 Welcome everybody to the January Health Policy and Bioethics Consortium. We're going to be covering treating healthy clinical trial participants and some of the ethical and practical issues involved. My name is Aaron Kesselheim. I'm a professor of medicine here at Broom's Hospital at the Portal Research Center as well as at the Center for Bioethics. And Leah Rand and myself organized this consortium and are excited about getting 2023 kicked off on a good note with this really excellent topic and group of experts. Next slide. So just as a quick reminder of some logistics, please ask questions. Feel free to enter questions in the Q&A feature along the way. There'll be some time at the end that'll be dedicated to questions. And the Q&A function button is the right way to do that. If you have technical issues, you can put those in the chat and we can help you. But if you have questions for discussion or for the panelists, please put those in the Q&A. If you want to talk about these on Twitter or Mastodon or Post or whatever social media you're using right now, we use the hashtag HMS Bioethics or hashtag Policy Ethics as a way to follow the conversation. And if you have questions about future programming at the Center for Bioethics, feel free to check out the Bioethics website. Next slide. The goals, as always, of these consortia are to try to articulate key issues in the healthcare system that involve ethically challenging policies and practices, bring together experts with different perspectives to consider various solutions and to try to stimulate conversation and further evaluation of the topic. That is everybody's homework. So we're getting set up for the rest of the year. We're going to talk about climate change in February. It would have been reasonable potentially to talk about climate change today when it is 60 degrees in Boston, but instead we're going to talk about it in February. We're going to talk about open access innovation for vaccines in March and discriminating devices and racial equity in April. So get these on your calendar and more information is available online on the Bioethics website. So to introduce today's topic, I want to turn the floor over to my co-organizer, Leah Rand, who is a colleague of mine in Portal, a faculty member in the division in the Center for Bioethics and has a lot of expertise in ethics and ethical theory. So Leah, thanks for helping organize the session. Thank you, Erin, and I'm really looking forward to today's discussion, which arose from a particular interest of mine. I'm delighted to welcome Dr. Benjamin Silverman, who will be monitoring today's discussion. Dr. Silverman is an academic psychiatrist with a background in medical ethics and addiction psychiatry. He has over 10 years of experience in analyzing ethical issues posed by scientific research, building on his clinical training in psychiatry and addiction psychiatry. He currently serves as an IRB chair at the Mass General Brigham IRB, which is responsible for oversight of human subjects research at McLean Hospital, Massachusetts General Hospital, and Brigham and Women's Hospital, among others. Previously, he's been the chair of McLean Hospital IRB. And in these roles, he has been responsible for scientific, regulatory, and ethical review of human subject research protocols across multiple large academic institutions. And as part of this work, he routinely counsels investigators on scientific, regulatory, and ethical issues, both informal and informal presentations to help move forward science in a broad way. Holly Fernandez Lynch will be presenting first, and she is an assistant professor of medical ethics in the Department of Medical Ethics and Health Policy at the Perlman School of Medicine at the University of Pennsylvania. She co-chairs the School of Medicine's Research Ethics and Policy Series and serves as an assistant faculty director of online education initiatives in the department, where she helps lead the Master of Healthcare Innovation. She also has a secondary appointment as an assistant professor of law at the University of Pennsylvania at Cary Law School. Professor Fernandez Lynch is the co-founder and co-chair of the Consortium to Advance Effective Research Ethics Oversight, A collaborative effort in established in 2018 to understand, evaluate, and improve IRB quality and effectiveness. She served as a member of the U.S. Department of Health and Human Services, Secretary's Advisory Committee on Human Research Protections. She is currently a member of the boards of Public Responsibility in Medicine and Research, the Primer, the American Society of Law Medicine and Ethics, and the NYU Working Group on Compassionate Use and Pre-Approval Access. She also serves as the ethicist in residence at the Robert Wood Johnson Foundation. And prior to joining Penn, Professor Fernandez Lynch was here at Harvard as the executive director of the Petrie-Flam Center for Health Law, Policy, Biotechnology, and Bioethics, and was teaching faculty in the Master's of Bioethics program. So it's wonderful to have her back with us today. She will be followed by Jill Fisher, who is professor of social medicine and core faculty at the UNC Center for Bioethics. Dr. Fisher is a social scientist with a PhD in science and technology studies from the Rensselaer Polytechnic Institute and expertise in medical sociology and research ethics. Dr. Fisher has published three books, which I highly recommend, and over 50 peer-reviewed articles and book chapters. She is the recipient of approximately $4.9 million in funding as a principal investigator on grants from the National Institutes of Health and the National Science Foundation. And in addition to her work on clinical trials, Dr. Fisher has published on the social construction of Munchausen Syndrome, tattooing as a cultural practice, gender and science, hospital tracking and location technologies, non-human animal research and qualitative methods. I'm really excited to welcome this wonderful panel with to us today and over to you, Dr. Silverman. Great, thanks so much. Thanks so much to the audience for joining us today and thanks very much to Dr. Zoran and Kesselheim for organizing, hosting and inviting us to this meeting and for this discussion on this really interesting and important topic. So to introduce today's session, I thought it might be helpful for me to describe some basic concepts related to participant remuneration and clinical research and to discuss how IRBs traditionally approach them. Without getting into detail, there's been a long and vigorous debate about paying subjects for clinical trial participation and remuneration to subjects is now widely accepted as a standard practice. We generally classify remuneration as compensation for time and effort or inconvenience expended by research participants during their participation. Remuneration is not meant to be a benefit of participation and is not considered as a benefit when IRBs assess the approval criteria for a study. Of note, this is distinct from reimbursement or repayment for out-of-pocket expenses incurred while participating in research, for example, travel or parking, which we would hope would always be covered to the degree possible. In addition to compensation for time and effort, remuneration also serves a function of incentivizing clinical trial enrollment or completion, and this is certainly a topic of ongoing discussion. The traditional IRB or ethical concern around participant remuneration really centers on the fear or risk of paying people too much. In other words, offering a payment that causes undue influence on a potential subject and their decision to participate. So to say that another way, essentially, we worry about excessive payments, motivating someone to participate in research or take on risks that they would otherwise not take on. And I think that stance from IRBs has likely kept payments lower, perhaps too low throughout the years. Equally important, if not more important, and actually less traditionally focused on by IRBs is the risk of paying people too little. For example, many of our studies offer really more symbolic payments and don't meet what we consider a standard minimum wage. And I think this concern over whether participants are compensated fairly will really be a key question for today's session. That concern is amplified in phase one research, which we're focusing on today where healthy volunteers enroll and are exposed to often unknown risks, for example, first in human studies with no possibility for direct medical benefit. Because of that, and because phase one studies requires significant time commitment, they, they do often call it usually offer more compensation. And as a result of that, when we look at then who actually enrolls in phase one studies, I think we'll talk about that today. We really must ask the question as if we're exploiting certain populations or unfairly distributing the burdens of research. So to wrap up from the IRB perspective, but by way of introduction, I'll just note that traditionally, I think the goal of IRB oversight of research compensation is to ensure that stipends paid to research subjects are both fair. And without causing undue pressure to participate. That said IRBs tend to be very conservative. And I think most IRBs hold a concept that monetary compensation is not intended to be the only motivating factor to induce subjects to participate. And that's certainly the case for some phase one studies, for example, enrolling non healthy volunteers like cancer studies or in certain research communities like ALS research community, but at least in my personal opinion I think for many healthy volunteers, really the financial incentive is the primary or perhaps only reason for participation. In some cases I worry that IRBs and researchers and others essentially stand behind a description of compensation for time and effort to avoid feeling some discomfort about what we're actually doing which is paying people to enroll in research or for use of their research for research and I fear that in the process of kind of hiding behind that we really risk not not paying people enough to fairly compensate them so I know we're going to talk about all of this and more today and I'm really looking forward to the discussion and with that I will turn it over to Dr. Bernadette Lynch to get us going. Okay, well thanks I don't have to give my talk anymore because you've just you know established all the principles really, really nicely. Hang on one moment and I'm just going to share my slides for everyone and can you see those okay. Okay, great. Well, thank you for having me here today I'm really looking forward to talking about these issues with everyone. And, you know, Dr. Silverman has set up the challenge really well. We were asked to talk about how do we treat healthy clinical trial participants fairly. And I'm going to talk about paying them fairly before turning things over to Dr. Fisher to talk a bit more about what things will look like for a phase one healthy research participant. So, you know, we've just heard some of the reasons that a healthy person might enroll in clinical research there is some empirical data, much of which Dr. Fisher has collected herself. But over the course of several decades right we've talked to healthy people and rolling in various types of research, and you know certainly altruism plays a role for some communities more than others. People say things like, I'm really interested in science or I was just curious or bored or you know, sometimes people raise thrill seeking kind of reasons for participating in phase one research. But most of the time, it's money, right, there is a reason why people are enrolling in these studies that they're not going to get direct medical benefit out of participating in. I thought it would be helpful for us to start with a case. I want to talk to you a little bit about challenge studies challenge studies were something that we're really flying under the radar for most people before coven. We have a research design and which healthy people are intentionally exposed to a pathogen, in order to learn more about that pathogen, or to learn about the effectiveness of various prophylactic interventions or even treatments and ways that would be difficult if you had to wait for people to be naturally exposed to that pathogen in the field. So these are commonly used for setting the common cold influenza malaria, basically typical for naturally self limiting or easily treatable diseases that were going to kill people in these studies and even if they experienced some, you know, negative sequelae of the infection, we're able to mitigate that and treat them really quickly. Now, there has been an emerging ethical debate about whether we should use the challenge study model for emerging infectious diseases that are not naturally self limiting or necessarily treatable. So with this came up in the context of Zika virus proposed challenge trials in that context, as well as more famously in the context of potential SARS-CoV-2 challenge studies on the argument that this might help speed vaccine development saving many more lives, but also was more controversial because higher risk of serious morbidity and mortality with these emerging infectious diseases. So what you see on the screen here, don't read too much about the details, a lot of text but these are the details of a SARS-CoV-2 challenge study that was done in the UK. So this was a study specifically to develop a human challenge model for this pathogen. It was not, you know, to study a vaccine or to do any kind of efficacy testing of any intervention it was just to figure out how much of this does it take to infect people and what does the course of the infection look like. So they enrolled 36 healthy participants ages 18 to 30 who had not previously been infected or vaccinated from March to July of 2021 and they had extensive screening that was intended to minimize the risks that these participants would face. The participants were held in a quarantine unit for at a minimum of two weeks and in addition to being exposed to the virus were subjected to a whole bunch of tests, blood tests, EKGs, various assessments and stands and diaries and then after they left quarantine lots of follow up over the course of a year. So you can see in the flow chart here that lots of people nearly 27,000 people had registered their interest in participating in this challenge study online, very atypical, but there was a big kind of public relations push around this kind of study. So, which is just to say lots of people were willing to participate and then of course as I mentioned, got down to just 36 volunteers for this particular study. Oh, shoot. Okay, we are going to do a poll everywhere. And I hope that this works so you can see the instructions at the top of the screen there you can either do this on your computer by going to the URL that you see at the top, or you can text my name Holly F Lynch to that number 22333 and vote. I'm going to give you a second to do this and the question that I'm asking you to vote on is just based on those very preliminary details that I've provided, would you be willing to approve this study if you sat on the IRB. And maybe Leah or Benji, you could just tell me if this is working for you. And then I'll move on to the next slide where it will show us the results. It's certainly working in terms of being able to answer the question. Great. So I'm going to give it, you know, like three more seconds before I move to the next slide. So I don't sway anybody as a vote. All right, so we have a mix of perspective here a couple more votes are coming in. So it looks pretty evenly split a third a third a third although changing as we go. At least some of you would be willing to approve this study given the safeguards that were in place the potential social value and what you understand about the risks and benefits of participating in this kind of research. Okay, in the interest of time I'm going to move to the next bit of information that I want you to have about this study. Which is. Okay, so in this in this particular challenge study participants. This is from the publication, which you can see at the citation at the bottom of the slide here is the language that they use participants were given a donation. That's not a typical language around payment of about 4500 pounds, which is the equivalent of just over $6,000 to compensate them for the time and inconvenience of taking part in the study, and a little bit of information about how they went about calculating this using the National Institute for Health Research formula and the UK national living wage. Okay, so we have another poll coming up. So, does this information about payment change your perspective about whether you would approve the study do you think the payment makes the study ethically stronger ethically worse doesn't change the ethics of the study or maybe you're not sure. So you should be able to vote again. Holly just to let you know, the last slide the results didn't actually show up so you. Everyone. Oh no, they were showing for me. Shoot. Okay, I'll tell you the results if they don't show up for you. Exactly. Thank you. Okay, well then if you can't see them. It doesn't matter if I see you won't sway your, sway your perspective. Okay, so the results are are coming in. Okay, it looks like about a third of you voted that the payment makes the study ethically stronger, but 28% of you think it makes the study ethically worse, and a third of you 34% say the payment does not change the ethics of the study. All right, now one more poll here. Do you think about the amount of payment. Do you think it's reasonable coercive unduly influential exploitative, none of the above and I recognize you can only vote for one of these. So just choose the one that is closest to your perspective on that about $6,000 payment that these participants received. It's an easy crowd about two thirds of you think that the payment sounds reasonable 12% say coercive 16% say unduly influential, and a handful maybe one or two of you are saying, none of the above but nobody thought that it was exploitative. Okay, well I apologize that you couldn't see the results but you have to trust me that that's that that's where they came out. So I use that as an example of a study that was really burdensome to be a part of, and although they really minimized the risk to the participants, and ultimately you know no participants experienced major, you know, any serious harm from participating in the study, we of course didn't know that at the outset so this was fairly ethically controversial to have run this study. Didn't get a lot of attention once it actually happened, but there was a lot of discussion about how payment should be set in this kind of project. So, so what I want to articulate to you, you know, thinking about that example and others that you may have come across in your own work is that payment can be critical to study success right there's probably not enough lists to fill the phase one studies that need to happen for drug development to succeed. The SARS-CoV-2 challenge study was unique right in the midst of what we hope will be a once in a lifetime pandemic. So there were lots of people who are willing to kind of contribute to that not necessarily the case for other early stage human subjects research. But what we know empirically is that healthy participants say payment is necessary for them to be able to participate right to cover their costs to make them willing to participate, but it is not sufficient. And over and over again we see data where a healthy research participants say, look, I wanted to get paid, but I wasn't blind to the risk, and I will decide which study to be in based on how risky it was. And we also know that payment is absolutely common in the context of healthy participant research, although we don't have a great set of benchmarks to know how much people are getting paid their spotty reporting in the clinical literature and no kind of universal database where these payments get entered. We have empirical data beyond healthy participants alone. And so we know that payment can be effective in improving recruitment to trials which is what you might hypothesize, but it is not always effective and so maybe we're not paying people enough, maybe the research is too risky or burdensome in other ways. So it's one lever, but it is not the only lever that we need to push to make sure that people are enrolling in important research. But there have been some empirical analyses of what's called unjust inducement, which is what Benji mentioned before, where we worry about over-enrolling disadvantaged populations in research. In fact, you may have seen a recent stat news story that was articulating or covering a recent research study in which payment higher levels of payment were successful in mitigating income and race enrollment gaps in a study that would have led other people to submit blood samples to participate. So basically what these researchers found was that at lower payment levels you were getting more high income white participants, and it wasn't until you got to very substantial payment levels that the income and race enrollment gaps were closing. So in addition to being potentially important as a matter of recruitment, payment is a matter of fairness and respect to research participants, which is what we're hoping to talk more about today. These participants, whether it's in the SARS-CoV-2 challenge study or other phase one research are contributing a valuable service to science. Every other entity is getting paid, right? The researchers are getting paid, the research staff is getting paid, the site is getting paid, the company is eventually going to be getting paid, assuming that their product ends up being successful. So why should the participants whose participation is absolutely critical be the only ones who are cut out of it? So being altruistic is okay, but that should not be the kind of moral expectation that we have of research participants. And Benji has already flagged that low payment can be unfair and exploitative. And just so we're all on the same page, when I talk about exploitation, what I mean is taking unfair advantage of people. And just check my stopwatch and realize that I didn't press it. So someone's going to have to flag me when I, maybe Benji, you could give me like a five minute warning when I'm almost at time if that would be okay. And so the next point that I want to raise is that even though payment is absolutely critical, it is also ethically fraught in a number of ways that Benji introduced at the start. So in order to have valid informed consent to research participation, we want to make sure that people have the capacity to consent that we're disclosing all material information to them that they're able to comprehend that information and then make a voluntary decision to participate. So outside some exceptional circumstances, research without valid consent is unethical. Now, coercion and undue influence are the things that give us some some worry when it comes to payment. So if payment is coercive or unduly influential, then it would be interfering with valid consent and we would have these significant ethical concerns. But how do we know, right? How do we know if payment is coercive or unduly influential? You might think we could look at the research regulations. Unfortunately, they are not much help at all. So I've cut and pasted some text here from the relevant regulation they do not mention payment at all. Instead, what they say is that in the context of seeking informed consent, investigators should only do so under conditions that minimize the possibility of coercion and undue influence, which are not defined in the regulatory text. Now, there has been some federal guidance about ethical payment for research participation. The guidance says, you know, payment is common and in general acceptable. Well, that's a good thing because it's happening all the time. But they also note that it should be just and fair, but they express some concern about excessive and inappropriate payment with the potential to compromise voluntary informed consent. And then they go on to warn IRBs to be vigilant about minimizing the possibility for coercion and undue influence. As Benji, you know, highlighted at the beginning, how are IRBs vigilant, restricting incentives for participation. So what we end up with is this one sided focus on high payment and not nearly enough concern about the exploitative unfairness of paying people too little for what they are undertaking as research participants. And so that's one of the main messages here is that we have to think about low payment, not only potentially too high payment. Now, Benji had also mentioned that IRB is when they're assessing the risks and benefits of research are not allowed to consider payment as a benefit that offsets risk. In other words, you cannot include a really high payment in your research in order to make it approvable. The IRB has to assess whether the research is approvable, separate and apart from payment and that becomes really ethically important in ways that I'll describe in just a moment. All right, so the feds are starting to acknowledge some nuance at the very least they articulate that reimbursement for travel and lodging expenses does not raise any issues regarding undue influence so that's a step in the right direction, but they still articulate that IRBs need to be sensitive to other types of payment. So, one really maybe a bit pedantic comment that I want to make here is that payment is not coercive if you understand coercion to be defined as a threat to violate somebody's rights, or a threat not to fulfill an obligation that you have to them in order to get them to comply with something you want them to do. And the other party has no reasonable alternative but to comply. Payment is not a threat, right, a genuine offer of payment to be a research participant is not a threat to violate somebody's rights. It's not a threat to take away something to which they are otherwise entitled. Even if the payment feels like an offer that's too good to refuse right oh I need to be in this study I've got no other opportunity to make this much money. It's not a coercive threat so I would like us to put that language aside in this discussion. Coercion is possible in research right you could imagine a physician saying I'm not going to treat you unless you participate in my study, but coercion is not stemming from payment in these examples. But payment can be unduly influential. So if we think about the definition of undue influence that's when we have an excessive offer that leads to a distortion in somebody's judgment. It makes them not able to understand risk it makes them skim over or be blinded to the risk. And then that leads them to make an unreasonable decision to take on a risk of harm or burden that is against their self interest. We need to differentiate between undue influence and mere influence. So lots of times I hear people say, well that person wouldn't have participated in the research if they weren't getting paid that much money. To which I say, would you go to work, unless you were getting paid. Right, you know, we can be influenced by money in ways that are not bad, or harmful. So a mere influences just when you have an attractive offer that leads to a reasonable judgment and a reasonable decision. We are not worried about mere influence caused by research payment. Now I mentioned before the role of IRBs in evaluating the risks and benefits of research and making sure that they are reasonable before, you know, before payment is allowed to proceed. Benji, I saw that you raised your hand but I cannot see anybody so I don't know if you want to jump in. Oh, just to say five minutes left. Okay, awesome. I'm going to go faster. So, so the fact that IRBs are making sure that the research is not unreasonable to ask people to participate in is going to play a big role in minimizing the possibility of undue influence. Okay, if you, if it's not unreasonable to participate, then we don't need to worry about paying people too much. Now, IRBs are not perfect. They can't account for idiosyncrasies in individual participants, they're reviewing research for populations. There could be, you know, some member of the target population that's eligible to participate but there's something special about them that the IRB couldn't possibly have known. So, if you think about a study that has a risk of a permanent tremor causing a permanent tremor, you know, you're not going to have an exclusion criteria for concert pianists in your protocol, but it might be particularly risky for a concert pianist to participate in that study. Now that person could potentially be unduly influenced to participate. But we also cannot eliminate the possibility of deception, right, payment could cause people to lie about their eligibility to participate or lie about their, their continued participation, for example, if they're experiencing adverse events that would make them eligible to continue participating and that's risky for them, and it also poses a risk to scientific integrity. I'm going to skip over this, I'm going into too much detail but we do have some evidence that money induces participants to lie about their eligibility. I was actually part of a research team where we tried to study this more specifically. Just to cut to the chase what we did was we did a survey through GFK Knowledge Networks which was a nationally representative online sample of adults. And the hard thing about studying whether people are lying to you is that it's hard to know whether they're telling the truth. So we did a survey where we told people you're eligible to participate based on whether you have or have not had a flu vaccine in the past six months. And then we told them how much we would pay them if they were eligible. So for example, you're eligible if you had a flu vaccine will pay you $5 and then we said, did you have a flu vaccine. So they have a motivation to be untruthful so that they could get the money, and we could compare them to the group that was told they would be eligible if they had not had a flu vaccine. In a random sample you would expect those numbers if there was no lying to match right the number of people saying yes they've had a flu vaccine and each of these groups should be the same, but that is not what we found. As you can see in the red box here, those numbers in the middle 1621 15%. That was the difference between the two groups right we those numbers should be zero if everybody was telling the truth. So we were seeing a fair bit of deception in our sample. We also tested to see whether payment amount would cause more lying. And we didn't actually see that so if higher payments led to more lying what you'd see on this chart would be results along dotted lines, but really we're seeing a clear deviation from the blue line that's the lying, but the payment amount didn't really matter too much. So let me skip ahead here. The other challenge I wanted to flag is that IRBs might just fail in general right they are, you know supposed to be making sure that research risks are reasonable before they're offered to research participants. We might have conflicts of interest influencing IRBs they might face gaps in their expertise, and we have to acknowledge that IRBs are largely entities that have to rely on trust, they have to rely on the researchers telling them honestly what they are going to do, and then they're doing paper based review, they're not going to the research site, they're not overseeing the consent process in real time. And so it is totally possible that risky and unreasonable research might slip through. This doesn't mean that payment should necessarily be low right IRBs don't have to eliminate the possibility of undue influence, they have to minimize the possibility of unfluent undue influence and they need to balance concerns about payments that might be too high against concern about that could be too low. So we can acknowledge right some idiosyncratic participants might slip through, we might be worried about deception but before we lower payment to avoid deception. We should think about you know objective criteria for enrollment and adverse event reporting, educating potential participants about the risks of deception and improving IRBs abilities to weed out unreasonable research. I think it's really clear about this. If research is unreasonable. The solution is not oh well pay people less to participate in the unreasonable research. The solution is no we have to make sure that the research is reasonable. So that is a concern that extends far beyond payment. Okay, so very briefly just to kind of flag a couple of terms that Benji used at the beginning reimbursement compensation and incentive. If we think about the function that payment is playing that can also help reduce our concern. So reimbursement is payment for out of pocket expenses and I would like to articulate that that is a matter of fairness, we should not be expecting people to pay out of their own pocket to contribute to good science right that we all need people to participate in in order to generate scientific knowledge and medical benefit. So that's something that I don't think should be dependent on the budget, I think, you know you should have to budget to reimburse people's out of pocket expenses and we are not worried about undue influence in the context. Nobody is participating in research, just to get their out of pocket expenses covered compensation right so as Benji mentioned this is a type of payment that is intended to compensate people for the time effort and burden that they take on as research participants and this is a matter of fairness right people should be fairly compensated for their contributions. All compensation is trying to do is make research as attractive as comparable non research activities. So there too we should have lower concern about undue influence it's not intended to provide a net benefit, it is intended to make participants whole incentives is the area where we really might need to pay a bit more and think about undue inducement incentives are payments that go beyond what's owed as a matter of fairness. Okay, so they are above and beyond reimbursement and compensation. Their purpose is to encourage recruitment and retention by making research participation even more attractive than other things people could do to make money. So undue inducement is possible here. But again remember what I told you empirically right we're not seeing that payment compromises people's ability to recognize risks. And if we think the research is reasonable to participate in, then we can worry a lot less about incentives. So whereas reimbursement and compensation are owed as a matter of fairness incentives are not necessarily owed but you might need them in order to get adequate recruitment for your study. So where I will leave things before we, you know, move on to to Jill's talk and the discussion is to highlight something else that Benji said, sometimes I worry that IRBs, when they express concern about research are really expressing discomfort with this study that has been approved concern that the study is too risky or burdensome. And so we should not be paying people to participate in it. But if the study is too risky or burdensome and we shouldn't be approving it in the first instance so payment cannot make the study itself unreasonable or reasonable those things need to be treated independently. So I will, I will end there and maybe during the Q&A we can talk a little bit more about fair compensation for research related injury, which is a little bit different from other types of payment but also another way to make sure that we are treating healthy participants fairly. Okay, no stop sharing. Thank you. Thanks so much Holly over to you Jill. So, that that was a great kind of overview of the issues that I want to touch on with my talk so I ended up titling what I'm going to talk about today as research payment as financial risk, healthy volunteers experiences and based on trials. So this is kind of turning the typical discussion about research payment on its head in some ways to kind of focus on how actually paying people might be a risk that we actually don't disclose to them so hopefully that will make more sense in a little bit. And to just note here when I talk about these one trials, I am of course talking about first in human trials so when it's literally the first time investigation on new drug is given to a research participant, but from the perspective of healthy volunteers particularly those who tend to enroll serially or repeatedly in these kinds of clinical trials. They don't necessarily distinguish between the kind of true phase one trials and other trials that are that need healthy volunteers. So for instance, there are lots of healthy volunteer trials that are metabolism studies or drug drug interaction studies, or the kinds of studies that need to get bio that need that help get generic drugs on the market so bio equivalent studies. So when I think about phase one trials I kind of group all of these things together because these are sort of the whole array of studies that healthy volunteers are participating in. And I'm going to just give that as context because I'm going to talk a little bit about how much healthy volunteers actually earn from clinical trials. So we could kind of situate this as a way to think about whether or not there is potentially undue inducement happening or how fair compensation actually is. I just flagged it when Holly was talking about challenge trials but I do want to just flag it again because it's really really important but for the most part these clinical trials that involve healthy volunteers really are very burdensome compared to a lot of phase two or phase three there are a lot of times that often healthy volunteers are asked to be confined to a research unit for some or all of the clinical trial and this could be days or even potentially weeks that they're confined. So for instance, over the course of my research on healthy volunteers. There were at least a few trials that were 30 or more days that participants literally were locked into a research facility. So it really does kind of change how we think about what might be fair and how much potentially is owed to healthy volunteers who enroll in these trials. So the going rate in the US for phase one trials kind of depends on the region of the country, but for the most part these trials pay about 200 to $250 per night that healthy volunteers have to spend in the clinic. And based on the research of my research team we found that the average clinical trial phase one trial pays about $3,000. What's interesting to is that a lot of the research clinics really do give preference to repeat participants, and this is because the clinics can rely on them to know what's required of them to actually stick it out through the entire study. They tend to be more compliant with what needs to be done during the clinical trial and so there are a lot of healthy volunteers who want to participate in multiple clinical trials of this sort, but also the research clinics themselves want to have those participants. So I think that's another important dynamic here that needs to be underscored. So oftentimes when I talk about healthy volunteers you know I think a lot of people have this vision of healthy volunteers as college students who are enrolling in these trials for extra money, but at least in the US when we're thinking about phase one trials. This isn't actually the typical demographic at all of who participates. So it's mostly men and this is in part because of inclusion exclusion criteria that make it difficult for females of childbearing potential to enroll and I'm happy to talk more about that during the q amp a But really importantly, there's a disproportionate number of minority participants who enroll in these clinical trials so on the East Coast and the Midwest it tends to be mostly black participants on on the West Coast it tends to be lots of Latino participants. And most participants are between the ages of 20 and 45 and in fact the majority are in their 30s and early 40s so actually it's not so much the younger participants who are enrolling in these trials. As I've already noted these trials require people to consent to an inpatient confinement so it starts to make sense like who you know what their social situation might be and so most of them are unemployed, or at least have had an unstable employment history as a result mostly their lower income and often they have low educational attainment. In addition, many have a history of incarceration in the US there's quite a bit of discrimination against people who have a criminal record and so these clinical trials are potentially an opportunity for people because there's the people who have a criminal record are not barred from participating in clinical trials and likewise, many participants are immigrants to the US some of whom are not legally permitted to work and so again like without, without that sort of impediment to earning an income, it does make clinical trials an attractive option for many of these individuals. And in this context when we're kind of talking about diversity and how do we improve diversity and clinical trials. It's really interesting to look at phase one healthy volunteer trials, because, you know, at least from my perspective this higher percentage of racial and ethnic minorities and these trials really doesn't feel like a recruitment success and so this is kind of a question that has motivated my work of really teasing out well why doesn't it feel like a recruitment success. And so I've published a book in 2020 that really explores phase one trials. And I really kind of grapple with this paradox of minorities participating in the riskiest studies that have no direct benefit. And so it over the course of the book, the primary argument, especially that's important for today's conversation is that it's really the racial and economic inequalities in the US that create a market of healthy volunteers for phase one trial so essentially because we have so much social inequality in the US, it really does sort of create the context for why this, these groups of people would be particularly willing to enroll in phase one trials. The book also looks at validity concerns and how we have to be also aware of how phase one trials tend to make new drugs appear safer than they are but that's sort of a different conversation than what we're having today. So just to give you a sense of how people talk about their financial motivations, Lewis told me, I wanted to make some money it's definitely not because I want to save the world, let's get on the record right now know I don't want to save the world, I need to make money. And of course, you know, a lot of times participants might reference altruism and Holly flagged this as one potential reason why healthy volunteers might enroll in trials. And I think from the perspective of a lot of the participants that I've spoken to you over the course of doing this research, they acknowledge the social benefit and I think they appreciate the fact that they could be contributing to science or the development of new medications, but that's not their motivation for And a lot of participants, especially when they're thinking about their very first trial and why they enrolled in that first one they do kind of flag that they were in a situation of financial desperation. So for instance, Manny, and these are all in quotes because they're pseudonyms by the way, said, you know, where else am I going to get this income my cars broke down you know what are we going to do if I don't pay my parole I'm going to go back to prison. That's pretty much how I see it as income, that's for real, and anything else is maybe helping out you know seeing what the medicine does to. And so you know, there's definitely these situations where participants find themselves in where they do need some income and they typically need it relatively quickly and so there's this offer of the compensation that participants can get from a phase one trial that's a lump sum. That is incredibly attractive for a lot of these participants. And as far as why they might keep and enrolling in clinical trials I think Wesley demonstrates or gives an exact kind of explains this really well so he says, you know I think I'll keep doing them until I get old like I can't do no more I mean I'm always going to do studies you know because I, because I know I can always cash because sometimes you can get a big chunk of money and you can get out of your debt for a little bit of time you know. But you're going to always be in debt you know unless you hit the lottery because the bills keep coming back as fast as you can they come back. And so this sense that in some ways without a robust social social safety net. It doesn't depend on the government or states that clinical trials sort of provide a type of social safety net that participants can rely on that they know that if they can just qualify for these trials that it is a source of income when they need it. And of course a lot of participants also are these kind of professionals that want to do studies exclusively and so I wanted to give you an example of one of the participants who was in this position. So he said this has been it he said probably the biggest personal gain I've ever had is that the money comes in a large lump sum I've made more in a month and most people make in half a year. What it came in was like 36 days. It was like $7300. Never have I had that much money in my possession at one time. It's not a lot of money but it's enough to really do something you know it's enough to have someone of a free life. I don't consider this a career, meaning clinical trials, but at the same time busting my home at McDonald's for $8 or $9 an hour and bringing home $900 to $1,000 in a month. I don't make that in a week just doesn't seem feasible to me you know, like doing the lab rat thing I've grown accustomed to a certain kind of lifestyle, having lump sums and money whenever I need it, you know, and being able to do whatever I want. But then he kind of transitions to talk about how it's not necessarily as good as it seems. So he said, the thing that the lab rat thing lacks is consistency you know, if my rent is due and I get into a study and the study gets canceled. If something happens like my muscle enzymes are up or something's off and I don't get into the study I'm screwed. It has its pros and it has its cons and that's probably the biggest con for me is just that you know it's not guaranteed. Not only are you competing with yourself your own body you're competing with other people you know. So this was very a very common thing theme among participants that it was definitely not a certain thing it was nice to know that there were studies out that there that they could screen for but it was very difficult to feel like it was income that they could absolutely guarantee or count on. So, um, my research team was really interested in just kind of looking at how much do these clinical trials pay and so in a longitudinal study of healthy volunteers we asked them to report to us about the clinical trials they were screening for and participating over the course of three years and over that three year period, we got about 1000 clinical trials from this database of 131 participants who are reporting their clinical trial screening and so we were able to kind of look at not only how much were they earning, which I'll show you in a moment but also what sort of the range of how much these studies pay. And I already mentioned that the average compensation is about $3,000 but you can just see here that the vast majority of studies pay less than $4,000 and very few are paying in these really high range of over 6000 or certainly over 10,000. So, as far as how much participants can actually earn in over the course of trying to do clinical trials, what we found was that in general participants tended to screen for about three clinical trials each year they participated in one or two, and they earned roughly $3,000 annually. And so, you know, I think a lot of times when we look at these amounts of how much clinical trials pay it actually does sort of ignite the imagination of wow you know like these studies really pay a lot, potentially participants can really earn a ton of money, but on the ground participants really weren't earning as much as, as it might have seemed and in fact, in some cases participants were even surprised that they weren't earning as much money. In our study we were reporting back to them each year of what they had given to us and data to say like oh look you know you screened for this number of studies, you earned this much money and some of the participants were really surprised that they earned as much as they thought they did, which was kind of an interesting dynamic. Even the participants who you would kind of think of as these professional participants, they too didn't, you know this inconsistency and payment really came through that there was a lot of volatility and how much they earned from year to year. So, so for instance, in one year, our top earning participant did earn almost $40,000, which is pretty incredible he had to participate in eight clinical trials that year. But in the, in another year he'd he'd earned less than $20,000. So again, I think it really also shows that some participants are putting in a huge amount of effort to enroll in these studies. But it's not guaranteed and they really in a sense have to put in a lot of effort if they're really trying to earn a lot of income from from trials in this way. And participants do oftentimes feel like, although they're motivated by the money and they are doing it for the money that they do feel exploited in some ways and they do feel like the industry itself is earning a lot of money off of their participation and they're really sharing in that fairly. So for instance, I think this quote kind of gets at that. I'm surely told me the drug companies the academic institutions or whatever it is. This huge wheel that turns you know to power clinical studies. Yeah, it's just so flip and capitalistic you know when you think about it. Everybody lowering their prices they've had a participants, the sponsors are just cheering themselves you know because they're actually making more profit off of people, meaning healthy volunteers who are ignorant and desperate I would say. Another participant was commenting on the huge amount of variability and clinic conditions with noting that some of these research clinics are really quite nice and comfortable whereas others are not. So he said, different clinics are different. I understand you have like the major pharmaceutical companies and you have the middleman actually test the drugs for them. It's kind of getting a little crazy now because like these different places it's like you know, it's like a manufacturing plant now and how they treat healthy volunteers processing them in and processing them out. I mean it's getting a little out of hand and there needs to be more regulation as industry. All the veterans and that's how he kept referring to the healthy volunteers who had been doing it for a long time. And I've said that's it they need to regulate this it's getting out of hand now. So really interesting to think about healthy volunteers actually advocating for more regulation around clinical trial participation. But I want to pivot now to talking about compensation in a really different way. This is based on a paper that I have coming out with my colleagues, Maggie Waltz and Arlene Davis do to come out in the summer of this year that looks at taxes and compensation as tax income and sort of the financial and legal risks that come along with phase one trial participation in particular because of the higher amounts of compensation associated with these studies. So for tax purposes healthy volunteers are independent contractors. And I think now especially with the gig economy, we could really see a lot of parallels between how healthy volunteers are paid in clinical trials with how potentially Uber drivers are paid. And so there's definitely important tax implications because from the IRS perspective, participants are self employed and so they need to pay self employment tax which is oftentimes higher than if you were employed through an employer per se. And as part of what we did in this study, or in this paper we looked at what do informed consent forms typically say about tax liability and there's very little, essentially our paper does give a few examples. But there's, there's not that much information about the fact that healthy volunteers again are going to have to pay taxes and what typically is in there when it's in there is it's very opaque language that I think is potentially either confusing or it's something for that would be really easy for participants not to pay much attention to. And so, for this topic we ended up really looking at the interviews that we had conducted with healthy volunteers to see you know how did taxes come up over the course of talking about compensation and you know what were the different things that they flagged as important. So one of the things that was very striking and actually what motivated us writing this paper to begin with was that a lot of participants just believed that it was tax free money like that they claimed that a lot. And that that was one of the nice things from their perspective of participating that they wouldn't have to pay taxes that no taxes were being taken out of this check that they might get. However, for many participants that led to the shock of getting the 1099 at the beginning of the next year. So you know if you don't expect that you're going to be paying taxes on it and all of a sudden you're getting a notice that your income from such and such research clinic has been reported to the IRS. And that was really distressing to to many of the participants that we interviewed. Interestingly to some of the participants who did do clinical trials full time talked about how it was really important to educate yourself to navigate the tax system and to really see yourself as an entrepreneur. So somebody that needs to keep your receipts so have all your expenses so that you could have tax deductions and stuff when you file your taxes. Another really important theme that came out of looking at our interviews with healthy volunteers was just how a lot of participants of the ended up avoiding reporting their trial income at all. In some cases not filing taxes. And so the participants were aware that doing this was actually a huge risk to them. But it was also something that sometimes they felt that they had to do so for instance Roman said, on every time that you take that money it's technically right at that moment tax free. If you ride under the radar which I did this in the beginning of my study career doing studies I did just enough whereas I didn't have to pay taxes because I was scared to pay money because I didn't know how I was going to pay it. I was like wow if they tax me off this tax free money so to speak I may owe them a lot of money. That's when the similarity of the drug trade and this trade go hand in hand because at that point you're doing something semi illegal you're you're not trying to pay your taxes. The drug dealer he's out there trying to avoid the police he's trying to stay a step ahead of them. I'm trying to stay a step ahead of the IRS. You know there definitely is a huge burden of tax debt for some of these participants. And so for instance, in our interview with Steve, he was talking about how he hadn't paid taxes in very very many years I think he hadn't paid his taxes in 20 years. And one of the reasons he was suddenly motivated to file taxes and to try to get everything up to date with the IRS was because he was applying for a fiance visa for his partner with him he had a child. And he wanted to be able to bring her to the US and bring his child to the US and essentially it was one of the conditions of getting this a fiance visa that he had to have his tax that he had to be up to date with the IRS. And so anyway he told us I probably will owe $35,000 meaning once he had it all settled with the IRS. Most of that is because what the IRS sees on all those years is me doing clinical trials where they didn't take any taxes out you know I just got paid in checks without any taxes withheld so I'm supposed to pay taxes to the IRS all those years for all those clinical trials. Another participant talked about he how he too was struggling to pay about a $12,000 tax bill with the IRS and was negotiating how to have a payment, a payment system in order to get on track to pay off this debt. So, you know when we're thinking about this tax liability it's, there is potentially a huge burden on participants particularly when it's not necessarily easy for them to save that money and be able to, you know hold on to it for tax season. And in fact you know I think one of the other things that was really striking about talking to participants to was even just finding out that thanks Benji, but finding out that they. Many of them didn't even have bank accounts so a lot of them were unbanked so if you're unbanked how do you really set aside this money for tax purposes. What we saw was that participants were really that in some ways that the clinical trials created sort of perverse incentives that were coming that were stemming from tax liability so in some instances we saw that participants were trying to stay below income threshold so they actually didn't want to participate in in in more studies because they were trying to save themselves from from getting a tax bill potentially. In most cases we actually saw that participants were enrolling new clinic in enrolling in new clinical trials to pay last year's taxes. So for instance Lee told us you know some people that have put in years doing studies and the first things those pharmaceutical companies might say is well look at the money you've made over the years. But it's not tax free. That's why we got to do another study so we can pay taxes. So you know some of these participants are going to participate no matter what it's not just that they have a tax bill coming do, but the fact of the matter is they do see clinical trials as one of the ways to actually be able to pay what they owe to the IRS. You know this is what starts to really worry me that it's another way that potentially we're taking advantage of healthy volunteers and it's sort of an invisible way that we might be taking advantage of them because essentially what what starts to happen is that the compensation for participants is less than it may seem so when they're offered a certain amount to enroll in the clinical trial. It seems like that's really what we're we're guaranteeing them that what we're offering them. But in fact, it's something less than that and it's something less that's often hard to calculate because it's hard to know what an individual's tax liability is going to be or what they're going to owe on taxes for a specific trial. So, for instance, Travis said, after you know minus the taxes the time the travel the this the that you know how many screenings you have to go to an all, you know just at the end of the day it just you know it was a lot less than what you actually thought you were making. Another issue that kind of came up to was participants worry that they could actually be harmed in some way by the trial and then still have to pay taxes on it so Sylvester said, I don't think we should have to pay taxes on this money, because you shouldn't have to pay taxes for a thing like this, because we're doing nothing but service to the people and nothing bad comes out of this it's 100% all good. What's coming out of it is if something happens to you in a study to you, your own person and then you have to deal with that, then you didn't get much from it, but that one check and then you still have to pay taxes on it. And so, you know, I think that this idea about whether or not research participation should be taxed is definitely something we need to talk about more. And then, in fact, we are Rand and Aaron Kesselheim recently published an article in clinical trials called payments for research participation, don't tax the guinea pig I love that title. And so I think you know this is definitely something we need to think more about. And it's, I think another really critical aspect of thinking about fairness here. And by just saying you know that we have this system of phase one trials that's a core part of the drug development process so the regulatory system requires phase one trials and those clinical trials are typically healthy volunteer and then we have healthy volunteers who are incentivized by the financial compensation, but that they have to have the time and ability to be confined for long periods to enroll in these studies, and that the US context of social and economic inequalities funnels people of color into these trials because they often don't have better options to earn income. And you know, there's just this kind of ethical issue from my perspective that emerges from this promise of financial freedom that these high amounts of compensation seem to offer but participants. You know, it's very rare that participants see that or report that the trial compensation really was transformative in their lives it's usually it is just something that helps make make ends meet and then something that they may have to do again when they need that money again. And then as I've been saying over the last few minutes, you know the compensation may appear substantial, but not only doesn't it provide financial security but it even comes with financial and legal risk from taxes. So I will end here and I look forward to the questions and our discussion. Great. Thanks so much, Jill and Holly wonderful presentations and we do have some questions coming in so I'll just jump right in to use our time so one of the questions that I think is really interesting that came in early on, I think during Holly's talk and it was on my list to kind of ask about as well as to, to ask for you to comment on essentially how this applies to international studies. And when we think about their payment we think about paying people equally but what about when you go to situations where you know the expected wage or the annual wages much different than what we might expect and and how do we, how do we think about those issues in this context. Yeah, I can say a few words about that to start. This is an example where you don't necessarily have to pay people at different sites, the exact same amount, right you want to apply the same principles to determine what you should be paying them. But, you know, a dollar in one place is going to mean something different, you know, in another part of the world. So, you know, a couple of things to keep in mind might be what is the, you know, the minimum wage in that area. Is it a living wage, we should not peg research payments to exploitative minimum wages. Now the challenge then becomes if you pay the equivalent of a living minimum wage, or, you know, it may not be minimum wage that's a that's a that's I'll leave that aside I'll come back to that in a second but if you pay more than the minimum wage in a given area than research becomes more attractive than the other alternative options that people have to make money. Then you're no longer in the compensation zone you're in the incentive zone. And so the concerns about undo inducement tick higher. But the, the, the need to pay fairly, then kind of ways against this concern about undo influence so my, my personal perspective is that you ought to target the living minimum wage, right, and then pay related to that wherever the wherever, you know, in the world the research is being done, and then you come into challenging questions about if you have people in confinement for 30 days, are you going to pay them 24 hours a day, or are you going to pay them only when they are actively engaged in research activities. Well, if they're confined, they may not be able to make other income, right so that suggests you ought to pay them for the entirety of the time that they're there so I don't mean to suggest that there is a single formula for for how to go about doing things but we ought to think about comparable non research activities and target payment accordingly. And it doesn't have to be the exact same at every location where a study is being done. Thanks so much Holly Joe anything to add. So I've primarily studied the US or only study the US so I don't, I don't have any kind of empiric empirical examples from international research but I think, even in the US this can be a bit of an issue that participants, especially those who might go from clinic to clinic or participate sort of in a range of areas that, you know they note that there are payment differences across these geographic areas and so in some ways that can incentivize them to travel that at least in the US, Texas has a reputation for paying more than in other parts of the US and so, you know, I think they're probably should be more effort to try to have some kind of standards for how much clinical trials are offering so that it's not I mean and I guess you know this is part of the vicissitudes of the IRBs of you know that one IRB might approve one amount or research clinics or sponsors are motivated to offer less amounts that it does create these differences and how much different trials offer and I think that does create different kinds of problems, including for fairness not only for individual participants, but kind of just thinking about this whole system in kind of in general. I just underscore really quickly I mean that that point about fairness that we that we're focused on here is so critical because you can easily see a race to the bottom where you say oh our competitive site. They're only paying people this much so we just have to pay slightly more than that in order to encourage people to you know enroll here thinking about it in that market based way rather than thinking about what is the value of what this is contributing to science what is the burden that they're taking on and we didn't talk about payment for risk. So I've argued that we ought to pay people for time and burden upfront because those are things that you take on no matter what the risk right is a potential harm. It's acceptable to say we're not going to pay you for the risk. We're going to pay if the harm occurs right so this came up in some of your comments Jill right that you know, look we we have to get tax even if we get hurt. We have an abysmal approach to paying people for research related injuries and and not just you know, paying for their care but making sure that they have the equivalent of something like workers comp right covering their other costs that if they're unable to work. If they die right that we have some mechanism to financially compensate for that. It's not something that's required by law, despite basically every commission that has ever looked at this saying it is something that ought to be required it's just something that's left site by site for for studies to decide how they're going to handle this, which is a huge problem. That's a great point and something that we end up, you know in IRB world, essentially arguing with sponsors on the wording, you know on a daily basis of exactly what some of that coverage looks like I don't know how if you want to comment on you know more about it than I do the difference in Europe around the subject insurance and potential payment for injury and things. Yeah, I mean, so I don't have specific knowledge in other jurisdictions, other than to say, you know, there are, for example, India is one that kind of stands out as having a legal requirement to cover research related injuries, it can be much other countries where they have a national health care system. It's particularly bad in the US because we don't have a system where everybody is insured and able to get care, regardless of how they are harmed. But yes, this is something that the US is very far behind and making sure that we're caring for participants appropriately. I'm not an expert either but I think there are some European countries that essentially require the sponsor to get insurance, essentially to cover, to cover subject injury. One of the questions that came up is based on the conversation we just had is there any evidence of sponsors or CROs, etc, essentially moving research to places where the living wage is less essentially to take advantage of that. I don't know if we know that. I don't know for sure whether or not that happens but I mean I do think that I think that there's sort of, you can kind of see the sponsors are sort of stratified like that the, the largest sponsors tend to go to the most legitimate CROs or US clinics whereas some of the smaller, maybe startup kinds of pharmaceutical companies or biotech companies that are essentially developing a product that maybe they hope will get licensed to a large company. They have the budget so I don't know necessarily that they're training intentionally go to these places that are undercutting the participants necessarily but I mean I think that that is part of this market that there are sort of the budget CROs or the phase one units that that exists and that they charge less for running the studies, but they also it does sort of create an opportunity to pay participants left less to Yeah, I mean it's an issue across across the drug development spectrum right so looking beyond beyond phase one. That's why companies take their studies abroad. Financial reasons are one right it can be a lot cheaper to do research elsewhere. You may have people more willing to participate in order to gain access to the care and attention that they'll receive in a study that they might not otherwise have access to. And then there, you may also have people in the US who are unwilling to participate in the research, either you know for example maybe the drug already got approval here, but there are further studies required to know whether it works. And sometimes have to go elsewhere where the standard of care is different in order to do those studies. So that's a much broader issue about exploitation of global global populations, although I will say that's something that FDA has been talking about more more and more recently about when they will accept data that was for trials conducted elsewhere and when they want to see domestic participants. Thank you. There's a bunch of questions that are all kind of interrelated to the tax questions I did put in. Joe you referenced Dr. Ranvin Kessel Heinz recent paper I put that in the answers in the Q&A because I think it's a great paper as well and great title and good for people to see that certainly agree with the message they share but some of the questions that are here about essentially is there a way for people to, you know, use hospital web portals to get their tax documents in one place can research assistants discuss the tax issues and help them get bank accounts. What's the easiest way to make sure that income. Well, is there a way to essentially get any tax credits or exemptions. I don't know if I want to, Joe if you want to talk anymore about any of those kind of topics on the tax there's just a lot of questions there. Yeah, so I mean I think, I think researchers can do a lot more to inform participants about the tax liability I think so in our forthcoming paper we do have some sample language that potentially could go into consent forms to try to cover this better. I do think that it really needs to be flagged for participants that they will owe taxes on it. I think, in general, a lot of times the research teams don't love to talk about the compensation, because I think especially with healthy volunteers there's the sense like well they're so focused on the money like that's not what we need to spend time talking to them about we need to really talk to them about the risks of a study. You know I really appreciate that the research teams have that perspective but I think in this case too there is this financial risk that really does need to be flagged as well. But yeah I mean I think that it would be pretty difficult for research teams to also help participants with their taxes but at least for participants to know that they are going to owe money on it is really important. I don't know so much about how to actually change the tax system I don't know if Holly if you have thoughts about that I mean I think it would really require a bigger regulatory shift probably would take an act of Congress to I'm not sure. So it's not something that would be particularly easy to change but I do feel like there is a need for that kind of exemption from for this kind of income. Yeah, I mean definitely would require legislative change. And you know I think Leah and Aaron's paper is really people on on this meeting should read it because it offers a couple of different examples and suggestions but for one. In an analogous circumstance we could think about live organ donation and there are all of these incentives to encourage people to be live organ donors. You know including like time off from work and you know covered in these kinds of incentives. Now you can't pay for the organ. And you can't incent you know offer incentive payments for people to do that and the reason you can't is elite is against the law to do that so they are different models despite, you know, as some of Jill's participants articulated, both of them are using the body. And in fact, you know the live organ donors are helping one person, right, where the research participants, ideally their contribution is going to be multiplied, you know, over the, you know, over the course of scientific development so there is I think one reason to suggest that we would appropriately incentivize people more to participate in research, including by reducing their, their tax burden, but at the very least we should make the tax burden clear to people. And so many people, like I'm not at all surprised they're awesome results Jill I'm like I'm so glad that you have that empirically demonstrated but I don't find it surprising. And so many people, right, they just, they look at their paycheck, and they're paste up and say, oh, this is all I owe and if they didn't take it I must not about it, right people get surprised by their tax liability, all the time. So of course it's going to happen in research, especially when we use this completely dodgy language about the that they received a donation, right these challenge study participants received a donation. Or they were reimbursed or they were compensated. No, they were paid, they were workers in my opinion I've got a whole paper about research participants as workers right they're workers. But we do all this song and dance that they're no no no they're not workers they're volunteers and all of this stuff no they're providing a service they expect to be paid. And so we have to help them understand that this is a regular paycheck that will be taxed accordingly. Yeah, I totally agree with that and I think it, you know, anytime you deal with lump sum payments people end up getting in trouble with not realizing you know getting not realizing they're going to have to pay at some point and outside of the research context. And so one, one thing you could do right is pay people more like to meet their expectation. The study you thought this was how much you were going to get. We don't know exactly what your tax circumstances were but we are topping it off, you know, with this average amount, something like that could be potentially beneficial. Yeah, no I totally agree and, and, and, you know, we do require our researchers to talk to people about this you know I think it's challenging though because you know it's, it's often a brief conversation in the context of a very long consent process and form and and and the themselves are often not familiar with the tax implications and so first you have to educate the people even you know doing the teaching about this to the subjects. And I think the important thing is you know we certainly include language and consent forms but it's actually important to tell people at the very beginning of the screening process basically so you don't waste their time, you know, by the time they get to the consent process or some of those. And then of course we also, it's very hard to track multiple enrollment across various studies right people researcher knows a subject and whether they enrolled in multiple studies in their lab but not necessarily elsewhere so really hard. One of the questions that I think I'll you just kind of brought to my mind I think came up in the questions and also I kind of was on my mind is, you know I've thought a lot about, you know the cost of living has gone up, obviously recently inflation other things, but our clinical trial budgets have not necessarily gone up to reflect that our payments to research participants have not necessarily gone up to reflect that right we have some standard, standard amounts that we think about that probably haven't been updated and you know, a decade or more and clearly not keeping up with with 2023. And, and the question that you raised Holly that made me think about it was this you know maybe you need to pay people more to compensate for the, for the tax burden but just paying people more in general. So what do you do, you know the question here on chat is, you know what do you do when it gets to the time of the IRB, and they feel that somebody needs to get paid more and you know essentially how do you, how do you, how do you say, people need to get paid more if it's not necessarily in the budgets, and you know I can certainly answer as to what we do from an IRB perspective but I'm curious to hear Holly and Jill kind of your take on that and you know how. To me if IRB is feel really comfortable saying a payment amount is too, too much and wanting to lower it that they should also feel very empowered to say you're not paying a sufficient amount this is an unfair amount that you want to offer to participants this is potentially exploitative so I mean I think this feeling that they're confined to budgets is not is not necessarily a fair perspective on it and I think that, you know there has to be a move to try to increase the compensation somehow and it does seem like IRB is have a lot of power here to start helping shifting this to become a fairer, a fair wage or fair amount of compensation. I totally agree with that Jill I mean I will disclose that I get really frustrated when people say we don't have the budget to pay our research participants, because you should have budgeted for it. And the IRB would not accept a research protocol that had, you know, too few research coordinators or had, you know, to two little monitoring for safety and the, you know, if the researcher said well we didn't have the budget for it, he would say, sorry, you can't do your study. This is a core component of what it means to do good research to treat the participants fairly. You have to put it in your budgets. So I don't mean to lay it all at the IRB's feet. I think it's a really multimodal problem because you have investigators who say well I love to pay more, but the IRB won't allow it. And then you have IRBs that say well we wish we could tell people to pay more but they say they don't have the budget for it. And the researchers say well we, you know, had to slash our budget because NIH would only give us this amount of money with you know all of those things are true. Right. And I don't mean to suggest anyone's being duplicitous. So maybe it starts with the funders, right, and the, you know, both the federal funders and the industry funders saying we are going to make this an expectation of ethically acceptable research and we're going to pay for it. Yeah, agree 100% and would say that there's absolutely times with my IRB hat on that we've said you need to pay people more or you need to pay for this visit and, and you do pushback basically in the same way that we as Joe as you mentioned would say well that's too much you know that it can go in both directions and I think as, as I kind of alluded to at the beginning and as Holly I think you talked about, I think IRBs, there's some discomfort, you know that I do think there's this, there's this, this, because of the, I think because of the long history of being so scared of, you know, overpaying people I think that there's a lot of discomfort around this and I'm so glad that we're having conversation like this to try to try to address that head on to say you know actually, we probably need to be paying people in, in, in most circumstances, more so than we need to be concerned about paying them too much. So I know we're at time I think essentially I don't know that that's fine with Dr Rand if you have anything else to say to wrap up. I want to thank the three of you again for your time and conversation plug for the paper which was really motivated by all of your excellent work, bringing forward the challenges on payments that exist and what it means to treat people fairly. And thank you to all of our attendees as a reminder will be back again next month to talk about climate change and health. So thank you for joining us today. Yes, thank you all very much. It's really great conversation. Thank you for joining us and great questions everyone. Thanks so much. Thank you.