Yella Hewings-Martin, Ph.D.
Nathan volunteered for a COVID-19 vaccine clinical trial. Lindsay is a pharmacist and the drug content integrity manager at Healthline Media. In our conversation, we discussed the realities of taking part in a vaccine clinical trial, side effects, vaccine hesitancy, and the ethics of unblinding a trial during a pandemic.
It’s been a year since the first cases of what would later become known as COVID-19 were reported in China. Vaccines to prevent people in high priority groups from developing the disease are starting to be rolled out in several countries.
But will vaccines successfully end the pandemic? This strategy can only work if enough people receive the vaccination.
At this crucial turning point in the pandemic, I spoke with two people who shared their insights into COVID-19 vaccines.
Nathan Richardson is an executive at Red Ventures who volunteered for the Pfizer-BioNTech phase 3 vaccine trial. Lindsay Slowiczek is a pharmacist and the drug content integrity manager at Healthline Media. Both currently live in Florida in the United States.
In our conversation, we discussed Nathan’s motives for volunteering for a vaccine trial and his experiences. We also talked about vaccine hesitancy, side effects, and the ethical implications of running a clinical trial during a pandemic.
From the Peace Corps to a vaccine trial
My first question for Nathan was why he volunteered for a vaccine trial. He told us that he was a Peace Corps volunteer in his early career, during which he participated in several studies that investigated experimental treatments.
Nathan: “I had read in the press that Pfizer [were] looking for volunteers for their trial. And I made a calculation that, at this point, they had 15,000 participants already.[As] a multibillion dollar company, that had a lot at stake in [the sense] that the chances of the vaccine trial being damaging to me were pretty low. I thought I could contribute to help advance the need for a vaccine by volunteering.”
Pfizer started recruiting volunteers for their phase 3 vaccine trial in July. By November, the trial had over 43,000 participants. Nathan took us through the details of his experience of the trial step by step.
Nathan: “So the experience has been quite a journey. And it’s definitely been eye opening into all [the work that is] involved in a vaccine trial.
I first submitted my name and contact information on Pfizer’s site, where you can find a list of all the vaccine trials that they have underway. I was contacted by a representative asking for additional information during a prescreen. And then, I was contacted a few weeks later by a trial site that wasn’t too far [from] me.
They asked me to go over and sign some releases, which I did. A few weeks later, they had collected all of my healthcare information from my primary care physician and put that into what I thought was a fairly robust dossier. It was a three-ring binder that was about 3 inches thick of my health record.
At that point, I was invited to go in for the first shot. [At the appointment,] they went through [a lot of documentation,] drew blood, and did a COVID-19 test.
Then, they moved to warm up the vial of the first shot of the vaccine. About half an hour later, I got the shot. [They] ask you to wait for another hour to make sure that you have no adverse reactions, and then I was free to go home.
The whole process, from the time I submitted [my details] onto the Pfizer vaccine trial website to going in [to have the shot], probably took a total of 7 weeks.[When] I left the trial site the first time, they sent me home with an at-home COVID-19 test kit as well as ensuring that I downloaded TrialMax, which is the vaccine trial monitoring system. So it’s an app that I report in weekly whether or not I’ve had any symptoms related to COVID-19.”
Getting the second shot
Nathan went back to the clinical trial site to have his second shot 3 weeks later. Similar to his first experience, the trial team took a blood sample and administered a COVID-19 test.
This time, he was prepared to stay for a while after his shot and brought some reading material to occupy him.
Pfizer have sent out communications to him on a number of occasions. They told him when they planned to submit their trial data to the Food and Drug Administration (FDA) for authorization, and they also told him that they would keep him informed of the results of this application and the next steps.
I asked Nathan if he was nervous at all to have an experimental vaccine.
Nathan: “Peace Corps volunteers are guinea pigs for a lot of different things. [Also,] I’m much more confident in Pfizer having been thorough [in testing the safety of] what they’re inject[ing] into my body than [many of] the other things that I do on a day-to-day basis.”
All in all, I’m impressed with the thoroughness and the deliberate, intentional way that they’re going about this. It seems very scientific and evidence-based, and they use a lot of documentation to make sure that they’re getting this right.
As for the technology that underpins the Pfizer vaccine, Nathan felt that he was well-informed.
The Pfizer vaccine is the first of its kind to have authorization for use in humans outside of clinical trials. It uses messenger RNA (mRNA) technology.
Fear of the unknown
Most vaccines use a whole virus or bacterium or a part of it to teach the immune system how to defend itself in case of a future infection. Rather than delivering a viral protein in the vaccine, an mRNA vaccine instructs our cells to make the SARS-CoV-2 Spike protein, which the virus uses to gain entry into our cells.
Some people may have concerns about the safety of a vaccine based on novel technology.
Lindsay: “To most people, this technology literally came into being because of this pandemic, when in fact, it’s actually been studied and looked at as a potential mechanism for vaccines for several decades now.
There [is] a history of research for this type of vaccine for SARS and MERS. And I think hesitancy about the technology itself is based on a lack of information.
It’s incumbent upon public health institutions, our government, and our healthcare professionals to convey that information that this isn’t brand new, this has been around a while, it just seems brand new because it’s not part of everyday conversation.
It hasn’t been in the media because there hasn’t been a need for it to be in the media. Because it’s been studied so extensively for other conditions, like SARS and MERS, scientists were able to pivot really quickly and [use] what they know about the mechanism for those conditions and apply it to SARS-CoV-2.”
Lindsay also shared with us why she thinks some people may fear that a new type of vaccine could cause unforeseen side effects.
Lindsay: “I hate to say it, but the flow of information has just not been optimal or ideal.
So I think it’s really [important] to provide clear and consistent messaging about the safety data related to this vaccine, to Moderna’s, [and] to AstraZeneca’s.
Related to that, I think we need to be able to be clear and transparent about the actual data […], not so much filtered through the lens of any particular media or particular site.
I think, as far as what people are concerned about with this, [it] isn’t so much [the] specific side effects from it. It’s more just the unknown. And the general mistrust in the situation that the pandemic has brought about.”
Nathan didn’t experience much in the way of side effects. He recalled a slight headache and feeling just a little off, which he said may have been due to an unrelated running injury.
If he had experienced side effects, he would have logged these in the TrialMax app. At the next follow-up visit at the clinical trial center, the staff also asked him about any side effects.
Lindsay: “I’m curious, Nathan. Did you notice any difference between the first shot and the second?”
Nathan: “No. So that’s why I think maybe I had the placebo. But on the flip side, I rarely have side effects from medicines or shots.”
Lindsay: “I think that that really just highlights that it’s going to be very unique to the individual getting it.”
Side effects of vaccines are relatively common. For example, around 80 percent of people have mild or moderate pain at the injection site after receiving a shingles vaccine.
Lindsay: “I think most people can remember times that they’ve gotten the flu shot, and at the very least your arm is a little sore, or you feel a little sluggish that day or the next day.
Maybe you experience a headache. It’s more rare for someone to actually feel sick or actually feel like they’re experiencing fever or nausea or chills or anything like that.
However, [from] the data that we’re seeing, particularly from Pfizer, and the Moderna trial looks very similar in this regard, […] most people will experience injection site pain, something like almost 85 percent of people.
Most people, about two-thirds of people, will experience fatigue, headache, muscle pain, that type of thing. But they are seeing that those symptoms resolve either on their own or with something like over-the-counter Tylenol or ibuprofen within 1–2 days.”
Fears over the safety of vaccines and potential side effects are some of the biggest factors contributing to vaccine hesitancy.
‘Reach out to somebody’
The fact that people are concerned about vaccines is nothing new. However, the pandemic has certainly added fuel to the fire.
In a December 2020 article in Psychological Medicine, Prof. Daniel Freeman — from the Department of Psychiatry at the University of Oxford — analyzed vaccine attitudes in a representative sample of 5,114 adults in the United Kingdom.
“First, the good news: We found a substantial majority in favor of a COVID-19 vaccine, with 72 percent willing to be vaccinated,” he wrote in a blog post about the research.
“But this isn’t enough to be truly considered a consensus. [Sixteen percent] of the population are very unsure about receiving a COVID-19 vaccine, and another 12% are likely to delay or avoid getting the vaccine. One in  people describe themselves as anti-vaccination for COVID-19.”
In the U.S., a recent poll from the Kaiser Family Foundation showed that the percentage of people who would likely or probably have a COVID-19 vaccination if it was deemed safe by scientists and available for free rose from 63% in September to 71 percent in December.
For Lindsay, engaging in conversation with someone who has concerns about COVID-19 vaccines is critical.
Lindsay: “I think the first thing to [do] is figure out why. You need to listen to someone’s concerns, try to understand where they’re coming from, and have empathy for where they’re coming from about that hesitancy or that mistrust.
Because often, like we discussed, it’s related to a lack of information. And you might be able to provide that clarity or point them in the direction of the evidence so that they can look at it themselves and make an informed decision for themselves.
I plan on getting the vaccine. I recommend it to my friends and family. Because I’m confident, like Nathan’s been describing, in the rigor of the trial’s design and the follow-through in collecting [those] efficacy and safety data.
I would recommend that anybody who is hesitant about the safety of the vaccine […] reach out to somebody.
If you don’t have a science background, or you don’t have a healthcare background, reach out to somebody in your life or ask around if there’s anybody in your friends’ or family’s lives who can have a conversation with you and describe what the study looked like [or] describe what the results mean. So that you can make that informed decision for yourself.
Or, if you do have that background knowledge, go to the FDA site and look at Pfizer’s data, look at Moderna’s data, and see if the risk versus benefit ratios there make sense for you and if that’s something that you feel comfortable with.”
The ethics of unblinding a study
Nathan was convinced that he was in the placebo group in his clinical trial. Pfizer have informed him that he will have the option to find out which group he was in at his 6-month checkup.
At the same time, if he was in the placebo group, he will be able to receive the vaccine.
The ethical implications of running a placebo-controlled vaccine trial during a pandemic are complex. Regulators such as the FDA need to know that any experimental vaccine can significantly reduce the chances of developing the disease if they are to authorize or approve it.
Having a placebo group is, therefore, standard practice in most vaccine trials. But at what point does it become unethical to expect volunteers to remain in the placebo group if a potentially life saving vaccine is available?
There are no easy answers to this question.
Nathan: “If I am [in the] placebo group, I would surely get the vaccine. There are some people in the trial who think that they should unmask it earlier.
But, you know, as a generation, we’ve been asked to sacrifice so little for our country or for humankind. Let’s just […] do the right thing to get the science right, to get the right people vaccinated the right way.”
Lindsay: “I would just like to add to that. Given what we know about the scarcity of the available vaccines at this point, there is [an] ethical debate about whether [to give the vaccine to] the placebo group.
When you went into the study, Nathan, there was no promise that you would get the vaccine. [Your participation] was clearly described within your informed consent and the [study] protocol.”
Nathan: “That’s right.”
Lindsay: “The ethical debate exists that you [could] be taking away a vaccine from somebody who would be considered one of the priority eligible candidates for the vaccine, given the scarce resources that we have.”
Nathan: “I hope that we get this right, that frontline workers are vaccinated this month [or] within the next month, and that [older adults] are taken care of really quickly in January.
I actually feel calm [and] confident that the vaccines are going to be delivered and distributed to the people [who] need [them] within the next 2 months. I think the question of the next batch of people to get the vaccine, which is where people in the trial would probably fall, [and the] ethics around it are challenging.”
Nathan called for strong leadership, backed up by science, to develop a fair vaccine distribution plan. He also emphasized the need for clear communication.
Nathan: “As a trial participant, if they said, ‘We need to push [your vaccination] out a month because we still have to get the frontline workers or [older adults] taken care of,’ I would not object to that. I think it just needs to be communicated and in an effective way. Ethically, I think most people should fall in line with that.”
What are the biggest challenges?
At the end of our conversation, we reflected on the challenges that we each felt needed to be overcome if vaccines are going to be our way out of the pandemic.
For Lindsay, a big factor is vaccine hesitancy — specifically getting people to trust the vaccine’s benefits. She also pointed to the need to collect enough safety data to allow children and people in vulnerable groups, such as pregnant people and lactating mothers, to have the vaccine.
For Nathan, the major stumbling blocks are misinformation and setting up successful vaccine distribution networks — not just in the U.S., but globally.
A coalition of international organizations recently estimated that only 10% of people in 67 low income and lower-middle income countries would be able to have a COVID-19 vaccine in 2021, as richer nations have bought the majority of available vaccine doses.
Vaccinating the world will take time and the commitment of sufficient numbers of people. As Nathan pointed out, this strategy also hinges on distributing vaccines on a global scale.- Medical News Today