Speakers:

• Scott Schliebner, Sr. VP, Clinical Development Services and Head of Rare Diseases and Orphan Drugs, TFS HealthScience
• Alison Sampson, Head of Rare Diseases and Orphan Drugs (Europe), TFS HealthScience
• Samaya, Moderator

Speaker 1 – Samaya (00:10): 

Well, good day to everyone joining us and welcome to today’s Xtalks webinar. Today’s talk is titled Pediatric Rare Disease Studies: Patient-Centric Approaches. My name is Samaya and it’s my pleasure to be your Xtalks host for today. 

Today’s webinar will run for approximately 60 minutes. This presentation includes a Q&A session with our speakers. This webinar is designed to be interactive, and webinars work best when you’re involved. 

So, please feel free to submit questions and comments for speakers throughout the presentation using the questions chat box, and we’ll attend to your questions during the Q&A session. Now, this chat box is located in the control panel on the right-hand side of your screen. If you require any assistance, you can contact me at any time by sending me a message using this chat panel. 

We also have a handout available about type one diabetes in adolescents. Audience members, you can download that through the handouts tab in your control panel. At this time, all participants are in listen only mode. Please also note that this event will be recorded and made available for streaming on Xtalks.com. 

 

Speaker 1 – Samaya (01:28): 

At this point, I’d like to thank TFS HealthScience (TFS), who developed the content for this presentation. TFS HealthScience is a global contract research organization (CRO) that supports biotechnology and pharmaceutical companies throughout their entire clinical development journey. In partnership with customers, they build solution-driven teams working for a healthier future, bringing together nearly 700 professionals. TFS delivers tailored clinical research services in more than 40 countries and supports customers with comprehensive solutions through three strong business models, clinical development services, strategic resourcing solutions, and functional services. 

Now, it’s my pleasure to introduce our speakers for today’s event, and our first speaker is Scott Schliebner. Scott recently joined TFS as Senior Vice President Clinical Development Services and Head of the Pediatric, Rare, and Orphan Disease business unit based in the U.S. Scott has more than 25 years [of experience] in clinical drug development having worked across the biotech nonprofit, small CROs and large global CRO sectors. 

 

Speaker 1 – Samaya (02:45): 

Scott also serves on the board of directors for two rare disease focused nonprofit organizations, uplifting athletes and angel aid, and he serves as a strategic advisor for GVA, bioinformatics, Halo Health Systems and Adamic Medical Innovations. 

Our next speaker is Alison Sampson. Dr. Alison has over 20 years of clinical research experience. She has a project management background leading both clinical and cross-functional teams. Alison has experience in a wide variety of therapeutic areas with expertise in rare diseases in neonates and adolescents. 

Currently, Alison oversees clinical trials involving rare disease pediatric patients or orphan drugs. Her department works with centers of excellence, patient groups and registries to promote study awareness. Now without further ado, I’d like to pass control to our speakers. 

Scott, Alison, whenever you’re ready, you can go ahead and get started. 

 

Speaker 2 – Scott Schliebner (03:51): 

Excellent, thanks Samaya. First, let me just thank everyone. Good morning, good afternoon, depending on where you are. Thank you for joining our presentation today. We’re excited to share some learnings from the field in the rare and pediatric space, of course focused on patients through and through. I hope there’s some valuable lessons learned here for you. And of course we do have a chat function as well. 

So, if there’s a question you have as we go along, please don’t be shy, ask your question and we will do our best to get to all of them at the end of our presentation. And with that, I think we can advance a couple slides. And Alison, I think you can get us started when you’re ready. 

 

Speaker 3 – Alison Sampson (04:46): 

Thank you very much, Scott. Yes, indeed. Thank you everyone for joining as well from my side. So, patient centricity has become quite a buzzword in clinical research and in the new ICH version six, there’s a whole new section in patient centricity. So what is patient centricity? What is it? 

Patient centricity at heart? It’s really putting the ultimate stakeholder in a clinical trial at the center. They are the ultimate stakeholders and it’s designing a clinical trial process, supporting the patients and making the whole clinical trial experience the best we can. And that takes not only into account the patient but their immediate family and what they need and want from a trial, which is not necessarily what we’ve done in the past. 

And it says here in this definition, and it’s very much true, it’s a mindset, it’s a, of thinking about developing a trial and then what the process would be for parents and or children or patients, how that would go and what things can we do to make it better. And the last bullet point here is why should we bother? 

 

Speaker 3 – Alison Sampson (06:21): 

In this slide we talk about what a rare disease is. A rare disease; the definition varies depending on where you are. It’s different for example, in the U.S. to Europe, but roughly it’s a disease that affects less than one in about 2000 people. Although rare diseases by themselves are rare, so obviously one in 2000, not very many. Collectively, they’re not rare. Lots of people suffer from a rare disease, and every year, we identify more and more rare diseases. As our technology with genotyping improves, we’re identifying large numbers, more of rare disease that we haven’t identified before. 

You see here, that 80% of rare diseases are genetic. With that, goes hand in hand the prevalence in children. So, about half of a rare disease occurs in children and the two often go together. And because we don’t understand about 80% of rare disease and what causes it, or how the disease progresses, still at about 30% of children are dying before the age of five from a rare disease. So, obviously we need to do more research and that research needs to be better. 

 

Speaker 3 – Alison Sampson (07:44): 

So, just really summarizing what I’ve just said, rare diseases, are not that rare, particularly about one in 10 people who live worldwide with a rare disease. Not all rare diseases are life-threatening. So that’s something to bear in mind, but many of them are serious and severe. And you can see here [on the slide] 95% of rare diseases have no FDA-approved treatment and as I mentioned earlier, about 80% are not well understood. So, it’s a growth segment in drug development as our technology advances, particularly in gene therapy and stem cell therapy and those sorts of advanced therapies. 

Going back to rare diseases in children, and as I mentioned, the two often go together, definition of a child can vary depending on where you are in the world, and this is just some tables here [on the slide] of how it might vary. So, particularly the adolescent age group can be different depending on where you are. If we’re working in different areas of the world and we often are in rare disease because we have to go where the children are, then we need to look carefully at what we do and the things we put in place and what the definition of an infant or a toddler or a child is in that particular country or area. 

 

Speaker 3 – Alison Sampson (09:17): 

This is quite astonishing statistics. Pediatric trials will only make up about 17% of all trials and that’s generally because they’re very hard to do. Childhood is fragmented, you get fragmented cohorts in terms of age. So, the response to a drug in a baby would be very different to the response to a drug in an adolescent. And this makes for complexity in pediatric trials. 

One of the many reasons why they make up less than 20% of all trials. And then of that 17% half, so around seven or 8% are unpublished or unfinished. One of the two and 20% of pediatric trials are discontinued early. So, there are many reasons for this and you can see the reasons below. A lot of it is to do with things that we can fix. Family inconvenience, expense, too many appointments travel quite often in around pediatric studies, parents have to bring other children with them, other young children and that does cause hassle. 

 

Speaker 3 – Alison Sampson (10:36): 

They [children] miss school, parents miss work, and all these things can be addressed, and this is the heart of patient centricity. It’s not the best process for the parent and the child. What we need for them is to take part in these trials. And the second statistic on here is that one in five parents and children come to their first visit and they never come again because of these reasons. 

That’s why we need to bother with patient centricity because we need to address all these issues so that we get children into these clinical trials and we reduce that draft statistic of 30% of children dying before the age of five. 

 

Speaker 2 – Scott Schliebner (11:21): 

Great, thank you, Alison. Well, with that background on what patient centricity is, little definitions on pediatric and rare disease, and again, keep asking that question, why bother? 

This is a little bit of a buzzword when we talk about patient-focused approaches, but again, why bother? Is this really worthwhile or is this just a buzzword? We’ll talk a little bit more about why we think this is so important and if you’re not fully on board, by the time near the end of our presentation, we hope you’ll ask some questions so we can further convince you about why this is key to clinical development. 

Before we talk a little bit about that, in front of us is the slide, the traditional clinical drug development paradigm. I want to briefly walk through this. I think this highlights again why there’s some areas for improvement, why we can do better when we think about patients. 

 

Speaker 2 – Scott Schliebner (12:16): 

So, by starting at the upper left and then kind of proceeding in a clockwise fashion, this is how we would typically sort of look at a new clinical study. There’s a clinical protocol that goes through a lot of development and eventually is approved by a multidisciplinary team of preclinical and clinical and medical, and operations. Then, we move this out, and we start to select investigators. 

We go through an ethics or IRB approval process for that particular study. Then, we start thinking about the participants that we’re going to recruit. As we circle through this and patients are enrolled, data is entered and analyzed, and eventually, we’re presenting, filing, and registering that data. 

This is this sort of traditional paradigm, right? We develop a protocol oftentimes as I like to say, it’s in a conference room in New Jersey, insulated in a bubble, and then we move to our clinical sites and then we start to think about participants or patients. 

 

Speaker 2 – Scott Schliebner (13:18): 

This is the way clinical development has largely operated for 30, 40, 50 years without a lot of really fundamental changes to the flow. What’s wrong with that picture of clinical development? Well, first starting here on the left was that protocol designed with any input from patients, from caregivers, from the site staff that’s going to execute the study or maybe from home healthcare nurses or other providers who will be involved. 

I can’t tell you many times we’ve seen a schedule of evaluations in a protocol come out for things that all need to happen in one day. And when you actually put that in the hands of a clinical site coordinator (study coordinator or CRC) and they look at that and they say, well, we can’t do radiology scans in the morning and then move down to a physical therapy suite and then move over to genetic testing. 

 

Speaker 2 – Scott Schliebner (14:12): 

We can’t do all these things in the same day. We should have thought about this. It would’ve been nice if you asked for our input. Moving along here is the schedule of assessments, which is really the nuts and bolts in the crux of a protocol when evaluations happen and what happens is that realistic and feasible for patients? 

I know in that proverbial conference room where this protocol was developed, we checked all the different boxes in the schedule of assessments of the blood draws we wanted at certain time points and the scans we wanted to happen here. And all of those data and exploratory endpoints were sort of put together on a protocol, but at the end of the day, we’re asking human beings to go through that process. 

Is it realistic what we’re asking and can people handle it further? When you get to the eligibility criteria in a protocol, we obviously have inclusion and exclusion criteria. Again, without sometimes some external input or pressure testing these criteria, we outline what we think the ideal narrow controlled patient population would look like. 

 

Speaker 2 – Scott Schliebner (15:19): 

And a lot of times there are very few, if any, patients who actually meet all of those criteria. What seemed good in theory for eligibility sometimes isn’t so good in practice when it comes to finding patients further. 

Does a study actually appeal to patients? A lot of time and effort is put into that clinical protocol. Again, sometimes that’s done within an insulated bubble without external input. Does the study appeal? Is it measuring endpoints that are meaningful for patients? Is the schedule of assessments just too much for families to handle? 

The burden of participation is extensive. It includes not only just as Alison said, hassles and time, but often travel. It also costs money to participate in a clinical trial and that money can be things like missed work, childcare, travel and logistics and things like that that are sort of hidden costs that we need to sort of think about those barriers that patients have and try to get those out of the way. 

 

Speaker 2 – Scott Schliebner (16:21): 

So these are a few things that I think is wrong with the traditional clinical development paradigm. So really the question kind of down here on the bottom, sort of like why bother with patient centricity? Well, why can’t we just continue to design studies the way we always have? Why can’t we just keep doing what we’ve done? 

I’d like to go to the next slide please and talk about why this isn’t working. So, in front of us is a little bit of data I will share, and this is the current clinical trial landscape from earlier in 2022. This is all sort of therapeutic areas, not necessarily rare in pediatrics, but it really highlights that we often design studies that don’t really work for our intended audience, the patients themselves. So, on the left are some metrics on the right is the impact of those metrics. I’ll just start off by starting with every year we have more clinical trials requiring more patients to enroll. 

 

Speaker 2 – Scott Schliebner (17:19): 

Earlier this year we had more than 300,000 clinical trials that were active or about to be opened requiring 40 million patients to enroll. For those of you in clinical development very well that clinical trials and drug development does not move forward and less patients participate and we rely on their data. The fact we need so many patients, you can see the impact of this. We now have more than half of all trials are delayed simply to recruitments. 

So, you can see we’ve got more studies requiring more patients and we’re putting out studies that don’t really work for people and the result is it’s delayed. Further, when we look at some other metrics, the far majority of patients live more than two hours from traditional academic medical research sites. What does that mean? That means even if patients do enroll, more than 30% of them tend to drop out before the study ends because traveling to and from that clinical site is too burdensome. 

 

Speaker 2 – Scott Schliebner (18:22): 

Travel is the most significant burden we’ve heard from rare disease patients When we ask them and we do surveys and I’ll share some more survey data in a moment. It’s that time back and forth to clinical sites that delays enrollment, it hurts retention and it impacts overall timelines. Of course, DCT paradigms now help part of this, but they’re only part of the solution. Lastly, when we think about studies that don’t really work for patients who aren’t designed for our intended audience, the majority of clinical trial participants still are male, they’re Caucasian and they’re not necessarily representative of the overall population. 

So, we have some issues around access and equity as well as not just good science by continuing to put studies out that aren’t really reaching the people we want to reach. Next slide please. So that’s the landscape, that’s what we’ve seen. But, if we’re going to be patient-centric and we’re going to be patient focused, then we need to talk to patients and we need to learn from patients and we need to listen to what they have to say. 

 

Speaker 2 – Scott Schliebner (19:27): 

So, there was a recent rare disease patient survey that included data from 458 rare disease patients and this group of patients that we asked questions of had either participated in a clinical trial or they had not participated in a clinical trial. And as you can see on the top of the slide, for those that did participate in a study, we asked them what were the biggest barriers that you faced in your personal experience? You can see travel again was number. 

I think that was number one, two, and three in terms of the top reasons travel and time again, there is a little bit of a financial strain if we’re asking people to leave work or get childcare or pay for some expenses for travel to maybe be later reimbursed. That’s just another burden for families that are already managing a rare disease. And, of course, there’s strain and there’s emotional aspects of this as well. 

 

Speaker 2 – Scott Schliebner (20:22): 

For the other group of patients who have not participated in a clinical trial, we wanted to know why. So we asked ’em the number one reason most of them didn’t participate was that they did not meet that eligibility criteria. It was too narrow, it was looking for a artificial patient that didn’t really exist. Number two reason was that the trial itself wasn’t enrolling any longer. Sometimes we go through all the process of opening up a clinical study at a clinical site and the window for enrollment might only be six or 12 months. 

And if that patient isn’t interacting with an investigator and hearing about that trial in a timely manner, that window of enrollment can close before that patient’s even aware trial site was too far away. Again, that gets to travel and time is another issue for why they didn’t participate. And then a lot of times you hear that trials are never even discussed with patients, whether it’s not top of mind of an investigator or there’s not enough opportunity in a patient physician interaction, sometimes we’re not even communicating the opportunity that’s out there. 

 

Speaker 2 – Scott Schliebner (21:26): 

So, this was some insight. Again, 450 plus patients, why did you participate or why didn’t you participate? It shed some light on some of the barriers in the rare pediatric population. I want to shift gears a little bit after talking. Why bother? 

The traditional clinical development landscape has included this process that’s a little outdated and occurs in a bubble and now we see the impact of that in the industry by studies being delayed and running behind schedule. So, as we shift into what are some solutions for this, how do we overcome some of these barriers? We immediately start with including the voice of the patient and the family early in the clinical trial design process. Not just once a protocol’s done and finalized and submitted to ethics, but early on let’s include patients in, let’s get their feedback on the design understanding if they can actually complete and enroll in a study and if it appeals to them. 

 

Speaker 2 – Scott Schliebner (22:34): 

So, there’s a lot of different ways we can do that. Of course, we can hold patient focus groups, we can do live protocol simulations, we can talk to parents, families, caregivers, advocacy organizations and run this concept by them and ask if their constituents can, this would appeal to them. Again, they are the ultimate customer, they are the ultimate stakeholder. They are who we rely on enrolling to move things forward. 

It is a little ironic that historically, we’ve not really asked for their input for what they’ve thought about the trial that we require of them. In addition, of course, many of you have been involved with natural history studies or registries. This real-world data (RWD) really provides some great metrics on disease progression, what characteristics make up a disease? It can help us choose eligibility criteria that are realistic. And then of course working with organizations out there. 

Patients know their disease the best. They know what they need, they know what they can handle. Taking that protocol development out of a bubble and actually interacting with patient organizations doesn’t have to delay protocol development timelines. These things can be done in parallel. It’s just a matter of, as Alison said, changing your mindset to be thinking about your ultimate customer maybe a little earlier in the process.  

We can move on to the next slide. I’m going to hand it back to Alison. 

 

Speaker 3 – Alison Sampson (24:05): 

Yes. Scott, as you said, it’s very important to explain what it is to take part in a clinical study picking up on the natural history studies. It’s quite common now to run a natural history or a real world evidence study followed by a therapeutic study. And the reason that we do that is because as I mentioned earlier, quite a lot of rare diseases are not well understood. 

So, to actually run a therapeutic study, it’s very useful to know how that disease progresses, what complications they might have. As you said, it could influence inclusion exclusion criteria. So that’s something that’s very useful and can actually change the whole landscape for a disease. Once there is good understanding of the disease progression for particular mutation for example, then this is really valuable information, not just for the ongoing study but for all ongoing studies that information about how the disease progresses is really, really important. 

 

Speaker 3 – Alison Sampson (25:11): 

However, to recruit parents and children into study that’s not therapeutic is very tough. And as we mentioned earlier, to overcome the barriers of travel, of finance, of hassle, all the rest of it, a natural history study is really not that attractive. So we need to make those studies and also the therapeutic studies, but particularly these foundation stones of understanding the disease attractive to parents and children. 

And with all studies actually irrespective with a rare pediatric or otherwise, the better a parent or a child or a patient is informed about the study, it’s well documented that they’re more likely to buy into the study and consent and be retained. As we mentioned both Scott and I earlier, huge dropout in pediatric studies, rare or otherwise. So what we’ve looked to do is to try and improve the informed consent process. And here I’m just going to talk about what are the tools we have, but there are many and anything that improves this process is worth having. 

 

Speaker 3 – Alison Sampson (26:23): 

So what we are doing in a current study is we’re using an informed consent flip chart and that has been carefully designed so that one side, the person taking the consents of the investigator or the sub investigate is looking at all the points he needs to go through with the parent or the child, depending if the child’s old enough. And then on the other side there’s that same information but nicely presented to the parent or the child in a much more simple way. And this process is in addition to the informed consent process or the asset process. 

As we know, informed consents now ever longer pages and pages now of quite difficult language, which is often required for legal reasons and then hard to simplify. So these tools that we are developing are in addition to that and to get the parents or the children to understand why we’re doing the study, what’s in it for them, if there is anything, if there’s any therapy or not, and really get them to have a good understanding of what it’s going to be to take part. 

 

Speaker 3 – Alison Sampson (27:36): 

How many times are you going to have to come to the clinic? Are they invasive procedures? Are they going to hurt? Are we going to get any reimbursement? Will we get help with travel? So all these things, all this information we aim to give to parents and/or children in this process. And this particular flip chart does make for a very nice standardized process across sites. Sites using this flip chart run through all the points on the flip chart, which hopefully covers all the points in the consent form. 

So, at a minimum, we’ve got that. And then anything more that the site tells the parent, or the child is a bonus. It is a very nice consistent consent process which is robust and one that you could rely on. And as we move obviously forward into more technological ages. I mean I’ve seen iPads used electronic tablets, all sorts of ways that this information can be given to parents or their children at time of consent. Next one please. 

So, this is just going back to as we talked about the study burden and I think Scott, you were going to go through some of some of the things that we can actually mitigate. 

 

Speaker 2 – Scott Schliebner (28:54): 

Yeah, happy to do that. I see that we also had some additional attendees join since we got started. I wanted to pause for just a second and remind you that we do have the chat function over within the tool that you can list some questions. We’ve talked a little bit obviously so far about what is a rare disease, what is a child definitions of things like that traditional drug development process and why it’s not really working. We need to evolve and we’re starting to talk about a little bit of some solutions. 

So, if you’ve got a question, feel free to populate it in the chat. We’re a little over the halfway mark, but we want to make time for that. Also, if you don’t have a question but maybe you have a comment or you have an experience that you’ve from your own experience with study something that you’ve done that was a nice patient-centric approach that you’d like us to share with the audience or anything needing clarification, we’d love to hear some of your input and we’ll get to those questions shortly. 

 

Speaker 2 – Scott Schliebner (29:52): 

So shifting a little bit here to thinking about, we talk about patient centricity, we talk about including patients in the process and the voice. Alison’s highlighted a nice little practical tool that can be used to better educate and inform and communicate. So what I’d like to talk about now is just the burden of study participation. So the clinical trial that we’ve designed, what we’re asking patients and families to participate in. Again, in the context of rare and pediatric studies, we know that we’re almost always dealing with, it’s either a child and a parent or maybe it’s a parent and a caregiver or maybe it’s an elderly family member and someone younger taking care of them. So we’re really talking about enrolling an entire family in a study for the most part in this space. And when we enroll a whole family in a study on top of the rare disease or the pediatric considerations they’re already managing, there’s a burden to the study. 

 

Speaker 2 – Scott Schliebner (30:54): 

So, we’ve talked a little bit about this already. So in front of us is a couple points regarding the trial design and things we can do to make it easier for patients. So again, involving patients and advocates and caregivers early and upfront in your design process. I can’t tell you how many times we’ve looked at final protocols and said, this is great. Here’s a couple comments. And usually a response we get is, well, the protocol’s final and it takes too long and it’s too expensive to amend it. So we’ll think about that the next study we do. 

So, that’s great, but let’s move this conversation further upstream so we can involve those patients and get that feedback before we finalize that study. What levers can we use? And by that, I mean within a study, within the different visits and assessments, we’re asking what levers can we do to push and pull to make things easier? 

 

Speaker 2 – Scott Schliebner (31:53): 

So in the world of post pandemic 2022, we can readily use telehealth. We can readily use home healthcare nursing, we can readily use wearables and other remote data collection devices. We can make studies more easy and friendly for patients that lowers the burden of participation. It might require us to think a little bit differently. 

It might require us to incorporate maybe another vendor or solution into the process might require us moving something away from a clinical site to a patient’s home. But there are things we can do to make a study easier for patients. And sometimes just opening up that schedule of evaluations and asking yourself, is this time point critical? Is this data point essential? And does a patient have to go to a clinical site for that or is that something that can be done remotely? 

On the lower left here, this idea of this field of dreams, of course if anyone’s seen the old kind of fantasy baseball, we used to open these studies up and say things like, well, patients will come, we’ll open the study up. 

 

Speaker 2 – Scott Schliebner (33:04): 

Our drug is so great, they really need something. They will come, they will join the study. We’ve learned pretty clearly and the data shows patients will not just come if it’s really burdensome, if it requires a lot of travel and time and if it just takes a lot from them emotionally, financially, otherwise they won’t come, which is why 50% of studies are now behind schedule. 

So we have to lose this idea of, oh, just deal with the inconveniences. We want to flip the conversation a little bit back to mindset, what do our ultimate stakeholders need and what can they handle because we do not move forward without the patients enrolling. So on the right side of the screen, there’s a couple other pieces here around solutions, decentralized trials. We can talk a little bit more about that. I’m hoping there’s a couple questions in the chat on that. 

 

Speaker 2 – Scott Schliebner (33:58): 

But thinking about meeting patients where they are geographically, but also maybe thinking about their age, their technology savvy, their ability to, some patients would love to have nurses come to their home for assessments. We’ve also spoken with patients who say, I live with this disease all the time. I really don’t want any healthcare professionals coming to my home. I want to have this be a safe bubble where I don’t deal with a clinical trial in my house. 

So, it’s about sort of learning where your patient’s at and customizing something for them. Patient concierge, patient navigator solutions are out there to help patients either in the upfront screening process or educating and informing them about the study, connecting them to clinical sites, but also being a support line for them if they have questions, if they need help coordinating travel, if they need help coordinating any other aspects of a study, we can create some type of support system the way other industries do for us as customers, the way we can reach out to a chat or a phone line to help us. 

 

Speaker 2 – Scott Schliebner (35:08): 

And lastly, back to this whole back on my soapbox, including the patients in the design. You can also include the patients throughout the process. So once your protocol is final, getting feedback on patients during how was your study experience? Would you enroll in this trial again, what are some things we can do to make this easier for your family? And then of course, involving patients after the fact and making sure that we communicate study results to them is really important. 

So, the burden of study participation is real. There are things we can do to minimize it. Here’s a couple ideas I hope that you’ll take down and consider when you’re moving forward with your next study. We can move to the next slide please. Thank you. So burden reduction. So if we make studies less burdensome and easier for patients, more patients enroll, dropout decreases, studies move along faster, clinical development costs actually go down and the entire cost of developing medicines decreases. 

 

Speaker 2 – Scott Schliebner (36:16): 

So, there is a trickle-down waterfall effect of the clinical protocol. If we can make it more patient friendly, the downstream effects on everything we’re doing become a little easier and a little more efficient. The impact can be dramatic. Less burden of course means that we’re also probably getting a more representative and non-traditional patient population, which is what we want. That can lead to more diversity. 

Of course, at the end of the day, we’re here because we want to conduct good science, we want to protect patients, but we also want to make sure that we’re conducting studies that are representative of the population that’s going to later use that new therapy. Okay, so let’s say you’re fully on board with this concept. Let’s say you love patient centricity. You want to include patients in the process. But let’s say you have colleagues who are skeptical and think this is just a fuzzy, soft, nice concept or a buzzword or a trend that’s going to go away. 

 

Speaker 2 – Scott Schliebner (37:21): 

Maybe you’re concerned about the impact or it delaying things for you or perhaps the cost. There’s a copy of a paper here by DIA and the clinical trial transformation initiative that also takes us a little further. So if you need some ammunition to bring to your colleagues, not only is this the right thing to do for patients, not only is it better science, it actually has a financial return on investment. 

There are dossiers and data out there that show making your study patient friendly saves you money. It saves you money in the short term and in the long run. So happy to share some details if you haven’t seen this paper before, but if you need to, if you’re on board, but you need to sort of show the financial component to others, there is a good rationale for why we want to do this. 

I’ll turn it back over to Alison on the next slide. I do see a couple of questions coming in. Thank you. We’re going to get to these shortly. 

 

Speaker 3 – Alison Sampson (38:20): 

Scott, yes, I love your analogy with the field of dreams and many times worked on studies where the patients haven’t come. One of the things that we are doing not only in the rare pediatric space, but in general for clinical research, it’s to develop a trial identity. We do this for a number of reasons. Probably the main reason is it’s just nicer. 

Most protocols are a mixture of numbers and letters and it’s quite personal and certainly they’re quite long, some of them not very memorable. In a clinical trial where you’re going to rely on things like referrals or feedback from other investigators or advocacy groups or parents themselves, it’s just useful and nicer to give a trial a name and that name can really reflect some of the aspirations of the trial. 

It can obviously be a logo which could represent some of the colors of the sponsor company in general. It’s not a very expensive thing to do and it’s something that we really recommend, particularly for trials where recruitment is going to be hard and by definition, rare disease trials, recruitment is hard. So, this is something that’s one of the things, not a huge amount of money that would make a difference. And many of the things that we can do to mitigate some of the barriers to run pediatric studies don’t cost a lot of money. Some do, but yeah, this one doesn’t. 

 

Speaker 2 – Scott Schliebner (40:13): 

Great, great. So, there’s some good questions. One of the questions that’s come in from the chat, which kind of feeds right into this sort of slide, is a little bit about, what are some new advances in decentralized trials in regard to rare diseases? 

So, for those of you following along here, if you rewind back to pre-pandemic time, there was some buzz around decentralized models. We were calling them hybrid or virtual studies. There was a little slow adoption. This was a new paradigm. We got nervous about moving things away from clinical sites. There was concern about that. So once the pandemic hit and we realized that clinics were closed or patients couldn’t travel to a clinic and we needed some other kind of solution, we very rapidly pivoted as an industry into DCTs, which have really, honestly, kind of adopted some practices that we’ve used in the rare disease space for quite some time. 

 

Speaker 2 – Scott Schliebner (41:17): 

So when you talk about advances in this space, decentralized to me and maybe to some of you is really a spectrum from on the far left is something that is completely site-based to the far right would be something that has no brick and mortar site visits whatsoever. So historically, that whole traditional drug development paradigm, we’ve all been very site-based and we’ve seen that the burden on patients of travel and time and expense is real and it affects them and it affects our trials and that’s why we’re behind schedule on so many. 

As we move along that spectrum to taking some things away from a site and making them more virtual and bringing them to patients where they are, we move into more of these typical hybrid DCT models where we’re typically relying on, in the most case, telehealth where we can do video check-ins. We’re relying on nurses who can travel to a patient’s home not only to do blood draws and physical exams, maybe to support and train on drug administration and there could also be some other evaluations that occur there. 

 

Speaker 2 – Scott Schliebner (42:27): 

We’re also seeing mobile labs being developed in vehicles that can actually travel around and bring things like a CT or an MRI scan to a regional location. We’re also seeing groups like CVS and Walgreens and Walmart start to open up things like minute clinics in remote rural areas to allow for some clinic visits and sort of satellite visits to occur for a clinical trial. So, I think that’s another new development is that we’re seeing this DCT model move towards what makes it easy for patients. 

Some studies of course, are going to really need to rely on a lot of site-based evaluations and administering a gene therapy or conducting a PET scan is not probably going to happen in a patient’s home in the near future. But the reality is that there are many things that can move. And so it comes back to that. 

Take a look at your study, go right to that schedule of evaluations and really do a deep dive on what has to happen at a site and what can maybe move towards more of a hybrid or patient focused approach. So, the graphics in front of us speaks exactly to that. Moving on to the next slide. I’ll hand it back to Alison. I think we’re right near the last of our slides and glad we’ve seen a couple of questions come in. 

 

Speaker 3 – Alison Sampson (43:52): 

Yeah, indeed. Actually, I did see a question about the flip chart, and this takes us into the realm of vendors that we use. The flip charts that we’re using currently on our rare pediatric studies are being developed by medical communication agencies, and they are actually quite a lot of work. There is no one size fits all, but it’s worth the input into producing some quality parent facing materials because we want to keep those parents and those children engaged and in our studies. 

So yes, it’s not a cheap thing to do. Yes, it takes time. Is it worth it? Absolutely. And then there’s some other centricity vendors that we use at TFS and there’s a longer listlessness, but just to give you a flavor of the sorts of things that we use. So, travel reimbursement is something that is very common and as Scott said earlier, many of our patients live some significant distance from the trial centers. 

 

Speaker 3 – Alison Sampson (44:54): 

And just to pick out one concierge who’s actually a very nice vendor, they usually have someone who speaks local language dedicated to the trial and to the parents and child in a particular country. Not cheap, actually, none of these services are particularly cheap. 

But as Scott mentioned, yes, it costs more, but ultimately if you want your trial to succeed, ultimately there’s a cost saving because you’re much more likely to have a successful trial. And then there’s other things just quickly going through this. Prepaid credit cards so that parents can offset things like meals when they’re at the clinical site, vouchers, travel assistance, hotel assistance, even I knower definitely do babysitting type assistance for other children. 

So, as we said before, these things all cost, but ultimately it is worth doing because if you manage to keep your parents and your child in the trial and they don’t leave after the first visit because it’s too difficult, then ultimately there is a saving there and you’ll get a successful trial with successful data and it won’t finish in the 50% group that never finished and it go by the wayside. So there were many vendors that we can use and are using and you can use to mitigate some of these burdens to participation. 

 

Speaker 3 – Alison Sampson (46:34): 

And this is just a quick one. I know we’re coming up. So this is one of the things we developed particularly at TFS for parents and children. And this is a parent facing document which we customize for the particular trial. And this is to get the parents to think at the time of consent more critically about whether the trial is right for them. And it’s a questionnaire, we don’t collect it back, it’s just to get them to think critically about is it right and to prompt them to maybe to ask some questions. So can they take time off work? Can they bring other children with them? Would it be too burdensome? Are they against perhaps some invasive procedures that the trial protocol has in it? 

This is what we call it, the stepping stones, and it’s better for the parents to withdraw or not even start a trial then to come to that first visit and never come again. It’s better for them not to consent at all if they think the trial’s not right for them. So this is something that we’ve developed to try and stop that massive dropout right after the first visit. 

 

Speaker 3 – Alison Sampson (47:44): 

Hopefully we’ve shown you some things that you can do to make a more patient-centric clinical trial. Either for children are old enough to be patients themselves or for parents and children. There are many things we can do. We’ve only, as I say, shown you a flavor in the time that we’ve got of the things that you can do. But it’s really important that we think very carefully about the whole design process from even pre protocol right through to Scott mentioned providing results back to parents. How can that be a nicer process? Because if it’s nicer, if it’s better, we’ll all benefit from that. 

 

Speaker 2 – Scott Schliebner (48:27): 

Thank you, Alison. Excellent. So, we’ve got some questions. I know Samaya, I think, is going to jump in here, but again, we’ve covered a little bit on what is a rare disease, what is a definition of a pediatric patient, and additional drug development processes sort of not really working. We need to evolve. We’ve given you a couple of practical ideas and tools around thinking about changing a mindset and actually implementing some changes. It’s been some good questions here as well. 

Samaya, are there a question or two that you wanted to make sure we all hear and can address? 

 

Speaker 1 – Samaya (49:05): 

Thank you, Scott. Yes, so audience members, you can still continue sending questions for Scott and Alison. Yes, Scott, we did receive some interesting questions. So, I’ll start off with the first question. Scott and Alison, that question is, 

“What are your thoughts on the new version of I-C-H, I-C-H-E six R three and the patient centricity requirements?” 

 

Speaker 3 – Alison Sampson (49:28): 

It’s very nice to see that in the ICH guidelines, and I think I touched earlier on the fact that patient centricity is a mindset and that it’s something that we need to think about throughout the whole trial process. That new version of ICH, I think annex two, is due later this year. Also looks at diversity in patient recruitment, which Scott touched very nicely on. 

So, going forward, we want diversity. We don’t want half of our patients to be middle-aged men who are white because they’re not representative of all people with a rare disease. And there were many as I mentioned. So, it’s very good to see ICH go this way. And yeah, I think it’s validation that patient centricity is good for everybody and is even cost effective. 

 

Speaker 1 – Samaya (50:24): 

Thank you, Alison. And we have another interesting question from an audience member and that question is,  

“Patient and KOL involvement early on in study design is one aspect of optimizing the clinical trial planning and conduct. What about optimizing the country and site selection feasibility?” 

 

Speaker 2 – Scott Schliebner (50:47): 

Sure, that’s a great one. Yeah. Well, we’ve talked a little bit about patient input. Let’s not forget about our investigators and KOLs that actually need to implement these studies, right? It’s a great question! So, as we include that input in the rare pediatric space, you have some additional challenges as we’ve outlined above and beyond more typical indications. 

When you’re thinking about which countries you want to take your study to, it comes down to some of it is where are patients? So, we work in a lot of different areas like a beta thalassemia study where you may only see patients in certain geographic regions associated with some different ethnic backgrounds. 

So, you may have to go to certain regions, maybe some untraditional areas to enroll your study in to find those patients. Another consideration is thinking about a rare disease. Alison and I are working on one right now. 

 

Speaker 2 – Scott Schliebner (51:42): 

It’s a very rare dermatologic condition. There’s only a few highly specialized centers that can actually sort of manage patients with this complex condition. So that almost defines which countries we can go to. So we’re looking at a host of countries where there are these specialized centers, there’s other good countries that are just not even an option because we don’t have the centers. And then lastly, I think when you’re thinking about where to take your study to and optimize it, also, you can think too about are there country level disease specific patient organizations in those countries? 

For example, let’s say there’s a specialized center in Germany, is there also a patient advocacy organization in Germany that might have a registry of all of the patients in Germany that might make Germany really easy to open up a study and connect with patients? Some countries don’t have that kind of developed yet. So those are a couple considerations around specialized centers, thinking about disease background and where that occurs and advocacy organizations. And Alison, I welcome anything if you’d like to add to that. 

 

Speaker 3 – Alison Sampson (52:59): 

Yes, I think just to touch on the fact that for rare disease we often have to go where the patients are and they tend to be all over the place. I’ve worked on a study to recruit a hundred patients from a hundred sites. That was all over the world and I think we have to be prepared to do that to make our trial successful. So yeah, I think it was indeed a very good question. But yeah, we have to be prepared to do all sorts of things to make these trials work and it is important and it’s worth it. 

 

Speaker 1 – Samaya (53:32): 

Great. Thank you, Scott and Alison. Our next question is,  

“What new development trends in the next five years are in the rare disease space with the advancements of CRISPR and other gene therapies, what does the next five years look like in your opinion?” 

 

Speaker 2 – Scott Schliebner (53:53): 

Great question. Alright, break out your crystal ball here. Well, one thing I’ll jump in to start, but one thing I think we’re seeing of course is every year we’re seeing more and more rare diseases become identified, right? We’re learning more about the genome, we have more sophisticated genetic testing, something that we used to think of as a disease now as a condition with four subtypes. So we’re learning more. 

I think we’re going to see more and more disease types. Some that aren’t even rare, become further subdivided into, we see this in the oncology space where we’re looking at a tumor type with a certain kind of mutation or things like that, and you end up with just a little slice of those patients. So I think some of the rare disease learnings will get applied to some other therapeutic areas, I think, which will be great. 

 

Speaker 2 – Scott Schliebner (54:49): 

I think we’re also getting improving improvements on, for those of you who’ve been in the rare space for a while, you’re familiar with the term diagnostic journey where patients and families often have to go through multiple, multiple physicians and healthcare systems to even try to find the accurate diagnosis for what they have so then they can start to pursue a treatment. I think that part will start improving quite a bit. I think you’ll also see more and more pharmaceutical biotech companies as well as labs and other testing facilities slowly continue to move into the rare space because again, collectively rare is not rare. When you take all of these little rare diseases, they add up to 10% of the population. So there’s a lot happening out there. Those are a couple things I guess that I think of high level. Anything you’d like to add, Alison? 

 

Speaker 3 – Alison Sampson (55:44): 

That was a wonderful answer, Scott. The only thing I’m really thinking of is patient-centricity. I think now we’re seeing even in regulatory forms, I’m thinking of the MHRA where they’re asking, have you asked any patient groups? Has there been any patient centricity input into this protocol? People start to look for it now. It used to be a nice to have, but it’s become so much more important. So, I think going forward, I think the involvement of patients and in the rare disease space, I think you also said that a lot of them been through quite a journey, particularly in the less severe diseases adulthood without having a proper diagnosis. 

So, I think that’s going to improve. I think with all the things that we’ve got, I mean, there are companies now that have online patient groups and information is much more readily available about rare disease. So I hope that those sorts of things will improve and that patient centricity will perform a much bigger part of a trial and it’s not just in yougo and suck it up basically. If it’s two hours to the site, that’s tough that we are going to be doing more of. Well, we can have the nurse at home or we can provide travel assistance for you. That will be a lot more of that too. 

 

Speaker 2 – Scott Schliebner (57:09): 

I totally agree. I realize we’re almost out of time here, but the concept of patient centricity and thinking about patients as again, the ultimate end stakeholder here won’t hopefully be a novel concept in the future. This will just be baked into our process. So we see other industries, we see iPhone makers putting cameras on a phone, not just, they don’t build a new phone with a camera to say, oh, I wonder if our customers will use this, right? It’s all driven by the customers. 

So, that idea of other industries are following the lead of what people want. I think we can do a little better in clinical development of following the lead of what our patients want and hopefully that’ll, and even extending beyond patient to family and starting to think about caregivers as well as part of that whole entire sort of family really that’s enrolling in a trial. I’m hoping that that gets fully kind of baked into how we design studies. 

 

Speaker 1 – Samaya (58:14): 

Wonderful. Thank you, Scott. And thank you, Alison, for all of those answers. We reached the end of the Q&A portion of this webinar, but attendees, not to worry! The team at TFS HealthScience may follow up with you later on. 

If you have further questions, you can go ahead and quickly jot this down info@tfscro.com for further questions or comments. I know that we did receive a lot more questions, so attendees keep using this if you do have more questions. 

I want to thank everyone for participating in today’s webinar. You will be receiving a follow-up email from Xtalks with access to the recorded archive for this event and a survey window will be popping up on your screen. Your participation is appreciated and will help us improve our webinars. 

I’m also about to send you a quick little link in the chat box right now. You can use this link to view the recording, so that should take about one to three business days. You can share it with your friends or colleagues, whoever might be interested in as well. 

Now, please join us in giving a big thank you to today’s speakers, Scott Schliebner and Alison Sampson for that fantastic presentation. We hope you found this webinar informative. Have a great day everyone. 

 

Speaker 2 – Scott Schliebner (59:28): 

Thanks, everyone. 

 

Speaker 3 – Alison Sampson (59:29): 

Thank you. Thank you, everyone. Thanks for coming.