Trials with Maya Z

Maya Zlatanova, CEO TrialHub (00:00)
Hello, everyone. Welcome again to another episode with Trials with Maya Z And I'm today with a dear friend of mine, have to say, because I met Ilknur some time ago, a friend of mine introduced me to her. And since then, I have to say that I've been always amazed by her and her experience. Lately, I've been interviewing mainly patient advocates and patients around

Ilknur Lechthaler (00:06)
you

Maya Zlatanova, CEO TrialHub (00:25)
the importance of underspending the patient journey before starting any clinical trial. And I decided that it's time to really go back to the experts who are actually planning clinical trials, who are actually operationalizing the clinical trials. And one of the first people I thought of was actually Ilknur Lechthaler Ilknur has many years of experience starting from a CRO and then moving her career to more sponsor companies, smaller, bigger organizations.

I reached out to her some years ago when I was like trying to figure it out a few things around our product development on TrialHub And since then, I've been really amazed by the volume of information that she has and the type of experience that she has. So, Ilknur before we start, if you can introduce yourself briefly, and then I'd love to hear your opinion about the standard of care is importance in clinical trials.

Ilknur Lechthaler (01:23)
Yeah, thank you so much, Maya. I'm really thrilled to be here today. So thank you for the invitation. So I'm Ilknur Leichthaler. I have been nearly three decades

in the industry and drug development, clinical operations across a very wide range of therapeutic areas. And I've learned that success in this field goes beyond managing projects. So it's about understanding the complex connections between research development, the regulatory requirements, the commercial landscape, and most importantly, the patient journey in clinical trials.

So understanding the local standard of care and leveraging this knowledge to drive effective strategies is crucial. So I'm excited to share my insights today and explore how these elements can truly transform clinical trials.

Maya Zlatanova, CEO TrialHub (02:12)
Thank you very much for making the time, Ilknur. I'm currently focusing my mini -series on understanding why it's so important actually to understand the local standard of care before starting any clinical trial, while planning clinical trials and while you're conducting clinical trials. So from your career, how did you think about and how do you today think about standard of care and do you even take it into consideration?

Ilknur Lechthaler (02:42)
So when I go back 30 years ago, I think this was a very unknown field. And I think only during the last 10 years, there is some awareness how important that is. So said that, skipping country -specific patient journeys or a standard of care, that is a significant challenge to the industry nowadays.

And I think it's very important to have a deeper look into that. So it's true that time and resource constraints often lead companies to take a more generalized approach, but this can be a very costly mistake in the long run. When companies overlook the nuances of local patient journeys and the standard of care, they risk not only delaying trial timelines, but also disengaging the very patients they hope to help.

So, yeah, let's explore this a little bit. You know, let me start also with the patient journey. In each country can differ drastically due to factors like the healthcare infrastructure, cultural attitudes, economic conditions, and even the availability of medications. So for example, the treatment that's considered standard of care in one country might be inaccessible or even unknown in another.

Right? So, but not tailoring trials to reflect these differences, companies might face recruitment challenges, higher dropout rates, and ultimately results that aren't truly representative of applicable on a global scale. said that, know, I mean, not looking into standard of care today really may

cause huge delays within your clinical trial. So another aspect I think, which is also very important is when patients don't feel that a trial is relevant to their specific needs or situation. So their motivation to participate is not really that big, right? This can lead to slower recruitment and even higher costs as companies try to compensate for these gaps, right?

Maya Zlatanova, CEO TrialHub (05:08)
Mm. Yeah.

Ilknur Lechthaler (05:10)
On the other hand, know, when trials are designed with a deep understanding of the local patient journey and standard of care, that may lead to quicker recruitment, more engaged participants and data that is more meaningful across different contexts, right? So in my experience, you know, the upfront investment in understanding these local nuances, like standard of care,

patient journey pays off significantly in the latest stages of a trial. So nowadays I think this is really really very important. It's not about you know just getting more patients on board but about ensuring those patients stay engaged you know throughout the trial and that the results are both relevant to and actionable in the real world.

Maya Zlatanova, CEO TrialHub (06:02)
I actually I have a question to you, Ilknur I understand and thank you for emphasizing how important it is to have the standard of care nowadays. You mentioned something at the very beginning. Let me see if I understand correctly. You mentioned that this standard of care understanding of this local specific standard of care became more of an importance in the last 10 years or so. And I have two questions here. I'll start with the first one. What about before that? Like,

Let's say why standard of care was not a factor in earlier years when you were like still planning clinical trials, you still have the same agenda. You want to have successful clinical trials. How come this was not taken into consideration? Was there any particular reason, old habits, traditions? What was the reason? Any thoughts about that?

Ilknur Lechthaler (06:52)
So I think in the past we may not have really focused on looking at the standard of care. I mean, to be honest, the recent companies I've been working with, they have been looking into it and it was very beneficial. So I don't want to speak for others why they haven't looked into it. Maybe it was very strict timelines or even lack of resources to deep dive or

Maya Zlatanova, CEO TrialHub (07:07)
Mm -hmm.

Ilknur Lechthaler (07:22)
you know, a different type of strategy the company was following and, know, without considering that, if you don't look into standard of care, you might lose by failing getting the number of targeted recruitment rate, right? So because they're so

think one key point or what is really critical to understand the local standard of care and the patient journey before initiating any clinical trial is of utmost importance nowadays. It's a step that unfortunately is sometimes overlooked due to time and resource constraints, as I said. But skipping or doing this oversight,

Maya Zlatanova, CEO TrialHub (08:12)
respect.

Ilknur Lechthaler (08:15)
comes down with a significant challenge down the lines. So I think looking into the standard of care is essential. Essentially, the typical treatment patients receive for a condition in specific region. And even this differs from country to country. So what is applicable in

Maya Zlatanova, CEO TrialHub (08:19)
Mmm.

Ilknur Lechthaler (08:43)
in one country or one region doesn't mean the same standard of care is available in other countries and other regions. So, and then you start with not meeting your in -and -exclusion criteria because you haven't considered to say this is part of our inclusion or exclusion. And then all of a sudden you realize you're losing quite a lot of patients because of your strict in -and -exclusion criteria.

you haven't considered that this medication is part of their standard of care. know, so said that it's really important that you also consider these variations and yeah, that you align what patients are currently receiving in the respective country as a treatment.

Maya Zlatanova, CEO TrialHub (09:38)
And I wonder, is there any difference, first of all, how early in the clinical trial planning process do you have to start considering that? That's my first question. And second one, is there any difference whether you're planning a phase one versus phase three clinical trial? mean, does that standard of care play a bigger role in the different phases? And also how early in planning of these phases do you need to start considering that?

Ilknur Lechthaler (10:06)
Okay, let me start with the second part of your question, which phase of the trial? So I don't think, you know, phase one trials, it's really that important, right? Because you in most of the cases, you go into healthy volunteers. So that is not an issue. However, even for phase two, where you have a small population, I don't think that is really necessary. But I think for your phase three, you should be starting planning during your phase two trial to look into this.

Maya Zlatanova, CEO TrialHub (10:12)
Thank you.

Mm -hmm.

Ilknur Lechthaler (10:35)
Because coming to the first part of your question, it's part of the feasibility and maybe even one step before the feasibility where you should be looking at. you know, it actually comes with the protocol development, right? Because if you don't consider, you know, these differences, how you, you know, provide a protocol which includes all the factors,

If you don't consider all of these factors, at the end, during your trial, you will be ending up with amendments. Of course, there's no perfect world, you always have an amendment. But a nightmare which I have been facing was when you started having local amendments. What a mess. What a mess. You have 52 countries and then you start having...

Maya Zlatanova, CEO TrialHub (11:13)
Of course.

Ilknur Lechthaler (11:32)
global amendments, local amendments, then you have even different type of components. I can't remember if we had in an exclusion or we had differences or nuances, different nuances. now imagine at the end of the day when you're going into your statistics, I mean the poor statistician who needs to deal with

Maya Zlatanova, CEO TrialHub (11:44)
you

Ilknur Lechthaler (12:02)
all this data points and information, right? So this is really a nightmare. And you do not want to have that. So, of course, you know, it needs time to plan upfront. And usually, you know, you have CROs doing that, especially if you're a small biotech, you don't have the resources, you don't have the capacity, you may not even have the knowledge to do so, right? But you're sourcing out, you have a service provider, a CRO.

Maya Zlatanova, CEO TrialHub (12:14)
Hmm.

Ilknur Lechthaler (12:31)
and you're expecting them to do that. unfortunately, you know, not all of them do perform a proper feasibility and do look into the standard of care. And sometimes it's not even required by the sponsor, you know, where they say, no, no, no, we need to save some costs. You you don't need to look into that, which is a pity, which is a pity. What you don't pay upfront, unfortunately, you pay later. Yeah.

Maya Zlatanova, CEO TrialHub (12:57)
Yeah, you pay after that.

Ilknur Lechthaler (13:00)
Exactly.

Maya Zlatanova, CEO TrialHub (13:02)
I have one other question. It's more like chicken or the egg type of question. So I have to say that I've been supporting different clinical trials in country selection. But even today, I can't say I have one formula. And I wonder if you have a formula. So do you first start with this is the ideal patient profile, let's say the biostatisticians came up with this patient profile based on different

let's say like the molecule, like the end point you want to collect and all these types of things. And then you find the countries based on, let's say, where can I find more of these patients and understanding their standard of care to know at what stage they become eligible for the given clinical trial? Or is it the other way around? You have a list of countries. You decide to go there and then you have to adapt the protocol according to these countries. How does it actually work?

Ilknur Lechthaler (13:58)
Hmm. I was... Yeah, so, you know, having worked for biotech, need to be very creative. And I would say it has been a mixture, Maya. It has been a mixture.

Maya Zlatanova, CEO TrialHub (13:59)
It's a very, very.

Yeah. So you're doing both. You basically have the protocol, you also have the countries. So you hope that with the first match you did the work or you just end up having amendments. Like you said, is that what happens?

Ilknur Lechthaler (14:25)
Yeah, so, you in an ideal world, you know, you do your homework before you start, right? And during the last 30 years, I have realized, you there is improvement. There's an improvement and you may have seen, you know, my career and, you know, from all the companies, I did see that, you know, the time has changed, people have learned and it's going to the right direction.

Maya Zlatanova, CEO TrialHub (14:33)
Hmm.

That's great.

Ilknur Lechthaler (14:56)
And considering now my past experience, obviously you have an idea, you have a vision, you want to go to that mission, sometimes mission impossible, and then you have people who are really keen to get this work. then actually the stress starts.

I mean, it's a lovely stress, but it starts. what I'm trying to say here is if you, you usually you start, you think, you know, you have also commercial site where they say, you know, so if we're going to have something which works, we want to go to these markets because at the end of the day, you also want to get, know, you want to be reimbursed for all that efforts and all the money and time you have spent.

So, do have an idea of countries where you would like to get approval at the end of the whole story. So, you're not looking just to that particular trial, you're looking to the whole life cycle. So, and if you start from the end, where do you want to go and market that product? Obviously, you need to include these countries into your clinical trials.

regions you don't need to go to all the countries within that region. There might be acceptance, if you have performed here we are going to accept that. I think that was the case for example in Scandinavian countries but don't nail me down on that.

Maya Zlatanova, CEO TrialHub (16:39)
Mm

Ilknur Lechthaler (16:43)
And then you rely on the expertise of your CROs, right? Because they're telling you, we have been performing so many trials in this indication and we do have, the best, and I'm just giving some examples, know, top recruiters in this indication have been in Germany, in Italy, in the US, in Latin America. So you obviously do rely and you do, you know, ask some questions. So,

Give me some numbers, how many sites did you have? How many did they enroll? How many competing trials are running nowadays in these sites? And then, another very important aspect is you look into the regulatory requirements and timelines. Because if you only have a six -month period for recruitment, I'm just making up that number,

Maya Zlatanova, CEO TrialHub (17:39)
Yeah.

Ilknur Lechthaler (17:41)
But you know that within, I'm just saying Latin America, in some countries you need four months at least for the approval time. So then you start to rethink, should I include this country because the regulatory requirements are too long and it's for the lifetime of my trial, it's not sufficient. Let's say you have a trial which is going to run two years.

So then it might be a different story where you think, OK, it may take up to six months to get regulatory approval, but it's worth going through that because there are a lot of patients which we could recruit in our trial. So to give you a short answer, it's really a mixture of both options or both.

statements you made, it really depends a little bit on you as a company, what are your requirements? What are your timelines? What is your budget? Where do you want to go? Right. And don't forget, many of the biotech companies are, you know, I mean, people are making investments and they want to see a return in their of their investment. Right. So you need to tell the investors, you know,

usually they give you little money, little timelines, and then you have to speed up and really just spend the money little by little. So that is also another factor which you need to take into consideration. But overall, think companies need to invest time upfront in understanding the specific healthcare landscape of regions where they are conducting trials.

Maya Zlatanova, CEO TrialHub (19:18)
Yeah, that's the problem.

Mm.

Ilknur Lechthaler (19:36)
This means conducting thorough country specific assessments, collaborating with local healthcare providers, and even engaging with patients to understand their experience and needs. I think that might be very helpful. It might require more time and resource at the beginning, but the payoff is huge in terms of smoother trial execution, faster recruitment, and more

meaningful results. So, it's at that, you know...

If you take this into consideration at the beginning, I strongly believe that you will have less headache during the trial, at the end of the trial. I have even had where we did have to involve another CRO where we had to transfer a trial to another CRO because of poor

performance and so you do not want to go through that. This is really a nightmare and today I think we should be wiser, smarter, learning from our past experience and really properly thinking about

Maya Zlatanova, CEO TrialHub (20:46)
Mm -hmm.

Ilknur Lechthaler (21:11)
What do I get if I invest a little bit more time in my feasibility, look into the standard care, the patient journey, which really helps a lot at the end in order to have most probably a more successful recruitment and trial.

Maya Zlatanova, CEO TrialHub (21:37)
Yeah, most possible. Yeah. Ilnur, thank you so much for these insights, for the stories that you shared. I already made a note that we need another episode on what it's like to move from one CRO to another. Because I am sure it's a nightmare. And I'm pretty sure many people have gone through that. But actually, even more people will go for that. I hope not. But this happens. Thank you so much for emphasizing on how important it is to...

start early and I agree with you, things are getting better. People have recognized mistakes from the past and now actually are going back, what can I do, like the so -called post -mortem, what can I do differently? And thanks to people like you with your experience, with your energy, I hope we'll have more successful clinical trials. Thank you so much once again.

Ilknur Lechthaler (22:29)
You're very welcome.