Guardians of Trust in the Quest for Scientific Truth

Transcript:

Narrator: 0:01

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

Dr. Michael Koren: 0:17

Hello, I'm Dr. Michael Koren and I'm the CEO of the ENCORE Research Group, and I'm also a certified principal investigator that has been involved with clinical research for virtually my entire career and I'm privileged today to have Dr. Mitch Rothstein as part of this discussion, and we are here today to welcome you to the research family.

Dr. Mitchell Rothstein: 0:41

Hi, I'm Dr. Mitchell Rothstein and I've been with ENCORE Research Group part-time for about the last eight years. However, prior to that, I did work with ENNCORE Research doing clinical research studies out of my private practice for about 10 years prior to coming on board, and I'm privileged to sit here with Dr. Michael Koren, who's past president of the Academy of Physicians in Clinical Research.

Dr. Michael Koren: 1:08

Well, thank you. Thank you, Mitch. I've always thought that research is a tremendous privilege, and when you think about it, we get to experiment on human beings. So how cool is that as a physician. And how exciting is that as a scientist and how nerve-wracking that is as somebody that actually cares about what we do and knows that not only is there the potential for doing wonderful things for people, but we always need to be on the lookout for harm.

Dr. Mitchell Rothstein: 1:42

Yeah, I think one of the issues as physicians and healthcare providers in general, when you assume that mantle of responsibility, it is nerve wracking but at the same time, as you pointed out, it's probably one of the greatest achievements that I can think of you can attain is having the responsibility of taking care of other people, right. And that's one of the things that attracted me to medicine before I even became a physician.

Dr. Michael Koren: 2:09

Right. So we are thankful for that trust, but we also understand the responsibility and we're speaking as physicians now, but this applies to anybody in the clinical research realm. So if you are a coordinator or a manager or somebody that is taking on a regulatory role or a support person, we are all involved in this process of treating human beings, learning from fellow human beings, and with that wonderful privilege comes this responsibility. I like to call it an unwritten contract. So what we will do is we will conduct the research per a protocol. It's very important that if you conduct research outside of a protocol, it's unethical. We always have to lay it out, what we're going to be doing, so that the patients understand that and the rest of the world understands that, and that there's a systematic approach for how we collect the information.

Dr. Mitchell Rothstein: 3:00

Absolutely, and while you're collecting that information, you also have the added responsibility of being your patient's advocate. So, during the course of a study, if there are adverse events or if there are questions that arise or if there's a change in the protocol. That all has to be not only explained to the patient, but you have to act as your patient's advocate in their best interest.

Dr. Michael Koren: 3:22

Absolutely so. We have an unwritten contract. We have an informed consent, which is more of a written contract, but we also have an unwritten contract with the patient and that is to understand their value proposition, the reason they're involved in research and try to produce that, for the patient to deliver it so that they're fulfilled. And that value proposition may be to get relief from the suffering, from whatever their condition is. It may be getting a less expensive access to medication, ie they don't have to pay for it when they're doing research. It may be to have connection with the staff and having somebody to listen to them and getting some nurturing. It may be that they want to leave a legacy, they have a condition that has a genetic component and they want to help their kids. It may be for money. Some people do this because they get stipends and that's okay. But whatever that may be, we need to understand that and do our best to deliver it.

Dr. Mitchell Rothstein: 4:18

Absolutely. I think one of the things I discovered becoming part of the research team was that, as you pointed out, people have different motivations and I think one of the things that drove that home for me was during the COVID trials. When we were doing the COVID vaccine trials, we had a woman who was participating in the study. It was in her mid-40s and she was very excited about being in the study and I asked her you know her why she was so excited. She goes well, I'm going to be part of history, and that was her motivation.

Dr. Michael Koren: 4:52

Yeah, yeah. And finally, we're also a business and we have no qualms about that. We think we're excellent at what we do. We do it at a very high level. We are profitable. We think we're excellent at what we do. We do it at a very high level, we are profitable. And because we do things well, we hope that we actually get paid more than other people that may not do them as well. And that's the beauty of what we do is that, at the end of the day, the profits of our business are a way of recognizing the quality of our work.

Dr. Mitchell Rothstein: 5:18

That's absolutely true, and I think the same type of attitude about being meticulous about the medical aspects of the patient care also transfers into the logistics of the business of the product. The way you do one thing is the way you do everything.

Dr. Michael Koren: 5:36

They're absolutely aligned. High quality should mean better profits because, ultimately, the sponsors who pay for our work want this to be of extremely high quality. They want us to follow the protocols to the T. They want us to deliver positive experiences for our patients and ultimately find out the truth behind the data. The beauty of what we do is that we don't have any vested interest in the outcome. Our vested interest is in providing the truth. So let's get into some of the very specific details of the categories of what clinical research professionals need to understand, and I actually led a group on this at the Academy of Physicians and Clinical Research a number of years ago.

Dr. Mitchell Rothstein: 6:20

Yeah, published a paper. Yeah, there we go.

Dr. Michael Koren: 6:21

Thank you, yeah and the FDA has actually looked at it and they love it and everybody should know about the paper. We can show it to the camera here and hopefully it's something that you'll read at some point. It's primarily directed at physicians, but the lessons apply to everybody. So the categories, let's get into that.

Dr. Michael Koren: 6:41

So let's start with ethics and subject protections, number one.  So give us a little backround on your role as an investigator. And what that really means.

Dr. Mitchell Rothstein: 7:02

s an investigator I think my role in any give interaction or study centers around the first priority, which is establishing informed consent with the patient. So the patient needs to understand what study we're doing, why we're doing the study, possible advantages to them or disadvantages to them that come with the study, and the fact that they have free will as to whether they want to participate in the study or not, and that they understand all these things and that they can sign consent for that and participate in the study with an open mind and knowing that there is no coercion involved, that they're in control of what goes on.

Dr. Michael Koren: 7:40

And there's visibility in terms of what the expectations are.

Dr. Michael Koren: 7:43

Absolutely so we're going to lay out in the informed consent process and the form that this is what the expectations are at this time period, this time period and that time period.

Dr. Michael Koren: 7:52

So, to your point, everything that we do with patients is based on that informed consent and, from the employee perspective, everything is based on these ethical principles and informed consent is one of them.

Dr. Michael Koren: 8:04

Free will, of course, is a big part of what we do and informed consent is one way for patients to show that they're going into that with free will. But there's some other elements to it as well and we always have what we call respect for persons, which is an ethical principle that we understand when patients are having issues and we do the best we can to accommodate those issues within the strict confines of a protocol, and sometimes that creates a tension. We also know that a part of our ethical obligation and a regulatory obligation is to make sure a third party can review the research, which is why we have IRBs Institutional Review Boards that look at each protocol and have to approve it. They have to approve the informed consent, they have to approve advertising and they have to be aware of certain things that may happen during the course of the study that could change the risk of the study with regard to patient risks and responsibilities.

Dr. Mitchell Rothstein: 9:03

Right, and I think it's also important to know that every study that's presented to our group has to pass the smell test. So if we don't think a study is valuable to the medical industry or to the patient population, we're not going to participate in it.

Dr. Michael Koren: 9:24

Right. So as a person, maybe on the regulatory side, you need to know what type of things are communicated with the IRB. As a coordinator, you need to understand all the elements of informed consent. You also need to know what to do under unusual circumstances. So say, for example, somebody has a situation where they become incapacitated while they're in a research study. Do they continue in the study? Who makes decisions for that person? So there's a multitude of issues that get into these ethical elements and also subject protections, meaning that there aren't any risks that are knowable, that we don't share with the patients. Okay, number two is regulatory and operational excellence. We are a highly regulated field and we will be looked at based on how well we comply with all these regulations.

Dr. Mitchell Rothstein: 10:12

Yeah, there's a whole department of the government that only operates to regulate us.

Dr. Mitchell Rothstein: 10:17

There you go department of the government that only operates to regulate us. So we have thousands of tax-paid employees that are looking over our shoulder to make sure that we do things the way the protocol is designed to get results that we know will then be reliable and be a benefit to our patients. So part of our excellence. Our pursuit of excellence involves making sure that we don't leave room for any regulators to find error with what we do. So we try to follow every item to the letter and not leave room for any discussion.

Dr. Michael Koren: 10:55

Correct. There are two major pieces of jargon that everybody should know. Number one is what's called GCP, or Good Clinical Practices, and that's all the government regulation that applies to how we conduct clinical trials. So things like adverse event reporting, make sure that an IRB is involved, retention of patients, retention of records all these sorts of things are covered under GCP. The other one is 21, CFR, which is the actual Code of Federal Regulation CFR, Code of Federal Regulation and 21 is the whole section about food and drugs. So just so you know, the whole government runs under a bunch of rules. The first rule, number one, is about the presidency and we're down at 21, food and drugs, but you know, at least we're in the top 25. So those are all the things that regulate and again, our discussion isn't about every single rule, but just understanding that we fall under all those rules. Right, Okay, number three scientific knowledge. At the end of the day, we're doing research. That involves things like statistics. It involves therapeutic areas. You can mention your therapeutic area.

Dr. Mitchell Rothstein: 12:17

So I'm a specialist in sleep disorders, pulmonary and critical care medicine and, as you said, in all these different study areas, we need to have some oversight from people that do have expertise in these areas to make sure that what we think we're collecting data for is actually going to prove to be factual information that will help our patients and not just side information that doesn't really amount to anything in terms of improving patient care.

Dr. Michael Koren: 12:47

Right. So, again, depending on who's listening to this, they may have different roles in terms of scientific knowledge, but, as a simple one, if you're in a situation where the physician support or the ancillary support it could be a nurse, practitioner or somebody else that has sort of content expertise if that doesn't match with the protocol, then you have a problem. So you, as a pulmonologist, probably wouldn't be doing studies that involve gynecology. You know simple things like that, and this is one of the elements of scientific knowledge so that the principal investigator, who is ultimately in charge of the study, can put their scientific knowledge into effect when necessary to answer questions that will come up during the course of a patient's participation.

Dr. Mitchell Rothstein: 13:36

Yeah, and the studies that I initially participated in were insomnia studies, which was a natural fit for me as a sleep specialist.

Dr. Michael Koren: 13:44

Correct. Number four is patient care. So, even though we're following a protocol and we're not technically the providers for the patients, there are still patient care elements to what we do.

Dr. Mitchell Rothstein: 13:57

For example, we had a patient that presented for a study involving a heart failure medication and at the time of their presentation, one of their laboratory numbers was way out of line. So, in terms of what our responsibility was in providing adequate protection for the patient and medical oversight was, we had to follow that up and figure out why that lab value was so out of whack and how to remedy the situation for the patient and ensure that it didn't provide any risk to the patient.

Dr. Michael Koren: 14:32

Right, exactly, and these things come up all the time. Let's say, a patient's doing great in a study but has one side effect. You're not sure if it's related to the study or not. Do you stop the study? Do you give them a medicine to mitigate the symptoms that they're complaining about? One of our famous cases is somebody that's in a hypertension study. One of our famous cases is somebody that's in a hypertension study and is doing really well in terms of blood pressure control never had their blood pressure controlled so well but has a side effect. Well, do you let that patient drop out? Do you encourage them to drop out, or do you try to explain to them what's good? What's happening is actually favorable and maybe you want to stick with it for a while.

Dr. Mitchell Rothstein: 15:08

So these are all patient care issues, and the other part of that, too, is that you. I think one of the things we pride ourselves on is ensuring that the patient's primary physician is also aware of anything that develops during a study that might impact the patient's long-term care, absolutely, absolutely.

Dr. Michael Koren: 15:25

And then finally five is leadership and business management. So what I like to tell people is that you could be the best researcher in the world and do wonderful things for your patients, but if the cost of running that study is five times more than what you get paid, you're not going to last very long, right? So your wonderful services will be for naught. And sustainability of the business model is also very, very important. So how does that translate? Again, any place in the organization, if you can save costs for us, that's great. Obviously, if we need to spend money to do things right, we're happy to do that. On the other hand, if there are two alternatives and one is less expensive, we'll use the less expensive alternative. Also, being efficient with your time is very important, and, as a basic principle, we know that the first patient that does a study costs the organization way more than the 10th patient and way more than the 50th patient, because as you do things, the more you do it, the better you get at it and it becomes more efficient.

Dr. Mitchell Rothstein: 16:23

Yeah, and I think part of that experience also is the customer service aspect. So as a business, I think probably compared to any other industry, our customer service far exceeds the level that any other industry model would have. And that's reflected in that our patients that once they participate in one study, 99% of them want to participate in another study.

Dr. Michael Koren: 16:48

And great point and that customer service of course has to be balanced with making sure that they're participating in the protocol, because ultimately that's how we get compensated. So when we sign contracts with sponsors, we're signing a contract to produce data that they can then ultimately present to the FDA or other authorities, and so if we never get to the point of producing the data, all that good work is lost. Right, absolutely so. In any event, this has been a great conversation. Thank you for listening.

Narrator: 17:19

Thank you. Thanks for joining the MedEvidence podcast. To learn more, head over to MedEvidence.com or subscribe to our podcast on your favorite podcast platform.