Managing Clinical Trials Amidst Skyrocketing Costs — Study Design, Global Work, Partnerships, and More | LSI USA '25

Jeff Chu  0:07  
Well, good afternoon. Everybody. Everyone grab lunch. Are you ready for this? What's exciting topic? Yeah, so my name is Jeff Chu co founder, managing partners of Features Capital. We're an early stage Medtech venture fund. This topic is dear to my heart. You know, at the end of the day, clinical trials are typically the it's the key value inflection point for most startups, but it's rarely managed well. Oftentimes we take a step back, we hand it off to CRO and we hope we get the results that we want to see. And it's an incredibly inefficient process, and often that leads to higher costs and longer term time. I think the last stat I saw it, I just pull this up the other day, was that almost depending on the study, 60 to 80% of all clinical trials are taking longer than expected. Clinical Trials represent 60% of your total R D cost, typically for any startup. So it's a huge part of your budget. It's taking longer than we expect it to take. Patient Engagement is low. Patient recruitment is low. And so there's there's got to be better ways to do this. And so hopefully what we could do is with our incredibly diverse and broad panelists that we have here across the industry, in various different spaces, provide some of the collective knowledge and share some of that collective knowledge with all of you, so that you could be better equipped to manage your clinical trials and better empowered to do it well. So that's the hope, hopefully we get there. This is a workshop. So you know, what makes the what makes the quality of this go up is the engagement that we have from our audience. So I would encourage all of you to come speak, ask questions, tell us about what you're going through today, and seeing how we could be helpful, I think, is the best way to approach this. So So before we dive into things, I'd love to do some quick intros. So Denise

Denise Bronner  1:57  
Hello everyone. My name is Denise Bronner, and I am the founder and CEO of impactful ventures, which is a consulting agency that helps pharma and Medtech companies navigate the space properly. My previous experience has really come from academic consulting and even working within pharma and helping with global clinical trials, so really understanding how to do patient identification, site feasibility and things along those lines.

Marc Jones  2:20  
Hi, my name is Marc Jones. I've been in industry for 30 years now. The last 20 or so, I've been in healthcare. I lead a diagnostic company in the area of neurodegeneration, leveraging augmented reality, we're looking at how the brain networks function, and by doing that, providing an objective measurement of whether people are moving toward dementia. This is a apropos topic. We've done multiple studies in the last few years. And as Jeff mentioned, this is a hugely costly area, and even when you plan well, you're going to run into challenges. So I'm looking forward to the conversation, learning from each of you and some of the areas that you guys have had experience. Very, very pleased to be here. Thank you.

Angela Paterson  3:06  
I'm Angela Paterson. I'm a Principal Consultant at CS Life Sciences. We are a quality regulatory and clinical consultancy specializing in helping start up University spin outs to get to market. And part of that is helping with that clinical strategy, making sure that you get the right clinical data that works for you for all the markets that you want to rotate.

Jeff Chu  3:27  
Great. Thanks. And so for us to gage where we could spend the most time that's gonna be most useful for everyone in the audience, love to do a quick survey here. So who in the audience is thinking about getting ready to do a clinical trial? Couple hands, yes, who is in the middle of a clinical trial? There's still things that you can do, even if you're in the middle, to be successful, and who's done a clinical trial in the past? Lots of hands, great. And so again, this is a workshop that's meant to be engaging. I think the content where we focus our time and effort to really going to come and be driven by the people in the audience. So I encourage all of you to ask questions. I was thinking of a way to frame this so we could have a most efficient conversation. And the most natural thing that we thought about was thinking about this from a clinical trials journey. And so at the start of the journey, obviously you're thinking about the clinical trial strategy, then we'll talk about clinical trials optimization. We'll talk a lot about the patient recruitment, retention and engagement, which is important aspect. We talked about, where all the inefficiencies are there, and the costs that are associated with that. And then the last part, if we have time, we'd love to chat about some of our experiences and how we can leverage clinical trials, not just to get the regulatory approval, but to get additional data that's going to be useful for your business, whether it's on clinical at on clinical adoption or other value propositions down the road, to help later on. So So with that, I'm going to throw it over to Angel, and let's get the conversation started around clinical trial strategy. And again, please engage with us. We're here to help. So let's make this a incredible. Helpful and engaging conversation.

Angela Paterson  5:02  
Okay, so most people now come to us first, because it's somewhat easier to get through fighting a PMA process than it is to get cleared in Europe. So you may need to do a clinical trial to get through those processes in the US. However, if you want to use that data to go back to Europe, you need to be collecting the right data. So in Europe, there's this thing with MDR called safety objectives and performance objectives. You need to be establishing those very early before you've designed your clinical trial, and that is to make sure, despite your safety endpoints and your performance endpoints that you need for maybe FDA, that you also cover these other things that the Europeans are looking for. Because otherwise you could spend millions on a clinical trial and go to Europe and they say, No, the data is no good. The other aspect is you can do a joint clinical study between the US and Japan. Usually, the way that works is that you would have most of your patients in the US and a small cohort in Japan. It all needs to be agreed with PMDA. They have a nice process, which is like the US Q sub process, but in Japan, you can talk to PMDA, it's not terrifying. And you can agree a protocol, which is a joint study between the US and Japan. So ideally, when I'm working with people to design studies, we want a single study that gets them everything they need for Europe, Japan and the US. And if you've got that, then you're pretty much set for global sales when you have your data.

Jeff Chu  6:51  
Yeah, super helpful. Is, is it ever, I always say this in jest, it's never too early to engage with the regulatory body.

Angela Paterson  6:58  
No, it's especially in Europe, it's, it's not really possible, and they have a process. But it's, is not really a process. It's a nod to the Pro, the Q subs, that JP, that Japan and the US have. So they will give you an opinion, but usually that opinion will be, yes, you need to do that. They won't. They won't give you advice. Yeah, if you go to fda, they will give you advice. They will tell you if your protocol is good or bad. They will tell you what else they want to see. Japan is the same, little bit more complex. But if you go to them, they will talk to you. They will tell you what's right, what's wrong, what else they want to see Europe, not so much. They'll wait until you've spent a lot of money submitting a file, and then they'll tell you what's wrong, and that by that point, it's far too late to fix it.

Jeff Chu  7:56  
Maybe we could zoom out a second and Does anyone in the audience? I mean, if you're working on a clinical trial strategy right now, do you know even what goes into a clinical strategy? What does a good clinical strategy look like to you? Any thoughts? What are some of the key components that we'd expect to see? Primary endpoints would be my first gut check, right? That's a good one. But what else? There's a lot that other things go in there. Maybe on our panel, 

Marc Jones  8:27  
we got some shy people here today. 

Jeff Chu  8:29  
It's the taco lunch.

Marc Jones  8:33  
I mean, I think that with a lot of things in life, we want to start with the end in mind, what is the ultimate goal here? Now, for those of you that are in here, I'm more of a device diagnostics who's done or will be doing device for diagnostic studies in the next couple years. All right, so I'm not saying that this isn't appropriate to therapeutics other areas, but I've done s AMD as well as I BD type things. The the FDA approach is safety and effectiveness, which is important, but that's threshold. That's like oxygen. You need it to breathe. What they're not as con, what they're not as concerned about is whether you're going to be successful commercially. And so you got to ask, what we ultimately want these clearances so we can commercialize products, so they can be used, so they can advance health care. So what is adoption? And we'll get to this at the end, probably more specifically, but start with what you're looking for at the very end, because the minimum set of that endpoint might be satisfactory to FDA, but it might not be satisfactory for the adopting community that you're going after. So make sure that you don't narrow the aperture too low. I know that many of us are scrappy startup entrepreneurs, and we can't do 10, $20 million studies and having all the data, so we tend to start shrinking them, but make sure that you don't narrow your studies so much your endpoint, so much that you end up getting a cleared product that you can never sell, because it's not without doing additional studies. Now maybe the strategy is get it cleared, and that's a value inflection. And so you can raise capital and do the bigger study that you want, but make sure that you go into that with your eyes open. And,

Jeff Chu  10:01  
yeah, yeah. 

Audience Member  10:02  
Study Design, from the get go, 

Jeff Chu  10:05  
yep. Study Design, protocol design, it's another key component. Now you have your clinical endpoints, you need to know how you're going to get there. Any other thoughts?

Audience Member  10:14  
Pick the right position Barkers, because ultimately they're going to be the champions and the posts on the podium and start there. But in the publication, and they're going to be your first way for commercial activities,

Denise Bronner  10:25  
I agree. And I think a lot of times we would tend to think about going with KOLs initially, but a lot of times they may not have the patient volume that you're looking for. So yes, they may be a strong voice in industry. Good for that type of vocal, type of presentation for you, but when you're thinking about, really, who is seeing the patient? Sometimes, having a mix of physicians is going to be very important for

Marc Jones  10:45  
that. Yeah, I'll just jump on that. It's very easy. I've been part of studies where you get a group of clinicians that are experts in that field. It's almost, it's almost like a mafia group, right? They're like, everybody knows who they are. They go to all of the functions, they speak at all the conferences. But they actually don't have resonance beyond an academic world. They don't speak to the type of folks that would adopt. So making sure that you go well outside of that to get because you will narrowly define a study that suits those very insular interests of that smaller group.

Denise Bronner  11:13  
And we've also seen too sometimes, when you go with those type of KOLs, that they are not that great at recruiting patients, sometimes that well. So there's a give and take on Who do you want to pull in for that, also keeping in mind, because, again, you're trying to stay on budget. Who do you actually want to have on your study as well?

Jeff Chu  11:28  
Yeah. And then expanding from that point, it's actually site selection, right? Are these qualified sites? Can they actually manage the data collection, and could they manage it efficiently? Yeah, I've seen way too many times where the data collection is sort of a little haphazard and they spend way more time trying to clean up the data, spending months to do that, when it could have been automated up front, if they thought about it well. So thinking about who the support staff is, who's going to do the follow ups. How do we collect the data? All that stuff has to come into play as well. And luckily, in this, in the day and age that we live in today, there are lots of tools that exist to help facilitate that

Denise Bronner  12:01  
process. As I said, that's where I think having strong strategic partnerships beyond the sites are important. So if you do partner with certain types of vendors, or even being able to say you may have a certain site because they do have the capabilities, but there may be surrounding sites that you can have as referral hubs to kind of funnel patients to that site. We've seen that type of model,

Marc Jones  12:19  
yeah, and don't rely on your CRO to be your gatekeeper for ensuring your study is running. Well, you're getting quality data. They're going to take a lot of money out of your out of your bank account, and they're going to do the minimum necessary. Now, this isn't the dig on TROs. I find them incredibly important. You know, my company completed a study last year. It was incredibly important study. It's going to be a seminal publication for our company. We spent a lot of time designing it. It was perfect. And then the study started, and it was like, Well, this was a horribly designed study. It's not going to get us the endpoints we need, so we had to pivot. But what was very interesting was the sites that are that were selected, that our CRO helped us select, were were great for recruiting, but the people doing the work that we were comparing ourselves to didn't actually have the requisite skill set, and so as we were, as we were doing our medical source data verification, which fortunately, we were doing throughout the study, don't wait to the end, we identified significant gaps that would have put a multi million dollar study at risk. So inspecting your expectation going into it is really, really critical, otherwise you'll get to the end of the study and you're going to get a result that you weren't expecting or a result that you didn't want to see, for something that could have been managed and corrected.

Denise Bronner  13:29  
And I had to say, with CROs is some of the sentiment that you'll hear from sites is that they're really not a fan of them. So managing that relationship between CROs and sites is important, because a lot of times you'll have sites kind of bypass a CRO to come talk to you, and that can cause a major conflict. It just gets really messy. I

Angela Paterson  13:48  
see in devices where the sponsors, the medical device companies, try to cut costs by really cutting on the clinical monitoring. Sometimes it could be a long study, and they'll maybe only do two monitoring rounds, and then the last per close out, and then you go to close out, and nothing is right. You know, there's patients that shouldn't be there, there's a es, adverse events that haven't been reported. There's all sorts of things going on or going wrong that nobody knew about, and you're at the appointments close out, they've got a submission coming up. They want to do data cleanup, and sometimes it takes six months to a year to just fix the problems in the study. So it may seem like the monitoring is just a waste of money, or, you know, extra checking, extra auditing, but it's so valuable for making sure that when you get to the point where you've got all your patients, that you can actually close out when you want to close out. Yeah, yeah. I do want to spend a little

Jeff Chu  14:50  
bit more time on selecting a CRO and going through that process and how you think about it. Hopefully that's helpful. Maybe some others in the audience could add to that as well. But before I move on to that topic, I. Want to circle back to the O us question on clinical trials. You brought it up before Angela. And so one of the things that we see often is that people go to do their first in humans, outside of the US, right? And so how many people in the audience have gone outside of us first in humans? Should be quite a few. It's cost effective. It's a good it's a good way to do things. It's a good way to iterate the product. What I don't see oftentimes is people who actually engage in the FDA process. So they go to us first in humans, but don't really talk to the FDA. And that's a great point to be talking to the FDA. Tell them what you're doing, show them what you're doing. Do those cue subs get aligned so that you know that the endpoints that you're generating outside of the US are going to be useful for your EFS application, right? You're thinking through that process. So get alignment there. Yeah. So moving on to the next topic, which is the clinical trials optimization. So now that you've gotten a clinical trial strategy, we're executing it. Now we're thinking about, how do we actually run this process? So typically, the one of the first steps is selecting the CRO we've talked a little bit about some of the things, but top levels, if we start at 20,000 foot view, how do you guys think about like, identifying and selecting? There's so many options out there. What are the factors that you think about?

Marc Jones  16:14  
Well, I mean, the companies that I work with, we rely a lot on referrals of peer colleagues that have had experiences, that have run complexity, the types of studies that we're trying to run. What issues did you have? If there have been no issues? I typically actually tend to avoid that, because I don't think that I'm probably getting a thorough review. I think that there's a lot of good CROs out there, and I do think that they are leverage points for getting a study run. It's just the bigger thing in my mind is making sure that, as you're budgeting your cost for the study, that you're not allocating so much to the CRO at the expense of your own team. You know, again, everybody's budgets are different, but I would you know you probably have a regulatory quality person. Maybe it's a fractional regulatory quality person. You probably don't have your own CRA or clinical trial operations manager if you're spending millions of dollars on a study, I strongly recommend having a full time, at least a full time person, even if you've got a CRO just holding their feet to the fire, as you mentioned, the cost of fixing an issue at the end when you're monitoring is is logarithmically more expensive than early on when you're doing source data upfront. So having the people that can hold the CRO and having regular cadence, don't just set it and forget it, this has got to be a major focus. So I don't have a magical wand in how to select a good CRO. It's kind of touch and feel. It's, you know, I work with multiple some of them been great. Some of them been just okay. Sometimes there's academic universities that actually operate as CROs, and they're and they do this a lot, and I've had good success there, and you can get that oftentimes much less expensively. So just look at your options, talk to people, but make sure that you stay involved. I think for

Jeff Chu  17:57  
me, when I see that you know, the biggest predictive factor whether or not you're gonna have a successful outcome with the CRO is whether CRO is whether or not you have that full time CTA person, I mean, John, honestly, that's that's a huge driver, making sure that we're keeping them accountable, to keeping them on on track, you know, because they're going to fall behind quickly on patient recruitment, and what are they doing to adjust that, how they're working with teams. So, yeah, it's a lot there.

Angela Paterson  18:20  
I think another thing with CROs is, when you get a quotation, just check what they're giving you, because quite often the quotes are extremely complex. You know, it's line by line. Cost per minute almost. But when you get to the end of it, you realize you've got no protocol, you've got no investigators brochure, you don't have a CRF, you have you don't actually have a study, you've just got project management. And that happens a lot. There's a lot of people that say, Yeah, we're a full service CRO, but they don't do any of the paperwork you actually need to run a study. So it's that's just be very cautious when you're reviewing these things, make sure you're getting what you think you're paying for. And I think

Jeff Chu  19:01  
when you have more experienced team member internally, I can't stress this enough like having internal capability yourself who's looking out and aligned your with your interest is such a key difference maker. It's, it's, I would, I would. I see far too often where people don't want to spend those costs. But think about it, 60% your R D cost is in clinical trials, and you're not going to hire. And you're not going to hire an internal person to manage this for you. No, that's crazy to me, right? Yeah, and the entire business is depends on this.

Angela Paterson  19:33  
So yeah, I think as well in everyone knows medical devices, the goal posts move all the time. When you're a startup, goal posts move daily almost. And when you're working on a clinical trial, it's the same. The goal posts move the what people need, what people want, move all the time. So when working with CROs, just be aware of the words change control, because change control means money. It's. So if your quote is for a delivery of a study, yes, then that should include the study and any changes that happen to happen in it. But if there's lots of words change control all the way through your quotation, then you know that every time you change anything that's going to cost extra, yep,

Jeff Chu  20:16  
just like in the quality world, 

Angela Paterson  20:18  
exactly.

Audience Member  20:21  
This is less of a question than a comment. As the life sciences Trade Commissioner for Canada, you know, I will put it out there is, if you're looking to reduce your costs and have great clinical trial, clinical trial data and capable sites, CROs, you can't not look and consider Canada as as your first in man site or running more of your trials in Canada, right? There's a lot of information. Costs are greatly reduced. There's grant funding available to do the r, d or clinical trial work in Canada. So without doing a full spiel, consider Canada. We do have a booth here, and we're happy to talk

Jeff Chu  21:01  
nice. Well done.

Audience Member  21:03  
And the clinical data coming back is not tariffed. Oh,

Jeff Chu  21:10  
you're gonna go there. 

Audience Member  21:11  
Even the work being done not Tara. 

Jeff Chu  21:13  
How about data privacy?

Audience Member  21:16  
Not, not a problem. Obviously, all the all the sites that you'd be looking at are engaged in all the top clinical trials that are being done now anyway. So data, privacy, you know, clearly, you know, top of class as well. Cybersecurity, they're top notch. 

Marc Jones  21:31  
This is actually an issue if you're doing global clinical trials that we faced a lot, particularly in our test, we're doing speech language, motoric and augmented reality tasks. So we're, we're getting all types of modalities and that information. In some places, Germany, for example, you can't record people's speech and language, so correct as you're thinking about your clinical trial design, you can design the perfect thing, and then when you go to execute it, if you're thinking going across geographies, and all of a sudden it's like, we can never repatriate that data back so it has any value. So make sure you're thinking about GDPR and various restrictions. 

Denise Bronner  21:32  
That's a good point, because when you think about, at least in the US, when you have to collect certain type of demographic data about patients as well, a lot of that is also not allowed to be collected outside the US as well. So

Jeff Chu  22:15  
all right, we have

Audience Question  22:17  
a question. So on one end, yet can our purpose? De Nore in an outside us location to do trials, we had a couple colleagues of the network that are dragging us towards places like Kazakhstan. Is there any like as you go through the radio up outside the US and you're balancing, you know, access to patient populations and economics, is there, like no go zones? Is there? Is there places that are kind of hidden gems that people should be aware of? 

Angela Paterson  22:48  
The the data coming out of Kazakhstan, Uzbekistan is actually pretty decent. And I've seen first in, first in man, done in South America with no consent whatsoever. Obviously don't go there. But when, when it comes down to, there is somewhat of a, almost a snobbery about clinical data. When you go to clinic, you might be able to get your device cleared with the data from somewhere like Uzbekistan. However, when, when you go to sell in the US, there's this hierarchy of clinical data, and we'll say, Where's your data from? Thailand? Oh, we don't like Thai data. Have you got us data? We don't like Turkish data. Data Turkey is phenomenal, yeah, but the US clinicians do not buy it. They're not they don't see the value in it. So you end up having to do registries and other expensive things to collect data in the US to get the traction with the clinicians to actually buy your device. So you've gone to all the effort of getting on market, and nobody wants it because your data is from

Marc Jones  24:00  
Kazakhstan, yeah, yeah. And this goes to the beginning point that I made about starting with the end in mind, because you may be able to get through a regulatory process, but to your point, can you get adoption? And I've run studies all around the world, most recently in Greece, amazing data, but these were internal studies, and as we talked to people, they're like, and then the other thing too is, what's your intended use population? Because if you are going to the FDA, ultimately you need to make sure that there's parity, and then it matches the intended use population.

Jeff Chu  24:29  
We have four minutes left, and I do want to touch upon again we spoke about early on, 30% of all the cost overruns are 30% of all your clinical trial costs are associated with with patient selection, patient recruitment, and so

Audience Question  24:44  
Paul, I should ask you, yeah, it tied into what you just said. How do you deal with loss to follow up? Because that did some studies. Gary, that's just a mess. And obviously, if you're losing your patient because they don't come back or whatever, they say, your your cost. Yeah, now through the Roche the data, get a recruit from crime, any secrets to, you know, helping with that, or putting things in place to try to minimize loss of power. 

Denise Bronner  25:09  
So I do know that there are some vendors that are out there that have a system in place where they have, like, a study buddy, so the patient has someone that they can kind of always, like, kind of check in with, and that also helps to build up a long term relationship with that patient. So let's say they're able to get in contact with the patient to figure out why, whether something traumatic happened in their life or whatever the case may be, at least you're getting an information as to why you lost them. But that also helps to as they're keeping in touch with that patient that you're starting to see if they're starting to deviate. So if you need to implement other types of you know, support systems or things along the lines for that patient, you're getting it early, you're being more proactive than reactive. But I've seen that type of stuff work. But again, it's an added cost, but at least it's a way for you thinking proactively, how you can keep the patient in 

Audience Question  25:52  
maybe cheaper, then 

Denise Bronner  25:52  
it might be cheaper in the long run. 

Jeff Chu  25:55  
uestYeah, lost time is critical, yeah.

Marc Jones  25:57  
So I think the other thing too, and I can't, I have notions as to why it was successful, but I've used a couple of times, and couple of times which my idea wasn't. Goes to the great person that was full time. We created a across our multi sites that, in the case of this study, was eight sites across the globe. We created a bi weekly clinical trial report that we sent to all sites, and we showed how each site was performing. Yes, how many people are recruiting? How many people have been lost to follow up where we and just bar chart across? And it's interesting how that creates a little bit of a competition. It does among the PIs and among the site staff. And again, what gets measured gets met. The old saying goes, and when people start seeing that they're being tracked, it's a mad it's amazing what types of behaviors you see change

Denise Bronner  26:40  
 yeah. And I think the other thing too is allowing also for sites to kind of share best practices. That's something that we've also seen. It has worked really well. So if you are putting it out as a report, you could say, hey, here was a challenge that this slide to face. This is what they did to fix it. Or does anyone have any suggestions that also was a great way to kind of create camaraderie, but also create competition as well.

Angela Paterson  27:01  
The main thing that I see with patient retention is the burdens and patient you know, if there's, if it's too much, they just lose interest. You know, they're not, they're not interested in that 50 bucks that they're going to get at the end. Yeah, it has, you know, if, if it's weekly, if they've got to go, go to site far too often. They get bored, especially if they happen to have the non active device or the placebo or whatever. So people get lost that way. So it's trying to keep that burden as low as you possibly can with and still get the data that you need. Yeah,

Marc Jones  27:37  
I just want to highlight, very quickly, you said patient centricity, and I think that that's what this is all about. It's very easy. And it's very easy to default to getting all your smart people in a room at the very beginning and designing the perfect it's kind of like The Simpsons, where Homer Simpson designed the perfect SUV, the canyon arrow. I'd encourage you go watch that on YouTube tonight. You'll you'll understand where I'm going. You can kill patient interest very quickly and not get anything. Yeah,

Audience Question  28:06  
just on. I know we're running out of time, but decentralized versus centralized to make it easier on patients, any thoughts or, I mean, I know that kind of in a movie continuum. I don't know where we are today, but the less we can refer patients coming central ideally is going to be better is that, are you seeing that in practice, or worry about it's

Denise Bronner  28:24  
possible it is. I think it just you have to be very smart about how you're doing that, and if you're putting the decentralized components of the trial in a space where patients actually can have access to it, because a lot of times they'll think of doing, you know, wearables, or having, we can go and get certain labs done, or things along those lines at different places, but are you in the right spot for those patients? So

Jeff Chu  28:46  
Great way to end it. Well. Thank you. Everybody. Loved the conversation. Thanks to our panelists.