Trials with Maya Z

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Maya: Hello, everyone, and thank you again for joining Trials with Maya Z. I'm very happy that today I managed to bring Jacqui to a discussion, a good friend of mine who I met at one of the industry conferences by chance, literally, but it turned out to be one of the most insightful people that I met.

And since then we've been [00:01:00] chatting about all challenges within the clinical research industry, and I decided to invite Jackie today because it became very trendy to speak about diversity in clinical trials, to include more and different people in clinical trials.

And when we speak about diversity, we sometimes forget that even pediatric research is a way to diversify clinical trials. And Jacqui is one of the experts that I know who is super passionate about pediatric research. Not only passionate but super experienced in that area.

Jacqui, why don't you first start by introducing yourself?

Jacqui: Hi. Thank you, Maya. Yeah, it's been a lovely time getting to know you better over the last few years. My name's Jacqui Whiteway. I've been in the industry for over 18 years and I'm a scientist by training. I [00:02:00] was in clinical research. I was in a small biotech and as I got interested in the clinical research industry, I went into a CRO. And a CRO was a fantastic way to learn a lot about the industry and lots of different types of trials. Through that, the bulk of my time I got into the feasibility, which is really how I connected with you, Maya. And feasibility is really about getting into clinical trial planning, not site selection, but true feasibility. And when I was working on those trials, the most interesting are, perhaps, the least feasible or the most challenging. So those are usually rare disease indications, which are often among pediatric populations.

So through that work, I got really interested in the pediatric populations and the challenges there. [00:03:00] And then at the CRO I was working at, we started a Center for Pediatric Clinical Development and I joined that in 2018. And it's the ICON center for pediatric clinical development. I could have my full-time day job focused on pediatrics. Yeah, so it's really exciting. It's bringing my science, again, the scientific background, but really I am learning how to address the challenges that pediatric trials encountered.

Maya: So speaking about challenges in pediatric research, what makes it so hard to plan pediatric clinical trials, Jacqui?

Jacqui: Well, there's a number of things.

Maya: Where do you start?

Jacqui: Yeah. So many things. I mentioned the rare pediatric overlap. Kids don't get that sick, [00:04:00] right? So there aren't a lot of kids that are six when you're talking about a pediatric trial and super aware of this.

Recruitment rates. How do you find these patients? Right? So there aren't that many of them. You're dealing with logistics and lots of sites and perhaps lots of countries and really trying to find these patients, these kids. So, that's a challenge that comes perhaps from a good thing.

Another is you're treating the whole family. You aren't just dealing with one person. You are addressing a whole family and really a whole community. There are siblings, there are parents, there are work schedules, schools, there's so much to consider when you're engaging with [00:05:00] and communicating with the child. That's a challenge, right? You need to make sure that they understand what they're going through as well as the parents or the guardians and that sort of thing. I would say, also, as an overarching challenge is a fear and, I mean, fear on a whole lot of levels, and we'll probably get to that.

As species, children are vulnerable. Right? And you go back in time, and perhaps children weren't perceived the way we look at children now. You know, you think of the smallpox experiments, just taking kids and treating them and then we swung the other way, where we were like, "Oh, let's not treat kids because they're vulnerable." And that's terrible. And frankly, [00:06:00] what we and I experience a lot with family and friends is, "Oh, what do you do? Clinical trials? Oh, what is that?" Well, more people know what clinical trials are now, but I'm in pediatric clinical trials and they're like, "Whoa. How can you experiment on children?" to which you respond, "The medicines that are used on kids, most of them haven't been tested on kids, so is that any better?" Right? So you're using untested medicines in a completely unregulated atmosphere.

So there's fear to test or experiment with kids. And so we say, we want to protect children through research, not from research. And that's where that's coming from. There's also fear from industry professionals who, like me and you, [00:07:00] we have kids and the first thing we think of is, "Would I put my kid in this trial?" Or, really relating to the people who are in the trial. If you step back and you look in our world, and again, you're very familiar with this when you're using data to try to find recruitment rates and that sort of thing, they don't look good when you're looking at recruitment rates for kids. And then you're doing things like having to deal with parents as well as informed consent and a lot more logistics and opening up sites for fewer patients a lot of the time. And so there are costs and logistics. So that's another kind of fear, right? So on paper, when you're going to plan the trial, and it's a lot of work compared to adult trials for less outcome, maybe [00:08:00] on the surface, I would argue that's not the case. But when you first come to it, yeah, it's fear of the unknown. It's not fitting into the cookie cutter. You gotta think a little differently. Right? You think one of the reasons why we've connected is we think differently. We want to think creatively. Don't be afraid to do something different. Look at where we are right now in the industry and with COVID-19 and decentralized trials. It's a good thing a lot of people were already thinking differently. Otherwise, we'd be in a lot of trouble.

Maya: Maybe with pediatric research, we just need to be one level more creative. You're absolutely right. You mentioned decentralized clinical trials, so I wonder, do you think now decentralized clinical trials are making pediatric research better?

Have you seen any stories to tell? Maybe it doesn't work better now?

Jacqui: Well, that's the million-dollar or billion-dollar question, right? We're asking that all the time. As [00:09:00] with anything else, and as with kids, I'm going to back up a little bit. With pediatric trials, we've got a whole bunch of adults who have been doing clinical trials for a long time, and a lot of the stuff we try to copy and paste into pediatric trials. And it doesn't work. And that's where the fear comes, "I don't know how to do this. Let's just not do it." With decentralized trials, there are a lot of assumptions made. This goes for adults too, in that everybody will like doing decentralized trials. They'll like having at-home visits, they'll like to have telephone calls instead of visiting. But is that actually the case? And I think there's been some work, I've seen some surveys and that sort of thing that's showing that's not always the case for some things. It's not for others.

And, as we've talked before, [00:10:00] we can imagine being a patient. And sometimes you want to be in front of the doctor and for kids, the answer is Yes and No. Right? Because of course, there are different situations. You've got these siblings, you've got school and you're supposed to do this visit.

I mean, a clinical trial comes with all these visits, and what if it's just a few questions or check-in and you can do that on the phone, right? Yeah. Can you do a purely decentralized trial with kids? So far, no, I haven't seen that. The only full-on decentralized trial I've seen is for adults. But you certainly can bring a lot more there. But what I would say is, and this might inspire fear in the professionals again, it needs to be flexible and adjustable, not just based on the trial, but on the families. "Do [00:11:00] you want to come in for this visit or do you want to do it on the phone? Do you want to have home health?"

I mean, home health sounds great. Look, this family, this dad has to take his kids in to get a blood test for this trial. It's on top of the standard of care and that's a whole other conversation, right? We should be trying to make the standard of care aligned. So you've gotta go for the blood test or you could have home health come and do the blood test.

Well, that sounds fantastic, and I admit when I first heard that, of course, everybody will want that. But step back and think. You are having a professional come into your house, I'm seeing your house. You might not feel comfortable about that. Maybe you have a reactive dog like me. So you've got to find somewhere to put them, but maybe a lot of people do. So I think it's about flexibility. Ask the patient, right? Ask the family. And be adjustable. And again, there's a fear there [00:12:00] because when you were trying to plan your trial and you've got all of your milestones laid out and that sort of thing, it's like, "Should we make this visit remote or should we make it in person?"

Maya: Maybe that's not the right question. Let's make it available. You're bringing up a big topic here because that's something I've been also thinking about a lot. We shouldn't think as you said, we shouldn't be the decision-makers. Should we include home visits or lab visits or whatever visits or wearables at home or not?

The decision should be with the families, with the patients, and with the kids. Basically, it's about the entire decentralized movement. The decision should be with the patient and the caregivers. The only thing here is that it's super [00:13:00] complicated from the logistics perspective to make this possible.

So yes, it's great. It's ideal to provide all these options to people for them to decide. But how do you make it realistic and how do you handle logistics and how do you then ensure safety? I think maybe with time, we'll get to that, I think everyone dreams about this world, but let's see when this will come.

So, okay. I understand that with decentralized clinical trials, there are pluses and minuses, but is there anything that we should change in pediatric research so that it's more successful?

Jacqui: Well, I think we need to start thinking about it earlier. I think we can say that for all, but even more for pediatrics and one advantage of pediatrics again is that [00:14:00] normally, the bulk of trials start in adults and then they go to pediatrics. Now that's a whole other topic too, because there's this huge delay in getting these drugs, these safe drugs to kids, and we want to reduce that time.

But at the same time, you do want to make sure it's safe for adults too. It is a vulnerable population. And that is a whole other topic. Doing things like extrapolation trials and different types of controls and that sort of thing. I'm almost losing my train of thought there. So what do we want to change? To me there are a lot of things we can change and plan early, we have the opportunity because you have the adult trials, the regulatory authorities, the main ones, right? [00:15:00] Europe and the US require pediatric plans.

So that's trying to encourage that. In the industry, we definitely see a variable understanding of when to start doing that. And also, it's seen as, "Oh, I gotta do it." So, I've talked to a number of people at a bunch of companies from the pediatric perspective, successful companies are the ones who actually put pediatrics first. So, they're planning their adult trials. They have an asset, right? They get together and they go, "What are all the different trials we want to do? What are all the indications this drug can be used for?" But they should also be asking "Is this relevant for pediatrics? Even if it's 10 years now in the line.

And let's start planning for [00:16:00] that now. And by planning for that now they can do a number of things. They'll get their pediatric plans in place. There are incentives, if they do these, they'll get them done on time. They'll be efficient. They'll get the right testing done with the fewest number of patients.

One thing is getting adolescents into adult trials. That's almost a low-hanging fruit. Yes, sometimes it means a few different sites that you have to use. It's a different population and adolescents are a whole different challenge.

I got teenagers. Well, they're not small adults, but they're not big kids either. They're their own interesting population. That is almost a low-hanging fruit for getting adolescents into adult trials. But you can't do that at the drop of a hat, right?

And if you do, you're gonna make [00:17:00] mistakes there. There are so many things, quite rightly, all the hoops we need to go through, for good reasons, so start planning them right at the beginning, and ask those questions. So I've spoken directly with a couple of sponsors who have had what I would call a pediatric champion within the organization, who says, "What should be done differently early to bring in expertise?" So for those pediatric plans, for the protocols, oh my goodness, the number of copy-paste from adult protocols, and I won't say any details here because they're real paste scenarios in the eligibility criteria. Yeah. You know, things regarding looking at [00:18:00] smoking for neonates and stuff like that. And you're like, obviously this is being copy pasted. So think early, and bring in experts.

And the fear enters there. They're like, "Oh no, that's too much cost. We don't want to think about it." or, "We'll cross that bridge when we get there. It's a lot easier to cross that bridge if you've planned it and it's not as scary as you think. I mean, I'd be lying if I didn't say there were some extra logistics and challenges, of course. But you're not the first. And if you are the first, take advantage of that. I mean, that's kind of exciting to me.

Maya: Yeah, I like your attitude. Definitely. Let me ask you about these pediatric plans because you said bringing some expertise, someone should think about pediatric research early on, but that's not realistic for most companies.

For most of the small biotech companies, rarely have enough resources for adult clinical [00:19:00] trials. And what about pediatric research? So what's your observation? How many of these biotech companies actually even know that they should be planning like this, that they should be co-creating these pediatric plans?

I think there is a lack of awareness from what I've experienced. What do you think?

Jacqui: There is a lack of awareness in the pediatric world. There's been a lot of changes in the regulatory agencies and the requirements, the legislation, they're changing all the time.

You're aware of a number that has just been changing recently and being from Canada, for example, Canada has finally got some real pediatric legislation. Those changes are happening all the time, and that's where expertise helps. The Race for Children Act. I don't know if you're familiar, but it came into effect in 2020 and there were a few years leading up to that. And [00:20:00] yet we're still finding some companies usually small who aren't aware of it. I mean, one of the big changes the Raise for Children Act has, is for pediatric oncology, and as an FDA requirement is that for cancer drugs, even if there's orphan drug designation, even if it's a rare disease.

Typically, you don't have to do your pediatric plan, but now you do for oncology and the mindset of a lot of people is, "Oh, we don't have to do that because it's a rare disease." Pediatric cancer is technically a rare disease. And you're like, "No, no, you do. And if you don't have that plan, you can't submit your NDA or your BLA."

So, now you've got a little bit of a delay, there can be a little bit of a rush. And we've seen a few examples of that. And there's the expense. You say, "Well, [00:21:00] I think pediatrics really brings a lot of passion and dedication from a lot of people, ourselves included. Right?" It's sometimes just that question, that I would seek out expertise in. It doesn't always need to be paid for. Just talking to the FDA, I mean the FDA being US-centric here. But of course, the EMA too, want to have those questions come to them and they have a lot of free resources to discuss that with you. And then really early on in stages, as you know, with feasibility as well, a lot of the organizations such as the CROs, there's some free expertise to be provided there as well.

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Maya: So Jacqui, in a lot of cases you mentioned adolescents and I wonder: Is there a big difference between adolescent clinical trials and younger kids? Or, or maybe adolescents and adults as well. Maybe you can just compare the difference between these three categories.

Jacqui: Yeah, yeah. Well, yes and no again, so adolescents, as you're well aware, they're in this interesting situation. They desire a lot more autonomy, right? And they have a lot more autonomy and they have a lot more going on that they're doing themselves. And the grownups have a lot less control, right? Yeah. So with, at least with the little kids, and you're doing a [00:23:00] trial and you're like, "Okay, we're going to your visit," or, "The nurse is coming. With an adolescent, there's less control.

So there's a lot more needing of connecting by staff, by clinical trial staff, by connecting and really understanding the adolescent because you and all of us are consulting with them, giving them that autonomy. Now at the same time, it's still their parents who have to give permission.

Yeah. The informed consent. And then with that, you have a whole host of other things that come into play. For example, you're dealing with sexual health, you're dealing with birth control, and you're dealing with pregnancy, and who talks to them about that? So again, that comes to really how in a clinical trial, if you get pregnant, you're typically kicked out of the trial.[00:24:00]

Now, if you were in that trial, you would be told, "Okay, this is why you're out of the trial." Now, imagine a teenager. Their parent has signed the permission for them to be in the trial. Well, the parent is gonna be told while they're kicked out of the trial. But your medical age of consent and your legal age of consent is different in a lot of countries.

So you're dealing with those types of new, different considerations. So it's more challenging with that. At the same time, you're getting to engage more directly with your patients. So if you're talking to them and you're treating them with respect, then that's helpful.

And then, biologically, yes, they're still growing, but with regards to weight [00:25:00] and metabolism, it's a lot more similar to adults. And so that's why we really encourage looking at the addition of adolescents into adult trials and young adults. So, it's the AYA population, the adolescent young adult, AYA.

This arbitrary cut-off is at 18 or 19 or 16 depending on where you are, but typically we think of 18. It's quite arbitrary when it comes to physiology. And then from a medical perspective, often you're having the pediatric physicians or pediatric sites who are following those kids past 18, in cancer can be up to 29.

So even when the logistics, the fear of trying to address those logistics, and so a lot of the [00:26:00] time we as professionals and sponsors are like, "Oh, let's just leave them out for now." Perhaps, let's just focus on these sites. We don't want to open up different sites or that sort of thing. Well, realistically you should be, anyhow, it's just better to think of it earlier.

Bring in the professionals, give raising control, talk, and communicate. Communication is a huge thing, Maya, we haven't even got to, what would I like to change? You'd ask. Yeah. That is a big thing. How to communicate with the kids is huge.

You will have seen, especially for informed consent documents. These things are on dozens of pages. And as a scientist, I've read these and not understood them sometimes for adults, or I've understood them and said, "I'm not sure your general person going into a trial getting radiation [00:27:00] knows what a Becker roll is.".

I do, but I'm pretty sure most people don't. For kids, you see the same. It's fascinating to me. I came from a scientific background, not a pediatric background. Fascinating for me to see these and they're not nice tables or pictures a lot of the time, or they're more addressed at the legal requirements rather than trying to help you understand what it is. That would be a huge change.

Maya: By the way, you're starting an enormous topic and, actually, I'm inviting to the podcast a lady, she's a professor in translating complicated literature, medical literature to patient language. She's not coming from a clinical research world. But at the same time, [00:28:00] she's dealing with these complexities all the time. And I think we can actually learn really good lessons about communication in healthcare. How do we communicate complicated topics?

The biggest problems in healthcare, the biggest issues come from communication. How much time do doctors and nurses have for communicating things with patients, how they're communicating? We have really high expectations of what doctors and nurses can do and have the time to do. Anyway, you raised a really big topic here

Jacqui: I see three chunks when you talk about changes or focuses, and I've thought about this before, and, you know how we like to simplify things sometimes.

So, there's [00:29:00] control. Giving control and speaking to the patients. There's communication, which we just said. So that's two Cs. And another is comfort. So a big thing in, I would say probably all trials, but for pediatrics especially, is anxiety - anticipatory anxiety and trauma, real medical trauma.

And that sounds like a really strong word. This is a big area of exploration for me. Medical trauma can arise for pediatric medical trauma for kids as well as their care circle, so their caregivers, through a traumatic disease or a [00:30:00] procedure and it's different by the person like I'd mentioned before. You know, how many people like needles, how many people have phobias of needles, and why do they have those phobias of needles? And are needles really that bad? So you think of clinical trials, they have all of these additional tests, lots of just using needles.

I mean, think of a PK trial, even a vaccine trial. Yeah. You know, but you're always taking blood and you're jabbing and everything. And it can be traumatic. And if you're dealing with a disease where somebody has been, or a condition that's long-standing, it's for kids. Again, it's rare for the most part.

But that means these are some really troubling conditions that the families had to deal with. And so they're coming into the situation with some trauma and then we can exacerbate it. Exactly. So the comfort, the third C I would see as [00:31:00] a big change in the industry because that is not addressed.

You mentioned this person who's not in the clinical trial world. There are a lot of physicians, a lot of nurses, and a lot of caretakers, who are addressing trauma, like trauma-informed care at their sites. I think we need that in clinical trials. I think we need to support sites in recognizing when somebody comes through the door, the child, the family, sometimes they've had to drag their kids there and they're yelling, it's just a needle.

Well, again, how many people have longstanding phobias? If you think back to your friend or anybody you know, or your children, every one of those experiences can turn into something bigger than it is. And we can dismiss it. And we have our, you know, scheduled events [00:32:00] and we're like, come in here and take these blood tests.

And the first thing we'd say is, to reduce those as much as possible. But what can you do? What comfort can you provide? And in the clinical trial structure, which has struck me recently, is there's nothing in there that requires you to address that. And in fact, there are almost disincentives, as it falls into the patient engagement.

There is a patient comfort bucket with some arbitrary dollar cap, and you're like, "No, no, but wait a minute. Think about the patient. If you could provide something and everything is through the lens of incentive. Oh, well, are you incentivizing them to join the trial? There are ways around that. Don't fear it, right?

Yeah, yeah, yeah. Absolutely. Yeah. Do something that'll help. And there are a lot of organizations, there are a lot of parents and groups who are trying to bring awareness to this. But [00:33:00] again, as a parent trying to drag your kid to an appointment and each one could get harder if it's a bad experience. Like, my daughter had a blood test when she was young and they had to strap her down in one of those big veco things.

Yeah. She's not gonna go for another blood test if you're in a clinical trial. You have to do it all the time. And you don't have to do that. That is called the dropout rate in our lingo. So it can be a win-win. Just having some empathy and recognition for the long term. And then I'll get off the soapbox cuz then we can get into the long-term health consequences of these traumatic events.

And we have a role there as clinical trial professionals, but we're finding, I'm finding personally in a lot of situations, "Hey, what comfort can we bring, um, to this situation? There are a lot of [00:34:00] tests. There's a lot of going to the hospital. Kids can start being terrified of going to the hospital, even driving by the hospital when they're not going, can inspire anxiety. And what happens usually, is the parent starts not going by the hospital until they have an appointment. So there's avoidance, right? But what if there's a simple tool, like kids are amazing because they have these superpowers usually through playing and imagination, and while they have these huge fears, there actually can be easily got around through them by tapping into the play?

Maya: So yeah, if I'm to summarize, maybe we should stop, like most sponsors, CROs, maybe we should stop thinking, investing money and budgets into enrollment assistance only, and start investing in more psychotherapists [00:35:00] and the psychologists and services because there are plenty of services by the way, like nowadays, especially after COVID-19 plenty of services that provide you with even remote support.

And maybe investing in more pleasant and interactive content, not just documents, but maybe videos and maybe rooms for kids and maybe even theaters and bring together the kids. There should be a way to bring this comfort. Because you're absolutely right and it's not just for pediatric research, it's across the board for all sorts of clinical trials.

In some countries, if you are, for example, a patient living with cancer, you should go to some sort of psychotherapy, for example. It's a mandatory thing. Maybe that should be mandatory also when you're in a clinical trial, no matter the disease.

Jacqui: What the [00:36:00] solution is shouldn't be mandatory. But maybe the requirement to look at it - assessing what level of trauma or anxiety might be provoked by this.

And if it meets certain criteria, then you are obligated to address this somehow. And maybe it's by counseling. And I just did see one of those this past week, and then there were all these regulatory challenges. They're like, "Oh, well, will we have to do all of these requirements because we're providing this completely voluntary counseling session, right?"

So suddenly there was all of this. And so that kind of scares them away. It takes some really committed individuals in these companies, but we have those. Look at our industry now. We've done such amazing things. We can do this.

Maya: And we can also look from other industries, examples, and [00:37:00] just try at the end of the day, it's worth it. We need to try and start somewhere. Jacqui, that's been an incredible conversation. I have one last question. Before we started you and I was discussing that both you and I were parents, in your case, teenage kids, in my case, younger kids.

And I just can not ask you this question. Would you agree for your kids to be a part of a clinical trial? How would you feel about it if you have to agree on that?

Jacqui: Yeah, that is a fantastic question. It would depend on the trial and. If you have an untreatable condition, and there are no other options, then maybe, but I can tell you as a professional, as you would, you know, my answer would be yes, [00:38:00] if the need was there, if it was a well-designed trial, I'd be looking at it super carefully. I'd be like, I am not reading a 50-page informed consent and I want to have the scheduled events really clear.

I want to know why I have to go in for that test because I don't understand all of that. That's where bringing people in before patients can help cut down on that. Because the advantage of the trial is you have more access to care, and you have more time to ask those questions.

I'm a scientist. You have more access to science and doing something cutting edge, but I would want there to be recognized for what we were going through. And a big thing is too, I would discuss it with my child in a way that they would understand and, [00:39:00] frankly, right now, as having a teenager, I mean, he may say no.

And I would respect that, of course. And fear, again, would need to be a factor of my own fear, child's fear, um, that sort of thing. And actually, the first pediatric clinical trial that I worked on was in my feasibility days and it was one of my very early feasibility days and it was for three to five-year-olds.

And I can't go into any details about it because it'd be obvious what it was. But I remember talking to the sponsor because it was not feasible. And I remember talking to my contact when we were in the big meetings. Everybody's talking in. But then when I talked to her and she was a parent like we got to know each other first and I said to her, "Look, would you [00:40:00] put your child?" I was getting very frustrated because it was not feasible, a big No. And I said, “Would you put your child on this trial?" And that is what got through. Exactly. So it's a question we all need to ask.

Maya: That's exactly the reason why I asked you this question.

I ask myself all the time when we discuss pediatric research and I always say, I can speak about myself, of course, I'm ready to do whatever so that my kids are healthy and well, and live wherever and succeed in life. But then they will be always this if am I doing the right choice for them because it's not my life.

It's their life. It's extra responsibility. Yes. So I better know really well what sort of a risk I'm taking and I need to understand. So going back to communication, and again, I wanna end this episode with a kind of like an appeal to everyone who is working in pediatric research or maybe not, [00:41:00] or haven't started yet.

First, start planning earlier, like Jacqui said, start planning earlier and ask your question, “Would you agree for your kid to be a part of this clinical trial?” And then think twice. What sort of a protocol, what sort of a setting, and how much and where are you going to invest your budget? Yeah. Jacqui, thank you so much for this insightful conversation. I'm pretty sure that many people will try to continue this discussion with you privately and please go ahead and connect with Jacqui. She's amazing. Thank you once again.

Well, thank you so much. This was such a joy. It was nice to have a conversation and love talking about our shared passions.

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