Research Update: Part I

You. It's great to be with everybody once again. We've been getting lots of questions in the clinic as well as online about the upcoming COVID 19 vaccine as well. Questions in relationship to the research, the data out there, and some safety concerns as well, and some general concerns about the validity of clinical research in regards to the COVID 19 vaccine. So what I'd like to do is take three different videos to talk about these three different concerns and hopefully this will educate everybody enough that they can start reading this information, looking at the news articles, et cetera, that are out there and make good educated decisions for themselves and their families and their loved ones. Ultimately, our goals are to educate, encourage and empower, and hopefully this will help you as we roll out the COVID 19 vaccine. Now, to keep things in perspective, November 20, I believe, was when Pfizer submitted their information to the FDA for review. And, and the review date as of now is December 10th. What that means there's about three weeks between the input of the data to the FDA and the review and them making a statement. So that's where we're at right now. We're in this limbo stage between the data being put in and the actual review by the FDA. And that's causing a lot of consternation, confusion, etc. So that's part of the impetus as far as what we're doing right now. So today I'd like to talk about clinical research and just review that a little bit in context of the COVID 19 to help us get a little better grasp of what is actually going on. So phase zero trials, a lot of people haven't really discussed the concept of a phase zero trial, but this is actually the preclinical research, this is the lab research, the bench research, the animal research that's done previously to find out what might be the mechanism of action of a drug or a vaccine, how does it affect animals, Is it safe in animals? And the. Is it safe to take to the next step? Now, to keep this in context of the current COVID 19 vaccine, is that we started doing this with the SARS virus in 2003, then the MERS virus in 2012 and 13, with the plaque form, as well as the concept of mRNA, so the idea of a nanoparticle platform, which are small balls of fat that can take an MRNA into a cell, and, and the idea of using an mRNA, which is what the Pfizer vaccine study as well as Moderna are, actually is not new, that started a long time ago. And the research in the MRNA vaccines actually is about 20 years old. So this is the, the culmination of literally decades of research. So that's the first phase of phase there. Phase one is first in humans. This is basically looking to see if is something safe and might it have the ability to go onto a phase two trial. So again, phase one is the first in humans looking at safety, best dosing, et cetera. It's built on all the previous work that comes before it. So first you have to have information from animals, bench research to even get you to the phase one. Phase two is the goal is to evaluate whether a drug actually has biological activity. So in the case of the COVID 19 vaccine, does it actually create an antibody response? Does it actually activate the immune system? And that data was being compounded, put together in a combined phase one and two studies in the January timeframe up through till March timeframe. So again, that has already happened and then gets you ready for phase three, which is where we're at right now with both Moderna and the Pfizer vaccine study. Very similar platforms, very similar technology. I can only directly speak to the Pfizer because that's the one I'm personally involved with as a medical director and principal investigator work on that study. So that's my field of expertise. But I think the big thing to think about, remember in phase three studies is phase three studies tend to be very long. In the case of the Pfizer study, about two years. Now anybody who wants to actually review the protocol, I personally cannot give it to you because I've signed confidentiality stuff, etc. Etc. Saying I'll abide by certain rules and regulations in clinical research, I'll follow the Internal Review Board, etc. But Pfizer has put out their, their, their protocol, so you can actually pull it up online if you have any concerns or questions about inclusion, how they get patients in the study, the design, etc. If you want nitty gritty details that is actually out there and available for anybody to look at, and below this list I'll actually put a link for ClinicalTrials.gov that allows you to look at all the ongoing clinical trials in the United States that currently are in review or being done. So that's a powerful tool for those who want to actually take a deep, deep dive. But the thing to remember with the phase three trial, with the Pfizer vaccine in particular is it's a two year trial and so a lot of the data points they talk about as far as efficacy for deaths, does this vaccine prevent deaths, Hospitalizations, does this vaccine prevent hospitalizations? Which you have to realize that's a two year process. Typically we have to keep in mind that 50% of the adult population who gets exposed to this virus will have no symptoms and about 80% of the children will have no symptoms. So it's not just enough of the vaccine to prevent symptoms because that's a large part the population already has that as far as getting symptoms. You know, people can get symptoms of a coronavirus, head cold, lung infection, but most of those people will not be hospitalized. So you have to have a big net. And the Pfizer vaccine study is about 43,000 people to cast realizing that most people who get this won't even have symptoms. And so you're narrowing down the population to people who get symptoms. And then of those who get symptoms, the vast, vast majority of those won't even be hospitalized. Last time the numbers I remembered, about between 5 and 7% of people who get this will actually need to go to a hospital or urgent care kind of place, er to get care. So that's even the smaller subset of the population, and even a smaller subset of that population actually will be admitted to the hospital. So in order to get data about as far as how many people deaths are being prevented by the vaccine, hospitalizations being prevented by the vaccine, severe lung infections being prevented by the vaccine, we might get that data in a year or a year and a half. We just don't know currently. So that's where, you know, realizing that this is being put forward to the FDA for emergency usage only. And we'll talk about that and video two what that looks like from the CDC perspective. But that's what we have to realize. The preliminary data that was put forward to the FDA as of November 20th for review on December 10th was only to show that of the, I think it was 183 people in the Pfizer at that point in time who got sick. 95% of them who got sick did not have the vaccine. You know, they were looking for between a 60 and 70%, you know, success in that range. So this 95% is much greater than they expected. And that's the reason why this information was put on to the fda. Again, we have to remember we're in a worldwide pandemic. So the usual rules of engagement, when you're in a battle area, you're on the front lines, you don't go through the usual routine because again, that might be years and years and years. So we have to Know the kind of data that's being put to the FDA solely to say that the people who got sick with this, the vast, vast majority, 95%, did not get the vaccine, which suggests highly, highly, highly that, that this vaccine actually is effective. For preventing hospitalizations, we don't know. For preventing death, we don't know. We just know that for getting symptoms, it appears to be very efficacious. And that's where, you know, phase four study, which is post, post marketing research, goes in to see that's, that's what every doctor in the country is a part of. If someone gets a medication has a bad side effect, we're supposed to report that. And over time you get these databases of build up to say, hey, this new drug Vioxx might cause strokes, this new cholesterol medication might cause liver issues. That's where we learn. A lot of that stuff is in this postmarking phase for research. But we have to realize we're in phase three for the next year and change, almost two years because the studies are still ongoing. What is emergency usage or what is orphan drug status? Well, there's several special situations that the FDA has set aside saying if someone falls into certain categories like a severe cancer for which there's no treatment, a severe illness for which there's no treatment, and there's already a drug that can be used, but it's very risky. Well, that's what a drug orphan status is. Those are particular drugs that are already in market that may be helpful but have a high risk. And so a physician can have a special application to the FDA and say, hey, can I use this for this patient with this incurable cancer, with incurable heart disease, with a bad neurological condition, als, whatnot, to use this high risk drug. And that is actually orphan drug usage. The other thing is emergency usage, where in this case with the COVID 19 studies are ongoing. It appears very useful, it appears to be very, very safe. But we're in a crisis situation. Worldwide pandemic, that's where we're at right now. So we have to realize that that's what's going on and interpret the data that's out there. In light of that, we have to realize that the FDA has not even reviewed this information as of yet. So of course the average physician, the average practitioner, the average news person, reporter won't have access to this information because the FDA just got the information on the 20th of November. And so that's where realizing how the usual course of information being put out there happens and then hopefully as the FDA reviews it, then being open with us, open with information and the expectation is if this is approved by Pfizer that then by, I'm sorry, by the fda. But then Pfizer will push for a peer reviewed journal to actually publish their data and get that published. And that's when the, in the preview, pre published things like Medrxiv, which a lot of people have been looking at over the last three to four months or six months, that then the scientific community has access to the pre published information before it gets published for further review and then gets published. You can see how this process is very slow and tedious and methodical and it's meant to prevent bad information from getting published. But we also have to realize is that 50% of all published literature is later found to be false. That's some interesting data from Dr. Ioannes that he published in PLoS several years ago that half of the stuff out there is later found to be false, which is a very interesting thing to think about in the publication world. There's a negative bias against negative studies. Now as a, as a physician I learned from other people's mistakes. I learned from reading case controls, I learned from patients I work with. And so an important part of learning is actually failure, meaning that resistant patient, that resistant treatment option and working through that. In the publication world, native studies typically are not published. So the general scientific community does not have the advantage of learning from studies that fail and figure out why did it fail and how can we figure out why we typically only get published articles from successful studies. That's something else to keep in mind as well, that there's a, there's a publication of bias against negative studies and for positive studies. And we'll talk about this in the third video in the series, but how that's being misinterpreted by laypersons and put out there for your consumption. So anyway, that's our first video and next video we'll talk actually about the cdc, their guidelines for distribution and when you can expect to get the vaccine if it's Approved by the FDA on the 10th of December. Thank you.