KNOXVILLE, Tenn. — We know there are many questions about the COVID-19 vaccine trials as researchers and pharmaceutical companies work to find a way to end the coronavirus pandemic.
We asked what you wanted to know and took your questions to Dr. Bill Smith, who is heading up the human clinical trials at Volunteer Research Group at UT Medical Center.
The following is his conversation with WBIR anchor Robin Wilhoit.
Q1: What are the ingredients in the vaccines?
Smith: Well, in the ones that are currently under investigation in the US are RNA vaccines, meaning that they're addressing the genetic code of the virus, one is an attenuated virus, meaning that the virus is non-reproductive, and that stimulates a response. One is using a piece of protein that is introduced into the cell by another innocuous virus so that there are different technologies all being investigated. There also are others to come that just use a piece of protein that has an adjunct, another compound to help it stimulate a response. So there are multiple different methodologies currently under investigation.
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Q2: What is the point of having a placebo in the trial?
Smith: Well, the placebo group in these initial trials is critical to knowing if the vaccine works or not. Since we do not have any effective vaccine, we randomize people, so that we don't know, they don't know, whether they got the real vaccine or the placebo, once there have been a certain number of people develop COVID in the trials, they will then look at those individuals and determine if they were on the real vaccine or the placebo. If there is a 75% reduction, then they will be able to approach the FDA for tentative emergency approval.
Q3: Why should I participate if there is that chance that I just get the placebo?
Smith: Well, it's always a concern. However, my feeling is that having a chance at getting a vaccine, even if it's 50%, and the likelihood of some protection is a whole lot better than 0% of getting any protection. Plus, we have to have these trials and the development of these vaccines before life can get back to any semblance of normal.
Q4: How many people are having bad side effects compared to good?
Smith: Well, a significant percentage of the people that get the vaccine are having minor symptoms that's expected with vaccines, sore arm, just generally feeling bad, some fever. This generally is gone within 24 hours, that responds to Tylenol, and that is the vast majority. There have been a few more concerning side effects and has actually resulted in a pause in two of the trials while those side effects were investigated very thoroughly. As much information as possible about the vaccines and all the people in the study were reviewed and then the FDA and the European authorities have chosen to reopen these.
Q5: Will President Trump decide on the vaccine or medical officials?
Smith: President Trump does not decide on the vaccine. There is a well-established approval process within the FDA that will determine when the vaccine is possibly able to be approved. That process, that cannot be altered by the president or anyone else, and it's well-established and it's professionals that evaluate vaccines and drugs as their job.
Q6: Why are they (pharmaceutical companies) being protected from liability?
Smith: Well, what has happened here in order to get these vaccines out more rapidly, is that in a normal development process, we would do the first part of the study in them and look at that data in its entirety over several months, not just the safety data. Then decide what chance the vaccine has to work and decide whether it's commercially viable with the risk and the benefits to proceed with its development. Then they would do phase 2, look at the same information, and then proceed not just at the safety, but the whole group of information, antibodies, everything else. Then they would go on to phase three. By doing it this way, there are months of delays, to do the entire database analysis, to get the vaccine levels in the blood, to get all the antibody levels, a lot of information has to be obtained very quickly.
So that what is done with Operation Warp Speed, is that the government has said, we understand that this vaccine may not work so we're willing to help fund the cost of it and to indemnify you against the risk from this because we are going at it at a faster pace than normal. However, the part of the data that is important to us for safety reasons, there are no shortcuts being taken there, that data is being analyzed thoroughly and ongoing, and probably even more intensely in the early stages than in a routine trial. The second part of that process is that the government is underwriting the cost of producing several hundred million doses of vaccines before they even know if it works. So that even though the pharmaceutical companies are assuming part of that financial risk, the government is also doing so, which enables them to have several hundred million doses available, if the vaccine is effective, rather than waiting until they know that the vaccine is going to work and then to start producing it.
Q7: Are COVID-19 vaccines being tested on the medically and elderly vulnerable for a documented response?
Smith: Absolutely. In the early phase studies, you want to take your healthiest individuals and make sure that it's safe, and that it's giving appropriate antibody responses. Then in these large phase three trials with 30,000 individuals, like in Moderna; 44,000 like in Pfizer, you have the ability to include elderly, to include people with all the underlying high-risk conditions. That's preferred. We also are making a real push to recruit minorities because they are the highest risk population groups. So all of those are being done. In fact, in one of the studies, they're even allowing HIV subjects who have a good CD4 count.
Q8: Why have some vaccine trials been paused? You touched on this a little earlier. What can you add?
Smith: The two trials that have been paused because there was a side effect that was unanticipated, was not something that is routinely seen with the high incidence of vaccine trials. So they have gone back and looked at all the data to make sure there are no signals, no indication that something bad is happening that we have missed. These pauses happen all the time in drug development, and it's just a sign that safety first is being maintained and that the process is working. Anytime you don't have a good understanding of what is going on, you stop, you analyze all the data possible. Then you get the best experts you can find to review all this and determine if it is truly safe to go forward. So that is exactly what has happened in both of these trials. Once again, it's not that there's a failure, this is something we see all the time. It's that the process is working. Even though there is a huge desire to complete these trials as quickly as possible, safety comes first.
Q9: COVID-19 is a virus as are the flu strains. The flu shots are made by growing the virus killing it and putting it in an injectable media. What makes the COVID strain so different to take so long, the process is already established, tried and proven?
Smith: Well, first of all, the COVID virus is a different virus than the flu virus. We don't have all of the experience there that we have with flu. Typically, a flu virus vaccine, the clinical trials start about three years before that year's flu vaccine is released. So it's not that the process is taking longer, the process is actually going much more rapidly. It's just that we don't have the luxury of planning two years, three years down the road, like we do with the development of the flu vaccine each year. So it's actually faster.
Q10: Why is Pfizer testing on kids now? Why would parents let their kids do this? How do kids become part of this study?
Smith: Well, obviously, at the end of the day, you want to be sure that the vaccine is safe in all populations, and we want to be able to protect our children with a vaccine, particularly those that have underlying conditions and that are at high risk. The only way that we can know that it works and that it's safe in children is to actually do those studies in children.
Q11: This is a two-year study, at least some of them are two-year studies. So if that is the case, why are so many people saying a vaccine could be ready early next year?
Smith: Well, we are all hopeful that a vaccine will be ready either the end of this year or early next year. However, that's not the end of the process. For those people that received the vaccine, we need to follow them for a period of time so that we know their antibody response is long-lasting, we don't know if these vaccines are just going to work for six months, they're going to work for a year, if they're going to work for two years, how often people are going to need revaccination are revaccination is going to be effective. All of these kinds of questions still need to be answered, even though the initial effectiveness question may be answered and large numbers of people being vaccinated.
Q12: Many people feel this vaccine is rushed. How long is it usually take for a vaccine to be approved? Number one, it typically takes longer than the estimated time for the COVID-19 vaccine to be developed. Why the disparity?
Smith: OK, well, a couple of reasons. First of all, it takes anywhere from two to five years, typically to get a vaccine approved. A large part of that is due to making sure it works at each phase before you go ahead and proceed because of the financial consequences as we're developing these. You don't want to spend your resources on vaccines that are not going to work. So we get the results from each phase. Then we plan the next one, and it's a slow process. It's one that has a higher success rate at the end with COVID. That concern has been eliminated because of the urgency of getting a vaccine so that the government has stepped in and helped underwrite the cost of this development and has enabled things to move much more rapidly. The focus to be totally on safety, as it should be in the beginning, as well as the efficacy that's in the later trials, that's looking at what reduction we actually see in the population. So absolutely, it is gone very much quicker. Another part is all the regulatory delays. This is the first priority of all the regulatory authorities around the world. So reviews that normally could take six months on now take a few weeks because all their resources, as much as needed, are focused on making COVID [vaccines] as rapidly as possible in determining if these vaccines work, and they may not all work. I mean, the plans are that only a portion of the vaccines that are in Operation Warp Speed are actually going to be effective enough to get approved. That's why having all of these different mechanisms, different types of COVID vaccines being investigated at the same time is so important.