Transcript
Speaker: Welcome to Clinical Data Talks, a podcast brought to you by CRS-Cube. I'm your host, Sylvain Berteloux. Join me and industry experts as we discuss the latest trends impacting the world of clinical data.
Speaker: Today, I'm thrilled to welcome Vivienne van der Waal, an industry veteran with extensive experience across various areas of clinical research.
Speaker: As the founder of PTNR, an independent clinical site she has successfully led for nearly 30 years, she brings an invaluable on-the-ground perspective to the show.
Speaker: In this episode, we will be drawing on her deep expertise to discuss how to make clinical sites want to take part in clinical trials.
Speaker: Hi Vivienne, how are you doing today? Good, and thank you for having me. I'm thrilled about participating today. Well, thank you for joining. I'm also thrilled because it's ah not always that you can talk directly to people who do clinical research day in, day out. So I'm sure it's going to be extremely interesting ah And we're going to start with the the hard part, I would say, because when we last spoke, you shared with me a striking number about clinicians who drop out from clinical trials or from the clinical industry.
Speaker: So could you share that number with our audience and share with us what you think that means? So the number I shared was actually the physicians that are not conducting a second trial after they've conducted their first trial. So we kind of call them the ones and done. So to do one trial and then they say, I'm not going to conduct another clinical trial as a PI or as a sub-I.
Speaker: And for me, that is a worrisome number because There's a group of physicians that have been conducting clinical trials for many years that are getting closer to a retirement age within now and the next 10 years. So we need new physicians to move into the business, to be able to do all the clinical trials with all the drugs that we have in the pipeline.
Speaker: And if we can't find physicians of whatever age to pursue a career in doing this, then we don't have the best treatment options for our patients coming to the market.
Speaker: So yes, for me, it is a worrisome number that so many physicians are thinking and willing to conduct a clinical trial, but after their first trial, they say like, no, I'm not in for a second one.
Speaker: Yeah. it's worrying, if like like like you said, because without physicians, we can't really run clinical trials.
Speaker: um Do you have any feel for like what the primary drivers are for them not to want to do a second trial? um Syscript. Syscript is the research group in Boston led by Gangets. They're doing research on that and they're doing, they did it in the US and they're also doing it in Europe. And I reached out to him earlier this week if they had the results available, but he didn't have them available yet. But
Speaker: We did collaborate a bit and we we had preliminary thoughts about it. And one of the things that I hear a lot of young um or well, not young people, but people that are going into the business saying like there's the complexity is partly the protocol, the kind of patients we're looking for. But the whole data collection that we're using so many tools, so many portals, so many service providers in one clinical trial, that is ah it is a challenge to understand the complexity of that.
Speaker: You called me a veteran, makes me feel old. But I've been in the business for a long time where everything was still paper. we didn't you know In the early days, we didn't even have internet. So that was kind of like a slow pace where you were doing things on paper and then the CRA would come in and They had you know the the papers where they split apart and one was taken back to data management and they would type it in and ah you would get effects with some questions, with some queries and going back. So the pace was very slow. And then little by little, we moved into EDC in a time where I, for each and every trial, from each and every sponsor, I had a laptop. So we had stacks of laptop. per study, per sponsor. um
Speaker: So we move to all these you know systems and moving into a complexity of systems and the speed of systems that if you're new, it's quite a daunting and overwhelming thing to understand how to navigate through all of this with with your patients.
Speaker: And I think that's one of the reasons, and I've seen it in my clinic, where coordinators have said like, no, I wanted to be with patients and not spending all my time sitting at a computer or and ah an iPad and and doing troubleshooting issues that I have with my patients or with the technology.
Speaker: So it's interesting because we talk about technology Or at at least I read in the industry, like from the vendor side, that some technology enables better or more interaction with patients. But what you're describing is the opposite, is that technology takes you away from patients and you have less time for patient contact.
Speaker: is Have I understood that correctly? Yes. And it's funny. And literally earlier today, I posted a little thing on LinkedIn that I had a conversation with a sponsor and they were, this was a feasibility and they were explaining to me that their trial was very patient, um, centric, but for them patient centric was that we are gathering so many data from this patient that we put the patient in the center, but it was a lot of patient and side burden.
Speaker: to have that patient in the center. So patients, we all talk about patient centricity, but patient centricity is for me also less burden on the patient. The patient is not the person that has a job providing the data.
Speaker: We are using them to get data and we must make it as simple as possible, but giving them e-diaries and wearables and all these other tools and giving us all these tools, where it were We're facing bugs and bottlenecks, as I call them, in implementing it. And the systems are all standalones. They're they're silos. It's not a logical,
Speaker: flow or an ecosystem where you go through, it's not one one one ecosystem. It is all different service providers providing this for the sponsor. And even if I do a second trial with the same sponsor, they might use different service providers again.
Speaker: so and and and I think that is making it a challenge. And to give you an example of something that happened a little while ago, we were doing an obesity trial.
Speaker: and patient had a diary and they were getting a scale and they were they had to do all these these things at home. And about two months into the trial, one of our patients came in and he put everything on my desk and he says, I'm begging out. And I said, why are you begging out? He said, I have to write down everything that I eat. I have to be on that scale twice a week. I have to enter the data into your your your e-diary. I have to do this. I have to do that.
Speaker: And I just know I'm on a placebo because I don't see any changes in my weight. And so if he would just not be on that scale every other day and entering the data and just visit my clinic every month or every two months, according to the protocol, I would be able to motivate him to continue in the trial and you know and and tell him we're doing our best Your data is still a very valuable, despite the fact you might be on a placebo group or you might be an non-responder. But for him, every other day on the scale was literally a moment where realized I'm doing all of this and I'm not benefiting from it.
Speaker: And I cannot do that for another 18 months because that was how long the trial was going to last. And I could totally understand that. And I totally respected that. It really pains me to hear that. yeah I don't have any other way of of saying it.
Speaker: Not only from the patient point of view, I mean, it's tricky, obviously, when you're not necessarily getting benefits to carry on in a trial.
Speaker: But what pains me as well is the fact that we... Data, like when when ypro came out And when more like wearable devices and so on came out, it was presented as something that would be valuable for everyone in Trials because we would be able to collect more data that would be meaningful.
Speaker: By hearing you it sounds like collecting more data is the burden rather than something that helps sites or patients. It depends on how you collect the data.
Speaker: You know, if if it's something that is collected automatically, like for instance, when you're doing a diabetic trial and they already have to do their finger picks or you have the continuous close device, that's not extra work and that's very valuable data.
Speaker: But, um, keeping a food diary, of every meal that you have for many days in a row and not getting any results or you see that yeah and even I challenge like what are we going to do with all that data?
Speaker: With everything he ate, every you know snack in between, every drink that he had. you know is it you know In the beginning that's valuable information so I can guide a patient like what's the better choices in your food, but having to do that every month for a couple of days for 18 to 20 months in the trial, it is bothersome and I really challenge the sponsor like is this What kind of data does this bring you? And also, what's the value of the data? You know, patients in the beginning are very willing to write everything down.
Speaker: But the longer you're doing this, the quicker you will just write write something down. um I myself participated in a clinical trial during COVID, which was a totally virtual trial.
Speaker: um And every now and then I get a headache. You know, that's what life brings me. And during this trial, I had to fill out a form when I had a headache.
Speaker: But the form that I had to fill out was giving me a headache itself because it was so many questions about just a regular headache. that at one point I stopped filling out the form and I said, I don't have a headache. I just start to not report my headaches anymore.
Speaker: if They could have simplified it saying like, okay, so you have a headache. Is this a different one or is this worse or is this... And then they would still have collected all the valuable information, but it would not have been bothersome for me.
Speaker: And that for me showed exactly what patients were, that's why I participated. That's why I wanted a lot of people in the industry to participate in this hybrid trial to understand what are we asking our patients and how much,
Speaker: information are we really using? I heard that about 60% of the data that we have collected in a clinical trial, eventually it's not being used. It is nice to have, we might use it in the future. We might use it for AI learning or something like that.
Speaker: But literally for the trial itself, right then and there, we're not using 60% of the data. We're storing it somewhere, but we're not using it.
Speaker: And for me, i don't think that's fair towards patients to ask them to provide all that data if we're not using it. We're potentially might be somewhere in the future using it.
Speaker: Yeah, yeah, I agree. It's a lot of investment from patients. yeah i run patient advocacy podcast as well, i and I've been able to talk to people who have taken part in clinical trials.
Speaker: ah It's interesting because where our industry focuses on data, patients don't focus on data at all. They they focus on benefits, quality of life, and so on. So it sounds like...
Speaker: There's a discussion that's needed there so that everyone understands it. That brings me to something else i wanted to ask you actually, because we talk about engaging patients in protocol design. yes It's not necessarily done widely, but I think it's getting something that that is becoming a thing in our industry.
Speaker: Do you think sites are consulted as well? I see it more and more, unfortunately. You know, some sponsors think that by sending out ah ah feasibility with just a one-page protocol of idea, basically, with three in-exclusion criteria, is getting valuable site input. But that's, you know, that's such a high-level information we can provide them on the protocol that that's not an input. But I've seen sponsors reaching out to sites saying like, can you can you sit at a drawing table with us to look at the protocol, but also look on on practical things. Also like, how do we do the lab?
Speaker: ah you know and um How many tubes do we have to draw to get to the endpoints? What kind of data do we collect? Can we collect them? through a wearable or through an e-diary, is there another way to collect them? So I do see more and more sponsors asking sites to to be involved. And to tell you a funny story about that, I was invited after i did a phase two trial where a lot of things went wrong that could have been prevented if a site would have been at a drawing table. So I took the opportunity because I knew somebody very well, with that sponsor to call him up and say like, hey, this is what happened, but this could have been prevented. And about couple months later, he said, we're setting up the phase three trial, which would be part of of the group. And I have another physician in the in the US joining us as well. And so that's fine. We've never met before. but literally during one of those meetings, she said, I think I found my twin sister in the Netherlands and I started laughing and I said, what do you mean? She said, you know what? Everything I hated in that phase two trial, you hated as well. Everything you came across, we had an issue with as well. Every solution i have, I agreed with her.
Speaker: Just showing that it's not a single site issue. It's not that every site is willing or capable of speaking up. but every site is is is struggling through that.
Speaker: And when you think that you're doing a multinational trial and all sites are figuring out how to navigate through all the systems, they're developing their own source documents. They're all trying to find solutions for patients. That's an awful lot of time and money. We're investing as sites ourselves that I think we should do it together.
Speaker: you know, all the stakeholders together, which just do you know, have one or two people developing it instead of 50, 100, 150 sites doing that on their own.
Speaker: Yeah, that's a very good point. When you've been involved early on in discussions with sponsors, have you seen a positive impact in how the trial is run? um Yes, um we least we do see improvements and what more so, and I think that that is for me the return of investment when I when i do these things is, as I say, we don't know what we don't know. And then they realize the things that they don't know. And that's when they have to reach out to the site to get that feedback.
Speaker: So they might not have integrated everything into that new trial that we were conducting. But I did see an awareness within that company that they continuously now are collaborating with me and other sites on every step along the way, whether it is implementing of an ETMF, whether it is, you know, um What EDC works best for you? What vendors do you like working with? What vendors are struggling to work with?
Speaker: Which help desks are good for sites? So it's literally not only a protocol input, which is crucial to have for sites and patients to say, you know, this is feasible in the protocol and this is not feasible, but you can have a very good protocol. But when everything around it is not functioning in a good way, when the and the EDC and the ECOA and the E-Pro and everything else is not working very well, then you're still struggling.
Speaker: So now I see those sponsors that we talk to understanding everything else around it. Because everything else around it, when that's failing us, whether it is a courier that's not taking a day to take our blood samples from here to the lab, but takes three days to get it through the lab, meaning that these are all lab samples and then they are thrown away.
Speaker: it is still considered a protocol deviation at my site, but I never chose the courier service and it's the lab that did that, but it's always a protocol deviation at my site. And then I'm being retrained and I said, you can retrain me as much as you can, but it's not going to solve the issue.
Speaker: So if they only look at protocol deviations at a side lab, but don't understand, what is actually the cost of the protocol deviation, that it might be a courier or it might be a failing device, or it might be help desk not being available at the time when I need it and therefore I'm not compliant anymore. I think that is very important for sponsors to understand that that's it's not just the protocol, it's the whole protocol setup, the study setup, the c clinical operations part.
Speaker: Yeah, it's interesting because From the sponsor point of view, I imagine that there's a protocol deviation. You address it in a certain way from the sponsor point of view.
Speaker: But what you're saying is that you need them to engage with you to go further down to the actual root cause of the issue, which is, a well, corrective action 101. That's what you should be doing.
Speaker: and there's There's another aspect that we haven't talked about, and um I wonder how it impacts sites. So in the industry, i'm sure you're aware that there's a constant push to go faster, reduce trial timelines overall, which in itself could mean reducing startup, maybe site initiations, but also at the end, trying to get results
Speaker: data analyzed as fast as possible. Does it have an impact on clinical sites at all? Yes, and we're facing it actually during this time and moment as we speak. So a sponsor has us ready to start, but they haven't had the approval yet, but they still want us to schedule all our patients, that as soon as the approval is there, that we can screen and and randomize our first patients as quickly as possible.
Speaker: um But I have all my patients planned for next week and we still don't have the approval and they still have to, after the approval, have all the systems up and running. So literally after this call, I need to reschedule all my patients.
Speaker: um and Fortunately, these are patients that we've known for a longer time. We explained what we're going through. And I do understand the competition is fierce. Fierce to get a drug on the market as quickly as possible. So what I see is that in the um the part before the actually conduct of the clinical trial that's happening at the site, they're trying to speed up the timeline. they're trying to squeeze everything together. And of course, AI is a wonderful tool where they can do a lot of things
Speaker: far quicker, write a protocol quicker, develop EDCs much quicker, do all that. and so That timeline is is being squeezed. and I also see at the end part, you know the data analysis after the data capture log, the analysis, safety reporting, that is also being squeezed. They're squeezing at the beginning, they're squeezing in the end. and so In between, there is us. and so They expect us to to be as fast as possible. However, if you need to measure something in a human being, you can't fasten up that timeline. So if you, as I said, you know, if you're doing an obesity trial, you can't squeeze that into two months. You still need that year or two years, whatever you want to measure, or a cardiac prevention trial, you need those three to five years to follow up on these patients. You can't squeeze that. So the only place where we as a site can squeeze is speeding up that that startup timeline. So from from feasibility to first patient and and that's where we squeeze and where in the old days you would get everything, you know, coming to the side, then you get an initiation visit and then you could start the clinical trial and you would line up your patients. Now they accept, they expect you to do a lot of things simultaneously. So there's a contract negotiation, there's the approval, there is your patient screening. They all want everything to be happening simultaneously.
Speaker: What I do try to explain to sponsors is that you know sometimes we need to work hard to find patients. We need to reach out to the community or social media. So we need to have the approved materials to be able to do that. um is I need an informed consent form to give to the patients. And so i can only get that informed consent form after approval.
Speaker: um I do see sponsors now doing the initiation visits weeks before they expect the approval. Then, you know, and even an investigator meeting having three months prior to expected approval just for them to tick the box, we've done it all.
Speaker: But in the meantime, I've done a hundred and other things and I have to dig myself back into all the materials before I can see that first patient.
Speaker: The other thing is, you know, they they wanted me to line up all my patients. So I did that. um But now that we don't have the approval and I have to move everything into another week, two weeks from now, my resources have to move as well.
Speaker: And patients do have life as well. They, you know, it's a summer holiday. They go away on a summer break. So we're, we're, um expecting a lot from patients but sponsors are also expecting a lot from from us it's not that i'm sitting around all day with my arms crossed waiting for them to come i have to generate an income by doing visits to be able to pay my stuff and they can't just be sitting there waiting for the approval so I also ask sponsors like be be open about your timelines. If you expect a delay in the approval, don't tell us a week before you expect the approval, but you probably know that already one or two months before that there might be a a delay. So I can re rearrange my resources.
Speaker: um Or, you know, in the past, I've even declined a trial because i expected it to be fully focused on the other trial. only to find out that that trial was going to be six months delayed. And I tried to get myself back in the in the original trial that I had declined.
Speaker: um So yeah, that that that is a challenge where, and I really do understand the time pressure and time is money also in this industry, in any industry that you want to move forward.
Speaker: But in the end we're dealing with patients and we should be respectful to these patients and understand that they have a life and this is just the minor part of their day-to-day life and accommodate that and respect that and get them involved when we can
Speaker: yeah I fully agree. And I hope a lot of people will will actually hear this and actually like really take this in because it's very important. And it's interesting how listening to you, was thinking we've got a process on one end and we've got people at the other end and we don't have something like do the process does not include empathy. And what you're asking is empathy with your patients, with yourself as well, and your staff, because you're not just waiting for things to suddenly happen. So, yeah.
Speaker: Thank you for saying all this. I think it's it's very valuable for people to hear that. Well, I think you've given me the opportunity to share that. My pleasure. I have one last question for you, which I love asking everyone.
Speaker: What's the best piece of advice that you've received in the past and that you apply to your work there?
Speaker: There is a lot of advices I've been given over the years. One that always keeps popping up in my in my head when I'm when I'm doing my job is, well, there's actually two.
Speaker: And it's kind of my my upbringing by by my dear dad. And he said, research everything and keep the best. And so I think when we're looking at devices that we're using, when we're looking at systems that we're using, I think we should look at all the systems and keep the best one, not the most cheapest one, not the one that does the quickest startup, but look at the whole thing. What is the best and giving the best to the patients?
Speaker: So I think that is one of the things I live by in my day to day life. um but also in in in clinical research. But also when I pick up a clinical trial, if I do have feasibilities for couple of trials that are more or less the same, I will try to choose the one that is best for me as a scientist, which is best for for my patients.
Speaker: um Because then I can deliver what I feel i i can deliver, yoke the best thing I can deliver back to them and the sponsor. Yeah.
Speaker: Nice. I like that. It's great for me because I pick up all those great advice through through the podcast. So I love it. Thank you. You should write a little book about them.
Speaker: You know. but Maybe I will. Yeah. Well, Vivienne, thank you so much for your time. i First of all, I really appreciate it because you're running a site. So I appreciate you taking time off your days ah for for that. But also,
Speaker: ah really so much that you shared today that hopefully you will change in the in the future so that it's easier for sites to to work together with sponsors and support their patients as as well as possible.
Speaker: And you know, to sponsor Ciro's that are out there, there are more than enough sites that are willing to collaborate and give their input and sit at a drawing table where you can pick their brains.
Speaker: you know there There are more than enough people out there that are willing to do so. So um go and find them.
Speaker: Amazing. Thank you all for listening or watching today. you can find more episodes of Clinical Data Talks on the CRS-Cube website.
