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Welcome to the MedEvidence! podcast, hosted by Dr. Michael Koren. MedEvidence, where we help you navigate the real truth behind medical research with both a clinical and research perspective. In this podcast, we will discuss with physicians with extensive experience in patient care and research. How do you know that something works? In medicine, we conduct clinical trials to see if things work! Now, let's get to the Truth Behind the Data. Contact us at www.MedEvidence.com
MedEvidence! Truth Behind the Data
Evidence and Ethics in Healthcare Research with Dr. Zeke Emanuel Part 2 Ep 330
The conversation between Dr. Michael Koren and Dr. Zeke Emanuel continues in part 2. Bioethicist Zeke Emanuel dives into the unethical Tuskeegee study and landmark Belmont Report in 1979 and how many safeguards to clinical research are currently in effect. They doctoral duo also talk about how in spite of the potentially off-putting document-heavy nature of current clinical research participation, it is still a good care option and a moral obligation for those who benefit from the fruits of medical research.
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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:We'll definitely have to bring you back to dig into those really important questions in a much more detailed manner.
Dr. Ezekiel Emanuel:I have absolutely no hair.
Dr. Michael Koren:Yeah, but I want to spend the rest of our time together focusing on the ethics part of the equation right now, and we talked about the Belmont Report and I've been interested in that as well.
Dr. Michael Koren:I'm a cardiologist and certainly somebody that's done a lot of research but also been really interested in all these ethical tensions that occur in the clinical research realm.
Dr. Michael Koren:And, just for everybody's knowledge, the Belmont Report came out in 1979.
Dr. Michael Koren:There are three overarching principles, which is Autonomy, or what we call respect for persons and that's actually changed over the years, which is kind of interesting and this is the concept that all consent for study should be free consent and, for people who may not have full autonomy or full knowledge, that we help them appropriately. Then we have Distributive Justice, which is that the burdens or the risks of research can fall on the same people all the time. And then we have Beneficence, which is our responsibility to try to make all the research studies as beneficial as possible and to reduce risk for the patients as we design them. So those are the three basic principles and the reason I'm bringing those up is because we're super interested here in MedEvidence of the concept of research as a care option, and you and I were just talking about before, when we say that it's fundamentally different than research as a treatment option. So maybe I know that you've done some work in this area, so maybe you can educate us a little bit more on that distinction.
Dr. Ezekiel Emanuel:Well, this is actually one of those interesting areas where, you know, I looked at the Belmont report and I thought, you know, and in 79, laying out those three principles was very important, but I think they didn't get it quite right. And part of what one of my most famous, most highly cited let's put it that way, articles is what makes clinical research ethical, and we delineated that there are seven principles that you actually have to do. One is there has to be social value to the research. You know, if you don't disseminate your results, if you don't make them available, if it's not answering an important question, you shouldn't be doing the research. It's got to be scientifically valid. Are you going to get it, are you designed it to get it, A real answer, because if you're doing a randomized trial of 20 people and you know you don't have some whopping big effect, the data is going to be garbage and you can't put people at risk for no scientific advance
Dr. Michael Koren:Right.
Dr. Ezekiel Emanuel:Third thing is to fit to, as you put it, the distributive justice one. You have to choose fairly the people who are going to participate. You can't say, for a super beneficial study, heavily get people who are well off or connected to the board or whatever, and for a highly risky study, get only people who are minorities or low income or low education. And then you know you have to have a review, independent review, because as researchers we're always biased for our research. So you need an independent review. We have an IRB system. Doesn't have to be that system, it does have to be independent. And then you have to have informed consent. And then we added the last one, which is look, people participated in research. You have to disseminate that and you have to inform them what was learned. You can't just forget them. So all of these are really important. One of the things and again, you know, being trained as an oncologist, it was sort of at the Farber mother's milk that you know that clinical research is the best way to go and we were always trying to see why that people should get on research studies. And there are good reasons to think about it. It's standardized. Some of the smartest people in the world have worked on developing a protocol so that you know you are getting good standard of care and you're getting all the right tests and treatment. And there's people looking at your situation there's people looking at the data to make sure that nothing's going awry. So I think that there's a lot of positives there. Actually, thinking about your point that you made at the start, I think you know it led me to write a paper which I talked about people's obligation to participate in research.
Dr. Ezekiel Emanuel:When the Belmont report was written, a lot of that was like protecting people from research. Why did we end up with the Belmont report and the whole presidential commission? Well, we ended up with it because of a scandal, the Tuskegee scandal, and this was the response to the Tuskegee scandal. To try to make sure it wouldn't happen again, we'd have bioethicists thinking about all the ethical issues and that framework right. Research is dangerous, research is risky, research is going to hurt people is what led to the Belmont report and the regulations. And my view is we, because of the Tuskegee, largely because of the Belmont we did put in a infrastructure, including IRB review, including informed consent, to protect people.
Dr. Ezekiel Emanuel:But once we had that structure, we could be pretty confident that research was safe. And again, it also meant that all of us who take a pill every day we're the beneficiaries of that research right. That pill has been shown to be safe and effective and so we benefit by someone else having participated in the research. I think that actually gives us an obligation as people to actually participate ourselves when the opportunity presents itself. And I think we have. We, the bioethicists, the medical community, spend so much time trying to protect people. We haven't thought about our obligation to participate in ethical research. Now, it has to be ethical. It has to have a risk benefit ratio where the risks are appropriate to the benefits. It has to be that people are fairly selected, it doesn't target one vulnerable group, etc. But if it fulfills all that, we do have, I think, an obligation which we don't talk about in America, very much.
Dr. Ezekiel Emanuel:We don't say it.
Dr. Michael Koren:I think those are amazing points and I like the emphasis on encouraging people to be part of research, but not only for societal benefit, but also for personal benefit.
Dr. Ezekiel Emanuel:Yeah I always think it's a 2-for-1. It's good for you, but its good for people around you. And by the way, since many of the things we research. Have, you know, a family
Dr. Ezekiel Emanuel:lineage relationship or raised in the same environment. You may in fact be benefiting your family by what you do, because you advance the science and knowledge of some condition or disease or a genetic disorder, and that's all very, very important, I think.
Dr. Michael Koren:Yeah, there's a really interesting nuance in the Tuskegee scandal. I want to get your take on this, which is as you know, but I'm articulating this for the audience. This is a study that started in the 1930s let's look at the natural history of syphilis when there really wasn't any treatment for it, and this study continued for close to 40 years until there was an expose in the Washington Star that talked about how this research was going on and the men about 400 black men, who are uneducated were not told about their participation in research, and this happened for over 40 years, and this is, of course, quite scandalous. It's horrible, it was exploitative, but there's another side to it that's interesting. One is that there was actually a lot of learning from it. So, while we've apologized to these men that participate in the study, we've never thanked them for being in the study. Thank you for allowing us to learn, and we've never done that, and I think that's a miss.
Dr. Michael Koren:The other thing is that it's an interesting dynamic between racism and socioeconomic issues. So the Tuskegee study was actually performed at a traditionally black university, tuskegee, and during the course of this 40 years, the government was very involved, by the way, doing some horrible things, like, for example, when members of the Tuskegee study group were drafted into the military, they were not allowed to get penicillin shots because it would mess up the study. So that's just absolutely horrible. But the government also was in consultation with African-American groups during this whole discussion. So as late as 1969, the CDC evaluated the study and felt like it should continue under the current rules, including consultation with black physicians.
Dr. Michael Koren:So here again is this concept that has been, I think, somewhat misunderstood by the general public, that this was a socioeconomic gulf between the physician community, the medical community and people who are not educated. And we've made a lot, a lot of progress, as you point out, with IRBs and informed consent forms, et cetera. In fact, if anything, we may be going overboard, because when you have a 35-page consent form that changes every week, you're not going to necessarily be communicating with people that have less than a high educational level, and so, when you think about these things, they're ways of excluding people who are in lower socioeconomic classes from participating in something that's not only important for society but important for them in terms of both direct and indirect benefits, including being in a medical community, having really good, ethical, smart people looking out for you and then knowing how to navigate the health system, because you have somebody that's helping you in a very complex set of rules that we all have to navigate. So I don't know your reaction to that, but I'm curious to hear it.
Dr. Michael Koren:So I don't know your reaction to that, but I'm curious to hear it.
Dr. Ezekiel Emanuel:So I think that there's some controversy over whether the study ever -needed, was beneficial the sense of adding to scientific knowledge, even in the '30's. Because there was a fair amount of understanding of the natural history of syphiis, and part of the idea was, well was a natural history, and this is where I think some of the racism, even at the start, came in: was the natural history different in black men than in whites. And so I think there is some controversy on whether in fact, from a scientific standpoint, it needed to be done. It was quite clear that when penicillin became widely available and effective against syphilis, that it was consciously and explicitly withheld. That is clearly unethical.
Dr. Michael Koren:That's absolutely horrible.
Dr. Ezekiel Emanuel:No justification for that. And that is 20 years before the whole thing, easily 20 years, maybe more, before the whole thing ended, as you say, on an expose by one of the staff members who was upset by the situation. It also did, as you point out, it was done in conjunction with African-American leaders and physicians in the community and that you know that power dynamic, socioeconomic dynamic, education dynamic I think was problematic and there was no one who was necessarily looking out for the sharecroppers who were enrolled. And I do think you know one of the problems that has resulted, and I think you point out very well, is you know we now have this apparatus and infrastructure to protect people through IRB review and informed consent and it's, you know, one of the reasons I launched a revision of the regulations is it's become encrusted, nothing sticking around. And you point out one of them. Our informed consent arguments are way too long for what they do.
Dr. Ezekiel Emanuel:They're written at an average 11th grade level. They have way too much boilerplate. It's part of the area I've done a fair amount of recent research in getting back into this informed consent thing. I've shown that, for example, the COVID vaccine informed consents were 40 pages, outrageous, and you could reduce hundreds of words to a short sentence. We have worked with a couple of drug companies that are very interested in trying to reduce their informed consent form text; and make it more readable and bring the age down of the reading level down so that they could get more people involved. It does you know, when you have a big document like that, it intimidates people, or they simply ignore it and just trust whatever they're told about it from the doctor or from the nurse who is telling them about the study. That's not exactly what you want.
Dr. Michael Koren:Well, it sends the wrong impression. So if it requires a 40-page document for you to be in it, you think, oh my God, this must be incredibly risky, what am I signing up for? And, quite frankly, there's really no way to assess the true risk within those 40 pages.
Dr. Ezekiel Emanuel:Well, again, one of the things I've long argued is look if you have an IRB that's well-functioning. The main thing that they're really got to be entrusted with is the risk-benefit ratio, the right risk-benefit ratio.
Dr. Ezekiel Emanuel:Do we have enough knowledge. That's not to say you know things can turn out to be risky, even though an IRB approved them. That's why we're doing the research, because we don't know the full measure of the risk or the benefits. But you have the value of an independent group looking at this and assessing the pluses and minuses of that research study, by the way, which you don't have in regular clinical medicine. Not everything in clinical medicine has been tested to the degree that drugs have been tested.
Dr. Ezekiel Emanuel:That's one of the big problems, I think, is we have a very uneven system. The devices don't have to go through the same rigorous, randomized, controlled trials and things like that. So I think we've overdone it in the 45 years since the regulations have been written and I think we need a fresh examination. But this is like many things once you write it down and it becomes institutionalized, it gets very hard to reform things and people have sort of standard operating procedures which are not necessarily conducive. And again, a lot of that is built on the idea that, well, research is really risky, well, life has got some risks and we've got to put it all in context, and that's actually one of the things I've written a lot about how do we compare the risks of research with the risks of everyday life. It turns out, given the risks of everyday life, turns out, given the risks of everyday life, the big one for most adults, driving. The big one for kids other accidents, drownings, things like that, and so playing sports also.
Dr. Michael Koren:You're much safer in the research office than you are out living in the world.
Dr. Ezekiel Emanuel:It's one of the important points and I think we don't sufficiently make that comparison. Well, how risky is everyday life? We just assume, you know, we become habituated to the risk. Every time you put your key in that car, what's the chances that you might? You know, chance are about one, and I think it's one in a hundred, of being in an accident every year, and I forget all the data, but it's not trivial.
Dr. Michael Koren:Sure, no, absolutely so. Would you have a family member do research?
Dr. Ezekiel Emanuel:Oh, I do research. So, um, um, my kids were raised with, uh, lots of talk about medicine. They went off to college, Every one of them participated in clinical research studies. \I every year participate in a flu vaccine study. They take out a large amount of my blood after the vaccine. I participated in MRI studies. I participated in studies about concentration and shocks. I even got that protocol changed. I'm not shy about talking up. I've tried to get into a variety of cardiology studies because I have a high cholesterol, but it's high because my HDL is very high.
Dr. Michael Koren:That's good!
Dr. Ezekiel Emanuel:I never qualified for those studies and so, yeah, I think again. I have the view that you know we're all the beneficiary of people who've enrolled in clinical research. We ought to do it when we can.
Dr. Michael Koren:Do you feel cared for in those studies?
Dr. Ezekiel Emanuel:Yeah, I feel look, I will actually tell you what I do is I feel like I'm making my small contribution to making healthcare better in the future.
Dr. Michael Koren:Yeah, and again, just to sort of reiterate my point, when doctors talk about treatment, it's what we know, that you're getting as part of a plan to create some therapeutic benefit based on what we know or we think we know, whereas in research we don't know that usually, and so what we can provide is just that being a part of a community learning about your health condition, hopefully identifying other things that may help you live a better life, for both yourself and your loved ones.
Dr. Michael Koren:So, there's lots of elements of care that are separate from the treatment elements, what we do as physicians.
Dr. Ezekiel Emanuel:Absolutely. I mean treatment's only one. As you point out, treatment's only one very small part of what medicine is about.
Dr. Michael Koren:Absolutely, absolutely. So, This has been a great discussion. I've enjoyed every minute of it. So just to kind of summarize, what's your view for the next five to 10 years for yourself professionally, and what maybe you predict for us in terms of the research world?
Dr. Ezekiel Emanuel:Well, I'm going to keep working, keep writing. I've got after the book I'm working on right now. I've got two more ideas, one of which is about how to retire. I think we do it Well. One of the things I've become very interested in is the impact of what we do during retirement, how that affects dimentia, cognitive decline, what we do, how we could do it better. I think many people could use advice about how to do it better. I think there are certain things that we're discovering that can, if you do it right. One of the problems is we often just retire instead of retire with a plan. I think everyone needs a plan for retirement. Anyway, that's another book.
Dr. Michael Koren:Well, you had a plan in medical school, so I'm sure you'll have a plan for retirement.
Dr. Ezekiel Emanuel:Then I've got another book after that, so that'll take me to 75. And then, who knows?
Dr. Michael Koren:Well, that's one of your controversial statements, I think. If you want to address that, one of the things you're known for is I think people maybe have misinterpreted that, but the general interpretation is that Zeke Emanuel thinks you hit 75 and just hang it up and you go out to pasture and never come back. So maybe you can address that statement
Dr. Ezekiel Emanuel:You're 100% right.
Dr. Ezekiel Emanuel:That's very wrong interpretation. So the title of the article is called why I Want to Die at 75. It was in the Atlantic 11 years ago, in 2014. As I like to tell people, you don't, as an author, you do not choose your title. That is left to the editors and publishers. Your interest in accuracy and their interest in selling a lot of magazines are not necessarily conjoined, right, and this is one where I did fight hard about that title and I lost.
Dr. Ezekiel Emanuel:Yeah, my philosophy is that I don't want life-saving like cancer chemotherapy after 75. I don't want an intervention where the purpose of the intervention is to prolong my life. On the other hand, if you know, I was in it. This happened to a friend of ours, which is why it's hot on my mind. But if I was in a ski line and someone came and barreled into me and knocked me down and I broke my hip, I would want that hip fixed. If I get cataracts, I want those cataracts replaced, even though they're not going to save my life. So I want to live a full life. I think I'm still living a pretty full life.
Dr. Ezekiel Emanuel:Uh, you know, two days ago I went out and rode 25 miles. Yesterday rode 15 miles on my bicycle pretty good clip 17 miles an hour. So, um, I'm very active and I try to do new things. This coming weekend I will harvest my honey from my beehives. So the problem at 75 is that if you look at the data, you know cognitive decline goes up, alzheimer's risk goes up, you know the wheels begin to come off the car, our functional capacity goes down, we lose a lot of muscle mass. You have to consciously maintain your muscle mass. I'm not planning to retire and hopefully cognitive decline won't afflict me. Um, but it does take um. You know there is a a very clear um inflection point at about 75. Is it true for everyone? No, a lot of people say, well, if it were just 80?
Dr. Ezekiel Emanuel:well, yeah yeah, the fact is 75, when it goes up like a hockey stick, um, and all of us think we're going to be outliers. I'm a little more sober about that. Not everyone can be an outlier. I'm talking about averages. Yes, there will be some outliers. I have done I taught a course and created a video on Coursera about Benjamin Franklin.
Dr. Ezekiel Emanuel:I think he's the most remarkable person ever born in an America. He was excelled at all sorts of things and he was an outlier. Everyone talks about his inventing bifocals. He was 79 when he invented bifocals. Not many people are inventing something that sticks around for 250 years in their 79th year and after that he still had more inventions that you know about the arm to lift up and grab something from a high shelf. Ben Franklin, he needed to grab his books. Anyway, he is a model, but not all of us are going to be like that, and so we have to think about what happens when we're not going to be there, and that was the point of the book. I told people my philosophy. I wasn't saying everyone should adopt my philosophy, but everyone should have a philosophy and they should think about a philosophy and they shouldn't just have it come upon them.
Dr. Ezekiel Emanuel:I don't particularly endorse, and I would argue with anyone who has a sort of what I call the Silicon Valley view of life, which is I got to live forever. What's the world going to be if I die? Yes, the world will continue, I can guarantee that, and I think trying to live forever is got it. You know, excuse me, but ass backwards. Right, the point is to live a rich life, right? If you make the focus of your life living forever, there's no content to it, there's no meaning, there's no fulfillment to it, and that, I think, mistakes what we are on this planet to do. We're on this planet to make the world better, to make our loved ones better people, to make ourselves better people, and not to just live forever.
Dr. Michael Koren:Well, speaking of Benjamin Franklin, there's a quote, I believe, from poor Richard's Almanac that is attributed to Ben Franklin, that the goal of life should be to live well, not necessarily live long. So that gets your philosophy. Although he did both, quite frankly, he lived long and he lived well. But I'd also argue that there are lots of people that make amazing contributions well into their 70s, 80s and even 90s. You look at people like Warren Buffett.
Dr. Ezekiel Emanuel:You and I may disagree.
Dr. Michael Koren:Yeah, so my brain works just as well now in my 60s as it did in my 30s in some ways better, and if I extrapolate that, it should be working really well by the time I get to 90. And so we'll see.
Dr. Ezekiel Emanuel:We'll revisit that in a few years.
Dr. Michael Koren:Yeah, we'll definitely do this again in about 10 years and we'll see if our views have changed. But again, I think that we're a wealthy country. We can support people. I think perhaps a little bit beyond the 70s and quite frankly, to your point.
Dr. Ezekiel Emanuel:No, no, no, Wait, wait, wait, wait. This is not about wealthy countries supporting people. This is about your personal philosophy. It has nothing to do. Even if you're magnificently rich, you'll support yourself. Blah, blah, blah.
Dr. Michael Koren:No, no, I'm talking about society, your philosophy, like contrast. As you know, in Great Britain, for example, there are limitations of what treatments are performed at certain ages.
Dr. Ezekiel Emanuel:Well, we know that in the United States it's the same thing, even if it's not a policy doctors, they don't admit 80-year-olds with the same thing as 70-year-olds to the ICU, et cetera. So I'm not sure I agree with that. Yes, we don't have a formal policy, but we have practices that people have imbibed, and you know it's anyway. And my article is not about public policy. It's very, very firmly in challenging each of us to have a personal philosophy about how we want to live, how long we want to live. You know I ask this all the time when I talk. You know you want quantity or you want quality of life. Oh, we all want quality of life. And then you talk to them and you know they just haven't thought through what that might mean. And when we get to that, you know the default of the system is quantity over quality.
Dr. Michael Koren:Easier to measure quantity versus quality.
Dr. Ezekiel Emanuel:Yes 100%.
Dr. Michael Koren:Yeah, so fair enough. Well, Zeke, this has been an amazing conversation. Thank you for being a guest here on. MedEvidence and it's been my absolute pleasure and hopefully we'll do it again very, very soon and you can share some of your amazing insights with us.
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