, but it could be five years. Medicine, science, it all changes so fast, and it's one of the privileges of being able to host these, is to learn from experts like yourselves. And Dr. Edenfield, let's drill down a little bit. How do clinical trials contribute to the development of new treatments and therapies?

Dr. Jeffery Edenfield: I think of clinical trials like the engine that drives healthcare forward. So, participation in clinical trials allows us to find new and effective and safe treatments. Obviously, if ever there was a perfectly safe and effective drug, we wouldn't need to do clinical trials in that particular incident anymore, but you and I both know those don't exist. So, every new treatment, goes through the clinical trial process, but think of it like an engine that drives things forward.

Host: Yeah, that's a good analogy there. And I'm just really excited. I was so excited about this topic. And Dr. Litwin, I'm sure that trust is important. So, I want to ask you, why is transparency and community engagement crucial in building that trust between researchers and participants?

Dr. Alain Litwin: Let me start by, you know, saying, at Prisma Health, you know, we work every day to earn the trust of our patients. We're the health system that the community trusts that most likely recommend their family, friends and neighbors. And we're not just clinicians, leaders, researchers, but we also engage and receive healthcare as patients and our families receive healthcare.

And so, I think, most importantly, you know, how do we build trust? And that's really transparency, right? It's really being very open about what we're doing, whether it's clinical care or research. I think that trusting relationship that we've built over many years with our community really helps with our research.

And so, again, when patients trust the medical care they're providing, they're much more likely to want to engage in research. And in turn, it goes both ways, right? So, our clinical care is so trusted because we offer state-of-the-art clinical trials delivered by a really credible group of investigators and research team members. Building and keeping that trust of our patients, our participants in our community is really vital. And how do we do that, right? You build trust by being very open about what are the goals and risks and benefits of engaging in a study, and just showing respect for potential participants. That helps people feel more confident in the research and what they're doing, what they're about to engage in.

And then, the other point here is that working closely with the community is just a core value of ours. Ultimately, we want to improve the health and wellbeing of our community, both locally, regionally, you know, nationally, globally. And in order to do that, you have to really understand community's needs, right? And the best research happens when we partner with the community to understand from the perspective of our patients, our community: what are the gaps in healthcare? What are the areas that we can improve upon?

And then, that partnership really shape the questions and the methods, and make the studies more impactful. Once you design that great study with transparency and partnership, then you can execute that study, right? You can recruit and retain participants, which if you don't have successful recruitment and retention, you're not going to be able to get results that are valid.

So, I think, most importantly, we just want to always include the voices of our communities, our research participants. And that also holds us to the highest ethical standards.

Dr. Jeffery Edenfield: And I just think it's important to acknowledge just how fragile this trust can be too. And we're at sort of a challenging time, perhaps with respect to America's relationship with science. But I'm always optimistic these things pass, but I don't think the average person knows that an institutional review board or an ethics board reviews every study for appropriateness and safety. And that those institutional review boards routinely include members of the community. So, even the very development of the study involves interacting with the community to begin that element of trust early on.

Host: Yeah. And just listening to you both, it does feel like, you know, trust is kind of a two-way street. And I love that word you used, Dr. Litwin, the partnership, really a real partnership with the community and the participants. And Dr. Edenfield, I want to stay with you. It seems so critical that there'd be a diverse population, a diverse participation, if you will, in clinical trials. So, maybe you can address that.

Dr. Jeffery Edenfield: I'm an oncologist. I'm a cancer physician. And, obviously, you know, clinical trials are central to how we make progress. And you really want your clinical trial to look like a trip to the grocery store, right? You want it to look like your community. You want it to look like your friends and neighbors. And historically, that's been challenging.

But I will say at Prisma, we've been strikingly successful at making the demographics of our clinical trials look like our community. And that's something of which I'm particularly proud. But I don't think you really know how the drug works and is it safe for everybody unless you actually study it in everybody. And history has shown us a number of occasions that when drugs have been approved on narrow demographics, that we discover brand new and important side effects, sometimes really dangerous ones once it's out after approval. So, diverse clinical trials are critical to safe drug development.

Host: Sure. Yeah. I want to follow up and just to get a sense from you, how do participants benefit from gaining access to new treatments before they're widely available?

Dr. Jeffery Edenfield: This will go to a point we're going to talk about later, but it's a study. You truthfully don't know if there's going to be a benefit. And so, now, all the more reason to be completely honest with folks when they're thinking about joining. But I will say that, and I do often say to patients, you know, everything that works today went through this process, right? And so, great example would be, you know, immune therapy for cancer, using your own immune system to fight. Someone had to join that trial, which revolutionized how we take care of cancer in so many ways. So, there is that potential benefit always when you join a study, that you'll get access to something peculiarly successful before it's available.

Host: Yeah, I've had the pleasure of learning more about immunotherapy, CAR T-cell immunotherapy, and it's really mind-blowing and sounds like science fiction. But as you say, real people, real participants are the ones who made that possible. And Dr. Litwin, is there like additional care and attention that participants can receive from clinical trial staff?

Dr. Alain Litwin: All clinical care really should be the way that we deliver research. Because obviously, there's the cutting edge ability to have a potentially transformative drug or have a device implanted or a new model of care.

But I think what often we all forget is like the intervention effect of the exceptional team, right? You know, you have a team of research nurses, nurse practitioners, investigators, the regulatory folks, study coordinators, right? These are the folks that get up every morning, who know their why, and they really totally understand, you know, what the transformative potential can be of that research and their building that relationship and that trust, right? So, they're, you know, following up with phone calls. If someone doesn't show up, they're falling behind to see what's happening, providing transportation and other ways to maybe overcome some of the social determinants of health. So, really, you know, that engagement, that social support, that compassion, that really has an effect in itself and often improve outcomes in the control arm and not just the intervention arm, right?

Host: I am sure. Yeah.

Dr. Alain Litwin: But it's something we pride ourselves on is, you know, that kind of extra care and attention that participants receive. And I know in our cancer institute, Jeff, I mean, you take that to the Nth degree.

Dr. Jeffery Edenfield: Yeah. And I think, you know, we've always told patients it really is just an extra layer of oversight, right? The human part of medicine often feels, you know, kind of hidden away, but there's a dedicated research staff member assigned to each patient on the trial, so there's contact in very real and tangible ways for patients when they're on trials.

Host: Yeah. And Dr. Enfield, I want to talk about safety. Because I was trying to think through here as I'm listening to you guys and trying to process all of this, trying to think about, like, what would be some of the objections? Why might a patient not want to participate or choose not to participate? So, let's talk about the safety measures that are in place to protect participants, and what are the potential risks.

Dr. Jeffery Edenfield: Yeah. Great question. And the staff is the number one. But in terms of, say, drug trials, new medicine trials, there's intense pharmaceutical oversight, provenance of all the drug, the lots. You know, everything is checked at multiple levels to make sure. The care plans are reviewed intensively with multiple persons, reviewing them for accuracy. It's invisible to patients, but, you know, we actually hold weekly safety calls on many of our trials where other investigators at other sites who may have seen something you haven't report a new side effect. And so then, you can go back to your patient and say, "I just learned this. Be aware if this something like this begins to happen to let me know." In so many ways, there's multilayer safety mechanisms in place for clinical trials.

Now, that said, you know, again, it's a study, it's an unknown. There's an element of the unknown in the clinical trial. And so, we do uncover side effects that weren't expected or side effects, which are perhaps more severe than we might have anticipated.

I think one of the good parts about being on a clinical trial is sense a person's access to healthcare is so much improved on one, that we usually find those things quite early. So, we're doing our best to minimize the potential risks. Some patients are worried about financial toxicity, financial risk associated with clinical trials. But in general, clinical trials are a less expensive way to get healthcare in many ways, since the cost of some of the procedures is offset by the study itself.

Host: Sure. Yeah, it's really interesting. And I'm interested in learning more from you, Dr. Edenfield, about the process, like the informed consent process. How does that work, and how are participants kept informed throughout the trial?

Dr. Jeffery Edenfield: Right. And I always tell patients, " These are the rules," right? Now, this document, this informed consent document, which now can be, you know, 15 to 20 pages long, it's very daunting for patients to read that. But the first thing I say, "This is the rules. This is what we're going to do together. And it basically says you're joining voluntarily and I'm going to explain the science to you as best I can and what's actually being proposed. What do we think are reasonable foreseeable risks, what we hope might be the benefit, but acknowledging that we don't know." We want to assure people that their enrollment is confidential and those records won't be shared unless it's explicitly stated that it will be.

We want to make sure that if an injury or a side effect that serious happens, that they're aware of the mechanisms for what to do about that and how they can be compensated. And really, it explains that you know, your doctor's your doctor. And even if you decide that you want to withdraw from the study, I'll still be your doctor. It's okay. The entire process is voluntary, and it places you at no risk for loss of healthcare outside of it.

So, I just really believe that the current informed consent process emerged from a lot of things we probably know we're not proud of in the '50s and '60s. Now, it is really a very important part of the clinical trial process. And I routinely tell patients that I don't expect them to sign it the first day. They get it, they should bring it home, discuss it with their family, their friends, their pastor, people they trust before making a decision. And we continue to work with them if we need to have additional conversations about, the trial.

Host: Yeah, no pressure to sign it immediately. I love what you said there about no hard feelings if they decide, you know, that the trial's not for them even after it started. You'll still be their doctor, which is great. Dr. Litwin, I want to give you an opportunity here to share some success stories where clinical trials have led to significant medical advancements.

Dr. Alain Litwin: So many stories. First of all, we're a learning health system, and a lot of our research is very pragmatic in a sense of improving quality, safety, our patient experience. So, one story was really led, and just another side here is that a lot of our researchers are also clinical leaders and top-notch clinicians and do it all.

So, one example is our Chief Quality Officer, Dr. Chang, she developed a novel. What we call sepsis integrator alert system within our electronic health record. And over a pretty short period of time, it led to a 25% reduction in death from sepsis. Now, we're one of the top 10% of all health systems in the U.S. when it comes to sepsis care. So, really hundreds and hundreds of lives that were, you know, saved from working with kind of practical aspects of our electronic health record in real time.

Talking about stroke, you know, in South Carolina fifth leading cause of death. Most of these strokes are what we call ischemic. We have in South Carolina, some of the best stroke outcomes now in the region. And one of our neurologists, Dr. Sivakumar, kind of recently published this research in New England Journal of Medicine, which transforms the way we treat with medications ischemic stroke, heart disease, another area, right? Heart disease, heart failure, leading cause of death in South Carolina in our country. Fifty percent of patients with heart failure hospitalized, and a team of doctors led by Guichard and McCann across both of our markets led an international trial called the PROACTIVE Heart Failure trial, it's a device trial. What it allows patients to do is measure pressures in their pulmonary artery at home so that care teams can kind of monitor these parameters and make adjustments in real time instead of every month or every three months. And we recruited the most participants across the country and it really demonstrated less death and less hospitalizations in the intervention arm.

We have cystic fibrosis, a pediatric lung doctor in the Midlands, Dr. Heather Staples. When I was growing up, the average person with cystic fibrosis in the '80s would only live until their 20s. Right now, what Dr. Staples was studying is a first in class oral once-daily medication for cystic fibrosis to now where if you get on this medicine as a young person, you can expect to, if you're born today, live into your late 60s or 70s with fibrosis, which is incredibly transformative.

Host: Amazing.

Dr. Alain Litwin: It is amazing, yeah. Finally, an area of passion to me is addiction and related comorbidities, specifically hepatitis C infection. And here at Prisma Health and with our academic partners, Clemson and USC, we led a national study, looking at how do we treat people who have substance use disorders, who are actively injecting drugs, a big problem across the country, and who live with hepatitis C, right? Which is a leading cause of liver disease and of death. And we showed contrary. You know, people often think, "Oh, if you're injecting, first you need to get into addiction care before you can get treatment for your other diseases." But we showed that over 90% of people can be cured. You don't really need to take all your medications. We obviously strive for that, but even if you only take half of the medicines, you still have very high cure rates. showed that this really vulnerable group of people have not just improved outcomes that lead to cure of hepatitis C, but improve other important patient-reported outcomes, less depression, anxiety,

improved behaviors, less sharing and injecting of drugs, less alcohol use. Improve quality of life, less chronic pain. So really important work that has informed, guidelines really globally for the care. And Jeff, you have other stories there?

Dr. Jeffery Edenfield: It's just funny this is the question because I saw a patient yesterday who actually is a young person, had a very aggressive breast cancer about seven years ago, and joined a clinical trial and had a complete response, and has been doing just fabulously. And maybe the definition of success is I got to see the baby picture yesterday. So, think about that for a moment, right? So, that to me is real success.

But I'll echo some of what Alain just said though, is Prisma is in a very interesting place. We've done twenty first-in-human trials here. And on several of those, we've given the first dose of a new medicine in the world. Our rare tumor program, you know, I have visits from several patients whose cancers disappeared on immunotherapy that they would've never gotten if we didn't pursue that treatment for their rare cancer. So, I mean, I think the success stories, we of course want to remember them, but there are many.

Host: These are my favorite podcasts. The ones where I learn a lot from experts. I smile a lot in reaction to things that I'm hearing. I got a little tear in my eye there. Hearing you talk about seeing the baby of this woman who survived breast cancer. It's just all-- I used the word earlier-- amazing. And I think that that's really appropriate. It's amazing.

And I want to get a sense from you here at the end, Dr. Edenfield, like how do people find clinical trials that they might be eligible for and maybe then consider participating in?

Dr. Jeffery Edenfield: The first and hopefully the most trusted source would be their physician. We are intending always to stay up to date, but it's hard. So, there are actually government websites for approved trials, and clinicaltrials.gov is another good resource, and they have a patient-facing portal, which makes it easy to search.

You can also, in many cases, find a support association for the disease of interest, and they will have links to clinical trials. But I think it really, hopefully, should always start with a conversation with your physician.

Scott Webb: Well, I really appreciate your time today. I know you're both really busy saving lives, you know, and all that good stuff and all that that implies, but it's just so great to learn from you to get your time, your expertise. Thank you so much.

Dr. Alain Litwin: Thanks so much. Really appreciate the opportunity to share.

Dr. Jeffery Edenfield: Appreciate it.

Host: For more information and other podcasts just like this one, head on over to prismahealth.org/flourish. This has been Flourish, a podcast brought to you by Prisma Health. I'm Scott Webb. Stay well.