Transcription:
COVID Vaccines and Children

Dr. John Lantos: Hi, this is John Lantos with the Pediatric Ethics Podcast coming to you from Children's Mercy Hospital in Kansas City, Missouri. We talk about ethical issues in pediatrics and some of the controversies that arise in clinical care and research. We are very happy and lucky to have with us today, Dr. Barbara Pahud who is the Research Director in Pediatric Infectious Diseases here and also an Associate Professor of Pediatrics at the University of Missouri Kansas City. She has been hard at work on clinical trials of COVID-19 vaccines. Thanks so much for joining us today, Dr. Pahud.

Dr. Barbara Pahud: Thank you so much for having me.

Dr. John Lantos: Just wanted to start by asking you what we know about COVID vaccines that are in the pipeline today.

Dr. Barbara Pahud: I think if people have been paying attention, today is November 19th, we had a lot of good news in the past two weeks. The first one came from Pfizer. Pfizer reported a 90% effectiveness of their vaccine last week. And that is a vaccine that is given 21 days apart. And then this week, Moderna reported 94.5% effectiveness of their vaccine, a vaccine that is given 28 days apart. And of course, as usual Pfizer then modified their data to report 95% effectiveness of their vaccine when they finished analyzing the data. And the conclusion of this is, for everyone, anything over 90%, I'm happy. Those little degrees of point differences won't make a difference. It's a very good news in the vaccine world.

Dr. John Lantos: So both those vaccines work well. Which other ones are currently approaching completion of the phase 3 trials?

Dr. Barbara Pahud: So there are many vaccines that are currently in production. I'm going to discuss mostly the ones that are being worked up through the CoVPN, that's the Coronavirus Vaccine Prevention Network. They assist as part of, as I'm sure you have heard, Operation Warp Speed. And they have focused on a limited number of vaccines, even though there's many other candidates around the world.

But in the United States through Operation Warp Speed, there's also the AstraZeneca vaccine. Some people will call it the Oxford vaccine, and this is the vaccine that we are currently testing here in Children's Mercy in conjunction with KU Medical Center. That technology is slightly different from that of Pfizer and Moderna. Pfizer and Moderna are messenger RNA vaccines. This one is also a messenger RNA vaccine, but the difference is that instead of being delivered inside of a lipid nanoparticle like Pfizer and Moderna, the Oxford vaccine or AstraZeneca vaccine is delivered inside of a chimpanzee adenovirus. We should be reporting data of that study sometime at the end of December.

Dr. John Lantos: Has there ever been a vaccine based on messenger RNA before?

Dr. Barbara Pahud: No vaccine produced through messenger RNA has ever been approved in the world or used. There are vaccines that have been used with similar technology to the Oxford AstraZeneca vaccine, including the one that was approved for Ebola. So we have experience with some of these newer technologies, but not all of them.

In addition to the Ebola vaccine, other vectored vaccines in preclinical development include some vaccines that actually treat cancer, for example. So an adenovirus will have inside a target that will help treat cancer that has been used in clinical trials. So not only infectious diseases, but other technologies have used this delivery.

Dr. John Lantos: And is there something about COVID-19 that makes messenger RNA the most promising or preferred technology?

Dr. Barbara Pahud: I think more than the virus itself, what happened is stars had to align. And so I'll give you the example of H1N1. When we had the H1N1 pandemic, all the VTEU or vaccine treatment evaluation units started testing H1N1 monovalent vaccines at the same time, pediatric, pregnant, adults and the elderly. And that is because we already knew how to do influenza vaccines. The only thing we had to do was find the strain, the H1N1 strain, put it in a vaccine that we already knew how to produce and deliver and test it.

With coronavirus, the difference is we already had some experience with other coronaviruses, such as SARS-CoV-1 and MERS. Those two epidemics had hit the world earlier. And some researchers had started working on developing vaccines against those two diseases. But as, you know, these two diseases never made their way around the world like this human coronavirus has. And so those studies were stopped early.

When this SARS-CoV-2 appeared in December, it was first finally analyzed in detail in January and people started working on the vaccine. They looked at the historical experience they had with corona viruses and the speed at which you can produce vaccines. Messenger RNA vaccines are much faster than the old technologies we've used, like the influenza vaccine grown in eggs or protein- based vaccines that the protein needs to be developed outside of the body.

So it's not that the messenger in specific is good for coronavirus. It's just that it's a new technology that can very quickly produce many millions of vaccines at once.

Dr. John Lantos: So when you say quicker, you mean the production is quicker.

Dr. Barbara Pahud: Yes, the production. And the fact that we already had some experience with testing of these vaccines in similar viruses.

Dr. John Lantos: Okay. Will they all require two doses?

Dr. Barbara Pahud: So far, most of them will require two doses. There's only one so far that probably will require only one dose, and that is the Janssen vaccine. But it may be that in time they will decide they actually need two. When we got the protocol for the AstraZeneca vaccine that we're currently testing, the original contract said one dose. And we were already planning to do two because we could read the data that it looked like a boosting dose was going to be needed. And it ended up being that way. So I think all of them will require two, but so far only one is still claiming to require only one dose.

Dr. John Lantos: Have any of the studies so far included children?

Dr. Barbara Pahud: One study, the Pfizer study, has started including adolescents. And we are currently in negotiations with Moderna here at Children's Mercy to start the pediatric trials with Moderna. But others are probably going to follow soon. As soon as they're done finishing their testing in adults, they're all probably going to move into the pediatric platform.

Dr. John Lantos: And would they just go down to age 12 or would they include younger children?

Dr. Barbara Pahud: They will probably include younger children, but they're going to do this in a step- wise approach. So they finish the adult studies, then they'll move on to teenagers. And when they see that the data is reassuring, they're probably going to move down to six months of age would be my guess.

Dr. John Lantos: So as a specialist in pediatric infectious disease, how are you thinking about the ways that these will be offered or rolled out for younger children in the coming year? Will we wait until the studies are done?

Dr. Barbara Pahud: Yes, I think we have to wait until the studies are done. We don't want to go down the path that both China and Russia went, where they launched vaccines into the public skipping phase 3 clinical trials. That's not what we want to do in the United States. The reason why we are able to offer vaccines and claim that they are safe is because we do clinical trials to ensure the safety of vaccines.

So I'm sure everybody has heard in the news we had some halting of some of these clinical trials due to adverse events that happened in the study. This is normal in clinical trials. If a patient has something happen to them and they're part of a clinical trial, you need to evaluate if the adverse event was related to the vaccination or not.

We need to do that with pediatric patients as well, just like when we launched the rotavirus vaccine, for example. The vaccine was tested in over 60,000 participants, was approved by the FDA, was released into the public. And nine months later, after 1 million children have been vaccinated, we realized there was an increased risk of intussusception. And we were able to capture that because we have data safety monitoring systems in place in the United States.

So nobody will get a vaccine that has not been reviewed thoroughly by the FDA, because we want to make sure that we continue to maintain the public trust in vaccines.

Dr. John Lantos: I know that you have been working hard on recruitment to these clinical trials, particularly, trying to ensure that underrepresented minorities are enrolling in the trials in sufficient numbers to get some meaningful data about the vaccine's performance in those groups. What   are you doing exactly? And how is that going?

Dr. Barbara Pahud: I think I'm going to answer for us what we're doing. Traditionally, when we do clinical trials, we stay within what I call the ivory tower, right? The confines of the hospital where we work, where we have our clinical research center that normally sees patients for clinical trials. It's a beautiful office with nurses and research coordinators and physicians, and the patients come to us.

What we have done differently in this clinical trial is we have actually decided to go out into the community and bring the clinical trials to the community members. And there's two different mechanisms by which we've done that.

Number one, we partnered with the NIH to get mobile units and bring the clinical trial to the participants. So these are vehicles that have two rooms inside for us to see patients. We have the capacity to process blood, prepare vaccine and do everything that we would normally do in a clinical research setting in a mobile unit.

So there's four different stops where we are taking this vehicle. The first one was Truman Medical Center, because we have a long-term care facility there where we are aiming to enroll patients over the age of 65, which are a high priority for this study. This week, the mobile unit is parked at Health Partnerships, which treats primarily Latinx community members. Next week, it's going to Wichita where it's going to go to Dold Foods to enroll, basically, workers that have continued to work throughout the pandemic to ensure that we all have access to food. And finally, we were looking at a church as well to enroll African-American communities in Wichita. The church ended up deciding not to participate. And so we moved that mobile unit to go to a clinic that is serving basically underserved communities.

The second thing we're doing in addition to the mobile unit is we have started doing clinical trials in sites that we have never done research at before. In Kansas City, that site is Swope Clinic. And the second one is KC Care Clinic. Both of them serving, one, African-American communities and the other one, primarily HIV and minorities and underserved populations, all of which could benefit from being enrolled in the clinical trial.

Dr. John Lantos: Historically, there's been a lot of distrust in the black community about medical research. Are you getting some pushback as you try to enroll patients?

Dr. Barbara Pahud: Absolutely. So the second part of your question earlier was how's it going? And I am happy to report globally it's going well. We have enough information in Latinx and African-American communities. But locally, it's not going so well. We've had a lot of resistance from the community. There is a lot of distrust.

I have tried my best to communicate to the public that the vaccine that we are testing is the same for white, African-American, Latino, native American. And I understand the historical reasons why there is this trust, but this is a very different process that we're doing right now and it's important for these communities to volunteer, to participate so that we can have enough data to ensure that the vaccine is safe in all communities that need access to this vaccine.

Dr. John Lantos: Studies in children are also ethically controversial and raise unique issues about consent and about risk profiles. What do you anticipate as the eligible populations moved down to younger and younger ages? Do you think we'll be able to get enough participants?

Dr. Barbara Pahud: I hope so, but I am worried, I will confess to you. Obviously, if we are seeing distress among the adults, imagine adults volunteering their children to do this might be even harder. I have no doubt that those that have already participated in the studies will be happy to have their children participate because they now know how the process works and they understand how it's safe and effective. But there's only a limited number of spots for people to participate. The pediatric trials, I'm guessing, are going to be smaller than the adult trial so maybe it'll be easier for us to recruit. Usually traditionally, it is mostly children from a certain socio-economical class and background.

And again, we're going to do a push to try to include minorities and African-American communities, Latinx and, children that normally don't have access to clinical trials. And that includes also rural children. That's why we're sending our mobile unit and participating with our partners in Wichita.

So we will continue to push and do the best we can to make sure that enrollment is diverse. But yes, the fact that they're children alone brings other issues such as imagine my daughter who is 12, she wants to participate, but I'm sure after she gets her first shot, she might be afraid of getting the second one, right? Because she's a teenager and she will not stop being a teenager in spite of COVID. And if a teenager declines to participate, nobody can force that teenager to do it. So teenagers need to ascent to participate in research. And if they don't provide that ascent, it's game over. And well, you know, they may just pull back once they see a needle or once they understand there's blood draws and they are allowed to do that. So it will be a different challenge.

Dr. John Lantos: Another issue that could arise is that the vaccine will be approved either fully or under an emergency use authorization for adults and some parents of teenagers or younger children may want it before the studies have been done in kids. What would you advise doctors and parents in that situation?

Dr. Barbara Pahud: Well, in this situation, it's actually an easy answer. If the vaccine is approved under emergency use, it will not be approved for emergency use in children until we have data for children. So if parents are deciding to withhold their children from participating, waiting for the vaccine, we're never going to get a vaccine if not enough parents let their children participate, because then we will never have the data that allows us to submit it to the FDA for the emergency use authorization.

So it's a difficult road understanding that for us to have that emergency use authorization, enough people need to volunteer. Just like we saw with Pfizer, 40,000 people, Moderna, 30,000 people. It's thanks to those 70,000 volunteers that America is going to be able to have an emergency use authorization vaccine. We need to keep doing that for all the other products that are coming behind Moderna and Pfizer and for the pediatric studies, or we will not reach that EUA and there will not be enough doses if we only keep two vaccines in circulation.

Dr. John Lantos: So the only way that parents will be able to get the vaccine for their children in those circumstances will be by participating in a placebo-controlled trial.

Dr. Barbara Pahud: And of course that means they may or may not get the vaccine because they could just easily get the placebo as you know. It's random and it's blinded.

Dr. John Lantos: And that's how we know whether it's safe and effective.

Dr. Barbara Pahud: Absolutely. And I think something else I wanted to discuss with you briefly, which I know is a difficult topic of conversation, but one we must have is anthropologist, Margaret Mead-- I think I pronounced her name correctly-- was asked once by a student what she considered to be the first sign of civilization in a culture. And even though most people would say, you know, the first pot, pottery or something, or, you know, a weapon or a building, she actually said it was a femur that had healed after being broken. And the reason is that in the animal kingdom, if you break your leg, you die. You cannot run from danger. And so whenever humans started helping each other, staying behind to help that person who broke their leg, that's your first sign of civilization.

So this is my message. We all need to do that. This is a time where we can't act selfishly and leave those behind that can't run and have a broken leg. We all want to get out of this. And in order to do it, we all need to line up, raise our sleeves and volunteer for these clinical trials, those of us who can do it so that others can benefit from the vaccination. If there's not enough people volunteering and signing up, we will not get out of this problem.

Dr. John Lantos: What have you seen among the healthcare professionals or doctors and nurses enrolling in the trial?

Dr. Barbara Pahud: Yes, actually, we have a lot of them enrolling and speaking of ethical issues in this podcast, one of the problems we are going to face is once the vaccine is available under emergency use authorization, we need to ensure that these doctors or nurses are protected against COVID, right? So we're probably going to have to unblind them and find out if they got vaccine or placebo, because those that got placebo need to get their vaccine under emergency use, because we need to make sure that they're protected.

So we are currently talking about that in the CoVPN and in Operation Warp Speed. How are we going to deal with participants that are frontline workers that need to get this vaccine as a priority if they enrolled in the clinical trial to be able to maintain the integrity of the data?

Dr. John Lantos: One of those conflicts between good ethics and good science. thank you so much for taking the time. I can only imagine how busy you must be with these trials. Is there anything else you'd like to say before we sign off?

Dr. Barbara Pahud: I think I would just like to thank everybody that has volunteered to participate in this study. And I hope anybody who is able and capable will consider doing it, especially for the pediatric trials. We definitely need the data. Thank you.

Dr. John Lantos: How do people sign up if they want to participate?

Dr. Barbara Pahud: When we have a study here at Children's Mercy, we will be advertising here. We still don't have it yet, so it's too early to tell. But, for the larger clinical trials, through the coronavirus prevention network. They can just Google Coronavirus Prevention Network and they will be led to a site where they can volunteer to participate in any clinical trial that they're eligible for.

Dr. John Lantos: And then somebody will get in touch with them.

Dr. Barbara Pahud: Hopefully, and that the website is www.coronaviruspreventionnetwork.org. And I said, hopefully because luckily there's over 80,000, 90,000 people that have registered. So in the Kansas City area alone, I can tell you, we had about 7,000 people that were eligible to participate in our studies based on their ZIP code. And we only needed a thousand participants. So we're only calling the ones that we can see.

So joining that registry does not necessarily mean you'll get a spot, but you will be helping us because it makes it so much easier for us to recruit when there's a list of people waiting to participate.

Dr. John Lantos: With these two studies, uh, the Pfizer and the Moderna study, were they entirely done within the United States or are they worldwide?

Dr. Barbara Pahud: Most of them have been worldwide efforts. Same thing as the AstraZeneca one we're currently doing. We have a site in Brazil and another one in the UK, and I think there's another one in South Africa. So most of these studies have been worldwide. Again, to me, that's a great show again of we're all joining arms together, forces together to bring this virus to a halt across the world. We can't think about this as an American problem or a, you know, individual problem. We all need to work together to get this under control.

Couldn't agree more. Solidarity is the guiding principle here. Once again, I'm speaking to Dr. Barbara Pahud, who's the Research Director in our Division of Pediatric Infectious Diseases at Children's Mercy Hospital in Kansas City and an Associate Professor of Pediatrics at UMKC. I'm John Lantos. This is the Pediatric Bioethics Podcast from Children's Mercy Hospital. Thanks so much for listening.