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Discussion Guide and Transcript
Season Two - Episode Six
Research Ethics Reimagined Season Two - Episode Six "Human Challenge Studies With Wilbur H. Chen, M.D., and Jake Eberts"
- In this episode of PRIM&R's podcast, "Research Ethics Reimagined," we explore human challenge studies for shigellosis, examining their role in vaccine development and the ethical considerations surrounding intentional infection of healthy volunteers. Our guests are Dr. Wilbur H. Chen, the Frank M. Calia, MD Endowed Professor and Chief of the Division of Geographic Medicine at the University of Maryland School of Medicine, and Jake Eberts of 1Day Sooner, who is former participant in a Shigella challenge trial. Listen on Spotify | Listen on Apple| Listen on Amazon
Discussion Questions
- 1.) Understanding Human Challenge Studies
- Dr. Chen explains that human challenge studies can be used at different stages of vaccine development, from understanding disease pathogenesis to down-selecting candidates to proving efficacy. How might this flexibility make challenge studies valuable tools in addressing global health needs?
- Eberts describes his experience as a challenge study participant, noting the rigorous informed consent process and ongoing communication about risks. What elements of the consent process seem most critical for ensuring participants truly understand what they're agreeing to?
2.) Ethics and Participant Protection
- Dr. Chen emphasizes the extensive safety protocols, including sleeping on the inpatient unit during the highest-risk period. How do these protective measures balance the ethical imperative to minimize harm with the research goal of studying disease progression?
- The discussion reveals significant debate around compensation levels for challenge study participants. How should researchers and IRBs approach the balance between fair compensation and avoiding undue inducement?
3.) Trust and Community Engagement
- Both guests discuss the importance of building trust between researchers and participants. What strategies seem most effective for fostering this trust, and how might these approaches apply to other types of research?
- Eberts advocates for better communication of study results back to participants. How might improved result-sharing strengthen the relationship between researchers and study volunteers, and what barriers exist to implementing this practice?
Key Terms
Human Challenge Study: Research in which healthy volunteers are intentionally infected with a pathogen under controlled conditions to test vaccines or understand disease progression.
Informed Consent: The process by which participants receive and understand information about research risks and benefits before agreeing to participate.
Neoantigen: A new protein that the immune system has never encountered, which can be used in vaccine development to trigger immune responses against specific targets.
Compensation vs. Payment: The distinction between reimbursing participants for their time, inconvenience, and risk (compensation) versus simply paying them for participation (payment).
Neoantigen: A new protein that the immune system has never encountered, which can be used in vaccine development to trigger immune responses against specific targets.
Compensation vs. Payment: The distinction between reimbursing participants for their time, inconvenience, and risk (compensation) versus simply paying them for participation (payment).
Additional Resources
- Wilbur H. Chen, MD, MS - Dr. Chen is an adult infectious disease physician-scientist with a specific interest in developing vaccines. With funding from the Bill & Melinda Gates Foundation, Dr. Chen is working with a Shigella challenge model and he worked on the development of a challenge model for Cryptosporidium hominis, according the University of Maryland School of Medicine; with funding from PATH (an international nonprofit organization, Program for Appropriate Technology in Health) he worked on a challenge model for heat-stable enterotoxin (ST)-only expressing ETEC.
- 1Day Sooner - Nonprofit organization advocating for healthy human research subjects and human challenge trials.
- WHO Guidelines on Human Challenge Studies - International guidance on ethical conduct of human challenge trials.
- Ethical Criteria for Human Challenge Studies in Infectious Diseases - Oxford Academic framework outlining ethical requirements for challenge studies, including risk assessment and participant protection measures.
- PRIM&R's Research Ethics Timeline - A resource for exploring the milestones of research ethics, including developments in women's health research.
Transcript
Please note, a transcript generator was used to help create written show transcript. Written transcript of podcast is approximate and not meant for attribution.
PRIM&R: Welcome to Research Ethics Reimagined, a podcast created by Public Responsibility in Medicine and Research, or PRIM&R. Here, we talk with scientists, researchers, bioethicists, and some of the leading minds exploring the new frontiers of science. Join us to examine research ethics in the 21st century and learn why it matters to you.
Catherine Batsford: I'm your host, Catherine Batsford.
Dan McLean: And I'm your cohost today, Dan McLean.
Catherine Batsford: Today we're thrilled to welcome Wilbur H. Chen, M.D., M.S., FACP, FIDSA. Dr. Chen is the Frank M. Calia, MD Endowed Professor of Medicine and a Chief of the Division of Geographic Medicine at the University of Maryland School of Medicine. He also serves as Chief of the Adult Clinical Studies Section at the Center for Vaccine Development and Global Health and director of the UMB Travel Medicine Practice. With a career dedicated to infectious diseases, vaccine development, and global health, Dr. Chen brings invaluable insights into how research can balance scientific advancement with ethical responsibility. In this episode, we'll explore the human challenge study for shigellosis, examining its place in the larger research process.
We also have Jake Eberts, a board member of 1Day Sooner, joining us to discuss his experience as a research participant for this human challenge study.
Welcome to the podcast. Thank you so much for being here. So, let's start with a human challenge study for Shigellosis. Can you tell us a bit more about the study in general and its goals?
Wilbur H. Chen: Certainly. My center, the Center for Vaccine Development and Global Health, has been interested in trying to tackle diarrheal diseases which afflict impoverished populations, developing country settings, places where there is lack of access to clean water, sanitation, and hygiene. For fifty years actually we've been doing this, trying to develop vaccines against diarrheal diseases for fifty years. So, this is the next iteration. The particular study that you're referencing is a collaboration in which we are working with colleagues at the Institute Pasteur in Paris, France.
They've also been trying to develop a number of different important global health vaccines, including a Shigella vaccine. They've been working on it also for decades. And so, we partnered together and put this together to evaluate their particular vaccine candidate. Our philosophy is to advance a vaccine, any vaccine. And so, we work with global partners on their vaccine candidates, as well as our own that we've developed in house.
We're an academic research institution, a university. We have some basic microbiologists that are devising vaccines, also trying to understand the pathogenesis of these pathogens. And again, we have our own candidates, but we have to have a number of vaccines in the pipeline to hopefully eventually have a successful vaccine. So, we want to have as many vaccines to evaluate along the line. So again, going back to the reference vaccine study, this is a vaccine that is an injectable vaccine.
There are other vaccine candidates that are oral vaccines that you just kind of swallow and then give an immune response in the GI tract, which is where you actually get the infection. So, this vaccine was evaluated with what we call a human challenge model. And that means that we take consenting healthy volunteers and bring them into an inpatient unit and infect them on purpose with Shigella. I have other studies where we infect people on purpose with other agents like influenza, dengue, other diarrheal diseases.
Catherine Batsford: Jake, can you tell us take us back to your decision to join a challenge study? I think you hear about it a lot, that things are going to trial and that they need participants. What brought you to that moment where you were like, you know what? Yes, I'm going to participate in this. Jake Eberts: Yeah. So, it was really purely by chance. I had no biomedical training or public health background, and I saw an ad on Instagram actually one day here in the DC area. Human challenges are relatively rare compared to the total body of clinical trials that go on, but there's a pretty high concentration of them at a number of institutions and universities here.
The ad I saw, and some listeners might remember the Oregon Trail game, the pixelated one back in the day that said, “You've got a dysentery,” on the screen. So, the ad, it was just like that and then below that in that little font, “Shigella causes dysentery. Help us prevent Shigella.” Most clinical trial ads are eye wateringly boring, really boring. They don't even register. This one did so, I clicked on it, and was generally curious.
I was working a full-time job at the time, you know, in the office and I had never heard of a human challenge study before. So, I vaguely knew that vaccines involved testing. I knew that there was a phases one, two, and three. I could maybe give you a generic sort of high-level description of what those involved. I wasn't aware that there were ever challenges involved because frankly, face value, that sounds a little bit medieval. Right? So, I learned about it a little bit, and threw my hat in the ring.
I read about the disease too. I was blown away. I thought Shigella/Dysentery had kind of gone with the way the pioneers. There I was quick reading on Wikipedia. Somewhere around a quarter million, even more at the time, people with Dysentery. I was thinking of people who die of it every year, particularly children. And so, I kind of joked with my roommate at the time, this is a great way to both make some money and be self-righteous about it.
So, yeah, I threw my name in the ring, and they called me. I eventually decided to go up to Baltimore where the good people at University of Maryland, Baltimore started the process of informed consent and all that stuff. So, it was a long, drawn-out process, but it really was by chance that I joined. Catherine Batsford: Dr. Chen, in this whole process, where does the human challenge study fit? Are you closer to the end or, I mean, you're still looking for the end, I'm sure, but when would it, something like that roll out to the general population? Wilbur H. Chen: Great question. So actually, the human challenge model is used in many different ways. It could be used very early on in just understanding disease pathogenesis. So again, going back fifty years ago, we didn't know what made cholera result in such violent diarrhea. So, we performed human challenge studies to understand the pathogenesis of cholera, and then we're able to determine that it's the cholera toxin that the germ makes that actually results in the diarrhea.
In the case of enterotoxigenic E. Coli, it's another toxin, heat labile enterotoxin. So that's kind of, you know, the use of human challenge models very early on before you have a vaccine or a therapeutic candidate that you want to evaluate that you can understand the basic pathophysiology of a pathogen, which again, there might not be animal models to be able to understand it. So, you have to use humans. That's one instance.
So, another instance is that you have a number of early candidates, and you need to what we call down select. Kind of pick out of the candidates that you've already developed. And you need to say, which is the one that we want to go forward with because we have a number that looks like they're working in the lab, maybe in some animal models, but we need to kind of select how do we pick that. That's one way that also human challenge models can be used early on with an early candidate that might not be the definitive one where we can have a human challenge model to say, yes or no, this one will go forward or not. This study that you're referencing, we had a candidate not so early on, but we wanted to determine whether or not it should go forward.
Now there is the last instance where you've got a candidate that maybe has gone through phase one and phase two clinical trials, and now you need to show efficacy. Efficacy studies are traditionally done in what we call field trials in large populations where you see the disease. Now in the United States, we see very little cholera, shigella, other diarrheal diseases, unless there's a defined outbreak, which you can't predict so you can do a human challenge study. That's what allowed for the cholera vaccine to be licensed and approved in the US. We were able to perform a pivotal efficacy study with a human challenge model as a phase three study. This is really the most mature vaccine and use of a challenge model. In this case, we were able to show efficacy with just the challenge model and not using a large-scale field study. Catherine Batsford: When you explain the purpose of the human challenge studies to participants or the public, how do you communicate the safety protocols? What does the informed consent process look like? I’m curious, from a researcher’s perspective, what is the thought process behind creating them. Wilbur H. Chen: Another great question that comes up very frequently, which is I, as an investigator my foremost concern is to design and implement a study that's conducted with the safety and welfare of our volunteer participants in mind. The consent process is one of the parts of the study where I spend a lot of time making sure that we have designed and implemented methods to communicate the risk of the study. I try to do it in as clear language as possible, and I try to do it as many times as possible. As a participant, you might hear it once and still not remember it. So I do it in an iterative way, which means I give an orientation talk and explain it; they read it in the informed consent form; and when I meet with them one on one—even while they’re in the study—I continue to communicate the perceived risks they might encounter at all stages of the study. In the vaccination stage, there's less of a risk, although they are receiving an experimental study vaccine or the placebo. The risk is really the highest when they are admitted to the inpatient unit and are about to encounter the challenge part of the study. When they have arrived at that point in the study, they have heard multiple times from myself, the study nurses and others about the risks of the study, and especially about what it really means when they get challenged. So, it means, you know, they're drinking a solution that looks clear but actually has the bacterium in it, and that they should expect the infection Shigella. And then I tell them, “What does Shigella infection look like? It's basically high fevers, diarrhea that might be bloody, and severe cramping abdominal pain—you know, those things combined.” So I really try to not paint it in a rosy way to make it sound less impactful or less risky than it really is, but I also try to not oversell because I do tell them that we have safety protocols that are in place as part of implementing the study. So, in other words, we're doing this in an inpatient containment unit where we watch them 24/7. There's always going to be a nurse available, and the principal investigator, myself, or another clinician. We are always immediately reachable.
In fact, I sleep on the inpatient unit for the first two or three days, where the highest amount of disease illness is at that time, because I want to be there within minutes of when they are experiencing their infection—the peak of their infection—whether it be nausea, vomiting, high fevers, or whatever else. I want to be there to be able to hold their hand and talk them through the situation, so that they understand that we are monitoring it and managing it. We give them IV fluids. We give them antibiotics when they need it. There are a lot of things that are built in for the safety and welfare of the participants.
So, all of that is kind of the infrastructure that we have designed over many years of doing these studies, to make it a standard across all our studies, that that's the standard approach, no matter which study it is. If it's a challenge study, we are monitoring very closely and managing very closely for the safety and welfare of our participants. Catherine Batsford: Jake, what was the consent process like from your perspective? I don't know anything about dysentery, and I know I would be hesitant to have it. Jake Eberts: Right. So, as you can imagine, for a human challenge trial, the consent process is pretty intense. Through my later work at the nonprofit I’m at now, which is really focused on human challenge trials, I’ve come to see a wide variety of studies across multiple countries and institutions. Most often, they involve a quiz—you know, kind of a sit-down session. Sometimes there’s a presentation. You also get a standard informed consent packet.
If you answer questions wrong, in my case, you had to go over them with the attending nurse. There’s also one-on-one time with the PI—the principal investigator. A lot of time is built into these processes because it’s a very serious thing, and you want to make sure that people understand what they’re signing up for.
In my case, this was a vaccine challenge trial. We were given two experimental vaccinations of this vaccine called SF2A-TT15. Over the course of about a month—well, really two separate months apart—we got the two injections. Then I came back about a month or two later for the inpatient period.
At any point, we could have withdrawn consent and said, “Nope, don’t want to do this anymore. Done. Bye.” But that was the process. It was both rigorous informed consent upfront and ongoing consent, where they check in to make sure you’re still okay with it. Dr. Chen and the staff were all very, very good about answering questions and things like that throughout the process. Catherine Batsford: So, you knew that you would get dysentery? Jake Eberts: Everybody in the Shigella trial, everyone got—it looked basically a little shot glass of this bacteria in solution that had been grown in a lab that has been used in multiple other Shigella challenge studies. Catherine Batsford: How did you weigh the risks versus the benefits as you were going through the consent process? Jake Eberts: For me, it was mostly that I already had a pretty high baseline trust in the medical research system. I think that’s probably not surprising. I read about the disease. I read the informed consent form. And what I came to learn is that these studies have been done many, many times using this exact pathogen.
This pathogen, Shigella flexneri, is not antibiotic resistant—because that’s the point of having a standardized pathogen sample for the challenge. There are antibiotic-resistant strains, but this particular strain, grown in the lab, was very controlled. They knew it would respond to the antibiotics we would be given. So that was one thing.
Really, the risk for me wasn’t death. We were extensively screened for markers that might predispose us to long-term complications. For me, the question was: is this worth the time, effort, pain, and discomfort it would involve? The dysentery—I can tell you from personal experience now—is not fun. I don’t regret it at all. I’m proud to have done it, and I would do it again, but it was some of the sickest I’ve ever felt in my life.
A lot of the risk, for me, was logistical. I had to take time off work, arrange my schedule, find someone to care for my dog—all that sort of thing. So in addition to the health risk, there were a lot of other considerations.
Ultimately, it came down to this: do I trust the research institution to keep its word, and do I think I have a decent understanding of what’s going to happen? And the answer was yes, based on both the informed consent process and the research I did on my own. So it was relatively straightforward. I wasn’t really concerned about the riskiness per se. I was more concerned about the peripheral stuff—knowing it would take a lot of time and that being sick for a couple of days would not be fun. Catherine Batsford: Thank you. Thank you for participating. Dr. Chen, from your experience, what strategies help build trust between researchers and the communities they serve? I think that could go further. The trust building that you're doing at that moment with your participants is enormous. Is there a way that you could build that out further so that the general population understands the thought and commitment? Wilbur H. Chen: Yes. Another thing we do as scientists who conduct challenge studies is that, when we take on a new type of study—say, for example, Zika in 2014—we start by talking about the possibility of performing challenge studies in an open forum. We held a public workshop with ethicists and other scientists participating in the discussion before we even designed the studies. These kinds of scientific forums give us space to consider how best to put challenge studies together. When we move forward, part of the standard approach is having an institutional review board—a local ethics board—review and approve our studies before we begin. We also spend a lot of time making sure participants understand what the study involves. That includes what it means to enroll, to be randomized, to receive placebo, to be challenged, to be discharged, and to withdraw at any point. These studies are voluntary; participants are not required to stay the entire time, so they may withdraw whenever they choose. They may also have questions about whether withdrawing early could raise health concerns, and we guide them through that. I think this ongoing discussion helps build the understanding and respect that we have for our participants. Dan McLean: Jake, if I could jump in for a second. I was curious, could you talk about your decision to participate in this research? What about the process to help build that trust for you and what could the scientific community continue to do to help future participants also have that feeling? Jake Eberts: I wish I had more trenched insight on this. I have a baseline, very high trust in the medical process. My father was a doctor, and after the pandemic I became acutely aware of how critical vaccines are for protecting public health and alleviating suffering caused by disease worldwide. So I went in knowing the University of Maryland was a good institution. I even read the Wikipedia page and didn’t see any major scandals about experimenting on people.
Substantively, it came down to that baseline level of trust. But even then, you don’t need a high level of background context. Day-to-day interactions with the staff and the PI were really helpful. Everyone was informative, kind, and willing to answer questions. That also built a lot of trust.
I would say that was probably decisive. If staff had rushed through or been disrespectful, regardless of my background level of trust in medical science, I would not have felt safe enrolling in a study. For me, it comes down to personal interactions. Getting people in the door might be difficult, but making sure you are kind, willing, and treating people as individuals makes the difference. Most centers do a decent job of this, but I only have my limited experiences here, so I can’t speak to the standard elsewhere. Dan McLean: I was also interested in what the reaction of your friends and families may have been to your decision to participate. Jake Eberts: Yeah. So, as you might imagine, there was a little bit of a, “Oh my God, what?” My father was a doctor, and my family is very pro-vaccine. After talking it through with my parents, they were supportive—if a little wary, in the way you might expect from parents. With friends, I think my dark sense of humor was disarming in some ways.
I’d joke, “Yeah, I’m gonna get dysentery for science.” I would explain that it’s a really intensive process and that it has been done many times for different diseases. The idea itself is not as medieval or insane as it might sound at first glance.
People were generally bemused but supportive. It was sort of one of those things—like how I feel about many professions—where I’m glad someone is doing it, but I’m glad it’s not me. Overall, people were pretty supportive, if a little weirded out. Catherine Batsford: How important is it to ensure a diverse population participates in the human challenge studies? Wilbur H. Chen: Well, I think it's important that we have diversity such that we are representing the general population. When we perform these studies, we want the study results to be generalizable. So, for example, if we had a vaccine and we only tested it in a white population, and I were to say to an Asian, I'm an Asian myself, you know, I think that this vaccine is effective. And then they ask me, well, what's the data in Asians? And I say, well, we haven't actually haven't studied it in Asians at all.
That's kind of on me as a scientist. It doesn't look good that we have failed to evaluate it in a more generalizable population such that I can say with confidence the safety and the efficacy of the vaccine. So I think that, you know, that's my interest to try to make sure that the populations that I'm studying are generalizable, such that I can make statements about the overall safety and efficacy of the product. Catherine Batsford: Do you think a better understanding of the compliance and review process would help foster more trust in vaccines and the general public? Wilbur H. Chen: Compliance review process, is that talking about the FDA or is that talking about like a IRBs? Catherine Batsford: IRBs. They're incredible. The work that they do. Wilbur H. Chen: Right. No, I agree with you. The local IRBs for the ones that have oversight over academic centers that perform challenge studies are well acquainted with the challenge studies. They probably had to have a learning curve, but the academic centers that are involved with challenge studies are only a handful. So that means only a handful of IRBs are probably well equipped, well versed with reviewing challenge studies. I think part of that expertise has to be built up so the IRB feels comfortable and confident that the study has the safety and welfare of participants in mind and that the ethical framework of the entire study has been fully thought through. That confidence means they may ask for more justification, background, or rationale for why we’re designing the study this way. A more experienced IRB would already understand the rationale and background and be able to more readily review the protocol itself. That’s where I think it really helps to have an IRB with experience. Catherine Batsford: Yeah. Do you think there are any misconceptions even among researchers about the IRB process? Are there ways that they could approach it differently from the research angle? Wilbur H. Chen: Yeah, I think there are scientists and researchers who may have never even heard about challenge studies and might be shocked that the scientific community is engaging in this, that we’re doing it willingly, and that IRBs are allowing it. I think not all scientists have heard of the rationale, the background, and the ethical justification and framework that has been developed and well established for many decades that allow us to do this. So I think, again, there are many scientists who are just not aware. It’s a niche field, and I don’t expect that all scientists understand or are familiar with it.
So I fully expect questions, and I’m always prepared to discuss them. Oftentimes, people are surprised that challenge studies have been done for many years and that there are publications on the ethical framework and the balance of risk and benefit for why we should be doing them. Probably during the COVID pandemic, we went through that experience again, when the scientific community was talking about challenge studies. I expect that we will continue to have this conversation, which is a healthy one. Catherine Batsford: Jake, I would love to talk a little bit more about the compensation. Do you think you would have done it even if you hadn't been? Jake Eberts: Absolutely not. I was an inpatient getting an experimental vaccine—one that had been shown to be not terrible in early phase one studies, with nothing terrifying coming out of it, but still a very early-stage medical product. That’s one thing. But being deliberately infected with a disease that can cause serious illness is not a walk in the park.
I spent about 10 days in inpatient quarantine with around-the-clock medical care. It was uncomfortable and often unpleasant. I’m proud of how they carried it out and don’t regret it whatsoever, but it was not, you know, a trip to the amusement park. It was not fun. This was actually when I became very interested in the compensation debate. The study I was in paid about $7,300.
Through some digital sleuthing and looking at archives of the recruitment pages, I learned that originally they had offered about half of that amount. It quickly became clear that wasn’t enough to recruit participants, so they increased it. Because I’m nosy—and because Maryland law allows it—I requested minutes of IRB meetings from a couple of institutions. I found that, at the time, the IRB was worried that $7,300 was too much money and might be coercive.
Later, in my advocacy work, I became very familiar with this debate over undue inducement and “coercion,” which I think is a really poorly applied term in this context. I would not have done it for free. I think it would be insulting to expect people to do it for free. People sometimes have this strange view of what some researchers call “research exceptionalism.”
That’s the idea that the rules we apply for fair compensation and treatment in other types of economic transactions are somehow reversed when it comes to research. Holly Fernandez Lynch, a professor at the University of Pennsylvania, has a great article arguing that those differences actually support paying people more. As research participants, we don’t have unemployment protections. We don’t have OSHA. There’s OHRP, the FDA, and other organizations that oversee research ethics, but the idea that we protect people—especially those who are financially vulnerable—by paying them less struck me early on as absurd. Even if well meaning, it ran flagrantly against my own experiences and the interactions I had with other participants. That’s what really pushed me into this debate. Catherine Batsford: Dr. Chen, I was interested in your take on the payment process and the ethical discussion around it. Wilbur H. Chen: Yep. The way I like to say it is that I don’t refer to it as a payment; I refer to it as compensation, because our participants are willingly signing a consent form and agreeing to take on risk. And with risk, there should be compensation—and that compensation should be appropriate for the size of the risk.
I also conduct blood-draw studies with healthy volunteers who provide blood, stool, or saliva samples for lab work. These are not from diseased people; they are healthy volunteer studies. The IRB calls these minimal-risk studies. The risks are basically the pain of the blood draw or the inconvenience of collecting a stool or saliva sample—so, not a lot of risk.
It’s the same amount of risk you would encounter at a regular doctor’s office visit if you had a blood draw to check your blood counts, glucose, or cholesterol. For minimal-risk studies, not a lot of compensation is offered. But challenge studies are on the other end of the spectrum. In those, we’re asking participants to willingly get infected and experience the illness of interest—malaria, dengue, influenza, Shigella, cholera. They are going to have that infection.
They are accepting that risk, so they should be compensated more than for a simple blood draw. Compensation also accounts for inconvenience—the number of visits, the time off work, the disruption to daily life. All of these things need to be factored in.
An inpatient study means participants are residing here for multiple days. You don’t go home. It’s not a hotel, a cruise ship, or a vacation. You are willingly allowing your body to be put at risk for science. Even though we’ve built in safety and we’re looking out for participants’ welfare, it is still a risk and an inconvenience—and that should be compensated.
So yes, there is a payment scheme. Participants are getting a payment, but I view it as compensation. The ethical framework is that I’m not paying them some arbitrary amount; I have a rationale for why I want to compensate them the way I do. That’s how I distinguish it. Dan McLean: One note I made is this very specific number of $7,300 that there is something arbitrary about the value or the cost of giving someone dysentery. So I don't know if you had thoughts on that particular amount. Jake Eberts: Typically, when you’re designing a study like this, the PI might propose the payment levels. Often, an IRB has a table or guidelines to go by, based on other studies or on hard limits the IRB has set. Payments usually follow those guidelines, and the IRB has the ability to reject compensation as too high—or, theoretically, too low.
That’s true for human challenge studies or any study involving compensation. Federal guidelines in the United States are vague; they say you shouldn’t unduly induce someone. The FDA and other parts of HHS also have different opinions on what constitutes acceptable. For example, the FDA considers it unacceptable to even bold the level of compensation in a clinical trial advertisement.
So it’s a patchwork system. Payments can feel arbitrary. I thought $7,000 was fair. I don’t think it would have been ethical if it had been higher, because higher payments can create logistical problems, such as incentivizing deceit. But once you pass $1,000 or $2,000, there will always be someone poor enough for whom that is life-changing money. You don’t solve the problem by keeping payments low; you just shift the issue onto a different group.
I’ve seen wide variation across institutions. I’ve sent polite but firm emails to some reminding them they hadn’t updated their payments in 10 years—and inflation had eaten away 30% of the value. Compensation often falls to the back burner. There’s a kind of conservatism and inertia that makes people unwilling to be seen as paying too much. There’s also stigma from the perspective of IRBs and PIs, who don’t want to be seen as bribing participants. Dan McLean: And to put it in context, what is the range? What is the high end and what's the low end of payment for participants? Jake Eberts: It depends massively on the disease. As you can imagine, there isn’t really good data on this. Work we did at one center tried to contextualize it. The highest I’ve seen so far for a completed trial is around $13,000, and that was for a Shigella rechallenge. They were trying to figure out how different strains cross-protect against each other after infection.
That’s an important question for immunology. If you’re designing a vaccine, what is the bare minimum number of Shigella strains you would want included, and how broad would the protection be? In practice, that meant participants were given Shigella once, and then a month or so later, given a different kind of Shigella. So you had to do it twice. That trial paid about $13,000 for roughly 20 days inpatient.
Challenge studies tend to be conducted at academic institutions or government bodies like the NIH. Rarely are they sponsored by pharmaceutical organizations. Part of that is because they often focus on neglected diseases or diseases with a low profit profile—things like malaria or Shigella, which have been eliminated in the industrialized world but still cause immense health suffering in developing countries. Bluntly, there isn’t much profit motive, so academic institutions often take on the work, and they tend to pay less. Budgetary limits and institutional IRB standards also play a role.
Contract research organizations for pharmaceutical companies, by contrast, are trying to recruit quickly. They are often willing to pay more. I’ve seen studies that pay $20,000 or more. But the consensus among ethicists is that you can’t really pay people for risk. Instead, higher-paying studies tend to be more unpleasant or intensive, or require very specific profiles of healthy participants—for example, someone with a particular genetic marker. That’s what I meant earlier about the market dynamic. Catherine Batsford: What do you think the public perception is around compensation versus the IRBs? Jake Eberts: I’m aware of one study in the United Kingdom that shows among research professionals, including PIs and research ethicists, that there is some divergence. The more standard view among ethicists is that you can’t pay too much, because you’ll unduly induce people and that’s unethical. The more popular view, so to speak, is that people doing something important, valuable, uncomfortable, and time-consuming should be paid fairly for it—and that should be a lot of money.
It ranges widely, and I think a lot comes down to how you’re introduced to the concept in the first place. If I tell you, “I did this, I was fine, I should have been paid more,” people are usually sympathetic. If you’re sitting on a well-meaning committee worried that participants don’t fully understand what they’re signing up for, you’re going to be reflexively worried about compensation. That’s an oversimplification, of course. There are also regulatory considerations and institutional competition—do you want to outprice another study?
In general, though, people are sympathetic to the idea that if the research is safe and produces valuable medical knowledge, participants should be paid well, because the social value could be immense. It’s good to pay people for the good they produce—the capital “G” Good. But again, it also depends on your background level of trust. If you believe vaccine research is inherently bad and pharma companies are out to get you, you’ll view compensation as bribery—buying off people and using the bodies of the poor for research. That’s not a problem you solve with lower compensation. It’s a background fact of civic life in the United States and elsewhere.
No one has ever clearly defined undue influence because it’s very difficult to define. The broadest definition is offering an incentive that causes someone to lose the ability to rationally assess risk and benefit, or to violate their own values to participate. The problem is, it’s highly individualized. What’s undue for you or me might not be undue for someone else. You can’t craft payments that account for that without knowing intimate details like someone’s income or risk tolerance. So undue inducement becomes a kind of bogeyman—something real to an extent, but outsized in its influence on policy and IRB thinking, dating back to the Belmont Report.
I hope there’s movement in academia on this. Scholars like Holly Fernandez Lynch, Emily Largent, Jill Fisher, Luke Linus, and Emily Anderson have highlighted the serious problem with how undue inducement is applied. Too often, the result is underpaying people already at the lower end of the economic spectrum, without actually protecting them. My hope is that rank-and-file IRB members will become more aware of this.
One thing IRBs don’t do—and it’s not their job—is inspect clinical sites. I sit on an IRB at a university in DC, and it underscored for me how detached the IRB is from day-to-day clinical practice. That’s understandable, but it means IRBs may not recognize that recruitment problems sometimes reflect issues with compensation. A less paternalistic approach would help.
I think there is a gradual movement toward that. I don’t think there’s a one-size-fits-all solution, but it’s something that can be fixed. It will probably require changing mindsets within IRBs and showing them the consequences of underpayment—not only in terms of social and distributive justice, but also in basic recruitment for important medical research. Catherine Batsford: Do you think there are institutions or countries that do this well? Jake Eberts: I think the United States is on the better end of compensation. In some countries—France, for instance—you are legally not allowed to make more than a set amount from clinical trial participation. I think it’s about €6,000. In some countries, compensation is outright illegal. I believe Colombia is one example. What ends up happening is that trials get exported to other places.
It’s very similar to discussions about blood donation and plasma payment. In the United States, we pay for plasma. In Ontario, people drive across the border to donate in Buffalo, New York. Then the United States exports blood products back to Canada. So the functional consequence of those regulations is not necessarily to decrease the supposed problem—if it even is one—but rather to shift it elsewhere.
The Shigella trial I did was sponsored in part in France. I can’t speak to their reasoning, but they probably could not have run it there. To recruit enough people, they would have had to pay more than the legal maximum allowed in France, so the study was conducted in the United States instead.
Some institutions do better than others. But I’ve also seen institutions that, while treating volunteers well, are very stubborn and hesitant to discuss compensation. For example, I’ve seen groups of participants write kindly worded letters to an institution saying: “We are being treated well, but we need to talk to your IRB about compensation practices. For this trial, they are inadequate, and that’s harming volunteers because people are dropping out early. That’s also bad for your research.”
When participants hand over an issue on a silver platter, saying, “Here’s a perennial issue in research ethics we’d love to talk about,” and the institution rebuffs them—that’s a good example of how uneven the engagement can be. Different institutions are willing to engage with participants at different levels. It’s incumbent on IRBs to take that seriously when it happens, but ideally they should be more proactive. Catherine Batsford: Absolutely. What advice would you give an early career researcher, who wants to prioritize ethics and trust-building in their work? Not just a human challenge study; it could be any study. Is there advice that you would give them? Wilbur H. Chen: This is a great question. The other hat I wear at my university is as co-director of the K-12 program, which is an institutional junior faculty mentoring award where we develop young faculty members’ research careers. Part of that development plan is ensuring they understand the ethics of research on multiple levels. If they’re conducting human research, they must undergo training in human subjects ethics.
They should also understand that no matter what type of research they perform, they have a responsibility to ensure the data they generate is rigorous and reproducible. In other words, research should be conducted in a standardized way so others can reproduce the results. A broader problem in science is that many published studies cannot be reproduced, which calls into question the validity of the original data.
My approach as a scientist is that all of my research—whether challenge studies or otherwise—should be done in such a standardized way that anyone trying to replicate it should be able to reproduce my data. That demonstrates the validity of the data, showing that it was rigorously produced.
For junior faculty, the core principle is to avoid sloppy science—changing methods as you go along or failing to plan properly. Experiments should be well thought out before they begin, and the same plan should be followed throughout. That way, the data is valid and reproducible. This is an emphasis I always stress.
So, going back to the ethical framework: research should always be approached in a way that makes it reproducible across other sites. I encourage people to ask themselves as they do their research: Are we conducting it ethically? Is it rigorous? Is it reproducible? Those are my mantras. Catherine Batsford: I think you often hear that there’s pushback—that once you get to the IRB, you have to defend what you’re doing. But you’re saying that if you lay the foundation correctly, then there’s no problem moving forward. Wilbur H. Chen: That's right. I feel like the IRB is my friend. Catherine Batsford: Yes! Wilbur H. Chen: They are basically verifying my methodology, my approach, and my proposal. If I were ever to propose something crazy, I would want the IRB to catch me, call me out, and say, “No, I don’t think you should do it this way. Consider these things.”
So I never feel antagonistic toward my IRB. I really see it as a collaborative partnership in which they are able to verify what I propose. Catherine Batsford: I had one last question. Once a study is finished, is there a moment when you can share the information back with the participants? Just out of curiosity—if you’ve done this, I’m sure you’d be wondering, “Did I help? Did it move things forward?” Wilbur H. Chen: We always intend to publish results in peer-reviewed scientific literature, which means they don’t go directly to participants. Oftentimes, after a study is performed and we’ve published it—or are about to publish it—we will either create a website to communicate the results or email participants individually to say, “The study results are done. You can find them here.” We also publish on ClinicalTrials.gov, which is a required registry and serves as a central clearinghouse for results.
If we have a really important piece of work, sometimes we release it with a press release, either with the NIH if they are a funding partner, or with an industry partner. There are different approaches for international research. In developing country settings, because technology for accessing websites is less available, what we often do when we are ready to publish is go back to those communities and hold a town hall in the local language, presented by local scientists. We report back: “This is the study you gave us permission to do in your village. These are the results. This is why we think it’s important.” We talk about the findings and also why it was important for them to engage in the study in the first place.
That’s something I wish we could do more in the United States. But it’s hard here, because people are geographically dispersed, have less time to attend, and it’s difficult to schedule multiple town halls. Still, these are the kinds of approaches we want to use to communicate the importance of the science back to participants. Catherine Batsford: Oh, I love that. Do you think as a participant, if you knew some of the data would come back to you, would you be more interested, less interested? Would it not matter? Jake Eberts: You mean study results? Yeah. I think some people feel—and I’m sympathetic to this—that there’s a lot of paperwork involved in clinical trials, everyone is very busy, and some participants don’t care. But it’s always shocking to me how rarely studies report back to people.
One of my former colleagues at 1Day Sooner deliberately contracted malaria as a graduate student. That ended up being pivotal in a human challenge study that contributed to what is now the R21 malaria vaccine. As we speak, that vaccine is being rolled out in West Africa and will probably save many lives. If my colleague hadn’t worked for 1Day Sooner, he likely wouldn’t even know that fact.
He got malaria, and there was no follow-up. That’s a pretty egregious example, because it’s not hard to send an email. And I think it’s a common problem—and one that’s easy to fix. Much easier than compensation debates. Just tell people what happened.
If, five years down the road, the study you joined contributed to a life-saving vaccine, institutions already have your email addresses in a binder somewhere. I get that having graduate students dig them up and send an update isn’t the most exciting use of time. But it’s a basic courtesy. And unfortunately, only a minority of institutions do it. Catherine Batsford: If you had to tell someone how to design a research study that would attract participants—something that would make you interested—what would you say? Jake Eberts: Yeah. I don’t think there’s a magic bullet. Some of it is topic specific. For many people, the issues are logistical. If you’re having trouble recruiting—and your study has already been approved by an IRB as ethical—you should consider raising the payments. That should be on the table, and the IRB should be willing to entertain it.
A lot of it is also pretty straightforward: treat people nicely and respectfully, and communicate clearly. One interesting thing I’ve noticed is that private firms are often good about providing clear information—for example, a 3D tour of the facilities—while other institutions are not as upfront about what will be involved. My willingness to consent is affected by baseline living conditions. If you put me in a small, dark room where I can’t leave all day, and it’s cold or damp, I’m not going to consent to that. If the Wi-Fi doesn’t work and I need to work remotely, or if I’m cut off from my family, that affects my decision.
Baseline quality-of-life issues go a long way. That’s not necessarily the IRB’s job to inspect, but those factors matter. Going back decades, there were zines like Guinea Pig Zero, produced by so-called professional medical research participants. They reviewed sites: “The staff here are really nice”; “The staff here are terrible”; “The blood draws here always take multiple tries and hurt.” Those kinds of reviews show that quality-of-life factors—comfort, respect, basic conditions—make people feel valued and respected and more willing to participate again. Catherine Batsford: Dan, did you have a few more questions? Dan McLean: I was curious. Did you ever meet any of the other participants and have a chance to connect with them about their experience? Jake Eberts: Yeah. Some studies, particularly respiratory virus studies, involve individual quarantine. You don’t want people cross-infecting each other. Respiratory viruses are obviously much more infectious, so you want to keep people contained. But for the Shigella one, we were in the curtain-pull-around-hospital-bed sort of situation. Dan McLean: And I guess my last question for you, and then I'll hand it off to Catherine is do you have any other plans to participate in another trial anytime soon? Jake Eberts: Yeah. So, right now, we are still in the phase where every single NIH study has been frozen, it appears, which is incredibly concerning. Just speaking personally here. But I think that I kind of joke with friends that once I should get, like, punch card. And once I get my third disease, I get, like, a fourth one free or something.
I'm blessed with physical health, and I don't have to worry about it. It's something that feels good to give back. So, the short answer is, yes. I would love to. Like I said, I live in DC, so there's just a cornucopia of fun diseases you can get for the greater good here.
A lot of it's just a question of logistics and trying to sign up and get in at the right time. Catherine Batsford: Well, as another member of the public, thank you. Thank you for doing it. Jake Eberts: Like I said, I wasn’t doing it purely for Mother Teresa’s sake—but you’re welcome. Catherine Batsford: That's okay. The end result was great. So thank you. And thank you for coming on the podcast. This was fascinating. PRIM&R: Thank you for listening to Research Ethics Reimagined, a podcast created by PRIM&R and produced by Syntax in Motion. Please subscribe and share with your friends and colleagues. To learn how to become a member of Primer, please visit us at www.primer.org. Be sure to join us next month as we continue our conversation with scientists, researchers, bioethicists, and some of the leading minds exploring new frontiers of science.
Catherine Batsford: I'm your host, Catherine Batsford.
Dan McLean: And I'm your cohost today, Dan McLean.
Catherine Batsford: Today we're thrilled to welcome Wilbur H. Chen, M.D., M.S., FACP, FIDSA. Dr. Chen is the Frank M. Calia, MD Endowed Professor of Medicine and a Chief of the Division of Geographic Medicine at the University of Maryland School of Medicine. He also serves as Chief of the Adult Clinical Studies Section at the Center for Vaccine Development and Global Health and director of the UMB Travel Medicine Practice. With a career dedicated to infectious diseases, vaccine development, and global health, Dr. Chen brings invaluable insights into how research can balance scientific advancement with ethical responsibility. In this episode, we'll explore the human challenge study for shigellosis, examining its place in the larger research process.
We also have Jake Eberts, a board member of 1Day Sooner, joining us to discuss his experience as a research participant for this human challenge study.
Welcome to the podcast. Thank you so much for being here. So, let's start with a human challenge study for Shigellosis. Can you tell us a bit more about the study in general and its goals?
Wilbur H. Chen: Certainly. My center, the Center for Vaccine Development and Global Health, has been interested in trying to tackle diarrheal diseases which afflict impoverished populations, developing country settings, places where there is lack of access to clean water, sanitation, and hygiene. For fifty years actually we've been doing this, trying to develop vaccines against diarrheal diseases for fifty years. So, this is the next iteration. The particular study that you're referencing is a collaboration in which we are working with colleagues at the Institute Pasteur in Paris, France.
They've also been trying to develop a number of different important global health vaccines, including a Shigella vaccine. They've been working on it also for decades. And so, we partnered together and put this together to evaluate their particular vaccine candidate. Our philosophy is to advance a vaccine, any vaccine. And so, we work with global partners on their vaccine candidates, as well as our own that we've developed in house.
We're an academic research institution, a university. We have some basic microbiologists that are devising vaccines, also trying to understand the pathogenesis of these pathogens. And again, we have our own candidates, but we have to have a number of vaccines in the pipeline to hopefully eventually have a successful vaccine. So, we want to have as many vaccines to evaluate along the line. So again, going back to the reference vaccine study, this is a vaccine that is an injectable vaccine.
There are other vaccine candidates that are oral vaccines that you just kind of swallow and then give an immune response in the GI tract, which is where you actually get the infection. So, this vaccine was evaluated with what we call a human challenge model. And that means that we take consenting healthy volunteers and bring them into an inpatient unit and infect them on purpose with Shigella. I have other studies where we infect people on purpose with other agents like influenza, dengue, other diarrheal diseases.
Catherine Batsford: Jake, can you tell us take us back to your decision to join a challenge study? I think you hear about it a lot, that things are going to trial and that they need participants. What brought you to that moment where you were like, you know what? Yes, I'm going to participate in this. Jake Eberts: Yeah. So, it was really purely by chance. I had no biomedical training or public health background, and I saw an ad on Instagram actually one day here in the DC area. Human challenges are relatively rare compared to the total body of clinical trials that go on, but there's a pretty high concentration of them at a number of institutions and universities here.
The ad I saw, and some listeners might remember the Oregon Trail game, the pixelated one back in the day that said, “You've got a dysentery,” on the screen. So, the ad, it was just like that and then below that in that little font, “Shigella causes dysentery. Help us prevent Shigella.” Most clinical trial ads are eye wateringly boring, really boring. They don't even register. This one did so, I clicked on it, and was generally curious.
I was working a full-time job at the time, you know, in the office and I had never heard of a human challenge study before. So, I vaguely knew that vaccines involved testing. I knew that there was a phases one, two, and three. I could maybe give you a generic sort of high-level description of what those involved. I wasn't aware that there were ever challenges involved because frankly, face value, that sounds a little bit medieval. Right? So, I learned about it a little bit, and threw my hat in the ring.
I read about the disease too. I was blown away. I thought Shigella/Dysentery had kind of gone with the way the pioneers. There I was quick reading on Wikipedia. Somewhere around a quarter million, even more at the time, people with Dysentery. I was thinking of people who die of it every year, particularly children. And so, I kind of joked with my roommate at the time, this is a great way to both make some money and be self-righteous about it.
So, yeah, I threw my name in the ring, and they called me. I eventually decided to go up to Baltimore where the good people at University of Maryland, Baltimore started the process of informed consent and all that stuff. So, it was a long, drawn-out process, but it really was by chance that I joined. Catherine Batsford: Dr. Chen, in this whole process, where does the human challenge study fit? Are you closer to the end or, I mean, you're still looking for the end, I'm sure, but when would it, something like that roll out to the general population? Wilbur H. Chen: Great question. So actually, the human challenge model is used in many different ways. It could be used very early on in just understanding disease pathogenesis. So again, going back fifty years ago, we didn't know what made cholera result in such violent diarrhea. So, we performed human challenge studies to understand the pathogenesis of cholera, and then we're able to determine that it's the cholera toxin that the germ makes that actually results in the diarrhea.
In the case of enterotoxigenic E. Coli, it's another toxin, heat labile enterotoxin. So that's kind of, you know, the use of human challenge models very early on before you have a vaccine or a therapeutic candidate that you want to evaluate that you can understand the basic pathophysiology of a pathogen, which again, there might not be animal models to be able to understand it. So, you have to use humans. That's one instance.
So, another instance is that you have a number of early candidates, and you need to what we call down select. Kind of pick out of the candidates that you've already developed. And you need to say, which is the one that we want to go forward with because we have a number that looks like they're working in the lab, maybe in some animal models, but we need to kind of select how do we pick that. That's one way that also human challenge models can be used early on with an early candidate that might not be the definitive one where we can have a human challenge model to say, yes or no, this one will go forward or not. This study that you're referencing, we had a candidate not so early on, but we wanted to determine whether or not it should go forward.
Now there is the last instance where you've got a candidate that maybe has gone through phase one and phase two clinical trials, and now you need to show efficacy. Efficacy studies are traditionally done in what we call field trials in large populations where you see the disease. Now in the United States, we see very little cholera, shigella, other diarrheal diseases, unless there's a defined outbreak, which you can't predict so you can do a human challenge study. That's what allowed for the cholera vaccine to be licensed and approved in the US. We were able to perform a pivotal efficacy study with a human challenge model as a phase three study. This is really the most mature vaccine and use of a challenge model. In this case, we were able to show efficacy with just the challenge model and not using a large-scale field study. Catherine Batsford: When you explain the purpose of the human challenge studies to participants or the public, how do you communicate the safety protocols? What does the informed consent process look like? I’m curious, from a researcher’s perspective, what is the thought process behind creating them. Wilbur H. Chen: Another great question that comes up very frequently, which is I, as an investigator my foremost concern is to design and implement a study that's conducted with the safety and welfare of our volunteer participants in mind. The consent process is one of the parts of the study where I spend a lot of time making sure that we have designed and implemented methods to communicate the risk of the study. I try to do it in as clear language as possible, and I try to do it as many times as possible. As a participant, you might hear it once and still not remember it. So I do it in an iterative way, which means I give an orientation talk and explain it; they read it in the informed consent form; and when I meet with them one on one—even while they’re in the study—I continue to communicate the perceived risks they might encounter at all stages of the study. In the vaccination stage, there's less of a risk, although they are receiving an experimental study vaccine or the placebo. The risk is really the highest when they are admitted to the inpatient unit and are about to encounter the challenge part of the study. When they have arrived at that point in the study, they have heard multiple times from myself, the study nurses and others about the risks of the study, and especially about what it really means when they get challenged. So, it means, you know, they're drinking a solution that looks clear but actually has the bacterium in it, and that they should expect the infection Shigella. And then I tell them, “What does Shigella infection look like? It's basically high fevers, diarrhea that might be bloody, and severe cramping abdominal pain—you know, those things combined.” So I really try to not paint it in a rosy way to make it sound less impactful or less risky than it really is, but I also try to not oversell because I do tell them that we have safety protocols that are in place as part of implementing the study. So, in other words, we're doing this in an inpatient containment unit where we watch them 24/7. There's always going to be a nurse available, and the principal investigator, myself, or another clinician. We are always immediately reachable.
In fact, I sleep on the inpatient unit for the first two or three days, where the highest amount of disease illness is at that time, because I want to be there within minutes of when they are experiencing their infection—the peak of their infection—whether it be nausea, vomiting, high fevers, or whatever else. I want to be there to be able to hold their hand and talk them through the situation, so that they understand that we are monitoring it and managing it. We give them IV fluids. We give them antibiotics when they need it. There are a lot of things that are built in for the safety and welfare of the participants.
So, all of that is kind of the infrastructure that we have designed over many years of doing these studies, to make it a standard across all our studies, that that's the standard approach, no matter which study it is. If it's a challenge study, we are monitoring very closely and managing very closely for the safety and welfare of our participants. Catherine Batsford: Jake, what was the consent process like from your perspective? I don't know anything about dysentery, and I know I would be hesitant to have it. Jake Eberts: Right. So, as you can imagine, for a human challenge trial, the consent process is pretty intense. Through my later work at the nonprofit I’m at now, which is really focused on human challenge trials, I’ve come to see a wide variety of studies across multiple countries and institutions. Most often, they involve a quiz—you know, kind of a sit-down session. Sometimes there’s a presentation. You also get a standard informed consent packet.
If you answer questions wrong, in my case, you had to go over them with the attending nurse. There’s also one-on-one time with the PI—the principal investigator. A lot of time is built into these processes because it’s a very serious thing, and you want to make sure that people understand what they’re signing up for.
In my case, this was a vaccine challenge trial. We were given two experimental vaccinations of this vaccine called SF2A-TT15. Over the course of about a month—well, really two separate months apart—we got the two injections. Then I came back about a month or two later for the inpatient period.
At any point, we could have withdrawn consent and said, “Nope, don’t want to do this anymore. Done. Bye.” But that was the process. It was both rigorous informed consent upfront and ongoing consent, where they check in to make sure you’re still okay with it. Dr. Chen and the staff were all very, very good about answering questions and things like that throughout the process. Catherine Batsford: So, you knew that you would get dysentery? Jake Eberts: Everybody in the Shigella trial, everyone got—it looked basically a little shot glass of this bacteria in solution that had been grown in a lab that has been used in multiple other Shigella challenge studies. Catherine Batsford: How did you weigh the risks versus the benefits as you were going through the consent process? Jake Eberts: For me, it was mostly that I already had a pretty high baseline trust in the medical research system. I think that’s probably not surprising. I read about the disease. I read the informed consent form. And what I came to learn is that these studies have been done many, many times using this exact pathogen.
This pathogen, Shigella flexneri, is not antibiotic resistant—because that’s the point of having a standardized pathogen sample for the challenge. There are antibiotic-resistant strains, but this particular strain, grown in the lab, was very controlled. They knew it would respond to the antibiotics we would be given. So that was one thing.
Really, the risk for me wasn’t death. We were extensively screened for markers that might predispose us to long-term complications. For me, the question was: is this worth the time, effort, pain, and discomfort it would involve? The dysentery—I can tell you from personal experience now—is not fun. I don’t regret it at all. I’m proud to have done it, and I would do it again, but it was some of the sickest I’ve ever felt in my life.
A lot of the risk, for me, was logistical. I had to take time off work, arrange my schedule, find someone to care for my dog—all that sort of thing. So in addition to the health risk, there were a lot of other considerations.
Ultimately, it came down to this: do I trust the research institution to keep its word, and do I think I have a decent understanding of what’s going to happen? And the answer was yes, based on both the informed consent process and the research I did on my own. So it was relatively straightforward. I wasn’t really concerned about the riskiness per se. I was more concerned about the peripheral stuff—knowing it would take a lot of time and that being sick for a couple of days would not be fun. Catherine Batsford: Thank you. Thank you for participating. Dr. Chen, from your experience, what strategies help build trust between researchers and the communities they serve? I think that could go further. The trust building that you're doing at that moment with your participants is enormous. Is there a way that you could build that out further so that the general population understands the thought and commitment? Wilbur H. Chen: Yes. Another thing we do as scientists who conduct challenge studies is that, when we take on a new type of study—say, for example, Zika in 2014—we start by talking about the possibility of performing challenge studies in an open forum. We held a public workshop with ethicists and other scientists participating in the discussion before we even designed the studies. These kinds of scientific forums give us space to consider how best to put challenge studies together. When we move forward, part of the standard approach is having an institutional review board—a local ethics board—review and approve our studies before we begin. We also spend a lot of time making sure participants understand what the study involves. That includes what it means to enroll, to be randomized, to receive placebo, to be challenged, to be discharged, and to withdraw at any point. These studies are voluntary; participants are not required to stay the entire time, so they may withdraw whenever they choose. They may also have questions about whether withdrawing early could raise health concerns, and we guide them through that. I think this ongoing discussion helps build the understanding and respect that we have for our participants. Dan McLean: Jake, if I could jump in for a second. I was curious, could you talk about your decision to participate in this research? What about the process to help build that trust for you and what could the scientific community continue to do to help future participants also have that feeling? Jake Eberts: I wish I had more trenched insight on this. I have a baseline, very high trust in the medical process. My father was a doctor, and after the pandemic I became acutely aware of how critical vaccines are for protecting public health and alleviating suffering caused by disease worldwide. So I went in knowing the University of Maryland was a good institution. I even read the Wikipedia page and didn’t see any major scandals about experimenting on people.
Substantively, it came down to that baseline level of trust. But even then, you don’t need a high level of background context. Day-to-day interactions with the staff and the PI were really helpful. Everyone was informative, kind, and willing to answer questions. That also built a lot of trust.
I would say that was probably decisive. If staff had rushed through or been disrespectful, regardless of my background level of trust in medical science, I would not have felt safe enrolling in a study. For me, it comes down to personal interactions. Getting people in the door might be difficult, but making sure you are kind, willing, and treating people as individuals makes the difference. Most centers do a decent job of this, but I only have my limited experiences here, so I can’t speak to the standard elsewhere. Dan McLean: I was also interested in what the reaction of your friends and families may have been to your decision to participate. Jake Eberts: Yeah. So, as you might imagine, there was a little bit of a, “Oh my God, what?” My father was a doctor, and my family is very pro-vaccine. After talking it through with my parents, they were supportive—if a little wary, in the way you might expect from parents. With friends, I think my dark sense of humor was disarming in some ways.
I’d joke, “Yeah, I’m gonna get dysentery for science.” I would explain that it’s a really intensive process and that it has been done many times for different diseases. The idea itself is not as medieval or insane as it might sound at first glance.
People were generally bemused but supportive. It was sort of one of those things—like how I feel about many professions—where I’m glad someone is doing it, but I’m glad it’s not me. Overall, people were pretty supportive, if a little weirded out. Catherine Batsford: How important is it to ensure a diverse population participates in the human challenge studies? Wilbur H. Chen: Well, I think it's important that we have diversity such that we are representing the general population. When we perform these studies, we want the study results to be generalizable. So, for example, if we had a vaccine and we only tested it in a white population, and I were to say to an Asian, I'm an Asian myself, you know, I think that this vaccine is effective. And then they ask me, well, what's the data in Asians? And I say, well, we haven't actually haven't studied it in Asians at all.
That's kind of on me as a scientist. It doesn't look good that we have failed to evaluate it in a more generalizable population such that I can say with confidence the safety and the efficacy of the vaccine. So I think that, you know, that's my interest to try to make sure that the populations that I'm studying are generalizable, such that I can make statements about the overall safety and efficacy of the product. Catherine Batsford: Do you think a better understanding of the compliance and review process would help foster more trust in vaccines and the general public? Wilbur H. Chen: Compliance review process, is that talking about the FDA or is that talking about like a IRBs? Catherine Batsford: IRBs. They're incredible. The work that they do. Wilbur H. Chen: Right. No, I agree with you. The local IRBs for the ones that have oversight over academic centers that perform challenge studies are well acquainted with the challenge studies. They probably had to have a learning curve, but the academic centers that are involved with challenge studies are only a handful. So that means only a handful of IRBs are probably well equipped, well versed with reviewing challenge studies. I think part of that expertise has to be built up so the IRB feels comfortable and confident that the study has the safety and welfare of participants in mind and that the ethical framework of the entire study has been fully thought through. That confidence means they may ask for more justification, background, or rationale for why we’re designing the study this way. A more experienced IRB would already understand the rationale and background and be able to more readily review the protocol itself. That’s where I think it really helps to have an IRB with experience. Catherine Batsford: Yeah. Do you think there are any misconceptions even among researchers about the IRB process? Are there ways that they could approach it differently from the research angle? Wilbur H. Chen: Yeah, I think there are scientists and researchers who may have never even heard about challenge studies and might be shocked that the scientific community is engaging in this, that we’re doing it willingly, and that IRBs are allowing it. I think not all scientists have heard of the rationale, the background, and the ethical justification and framework that has been developed and well established for many decades that allow us to do this. So I think, again, there are many scientists who are just not aware. It’s a niche field, and I don’t expect that all scientists understand or are familiar with it.
So I fully expect questions, and I’m always prepared to discuss them. Oftentimes, people are surprised that challenge studies have been done for many years and that there are publications on the ethical framework and the balance of risk and benefit for why we should be doing them. Probably during the COVID pandemic, we went through that experience again, when the scientific community was talking about challenge studies. I expect that we will continue to have this conversation, which is a healthy one. Catherine Batsford: Jake, I would love to talk a little bit more about the compensation. Do you think you would have done it even if you hadn't been? Jake Eberts: Absolutely not. I was an inpatient getting an experimental vaccine—one that had been shown to be not terrible in early phase one studies, with nothing terrifying coming out of it, but still a very early-stage medical product. That’s one thing. But being deliberately infected with a disease that can cause serious illness is not a walk in the park.
I spent about 10 days in inpatient quarantine with around-the-clock medical care. It was uncomfortable and often unpleasant. I’m proud of how they carried it out and don’t regret it whatsoever, but it was not, you know, a trip to the amusement park. It was not fun. This was actually when I became very interested in the compensation debate. The study I was in paid about $7,300.
Through some digital sleuthing and looking at archives of the recruitment pages, I learned that originally they had offered about half of that amount. It quickly became clear that wasn’t enough to recruit participants, so they increased it. Because I’m nosy—and because Maryland law allows it—I requested minutes of IRB meetings from a couple of institutions. I found that, at the time, the IRB was worried that $7,300 was too much money and might be coercive.
Later, in my advocacy work, I became very familiar with this debate over undue inducement and “coercion,” which I think is a really poorly applied term in this context. I would not have done it for free. I think it would be insulting to expect people to do it for free. People sometimes have this strange view of what some researchers call “research exceptionalism.”
That’s the idea that the rules we apply for fair compensation and treatment in other types of economic transactions are somehow reversed when it comes to research. Holly Fernandez Lynch, a professor at the University of Pennsylvania, has a great article arguing that those differences actually support paying people more. As research participants, we don’t have unemployment protections. We don’t have OSHA. There’s OHRP, the FDA, and other organizations that oversee research ethics, but the idea that we protect people—especially those who are financially vulnerable—by paying them less struck me early on as absurd. Even if well meaning, it ran flagrantly against my own experiences and the interactions I had with other participants. That’s what really pushed me into this debate. Catherine Batsford: Dr. Chen, I was interested in your take on the payment process and the ethical discussion around it. Wilbur H. Chen: Yep. The way I like to say it is that I don’t refer to it as a payment; I refer to it as compensation, because our participants are willingly signing a consent form and agreeing to take on risk. And with risk, there should be compensation—and that compensation should be appropriate for the size of the risk.
I also conduct blood-draw studies with healthy volunteers who provide blood, stool, or saliva samples for lab work. These are not from diseased people; they are healthy volunteer studies. The IRB calls these minimal-risk studies. The risks are basically the pain of the blood draw or the inconvenience of collecting a stool or saliva sample—so, not a lot of risk.
It’s the same amount of risk you would encounter at a regular doctor’s office visit if you had a blood draw to check your blood counts, glucose, or cholesterol. For minimal-risk studies, not a lot of compensation is offered. But challenge studies are on the other end of the spectrum. In those, we’re asking participants to willingly get infected and experience the illness of interest—malaria, dengue, influenza, Shigella, cholera. They are going to have that infection.
They are accepting that risk, so they should be compensated more than for a simple blood draw. Compensation also accounts for inconvenience—the number of visits, the time off work, the disruption to daily life. All of these things need to be factored in.
An inpatient study means participants are residing here for multiple days. You don’t go home. It’s not a hotel, a cruise ship, or a vacation. You are willingly allowing your body to be put at risk for science. Even though we’ve built in safety and we’re looking out for participants’ welfare, it is still a risk and an inconvenience—and that should be compensated.
So yes, there is a payment scheme. Participants are getting a payment, but I view it as compensation. The ethical framework is that I’m not paying them some arbitrary amount; I have a rationale for why I want to compensate them the way I do. That’s how I distinguish it. Dan McLean: One note I made is this very specific number of $7,300 that there is something arbitrary about the value or the cost of giving someone dysentery. So I don't know if you had thoughts on that particular amount. Jake Eberts: Typically, when you’re designing a study like this, the PI might propose the payment levels. Often, an IRB has a table or guidelines to go by, based on other studies or on hard limits the IRB has set. Payments usually follow those guidelines, and the IRB has the ability to reject compensation as too high—or, theoretically, too low.
That’s true for human challenge studies or any study involving compensation. Federal guidelines in the United States are vague; they say you shouldn’t unduly induce someone. The FDA and other parts of HHS also have different opinions on what constitutes acceptable. For example, the FDA considers it unacceptable to even bold the level of compensation in a clinical trial advertisement.
So it’s a patchwork system. Payments can feel arbitrary. I thought $7,000 was fair. I don’t think it would have been ethical if it had been higher, because higher payments can create logistical problems, such as incentivizing deceit. But once you pass $1,000 or $2,000, there will always be someone poor enough for whom that is life-changing money. You don’t solve the problem by keeping payments low; you just shift the issue onto a different group.
I’ve seen wide variation across institutions. I’ve sent polite but firm emails to some reminding them they hadn’t updated their payments in 10 years—and inflation had eaten away 30% of the value. Compensation often falls to the back burner. There’s a kind of conservatism and inertia that makes people unwilling to be seen as paying too much. There’s also stigma from the perspective of IRBs and PIs, who don’t want to be seen as bribing participants. Dan McLean: And to put it in context, what is the range? What is the high end and what's the low end of payment for participants? Jake Eberts: It depends massively on the disease. As you can imagine, there isn’t really good data on this. Work we did at one center tried to contextualize it. The highest I’ve seen so far for a completed trial is around $13,000, and that was for a Shigella rechallenge. They were trying to figure out how different strains cross-protect against each other after infection.
That’s an important question for immunology. If you’re designing a vaccine, what is the bare minimum number of Shigella strains you would want included, and how broad would the protection be? In practice, that meant participants were given Shigella once, and then a month or so later, given a different kind of Shigella. So you had to do it twice. That trial paid about $13,000 for roughly 20 days inpatient.
Challenge studies tend to be conducted at academic institutions or government bodies like the NIH. Rarely are they sponsored by pharmaceutical organizations. Part of that is because they often focus on neglected diseases or diseases with a low profit profile—things like malaria or Shigella, which have been eliminated in the industrialized world but still cause immense health suffering in developing countries. Bluntly, there isn’t much profit motive, so academic institutions often take on the work, and they tend to pay less. Budgetary limits and institutional IRB standards also play a role.
Contract research organizations for pharmaceutical companies, by contrast, are trying to recruit quickly. They are often willing to pay more. I’ve seen studies that pay $20,000 or more. But the consensus among ethicists is that you can’t really pay people for risk. Instead, higher-paying studies tend to be more unpleasant or intensive, or require very specific profiles of healthy participants—for example, someone with a particular genetic marker. That’s what I meant earlier about the market dynamic. Catherine Batsford: What do you think the public perception is around compensation versus the IRBs? Jake Eberts: I’m aware of one study in the United Kingdom that shows among research professionals, including PIs and research ethicists, that there is some divergence. The more standard view among ethicists is that you can’t pay too much, because you’ll unduly induce people and that’s unethical. The more popular view, so to speak, is that people doing something important, valuable, uncomfortable, and time-consuming should be paid fairly for it—and that should be a lot of money.
It ranges widely, and I think a lot comes down to how you’re introduced to the concept in the first place. If I tell you, “I did this, I was fine, I should have been paid more,” people are usually sympathetic. If you’re sitting on a well-meaning committee worried that participants don’t fully understand what they’re signing up for, you’re going to be reflexively worried about compensation. That’s an oversimplification, of course. There are also regulatory considerations and institutional competition—do you want to outprice another study?
In general, though, people are sympathetic to the idea that if the research is safe and produces valuable medical knowledge, participants should be paid well, because the social value could be immense. It’s good to pay people for the good they produce—the capital “G” Good. But again, it also depends on your background level of trust. If you believe vaccine research is inherently bad and pharma companies are out to get you, you’ll view compensation as bribery—buying off people and using the bodies of the poor for research. That’s not a problem you solve with lower compensation. It’s a background fact of civic life in the United States and elsewhere.
No one has ever clearly defined undue influence because it’s very difficult to define. The broadest definition is offering an incentive that causes someone to lose the ability to rationally assess risk and benefit, or to violate their own values to participate. The problem is, it’s highly individualized. What’s undue for you or me might not be undue for someone else. You can’t craft payments that account for that without knowing intimate details like someone’s income or risk tolerance. So undue inducement becomes a kind of bogeyman—something real to an extent, but outsized in its influence on policy and IRB thinking, dating back to the Belmont Report.
I hope there’s movement in academia on this. Scholars like Holly Fernandez Lynch, Emily Largent, Jill Fisher, Luke Linus, and Emily Anderson have highlighted the serious problem with how undue inducement is applied. Too often, the result is underpaying people already at the lower end of the economic spectrum, without actually protecting them. My hope is that rank-and-file IRB members will become more aware of this.
One thing IRBs don’t do—and it’s not their job—is inspect clinical sites. I sit on an IRB at a university in DC, and it underscored for me how detached the IRB is from day-to-day clinical practice. That’s understandable, but it means IRBs may not recognize that recruitment problems sometimes reflect issues with compensation. A less paternalistic approach would help.
I think there is a gradual movement toward that. I don’t think there’s a one-size-fits-all solution, but it’s something that can be fixed. It will probably require changing mindsets within IRBs and showing them the consequences of underpayment—not only in terms of social and distributive justice, but also in basic recruitment for important medical research. Catherine Batsford: Do you think there are institutions or countries that do this well? Jake Eberts: I think the United States is on the better end of compensation. In some countries—France, for instance—you are legally not allowed to make more than a set amount from clinical trial participation. I think it’s about €6,000. In some countries, compensation is outright illegal. I believe Colombia is one example. What ends up happening is that trials get exported to other places.
It’s very similar to discussions about blood donation and plasma payment. In the United States, we pay for plasma. In Ontario, people drive across the border to donate in Buffalo, New York. Then the United States exports blood products back to Canada. So the functional consequence of those regulations is not necessarily to decrease the supposed problem—if it even is one—but rather to shift it elsewhere.
The Shigella trial I did was sponsored in part in France. I can’t speak to their reasoning, but they probably could not have run it there. To recruit enough people, they would have had to pay more than the legal maximum allowed in France, so the study was conducted in the United States instead.
Some institutions do better than others. But I’ve also seen institutions that, while treating volunteers well, are very stubborn and hesitant to discuss compensation. For example, I’ve seen groups of participants write kindly worded letters to an institution saying: “We are being treated well, but we need to talk to your IRB about compensation practices. For this trial, they are inadequate, and that’s harming volunteers because people are dropping out early. That’s also bad for your research.”
When participants hand over an issue on a silver platter, saying, “Here’s a perennial issue in research ethics we’d love to talk about,” and the institution rebuffs them—that’s a good example of how uneven the engagement can be. Different institutions are willing to engage with participants at different levels. It’s incumbent on IRBs to take that seriously when it happens, but ideally they should be more proactive. Catherine Batsford: Absolutely. What advice would you give an early career researcher, who wants to prioritize ethics and trust-building in their work? Not just a human challenge study; it could be any study. Is there advice that you would give them? Wilbur H. Chen: This is a great question. The other hat I wear at my university is as co-director of the K-12 program, which is an institutional junior faculty mentoring award where we develop young faculty members’ research careers. Part of that development plan is ensuring they understand the ethics of research on multiple levels. If they’re conducting human research, they must undergo training in human subjects ethics.
They should also understand that no matter what type of research they perform, they have a responsibility to ensure the data they generate is rigorous and reproducible. In other words, research should be conducted in a standardized way so others can reproduce the results. A broader problem in science is that many published studies cannot be reproduced, which calls into question the validity of the original data.
My approach as a scientist is that all of my research—whether challenge studies or otherwise—should be done in such a standardized way that anyone trying to replicate it should be able to reproduce my data. That demonstrates the validity of the data, showing that it was rigorously produced.
For junior faculty, the core principle is to avoid sloppy science—changing methods as you go along or failing to plan properly. Experiments should be well thought out before they begin, and the same plan should be followed throughout. That way, the data is valid and reproducible. This is an emphasis I always stress.
So, going back to the ethical framework: research should always be approached in a way that makes it reproducible across other sites. I encourage people to ask themselves as they do their research: Are we conducting it ethically? Is it rigorous? Is it reproducible? Those are my mantras. Catherine Batsford: I think you often hear that there’s pushback—that once you get to the IRB, you have to defend what you’re doing. But you’re saying that if you lay the foundation correctly, then there’s no problem moving forward. Wilbur H. Chen: That's right. I feel like the IRB is my friend. Catherine Batsford: Yes! Wilbur H. Chen: They are basically verifying my methodology, my approach, and my proposal. If I were ever to propose something crazy, I would want the IRB to catch me, call me out, and say, “No, I don’t think you should do it this way. Consider these things.”
So I never feel antagonistic toward my IRB. I really see it as a collaborative partnership in which they are able to verify what I propose. Catherine Batsford: I had one last question. Once a study is finished, is there a moment when you can share the information back with the participants? Just out of curiosity—if you’ve done this, I’m sure you’d be wondering, “Did I help? Did it move things forward?” Wilbur H. Chen: We always intend to publish results in peer-reviewed scientific literature, which means they don’t go directly to participants. Oftentimes, after a study is performed and we’ve published it—or are about to publish it—we will either create a website to communicate the results or email participants individually to say, “The study results are done. You can find them here.” We also publish on ClinicalTrials.gov, which is a required registry and serves as a central clearinghouse for results.
If we have a really important piece of work, sometimes we release it with a press release, either with the NIH if they are a funding partner, or with an industry partner. There are different approaches for international research. In developing country settings, because technology for accessing websites is less available, what we often do when we are ready to publish is go back to those communities and hold a town hall in the local language, presented by local scientists. We report back: “This is the study you gave us permission to do in your village. These are the results. This is why we think it’s important.” We talk about the findings and also why it was important for them to engage in the study in the first place.
That’s something I wish we could do more in the United States. But it’s hard here, because people are geographically dispersed, have less time to attend, and it’s difficult to schedule multiple town halls. Still, these are the kinds of approaches we want to use to communicate the importance of the science back to participants. Catherine Batsford: Oh, I love that. Do you think as a participant, if you knew some of the data would come back to you, would you be more interested, less interested? Would it not matter? Jake Eberts: You mean study results? Yeah. I think some people feel—and I’m sympathetic to this—that there’s a lot of paperwork involved in clinical trials, everyone is very busy, and some participants don’t care. But it’s always shocking to me how rarely studies report back to people.
One of my former colleagues at 1Day Sooner deliberately contracted malaria as a graduate student. That ended up being pivotal in a human challenge study that contributed to what is now the R21 malaria vaccine. As we speak, that vaccine is being rolled out in West Africa and will probably save many lives. If my colleague hadn’t worked for 1Day Sooner, he likely wouldn’t even know that fact.
He got malaria, and there was no follow-up. That’s a pretty egregious example, because it’s not hard to send an email. And I think it’s a common problem—and one that’s easy to fix. Much easier than compensation debates. Just tell people what happened.
If, five years down the road, the study you joined contributed to a life-saving vaccine, institutions already have your email addresses in a binder somewhere. I get that having graduate students dig them up and send an update isn’t the most exciting use of time. But it’s a basic courtesy. And unfortunately, only a minority of institutions do it. Catherine Batsford: If you had to tell someone how to design a research study that would attract participants—something that would make you interested—what would you say? Jake Eberts: Yeah. I don’t think there’s a magic bullet. Some of it is topic specific. For many people, the issues are logistical. If you’re having trouble recruiting—and your study has already been approved by an IRB as ethical—you should consider raising the payments. That should be on the table, and the IRB should be willing to entertain it.
A lot of it is also pretty straightforward: treat people nicely and respectfully, and communicate clearly. One interesting thing I’ve noticed is that private firms are often good about providing clear information—for example, a 3D tour of the facilities—while other institutions are not as upfront about what will be involved. My willingness to consent is affected by baseline living conditions. If you put me in a small, dark room where I can’t leave all day, and it’s cold or damp, I’m not going to consent to that. If the Wi-Fi doesn’t work and I need to work remotely, or if I’m cut off from my family, that affects my decision.
Baseline quality-of-life issues go a long way. That’s not necessarily the IRB’s job to inspect, but those factors matter. Going back decades, there were zines like Guinea Pig Zero, produced by so-called professional medical research participants. They reviewed sites: “The staff here are really nice”; “The staff here are terrible”; “The blood draws here always take multiple tries and hurt.” Those kinds of reviews show that quality-of-life factors—comfort, respect, basic conditions—make people feel valued and respected and more willing to participate again. Catherine Batsford: Dan, did you have a few more questions? Dan McLean: I was curious. Did you ever meet any of the other participants and have a chance to connect with them about their experience? Jake Eberts: Yeah. Some studies, particularly respiratory virus studies, involve individual quarantine. You don’t want people cross-infecting each other. Respiratory viruses are obviously much more infectious, so you want to keep people contained. But for the Shigella one, we were in the curtain-pull-around-hospital-bed sort of situation. Dan McLean: And I guess my last question for you, and then I'll hand it off to Catherine is do you have any other plans to participate in another trial anytime soon? Jake Eberts: Yeah. So, right now, we are still in the phase where every single NIH study has been frozen, it appears, which is incredibly concerning. Just speaking personally here. But I think that I kind of joke with friends that once I should get, like, punch card. And once I get my third disease, I get, like, a fourth one free or something.
I'm blessed with physical health, and I don't have to worry about it. It's something that feels good to give back. So, the short answer is, yes. I would love to. Like I said, I live in DC, so there's just a cornucopia of fun diseases you can get for the greater good here.
A lot of it's just a question of logistics and trying to sign up and get in at the right time. Catherine Batsford: Well, as another member of the public, thank you. Thank you for doing it. Jake Eberts: Like I said, I wasn’t doing it purely for Mother Teresa’s sake—but you’re welcome. Catherine Batsford: That's okay. The end result was great. So thank you. And thank you for coming on the podcast. This was fascinating. PRIM&R: Thank you for listening to Research Ethics Reimagined, a podcast created by PRIM&R and produced by Syntax in Motion. Please subscribe and share with your friends and colleagues. To learn how to become a member of Primer, please visit us at www.primer.org. Be sure to join us next month as we continue our conversation with scientists, researchers, bioethicists, and some of the leading minds exploring new frontiers of science.
Research Ethics Reimagined guests are esteemed members of our community who generously share their insights. Their views are their own and do not necessarily reflect those of PRIM&R or its staff.