Announcer:
0:00
Welcome to the MedEvidence podcast. This episode is a rebroadcast from a live.
Announcer:
0:05
MedEvidence presentation.
Dr. Michael Koren:
0:07
So the genesis of this particular session came from our weekly Monday morning meetings. So we have a business meeting every Monday morning, starting at nine o'clock, and what we usually do is we look at the state of our company and then we look to see what's going on in the world and making sure that's not going to affect our company and then dig in a little bit more into what we need. To get the word out about research as a care option, which is really our mission, is to let as many people as possible know that clinical trials and research is a great way to get medical care. Obviously there's some restrictions about it, but there's some really nice things. For example, you never have to pay anything. Often you get paid, you get access to incredible people like you and our team, and it's a very unhurried environment.
Dr. Michael Koren:
0:57
Unfortunately, nowadays, when you go to most medical practices we're just rushing and rushing and rushing, trying to get things into the computer and moving on to the next patient, whereas in the research realm we spend a lot more time with each individual patient. So we've talked about that quite a bit at these sessions here and elsewhere, but what we haven't talked about is where clinical research stands in the overall politics and healthcare systems of the world. In the United States and unfortunately both you and I share the opinion that politics sometimes gets in the way of healthcare Would you concur with that
Dr. Mitchell Rothstein:
1:34
Absolutely
Dr. Mitchell Rothstein:
1:36
think one of the other aspects of research and research companies like ours is that when studies become available, not every study is accepted by our company to work on. So we want to judge whether or not what we're seeing has value and is going to have value to the community, and then whether or not the techniques in the study are going to give us the kind of answers we want so that we can present data to people to make good decisions with.
Dr. Michael Koren:
2:05
Right. So with that introduction, let's jump into the goals of this lecture. So first we want to help everybody understand the differences between a functioning government agency and a political agenda. Sometimes it gets mixed up, would you agree? Absolutely Okay. So we're going to get into that a little bit. Sometimes it gets mixed up, would you agree? Absolutely Okay. So we're going to get into that a little bit. We're going to explore controversial issues where politics influences healthcare, discussions, policies and outcomes. So we have a couple of case studies that look at that. We want to promote the role of clinical research as a truth engine. At the end of the day, we don't have any vested interest in the answer. Our vested interest is exposing people in our communities to this neat process and then providing the answer for the rest of the world. So we like to call that a truth engine. And then, finally, the most important goal of the lecture is to irritate and challenge every audience member without getting hit by any flying objects in the next hour.
Dr. Mitchell Rothstein:
3:04
In case you didn't get enough of that uncle that showed up at Thanksgiving. We're here to finish you off.
Dr. Michael Koren:
3:10
Okay, all right, so we got that straight. So one of the things that we teach in research is that we make, as human beings, we make all these associations, and that's a little bit different than using deductive reasoning to come up with conclusions, and it's just natural. Being human means you're going to make associations and you have to ask yourself is the association something that you should act on, or should you get more data? And a scientist and medical scientists particularly, we always believe don't jump to conclusions, ask for data, but let's just explore this a little bit collectively, okay. So I just want to get a sense for what the sort of the biases of the audience are. So who in the audience, by show of hands, thinks the government should be more involved in health care Okay, and who thinks the government should be less involved in health care, interesting, okay. So it's about two-thirds less, one-third more, okay.
Dr. Michael Koren:
4:17
Okay, so let's look at this picture
Dr. Mitchell Rothstein:
4:19
Now. Mike, you said my mom wasn't going to be in here.
Dr. Michael Koren:
4:21
All right. So, without mentioning anybody's name, who has a sense for who this person voted for in the recent election? Okay, all right. Okay, who did this person vote for? Who has a sense for who this person voted for? Okay, so these are associations. So let me change the narrative a little bit. Does your opinion change about this person if we tell you her name is Gwendolyn Carnegie Vance, head of college Republicans at Hillsdale College? So it probably does. So, again, we have these impressions, we have these associations and then, as we collect facts, we adjust our opinions and, in essence, that's what clinical research is, is that we have a hypothesis and then we test it. We get more data and test it, and we test it in structured experiments, and the resources that we use in these structured experiments are useful for people in our community.
Dr. Mitchell Rothstein:
5:24
Yeah, and the information that we get, whether it proves the treatment is effective or ineffective, is still useful information for everybody. So every study that we accept and most studies that you'll see have value. Either it's positive value I don't want to say it's negative value but it's more information that we can make better decisions with.
Dr. Michael Koren:
5:46
Absolutely. So let's talk about government agencies and, by and large, government agencies have very important functions and, by and large, they're pretty successful at doing their jobs. So let's jump into that a little bit more. So the agency that Dr. Rothstein andI touch base with the most is the Food and Drug Administration. So every study that we do, or that you in the audience have been involved with, has to be registered with the government through a form that gets sent to the Food and Drug Administration, called the 1572 form, and that registers us and points out that we're qualified to do the work that we do. And, by and large, this is a very effective organization and it's actually a pretty apolitical organization. So they call their mission the second bullet point, which is protecting and promoting public health by ensuring the safety, efficacy and security of drugs, biological products, medical devices, the food supply and cosmetics. So FDA is involved in making sure that the dairy products that you get at a grocery store isn't infected with some sort of bacteria, for example, and they're also the agency that makes sure that, before a drug gets on the market, it goes through incredible scrutiny to determine its safety and efficacy.
Dr. Michael Koren:
7:02
And what's interesting from my perspective is that the current commissioner, Dr. Robert Califf, is a Democrat, so I'm not sure he will be the commissioner next year, but he's a Democrat. I happen to know him because he's a cardiologist who was a professor at Duke University. Early on in my career I had a number of interactions with him and he was actually kind of a mentor to me to teach me about clinical research. Terrific guy, good guy, scientific guy, straight guy. I didn't know he was a Democrat until he actually got into the Food and Drug Administration. The flip side is Scott Gottlieb, who I don't know as well, but he actually went to medical school with my brother and was involved in training at Mount Sinai in New York. Also really straightforward guy. He was the commissioner under the first Trump administration. Scientifically based, really good guy, just terrific person.
Dr. Michael Koren:
7:52
So both these people on both sides of the political aisle, quote-unquote are medical scientists before anything else. So I can vouch for them and I can vouch for the fact that the FDA, by and large, does really good work. The other thing is that it's a relatively efficient organization. So if you look at the last line, you can see that their budget was $6.9 billion, which is chump change for the federal government, quite frankly. And what's interesting is that a little less than half of that comes from pharmaceutical companies and medical product companies, so that they can get higher up on the line. So when a drug comes through to be approved by the FDA, there's a waiting list and what the FDA will do is say okay, if you want to jump the line, you pay us a bunch of money. And of course, big companies are willing to do that. So, because time is money for them their profits are gained during the period of time of exclusivity through the patent programs They'll pay tens of millions of dollars to jump up on the line.
Dr. Mitchell Rothstein:
8:49
Sure and get their product out faster if it works.
Dr. Michael Koren:
8:52
Yeah. So when you think about it from a public expenditure standpoint, it's relatively modest and a good portion of the funding for the FDA actually comes from industry directly. Now there are other federal agencies. This is one you probably never heard of the Office for Human Research Protections and it actually was started by one of my medical school mentors named Greg Kosky, and Greg is an anesthesiologist. He practiced at Mass General in Boston for a number of years and he was brought down to Washington to make sure that there was some oversight agency to make sure that people in clinical research studies were being protected. So think of that. You probably never knew this, but when you're in a clinical research study, there's actually a federal government organization that's kind of out there to look over you. So that's one of the things that's out there. This is a relatively small organization. It doesn't cost a whole lot, but it's a layer of protection for people and they do their job well. On occasion, if we have a controversy, we may go to HRP and say what do you think about this In this world of cybersecurity? For example, what should be disclosed to patients about how much of their information is online? That would be a question that would come up and OHRP would give us an answer.
Dr. Michael Koren:
10:12
The other big organization is the National Institutes of Health. It's actually way, way bigger than FDA, so you can see their budget this current year is $47 billion. They fund a lot, a lot of medical research, a lot of medical research, a lot of medical research and academic medical centers. They fund a lot of basic science research we do. Clinical research means this is research on patients. That's what clinical means, but they do it. They fund other stuff. Have you ever had an.
Dr. Michael Koren:
10:36
NIH grant.
Dr. Mitchell Rothstein:
10:37
I haven't had one
Dr. Michael Koren:
10:38
okay, so uh, and they have a big influence on clinical trials issues. They also run a hospital outside of DC and they fund studies abroad too. They do, they absolutely do, yep. And then the CDC is probably the most controversial of all these and their 2024 budget was 9.2. Of all these organizations, I would say the CDC is the most political. Would you agree with that? Yes, okay, and they have an important role in terms of investigating, mitigating and preventing health crises. So, for example, if there was an outbreak of norovirus, the CDC would investigate that. So what Dr Hill was trying to do to prevent outbreaks, they would look at to see whether or not somebody dropped the ball. You had a chef that didn't wash his or her hands, or who knows what was not done that could have been done to prevent it. They're also the agency that is supposed to stockpile vaccines in case of bioterrorism. So we haven't seen a case of smallpox, for example. How long has it been now? 50 years.
Dr. Mitchell Rothstein:
11:42
Yeah, around 50, 60.
Dr. Michael Koren:
11:44
But we know that there are smallpox. The virus is being kept alive in certain places around the globe by certain countries and there's always the concern that that could be used as part of bioterrorism. So I believe that the CDC has stockpiled vaccines in case that were to be used as a weapon, so that the population could be protected relatively quickly. So these are the kind of roles for CDC. So by and large they do a lot of important things, but I think they may have dipped their toes into politics a little bit, and we'll talk about that in a second. You want to just mention about health care disparities and why that's a concern these days.
Dr. Mitchell Rothstein:
12:25
Yeah, so I think in the news all the time, at least from a medical standpoint, people are looking at differences between groups and health care and outcomes and how this is being addressed by the medical community itself really isn't clear to a lot of people, really isn't clear to a lot of people. We've been looking internally at diversifying the people who are participating in research or outreach to different communities in order to kind of overcome some of these perspectives and hopefully kind of come to resolution and understanding why there are differences between different groups in terms of their outcomes for the same type of disease process.
Dr. Michael Koren:
13:08
Yeah, and that's the key is the understanding why. So if there are differences, it doesn't necessarily mean there are biases. There are differences that we need to understand. And just comment on clinical trials, why diversity is important to us in clinical research.
Dr. Mitchell Rothstein:
13:22
Well, when you're trying to apply your findings from a research study to a population at large, if you have a very homogeneous group of subjects that you've done your research on say 20 to 30-year-olds that live in Hawaii their response to treatment might not be able to be extended toward the rest of the mainland US population. So you want to try to reflect the population that you're going to be delivering your research product to in your research itself.
Dr. Michael Koren:
13:56
Right, and that's a very important concept, although primarily we look at overall global results. Then we break down subsections of those results to see if there are any differences between different groups. So sometimes we see that there are differences between Europe and the United States because background medications are different. Sometimes we find that there are racial differences. So we know, for example, that African Americans respond to different heart failure drugs better than Caucasian population. So we've learned this all because we have some diversity in clinical trials and we can do these subset analyses All right. So, with this concept of healthcare disparity, we want to explore this a little bit, in a little bit more detail, because often this gets politicized, unfortunately. So which is the biggest healthcare disparity in the United States? Is it blacks versus whites? Is it the rich versus poor? Is it men versus women? Is it doctors versus lawyers, or is it? Let's look at the data. Okay, so who thinks it's blacks versus whites? A couple of people. Who thinks it's rich versus poor? Very interesting Majority of people.
Dr. Mitchell Rothstein:
15:09
Yeah.
Dr. Michael Koren:
15:10
Who thinks it's men versus women. Okay, a few. I think some people voted twice.
Dr. Mitchell Rothstein:
15:17
Well, I voted twice.
Dr. Michael Koren:
15:20
Doctors versus lawyers, okay. And who thinks we should just look at the data before we make an answer? Okay, it's a very intelligent crowd here, and so we're going to go along. Let's look at the data, because I think you would have no idea of knowing this without looking at the data. So let's study the data a little bit. So when you look at disparities probably the thing we would agree on that there's no nuance.
Dr. Michael Koren:
15:48
This is pun intended here. This is black or white, which is how long do you live by race, and so this graphic shows how long people live in the major ethnic or racial groups in the United States, and so you can see on the. This would be on this side of the slide. You have Hispanics, then followed by Asians, whites, blacks, and then Native Americans is on the other side of the slide. So the reason we set up like this is obviously COVID changed things a lot, and we want you to see what happened, see what was happening before COVID, what happened during COVID and then what's happened this past year, which is post-COVID. So really, really interestingly, you can see that the average life expectancy before COVID for a Hispanic person in the United States was 81.9 years, and it was 85.6 years for Asians this, by the way, is CDC data and for whites non-Hispanic whites it was 78.8 years. So you can see that Hispanics live three years longer on average than non-Hispanic whites, despite the fact that Hispanics have lower income than non-Hispanic whites. So who knew that? This is called the Hispanic paradox, that Hispanics in the US live three years longer than whites? Did anybody know that? Yeah, almost, and you never hear that. Or did you know that Asians in the United States, on average, live seven years longer than whites? Yeah, a few people knew that. So usually what you hear about is whites versus blacks and disparities, but when you actually look at the data, whites, blacks and Native Americans should be asking the Asians and Hispanics what are you guys doing right? That would be the more logical way of having this discussion about disparities, and it's really interesting, and I've spoken with a lot of Hispanic physicians and other people about why that is, and there's all different theories as to why Hispanics with an average lower income actually live longer.
Dr. Michael Koren:
17:49
Now, the other little subtlety about this slide is, if you look at what happened during COVID, hispanics were affected more by COVID than perhaps other racial groups, but even in 2020 and 2021, the average life expectancy of a Hispanic person in the United States was higher than a non-Hispanic white person, even though their drop from baseline was greater, and the belief is that Hispanic people were more involved in frontline activities, where they're more likely to be exposed to COVID, and for that they actually suffered disproportionately, as did Native Americans. You can see that in the far end that there was a big drop in Native American life expectancy during COVID. But on the bottom we actually have the statistics for the last available year, which is 2023. And you can see we've pretty much gone back to the pre-COVID baseline by and large. So Hispanics now are living 80.0 years on average, which is two and a half years longer than non-Hispanic whites. Asians are living seven years longer than whites, and whites are living about four years longer than blacks. So that's the answer to that question.
Dr. Michael Koren:
18:55
Next, life expectancy by household income percentile. So probably the best way of doing this is seeing what happens for the bottom quartile, the bottom 25% versus the top quartile. That would be better than maybe the bottom 1% versus top 1%. Yeah, I think so. Better than maybe, like the bottom 1% versus top 1%.
Dr. Mitchell Rothstein:
19:12
Yeah, I think so.
Dr. Michael Koren:
19:13
Anyhow. So if you look at the bottom quartile versus the top quartile, the bottom quartile lives 4.6 years less than the top quartile, for both men and women. So there is a difference there. But let's look at sex and these again, looking at numbers for 2021, which is a peak COVID year and the next year and you can see that, on average, women live significantly longer than men in the United States. In fact, that difference is at least six years. And even if you get to age 65, women live longer than men. It's about a three-year difference. If you get to age 65, you've gotten over childbirth issues and other things, maybe some bad behavior issues, but women live longer. And then, finally, doctors and lawyers live the same and they don't live any longer than the average person in the United States, for whatever that's worth, all right. So let's look at the numbers again Blacks versus whites the difference is four years. Rich versus poor the difference is 4.5 years. Men versus women is six years. Doctors versus lawyers the same. So what do you think of that, mitch?
Dr. Mitchell Rothstein:
20:26
So it almost makes you want to be a woman.
Dr. Michael Koren:
20:32
But of all these things is this the one we talk about the least.
Dr. Mitchell Rothstein:
20:37
Yeah, I don't think this ever comes up as an issue of disparity in any medical conversation.
Dr. Michael Koren:
20:43
Yeah, in fact, all we hear about is maybe biases against women in health care. So here's an example where the data and the politics may be not aligned. And I had an interesting conversation at a medical meeting. I was on a panel with a woman cardiologist and it was a study that was stopped early because the intervention was having benefit, and so she asked to look at the sub-analysis between men and women. It was a very pronounced overall difference and in this particular study, because men tend to have more heart attacks and have more problems, it was disproportionately men. So about 75% of the population was male, 25% was female big difference in overall outcome. But when you looked at the women as female, big difference in overall outcome. But when you looked at the women, there wasn't quite a mortality difference yet, and it was clear in men, but it wasn't clear in women. So she asked the question well, why'd you stop the study? Shouldn't you have continued the study to show that this actually works in women? And so everybody said, okay, well, that kind of makes sense.
Dr. Michael Koren:
21:48
Then I asked the question is well, how many men have to die to prove that women are also human beings? So there's two ways of looking at all these issues and the truth is that in most things, certainly across races, we respond the same. Women and men, remember, are genetically different. We have different chromosomes, at least one different chromosome, so there may be more differences there than between races.
Dr. Michael Koren:
22:12
But that's why we do the studies and you always have to be careful when you say okay, one group is being biased against by looking at the overall picture of a clinical trial, knowing that you can't unblind a clinical trial before you get the results. So in this particular case, let's say that we said, okay, the women are going to stay in the trial, but the men are going to come out because it helps men. Well, if I was a woman and said, hey, hold on a second, why can't I get this now? Why are you making me stay in this clinical trial when I know it works in men? So you can flip that script pretty quickly and that's why the evidence is so important. I don't know if you want to comment on this.
Dr. Mitchell Rothstein:
22:53
No, I don't know if you want to comment on this.
Dr. Michael Koren:
22:54
No, I'm not commenting on this, not again. Well, actually one of my classmates made this comment in a very prominent medical journal His name is Zeke Emanuel and he was an ethicist and he was actually involved in the Obama administration and he said well, the easiest way of getting rid of disparities is just get rid of everybody when they get to age 70. And I think she's willing to help us with that. But when you think about it, if we euthanize everybody at a certain age for certain conditions, then you wouldn't get rid of disparities. But is that health care progress?
Dr. Mitchell Rothstein:
23:30
I guess for some.
Dr. Michael Koren:
23:32
All right. So let's explore associations. Who in this room thinks vaccines are good? Oh, look at that. Who thinks vaccines are bad? Got a couple. More good than bad, okay. So let's go to another question. Who thinks a chemical or surgical gender reassignment is good? A few, okay. Who thinks a chemical or surgical gender reassignment is bad? Interesting, okay, all right. So people are a little bit more reluctant to raise their hands for that, I noticed. Okay, all right. So let's study these things. So I would argue that it's a bad question, because these are not good or bad things. What really we should be asking is these interventions right for the individuals who are considering these interventions? And that's the problem in politics is everything gets good or bad, you're?
Dr. Mitchell Rothstein:
24:29
either good or evil.
Dr. Michael Koren:
24:30
But in fact in medicine we know that you have to customize your decision-making to the individual.
Dr. Mitchell Rothstein:
24:36
Right, and is there evidence that the treatment we're talking about has a positive impact on the patient? So without that evidence, it's very difficult to judge whether a treatment is good or bad for anybody.
Dr. Michael Koren:
24:50
Right? So those are the two key components. Components is that you can't make any medical decisions out of context, and you probably should never answer a question about a medical intervention as good or bad without knowing the context of when it's going to be used, right? So let's look at our first case study, which is COVID vaccines in Florida. So why don't you start giving everybody some of the details? You might be familiar with it from the news, but go ahead.
Dr. Mitchell Rothstein:
25:17
So the current recommendations from the CDC are that everybody should get an annual COVID booster and that's based on information that we've gained from multiple long-term studies that we know COVID boosters reduce hospitalizations and death, and that there's new strains of COVID evolving all the time. In fact, omicron, which was something that was the height of the COVID pandemic a year ago, isn't even circulating anymore, so we don't have those specific antibodies in our system and one way to stay up with like your flu shot and now with RSV, is to get revaccinated to boost that immune system back up, because we know it reduces hospitalizations and death.
Dr. Michael Koren:
26:06
So the federal government, through the CDC, is recommending that everyone get a booster and quote. It's especially important if you're in a high-risk group, correct, okay, all right. So what do we say in the state of Florida?
Dr. Mitchell Rothstein:
26:23
Dr. Ladapo, Do you know him from medical school too?
Dr. Michael Koren:
26:25
No, he has a degree from Harvard School of Public Health, where I did some of my training, but not when I was there. So basically, what Dr Ladapo said was that and this is in red at the bottom of the slide is based on the high rate of global immunity and currently available data, the state surgeon general advises against the use of mRNA COVID-19 vaccines. Fascinating, curious. Yeah, yeah, well, okay, so why is this political?
Dr. Mitchell Rothstein:
27:00
Yeah, it doesn't seem like it should be.
Dr. Michael Koren:
27:03
Well, it's political because he said mRNA vaccines. Like why did he pick on those vaccines? Like I don't know if you know this, but there are actually about 140 different type of COVID vaccines out there. There are five approved in the United States and two of them are the mRNAs. So what was it about the mRNAs that he singled out versus the AstraZeneca vaccine or the Johnson Johnson vaccine, which is using older technology that can't update as quickly as the messenger RNA?
Dr. Mitchell Rothstein:
27:33
I have no idea.
Dr. Michael Koren:
27:34
Okay, and then there's something really curious here, and I highlight it. You won't be able to read it, so I'm going to read it for you. It says the most recent booster approval is granted in the absence of booster-specific clinical trial data absence of booster-specific clinical trial data performed in humans. Furthermore, this booster does not protect against the current dominant strain. According to approximately 37% of infections in the United States, there is currently limited data to inform whether these boosters offer any substantial protection against the virus and subsequent circulating variants. Although randomized clinical trials are normally used to prove therapeutics, the federal government has not required COVID-19 vaccines and manufacturers to disseminate their boosts to prevent hospitalizations or death from COVID-19 illnesses. Okay, so that's really curious from a number of standpoints. So the first one is this so this is actually a paper in the New England Journal that looked at the third dose of the Pfizer BioNT vaccine.
Dr. Mitchell Rothstein:
28:31
And I see a familiar name in the authors there.
Dr. Michael Koren:
28:33
Yeah, yeah, so we actually participated in this and I am one of the authors on the paper. So I was involved in this publication of these data and looked at everything before it was published. So, one, this came from Florida in part. Two, it's been thoroughly vetted. And three, it shows that the boosters were subject to clinical research. So that's a real curious thing that he would say there's no data on the boosters when in fact there are. Now what is true is that with each new variant of a vaccine they make slight tweaks in the messenger RNA sequence to make sure that the booster is going to be as effective as possible, which is only a possibility with messenger RNA, because in the old school vaccines it takes 18 months to actually grow the virus and purify it and actually get on the market.
Dr. Mitchell Rothstein:
29:25
It's remarkable, and even with that 18 months to get on the market, it was our best guess as to what we thought the circulating strains were going to be for. Like influenza, we didn't know whether it was going to be h1 and five or what combination, so we did our best guess but all our resources into that. Now we know what it is and we can make the vaccine Specifically for that organism, which is remarkable.
Dr. Michael Koren:
29:53
Yeah. And so, going back to Dr Ladapo's statement, he said based on the high rate of global immunity and currently available data, the Surgeon General advises against the use of the vaccine. There is nothing in there about high-risk people or people consulting their physicians. Oh my God.
Dr. Mitchell Rothstein:
30:14
Sounds like he overstepped a little bit.
Dr. Michael Koren:
30:16
I would think so. Yeah, I don't even like, is he really a doctor? Yeah, so with anything in medicine, you have to know the patient. How can you make any global statement about something without knowing something about the patient and the risk, global statement about something without knowing something about the patient and the risk?
Dr. Mitchell Rothstein:
30:40
So what is true is I could find some reason to disagree with the CDC on this.
Dr. Michael Koren:
30:41
What do you think? Yeah, I think there's Going back to this, going back to the CDC.
Dr. Mitchell Rothstein:
30:44
A fairly straightforward way to get to the bottom of this.
Dr. Michael Koren:
30:48
Yeah, do you think a 20-year-old, a healthy 20-year-old that's living on his or her own, needs to necessarily get a COVID booster?
Dr. Mitchell Rothstein:
30:55
No, I don't think in that situation.
Dr. Michael Koren:
30:57
So what we learned about COVID is that older people and high-risk people can have a devastating illness, but the truth is that most teenagers or young adults have very mild illnesses and you can't even distinguish it from colds or a mild case of influenza. So I think it's a fair statement to say that maybe healthy younger people don't need a booster I would agree with that and that everyone aged over six months should get it. I don't agree with that. Again, I think the CDC should say you should talk to your doctor about it. But I would agree with the. Second statement is that if you're at high risk, then it makes pretty good sense to get it, unless, again, you have a good reason not to so. In both cases, on the CDC side and on the Florida Surgeon General side, I think they didn't do the public a service by making these broad statements without saying know your individual circumstances, talk to your physician. And why single out messenger RNA, which actually has the most clinical trial data compared to the other modalities?
Dr. Mitchell Rothstein:
31:59
And is the safest.
Dr. Michael Koren:
32:00
Yeah, so that's that. So let's go to case study two. Oh, there's the other thing that's interesting. Just to get into politics, what I find to be incredibly ironic is the fact that often vaccine skepticism is associated with Republicans. When Operation Warp Speed was a Trump administration concept, you might want to comment on that.
Dr. Mitchell Rothstein:
32:27
Yeah, for the first time we developed an effective, safe vaccine in a matter of months, as opposed to almost a decade for vaccine development before. The estimate is that with the speed that this vaccine was developed, probably worldwide, it saved 20 million lives that would have perished without a vaccine waiting for that process to develop. And the oversight on the development of the vaccine was very, very high.
Dr. Michael Koren:
33:03
Very intense.
Dr. Mitchell Rothstein:
33:04
The amount of participants had to be increased during the trials to make sure it reached statistical significance and the adverse events were not accumulating to any significant degree of warning before it was let out. But this approach to vaccine development from a business standpoint really changed medicine as we know it and it's going to continue to change it going forward.
Dr. Michael Koren:
33:27
Yeah, oh great. And the last statement there is kind of interesting, which is vaccines are among the most highly studied and proven preventative treatments for disease. This is actually going back to the 1700s, when people used to do inoculations and they would cut an incision in somebody's leg and put smallpox pus in their leg wounds and that actually protected people way back in the 1700s.
Dr. Mitchell Rothstein:
33:51
It's one of the reasons we think that we may have won the Revolutionary War, because George Washington forced all of his soldiers to get inoculated with smallpox, and without that it would have been. Who knows what it would have been.
Dr. Michael Koren:
34:07
Well, okay, so let's get to case study two gender-affirming controversy. So I want to thank the US Supreme Court for cooperating with our schedule, and I don't know if you read the news today or heard the news, but the US Supreme Court agreed today to consider the case of parents and transgender teenagers from Tennessee who want to get treatment for gender-affirming care today. So thank you, Justice Roberts, for coinciding with our schedule.
Dr. Mitchell Rothstein:
34:31
Just a one-phone call.
Dr. Michael Koren:
34:34
So let's look at the evidence, so go ahead
Dr. Mitchell Rothstein:
34:39
Well actually yeah, so this which study?
Dr. Michael Koren:
34:43
This is a.
Dr. Mitchell Rothstein:
34:44
Dutch study.
Dr. Michael Koren:
34:45
So I'll give you a little context. So when you ask AI, you go to chat GTP and say what's the clinical trial evidence for gender reassignment studies? And this is what people come up with.
Dr. Mitchell Rothstein:
34:56
So the major study that has been promoted and used as the basis for gender affirming care in the United States was a Dutch study done several years ago and their population. This was a retrospective study, so not a look-forward randomized study. They looked at people that carried a diagnosis of gender dysphoria and they followed them over the course of several years and what they found was that in their particular study the average age of the patients entering this study was 15, not children like we've kind of transplanted to this country, and that in general patients showed an increase in suicidality of about two to three times over patients without gender dysphoria, but interestingly the suicidality occurred at an average age of 29, as opposed to what has been promoted in this country that if you have a transgender child or adolescent they're going to be at suicide risk and they're not really using the information that was gleaned in a study that doesn't really have statistical significance to begin with in a really proactive way in this country.
Dr. Michael Koren:
36:20
Right. So that's called an observational study, where you just look at a group of people and you're not doing the most important thing in a clinical trial, which is randomizing patients. So in order for a study to be valid, you have to randomize patients and say, okay, you're randomly going to be in this group or in that group and then we're going to see what happens over the course of time, to see if this random assignment makes a difference. And the other feature of clinical trials, which is required by the FDA for any drug development or any procedure, is that they're blinded, so neither the investigators or the patients are subject to biases as best as possible. Sometimes it's a little difficult to blind studies, but if you're giving somebody a testosterone pill, you can easily blind that. And then the other part of clinical trials is that all the baseline intervention should continue, based on whatever the state of the art is. So obviously supporting transgender kids should happen regardless of where they're randomized.
Dr. Michael Koren:
37:17
So the Dutch study was not randomized, it's just an observation. As Dr. Rothstein mentioned, they looked at suicidality 12 to 15 years after they were initially identified and that's the basis of this increased suicidality. But this study is also used, which was a study that was done in Australia where they randomized people either to immediate testosterone therapy or delayed testosterone therapy. So one of the effects of testosterone that's known is euphoria. Most people I don't know if any men here have been treated for low testosterone. There, unfortunately, was not an improvement in cardiovascular outcomes when you were treated for that, but your mood gets better.
Dr. Mitchell Rothstein:
37:55
You never see an unhappy bodybuilder.
Dr. Michael Koren:
37:57
Yeah, so testosterone does have some mood-altering properties. That's known in other populations, but in this population it was used as a reason that people should be assigned this quote unquote. But unfortunately it ignores one of the most important early studies that looked at giving sex hormones to the opposite sex. I don't know if you want to comment on that.
Dr. Mitchell Rothstein:
38:21
Well, I think, being a cardiologist, I think this would be more
Dr. Michael Koren:
38:25
I'm happy to jump in
Dr. Michael Koren:
38:28
So he's punting it back to me and I'm happy to give it to you. So there was a very, very important study called the Coronary Drug Project and that was designed in the 1960s and was done in the early 1970s through the mid-1970s, and at that point heart disease was even much more rampant in the United States than it is today, and men were way, way, way more likely to get that than women at that time. So people came up with the idea okay, well, why do men die of heart attacks and women don't? Well, maybe it's estrogen that's protecting the women. So they came up with this idea of giving men estrogen. If women live longer than men, doesn't it make sense to give men female hormones at some point to increase longevity? That makes perfect sense, doesn't it Sure? Okay, Well, unfortunately it doesn't work.
Dr. Michael Koren:
39:15
So they put 8,341 patients in a randomized double-blind clinical trial Again, very state-of-the-art type trial for the time. Randomized, double-blind clinical trial with a lot, a lot of patients. State-of-the-art type trial for the time. A randomized, double-blind clinical trial with a lot, a lot of patients. What they found is that there was an increase in mortality in the men who received estrogen versus placebo. Okay, so you never know what's going to happen in a clinical trial, do you?
Dr. Mitchell Rothstein:
39:38
No, you don't.
Dr. Michael Koren:
39:39
And this is an example of giving a sex hormone that's associated with one sex to the other sex and bad things happening. And in fact, not only was there an increased mortality, but they identified this relatively quickly. So both high and low dose estrogen groups in men were stopped. These patients were discontinued from study participation because they're having problems earlier than expected. So with that backdrop, don't you think we need more data before we start advocating these hormone replacement treatments for young people?
Dr. Mitchell Rothstein:
40:10
Yeah, I think there's so much about gender dysphoria that we don't understand. For example, in the years of 2018 and 2019, the number of children with gender dysphoria increased by about 20% per year in the United States Once the pandemic started for the years 19, 20, and 21,. The gender dysphoria diagnosis increased by 200%. And there's something called you've heard about a social contagionist. So when groups of people find something that they have in common the most commonly cited issues is groups of suicide that occur in young girls that that becomes kind of the peer. The most powerful force in the world is peer pressure, and if you're in a peer group that has something in common and your friends are all doing something, you do something. And I think, with this, gender reassignment studies whether it's through socialization, whether it's through chemicals, whether it's through surgery, when we don't even know what's driving it to begin with and what the natural history of it would be, is kind of reckless.
Dr. Michael Koren:
41:26
Yeah. So this slide talks about the politics of this. So Vice President Kamala Harris was asked about this, and she answered the question politically rather than medically, and I think it's fair to say it probably hurt her in the election. So what she should have said, which is what I would say, is we don't know the answer, we don't know. We don't know if this works, we don't know. We don't know if this works. We don't know who the patients are that should get it. If it does work. We don't know if psychotherapy is better. We don't know if treating depression is better, we don't know. And so to say that you supported in prisoners without actual data was probably a mistake, in my opinion, was a mistake, and I think it hurt her in the election. And so we would argue that we need to help our politicians understand that let's not make medical statements based on fighting culture wars, but let's make it based on medical data. That would be my conclusion. Thank you, you can clap.
Dr. Michael Koren:
42:26
And then, finally, on the other side of the political aisle, we have Robert F Kennedy Jr, who has been now nominated to be the head of Health and Human Services, which will oversee Medicare, etc. Etc. He's out there. He thought that autism comes from vaccines, which has been completely discredited. This was thrown out there by a discredited physician from the UK called Andrew Wakefield, but he was shown to basically fabricated all his data and it's been shown over and over again that this is not true. So that was one of RFK's calls to fame. In fact, we know that vaccines are incredibly important to prevent childhood illnesses and have a huge amount of evidence that backs up the use of them in the right people. Obviously, you don't give vaccines in the wrong people.
Dr. Mitchell Rothstein:
43:15
You give vaccines in people who it's intended for Inventions and progress that we've made in medicine. Vaccines, far and away, have saved more lives and produced better quality of life for people than anything else, far and away, but yet it's the center of controversy. There's a lot of other things that could be the center of controversy, but the one thing that we've done right in medicine is really.
Dr. Michael Koren:
43:49
this has become such a kind of political central issue. Yeah, so the right answer in my opinion again is that vaccines work really well when the vaccines are scientifically proven and given to the right patients, you know that's not that hard.
Dr. Michael Koren:
43:58
Right, okay, so saying they're good or bad. And then the other recent comment from Robert Kennedy is that he was against Ozempic, which we've studied in clinical trials. Ozempic is part of this GLP-1 class, including Manjaro and others, and it's been shown to help people lose weight, which is what you hear about, but it also shown to reduce heart attacks and strokes and lower cholesterol.
Dr. Mitchell Rothstein:
44:22
And improve blood pressure.
Dr. Michael Koren:
44:23
Yeah, all these positive effects. So to say that we're not going to be supportive of this, but we'll make sure that everybody gets three good meals a day. Your comments on that?
Dr. Mitchell Rothstein:
44:34
Yeah, it's out there and they actually did a study recently where they had this was a prospective study where they had 1,000 low-income families they gave $1,000 a month to quote for health care over three years and 2,000 low-income families they gave $50 a month to for quote health care and they looked at the end to see if there was going to be any measurable improvement in the health of the families that got the $1,000 a month after three years and at the end of the study there was no difference at all except the families that got the thousand dollars a month after three years and at the end of the study there was no difference at all except the people that got a thousand dollars a month.
Dr. Michael Koren:
45:12
They did use the emergency room more frequently and that was the only real difference they could see Because they had money for the copay Right, and that's unintended consequences. So read this. It says three meals a day and a gym membership for every obese American. Okay, all right. So let's say that you're 14% overweight and you need to be 15% to get this benefit, okay, and you just quit your job and you don't want to work. You say if I get three free meals a day, then I can make it. So if I were that person, I would eat like crazy for the next week, qualify for the benefit and then get three free meals a day. So you might find that you're actually promoting obesity rather than reducing it. Imagine that, all right.
Dr. Michael Koren:
46:01
So, anyhow, we like to talk about research as a care option.
Dr. Michael Koren:
46:05
Again, bottom line is that we need to put all these decisions in the context of individual patients and look at the evidence. For those of you that have participated in research programs, I think you'll agree that it's a tremendous way to get a lot of benefits that are provided by people like Dr Rothstein and our other staff members. You get knowledge. Sometimes you get stipends. When we ask our patients who have done one study if they would do it again, 99% say they would do a second study and more recently we're using this mid-evidence platform to have conversations like the one we just had here, with different PowerPoint presentations, articles and discussions. So hopefully you find this format useful and a way to kind of get to the truth behind the data by having experts talk about it and we don't always agree. There are times when we have disagreements, but at least you know where there's consensus, where there's disagreement and how we're going to learn about how to get better how to make health care work better for all of us.
Dr. Michael Koren:
47:04
And then, as mentioned by Helow. in our starting comments, these are some of the really really interesting places that we're working on right now. So we're doing an interesting vaccine study to prevent really some of the devastating effects from norovirus. You're involved in this chronic cough study as a pulmonologist. That is interesting. You have these people that just cough and they don't know why, and we're trying to help figure that out and come up with a treatment. We're talking about diabetes and obesity. Well, one of the concepts is maybe you're absorbing, maybe certain people are just born to absorb more nutrients and maybe if we do a resurfacing of their intestines so they don't absorb it as much, they would be better off. So we're doing that study as we speak, including getting this procedure done for certain people In heart failure.
Dr. Michael Koren:
47:47
In my area of interest we have a lot of really new technologies. Heart failure is one of the three leading causes of hospitalization in the United States and, because of the incredible cost of health care, we're trying to figure out better ways to keep people out of the hospital. And then we've talked quite a bit about lipoprotein, little a, which is the really, really, really, really bad cholesterol. So if you have a family history of heart attack or stroke, you'll let us know. We might test you for this. We will do that for free and maybe get you involved in a clinical trial. So, finally, we like to make people aware about the danger of preconceived notions, as we started. And a preconceived notion, by definition, is an opinion or judgment formed before encountering any evidence or firsthand knowledge. That's the dictionary definition and so don't fall for preconceived notions. Insist on evidence. So thank you very much for your attention. Thanks for joining the MedEvidence podcast. To learn more, head over to MedEvidencecom or subscribe to our podcast on your favorite podcast platform.
