Trials with Maya Z

Maya TrialHub (00:00)
Hello everyone, this is Maya Z and I'm here with a dear, I would say friend of mine because we already know each other for such a long time, Begonya Nafria. I met Begonya in Barcelona many years ago and there is no chance for like, there is no chance to not actually recognize Begonya because Begonya speaks loud about some of the most important challenges and some of the most important problems

of important problems that we have in clinical research, all around pediatric clinical research. Begonya is from Hospital Sant Juan de Déu And I'll leave Begonya actually to introduce herself. Welcome, Begonya.

Begonya Nafria (00:43)
Thank

Thank you, Maya, for the invitation to participate in this podcast. For me, it's a pleasure to contribute and to share my experience working at Sant Juan de Deu Children's Hospital. As you have mentioned, this is the largest pediatric hospital in Spain, and my role in the institution is to be the head of the patient engagement and research department. And mainly, my position is devoted, as you have mentioned, to work towards the rights of the children and the young people,

in the field of health research because we know that there is a room of improvement and we need more research and specifically better research for children and young people.

Maya TrialHub (01:25)
Yeah, absolutely. was sharing with you, Begonya, just before we started, that when I co founded Find Me Cure in 2016, I was telling the story to, I mean, I'm pretty open about the reason why. It was my sister having her disease and all the nightmare that we went through with her. But in 2016, actually, it was a big milestone for me as well because I became a mom.

And that's when I started seeing my sister's disease from the lens of the mom. And I was like, my God, like imagine if any of my kids, actually if I have to experience that, if your kid is sick and they have to go through research because they don't have treatment, it's just next level problems, next level experience. And I don't wish that to anybody. At the same time, we know this is happening, unfortunately.

So I'm so grateful for people like you and for hospitals like yours that you're fighting really for better access to treatment and for more engagement of these families in these projects, in these treatments and clinical trials so that at the end of the day we have more meaningful treatment at the end of the day. And begonia for the ones, yeah, I'm sorry.

Begonya Nafria (02:46)
Yeah, reality. Yeah, no, no, it's only to comment that the reality that we face in children hospital.

is that basically the disease is that we are treating rare conditions. There are many challenges along the journey. The first one is a diagnosis. Sometimes it's not easy and it takes years. And it's complicated if you don't have the opportunity to access to a hospital with the right expertise for this diagnosis. And 80 % of these conditions are genetic. It means that probably the onset of the conditions is at the moment of the birth

Maya TrialHub (03:05)
Mmm, yum.

Begonya Nafria (03:24)
in the very early ages of children. Another challenge is that when you have a diagnosis, the opportunity to access to a treatment. 95 % of the rare diseases have no treatment approved. It means that in some cases if we are lucky we can treat symptoms, but anything else. And at that moment there are many opportunities with gene therapy, cell therapy, everything under the name of personalized medicines, but this is not for everybody.

Maya TrialHub (03:25)
Hmm.

Mmm.

Begonya Nafria (03:54)
And there is also the best -case scenario to have a research project for a new treatment, a clinical study for your condition. This is probably the best -case scenario, but it's not in the majority of the cases what we have. In some cases, we don't have nothing to offer to these families. For the reason, as you said, it's really, really important to have more investment in research, from the basic research, of course, to the clinical research.

Maya TrialHub (04:03)
No.

Yeah, you remind me of a conversation I had with another friend of mine who also is very active in pediatric research. I think she's from the ICONs Pediatric Research Center. I'm pretty sure you know her, Jacqui She was telling me about this discussion, how ethical it is to run clinical trials on kids. And actually, my question, I think it was, let's say, whoever is involved in pediatric research will say how ethical is not to

research with kids because would you like, do you think it's better to provide a treatment to your kids without being validated that actually this is going to work or it wouldn't work. The other thing that reminds me is another conversation where we were discussing disease prevalence among kids and actually by default kids are supposed to be healthy. Unfortunately, sometimes they're not.

And that's why a lot of the diseases, if not the majority, and that's why you mentioned, I think you mentioned 80 or 90 % are these rare diseases. So by default, when you have a pediatric unit, most of the time you're literally facing with rare diseases. And then like you said, there are not many treatment. And the only way to get treatment is through research.

But Begonya I wanted to also understand a little bit more about the work that you're doing around patient engagement. And more specifically for the ones that are on LinkedIn, I'm pretty sure you saw Begonya, how passionate she was asking for contribution to a few surveys in different languages. That's actually regarding a very big initiative that Begonya started. Some time ago, I'm not sure when exactly you started this project, but very noble project. And I actually invited

mainly for you to tell us more about this project. What's the reason and where are you today and maybe how we can further support

Begonya Nafria (06:22)
Thank you, Maya, for asking me about this big initiative that, by the way, it's important to mention that has the support of a working group in Enpr-EMA the European Network of Pediatric Research of the European Medicines Agency. And the story about this research project started a year and a half ago, more or less, when I received the information about a specific situation that was at that moment.

identify let's say in our hospital but afterwards I saw that was common in other hospitals and at the same time I was thinking to do my PhD and to move forward with a project.

that could be relevant for the community of patients. And what we saw as a challenge or as an issue is that in pediatric clinical trials, as we have commented, basically we have experimental treatments for children in rare diseases. And these studies usually are not open in all the European countries. It's impossible because it's rare diseases, small numbers, and usually the involvement of countries, it's small.

numbers also. And in this sense what we have seen is that in some cases it's not possible the concept of the cross -border access to pediatric clinical trials because patients are excluded for the language that they speak for their mother tongue. In the case of Spain if you don't speak Spanish

Probably you are not eligible for clinical trials in our site or in others from Spain. Or also in some cases, also if you don't speak English, because let's say it's the language of science, everything usually it's in English. And it can be as, let's say, a plan B or another opportunity to incorporate patients from abroad. But seeing that in some cases, criteria about language has been used as an inclusion or exclusion criteria, it moved me

search if it's a common problem and I saw that it's a common problem across Europe because not always we are ready to incorporate patients in the 24 different European languages and in some cases it's the willingness from the research team that it's leading the study to adapt everything and also from the sites because not everything is a matter of the sponsor of the trial also the site needs to be ready but in other cases there is no willingness or no opportunity for this.

And specifically we saw that in some projects where the patients were excluded, where phase three trials, it means that they are really close, you know, to probably see if this treatment needs working good and it can have more benefits than risk in rare diseases, as I said, and in some of these cases with no approved treatment. And it's so sad from a side perspective, from a scientific perspective, saying no to a family because they don't

the criteria of the language, that it's the official language of the country where the study is performed. And this move me...

to start my research, to collect data, specifically at that moment I'm collecting data from sites, from the professionals that they organize clinical research units and they lead as API clinical trials from parents and young patients because I think it's important to learn from the experience of the ones that they already traveled to another European country for participating in a clinical trial, but also for the ones that they don't have this experience but to learn also

from these preferences because probably artificial intelligence, DCT options probably can reduce the burden of this trial because not everything of course, it's a matter of the language. We need to think that these families, need to move to another country. Sometimes it's literally move and live there. In other cases, it's many travels and to be overnight in another country, it's a big burden in any case when

trial is not performed close to the home of the families. And this is what we are at that moment exploring. Also, of course, learn from good practices from pharma and from academia. And the final, final outcome would be a guidance to provide some recommendations and facilitate the inclusion of patients in these studies. We cannot change the regulation, and there is no regulation specifically for cross -border clinical trials. But I think that it's important to take advantage of these good practices.

And the cases also of discrimination, learn and share these expertise across the different stakeholders working in in pediatric clinical trials to see if in a close future cross -border studies would be more accessible for patients.

Maya TrialHub (11:08)
Begonya, is there any regulation for cross -border treatments today? No. Is that actually the challenge? Because if we don't have a cross -border treatment regulation, maybe that's contributing to not having a cross -border clinical trials regulation as well.

Begonya Nafria (11:16)
Yeah, for dreaming, yeah.

Yeah, of course, if at some point we have a regulation, everything will be stayed there and there are rules that are established and the different stakeholders they need to follow. But as you can imagine, this is something that cannot be achieved in a short term. And there are also other initiatives. My project is only focused in language discrimination and in pediatric clinical trials, but also there is another big initiative led by EFPIA, the European Federation of Pharma companies and also EFGCP, the European Forum of Food Practices that also I'm

that it's looking for what needs to be improved and adjust to make feasible these cross -border studies like we have, you know, the opportunities for healthcare. But now it's, let's say, again, an initiative doing this research and, you know, putting on the table where are the needs and where are the preferences and hopefully, I don't know when, but hopefully, you know, use this information to promote to have some regulation at the European level because it's the way to

to everybody the same opportunities and in Europe, although we have many different countries, everything is managed under European regulations and hopefully at some point we will have this. But this is a long journey and I think that we are just starting, which is good, but we need to work a lot to provide evidence, lessons learned and put on the table of the people that at the end take the decisions to move forward with new regulations that this is a need and it's feasible.

of course as everything that we do it can benefit the patients.

Maya TrialHub (13:03)
Okay, so what are the biggest lessons so far from this project, from the data that you've managed to collect?

Begonya Nafria (13:12)
Yeah, the big lessons is that

Cross border clinical trials in pediatrics, let's say it's an it because the average of countries in Europe involved in trials, not specifically in pediatrics, it's really low. It's close to 3 .5. It's not a big number. It means that the probability to have a trial for the condition of your child in your country, it's really, really low. This is one of the lessons learned. It's an it there. Probably nobody identify also

issues that at some moment, you know, the sites we are facing because also I'm analyzing how the sites on top of everything that is, know, in the protocol, they help to provide the best experience to the families. And this is something that I want to highlight because the sites provide translators, people, you know, with the right expertise. Also, not only in the language, also in the culture of the families, they help to manage if it's

you know some you know visa or whatever because not everybody of course I'm focusing Europe but also sites from Europe we are receiving patients from outside of Europe and here the challenge it's bigger because we need to deal with you know visa and other specific you know administrative stuff and I want to recognize you know the role that the staff of the sites are doing because in one trial you can have sometimes patients and it's the case of our hospital that

All of them are from abroad and non -Spanish patients. And it means that you need to deal with your research nurses and all this stuff with families from sometimes five, six or different languages and nationalities. And I think that usually this reality it's not well known.

Maya TrialHub (15:01)
Yeah, it's kind of the invisible work of the clinical trial staff that is doing that is one more thing that contributes to their overall burden because the topic of clinical trial burden on the site is very famous, but we always speak about tech, the documentation, but you're absolutely right, Begonya. There is a lot of work around the patients themselves in the case of like a kid.

adolescent for example, you have to deal with their families and their cultural differences. Actually, yes, you're bringing a very, very, very good topic. Have you learned any good practices? Because you mentioned that you're exploring what happens with cross -border treatment. So is there a barrier? what is, okay, what are the main barriers for accessing cross -border treatment? Here I don't speak about clinical trials on purpose.

because I'm trying to understand, we learn something from cross border treatment and apply in cross border clinical trials? And one clarification also, if you can elaborate on that, what is the big difference, what are the differences between cross border treatment and cross border clinical trials?

Begonya Nafria (16:16)
Yeah.

Cross border treatment at the end, it's an agreement between the state members and the health systems. And this is established in a regulation and there are on place some specific procedures. But when we speak about clinical trials, our independent research project with the ownership of an academic institution or a commercial sponsor that it's the one providing the design of a specific study. The design includes the scientific piece, of course, that it's really, really important.

but also some other elements that are, let's say, more related to the experience of the participants, like the consent process, because it's mandatory, but also it's based in the process to really inform and be in a, let's say, decision -making process as a young patient or as a parent. This is a big piece where language is important.

because it's not only a matter to translate the document, you need to be sure that if there are specific questions during this process, someone can reply and you can understand this information. It's another big piece also in regards patient reported outcomes, quality of life, questionnaires, patient experience data, that not always we have all these instruments, all these tools translated into all the European languages. But it depends on the kind of questionnaire. If the questions are easy and it's the patient

one that needs to report probably they can be translated. I think that we need to find the right balance between be very straightforward about what is the state in the protocol and accommodate some you know solutions and something that I want also to comment it's about this human piece of research that in pediatrics it's not only the patient it's the whole family and as I have mentioned it's not only the kid with the parents there are siblings for example that also the

needs to move to another country to be six months or a year or even more. Also they travel and they live in another country and they need to go to school. There are many activities that sometimes we don't, you know, at the very beginning we don't realize that are around the clinical trials and it's not only the staff of the clinical research unit, our psychologists, social workers, people supporting as I mentioned the vice and administrative, you know, specific needs that they have. I think that

need to have a global perspective about research and what it entails. Of course, they are volunteers and they provide a common good for everybody with the participation in these studies. But I think that we need to think more in the patient experience and see how we can better design these trials. And something that also we face in general in pediatrics is that in Europe, it's mandatory to execute the pediatric investigational plan when there is an adult development.

And in some cases, these designs, it's impossible that they can fit in the daily life of a child. And also we have another reality and it comes to one comment that you did at the very beginning of this podcast. Children, have diseases that adults, don't have. Here it's the need to do a specifically research with children. Of course, we need to design from the ethical perspective, from the scientific perspective, the right protocol, but it's not also to extrapolate in

cases, you know, information from the adult set into the pediatrics because probably the condition is different or it doesn't exist and the same from, you know, conditions that only the children and the young people they have for the reason it's important to do better research, but also with children and young people and also encourage, you know, the people working in research to promote first pediatric research and not to wait sometimes many years after we have some adult development in this.

that they are so, so different.

Maya TrialHub (20:12)
You just raised another big topic, which is that first you mentioned that in many cases the doctors have to work within the clinical trials with families and patients coming from all over the world. But then also, how different are children treated in their own countries and does this impact their ability to participate in the clinical trial?

Begonya Nafria (20:41)
I think that the standard of care that in general everybody, because at some point all of us we are or we will be a patient, of course affect in many ways. One thing that it's research, always it's on top of the standard of care that you are following. And in pediatrics, we have mentioned that we are speaking about rare diseases and in some cases are very complex diseases that they have very frequent medical appointments. These kids are followed by many different medical experts.

add on top of this a lot of medical procedures, medical visits, complete questionnaires. We need to realize about this. And not always the standard of care is the same in all the European countries. For the reason the concept of diversity, it's at that moment on.

table on the discussion that also it's something that we need to have into account when we design studies in general, not only for pediatrics, also for others, because we need to realize that Europe is diverse. Every country also has their, you know, internal diversity and we need to be sure that the design of these studies fits the needs and the preferences of the participants. And this is the reason mainly about the department that I'm leading, listen the voice of the patients, the parents from the

beginning because it's when the protocol is designed and if we know which is the standard of care of these patients the protocol probably it's more easy to be you know adapted to the daily life of the patients because if we are adding a lot of burden the trial is so long they don't understand in some cases about the need to have a placebo arm formulation of the treatment that also is another challenge in pediatrics it's not the right one probably this trial is not going to move forward or is going to have recruitment

adherence problem. Involves the patients from the very beginning, ensures that the research will be better and of course according to the plan. This is basically the main goal to have you know a very detailed clinical trial protocol designed the right and the best plan for the research.

Maya TrialHub (22:43)
Okay, thank you, Begonya What about if we think the other way around? Because the story that you mentioned from the very beginning, how your hospital is dealing with patients, like with kids from all over the world, their families and these cross -border, I would say technicalities, because honestly, come on, I mean, we live in the world

AI, everyone speaks about how powerful this is, how this can solve everything. And I can definitely tell you translation is the least problem. It's more the human aspect. If you ask me, I'm pretty sure that it's you're the same opinion. But I kind of, while I was listening to you, I started thinking, do we want to solve the problem of providing these language, let's say document, the translations of the documents and the person.

at the hospital that is the center for doing clinical research, do we want to provide this support there so that these patients and families can travel and participate? Or should we think of a solution where, for example, your hospital is the big center for running the research, but they can remotely somehow coordinate this clinical trial with the local doctors, with the doctors of these families and patients?

Is this future even feasible and possible? Have you even thought about this scenario?

Begonya Nafria (24:13)
Yeah, in fact, this is one of the questions that I'm asking in the questionnaire to the parents about the acceptability, let's say, to travel to a satellite center. It means that it's close to your home, but it's not far, no, like the, let's say, the main site. I want to comment that there is no solution for all the studies and for all the conditions because working for many years now in the field of patient engagement and patient involvement, I have seen that every study, every disease, it's different.

that it requires to analyze specifically which countries are involved, which is the condition, which is the best experience for the patients because I have seen in some advisory activities that I have led that in some cases the families, are not worried about the travel. They prefer to do everything in the site. They don't want telemedicine or decentralization of some parts of the study. And this is for me a big lesson learned. One size

doesn't fit all the needs. And I think that it's an exercise that the research team that is behind every study you need to do from the very beginning. And the only way to do it is listening to the potential participants to these studies. Because if they accept some telemedicine solutions, if they prefer to travel to a site that can be closer but it's not the main site and they travel in less opportunities to this site, always there are intermediate

solutions, but for me the key thing is to sit down before you finalize the clinical trial protocol with patients and parents and specifically for this project which is the best option. And of course, I agree, there are solutions for translations, but usually the bottleneck, it's not only about to have this translation, because in some cases, you know, it's the sponsor, the ones that provide these or it's the site. For me, the bottleneck, it's

the validation of some tools and the approval from the ethics committee of this. There are still many elements, but the information that I'm collecting, it shows me that if we want, we can accommodate some translations and some things around that can make feasible discourse border clinical trials, at least solving the language barrier that in Europe, if we are saying that you cannot be discriminated for the language that you speak,

many other elements, we need to promote this and at that moment it's happening in some studies.

Maya TrialHub (26:44)
Yeah, absolutely.

Absolutely. And I just want to mention that at least for cross border treatment, there have been initiatives, at least I know one that it's very, I'm originally from Bulgaria, and I know that there is this amazing organization, it's a non for profit organization called Doctors Without Borders. I think that's the way it's called. And it actually unites a group of people, Bulgarians.

that sometimes even have some sort of a medical background, maybe not at all, but they volunteer to support families or patients when they have to travel for medical purposes in other countries, countries where they feel already established, where they know the system, will help them with all these type of things. So maybe we should be thinking about these type of, it's not simple because I know it's definitely not simple to start such an organization, but I'm just saying that there are these good practices.

out there that we can learn from and see how we can utilize. And I'm pretty sure it's not just in Bulgaria, I'm pretty sure in other countries. And if not, maybe these are the things that European Union should back up, like these type of organizations, not yet another software and yet another platform, though they also have place in the world of optimization. But like very often we forget this human aspect, the human interaction and

I've been interviewing all sorts of thought leaders. All of them have different perspectives. A lot of them also say how important it is to listen to the patient's voice.

And you precisely, you have this incredible expertise for many years, not only to advocate for patient engagement, but to actually implement it. What are these best advices that you can give us so that we can find a way to do patient engagement in a meaningful way and make our projects more successful?

Begonya Nafria (28:44)
Thank you, Maya, for this question. The list is long.

The first point of this list is to mention that involves children and young people in research, it's feasible because sometimes we take for granted that if we involve only the parents, you know, it's the right approach to protect them to be as a participant in these advisory activities. My second advice is beyond that, it's involve all the time that you can the patients, the pediatric patients, because probably the perspective, the outcomes, the insights would be different and also commend that it's

right. We have the conventions of the right of the children that it's know worldwide.

regulation that mentioned two points that I think that always are important to be commented when we speak about the involvement of patients. One is that the children, have the right to access to the best standard of care. And in some cases, you know, clinical research, it's the only opportunity that we can offer to them. And secondly, is that the children, they have the right to be involved in any decision that can matter to them and health needs to be in this list. We cannot take for granted that the parents all the time, they will have the same perspective and opinion

of the children. I think that we need to promote meaningful engagement and it means be done by experts because not everybody probably can lead activities in the setting of patient involvement and also with expertise in pediatrics and ambition that patient involvement needs to be part of the process. I always compare the role of the ethics committee and we cannot go forward with a clinical study if we don't have the green light of an ethics committee. For

patient involvement in pediatric clinical trials, hopefully in the future would be a mandatory step and ensure that we have really involved in a meaningful way the patients in order to have the approval of a clinical trial protocol because this helps a lot.

to recruit the right candidates, to follow the protocol according to the plan and not have issues in terms of adherence, to deliver better treatments, and at the end, offer a better care for the children that they live with a specific condition.

Maya TrialHub (30:52)
And this is also valid not only for pediatric research, for any sort of research. We all know that if we include the patient's perspective, we have better results. But if I am to summarize, we should stop assuming we know. We should stop assuming doctors only know. And we should start asking, asking everyone who is and will be involved in this whole project. Begonya, one last question.

When can we expect, I mean are you planning to publish the results of this project? Can we expect that? And how can we support you with this project?

Begonya Nafria (31:34)
Okay, interesting question. Of course, we will publish everything because this study is done for the common good, as I mentioned. It's coordinated also with this working group that I mentioned at the very beginning of this podcast from the European Medicines Agency for the Pediatric Research Networks. And basically, this year, 2024, our main aim is to collect data. There are different sources of data, sites. If you listen to this podcast and you work in a site, you can contribute.

a parent or a young patient also you can contribute because there is a questionnaire for the parents and also another one that is for colleagues working in pharma companies. This first year it's going to be focused in this data collection. We will analyze this information and hopefully in 2025 we can deliver a draft for a public consultation of this guidance providing these recommendations to demonstrate that the language barrier can be solved and for the reason we cannot exclude children and young people

for participating in cross -border clinical trials. is approximately the timelines of the projects and some specific scientific publications will be delivered. But now we are in the key moment and in the challenge moment to collect this data. And I want to encourage everybody that can listen to this podcast to participate and to help because as much answers we have across Europe and across different conditions, of course, the better for the outcomes of this initiative.

Maya TrialHub (33:00)
Yeah, and actually, maybe you won't be surprised, but many people will be surprised that the very same issue exists even in a country like the United States. I recently interviewed Dan Sfera, who has a site or at least one site that's with a lot of Latin American patients. And they have the same issue even though they live in a country where they know Spanish

Begonya Nafria (33:12)
Yes, it's

Maya TrialHub (33:26)
Yeah, it's the same point. Yeah. Anyway, I will definitely add all the links after the podcast. So whoever can support you in any way, please do that because it's important. It's also for our kids, guys. That's the reality. It's for us, for our kids, for our future. Begonya, thank you so much for your work, for sharing this work with me today.

Begonya Nafria (33:27)
They have.

Maya TrialHub (33:52)
and for spreading this passion because it is important. We need more people, I call them superheroes, to fight for better research because we all depend on that.

Begonya Nafria (34:05)
Thank you, thank you, Maya, for the opportunity to participate in this podcast. And I want also to thank you all the people that they have volunteered to help me in this journey, because nowadays these questionnaires are accessible in all the European official languages, because I have many people around me that they volunteer to do the translations, because I don't speak all these 24 European languages. Thank you so much to all these people.

Maya TrialHub (34:20)
Amazing.

That's how people unite. When you have the passion and the right project, the right mission, that's how you unite people. Yeah, congratulations and thank you. I also want to say thanks to all these people. Thank you, Begonya.