Let’s Get Ethical

About the Advarra In Conversations With…

The future of healthcare innovation hinges on research and clinical trials. Advarra sits down with leading experts to dig into pressing issues and explore cornerstone solutions. Join us as we discuss topics and trends impacting the healthcare of tomorrow and advancing clinical research to be safer, smarter, faster.

 

About This Episode

In this episode, Advarra’s IRB Chairs Luke Gelinas and Amanda Higley discuss hot topics in clinical research, including cannabis studies, returning research results, and data ownership.

Chapter 1: Attitudes and Advancements in Cannabis Research

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Hi everyone, welcome to the “Advarra in Conversations With…” podcast. We’re going to talk about some exciting topics, some topics that I think are interesting and exciting, from cannabis and clinical research to data sharing and ownership with participants and then, if we have some time, maybe touch on some novel ways of designing studies and its implication for therapeutic development. I’m Luke Gelinas, I’m an IRB chair at Advarra and I’m joined by my colleague Amanda today.

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Thanks Luke. I’m Amanda Higley I’m also an IRB chair at Advarra and I’m excited to be on the podcast for the first time today.

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All right, let’s dive right in! So, I’m really excited Amanda that you’re here, because you have thought a lot about our first topic which is cannabis and CBD in research, and so I think we want to talk a little bit about the use of cannabis or the investigation of cannabis and CBD in research, but before we did that I wonder if you have any thoughts on kind of the broader societal context in which the

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cannabis research is now taking place. We’ve seen sort of this great growth in research involving cannabis and CBD products and I’m wondering if you have any thoughts on sort of why we’re seeing that now and kind of where we’re at as a society in terms of cannabis and cannabis research.

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Yeah, you know I had lots of thoughts on this one and it’s near and dear to my heart, I think the biggest driver here Is that many states are now legalizing recreational and medicinal cannabis use? I mean it’s still illegal federally, so federally it’s still a schedule one drug, meaning that they consider it to have no medicinal value. But various states, so 37 states, have approved it for medicinal use and then 18 states have approved for recreational use

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In adults and there’s other things that have been happening too, with breaking apart kind of The psychoactive parts of the cannabis plant, like the delta 9 THC from the other components and then the other components have been made federally legal to use, and so, even in states like I’m in North Carolina even in states where cannabis use recreational or medicinal is not approved,

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You can still buy CBD at like the gas station so we’re seeing this huge uptake in people being able to get it on their own, which I think, is driving interest in trying to figure out what is, you know the medicinal value of you know CBD, which is a very interesting story, I think, and then also just people are more interested in what’s happening with cannabis, but that’s taken up against this like federal still illicit problem.

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Did public attitudes evolve and change in relation to things we were learning about cannabis through like sort of rigorous trials and federally funded research or was it more sort of like a societal and cultural phenomenon that was happening, apart from any advances in research, if that makes sense?

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yeah, that’s a great question, so I really think it’s more the societal aspects of it it’s the anecdotal like “hey this works for me.”

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Because cannabis is a schedule one drug and, meaning that the FDA or the DEA consider it to have no medicinal value we don’t see those randomized clinical trials of cannabis because number one you’re telling me can’t use it, it’s illicit, and number two you can’t patent it because it’s a naturally growing herb product right. And so, there’s not a lot of research on that side of it, what we do see is like the academic research, but a lot of that came from more of the abuse potential and like you know ways to treat addiction to cannabis or the cannabis effect on cognition, but we don’t see it so much with its medicinal value.

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So, it’s almost like you have this sort of cultural evolution in norms in the way that we view cannabis and now the research side of things is sort of like playing catch up to that or we’re sort of finally at the point where we’re like “okay, can we sort of can we figure out in a more sort of robust scientific evidence-based fashion exactly what the medicinal uses for this are?”

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Cannabis has been used for centuries. But back when cannabis was first used, and people were using it more medicinally, the ratio of THC to CBD was more equal. And then, as generations progressed, the ratio of THC to CBD started shifting so it became a little higher in THC and a little less in CBD because the THC was the psychoactive part, the hallucinogenic part.

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But it became sort of widely accepted that CBD was probably what was driving the medicinal value and effect getting from cannabis use.

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So, what do you think are kind of some of the challenges here? The big ones in your mind in terms of sort of facilitating further research and kind of facilitating robust clinical trials or different kinds of research about Cannabis?

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So for cannabis itself, like the entire cannabis plant that includes delta 9 THC, some of the difficulties are because it’s still a schedule one drug, to obtain it, you have to obtain the research grade cannabis and you have to apply for that through NIDA. Some other kind of requirements you have to do, you also have to have a special license from the DEA. To be able to administer it for research purposes, and then we have issues from the IRB side you know with extra confidentiality protections because it is still federally illegal.

Chapter 2: FDA and IRB Perspectives on Cannabis and CBD Trials

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One thing you mentioned earlier, which I find really interesting is that you can ask, sort of, how much money is there to be made here from you know, the development of cannabis products, as you said, it’s not something that’s patentable, and so we haven’t really seen the big pharma big industry pharmaceutical companies kind of get in on this yet

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So, I just was wondering, do you have a sense of kind of how good the Federal Government has been or how open they’ve been to funding research on cannabis and how sort of how open or not open DEA has been granting that sort of licenses you mentioned earlier?

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I actually, so I do think the FDA wants to see this research and mean they have several guidance out asking for the research I just think it’s all those extra hoops to jump through, but I do think they want to see it, I think you kind of touched on where we’re seeing it come from, though, is often like academic centers

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and not so much from the point of a large randomized clinical trial to look at it, and so I think that sort of hinders some of the you know moving forward at a quicker pace, funding is obviously a big deal,  There are quite a few studies, at least with cannabis and they mostly come from academic centers what we are seeing more, though, is this CBD side which doesn’t have the same requirements to obtain it from NIDA, for the DEA license.

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the difference with the CBD side of it is that. it’s like the wild Wild West as far as the regulations go because, yes, the 2018 farm bill was huge and legalized or made it not illegal to obtain, use, cross state lines all those things for CBD. So now, you can get it in all States and provinces and, but they also have not.

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approved it for any indication so it’s not a lawfully marketed drug. So then, when someone is submitting a study to the IRB looking at CBD for something like neuro muscular pain or nausea or as a potential treatment for smoking cessation then you’re looking at you need an IND for that as a drug.

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Which is confusing, I think, to some submitters and even just some IRB members, because you can go buy CBD at your gas station, but it’s not lawfully marketed, so I think that is sort of it’s confusing to people right now.

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for sure and kind of related to that I guess we’re getting into sort of the challenges of reviewing it from an ethics and scientific perspective. And one of the challenges it seemed to me is sort of the fact that there doesn’t seem to be one standard formulation of CBD out their right, so it varies in strength and it might vary in administration roots and, of course, that has implications for how you would study it.

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100% and then it has, I’m not going to speak with the FDA per se, but I think one of the fears, is that we don’t know. You know what it’s grown with, what kind of toxins and storing it all kinds of things so then if you’re trying to also look at it in a vulnerable population like pregnant women, then you have a whole other set of fears and concerns.

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I want to talk about a little bit about the ethical challenges here for IRB review and I think we’ve kind of been dancing around a little bit. But I wonder, we occasionally do review these and I’ve reviewed a handful of them, and one of the things that I’ve sort of noticed is that there is this uncertainty or uncomfortableness, or IRB members aren’t really confident in assessing the risk of these products, and I think part of the issue there is that they often seem to be evaluated

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In populations that are sort of vulnerable. Like I think we’ve seen studies evaluating CBD for things like sleep or alleviation of PTSD symptoms in military members let’s say so that’s a group who have PTSD, are vulnerable.

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They might already have number of medications that they’re taking so the polypharmacy issues and now you’re adding CBD or cannabis to the mix.

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And we’ve had sort of robust debates about the safety of that and whether you, for example, need to have an MD present and part of the study team to be monitoring. And it’s hard because, like you said, on the one hand, you can get both sometimes you CBD products in any gas station, but on the other hand, that doesn’t necessarily mean they’re safe, especially in conjunction with other drugs.

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Yeah, I mean you hit the nail on the head some board members or just in general, still have maybe the. Past kind of feelings of just like it’s not legal, it’s illicit, especially when we’re talking about just cannabis, in general, and so this idea that the risks are higher for a cannabis product, than they would be for any other drug that we’re seeing and it’s, not to say it’s without risk, but I think part of that is the empirical question right so we’re trying to look to find out.

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I do think I think one of the biggest concerns that I’ve had in board meetings is just this idea of like the potency and how does it compare from one study to another, and even you know how are you ensuring that it’s the same

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level of product throughout and those kind of things? That may be something that is just not well explained to us at this point, but something that potentially the dispensaries are able to achieve. This is more speaking, probably for a CBD product or you know something with lower THC.

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And I think it’s a real interesting question to what extent users of cannabis products are still kind of, run the risk of being socially stigmatized and whether that’s something that research ethics Board should be worried about?

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I think there’s been a big shift in that mindset and I don’t think we’ve reached like Canadian levels of acceptance yet. I really do think that if we saw more research on it, I think people’s mind sets would shift a little bit I think right now we just don’t know. We have so much anecdotal evidence and not a ton of like just empirical research to support it, like in clinical research.

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That’s a great point I mean a lot of the hesitation, probably just comes from uncertainty Given what you’ve seen so far, are you generally an optimistic about the ability of cannabis to sort of be used in medically helpful ways? Or do you sort of think the jury’s still out on it?

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Yeah, I think I’m past like the naive point that it’s the answer for everything you know. As A PhD work and I was looking at this one receptor for methamphetamine addiction and I was like you know, I was, however, 23 years old, and was like I’m going to cure methamphetamine addiction with one receptor.

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and now we know that, like probably not. Targeting one thing doesn’t work for everybody, I do think there is probably something there with CBD. I think there’s something, some medicinal value to CBD and I would you know very much look forward to seeing more robust clinical trials of CBD.

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Yeah, interesting well, the future is exciting on the score and we’ll see how things play out

Chapter 3: Data Sharing and Ownership

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We’re going to switch gears and talk a little bit about something that has been on my mind, for a while now I think we’ve probably all been hearing a lot about putting participants at the heart of research

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And really how do we sort of increase engagement with the public for research, how do we make sure that we’re respectful of participants and we’re building trust

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In the community? And one of the issues that’s sometimes raised in this regard is to what extent, or whether participants should be provided with or have access to research data, so, the data they generate in research and also the results of research studies generally.

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I think we’re at this really interesting moment where people are recognizing the value of data and starting to sort of raise questions within clinical research.

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One of the questions here is to what extent participants sort of own their data and have a right to control it within clinical trials and what use it could be to them, so I don’t know if you want to kick us off with some thoughts on this general topic?

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Yeah, I think it’s an interesting point I do understand people’s desire to own their own data or to see their own data, and in some cases, maybe compensate like you said. I think when it comes to clinical research and maybe even with what you described there’s something that makes me kind of pause a little bit in that providing people with medical data that they can’t interpret because it’s not validated, or you know it’s investigational or they don’t know what it means could potentially cause some distress, or worse, right.

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Right, I think you’ve kind of cut right to the nub of the issue here. So, in medicine, generally, I think we all, in the last few years, with the 21st Century Cures Act. We generally now have access to the information that’s in our American medical records, if we want it right, most of us can go on to a medical portal and look and see literally what

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information is in our charts which we probably couldn’t just a few years ago. And so, in that respect I think things have been changing but oftentimes if you participate in a research, study or clinical trial that information does not find its way back into your normal medical record.

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And so, there’s sort of this really interesting distinction that you just raised between data that’s generated in a research, study that is sort of validated in which we know how to interpret versus data that’s generated in a research study that’s uncertain

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And so how do we think about the risks inherent in that versus the benefits? And I do think there could be there could be some benefits right.

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I feel as though a big a big benefit here might just be a consistent showing respect for participants and say hey we realize this is your data, even though we are not fully certain what it means we want to at least offer it to you and having a conversation with you about it.

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Because it’s yours, and we want to acknowledge that. I think that could go a long way toward sort of building trust among participants and increasing sort of public, the positive public perception of research.

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yeah, I think if you could have that conversation like here look, this is what we found we don’t know what it means here’s what we think it means. You know. But then that could really you know, created a downstream effect right like a cascade of events that could lead to increased medical bills and stress and searching for something that maybe wasn’t really there’s definitely psychological risks right. There’s anxiety that could come about and I think the point you just made is a really good one.

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If you present someone with results that are unsteady, uncertain and there’s sort of a natural curiosity to know and to get to the bottom of it which might in turn lead to further tests, you know and more and more medical interventions.

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When it really isn’t necessary right.

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Yeah, it may be unnecessary and I think that’s a legit, legit worry and a legit concern,

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But there’s also cases where there’s uncertainty and other types of cases too and I’m thinking about sort of genetic sequencing like we have a pretty good idea at this point what the genetic basis for certain conditions are like bracket one for breast cancer or the gene for Huntington’s disease let’s say and there’s been this really interesting debate play out in the in the academic literature over whether we should be providing people, or under what conditions with that information.

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And I think there’s a sort of common sense feeling that we can’t really do anything to prevent Huntington’s disease at this case. we can tell you if you have the gene but we can’t do anything to necessarily stop it from occurring, so do people even want to know, under those conditions? Do they have a right to sort of decline to know? And I think it’s an interesting kind of thought experiment which way, would you want to know?

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That’s tough one, I mean I think obviously anybody can get their whole genome sequence and find out right, but if it’s short of doing that.

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If you’re going to study, where it’s done, and you know that data is available to do you find out, knowing that there’s really nothing you can do.

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Right.

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Or do you just let it play out, I mean, you know, and I guess that’s a personal decision, and maybe we should maybe, as you know, IRB especially, that is what we should be considering. Letting a person decide, because not letting them decide is sort of paternalistic right. We’re going to tell you; you don’t get a choice versus.

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yeah, I think it’s hard for an IRB to say “no we’re not going to permit” this in a situation where we are willing to offer it and it has the right, supports in place.

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Yeah, you mentioned the right supports in place and I think that is key. And what are those? You know what are the right supports in place? What do you think they are?

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Right so it’s a great question, I mean I think for genetic return of results, I think you need someone, like a genetic counselor who has experience in conjunction with physician, or geneticists who has experienced interpreting that particular you know gene, string of results and who can provide reasonable sort of next step recommendations about here it sort of your options, and contextualize the information for you, I think those conversations you’d probably happen in person or over zoom right.

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I think that could go a long way, like I would I hate to think of these kinds of sensitive results being returned like by a letter or in some impersonal way like that.

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one of the other areas that we’ve talked about in the past, Luke, is this whole genome sequencing and essential turn of results for vulnerable population, so for minors or for those requiring an LAR, People who couldn’t understand necessarily the results and or, in the case of a minor someone who didn’t have the chance to consent.

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The minors raise fascinating issues, I know there has been some discussion. There’s lots of pediatric bio banks right,

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And you almost like want to say, well you know you can go ahead and bank that material if you find anything should you recontact that child? should you recontact someone once they become an adult?

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Reach the age of majority and say hey, we have some results you might be interested in. I mean it’s so interesting to think about those situations like if you got a call, suppose your parents, had enrolled you in a pediatric biobank and now that you turn 18 you get a call from that bio bank saying, “hey we’ve got some results, would you be interested in the hearing them?” you’d be like what? what are they?

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but then I’ve heard the flip side there are you know parents, especially who you know you can get we’ve gotten so much of all valuable information.

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Oh yeah.

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These rare diseases from pediatrics participating in these kinds of studies so.

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agree that I mean certainly this sort of genetic analysis has been incredibly valuable and helpful for therapeutic advances, I think.

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This has been a lot of fun. It’s been great to chat with you Amanda!

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You too, thank you Luke it’s been exciting and thanks everyone for listening.

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