Why Being in a Clinical Trial May Reduce Your Medical Risk

Announcer: 0:00

Welcome to MedEvidence!, where we help you navigate the truth behind medical research with unbiased, evidence-proven facts hosted by cardiologist and top medical researcher, dr Michael Koren.

Dr. Michael Koren: 0:11

Hello, I'm Dr. Michael Koren, the executive editor of MedEvidence!, and I'm joined today by Dr. Murali Ramaswamy, who is a clinical trial professional like myself, who is really fabulous in the pulmonary area and has developed a really interesting business concept to help doctors get more involved in research, and is a like-minded physician who's going to talk to me about clinical research and this really important concept of research as a care option. It's funny we were just chatting before we got on the podcast and he used this term, which I love, Murali I love that term, and we like to make the distinction of research as a care option versus research as a treatment option, and so let's dig into that together and help people understand what we mean by that quote subtle difference, which is really an important difference. So please go ahead and introduce yourself to our listeners and viewers and let them know who you are, what your background is and how you got involved in clinical research.

Dr. Murali Ramaswamy: 1:15

Yeah, hi, my name is Murali Ramaswamy and I'm in Greensboro, North Carolina. I work at Cone Health and I direct the pulmonary fibrosis program there, but I'm also CEO and co-founder of Pulmonix Clinical Trials. I've been doing this for 10 years now and my specific interest on the clinical side is pulmonary fibrosis, as I mentioned. But I really love clinical trials because of the fact it's a care option for patients, but also because it helps really transform the clinical care in communities in ways that communities that don't have research or health systems that do not have research are not able to, and that's really my passion in my career.

Dr. Michael Koren: 1:59

Yeah, so I'm going to unpack some of those statements for everybody who's listening in

Dr. Murali Ramaswamy: 2:04

Absolutely.

Dr. Michael Koren: 2:10

And as I think you know the concept of MedE vidence!, You have two knowledgeable physicians talking about a topic and people glean insights from that discussion and it's a very open and honest discussion where we don't particularly have an agenda, but everybody can then apply that learning to their own individual circumstances. So when you talk about research as a care option, we like to make the distinction. It's not research as a treatment option, for the very basic reason that we don't know what treatment you're on. However, we do know that there'll be a caring environment and that people that get involved in research are more likely to do other things correctly in terms of their healthcare. Plus, they have resources who they can talk to about the questions that arise. So I know what's been your experience, or you can give us an anecdote or two, that kind of show that particular element of what we do as researchers.

Dr. Murali Ramaswamy: 3:00

Yeah, thank you. This is a really, really key point. One of the first things that I learned in my journey as a clinical trialist was this concept of therapeutic misconception, and oftentimes I would meet patients or I would meet other colleagues in my specialty or other specialties who would say well, we're treating this patient with a clinical trial, or you can get this treatment ahead of time, before it's approved. And I found that really puzzling and I actually found it a little unethical too, because it's one, it's not approved. Two, you could be getting placebo. Three, the probability of harm is actually higher than an approved drug, so there is risk involved, and so I really felt like this is not a treatment.

Dr. Murali Ramaswamy: 3:48

On the other hand, when somebody gets consented correctly and enrolls in a clinical trial program, they get the attention of physicians, they get the attention of care coordinators, they're getting blood work, they're getting pulmonary function tests. In my case, they get EKG scans. All those things can be valuable to a patient in terms of their health information, and by keeping these follow-ups they have a certain level of attention and there's also information that is garnered that can in turn, help their care.

Dr. Murali Ramaswamy: 4:23

So that's one piece where I think clinical trial participation can really help these patients. The second piece, of course, is the main motivation is to advance science, and so when we talk to our patients, we're always very clear cut as to the motivations as to why they should be in a trial, regardless of the phase. Certainly, later the phase, phase three, they can potentially have some therapeutic misconception, but earlier the phase, for sure, they're there because they want to develop science and maybe get some data for themselves, and so that's why I believe research is a care option and not a treatment option. Thank you for that. That's an important distinction.

Dr. Michael Koren: 5:04

So I agree with about 90% of what you said. There's 10% that I don't agree with and let me explain why. Okay, so you're absolutely right is that we don't want to call it a treatment option, because we just don't know what treatment you're on. In many cases for any placebo-controlled study, we just don't know. So we never want to give that misconception. Therapeutic misconception is an important concept because we don't know what you're on,

Dr. Michael Koren: 5:30

It could be placebo, but it doesn't mean that we don't promote the core values of that particular area. So, for example, as me as a cardiologist, when somebody is doing a cholesterol program that's using a novel agent to lower their triglycerides or their lipoprotein layer of cholesterol, I'm still reinforcing that they should take their statin drug and as part of that, we are reinforcing their treatment while we're studying a specific nuance of the treatment. And just that person being in the trial and getting that reinforcement is actually something that lowers their risk. You said that the risk is increased, but I actually think it's probably lower for two reasons. One is because we're reinforcing good behaviors. But the other thing is that when you're in a clinical trial, you're discovering side effects earlier. So even if when you use an approved product, you can have a side effect for months and months and months and months and no one's really looking at it to cut off the period of exposure to that risk or that side effect, whereas in a clinical trial we find it right away.

Dr. Michael Koren: 6:39

Not only do we find it right away for the individual patient, but we're collecting data all over the world, so we're finding it collectively for all patients. So if there's a subtle side effect that somebody should be looking out for, we have a system to identify that, and I'll make one other point. One other observation is that some approved drugs did not undergo the scrutiny of the current clinical trial environment. So one of the things we like to joke about in cardiology is that we have a 200-year-old drug in digoxin.

Dr. Murali Ramaswamy: 7:11

Absolutely

Dr. Michael Koren: 7:12

Never really went through clinical research. That is actually a pretty dangerous drug if you don't use it correctly. And so we actually have much more safety information about current drugs than older drugs, and a lot of current drugs or even drugs in clinical research are actually less likely to have side effects compared to stuff that's been on the market for a long time. So a lot of nuances in that, just to point that out.

Dr. Murali Ramaswamy: 7:37

Yeah, I agree with you on that. I think that's about risk control and I think clinical trials absolutely gives a tighter risk control with monitoring. And when I talk to patients, that's one of the things I emphasize. When they're worried about risk, I talk to them about how risk is controlled, not only through inclusion-exclusion criteria but the amount of follow-up that's involved, the amount of safety laboratory tests that are being checked. So they do feel reassured by that.

Dr. Michael Koren: 8:08

Right, so I want your opinion on this. This is a little bit controversial in our area and I love your opinion on this. So there are more and more people that are talking about the fact that when folks enroll in clinical trial patients enroll in clinical trials they're less likely to have overall medical complications, and managed care organizations are starting to look at clinical trials as a way of reducing re-hospitalizations, for example, for people with heart failure, regardless of what treatment they're on. Or they find that people have better diabetic control when they're in clinical trials, even if it's a blood pressure trial, that people just tend to comply with the things they should comply with better, and that actually reduces costs to the system and also improves overall care, even if the trial is not in the area that they're looking to reduce costs in. So I was just curious to see what you thought about that concept.

Dr. Murali Ramaswamy: 9:05

Yeah, thank you. So our health system is moving towards value-based care and this conversation has come up in the last year or so and I've struggled to find data behind that. But I'll be honest, I do not have data for it, but I've heard this conversation come up and I've also heard that when health systems have integrated research and they go for contracting with insurance companies, it's better because insurance companies love to see clinical trials. But whether the clinical trial is overall beneficial in the types of outcomes you are mentioning, I personally do not know.

Dr. Michael Koren: 9:44

Yeah, I love that answer.

Dr. Murali Ramaswamy: 9:46

I've heard this conversation. I've tried to look up PubMed and Google and not really come across anything. But, I've also heard this from my mentors in clinical trials that this to be true.

Dr. Michael Koren: 9:58

Yeah, that notion is out there and it's hard to find data to support it exactly. I don't think it's an unreasonable notion, but I think it should be looked at more formally before we start spouting this as a reason for systems to necessarily push clinical trials. But I do think it's a reasonable hypothesis and I think physicians like you can help us all figure this out and also look at the size of the effect, which is going to be important. We do know that in general, when people are involved in clinical trials, they tend to have fewer complications than would be predicted based on their perceived risk going into the trial. So one of my mentors, a famous cardiologist named Eugene Braunwald, would equip that. What he wanted to be when he grew up was a control patient in a clinical trial, because people seem to just do better when they're in clinical research. So that was another way of saying that and it's a notion that we believe in, that we have some data to support it, but, to your point, it's still a little speculative.

Dr. Murali Ramaswamy: 11:06

Yeah, I would concur.

Dr. Michael Koren: 11:07

Yeah, and then the kind of final thing I wanted to touch on during the time we have together is a little bit about your business model, and so why don't you help people understand, because I think it's kind of a neat little business model that people should be aware of.

Dr. Murali Ramaswamy: 11:21

Yeah, thanks for that question. So from a business perspective, the niche that we would fall under is what today is commonly called integrated research organization. Obviously, that term is very new relative to how long we've been doing research. So our business value prop, if you will, would be that on one side you have clinical trial sites that are agile, that have good domain expertise in running business has good margins, they're efficient, they understand GCP.

Dr. Michael Koren: 12:01

And that's good clinical practices for people out there.

Dr. Michael Koren: 12:03

That's the.

Dr. Michael Koren: 12:04

FDA rules on how you conduct research.

Dr. Michael Koren: 12:06

Sorry to interrupt you,

Dr. Murali Ramaswamy: 12:07

Yeah no, that's fine, but I think their weakness is being able to integrate research as a care, because they're not part of health systems, they're not part of clinics in general, and so that element as a physician, to me that element is really critical in being able to integrate research into the care plan. So on the other side are the big health systems that are bogged down by bureaucracy and they're very inefficient. They can be risk averse for example, delayed startup times. These things can really impede efficient research. They also add to the cost of drug development and I believe somebody like us who's integrated with the health system and who is independent can bring that efficiency, that somebody who is like a private trial site and can bring that efficiency into the health system and be able to execute trials and at the same time take away financial risk from the health system. But obviously research has good regulatory oversight from IRBs and FDA and the sponsors, so risk is controlled for the health system. So that's sort of a value prop and that's the sort of niche that we occupy in providing value for the health system. And the health system sees our benefits in two ways. Obviously, the direct cost when we use their services. That's very tangible.

Dr. Murali Ramaswamy: 13:47

But the biggest intangible benefit has been our presence has changed the face of our clinic, the pulmonary clinic, for example. When I started with pulmonary fibrosis 10 years ago, only 1% of the entire pulmonary clinic was pulmonary fibrosis. In the last 10 years, the volume of pulmonary fibrosis patients, without any marketing, has grown on an average 24% each year year over year for the last 10 years. Pulmonary fibrosis is now 7% of our pulmonary clinic. Patients don't go to other health systems.

Dr. Murali Ramaswamy: 14:21

Nearby is Duke, Wake Forest, Chapel Hill. They stay in the community. Occasionally we get patients from you know, out of our community as well community. Uh, and likewise, one of my colleagues is doing pulmonary hypertension work. Another one is doing some lung cancer screening work. They've all seen explosive growths in their clinic. Uh, just by the mere presence of research and uh, yeah, we are recognized as a center of excellence for pulmonary fibrosis. So there's, those are the kinds of benefits a health system is able to derive, and I believe the health systems, because they have to focus a lot on CMS and taking care of patients, might not have the core competency to do research well.

Dr. Michael Koren: 15:06

Understood. How does your day-to-day breakdown work between research and clinical practice?

Dr. Murali Ramaswamy: 15:12

Yeah, that's a great question. So right now I'm like 25% towards research, both as an investigator and as an administrator, and that risk is on my own and I would say that I'm really happy doing that. But that time is not enough. I probably have to scale my clinical down by another 25% at this point.

Dr. Michael Koren: 15:34

Yeah, yeah, I've learned that over my career that as you get more involved in research, it becomes something that you really have to dedicate time to, to get to the next level, the next level, the next level and finally, I love your logo. Who designed that?

Dr. Murali Ramaswamy: 15:47

Oh, it was my ex-brother-in-law in Minneapolis, but he's really good.

Dr. Michael Koren: 15:54

We might have to steal his talents. That's a pretty cool logo.

Dr. Murali Ramaswamy: 15:57

I'll make the introduction.

Dr. Michael Koren: 15:58

All right, Sounds great. Dr. Ramaswamy, thank you for joining us in MedEvidence. I enjoyed speaking with you and I hear we'll have some time together here in Jacksonville in the near future to talk some more. So thank you for enlightening our listeners and viewers and best of luck in your business.

Dr. Murali Ramaswamy: 16:14

Absolutely Looking forward to meeting you and spending time with you. Thank you, Dr. Koren.

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