Advancing health equity in clinical trials by addressing financial burden

Kari Abitbol:

Hi everyone. I'm Kari Abitbol with Endpoints News. Thanks for joining us for today's webinar, Advancing Health Equity in Clinical Trials by Addressing the Financial Burden. We're sponsored by Parexel and I'm excited to moderate today's expert panel. Joining us today for an exciting discussion. We have Rosamund Round, Luke Gelinas, and Libby Barksdale. If you have any questions during today's webinar, our panelists have reserved some time for questions at the end, so please hit the Q&A button at the bottom of your screen when you think of the question. This webinar will be available on demand tomorrow to re-watch or share with colleagues. And now I'll pass it off to Ros to get us started. Ros.

Rosamund Round:

Wonderful. Thank you very much Kari, and thank you to everybody who's joined us today to discuss this important topic. As Kari said, my name is Ros Round. I have the wonderful job of being vice president of patient engagement at Parexel, which means I get to spend all day long thinking about how we can make it easier for patients who join clinical trials and improve their trial experience. I'm going to introduce my co-speakers today shortly, but first I'm going to do a quick introduction to the topic. Health equity is obviously incredibly important. It's something that the industry talks about a lot, but what we hear consistently from patients is the financial burden of joining a trial can mean that they're not able to participate. So why is that so important and what can we do? So one of the things that we've been doing is working with my co-speakers today and others in the industry and thinking about this concept of financial equity or financial burden or financial neutrality or cost neutrality, it's also called, and what that would mean for patients.

Rosamund Round:

So we've done a lot of work at Parexel. We've got some reports available on our website called Discussions on Diversity, where we spoke to people from various under represented communities and heard from them about some of the barriers. And the financial piece came up a lot. One of the quotes we have, for example, was some patients are saying, "I can't afford the bus fare to get there." So sometimes what may not seem like significant financial burden can have a huge impact on patients. We also have a patient advisory council. I've actually just popped off our recent patient advisory council. We have 50 patient advisors around the world to advise us on our patient strategy. And we were talking about this topic, I'll share that more as we go, but it garnered a lot of discussion and people were saying it's not necessarily people just below a socioeconomic status who struggle. If you are not able to go to work or there's a significant burden of the study protocol, then that can mean that for people either of higher earning potential can still make significant issues for them too. So we'll be talking through some of that and some of those considerations.

Rosamund Round:

We've also run a global patient survey, and again, finances was usually in the top three for people, especially with the cost of living crisis and the way the world is at the moment. It is a real challenge for people. So what are we doing at the moment as an industry? Well, it varies from what I've seen so far. So thinking about the current landscape, reimbursement, or stipends are often provided in studies at conceptual level, but often not deployed necessarily through the trial sites effectively. That could be due to potentially the operational challenges. Maybe the site staff aren't trained correctly.

Rosamund Round:

Sometimes patients only get reimbursed if they ask. They don't always know that they need to ask. And so even when there is potential to reimburse patients, it's not always implemented. And also not everybody puts reimbursement programs on their trials. So there are various challenges. I mentioned operational challenges. There are also potential tax liabilities. There's potential impact on people's benefits if they get government benefits, but we will talk you through these in more detail. The pros, cons, the things we know, the questions still to be answered. We won't be able to tell you everything, but we will do our best and we're excited to have you as part of the discussion. So with that, I will first of all hand over to Luke to introduce himself and give you a bit of background on the role that he has.

Luke Gelinas:

Yeah. Thank you very much Ros. Hi everyone. It's really a wonderful pleasure to be with you here today. I'm Luke Gelinas. I'm the senior IOB chair director at Advarra. I spent a lot of time reviewing payment offers or payment proposals from sponsors and researchers. My training is in philosophy and ethics, and I'm very passionate about this topic. So again, wonderful to be here.

Rosamund Round:

Brilliant. Thank you. And Luke, for anyone that's not part of our industry, could you explain what Advarra is, please?

Luke Gelinas:

Yeah. Advarra is a large central IRB. We review lots and lots of clinical research, primarily clinical trials, phase one through three or four from a lot of industry sponsors. But we also review all sorts of studies and studies from academic medical centers and federally funded studies as well as industry funded.

Rosamund Round:

Brilliant. Thank you very much. And Livy, could you introduce yourself too, please?

Elizabeth Barksdale:

Yeah. Sure. Thanks so much Ros, and thanks again to you and to Endpoints for the invitation today. So like you said, my name is Libby Barksdale. I am the senior director of regulatory affairs and scientific policy at LUNGevity Foundation, which is a lung cancer patient advocacy group, primarily focused in the US. And my role there is working on our clinical trials or transforming clinical trials initiatives. You think I would know the name of my own initiative. Which we bring together stakeholders across the clinical trials ecosystem to identify pain points in the design or conduct of clinical trials and try to mitigate those so that it's easier for patients to get on trials and then stay on trials. So very similar to what you do Ros. And as part of that initiative, we've undertaken a project over the past year looking at, like you said, the issue of financial neutrality. We think that costs should not be an issue when patients decide whether or not to go on a clinical trial. And so both of you are participating in that initiative and I think we'll talk more about that in just a few minutes.

Rosamund Round:

Brilliant. Thank you. And just in case anyone that's listening hasn't heard of a patient advocacy group before or the shortened term, PAG, could you just explain to people what they do?

Elizabeth Barksdale:

Yeah. Sure. Patient advocacy groups run the gamut. Some are very focused just on providing support and care for patients, connecting them to other patients with the same disease or connecting them to support services. LUNGevity does that for patients with lung cancer. We also have education programs. We have clinicians and expert in the diagnosis and treatment of lung cancers speak with patients. We have education campaigns around biomarker testing and screening. We do advocacy work with Capitol Hill. We do make policy recommendations commenting on letters or proposals from different federal agencies. And then on my side we do regulatory work working with FDA and drug companies on clinical trial, streamlining, and efficiency.

Rosamund Round:

Brilliant. Thank you very much. Also, before we get into the discussion too much Libby, we wanted to just address some terminology pieces again to make sure that everyone listening knows exactly what we're talking about. So could you just explain a few of the different terms that we'll use today when we're talking about the financial side of things, reinvestment, stipends, that kind of thing, please.

Elizabeth Barksdale:

Yeah. Absolutely. So when we talk about financial burden, there's a lot of different contributing factors to that. And so some of those are out-of-pocket costs that patients incur specifically because they are a part of the clinical trial. So those costs can be medical in nature, it can be insurance co-pays or deductibles or procedures or visits that aren't covered by insurance that patients have to cover or they can be nonmedical costs, which is what we'll largely focus on today. So none of those would be covered by insurance. They would be totally out of pocket. And that could include travel to and from the trial site, lodging and meals while they're there. Maybe double those costs if they need a caregiver or companion to go with them. They could have child care, pet care or elder care costs while they're away. Lost wages. That kind of thing. So those are all what we consider nonmedical costs.

Elizabeth Barksdale:

And then when we talk about covering those costs, that could take the form of reimbursement or stipend like you said. So reimbursements, I think everyone is pretty familiar with. You provide receipts, documenting your expenses, and then your company or a third party or whomever pays you back. So with that, you provide the money upfront and then someone gives it back to you. Stipends on the other hand are fixed payments for discreet trial-related activities in the context of clinical trials. So for example, a study may provide a $200 per visit stipend or a $5 per week stipend if the participant completes an electronic diary, that kind of thing. So those could be provided at certain intervals along the trial or upfront just depending on how they're set up.

Rosamund Round:

Wonderful. Thank you. That's really helpful. I appreciate it. So as you mentioned in the intro, the LUNGevity Foundation has created this cross-industry working group where we're looking at this concept of financial burden and some of the considerations. What inspired you to initiate the project in the first place?

Elizabeth Barksdale:

Again, a number of factors. I think that's going to be our answer for a lot of things today. LUNGevity has long been a big proponent of clinical trial participation. We're often telling patients this is ... You should think of it as an extension of your clinical care. You can get some of the best care available on trials. At worse, you'll get standard of care therapy, what's out there, and you have the opportunity to get a potentially better or less toxic treatment through the trial. So we're always pushing clinical trial participation for patients. However, we know through surveys that we've conducted of patients and caregivers that there's a lot of concern around travel costs associated with clinical trials. And we have data showing that patients feel that in order to participate, they would need reimbursement for airfare, train fare, for lodging, parking, that kind of thing.

Elizabeth Barksdale:

So then in addition to that, we've heard from some patients who are on trials for which their travel and other nonmedical costs are covered, in a few cases through a prepaid credit card. And they talk about what a blessing that is. They don't have to worry about anything. All these extra costs are covered, they just have to focus on themselves and trying to stay healthy. But at the same time, and more frequently now, we're hearing from patients about huge costs and debt that they're incurring from being on trials when these kinds of costs aren't covered. And at the same time, over the past few years, there's been this growing realization of the lack of diversity in clinical trials and how this debt or even having to cover these costs up front could really negatively impact some of the different groups that we really want to encourage to participate in clinical trials. So really we went into this wanting to gain a better understanding of the landscape of the support for nonmedical costs, what's going on out there, to try to figure out do only some companies offer these and what would be needed to make them more widespread and more widely available to all clinical trial participants? Because we don't want to be telling patients to go on trials if they're just going to burn through all their life savings in a few months.

Rosamund Round:

So it can literally be as severe as that, like people burning through life savings on the cost of a trial in some instances. Is that what you've heard?

Elizabeth Barksdale:

Sometimes. Yeah. We did a quick and dirty survey just before we started this project and we asked patients, what has been your experience? Have you had your costs covered or not? And could you explain a little bit? And one of the respondents said, "No. I don't get travel costs covered or anything. I have good insurance, but that doesn't pay for it. I have a good job, but I am thousands of dollars in debt and I need to stay on this trial because of keeping me alive." And so that's the double-edged sword that patients are faced with.

Rosamund Round:

Wow. What a decision to make. And I would assume probably in an oncology trial that the costs would be higher maybe than in some other trials for an indication where perhaps the tests and procedures aren't the same or the visit duration is perhaps not the same. So well, I'm hoping that there aren't too many patients around the world facing that challenge that you can mention in particular there. So it definitely sounds like the project is something that comes from data and from what you've heard from patients, and I know that there were many of us across the industry that have joined across pharma and CROs and other advocacy groups and things as well. So is there anything more that your group's doing that you are hearing from either patients or how are you feeling that sponsors are reacting to the work that you're doing?

Elizabeth Barksdale:

Yeah. I would say that the sponsors have been fantastic throughout this whole program. We went into it thinking that this was largely a sponsor issue, that they weren't doing this, they weren't ponying up these support programs. And in our initial meeting last summer, what we learned is that they actually are, we have 13 companies present at this meeting, big and small, both pharma companies and CROs, and they said, yes, we do offer support for these nonmedical costs, but like you said, Ros for any number of reasons, a lot of times patients aren't benefiting from them. And so since that initial meeting, we had a lot of interest from the companies and keeping these discussions going so that they could learn from each other, try to make their programs more similar so that there weren't discrepancies from one trial to another. But then also to bring in additional stakeholders to better understand how they could make these programs more widely available or whom they needed to work with to make sure that some support was available to patients.

Elizabeth Barksdale:

We've now grown. We have additional drug companies and CROs. We have IRBs like Advarra. We have trial sites and we have provider professional groups represented. So ASCO and ONS and a few others. And so we've split the work into three different groups. So one group is identifying best practices for industry, talking about what is it that patients say they want to have covered and what is the justification for doing that? And then putting together a plan of how those costs can be covered in these support programs and then sharing that across industry and pushing here and there saying, oh, well this company does it, maybe we should do it so we don't look that, that kind of thing. And then another working group is really dedicated to looking at the tax and legal implications for both companies who offer these programs and the patients who take part in them. So like you said, there are tax and legal implications for patients. If they make money, if they accept payments in excess of $600 a year, then they may have to pay taxes on that. They have to fill in a line item on their W2s and companies have to notify the IRS that they did that.

Rosamund Round:

Apologies for interrupting. Four our listeners today, when you say the $600, is that just reimbursement or just stipends or a combination of both? What's included in that $600?

Elizabeth Barksdale:

To my understanding, the $600 would have to be income over and above what they would normally make. So a reimbursement wouldn't trigger that, but a stipend could. So one of the things we've talked about, are there other ways besides just reimbursing that we can provide these types of support so patients don't have to front these costs? And some companies seem to be getting around it by providing, like I said, these prepaid credit cards or using third party vendors, which we also have participation from some of them in our effort where they take care of booking all the travel and covering all the things and the patients have a dedicated credit card just for those purposes that they use and then this third party takes care of it. And to my knowledge ... And maybe Luke better. I think that that gets around the whole $600 limit because the patients aren't getting income from it.

Rosamund Round:

Luke. Do you want to comment on that?

Luke Gelinas:

I think that's right. So the reimbursement for out-of-pocket expenses and what you just described Libby, is I think essentially that. These third parties and sponsors are working together to make sure that participants don't have to pay out-of-pocket for travel and meals and parking. That's all considered reimbursement. And I'm not a tax lawyer, but my understanding is that it's non taxable. It's when you start moving beyond the reimbursement for out-of-pocket expenses and into the stipends for time, and burden, compensation, that's when that $600 limit kicks in. I don't know if you want to dive deeper into this topic now, Ros. I think this is a really important and difficult one. I don't know that we have a good answer for it. And I think it's incumbent on the research community essentially to be lobbying Congress to increase that limit or to make payment for research tax-free as it is, I believe in some jurisdictions.

Luke Gelinas:

I just learned that in Australia, I believe that payment for research is not subject to taxation. I think this can have a really profoundly negative effect. So you can imagine someone ... I think someone's already raised this in the Q&A who might not have a social security number. Perhaps someone who's recently immigrated to the country or who perhaps is receiving federal benefits, who's worried that if I make too much money from this research, I might lose my benefits. So I think that $600 limit needs to be clearly discussed with participants ahead of time, and it's just something that's a big problem right now facing these efforts.

Rosamund Round:

It's a challenge, isn't it? Because we want to do the right thing for patients and you don't want to inadvertently cause challenges for them due to a lack of understanding. I know obviously we've been talking mainly about the US but in the UK I've just started some discussions with the National Institute of Health Research and in the guidance from the MHRA, it says reasonable financial support for patients. It doesn't actually quantify it. So whilst it quantifies it in the US and that creates a challenge because actually maybe $600 doesn't cover the needs of the patient, here it's almost a different challenge. Because reasonable hasn't been clearly defined and so that makes people nervous about, well, what if it's deemed unreasonable and then what happens? So yeah, hoping to engage with our version of the IRS, the HMRC over here to look at that in more detail as well to see if we can understand both the tax liability, but also with the MHRA hopefully too. If anyone's listening from the MHRA, we're coming for you to speak to you soon to chat to them about what that meaningful reasonable looks like.So I think when it's quantified, it at least gives us a clear line that we know not to cross even if we think that line should be extended.

Rosamund Round:

So I guess that brings me to the question then, if we're thinking about stipends and reimbursement, what we want to do is make sure the patients aren't out of pocket. It's financial neutrality that you're not financially disadvantaged by being in a trial. We definitely don't want to be inducing people to join a study by providing tons of money to anybody. So in your view ... Libby, I'll ask you first and then Luke. What does fair, meaningful ethical reinvestment or stipend programs look like? What would you like to see in an ideal world?

Elizabeth Barksdale:

In an ideal world, I think all these costs should be covered up front. Patients shouldn't have to deal with reimbursement. I know that in some companies programs, they do have it set up that way, and I think that's great. I think as it is now, companies and the FDA are comfortable with having travel and lodging and meals, having all that reimbursed or covered, however you want to deal with it. But I do think we need to go a step further and look at the other costs that patients are incurring. If there are children that need to be taken care of, that cost should be provided. That expense should be covered for them. The same with pet care or elder care. Patients who have to take time off of work ... Some patients have sick leave or leave that they can use for this, but some don't so they're losing wages for that or losing vacation time. And that's an additional burden on them that could impact them sooner rather than later. But we should think about how do we address that? How do we compensate for those lost wages that lost time or for those lost wages, but then also time. The time burden.

Elizabeth Barksdale:

I think I'll talk about this more in a few minutes, but when trials are located ... When they're site-based trials usually at an academic medical center or whatever, and patients have to travel there, even if they're relatively close to the medical center, there's still a lot of time spent in transit, waiting, sitting around, and that's just hours and days of their lives that they won't get back. And so there should be consideration and compensation for that I think. In my ideal world, I think compensation for time and lost wages and upfront coverages for travel, lodging, meals, child care, all of that.

Rosamund Round:

Absolutely. As you were talking, it sparked a couple of thoughts. One of the members of our Patient Advisory Council, they said they had 25 vacation days a year. They weren't able to use sick leave for their trial participation so they used 23 of those days to be part of a trial, which only left them two days to actually go on vacation and have a break. That's a huge impact on someone's life. As you say, if you're on a trial for a year to only have two days off work, that's not going to help their long-term health by any stretch of the imagination. You talked about the time burden as well. So this is something else through our discussions on diversity work that we've done. But we were talking to some people of lower socioeconomic status who were saying that they use public transport.

Rosamund Round:

And so if I, for example, were going to the hospital, I would leave my house, get in my car, drive to the hospital, walk in. If you have low socioeconomic status and don't have your own transport, you might have to walk to the bus stop, stand, wait, take a bus, maybe change buses, wait. The bus may not drop you at the hospital. You might have to walk some more. So actually the time burden for the people that are most financially disadvantaged can be bigger than the time burden for other patients. And so I think that's a real consideration for us as well of how do people actually get here? Maybe reimbursing the bus fare isn't enough because it may only have cost £1.50 or $1.50, but maybe it took you two and a half hours versus 45 minutes if you were driving a car. So I think this is one of the things we'll get into more in the discussion is some of the complexities of these different considerations and how do you put financial weighting onto that. So thank you Libby. Luke, from an ethics committee perspective, what do you view as fair, meaningful, and ethical reimbursement and stipend programs? What's your ideal scenario?

Luke Gelinas:

Yeah. So I agree with Libby. I think at a minimum, we need really robust reimbursement programs that cover all out of pocket expenses I would argue. It's interesting that I think regulatory guidance is pretty clear on that. The CIOMS guidance says it perhaps the clearest. They basically say that research participants should not have to make a financial sacrifice to contribute to socially valuable research. So I think financial neutrality is the floor for me. Then I would go further if we're talking about the ideal and argue that in addition, there should be a stipend or compensation for time and inconvenience. It's really interesting. We have no problem compensating people for their time and their efforts and the burdens they undertake in other domains, the most obvious one being employment. And indeed we think fairness demands this. We think it would be unfair if you didn't pay someone for their time and burdens.

Luke Gelinas:

So I personally ... Maybe this is surprising coming from an IRB person, but I don't see why it should be any different in research. And we can debate the details of what that would look like. Some people think that you should pay everyone an hourly wage perhaps and perhaps the same hourly wage in a study given that they're doing the same things and that other people feel that maybe you need to be sensitive to the lost income of particular individuals which will vary depending on what that person's employment looks like. But I think we do need to think about moving beyond reimbursement and into more robust compensation plans like this. And I would go further and even argue that ideally I think burdensome interventions like lumbar punctures ... Painful stuff. Bone marrow biopsies and maybe the blood draws, I think we should consider compensating for those perhaps in addition to the hourly rate. It seems to me that adequately respecting and acknowledging those burdens might demand some compensation for particularly burdensome stuff like that.

Rosamund Round:

Such an interesting perspective. So as I mentioned at the beginning, I jumped off our patient advisory council meeting with some of our neuroscience patients before joining here and we were discussing this very topic of financial neutrality and what fair, meaningful, and ethical reimbursement looks like. And all three people that first spoke up had completely different views. So the first one said, "I think it should be a flat fee." So obviously in the US my understanding is that you get $50 a day if you have to do jury service. So they said it should be flat fee for everybody, then it's the same and then you get your expenses on top. So stipend, $50 reimbursement. But then we were saying, well maybe people of lower socioeconomic status, $50 could be seen as an inducement and we as an industry obviously want to be fair and ethical and do the right thing and not be inducing people financially to join a trial.

Rosamund Round:

Then someone else said, "Well, hey, I've got a decent job, but I should be getting whatever I'm worth, whatever my time is worth. You shouldn't be looking at me and micromanaging me and asking me to give receipts and stuff. You should just know that I'm doing the right thing. I'm giving you my time, I'm giving you my body and you should give me adequate payment for it. And I'll tell you what that looks like almost within reason." He was like, "Maybe it's a couple of hundred dollars a day because my time's worthwhile." And then another patient had an in-between view and she said, "Well, I'm not of low socioeconomic status. I've got a good job, but I'm self-employed and if I'm not working because I'm in a trial, say for six months, then I'll be so financially disadvantaged that I wouldn't be able to pay my bills and live to the standard that an individual needs to." So whilst she wouldn't be disadvantaged before joining the trial, if she wasn't getting that compensation for her time, then that would cause a really big challenge for her.

Rosamund Round:

And then we got into, well, how would we manage that? How would we look at what that sliding scale would be versus a flat fee? I don't want to go into her bank account or looking at her company finances and looking at what meaningful and fair and ethical would be for her so how would we manage it? And the main point that came from our advisory council members was that yes, people of lower socioeconomic status, it's really important to meet their needs, but maybe as an industry we're focusing on that end so much the way that we're thinking about health equity, we're thinking mainly of people of lower socioeconomic status and actually that's maybe not addressing the whole spectrum of other patients that there are.

Rosamund Round:

Elizabeth I know in some of the work that through LUNGevity, I think it's said 80% of oncology patients have burned through their life savings within two years of a cancer diagnosis because of the cost of treatment. And so even people that may be are financially very stable, illness and therefore for some clinical trial participation can have a massive impact on their lives. I don't know if it's true because I can't remember or read it, but I read that getting cancer is the number one cause of bankruptcy in the US because people lose their jobs or they lose their benefits. And so I think maybe we need to be as an industry thinking about the whole spectrum of what could happen rather than ... And those financial impacts for people that aren't maybe just of low socioeconomic status, whilst obviously that's critically important. So for we're everyone listening, the moral of that is we don't have all the answers, but whether it's a sliding scale or whether it's a flat fee at the moment, we're not consistently doing anything. So the work that we're doing together is to try and look at what those standards could be and work with the regulators and work with the governments, but we would like to do better. I think Luke and Libby, that would be probably the summary of that discussion. Would you agree?

Luke Gelinas:

Yes.

Rosamund Round:

So Libby thinking about ... Obviously we're talking about health equity. So what do you see as the potential impact of this on health equity?

Elizabeth Barksdale:

So there's different parts of this and different parts of the work that we're doing that I think could have a huge impact. So like we said, when you think about health equity, it's not just race and diversity, it's different socioeconomic levels, making sure both sexes, all genders are included, that kind of thing. And if we just go in thinking we're going to offer these programs to every participant, I think that'll go a long way in helping create that opportunity to participate. But one thing that we've talked about is taking a step back from there and making sure that all these groups, that all patients know that trial participation is an option, if there is a trial out there that's appropriate for them. And not the healthcare team, not making an assumption upfront that because of race or language or socioeconomic status that that patient wouldn't want to participate in just not offering it.

Elizabeth Barksdale:

One of our working groups is creating resources for trial site personnel. So in these discussions they have questions that are relevant both for cancer care and for clinical trials. Thinking about this is a schedule that you might be asked to follow, would you need help with the following? So travel, child care, that kind of thing. So the patient is thinking about it beforehand and then if there's a clinical trial that's open and appropriate for them, noting what that trial offers and how that matches up with what the patient's needs might be. And then also reassessing throughout trial participation, okay, you were fine before, how are things going? You maybe need help with this now. So it's an iterative process and making sure that first and foremost, everyone knows about the trial and is offered participation in the trial. I think that's where we start and that's going to have a huge impact on improving health equity.

Rosamund Round:

Wonderful. Thank you very much Libby. We're going to pivot now to ask Luke a few questions. Some of them are the same questions, but to think of them from the IRB perspective. So I guess the first question, Luke is I think some sponsors maybe aren't putting reimbursement programs into their packages because they're worried that they'll get negative feedback from the IRB or that it might seem to be inappropriate, it might hold things up because we all know that things move quite quickly during that review stage. So what are your colleagues looking for during a review when they're looking at reimbursement and stipend programs?

Luke Gelinas:

Yeah. I think there's a few things. The first is it's really helpful from the IRB perspective to have a sense of why payment is being offered or an explanation for it. So you can imagine being on the IRB seeing a study and there's just some number proposed. $800. You're like, well, where'd that come from? Why are they proposing that? So I'd encourage sponsors if they're reimbursing, which I hope they're, they make it clear what they're reimbursing for, what types of expenses they're proposing to cover, maybe what the ceilings on those expenses will be. $20 for lunch. If they are compensating for time and burdens, they make that clear and provide a breakdown just so the IRB can look at it and say, oh, well that makes more sense. I see how they got to that price point. The second thing I'd say is that it's important to be clear about the timing of payment.

Luke Gelinas:

And if you look at guidance from both FD and OHRP, they stress that payment should really be made at regular intervals throughout the course of a study. I think this is mostly for studies that are relatively long or that aren't just one visit or something, but for most clinical trials there should be some kind of payment schedule so that you're not withholding payment for long amounts of time or you're certainly not withholding the full amount to the end so that participants are getting it as they go. That could be helpful for both participants as well, you can imagine. But we always look to see that there's something in there about the timing of payment.

Luke Gelinas:

And then that brings me to the third one, which is really to be clear about completion bonuses. And we haven't really talked about this. My sense is that completion bonuses are most common in phase one research with healthy volunteers. We sometimes see them in other studies. FDA addresses this. They basically say they're okay completion bonuses within bounds. In other words, you can hold back some of the money or offer extra money as an incentive for participants to finish their participation. IRB Advarra will always look to see is there a completion bonus and if so, how much are they proposing for that bonus and is it reasonable?

Luke Gelinas:

I'll just say I think all of those things. So being clear about what you offering payment for and why, the timing, and then whether a completion bonus is being offered. It's good not only for IRBs to have that information, but it's also really important for subjects. Those things should be really clear I would argue to subjects when they're thinking about entering the study. I think subjects need to have all of that information to make a well-informed choice about whether they can afford to be in this study or just in their deliberation generally. Those are the three things that came to mind there, Ros.

Rosamund Round:

Brilliant. Thank you very much. And you talked a little bit about some of the current regulatory guidance around this. Is there anything you wanted to expand on a little more?

Luke Gelinas:

Yeah. There's a lot. You could say FCA and OHRP both have guidance as probably everyone knows. They both say that payment in general is an acceptable practice. It's common. As long as you don't pay someone so much that it raises concern about undue influence, both OHRP and FCA. interestingly say, payment should be just and fair. So there's a fairness element there. I did want to maybe make one note about undue influence because I've heard you raise it a couple of times Ros, this question of inducement. Because I think there's a lot of debate over these concepts of coercion and undue influence and how to understand them. OHRP does not mention coercion and their guidance at all, and recently FDA has finalized the guidance on informed consent where they basically say, when we worry about payment, we're not really worried about it coercing people. So I think the main worry for payment in terms of the risk is really the risk of undue influence.

Luke Gelinas:

Sure, we could spend hours talking about undue influence and how to understand it, but I just want to make one point which is that I would argue that undue influence, which is the bad thing associated with payment or the risk of undue influence only really occurs when payment causes something to go wrong with informed consent. When payment might get in the way of understanding important things that we want people to understand, perhaps it causes someone to ignore or underestimate the risks or perhaps it gets in the way of voluntariness. It might cause someone to maybe participate in the study in some sense they'd really rather not. So that's important because it means that ... I would argue that undue influence does not occur just because payment motivates someone to participate. And OHRP is clear about this. They say compensation may be an acceptable motive for agreeing to participate in research.

Luke Gelinas:

So the simple fact that someone is motivated by payment, they take that into account and maybe even in situations where it's the deciding factor. Someone says, without the payment, I can't really swing it, but with the payment I can. Even in those cases, I would argue they're not necessarily worrisome. I think the regulators are really only worried about situations where the payment is so high that it just swamps everything else and your deliberation. It makes you ignore the risk or underestimate them or in some other way prevents really robust informed consent. It's tricky though because you don't know, of course when that happens, which is at the nub of the debates around undue influence and payment.

Rosamund Round:

Very interesting. Thank you. I love your encyclopedic knowledge of these things. It's amazing. So how often are you seeing reimbursement submissions? How common is it in the industry at the moment? How far have we got to go to do what Elizabeth suggested and get it on every study?

Luke Gelinas:

Yeah. So my sense ... And this is just my intuitive off-the-cuff sense is that it's getting better. We see it quite a bit, but by no means do we see it in all studies. I think the only place where we see payment uniformly across the board is in phase one research involving healthy volunteers. I think that's its own category. I think a couple of further remarks, when we do see it, my sense is still that it's usually not enough to really cover all of the out-of-pocket expenses that we'd want to see covered. We rarely see things like child or elder care covered. We rarely see out-of-pocket cost related to copays or inductables covered.

Luke Gelinas:

And I think part of the reason for that is that there still seems to me to be a presumption among some or maybe many sponsors ... And I'm not sure about this. I think it's interesting, Libby, what you said earlier about sponsors being on board here. But my sense is that sometimes there's this feeling that in research that holds a prospect of direct benefit ... So like phase two, phase three clinical trials, there might be less of a need to actually reimburse. And you can see how that thinking might go. You think, well, there's a medical benefit here. The patient stands to benefit perhaps from the study and that it might be tempting to think that maybe we don't have to pay them as much or reimburse them fully because they might get that medical benefit. It seems to me that something like that is going on because the reimbursement rates do tend to go down as you move up from phase two to phase three studies where the prospect of benefit increases. I think that's wrong for a bunch of reasons, but the biggest one for me is just that even if there is a prospect of medical benefit, it's still going to be true that many people and people of lower economic means are still going to struggle with the actual out-of-pocket cost of participation.

Luke Gelinas:

So I think for those people, people who are economically vulnerable, this failure to reimburse, it's really an access issue. It precludes stem from accessing that research. And so I think we shouldn't encourage sponsors not to take the fact that a study might have a prospect of direct benefit as removing or lessening the need for robust reimbursement and compensation plans.

Rosamund Round:

And so if you were to state what fair, meaningful, and ethical reimbursement looked like, are you thinking slightly scale? Are you thinking standard payment? What are you thinking?

Luke Gelinas:

So a couple of considerations. One is that ... I'll just come out and say it. I think at Advarra we usually would prefer, and almost most of the time probably require that the payment rates be the same just because it seems slightly unfair to ask people who are undergoing the same interventions and giving the same time commitments to get different payment amounts. So the basic maxim would be something like equal pay for equal work. If participants are doing the same thing in study it seems to compensate them the same. I'm sensitive to you might lose out on people of higher income doing this for the reasons you gave earlier because it might just not be enough to compensate them for their timeliness from their particular jobs and so on. But that approach where you're saying, well how much does this individual ... How much do they earn? And trying to personalize it just seems like it's going to be an operational nightmare to me. And so I'm not sure that, even if we decided that was the fairest way to go, how feasible it would be to implement it. But I'm open to discussion on it.

Rosamund Round:

I'm sure there's much more discussion on the topic to go. I know that's one of the things we're talking about as part of the LUNGevity project and also with the NIHR as well. Yeah. How on earth would we manage it and implement it if we had a sliding scale? But I think from so many things you've shared with us just now Luke, it's very encouraging seeing the IRB's perspective and it does sound very fair and very reasonable and probably a higher degree of compensation than most people maybe who aren't in your expert shoes might assume would be seen by an IRB as being a positive thing.

Luke Gelinas:

Yeah. I think we're in this weird spot, strange spot. Just because historically IRBs, it seems like have been the ones that regard payment with suspicion and maybe place limits on payment offers. And my sense is that in the last decade or two, IRBs have come a long way. I think IRBs, especially central IRBs are much more open to considering more robust payment proposals. There's less resistance from IRBs. The strange thing is that if that's the case, I don't really have a good explanation for why practice hasn't caught up. In other words, if IRBs aren't the ones who are pumping the brakes and limiting payment, then why are we still not at a place where payment schemes are more robust? And Libby, back to your point. I guess I was just assuming that there's still reticence or skittishness on the part of sponsors to really offer robust payment plans either because they think the IRB will reject it when perhaps they want it or there's still worry among sponsors perhaps among their legal offices about things like undue influences and coercion and things like that. But I think IRBs are much more willing now to consider more robust payment plans. And in some ways it's a mystery to me why we don't see more robust payment than we do.

Rosamund Round:

So what do you think needs to change then to move the needle across the industry?

Luke Gelinas:

Again, it's somewhat of a mystery to me. And Libby, I'd be really curious to hear your thoughts on this too because I have just been assuming that really like you were assuming going into the LUNGevity initiative that it sponsors for one reason or another who aren't budgeting for it even though of course most cases they would've the ability to budget for it presumably, or they're worried about ethical concerns.

Luke Gelinas:

I think one of the things that should happen is that ... And this has been raised in the Q&A, is that we need to reframe this issue as a DEI, which is happening. And then we also need really both full participant advocacy. I'm cautiously optimistic that those things might move the needle. Reframing in terms of DEI, full participant advocacy. I'll also say that we have a real crisis of early terminating studies and just a recruitment and retention crisis. And so way too many studies begin, but then don't enroll enough people to be adequately powered or evaluate their objectives. And it seems like payment could really help there too. So I think bringing all those issues and trying to reframe things from DEI ... Let's do better on recruitment and retention, local participant advocacy. That's where I'm casting my hope right now.

Rosamund Round:

Libby, what about you?

Elizabeth Barksdale:

Yeah. So I'm going to pick up on one of the threads that you put out there, Luke and why sponsors might be reticent to include more robust payment programs. And so I think here we need to be careful again about terminology, whether we're talking about payment or coverage of costs. And so I think with the payment issue, one red flag for companies could be the anti-kickback statute where it could be perceived that, again, they're inducing people to be on their trial by paying them to do it. And there is ... I know the American Cancer Society ACS CAN, is working on legislation that would address that for clinical trials so that companies could offer at the very least reimbursement and hopefully some payment or compensation without running afoul of that.

Elizabeth Barksdale:

I think also for companies ... In our group, we're dealing with very passionate, sometimes DEI people or the patient engagement or program heads who see the impact of these trials on patients. They have more interaction with patients and so they're thinking of it from a patient perspective and again, wanting to help patients and benefit them and do everything they can to make this trial easier. But they're not the ones who have ultimate sign-off. So there could be internal pushback from legal or compliance or something where again, there might be some misunderstanding of FDA guidance or OHRP guidance, that kind of thing. Or really not wanting to cross any potential tax barrier or run afoul of any tax laws.

Elizabeth Barksdale:

I think another reason that they might be not taken up as broadly as they could be, even if companies offer them, is this actual or perceived burden on sites for implementing these programs. If it's a reimbursement program and if there's not a third-party vendor who's in charge of it, a lot of that work is going to fall to trial sites. And I think we've all seen the headlines over the past few years where site staff is just fleeing almost. A lot of sites, they don't have the manpower to do that. So it is an administrative burden on them to have to do it.

Elizabeth Barksdale:

What needs to change? I think making these sort of programs as uniform and as straightforward to administer as possible, taking advantage of the third-party vendors to do all these background administrative tasks. I think that will help. I think also trial design is going to play a part here. If we can move some of the trials closer to where patients are so we can decrease that trial time, decrease the amount they need to go in, streamline the schedule of assessments to some extent. That also is going to help with trial participation, with recruitment, and improving diversity and health equity as you'll have less of that type of burden on potential participants. So that was maybe a really long meandering answer. I hope I got to what you were asking, Ros.

Rosamund Round:

It's a wonderful answer. Thank you. Yeah. Thank you both for your expertise and your feedback and your perspectives. It's wonderful and it's an absolute delight to speak to you both and I hope the people listening today have learned something. I'm going to hand back to Kari who's going to facilitate the Q&A for us so we can cover anything that our listeners want to hear that they haven't yet had answered.

Kari Abitbol:

Yes. Thank you, Ros, thank you to the panel. This has been wonderful. So I'll just dig right into the Q&A. There's been a lot of questions coming in regarding patient stipends, payments or reimbursements. How should trial sites manage IRS compliance, specifically the collection of social securities on a W9, as sites are required to issue a 10 99 payment if payments exceed $600 in a calendar year? Do you view this as an impediment to DEI efforts as some patients may be reticent or unable to supply valid documentation?

Elizabeth Barksdale:

Luke, do you want to dive into-

Luke Gelinas:

Not sure I have much more beyond what I said earlier. Not being a tax lawyer, I don't want to be seen as giving tax advice, but I think it's certainly an impediment. I think it's important. I'll just say it's important, and I wish we saw this more in consent forms to explain the financial tax implications of payments upfront for the reasons I gave earlier is that you could have low income people whose eligibility for certain federal assistance programs is impacted. So I think you want to be really clear about that. But I don't personally know that we have a good answer for this yet short of we need to be lobbying Congress for better laws in this respect.

Kari Abitbol:

Great. Thank you. Anything else to add before we hit the next question?

Elizabeth Barksdale:

No.

Kari Abitbol:

All right. Reimbursements are given for patients that have insurance that site accepts. What about uninsured patients or other unaccepted insurance plans?

Rosamund Round:

That's a good question. Luke or Libby, do you have the response to that one?

Elizabeth Barksdale:

Yeah. I guess I didn't think that reimbursement was tied to insurance.

Luke Gelinas:

I wonder if [inaudible 00:55:07]-

Elizabeth Barksdale:

Maybe this is a different-

Luke Gelinas:

Insurer for that part of it. If you have insurance, you might be reimbursed by your insurer, but there are going to be some people who don't have insurance, so can't seek any reimbursement from an insurer or otherwise. That's how I took that question. Sorry.

Elizabeth Barksdale:

Yeah. And again, so here it would be my understanding that nonmedical costs wouldn't be covered by any insurance. So for those I wouldn't think that having insurance or not or Medicaid or Medicare would matter. And so I would hope that in theory, those programs would apply to everyone and that everyone should be able to just submit their receipts for reimbursement. But those would be for nonmedical costs, not for an additional CT scan that your insurance doesn't cover, that kind of thing.

Luke Gelinas:

The medical costs are really interesting and tough and maybe under-discussed, but we at Advarra always try to make sure that participants know that there's a line in the ICF that basically says this study might involve procedures that your insurance doesn't cover, doesn't fully cover. We really encourage you to reach out to them and see what they're likely to cover. I would love it if there was more reimbursement for out-of-pocket medical costs because I think it's a big issue, especially perhaps in oncology studies where it's very common for standard of care medications to be prescribed for protocol. And I'm certain that those patients on those studies have at least co-pays for those states. And I don't see really myself any ethical reasons why those costs shouldn't or couldn't be re-reimbursed.

Kari Abitbol:

Okay. Thank you. I think we have time for ... Let's see. One more question here. Are there tools and frameworks that can help research teams structured discussions or help think through the potential burdens of financial time or other when they're at the trial design stage?

Rosamund Round:

So I know within our organization we've built our own because we haven't seen anything elsewhere. Someone's mentioned on one of the other questions, there are various different kind of guidances in terms of what's fair market value for a patient's participation as an expert in our patient advisory council, for example. But I haven't seen anything certainly for a trial. So at the moment, what we see actually that the reimbursement pieces tend to vary by company in terms of what they deem as acceptable rather than having something that's comprehensive. So we've built our own. Anyone is welcome to email me afterwards if they'd like to learn more about it. I don't know, Luke or Libby, if you know anything more comprehensive and widespread. I think, I guess before you answer, as an industry, I feel like we're fairly early in really pushing this to be a big topic, and so that's why there are some unanswered questions, but Libby and Luke.

Elizabeth Barksdale:

Yeah. I don't know of any existing frameworks, but that is one of the things that we're trying to do in the best practices working group. And this would be for industry. I suppose investigators could access it if they're part of the trial design. But it's setting up these are the costs we think should be covered and at this level or to this extent and going so far as to provide justification for that. Whatever it is. OMB says, mileage should be reimbursed at this so that's what we say, that kind of thing. So that is one of the things that we're working on.

Luke Gelinas:

I was glad to see the question on this, and I put aside that link to look at later because like you, Libby, I'm not really too aware of much of that, but that could just be to my own shortcoming.

Rosamund Round:

Hopefully it's coming, living with all the wonderful work of your group and all of the partners.

Kari Abitbol:

Great. Thank you. I wish we had more time for questions, but unfortunately that's all the time we have for today. Thank you so much to everyone in the audience for tuning in. And thanks to Libby, Luke and Ros for sharing their time and expertise and we appreciate Parexel for sponsoring the discussion at Endpoints Webinars. If you would like to re-watch the webinar or share it with colleagues, a link for on-demand viewing will be sent tomorrow. I'm Kari Abitbol for Endpoints News. Thanks for joining us and we hope to see you at a future Endpoints webinar. Have a great day.