Why Aren’t Highest-Risk People Better Represented in COVID Vaccine Trials?
— More side effects can create delays and higher costs, says Sharon Inouye, MD
December 30, 2020
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Vaccination across the nation is now underway, with healthcare workers and those living and working in long-term care facilities among the first to receive the vaccines. Long-term and nursing home residents make up about 1% of the U.S. population, but have accounted for roughly 40% of all COVID-19 deaths, while those older than 50 are more likely to die from COVID-19 than younger age groups. However, they’ve accounted for less than a quarter of total COVID-19 vaccine clinical trial participants. Why are they so scarcely represented in trials?
To learn more, we chatted with Sharon Inouye, MD, MPH, a professor of medicine at Harvard Medical School and geriatrician at Hebrew Senior Life. She is also director of the Aging Brain Center at the Hinda and Arthur Marcus Institute for Aging Research. The episode kicks off with a discussion with 60-year old clinical trial participant Kelley Pick, to hear about her experience in a trial.
The following is a transcript of their interviews with “Track the Vax” host Serena Marshall:
Serena Marshall: Kelley, thanks for joining us here at “Track the Vax.” Tell me what made you want to sign up for a clinical trial.
Kelley Pick: To be honest, since COVID-19 started, I would say I’d stand on my head to make this go away and… late summer, I was watching TV with my granddaughter and a commercial came in, came on for our local station and said that Meridian was looking for participants age 55 and older to join the Pfizer vaccine study.
And my granddaughter said, “grandma, you should do that.” And I thought, yes I should.
Marshall: So she really was your impetus to go ahead and sign up. What did you think when you were signing up for this?
Pick: You know, a little hesitant, we thought, well, let’s check it out because we do have to do something to make this go away. And it was just a 40 minute drive and did it online. Registered online and they called back and answered all our questions. My husband said, well, I’ll do it with you. So the both of us did.
Marshall: Why don’t you walk us through that process?
Pick: We registered online, found the website, which was mentioned on the television commercial, and then we got a phone call back. Telling us that this was with Meridians Pfizer’s vaccine study, and they asked us some questions and we both qualified for the 55 and older study. So that was back in August.
And they said that we qualified and they’d be calling us to set up a time.
We got the phone call to come on down. And the first thing they did was to test us, to see if we currently had the virus or if we had antibodies showing that we’ve already had it.
And they did not want those type of participants. They were looking for clean people, I guess. So they can find out if the vaccine worked and we both did pass that test.
Marshall: Now, getting that vaccine though, I’m sure it must have been a little anxiety inducing. It’s a clinical trial. You’re not really sure what to expect. How did they prepare you for that?
Pick: They did. And talking to some other professionals, we were in phase three of the study; where, I think phase two is where they work on if there was any health hazards, more side effects. So we felt pretty confident being part of the phase three study that if they’re worth something’s in there, they had worked out.
So we were pretty confident going into it. We teased each other about growing a third eye, but… [laughter]
Marshall: Do you think that you and your husband received the same one? Whether it be the vaccine or the placebo?
Pick: You know, I would have to say, I doubt it just because they have a perfect 50/50 case study and I read up on it and I know where they feel so confident in the vaccine is that one spouse that was part of the study may get the virus and the other spouse does not. So we both hope we have the vaccine, but we don’t know.
Marshall: If they unblinded it and found out that you or your husband was a placebo recipient, would you then still go forward and get the full vaccine or would you wait it out?
So you could be that control group.
Pick: We would probably get the vaccine because to be honest, that’s why we signed up for the study. That we want it to move on with our lives and we feel the vaccine is so good. Um, we will listen to them and find out how important that is, you know, for the case study to continue. So. I can’t say that I’m a hundred percent sure that if I received the placebo, that I would say, no, I want the vaccine.
Like I said, I would listen to them and find out how many they need. But if all things are the same and it doesn’t really matter, I can’t wait to get the vaccine.
Marshall: And one of the things that they don’t know about this vaccine is long-term immunity, but also if you can still get COVID and be a carrier, pass it on, even though you might not have a bad reaction to it. Is that something that concerns you and your husband?
Pick: We definitely do not want to be COVID spreaders. And so, you know, we still would follow up on the professionals advice and do things like that. But as far as worrying about our own health, the vaccine is not near as bad, I believe, as getting the virus.
Marshall: It’s a new technology, mRNA vaccine. Did they talk to you about that when you went into it?
Pick: Yes. And they all so said that at any time that we would like to get a different vaccine, there would be no problem in dropping out of the study and getting a different vaccine. Right now, to be honest, we got this vaccine because of how close the clinic was to us. And I’m sure with modern technology we’re going to have a lot of great vaccines.
So we’ll just have to wait and see.
Marshall: What do you tell your granddaughter who encouraged you to sign up?
Pick: I told her I was doing this podcast today and said, if it’s alright with you, I’m going to tell them the truth about this. And I do feel it’s such a good conversation to have with our young children. She’s had to miss a few days of school because she was exposed. And she did not like that being at home.
So getting our kids back in school, those types are the really important things to get back to normal.
Marshall: Dr. Inouye , thank you so much for joining us here at “Track the Vax.”
Sharon Inouye, MD: I’m delighted to be here today. Thank you for inviting me.
Marshall: Dr. Inouye, we want to talk about some of the COVID vaccine trials and the age of those trial participants. Now we’ve seen in the COVID vaccine study for Pfizer, those over the age or above 75, we’re only 4% of the study, with Moderna above 65.
We’re only at about 25% of the study. Is that an acceptable breakdown of the cohort? When you’re looking at who’s getting these vaccines?
Inouye: Yeah. So Serena, those are really good questions. I would, of course love to see more robust numbers represented in both those trials. But I think the reality is they did make great efforts to try to include some of the population. And I know the group 65 to 75 included about 2200 patients, which was about 21% of their cohort.
But then, as you just said, 75 and older was only 4% of the cohort or about 1,700 patients. But I think it’s noteworthy to state that some of those, Older adults included also had comorbidities like hypertension, diabetes, chronic pulmonary disease.
So they really did make efforts to try to get individuals who would be more representative of our older adults. I don’t think though that any nursing home patients were included. At least there are, there’s no indication that they did. And so the testing in that population, I think has been very limited in both the Pfizer and the Moderna vaccines
Marshall: Why is it so important to specifically study those in nursing homes, if you’re looking at the age cohort that nursing home residents include?
Inouye: The hardest hit venue in terms of proportion of severe illness from COVID and death has been in our long-term care facilities in our country. That is a targeted priority group as identified by multiple expert panels and advisory groups, and they are being targeted in phase one of the vaccine release effort.
I think everyone would agree. It would have been beneficial if there, if there had been more testing in that population prior to the release.
Marshall: When you look at that age group, what we heard a lot about at the different committee meeting hearings on these two different vaccines where you could extrapolate the data and have it represent those older Americans pretty well. Is that not really the case or are there different reasons that that older group needed to be a more robust number in these clinical trials?
Inouye: That’s a really good question. Serena. I do think that the population in long-term care facilities tends to have more comorbidities, meaning more chronic diseases. They’re on more medications. A lot of times there’s a high prevalence of cognitive and functional decline. And also we know from other types of vaccination studies that the immune response may be less robust than in younger populations are, or even the same age populations that are not in a nursing home.
And so yes, to test both the efficacy of the vaccine and potential side effects of the vaccine in that population would have been helpful, I believe, but I think you can still extrapolate that the vaccine will have some effectiveness. I think it’s just not clear how robust that will be exactly.
And also the, what the exact side effect profile might be.
Marshall: As a geriatrician, does it concern you that there’s still so much we don’t know about that specific cohort these different vaccines?
Inouye: Yes. Well, I wear two different hats and as a geriatrician, yes, it does really concern me, and I think about it all the time and patients are asking me, should I get it? I’m not sure I feel totally comfortable that it’s been adequately tested. And my response is influenced by several factors.
First, is that in any kind of vaccine or treatment trial, you have limitations in what you can accomplish, right? In the clinical trials, there’s always that limitations. And even with the flu vaccines that we’re very used to giving to this population every year. The individual flu vaccines each year are not robustly tested in the nursing home population either.
And so that’s not unusual. And similarly for other treatments, they’re not always tested in older adults before they’re released to the market.
Marshall: Why is that?
Inouye: I think it’s the case because, frankly, there, there is some degree of age-ism in our country, and that population can be more challenging and difficult to study and can delay your procedures. It can be more expensive and there can be more side effects. And so I think, obviously if you’re a drug developer and you’re trying to develop something quickly and you want it to have the least side effects, then you are going to shy away from that population.
And there’s been a lot written about this in terms of cancer drugs, and cardiac drugs, and a lot of other treatments that are primarily the largest audience, the largest target population is older adults that the testing hasn’t been adequate in the past. And the National Institutes of Health has even created a new policy that older adults must be included in any trials that are funded by them.
Marshall: That’s interesting. That’s a new policy?
Inouye: It went into effect at the beginning of 2019, so fairly new.
Marshall: Quite shocking. It’s taken us this long to have that as a necessity.
Inouye: Exactly, exactly. And so that’s still an issue. And I think it’s both logistical, but also I think there is an attitude that it’s not necessary to include older adults. And that’s what I’m really trying to fight against.
Marshall: But how do you drum up interest in getting more older adults to want to participate in clinical trials?
Inouye: So there is huge interest amongst older adults in participating. And in fact, I had hundreds of people reach out to me after one of my articles came out about “how do I get into a trial or, I volunteered and I was turned down.” I can’t tell you how many times I heard that. Just an outpouring of interest. And, I think a lot of it depended on how physically close you lived to a clinical trial site and then just the strategy by which they were doing outreach. But I think a lot of older adults were very, very willing to participate.
I run studies and trials in the over 70 population and it’s just amazing how much that generation wants to contribute to science and to advancing healthcare and to leaving a legacy. And feel it’s very important. They feel it’s part of their mission. And I did want to say that I do think that’s another reason why older adults would be willing to get the vaccine, because I do think many of them feel it’s their public duty.
Marshall: Is that a different way of thinking one generation to the next?
Inouye: I think so. I mean, I see it very much in that older generation and I think it’s a different mindset, right? This was the same generation though, that lived through World War 2 and was used to doing things for the country and, do a lot of self sacrifice for the sake of the country.
And I kind of feel like that attitude has been lost in our country.
Marshall: You said though that a lot of them were turned away from the clinical trial, but it seemed that they were having trouble enrolling that age group. So what is the juxtaposition there?
Inouye: It’s similar to what I wrote up in my paper in JAMA Internal Medicine, that many of the trials had what I consider to be ageist, exclusionary criteria criteria that were unjustifiably, excluding older adults, like requiring that they communicate by text messaging, requiring that they have Wi-Fi at home that they were using regularly, that they would respond to immediate messages on their Wi-Fi.
You know, and that just, why can they call them on the phone? I’m not sure that’s why these particular patients were excluded, but there were also other criteria that didn’t seem well justified, like very well controlled, mild comorbidities. Didn’t seem like a justifiable exclusionary criteria. Maybe they had trouble with their vision or their hearing and that should be something you could adapt to and should not be an exclusionary criteria, but it was from some of the studies that we found. There’s no reason from a medical standpoint, right. That, that should be an exclusion.
Marshall: You would think that nursing home residents might be an easy group to include in a clinical trial because you have somebody there who’s essentially monitoring their vitals and their wellbeing on a day-to-day basis.
Inouye: Yup. Yup. I totally agree.
Marshall: That’s not the case?
Inouye: It’s not the case because I think they’re viewed as high risk. You may need to get proxy consent, meaning from a family member. And so it takes extra time. But I think the reality is the concerns that your results may not look quite as good, right, in that population. And so it may slow down your time to approval.
Marshall: So you’re saying because they have more comorbidities or have other factors that would play into how they received the vaccine, they might not be giving the clinical trial the results they’re looking for?
Inouye: Right because their immune response may be a bit less robust. And so they may get more infections despite the vaccine. And then there may also be more side effects.
Marshall: One would think that you would want to know those things before mass distribution of a product.
Inouye: One would think so. I agree, but I think that you can understand if you were on the side of expediency, right. That it may slow you down. It may make your results look worse and so…
Marshall: So we wouldn’t be seeing that 95% efficacy.
Inouye: We may not. You can call it age-ism or you can call it expediency. I would have wanted it tested in that population and I would have liked to see the results in that population.
But again, that’s rarely done with any treatment before it’s released.
Marshall: What are you seeing as some of the major concerns? Among older adults ….caregivers for older adults when it comes to getting the vaccine?
Inouye: Well, I’m hearing a lot that: “This has been so rushed. Are we sure it’s okay? Are we sure it’s safe? Has it been adequately tested? Do we know that it works? Do we know it’s not going to have side effects?”
Marshall: Those are a lot of the same questions we’re hearing among younger…
Inouye: …everybody, right? Yes. I think it’s all the same concerns and. And I totally validate where those questions are coming from. We have to admit that this project Warp Speed and all of these vaccines have been developed in an amazing process and amazing burst of incredible science, frankly, it’s a miracle.
But I think the best science has gone into it. The testing has been there. I think everything has been done according to strict guidelines and standards. As soon as my number is called, I’m going to be in line to get it. And I have a 91 year old mother. We are all firmly united that the risks to my mother of getting COVID are so much higher then the risks of side effects that could be serious, but we know are going to be rare.
But it’s a gamble that where, I think the equation is definitely in favor of getting the vaccine.
Marshall: When you look at some of the public prominent figures who we’ve seen getting the vaccine, some of the prominent older celebrities, or even politicians. Does that play a role in helping alleviate some of the concerns specifically among this subgroup who in some cases were alive during the polio vaccine. Saw the Elvis push — does that play a key role in maybe helping them decide to get it or not?
Inouye: I think it does raise confidence. I think when they see, people they admire and respect and trust getting the vaccine…I mean, it reassures me right, when Tony Fauci gets the vaccine, then I know like, I’m okay. He’s my hero.
This is really going to change the equation in our favor in favor of humankind. Once we can get everybody vaccinated.
Marshall: When we look at this vaccine, there’s two doses. How do you ensure uptake among this group of getting both doses? They might go in for the first and then the pain and the discomfort, dissuade them from following up with the second.
Inouye: Yeah, I think in the long-term care setting, that’s easier to control because they’re there in the facility. If it’s someone who has to go back. I don’t know exactly what healthcare professionals or like if it’s through CVS or Walgreens, I’m sure there are reminder systems and follow-ups.
I am hoping that people will get the second one because definitely, to go through the first one and not then make sure you have adequate immunity. It’s sort of like going through the pain and not getting the gain. And so I hope people will be willing to get both.
The side effects, they can be uncomfortable, no question. The painful arm and the flu-like syndrome for a day or two.
But, you know, those are signs that it’s working and probably similar to other vaccines that people have received.
Marshall: I want to come back to that question of age-ism. There was some debate when discussing who should get the vaccine and in what order …. essential workers versus elder Americans more broadly, not talking about those nursing home residents. Now we know older Americans are more susceptible to COVID.
We talked about how they have more comorbidities in some cases related to their age, but then there’s the question of the essential workers and the need to get the economy back up and running. This is definitely an ethical question, but is it one that ultimately… Does it come down to the question of age-ism?
Inouye: Yeah. It’s a really good question. I campaigned very hard for older adults to be included in that phase one. And older adults with comorbidities are included in that phase one. So that is the highest risk population in older adults as well in the facilities.
I think in part, it may have been influenced by age-ism, but also in part just by practicality. Right? You know, you’re only going to have a limited amount of vaccine early on, and it is, I do agree. It’s really important to have frontline healthcare workers, for instance, protected because they can also spread it, right?
Amongst many others, other patients who were very ill and then also that the staff in facilities, as well. In fact, I don’t know the exact percentage, but it’s been well-documented that many of the outbreaks in long-term care facilities are initiated or propagated by staff. And so I think that’s really important that staff in long-term care facilities be in that first group, which they are.
And so I think that will help both with spread and curtailing the infection. I mean, ideally what we’re hoping is everyone, right. Will be able to be vaccinated within a few months, ideally by the late spring. Definitely by the fall, it’s projected that there will be enough for everyone who wants to get vaccinated to be vaccinated.
Marshall: So, looking at this specific age cohort….Where do we go from here? What have these vaccine trials for Covid taught us when it comes to elder inclusion in clinical trials more broadly?
Inouye: I honestly thought a better job would be done. That’s really what I had hoped for because of knowing that, the population so affected with COVID was so disproportionately skewed to older adults. I thought this has gotta be the point at which this will change. This, this has gotta change it.
And in reality, I mean, some efforts were made, right. The age range in the Pfizer trial was 75 to 91. So there were efforts made to include people, in their eighties and even someone 91. So that’s incredible. But, as we pointed out at the beginning, it was less than 4% right. Of the overall trial population.
So, that was disappointing. Very small icing on the cake. It just wasn’t a genuine effort.
Marshall: So, did we learn anything as a society then?
Inouye: I don’t know….I haven’t heard a loud public outcry about it, which was disappointing. I had hoped that would happen. I think, when I talk to people working at the FDA about this, they also acknowledge this. They also predicted that there wouldn’t be very many included and that the argument was going to be well, this will all be testing, tested in post-marketing surveys, which is how most of the product testing happens in older adults.
After approval in what’s called post-marketing surveillance. And, I had hoped this would be different in that, because of the demographics of COVID that we could make it different. And so I’m hoping to continue to use this as an example, and as a platform for maybe changing things in the future.
I think people are stepping up and speaking out for our older population, but it’s going to take a while to make these major changes happen, right? And there’s going to need to be policy change and regulation change. And I was so disappointed when the FDA did not require older adults, a certain proportion to be enrolled.
That’s what I was so hoping would happen. And they did not require it. It was a recommendation, but no stronger than that. And that’s where we need to change things. It needs to happen at a policy level. And so I’m hoping over the course of time and with what we’ve seen here, what we’ve learned, what we’ve shown, that we can start to make those changes happen at the policy level.
Marshall: I hope that you’ll keep us updated on how those policy changes go as you continue to push forward on this issue. Thank you so much for joining us here at “Track the Vax.” One of the last questions we love to ask everyone. I know you mentioned it earlier, when it’s your turn in line, you do plan to get the vaccine?
Inouye: I do hope to get the vaccine. The system crashed at my hospital because of too many healthcare professionals wanting to sign up all in the same day. So, I decided to wait a little while longer to sign up.
I don’t work in the emergency room or in the intensive care units. So, I’ll probably be in the… I’ll definitely be able to get it, but I don’t know exactly when. But I’m hoping to be able to get it soon.
Marshall: Well, good luck. And thank you again for your time.
Inouye: Okay. Thank you so much.