Taboo Trades
Taboo Trades
Payment, Exploitation, & Clinical Trials with Holly Fernandez Lynch
In this episode, Holly Fernandez Lynch and I continue our discussion of clinical research ethics with co-hosts Rahima Ghafoori and Caroline Gozigian (UVA Law '23). In this Part 2 of our interview, we focus on questions of payment, exploitation, and trust. As a reminder, in Part I, Holly introduced the basic regulatory framework governing clinical trials, with a focus on laws and rules impacting payment. She also discussed the benefits of and concerns about human challenge studies, and shared some historical examples.
Holly Fernandez Lynch, JD, MBE, is Assistant Professor of Medical Ethics in the Department of Medical Ethics and Health Policy at the Perelman School of Medicine (PSOM), University of Pennsylvania. She has a secondary appointment as an Assistant Professor of Law at the University of Pennsylvania Carey Law School.
A lawyer and bioethicist by training, Professor Fernandez Lynch’s scholarly work focuses on Food and Drug Administration (FDA) pharmaceutical policy, access to investigational medicines outside clinical trials, clinical research ethics, and the ethics of gatekeeping in health care. Her specific areas of expertise include Institutional Review Board (IRB) quality, payment to research participants, research prioritization, pre-approval access pathways (e.g., Expanded Access, Emergency Use Authorization, and Right to Try), and efforts to balance speed and certainty in drug approvals, including pathways that rely on post-approval trials such as accelerated approval.
Links:
Lynch HF, Darton TC, Levy J, McCormick F, Ogbogu U, Payne RO, Roth AE, Shah AJ, Smiley T, Largent EA. Promoting Ethical Payment in Human Infection Challenge Studies. Am J Bioeth. 2021 Mar;21(3):11-31. doi: 10.1080/15265161.2020.1854368. Epub 2021 Feb 4. PubMed PMID: 33541252.
Shah SK, Miller FG, Darton TC, Duenas D, Emerson C, Lynch HF, Jamrozik E, Jecker NS, Kamuya D, Kapulu M, Kimmelman J, MacKay D, Memoli MJ, Murphy SC, Palacios R, Richie TL, Roestenberg M, Saxena A, Saylor K, Selgelid MJ, Vaswani V, Rid A. Ethics of controlled human infection to address COVID-19. Science. 2020 May 22;368(6493):832-834. doi: 10.1126/science.abc1076. Epub 2020 May 7. PubMed PMID: 32381590.
Largent EA, Heffernan KG, Joffe S, Lynch HF. Paying Clinical Trial Participants: Legal Risks and Mitigation Strategies. J Clin Oncol. 2020 Feb 20;38(6):532-537. doi: 10.1200/JCO.19.00250. Epub 2019 Jun 14. PubMed PMID: 31199697.
when people get anxious about paying participants, it's because they are actually anxious about the research itself. It is not problematic to pay people any amount of money, a million dollars to do something that is reasonable, okay? So the example that I always give is if I was going to mow my neighbor's lawn for free because I'm a nice person, it doesn't all of a sudden become exploitative for me to do it for a million dollars, right? Like the underlying activity is ethically appropriate and acceptable. If you are confident that the research you are offering people is ethically acceptable, you don't have to worry about payment, full stop. Right. You don't have to worry about paying too much. Yeah. Right. Right. So if the IRB has done its job or the additional layer of ethics review has done its job, then you should feel pretty comfortable offering people payment.
SPEAKER_02:Hey, hey, everybody. Welcome to the Taboo Trades podcast, a show about stuff we aren't supposed to sell, but do anyway. I'm your host, Kim Kravick. In this episode... Holly Fernandez Lynch and I continue our discussion of clinical research ethics. In this part two of our interview, we focus on questions of payment, exploitation, and trust. As a reminder, in part one, Holly introduced the basic regulatory framework governing clinical trials with a focus on laws and rules impacting payment. She also discussed the benefits of and concerns about human challenge studies and shared some historical examples. Holly Fernandez Lynch is Assistant Professor of Medical Ethics in the Department of Medical Ethics and Health Policy at the Perelman School of Medicine at the University of Pennsylvania. She has a secondary appointment as an Assistant Professor of Law at the University of Pennsylvania Carey Law School. A lawyer and bioethicist by training, Professor Fernandez-Lynch's scholarly work focuses on food and drug administration, pharmaceutical policy, access to investigational medicines outside clinical trials, clinical research ethics, and the ethics of gatekeeping in healthcare. Her specific areas of expertise include IRB quality, payment to research participants, research prioritization, pre-approval access pathways, For example, expanded access, emergency use authorization, and right to try, and efforts to balance speed and certainty in drug approvals. Okay, so Ryan actually had some questions about the UK study and some of the recommendations that you guys had had in your, and sort of the extent to which you would change anything there. So Ryan?
SPEAKER_01:Yeah, you already addressed part of what my question was getting at. Basically, I just wanted to know kind of what happened in actuality, because the paper was obviously written in anticipation of some of these studies. So I guess... Given that you know what happened kind of in the real world and how it played out, how did the article map onto what actually ended up happening? Did they take into consideration any of your recommendations or did they do things? Would you have done things differently?
SPEAKER_07:Okay. So this is one of the annoying things about being interested in policy, but being an academic is that often you make recommendations and then you're kind of like, and is anyone going to do anything about it? Anybody listening out there? Yeah. So the paper that I shared with you all was a paper in the American Journal of Bioethics that was a much condensed version of a report that our authorship team pulled together that was solicited by One Day Sooner. So in the summer of 2020, One day sooner came to me and said, you know, we are talking seriously about getting challenge trials off the ground. One thing we're wondering about is how should we ethically pay people? What do you recommend? And so we pulled this team together. We wrote this massive report in three weeks. You know, the report was very, very long. There's some, I'm not gonna get the adage, right? But like, you know, sorry, this letter was so long. I didn't have time to make it shorter. It was about a hundred page report and it was too much. We had an executive summary. We had a list of recommendations, but I think it was too much for them to really operationalize because they didn't say this, but reading between the lines, I think they wanted us to say, pay people this many dollars. And we didn't say that. We gave a framework for how one would think about how much, how many dollars you should you should pay. So we had some time to kind of refine things, think about them in a peer reviewed publication, which came out not too much later than the one day sooner report. So. The short version of the answer is I don't know to what extent our report was actually used in setting the payment amounts for that UK challenge study. In the UK challenge study, they paid people about the equivalent of about$6,000 for a two-week quarantine study, right? So they were in a high-level isolation unit and they received about, I think it was maybe$6,200. It was pounds, but the equivalent in dollars. So again, unclear to me whether, because I never saw a breakdown of where that amount came from. Maybe they found our worksheet helpful, maybe not. But really what we wanted that worksheet to do is offer not a set number, but a rationale of so that investigators could say, here's how we're going to get to our total. Here's how we're going to justify it to the IRB. Here's how we're going to justify it to the public when they ask, well, gee,$6,000 seems like a lot of money. Are you just paying people because you're worried you might kill them? Well, in that case,$6,000 seems way too low, right? So Where did those numbers come from? What's the rationale? That was the intent of our worksheet. Our working group had several ethicists as well as several challenge study researchers. So We obviously tested it with them. Do you think this is reasonable? Would this be helpful? Our very small group said, yeah, this would be helpful. And we did some legwork to try to get a better handle on how much people were paying in challenge studies. But that turned out to be remarkably difficult to get our hands on. It was not an easy thing for us to do in the published literature. And even just kind of like having these challenge trialists ring up their friends and say, You know, how much do you pay? How much do you pay? It was hard to kind of nail things down, which I think is a huge challenge, right? Because then everybody has to reinvent the wheel every time they're doing a study, figure out how much they're going to pay, convince their review board all over again.
SPEAKER_02:We're moving on to questions about payment. Before we did that, Holly, I wanted to ask you just one final question about challenge trials more directly. generally and about COVID trials specifically. I have seen talk again from Josh specifically, Josh Morrison from One Day Sooner and perhaps other folks. Do you feel like the calculus has changed? I think perhaps they were, my recollection is that they wanted to test the inhalers perhaps or were hoping to speed up questions about the inhalers. Do you feel now that the calculus has changed now that we do have treatments? But of course, the social benefit might or might not be less. How do you look at it now?
SPEAKER_07:Yeah, I mean, I think overall the calculus has not changed, but that's because both sides of the calculus have changed. So we have much more knowledge about SARS-CoV-2, who's at greatest risk, how we can mitigate that risk. And we have far less knowledge social value because we already have some vaccines, some treatments, you know? So the, so where do I, I haven't really, I haven't really figured out what my true position is on whether we should continue to pursue SARS-CoV-2 challenge studies, because I feel like I need to know more about the science of what exactly they would be used for. I could And I've heard, you know, the One Day Sooner folks and other proponents say, well, no, no, there's still value because, you know, we could test boosters. We still don't have great what are called correlates of protection, meaning how many antibodies do you need to, for example, how many antibodies do you need to see in someone's blood to know that they are in fact protected against getting infected? So there are certainly still open questions about that. about this pathogen, about the interventions for this pathogen, where I'm not suggesting that there is no social value. I think there could be legitimate arguments built around social value. My key message, though, is that, and this goes for all research, frankly, not just challenge studies, we can't just assume that there's social value because there's some interesting research question, right? It's not good enough to just have an interesting unanswered research question. You actually have to know or have a high probability that your study is gonna make a meaningful difference. And so in the Zika context that I mentioned before, we didn't have treatments, we didn't have vaccines. There was a high possibility of social value But we heard from companies who are developing Zika vaccines that they were not going to wait for the results of a Zika virus challenge study. So if they weren't going to wait, that really dropped the social value of doing the challenge studies. So it's a very complex ecosystem that's not Whether a study has social value is not just controlled by the researchers and the sponsors. They produce one bit of information or one subset of information that plays into this larger ecosystem that determines whether something will truly be valuable.
SPEAKER_02:Okay, so moving on to questions about payments. Caroline, can you get us started?
SPEAKER_04:Sure. Hi, Holly. So when you were analyzing the payment funnel and shifting the focus from considerations likely to arise across clinical research generally to research specific involving human infection challenge studies, how did you identify factors that would be particularly important to designing payment offers for these challenge studies?
SPEAKER_07:Yeah. So we had previous to thinking about challenge studies specifically, we had worked out this model of ethical payment, ethical types of payment, right? Reimbursement, compensation, and incentives. And then we had kind of thought like, what are the variables that could make you, that could influence how much money should be offered? What are things, what do people sometimes ask about? You know, should we pay if the study offers the prospect of medical benefit, right? For example. And so when we were thinking about the SARS-CoV-2 context, we thought, all right, what is distinct about this study? type of research. The most obvious thing is that people have to be isolated. And it can be really uncomfortable and a burden to be in quarantine in an inpatient facility for two or more weeks. We weren't sure at the time how long people are going to be isolated for. And sometimes in challenge studies, people can be isolated for just a couple of days. But I think often people don't realize it's very unpleasant to be isolated for that long. And so we wondered, that is something that might suggest you should compensate people quite a bit more because of that discomfort and burden. So that stood out to us. The other thing that really stood out to us was the concern about public trust related to challenge studies. So there were some people who said, Trust is so on the rocks right now because of everything that was going on with COVID that we should be really, really careful about doing anything that would public trust in science, public trust in research. And given that challenge studies are not something that people really have heard a lot about, maybe we should be worried about how payment would be perceived. Even if it was wrongly perceived, maybe we should keep payments fairly low so that it avoids claims that we are coercing or exploiting people for being in this type of study. We ultimately said, No, that is not a good reason to limit payment. The way to build trust is to help people understand why you would be doing this kind of challenge study in the first instance. And if you have a really strong rationale on that point, then you could also explain why it's so important to pay people to participate in this type of study. So those were some of the things that came up. We talked a bit about diversity issues. and whether diversity is important in challenge studies and whether it would be reasonable to pay to encourage diversity in challenge studies. And it was something that we ultimately decided was, you know, diversity in trials is generally an important concept, but these studies are so small that generalizability is not something that you're typically going for, meaning, you know, that diverse enrollment was not going to be like a core criterion for us to say, oh, you should pay people more to encourage participation in this kind of study. So those were some of the things. I mean, they... How did we identify them? It wasn't necessarily, I can't say it was terribly systematic. It was that we had a bunch of experts in the ethics of challenge studies and in the actual conduct of challenge studies. And these were the types of questions that we had been thinking about ethically or the types of questions that had come up for those trialists as they were deciding how to decide on payment offers in their own research.
SPEAKER_02:I'm going to skip to Bridget. You mentioned the main difference being that people had to be isolated and quarantined. And Bridget actually had some questions about that. So Bridget, I'm skipping to you and then I'll come back to some of our other questions.
SPEAKER_04:Sure. So when you discussed the COVID HICS trials in your paper, I was kind of like trying to put myself in their shoes and I was wondering if there are some methods other than increased payment that researchers use to ensure the trials are ethical because if you're shut off, like it makes me think of when you're in prison, you can't interact with anyone. And there are a lot of mental health repercussions of that. So I'm curious if you guys bring mental health counselors on for the project and if participants can communicate with one another to sort of share their experiences and can they leave their like isolation rooms, assuming that there's a system that will prevent them from coming into contact with anyone else.
SPEAKER_07:Okay. So I, I don't know the answer to all of those questions. They are, It's not solitary confinement, right? So for example, right? They can, you know, Zoom with family members. They can do all of those kinds of things. They cannot leave the unit altogether. I suspect that they cannot interact face-to-face with one another. The reason for that being, you know, so half of them, despite being exposed to the pathogen, did not actually end up having symptoms or getting infected. You wouldn't want them to be all in the same common room, and then those who did get infected infect the others because it was supposed to be a very controlled exposure. They would have interactions with the study staff who would be donning all of their PPE. They wouldn't be totally isolated from human contact, but they would be isolated from their family and friends for a period of time. I don't know about offering mental health counseling, but what I do think is really important is helping people understand what it's like to be quarantined, what the facility is like. So for example, I've heard... that sometimes challenge studies that will involve inpatient isolation will invite prospective participants to spend the night for, you know, before they even get exposed to something, spend the night, see if you can handle it, right? And if you can't, then you're not going to get exposed to the pathogen. You're not going to enroll in the study. So that's kind of a trial run. The other thing that can be really important is allowing new patients participants to speak to people who have done this before so that they have a better sense of what it's actually like to be in isolation.
SPEAKER_02:Caroline had a question regarding the lack of transparency in payment practices that you brought up just a few minutes ago.
SPEAKER_04:Yeah. So you actually were just talking about some of kind of getting at the essence of my question, but you mentioned that there's this pay lack of transparency for these payment practices and challenge studies and how greater transparency would be beneficial to promote consistency among payment when appropriate, as well as allow more careful examination by ethics review boards and participants. So obviously, pay transparency is certainly not unique to challenge studies. But what steps do you think would help increase transparency in this specific area of research?
SPEAKER_07:Yeah, so it becomes this really frustrating cycle, which is to say that IRBs might say, well, we have a approved this amount of payment in a previous study. And so that's going to be our standard. And then it becomes hard for investigators to push back against that and say, well, you know, we should be allowed to pay more because our colleague at another institution can pay more or what have you. Right. So the same reason that pay transparency is important in the workplace, it can be important in research settings. The the best Well, two possible approaches. One would be just a commitment to include in your research publications how much you're paying people. It has become increasingly common and even required by many journals to state explicitly that you've gotten IRB approval for your research. You could also have journal editors say, and how much were people paid? Not necessarily to like, you know, highlight ethical concerns that people are being paid too much, but to just normalize discussions that people were paid. This was kind of the benchmark of how much they were paid so that other people can learn from that. And then the other thing, there have been some efforts by ethicists to study payment and engage in benchmarking. So having just some kind of like public website that is analyzing information about study payment in challenge studies and in other types of studies There've been some descriptive attempts by which I mean, several years ago, there was a study by some bioethicists at NIH to benchmark how much people are paid for a research blood draw. How much are they paid for a spinal tap? How much are they paid to fill out a survey? How much are they paid for a one hour interview? Just to kind of get a sense of what's out there. That doesn't help us on the normative side though, right? That's just saying what people currently do. The concern is, people who participate in research are often woefully underpaid from a fairness perspective. And so you don't want to tie things to current payment, but at least understanding what's currently happening would help us better normatively assess what's happening and argue for change.
SPEAKER_02:So Holly, do you have a sense of what is causing the current lack of transparency? Is it just sort of a failure to pay attention to this issue? Or is there some reticence on the part of researchers to make this information available in part because they're concerned about being criticized or, um, What's there?
SPEAKER_07:A couple of different things. One is sometimes it's really hard to describe how much people are being paid because it's not one amount. So you might say, well, people are compensated for their travel expenses. And participants in this group of the study had 17 visits. And so they were paid this amount. But people in this other arm of the study only had 10 visits. So they were paid that amount. It just becomes very wordy. You can't say, oh, everybody was paid this amount of So it becomes complicated in that way. That's one piece of it. Related to the wordiness, unlike law reviews, clinical journals allow so few words. I know this because I'm at a medical school, so I publish in clinical journals. And It is luxurious to have 3,000 words for an original research paper. So even the sentence that you got IRB approval, you're kind of like, oh no, I need that for something more substantive. So explaining the specificity of how you paid research participants is not, I think, a high priority compared to describing the results and the implications of the results. And then the last thing is outside of journal articles, there's not a place to do it. Right. So there's not, you know, some public repository where people, where researchers could just say this, how much we pay. You could imagine clinical trials.gov is a repository of lots of information about studies. That could be a required element. Is it, is payment offered? What's it offered for? How much is the payment that's offered? Right. That would be really helpful to see.
SPEAKER_02:Okay. So, but so it's not, you don't have any sense that there is a, some reticence about making the information available. It's just that a mechanism for doing so hasn't been settled on yet.
SPEAKER_07:I don't think there is much reticence to publicize it. I mean, I certainly don't have any empirical data about that. But if I had to think about why people might be reticent, it could be a fear that they're going to be accused of exploitation or coercion or undue inducement because there are still those concerns about payment. For example, some international colleagues who've done challenge studies of malaria, I think, were covered by a local newspaper with the headline that including how much the research participants were offered in what was intended to be this big expose. Can you believe they're doing this study and they're offering people this much money? And really, they had done nothing wrong. And it was totally appropriate to do the study, totally appropriate to offer that money. But when you're trying to build public trust in research, that requires a lot of expectation of sophistication in your audience to look past the risk of an inflammatory news story. So that might be a source of reticence in some instances, but I'm not sure. Okay.
SPEAKER_02:We had a couple of questions about the three categories. And Caroline, we're back to you again.
SPEAKER_04:Yeah. So I was really interested in hearing a bit more about this incentive category of payment for clinical trials. So you mentioned in your review of Challenge Study payment information, none of the 18 payments specifically referenced incentives. So would you expect them to be spelled out in the payment information? Or especially from the perspective of participants, is this payment information kind of just generally lumped together as this number that they may get? Or is it broken out more separately? I guess I was just a little bit confused of how these work in practice. Or are these categories of compensation, reimbursement, and incentive payments more like categories that you think of as a research developer, that they're considering these categories as they're actually formulating what the payment mechanisms will be?
SPEAKER_07:Yeah, great question. I conceptualize the categories of reimbursement, compensation, and incentive as categories tools for the people who are trying to figure out how much payment to offer and how to justify that amount of payment. It is not at all typical that you would see a breakdown of payment types in an informed consent form, for example. But I actually think it would be very helpful to do that because it helps people understand a bit more the practical realities of what it's like to be a research participant. Here's the here's what you're being compensated for this study. It's because we expect that it's going to take this number of hours, this number of visits. We expect that these procedures are going to be particularly uncomfortable or burdensome. Like if you kind of broke it down for people, that would play an informative information factor. disclosure role that might be just a different way of presenting that information that might be found elsewhere in the informed consent form. It usually would be, right, the number of study visits, what actually is going to be expected of you. But when you associate payment specifically with it, it helps people understand like, oh, they are paying me to do this because it is burdensome and uncomfortable. That's brilliant. Holly, you should test that. That seems like a completely plausible hypothesis. Yeah. And, you know, it The one worry about payment is that people will focus on the total amount and get all starry eyed. Oh, you know, in this challenge,$6,200, right? That's a lot of money. But when you break it down to an hourly rate, for example, or what they're actually being asked to do, it helps people see like, how does this compare to other ways that I might spend my time or, you know, other ways that I might contribute. So I'm not familiar with anybody doing that. It is a testable hypothesis. Yeah. But I think the framework could be helpful to researchers. It can be helpful to IRBs. It can be helpful to research participants. Ryan had a
SPEAKER_02:related question.
SPEAKER_01:Hi. Yeah. So I generally agree with the proposition from the article that you shouldn't compensate based on opportunity costs. I think you mentioned in the article compensating a lawyer more than a barista. And that obviously makes sense. But But would compensating without regard to opportunity costs naturally lead to those with lower opportunity costs being overrepresented within the participant pool? And then I guess if that's true, wouldn't it necessarily be the case that poor or disadvantaged communities would be overrepresented?
SPEAKER_07:Yeah, great points and concerns, right? So in general, we want to make sure that we are Never recruiting from populations just because they are easy to recruit from, right? And by that, I mean like exploiting some disadvantage that they have that makes it easier to enroll them. Putting that aside, there are all sorts of activities that you would not be able to get a privileged person to do but are nonetheless critically important activities. So the response to that kind of scenario is not to say, well, we ought to just pay people less. It's to say we should pay them more because the more we pay, that is going to widen the pool of people who find this to be an attractive offer. It's going to be most attractive to the least well-off, but it's going to widen the pool of people who would consider participating. The reason
SPEAKER_02:why- Holly, why do so many of your colleagues not seem to appreciate that point? I'm sorry, but so much of the literature in this field seems to not understand that basic point.
SPEAKER_07:I have been working on it. I don't know. I know, I applaud you. You know, because there's a couple, I have a couple of theories about this, right? One is that when people get anxious about paying participants, it's because they're actually anxious about the research itself. It is not problematic to pay people any amount of money, a million dollars to do something that is reasonable, okay? So the example that I always give is if I was going to mow my neighbor's lawn for free because I'm a nice person, it doesn't all of a sudden become exploitative for me to do it for a million dollars, right? Like the underlying activity is ethically appropriate and acceptable. If you are confident that the research you are offering people is ethically acceptable, you don't have to worry about payment, full stop. Right. You don't have to worry about paying too much. Yeah. Right. Right. So if the IRB has done its job or the additional layer of ethics review has done its job, then you should feel pretty comfortable offering people payment. Where it becomes dicey is in two scenarios. One is if you are worried that there's something unique about individuals. They might be within the eligible population that it is reasonable to invite to participate in the study, but there's something unique about that individual that might make it particularly risky and against their interests to participate, then IRBs are approving for a population. They're not approving for a specific individual. So I don't mean to suggest that there's never any worry about undue inducement. So an example I've used with a somebody who wants to enroll in a study and there is a risk of nerve damage in the extremities. The IRB says, okay, we acknowledge that risk, but still there's maybe some benefit of being in this study. We think it's reasonable scientifically, go ahead. But then you have an individual participant who is a concert pianist, who is down on their luck and they could really use the money But if they have nerve damage in their extremities, they're going to be in trouble for their livelihood. That person could be unduly induced, right? You're going to have these exceptional circumstances. Then the response is to say, what are the benefits of offering payment to the population versus the risks to that individual? Can we minimize these risks? It's a trade-off, right? I'm not suggesting that we have a perfect solution, but it is in many areas of research ethics or life generally, like we have to do this balancing of whether the money is reasonable to offer. The other thing that people worry about beyond that someone's going to make a bad, they're going to reach a bad conclusion for themselves is is that the money is just going to blind them to risks that they should be paying attention to. They're just going to flip to the back of the consent form. Oh, that's the amount of money I'm going to participate in this study. And the solution to that is also not to pay people more, but just to really hammer home what the burdens and risks of participating are. Right. To kind of improve the consent process around those things that they might otherwise be glossing over. So, Ryan, to go back to your original question about, you know, disproportionate enrollment of people who need the money more. Yes, it is a possibility. As I mentioned at the outset, there have been a couple of empirical studies looking at that. They have not found evidence of uncertainty. unjust inducement, right? Like over-inclusion based on dire financial straits. But we know, right, that money has different value depending on how much of it you have. And we also know that, for example, many phase one trial participants are not people who are working on Wall Street or have lots of other streams of income. That being said, lots of people who are in phase one studies do it because they are artists or otherwise appreciate having opportunities to make money that are outside of the mainstream, right? So they're not being exploited. They are choosing that Okay, I want to be really careful how I say this. There is some exploitation in phase one studies, absolutely. Okay, but in some examples, you just have competent adults who are saying, this is a reasonable way for me to make money. And again, if that study is, reasonable to do, right? The risks and benefits of that study are reasonable to offer to these people, then it doesn't become unreasonable just because you're offering them a lot of money to do it. I'm going to add related to like the challenges I have in articulating these points of view about paying research participants is that oftentimes people act like research is so special that we have to be so much more concerned about payment than we do in other instances where, you know, as I, there's lots of things that people do that are unpleasant, uncomfortable, maybe even degrading. You're talking, I'm sure you're talking about them in this class where we say you can get paid to do it. And in fact, you know, when we think about risk, no one says, oh, we ought to pay the firefighters fighter less because their job is risky. right? You say, no, you should pay them more. And so there's often a disconnect about how people think about research versus how they think about other things that we get paid to do. The other misconception I hear all the time is people saying, well, the payment must be ethically problematic because people would not participate in the study unless they were getting paid. I wouldn't do my job without getting paid. And I love my job. I know. I always say that. Would you go to work if you weren't getting paid? Even if you love your job, right? There might be other things that you would do.
SPEAKER_02:Right, right. Exactly. I find a lot of the work, not yours. This is one reason you're here. I find a lot of the work in this area frustrating because sometimes I read it and I think, do these people not understand jobs, right? Like outside of the rarefied university or researcher setting, which as you point out are often risky, are often unpleasant, are often uncomfortable, especially if people are poor. Those are the types of jobs that are disproportionately filled by lower income people, right? And so the fact that the research setting might have those qualities doesn't rule it out as something that people might want to do, both as an income opportunity, if you pay them enough, And perhaps because they think it does some good for the world. I mean, you know, people like you don't have to, you don't have to be the fireman or the doctor or whatever, to want your job to have some meaning and some benefit for people, I think. So it always drives me crazy. I'm so pleased to hear you say these things. And I hope that everybody listens and not merely the, you know, 6000 or so subscribers to the podcast. Meghana?
SPEAKER_05:Yeah, so I wanted to build off of Ryan's question. I've been thinking a lot about that. I think it's a fine line between incentivizing diverse communities and potentially exploiting them. Although I do really appreciate your previous answer about respecting the competency of these adults. So I'm just wondering what the conversation is around setting this incentivizing uh payment it seems like a pretty abstract task and how um these directors i don't think it's the directors of the clinical studies that said the payments probably but how how that's they go about that
SPEAKER_07:i want to make sure i'm understanding understanding your question so When we think about exploitation, the basic concept is that we're taking unfair advantage of people. And so you can exploit people because they are in need and therefore, you know, desperate and would do, you know, the worry is like they're desperate, they'd do anything for money. The response to that type of concern about exploitation is to make sure that you're only offering reasonable studies. And that's, you know, when you hear about like, hole in the wall, phase one studies that are enrolling undocumented workers and really taking advantage of them, that's not acceptable. Obviously, that's not acceptable, right? And so somebody is failing in their oversight capacities in those scenarios. The problem is not the payment. The problem is the underlying conditions, right? That's one type of exploitation. But you can also exploit people by paying them too little and not giving them fair payment. And so when you think about people who are maybe desperate for money, they might be willing to accept less than the value of what they are offering and less than they are owed, right? And so we have to worry about exploitation on both sides. On taking advantage of people's dire financial straits, We've got to make sure that the research is acceptable and we have to make sure that we are paying them enough.
SPEAKER_02:I took Meghana's question and Meghana, maybe I misinterpreted your question. I took your concern to be, how do we draw the line between making sure that we incentivize diverse participation versus targeting particular... So in other words, we might feel differently about a study that says, as happened with the initial vaccines for the COVID vaccines, we don't have a diverse enough pool in this group. We need to go out to minority communities and improve participation there versus... let's go test this in low-income minority communities because we don't care about them. That's what I took your question to be, Meghana. Is that wrong?
SPEAKER_05:Yeah, I think that's the question, but I think it's answered through that two-step prong of making sure that the research is, the proposed research is ethical. And then also the emphasis being more on a payment minimum rather than a payment cap. Is that correct?
SPEAKER_02:But would that answer? I mean, I'm not sure that would answer the concern, though, would it, Holly? Because I think that listening to your answer to prior questions, you would say it would still not be okay to target a particular population just because they're easy, even if we thought the research was ethical and the payment was sufficient.
SPEAKER_07:So it would make it slightly better if you were paying them enough, right? But you don't want to recruit people for your study. just because they're there and accessible and you know that they would be willing to participate. Because that would be exploitative. When you're thinking about where are we going to recruit, you want that to be driven by scientific considerations. So let's take the example of international research, right? Zika did hit the United States, right? But if you were going to do Zika studies, you were going to do them in Central and South America because that's where the pathogen was having the greatest impact. That is a very legitimate reason. You've got to go where the pathogen is, as opposed to saying, let's go to Central America because we could pay people less to participate in our study there. And we know they're going to want to enroll because they don't have access to good health care. And so they'll get the benefit of being seen by doctors and whatever. That is... might be incidentally true. Like for the Zika example, you might, go there for a scientific reason, but then also have an easier time enrolling because there are these other added benefits to the research participants. But it's not exploitative to do that because you had a legitimate reason to be there in the first instance. The other thing I thought you might have been asking about is something that I don't have a pat answer for, but something I've been grappling with and I've been meaning to write a paper about is would it be reasonable to pay for diversity? Like to literally say we are going to pay diverse participants more because we are lacking in some capacity. And I haven't worked out my answer for that yet. And in part, it's because if the reason, it depends on why people are not, why diverse participants are not enrolling. Is the reason they're not enrolling something that could be affected by money? Like, would it even be an effective thing to offer? And then the other concern is whether if they are not enrolling for reasons of trust or lack of trust in research or the healthcare system, would payment make it worse rather than making it better? So those are some things I've been pondering around. Additional unanswered questions around payment that I wanted to get to in our a job paper, but didn't have the space to do.
SPEAKER_02:Yeah, this is a great issue. I think it's a good segue into our next set of questions, which are about representation and distrust in the system, which it strikes me that this dilemma that you posed goes directly to that question. Let me turn to Ryder. Ryder, your question was specifically about challenge trials, but I think that if you Ask it as a more general question, just following up on exactly what Holly just said. I think that it's a good discussion.
SPEAKER_00:Yeah, so I feel like Holly almost just exactly answered my question, which relates to price discrimination and payments being made to different communities based on the goal of achieving a representative sample. And you also touched on the reason why people may have distrust. such certain money really couldn't bring them to a willingness to participate. And I guess, you know, I almost didn't know if I should ask my question because I feel like you did answer it in large part, but I will hear more thoughts on that if you have
SPEAKER_07:any. Yeah, I mean, I think I hit on the main things that I would be interested in. The only other thing I'll add here is Sometimes there's a question about whether it will be reasonable to pay people in the same study different amounts. And it can be ethically controversial, right? Because you should pay people the same amount for the same work contribution, for example. But maybe some people are more valuable to the study than others. Maybe it's due to diversity. Maybe it's because they fill a particular other type of demographic, like a particular state of the disease that's not adequately enrolling. Or maybe you've just really... slowed down enrollment and you're not hitting your targets and you really need to get those last whatever 200 people in your trial can you pay a bonus to the last enrollees because you really just need them to get across the finish line I've written about this I think that there are the default expectation should be that we pay everyone the same amount who's contributing the same to the study but there are I've just given some rationales why it might be acceptable to pay some participants more. Again, it's a trade-off though, because you risk, if you pay those late comers to the study more, you could be signaling in the future that people should wait to enroll and see if you up your price, or they might feel aggrieved that they weren't paid as much for enrolling early. So you can address that if you have the funds by then going back and paying the people who are early enrollees a higher amount. This hasn't come up so far, but part of the reason that we made such a big fuss in developing the framework of ethical payment and having reimbursement and compensation and incentive and talking about the ethical rationales for each one of them is we tried to articulate that reimbursement and compensation are ethically obligatory. You have to budget for them. If you don't offer them, you have to have a really good reason for not offering them. Because so often people say, well, I don't have money to pay the research participants. And I think that's an ethical problem, right? You wouldn't say, I don't have enough money to pay the researchers, right? And so you have to build that into your research budget. Incentives, which I think, Ryder, you were getting at this point, Incentives are something that could be ethically obligatory to the extent that they are critical to getting the research done. If people are not going to enroll unless you pay them more, then they would be entitled to as a matter of compensation, then you've got a budget for that too. But I typically think of incentives as something that are kind of going above and beyond what's ethically owed to people for their contribution.
SPEAKER_02:So McKenna also had a question about sort of trust and the effect of payments and particularly pay transparency in the current environment.
SPEAKER_03:Yeah. So I had a question about sort of the stigma, as you mentioned earlier with the headlines about payment, even when the payment seems like it's necessary or appropriate. The headlines can blow it up and make it seem like it's not all right. And I just feel like with the current stigma around COVID and how that was mentioned, it kind of got me thinking about the conspiracy theories that have gone wild since the beginning of the pandemic. With medical distrust on the rise, what do you think can be done to mitigate the ripple effects of this with regards to HICs? Wouldn't releasing public payments, which I think would be a good idea, almost add fuel to the fire that there is some sort of conspiracy theory regarding the production of vaccines?
SPEAKER_07:So part of me is like, well, what can we do about conspiracy theories? Like, you know, I don't know that we should make any. I don't know that we should make any legitimate decisions trying to avoid conspiracy theories because they happen everywhere. no matter how reasonable you're being. So here's my response to your question is, I think the safest way to talk about payment is to not just do it in a quick, here's the amount that people were paid, move on to the next thing. But to combine the discussion of the amount with the rationale for how it was developed. Because so often you see pretty high numbers, but then when you actually break it apart, it's not that high considering what people were really being asked to do. And that takes the wind out of the sails of people who might claim that this is inappropriate payment. Now, if the concern is, oh, well, we're paying people because there's something nefarious going on, my response to that is, look, these people are owed payment because they are contributing something meaningful to the research and costing themselves time, effort, discomfort, burden. So we owe it to them to pay regardless of whether it's going to cause somebody else to go off the deep end. Okay. So Mary,
SPEAKER_02:final question to you.
SPEAKER_06:All right. So yeah, I am curious about your thoughts on HICS studies that are run at universities using primarily college students as the participants and how we fit all that particular setting affects the ethical payment calculation. And so I am a double hoop. And during my undergrad time at UVA, I had a friend who would sign up for several of these studies involving the common cold virus. And she's signing up for them because she didn't have family support. She really could use the money. And so they each pay, I think, like a few hundred dollars, if I'm remembering correctly. And there were multiple times that she had to take exam sick because the study just happened to align with the exam period. And so the situation definitely just struck me as wrong. And I'm sure there are plenty of college students who are just looking for some extra spending money and will sign up for the occasional study. But I am concerned about students who are in a similar position to the one my friend was in.
SPEAKER_07:So the reason I really loved your question was because I think it's a great example of how we need to separate our thinking about unfortunate circumstances and ethical payment. So what I'm hearing from your description is that You wish your friend had more support. And it's unfortunate that college students and other people find themselves without adequate financial support. And that leads them to do things that they might otherwise not want to do. right? And it could be probably other things that you've talked about in this class. It could be sex work. It could be donating blood. It could be babysitting for really horrific children. It could be working at a demeaning job where your boss yells at you all the time. There's lots of things that are truly unacceptable things, but nonetheless, they are kind of facts of the world. So I think the real concern that I'm hearing expressed in the story that you've relayed is that college students ought to have better support and more reasonable work opportunities to meet their financial needs. But I am not, unless there was some ethical concern about these challenge studies, that their risks were too great, that the pay was too low, that the isolation was too intense, probably not isolation in a cold study, but that if there was some underlying worry about the study itself, then I would say we have a concern that's unique to the research. Otherwise, it's just a concern about people having to do things that we wish they didn't have to do for money. And so I think it's really not actually a research ethics concern. There is maybe some element of exploitation in the convenience of doing challenge studies in a place where there may be lots of people who are in financial need. But again, I don't know that that means that we ought to pay less or not make those financial opportunities available. And that's actually probably a good point to close on is sometimes when we talk to people about fears about payment or ethical concerns about payment or concerns about exploitation in general, we have to say, would the person be better off if that offer had never been available to them in the first place. And I suspect that your friend would say, no, it was really helpful to have that money available. I made a competent choice. I wish I had other ways to make this money that may have been more comfortable, but I'm glad that this choice was available. So again, as long as the study itself was ethical, I think it's a reasonable thing that happens.
SPEAKER_02:Thank you so much for doing this, Holly. First of all, it was great to meet you. And I'm going to call this in person because because this is what passes for in-person these days. But it's great to be able to put a face with the name and with the work that I've been following for a while now and to hear you answer all these questions. And so we really thank you for coming.
SPEAKER_07:Well, it's been my absolute pleasure. I was so impressed with the document that got circulated with the questions. I mean, really, really thoughtful engagement. And what a cool idea for a class. I may have to We have to test this out at some point.
SPEAKER_02:Yeah, no, they worked hard on their questions. They put a lot of thought into it. So thank you. Thank you for indulging our many questions. I'm sorry we didn't get to all of them, but that happens usually. So not unusual.
SPEAKER_07:All right. Well, great to meet you. Okay, bye.
UNKNOWN:Bye.
