Trials with Maya Z

Maya TrialHub (00:00)
Hello everyone. I'm very excited today to present you to a new guest of my mini series around the importance of standard of care of making clinical trials more efficient. I met Kasia Harris a few years ago, to be honest, when we were just starting to work on trial hub or data intelligence platform for feasibility.

Kasia was one of the people that really stood out with her experience in feasibility in planning clinical trials. Back then she was part of a CRO then she moved to a big pharma company. So she has an incredible experience in what it's like to plan clinical trials on all sides and understanding all sorts of stakeholders, very forward thinking type of mindset as well. And that's why it was so natural when I started these mini series on standard of care.

and the importance of understanding the local standard of care to actually reach out to Kasia and invite her in a coffee type of conversation. I do have a coffee, don't sue me, but I do have a coffee here. And ask about her opinion. Kasia, welcome. And yeah, please let us know a little bit more about yourself.

Kasia (01:13)
Thank you, Maya Hi everyone. Kasia Harris. So what about myself? You already said that I am long time in the space. It will be 14 years doing feasibility, but as well long time in the clinical trial space.

I am privileged to know both sides, both CRO and pharma. So let's start and discuss standard of care.

Maya TrialHub (01:47)
I actually want to first explain why you said privilege because we had this conversation recently. Why people that have spent time both on doing feasibility in CRO and doing feasibility in a pharma company are privileged because there are differences in the way companies are doing feasibility and there are pluses and minuses but actually experiencing both gets you the pluses of having the volume.

many clinical trials while you're on the CRO to see a lot of of all sorts of protocols, all sorts of indications even and try to find the best way to like the best workarounds and make sure that these these protocols are actually feasible and provide your expertise. On the other side when you're the pharma when you're looking at your baby literally your clinical trial is your baby to make sure that you go the extra mile when you're doing the feasibility assessment of making sure that the company is the best positioned.

to conduct the clinical trial in the most efficient way. So that's why you're privileged and that's why also your opinion has always mattered to me a lot. So that's why, Kasia, before we dive into standard of care, I wanna hear your opinion. How do you understand feasibility, like running feasibility for clinical trials today?

Kasia (03:05)
Yeah, so you mentioned about say privilege, but as well the question is how we understand feasibility. And that's different as well being at CRO space and being at the sponsor site. So you can look at feasibility as a three way of looking at the data. Is it protocol feasibility, country feasibility and site feasibility?

Maya TrialHub (03:13)
Mmm.

Kasia (03:34)
very be involved very early in designing protocol, looking where the protocol can be executed, but as well where will be fit in a standard of care, which we're talking about. And then is the country feasibility? Is this protocol feasible in every country? And we're going back again.

how the patients going through the healthcare system and how much this protocol can be executed there. For example, is the drug that patient required to be on trial entering our protocol is reimbursing the country? So there will be patient pool that will be feasible for those patients to

enter in our protocol and there is a site feasibility where we selecting specific sites and sometimes depends on the country healthcare system. The sites or the doctor decides about how the patient is treated. They have this preferred treatments pattern. Other healthcare system are very strict.

what is the reimbursed when the patient is starting to have disease is diagnosed with the disease and then following second or third line and is a site specific then we call it standard at the site level standard of care that we can see

Maya TrialHub (05:19)
Hmm.

Kasia (05:22)
if the majority of sites or majority of doctors prefers the using specific therapy and how does it impacting number of sites we can select in the country.

Maya TrialHub (05:40)
You partially answered my next question, once again, what is the role of a standard of care, like understanding the local standard of care when you are doing feasibility? You actually were quite correct to mention that feasibility has a couple of categories of feasibility. Protocol, country, site feasibility. I would add patient feasibility, but maybe patient feasibility is let's say divided into the previous three categories.

Kasia (05:41)
Thank you.

Maya TrialHub (06:07)
What is the role of standard of care when you run feasibility? And I would ask to this question, is there a difference between different therapeutic areas where standard of care plays a bigger role and in others not that big of a role? I mean, from your experience.

Kasia (06:25)
So it's extremely important to know the standard of care in each country. Yes. I call it patient pathway. We discussed this. It's not the patient journey. I will distinguish between patient journey where it's more like from the patient perspective.

Maya TrialHub (06:41)
Hmm.

Kasia (06:50)
for me, patient pathway standard of care is how the patient once is having symptoms of something and going into the healthcare system and what type of drugs, procedures are available for the patient depends on the stage of the disease. when, for example, if someone has

see something happening on the skin, can a patient go straight away to dermatologist or must go to the family doctor to be referred to the dermatologist? And it will depends on the country. And then what the drugs are straight away reimbursed for the as a first line of therapy or need to

to pay more or are there other type of procedures as well the patient must have before the specific drug will be available to be prescribed for the patient.

Maya TrialHub (08:04)
options.

Yeah, sometimes now that you mentioned the patient pathway, I'm thinking about some rare diseases. In some countries, you may have only one hospital that gives you the final document for having this disease, for example. So knowing even this thing can actually make a huge difference in the way you select the country, select the sites after that. That will define whether you would have a referral site, because if that's the only hospital giving you this document,

you know this is the place that all patients go through and yeah.

Kasia (08:46)
Yeah, you know, another thing is, for example, in oncology, yes, chemotherapy must be prescribed by oncologists, but not in Germany, for example. So is as well depends on which specialization will be able to prescribe medication, what is the reimburse. So no knowledge of standard of care is a basic really because

Maya TrialHub (08:54)
Mmm.

Hmm.

Kasia (09:16)
Sometimes when we have a protocol and the sponsor thinks, yes, we can go everywhere, we can find out through standard of care that there is limitation of number of countries we can go because there is no reim bursed or it's not available. Very often approval of the

follow very quickly in Western European countries with reimbursement, where in Eastern European countries there is a lag and sometimes we're talking about two, three, four, five years that this drug will be not reimbursed. So if we're the protocol that we're thinking, okay, the patient must be treated in the first line with specific mechanism of action that is new.

Maya TrialHub (09:57)
Yeah.

Kasia (10:11)
our number of countries available is limited. then the next question is, okay, so how long is going to take us to recruit this patient, especially in the Western European countries where you have a more availability of a new medications and new mechanism of actions. What does it mean for our protocol and time when we will be able to enroll patients?

Maya TrialHub (10:40)
Do you think it's up in somehow like in any way if the availability of more treatments does it impact at the end of the day the motivation of patients to join clinical trials? That's something I'm discussing with patients but I want to hear your opinion.

Kasia (10:53)
Yes, absolutely. And especially we still using placebo in different, you know, in oncology, we don't using placebo for many, many years, but outside oncology, the placebo is still used. my recent experience is that the regulatory coming back saying, well, you cannot use only your

your drug with placebo, you must as well add standard of care and regulatory recently looking very closely how long the patient will be on placebo and demanding switching to standard of care after specific number of weeks for patients on placebo because yeah.

Maya TrialHub (11:51)
No, I was going to go one step back because you mentioned that when assessing the local standard of care that gives you an idea of whether you're gonna find the eligible patients. Sometimes it just reminded me of a case that we recently had where I don't remember the treatment. I was not involved in this project. I just heard about this and basically it was that the treatment was already reimbursed.

in the States two years ago. Basically, yes, I remember now that the inclusion criteria was such that it required patients to be on a treatment at least one or two years before they start the clinical trial. That was a part of the eligibility criteria. And in the States, that was possible because their drug was reimbursed two years ago. So there were patients that are at least one year on this drug already. And there was a pool of patients.

But that wasn't the case in Europe, where the majority of countries reimbursed that a year later. So you would be able to find these patients, but maybe a year later, because the patients that are currently out there were now on this treatment and they didn't have this one year in treatment. So even tiny details like this one can actually make a huge impact on the feasibility. It's just a story that I remember.

Speaking of that, basically, Kasia, what are the implications of not understanding the local standard of care before starting your clinical trial? What are these implications from your experience?

Kasia (13:33)
So the implication is that you're starting the study and you're not enrolling and you're asking yourself, okay, what is the reason? And then you're starting talking to the doctors and they're saying, well, you know, I don't really like the drug that you require the patient be on or...

you know, it's not reimbursed So in fact, I don't have this patient population, which is, you know, is interesting from the perspective we in feasibility, we're doing site feasibility, we sending sites protocol. We asking them, are you able to enroll patients? And they say, of course, then ten patients in a month. Yes, I will enroll and then

Maya TrialHub (14:17)
Mm.

In three seconds.

Kasia (14:31)
you know it's natural people sometimes do not pay attention, doctors are very busy so it's our responsibility as feasibility to make sure we understand and we're helping the sites to make sure they understand these nuances about the protocol because they're not paying attention because they're busy.

Maya TrialHub (14:39)
Yeah.

Mmm. Got

Yeah, yeah, so what you're saying is that of course we always need to do site feasibility Like the sites are essential as much as the patients at the end of the day. Otherwise, you can't run a clinical trial But when you do a site feasibility, let's say the exercise with the questionnaires, but that's what we're discussing now It's essential to be prepared how to prepare the questionnaire so that you guide them on

nuances of the clinical trial that may break the clinical trial, may be a bottleneck of the clinical trial. Is that what you're saying? Is that what you're trying to do before starting the site feasibility?

Kasia (15:36)
Yes, so you want to look at the country. So you want like is a protocol, yes, is my protocol, is my inclusion criteria or exclusion criteria limiting my patient pool? Because there could be procedures, there could be like you're saying the time of on specific drug or you know

Maya TrialHub (15:41)
Hmmmm

Okay.

Kasia (16:03)
because the standard of care is not only the drugs, yes, how the patient is diagnosed. So the great example is breast cancer, and neoadjuvant treatment. Who diagnose the patient and if it's an early stage of the disease, the patient can be sent straight away to surgeon and

Maya TrialHub (16:27)
Yeah.

Kasia (16:28)
when we want the study in your neoadjuvant space, suddenly we're losing patients because they're already in the process with surgeon and suddenly instead of 10 patients, we ending up with one that was caught somewhere there. So, you know, how long is beat in each stages or you need, you know, sometimes you have diseases that you can wait, like you can line up patients and

Maya TrialHub (16:37)
there.

Hmm. Yeah.

Kasia (16:56)
and you're looking at your database and saying, okay, I will have 10 patients and I will wait for the study start. But very often when we're looking at the patient in progression, you don't have time. So you need to catch the patients in this stage. And of course, right now with medical electronic records, can as well.

Maya TrialHub (17:15)
certain

Kasia (17:24)
line up the patients in a sense because you know the patient is currently on the treatment, the patients will progress and you can estimate some somewhere there but as well you like the the knowledge how the patients going through the system so if if the disease is progressing will the patient stay with the same speciality or will move somewhere

is coming to our side at this stage. So even is diagnosed with the disease for some times, maybe specialty changing as well, because this depends on healthcare system. So knowing standard of care per country is basics, is extremely important for timely execution of patient enrollment for the study.

Maya TrialHub (18:06)
Yeah.

Yeah, Kasia.

you're coming, you're currently based out of the States, like out of the, out of United States, but you're coming originally from Poland. And I wonder, is that the reason why you understand that there is a difference between the standard of care is of different countries? Because my observations are such that in many cases, speaking about electronic health records and the electronic medical records, like to be precise, a lot of

Kasia (18:30)
Correct.

Maya TrialHub (18:56)
U .S. colleagues I've been speaking to, because of the access to these electronic medical records, they do this protocol feasibility on top of these claims data electronic medical records, and once they do the feasibility there, they will assume, they usually assume, well that's how patients are treated. But tell me from your perspective, how different it is, the standard of care in the different countries. Is it much different?

Can you rely on electronic medical records that are in the States to tell you how a patient in Poland, for example, or a patient in Germany is actually being treated their access to treatments, their access to procedures, and so on and so forth?

Kasia (19:37)
I wish, but absolutely not. No, absolutely not. The United States has a different healthcare system. Everything is based on insurance. The doctors have much more flexibility.

Maya TrialHub (19:42)
So it's in our wishlist.

Kasia (19:58)
is rather what they want and want what your specific is what patient healthcare system will reimburse rather than standard. There is no, I call it no standard of care in United States where European countries are much more like it's not much more. They are very strict what you can or what you cannot do.

Maya TrialHub (19:58)
Mmm.

Kasia (20:25)
I know in Spain, Italy, I did a time ago this survey asking for what the site's prescribing and you could see that in United States there was many, many medications that investigators indicated they will prescribe. It was my preference of treatment when in Europe, very strict, 80%, 90%.

follow what was the guidance from the country, what they can prescribe. coming from outside, I don't know if he's coming from outside, he's just asking questions, is somewhere there different? Yes, what is available? How the healthcare system work? Where are you going? Germany has, I used to live in Germany as well.

Maya TrialHub (21:18)
Mmm.

Kasia (21:25)
the healthcare system is very different than any other country. So we must understand the healthcare system and then a patient how is going. And as well, we discussed this patient journey could be as well completely different from everything what we understand from the data side.

Maya TrialHub (21:54)
Yeah, speaking about the patient pathway, you mentioned Spain, you mentioned Italy, like we were discussing in the past, a huge part of the patient pathway, obviously that's coming from the healthcare system, but a huge portion of the patient pathway is actually defined by the reimbursement rules. So in many of these countries that you mentioned, Spain, Italy, you may have even the regional reimbursement rules.

which makes it even more complicated, which means that the site in Tuscana may have one set of rules and another site in Rome, for example, may have another set of rules for how patients, what type of access. And sometimes the definitions are very specific, even how much you're reimbursing that. Is it 20 %? Is it 80 %? And it's how much also plays a role in the patient's mentality, how do they perceive access? Because access has to do with, can I afford

Like literally, how much more money am I spending on other procedures and other drugs at the same time? And with the new treatments being even more expensive, that is a huge motivator or the other way around for joining a clinical trial. But speaking about the fact that it's different, like each in these countries is different. You've planned, I don't know how many, like how many phase three clinical trials where you have to assess many, many, many countries.

How do you do that today, Kasia? How do you assess the standard of care prior to the site feasibility so that you're better prepared to actually ask the right questions?

Kasia (23:34)
It's not like, so for anyone who will listen, you didn't ask me, but I will just go to trial hub to look at the standard of care because some companies have a local affiliates that they will go and check. So I will send request. It's very popular in pharma.

Even in CRO, we used to go to our local offices and ask, okay, can you tell me? But the question is how holistic it is because if I'm asking someone, can they really assess or can they miss something? Who is checking them? We know we all make mistakes.

Maya TrialHub (24:05)
Mmm.

Kasia (24:29)
is this really validated what they providing? I need to trust they it is but I will need to go it takes time they will gather information they will you know come back to me I will put everything in excel and it's not very efficient I would say and on top of it

If I ask today how I know that tomorrow will not change and typically we're doing country assessment very early in the process so that from the standard of care how I make sure that there is no change that will impact my patient pool in six months when we you know only US will be up and running quite fast any other countries will

Maya TrialHub (25:18)
Hmmmm

Kasia (25:27)
where standards of care really matter will follow six months later, three months later, four months later, six months later. So how can I be sure that something didn't change and impacted? So I will need to redo that instead of just going somewhere to the place and not bother people with additional requests.

Maya TrialHub (25:47)
Hmm.

Yeah. So if I understand correctly, doing the assessment once is not optimal. Like you do it once only because you don't have any other choice. But in the ideal scenario, you'll be able to check that regularly, even maybe throughout the clinical trial, because it's yeah, actually, I have such a case some years ago, where suddenly for just three months, there was a negotiation between the company and the government, like French government.

on whether they should reimburse fully or partially a drug. For these three months, the patients were without this option. And that was the best recruiting country, even though they had the highest competition in the past and they were betting on other countries back in the days, Ukraine, Russia, and so on and so forth. So even that little thing, even these exceptions can actually influence the speed of your clinical trial. So I understand, I definitely understand. Yeah.

Kasia (26:48)
So, Maya one more, because we're talking about the standard of care, but there is another aspect that sometimes we need to know about the standard of care or drug availability because of the comparator we planning to include in our protocol. yes, as well, that's regulatory,

Maya TrialHub (27:09)
Yep. And I guess the budget as well, Kasia, right? It does impact the budget,

Kasia (27:18)
If we thinking about to have a comparator, the question is, is it available in the country? And is it used in the country and at which stage? So if we planning the protocol in second line of the disease, is this comparator a proof in this country? Because as well, could be differences.

Maya TrialHub (27:18)
Hmm.

Kasia (27:44)
how the drug is used depends on the country. So one country can use the drug in first, second line or third line. Another country, the drug can be not even approved in the indication. This is in immunology, yes, where the one drug is approved in different indication like psoriasis, psoratic arthritis, atopic dermatitis, et cetera, et cetera.

It could be that at one country it's not cover all diseases that in additional country will be. So if we coming as a comparator with this drug, can we use a country which as well is extremely important to look at? So just an aspect as well of knowledge about.

Maya TrialHub (28:21)
Yeah. Yeah.

Kasia (28:39)
about the specific drug and how it's used in the country. Is it reimbursed Is approved reimbursed Et cetera, et cetera.

Maya TrialHub (28:48)
Yeah, thank you for this clarification, Kasia. I have one last question because I know we were running out of time, but what stops companies, and you've been on both sides, what stops companies from assessing the standard of care regularly? Because you mentioned in the ideal scenario you do it not just once, but throughout the whole even clinical trial. What stops them from doing that? What's the reality?

Kasia (29:11)
You will need to have a process. No, you will need to have a process and people that doing this because it's at the country level. So you will need to have a process system or if there is not system that does it like in in out like in the automated way. Yes. So you will need to have

Maya TrialHub (29:20)
Well.

automated way.

Kasia (29:40)
every six months or depends if because standard of care can change monthly three months every like really or every time the drug is reimbursed depends on the country so there will need to be someone that is sitting in at the country level checking and providing updates so is a lot of people if done manually

Maya TrialHub (29:46)
Mmm.

in charge

Yeah, and what if you're not in this country? Like for example, what happened with the war in Ukraine, suddenly Ukraine and Russia were out of, you know, the let's say not considered, I mean, I'm not saying this is the right thing, especially with Ukraine, but I'm just saying that many companies are no longer considering that as the country to go to and conduct clinical trials. And suddenly they started looking at new countries like Georgia and like Moldova and so on and so forth.

Kasia (30:26)
Yes.

Yes.

Maya TrialHub (30:37)
But let's say you don't have a local office, so what do you do then?

Kasia (30:44)
When you are in CRO, you're finding someone. When you are at the sponsor site, you're asking your CRO partner to check for you. But no, absolutely you are right. Then you need to trust. You will go and ask investigators during site feasibility, but you are already there. You're spending money to do site feasibility, instead of knowing straight away.

Maya TrialHub (30:53)
huh, okay, okay.

The investigators, yeah.

Hmm... Yeah.

Kasia (31:12)
Georgia is out of the thinking because they don't have a drug. So you need then to invest money. So it's not optimal apps like you write that the process will only work if you have affiliate or office or someone who can speak local language, know regulation, know the healthcare system. If not, it's unfortunately you don't have country intelligence.

Maya TrialHub (31:29)
open your eyes

Hmm.

Yeah, we'll do a webinar with my team to actually show how you can go around with like using different documents exactly like local documents and stuff like that to check it. It is hard. I agree with you, Kasia. It is hard. But then the options are you either ignore this country that may actually be your recruitment champion or you spend this extra money with the belief that the site feasibility will just confirm what something that you believe like something you assume.

Anyway, Kasia, thank you so much for this conversation. I hope that I can reserve the spot for one more conversation because there are so many other areas of feasibility. mean, today we focused more on standard of care, but I want to hear your opinion on the new ways of doing feasibility. I know you're also a big fan of the new technologies. You've built multiple platforms being part of different companies. So I'll reserve this spot for next time, Kasia.

Kasia (32:37)
Thank you. Thank you, Maya. A pleasure talking to you always.

Maya TrialHub (32:42)
same.