Trials with Maya Z

[00:00:00]

Hello, everyone. It's Maya again from Trials with Maya Z. And today, I have a very good friend of mine joining me in a very interesting conversation, Raymond from CRIO Clinical Research. Raymond is another entrepreneur, founder, and CEO of CRIO Clinical Research with a great background in clinical research. But Raymond, tell us more about yourself.

Yes, thank you. My name is Raymond Nomizu. I co-founded CRIO back in 2015 after having run and operated a clinical research site. I'm a lawyer by training. Never really practiced that long, jumped into the business side was a management consultant for a long number of years, and had a lot of experience consulting companies and strategy and process.

I like to think that I have a bit of an outsider insider perspective on clinical research. I have a foundation and process design and strategy outside the industry. But then when I acquired a clinical research site in 2012, that's when I became an insider and really learned the clinical trial business from the ground up, really understanding things from the site perspective mainly.

And since then pretty much tried to learn as many perspectives as I can in this industry.

I remember when we first met, that was a few years ago. It was right after the pandemic started. And actually, it was you and me and two other friends of ours, like having these conversations, what do we do next? How do we overcome the COVID-19 situation? What can we do to support the industry? So it was quite a lot of fun.

And I remember from our conversations, you always bring this perspective from the site. I know you you own the site and the crew is working quite a lot with sites. I know that you're in the middle of the storm and right now there is a storm, not only now, but in the last couple of years, but especially the last couple of months, everyone's screaming, do something. We need to support the sites. And there are plenty of solutions and technologies and so on and so forth, but we keep screaming, help the site. So, Raymond, tell me what is actually happening from your perspective.

Thank you. Excellent question. So I think this is the blind spot in the industry. And it's what I saw when I was running a site. Clinical trials are extremely enormously complex. Every protocol is different from another protocol. Every aspect of running a clinical trial is different from study to study from the way vitals are taken to the way ECGs are taken to what labs are taking to all the eligibility criteria.

It's an enormous amount of complexity, and historically, sites have not had great automation to manage that kind of complexity, and yet, if the sites are not equipped or capable of managing clinical trials, what happens? What happens is, quality suffers. There are protocol deviations. There are Kappa plans put in place.

Monitoring becomes extensive, right? So you start to hear these horror stories of, oh wow, we have to send another monitor over there. Oh, this monitor wasn't able to get everything done in that eight-hour day. Let's go back and send three more monitors in two weeks. And, oh wow, the PI hasn't logged in for two months.

Let's figure out what's holding up the closeout of the trial. So all the problems accrue to the sponsors. And... I know that there was a sentiment three years ago, maybe during the COVID pandemic that perhaps we could get away with the sites. We might be able to go right to the patient.

Well, no, that's not realistic because ultimately you still need a Pi So whether it's a fully virtual trial or a physical trial, you still need a PI To provide local oversight. And from a regulatory perspective, we really do want the PI to be independent of the sponsor, right? So you have to have this layer of locally entrenched, and we're still finding it.

You still need that physical site. You still need that physical presence. You need that investigator site that's independent, and that has a direct relationship with the patient. So the industry spent a lot of energy and resources trying to disintermediate the sites only to conclude, Hey, you know, actually, we do need sites.

And what are you doing with sites for the past 30-40 years, right? Giving them enormously complex protocols, giving them lots of tools and technologies that someone else is choosing, right? For the duration of that study, which may or may not align with site workflows. And even this movement towards DCT added to the complexity, right?

And so the sites have to juggle all this complexity, so of course they're struggling, right? So I could go on and on and on, but I think that's the core problem with this industry. And that's what CRIO was set up to do, is to address this by giving the sites that kind of end-to-end automation.

That makes them run efficiently and best quality at the point of capture. Right? And now with CRIO, we can actually start to tackle some of these problems that the industry has been struggling with for years.

That's great. And I'd love to learn more about it. But before that, because like I said, plenty of solutions out there and technologies. And you mentioned something that is very key here. So I'll bring you back to that. You said someone else chooses the solutions of the sites. And I know exactly what you mean, literally sponsors or CROs choosing the type of technologies and solutions that the site is then supposed to use during the clinical trial.

That usually results in sites having to use multiple solutions at the same time because they have different trials. So I understand the rationale behind The site must choose its own solutions and it should be probably one or two solutions for all of the trials that they're managing.

And that definitely provides better convenience. How is that possible from the sponsor's point of view? Like, have you thought about that?

Yeah, exactly. So that's the core problem. The way we view it at CRIO is we're going to focus on what we do best, we're going to make our platform interoperable and we're going to build APIs, and data information exchanges with other systems. We're starting with ePRO right now. We are very interested in setting it up for labs. We're very interested in sending up with IRTs. We can extend it to wearables. Basically, the idea here is that if we can start building partnerships with other eClinical vendors, we can then go to sponsors and say, hey, for your trial, here's a group of eClinical vendors that you can work with that work with our technology. And by partnering with them and with us, we can collectively deliver a solution for you because what we can do is we can close the last mile. So There's no reason why we can't be a better ePRO vendor.

right? We're a site-facing or desktop tablet oriented on technology, and when there's a non-compliance event or a safety event or some type of an event that comes from the ePRO that requires site follow-up.

Right? How is that done right now in the industry? The ePRO vendor will simply send an email or text message to the coordinator or say, hey, log into the board. Right? So that's yet another login. Right? And then the coordinators have all these logins for that study and they're busy. And what makes it worse is that the site management actually doesn't know that there's an alert. They don't actually know that there's a fault. Why? Because when I was a site director, I wasn't on the DOA log for all these trials, right? I actually wasn't allowed to go into the ePRO. So, if somebody didn't follow up, if somebody didn't comply if the patient wasn't complying with the ePRO requirements for a trial, which by the way can make or break randomization.

I didn't know that as a site director. Right. I knew conceptually that maybe they're in the run-in period and there's a certain minimum compliance requirement. So I could create a workaround where I could say to the corner. Hey, your job is to go into the portal and report back to me.

But I didn't have the tools and the information to enforce compliance. You know, at the coordinator, at the site level, where I can make sure that the people actually follow up, right? Because that's the key, right? You want the site to follow up with the patient to ensure compliance.

That's what's missing in the industry is that sort of closing at the last mile. So the way we're going to build our ePRO integration, is that we're going to, ideally, we want the sites to basically provision the ePRO from within CRIO. When EPO says, hey, there's been a noncompliance event site follow-up.

We want them to send a message to CRIO. We can create a workflow. And the site management will know that there's an event. There's an action that requires follow-up by the site staff. And then we're going to create a workflow and we're going to allow the site staff to resolve each of those issues as they come in.

And what that does is it provides full transparency for the site. Right now, site directors and site leadership are empowered to actually deliver on the quality. And that addresses one of the weaknesses of this industry, which is a lot of sponsors say, Hey, I've got these KPIs, right? Like one of the KPIs is.

Patient retention, or, you know, compliance with ePRO, right? That's actually one of the KPIs, right? Well, the site directors don't know those KPIs. I mean, I've never seen an industry where you work with another vendor and you have KPIs, but you, keep it secret from the leadership of that vendor.

Do you think it's a secret actually, or it's just a lack of communication? Because I don't think it's like a real secret.

No, it's not deliberate, right?

De facto, that's how it ends up. So you're not giving the management of the vendor, your scorecard that you're holding them accountable for. And so that's where CRIO can solve this problem. So rather than being an ePRO vendor, we want to create that ePRO workflow, right?

So we can close that last mile and make that ePRO more effective, right? And have that last loop there. And that's that concept. And, I can go on to each one of these vendors to whom we want to extend this so that we can have a site-facing platform with all the automation from end to end. And yet the sponsors can still pick the elements, the wearable elements, tie them into the site workflow, and get a better result.

Okay. It will be like a key to other ePRO-like vendors. Okay. But let me challenge you here. Does this mean that you have to literally go and work with all the ePRO vendors and they have to customize their solutions to fit your solution as well? How would that work?

Yeah. So the way we want to work with other vendors is we want to have a point of view about the workflow, right? Starts with our workflow. It should allow the sites to do what they need to do. It should allow the vendor to do what they need to do, and we need to articulate that workflow.

And the clinical vendors that we work with, that we partner with, should be willing to work within that framework. If they're not, then it doesn't make sense for us to support the integration, just for the sake of integration. Rather than have, if we had, say, ten partners, ePRO partners were making a number rather than having 10 different ways of working together.

What we want is 1 core workflow, right? I'm sure there's gonna be some variations, whatever, but we want to be able to go to a sponsor and say, because of which 1 of these 10 vendors you pick, they're going to interact with CRIO. Fundamentally, in the same way, you get the assurance that there's a complete workflow solution that works for the sites.

So you get the compliance that you want and we can take that. You don't have to worry about the inner workings of the integration, right? We certify to you that we've tested it in the sandbox and that it works. That the integration works according to, you know, the workflow that we've envisioned. So the only way the integration works is if 1 party kind of takes the lead and says, this is how you're going to operate with us.

And I think if we can get a group of eClinical vendors together on a platform and we work together, then I think we can have huge value delivery.

And what happens if the site works with another automation tool then

We actually are open to integrations with other site tools. So we have already started the journey to integrate with the EMR systems. We actually can now ingest medical records right from Any at least in America with any, hospital health system that's connected to the health information exchange.

And we want to take that to the next level that that care integration. We are willing to work with other eClinical vendors that meet site requirements as long as we kind of articulate those workflows. There is sort of one, element of our strategy where we do want to be proprietary, right?

That's clinical data captured by the sites. We don't want to negotiate with that, right? That's the essence of what we do, right? With that as kind of the basis of what we do, do we have to be The vendor that the site uses for accounting or financial collections?

No, we don't have to. Do we have to be the scheduling app that they use to schedule appointments? No, we don't really

have to. Um, we just have to integrate and interoperate.

So you see yourself as the ultimate collaborator, the one that builds the partnerships, you have this core that you know you're the best at, and then everything else can be worked through partnerships and collaborations. Wouldn't that make you something like a marketplace then?

Yes, another question then Raymond, you mentioned the EMRs. And that it's only for the States. Actually, that's one of the biggest issues that I see. Providers focus only on the United States and not necessarily being able to provide a solution from outside of the states.

And we all know that in most cases, phase two, not to speak about phase three clinical trials, they become global. Can such a partnership type of approach scale globally?

Yeah, that's a great question. And the way we handle global geographies is we have a regional server, we have 1 in the EU. We have 1 for the Asia Pac, and we can spin up new servers.

So the idea here is that we can keep the PHI localized, which addresses a huge regulatory concern. We can then interoperate with other vendors, obviously, they have to be GDPR compliant, but I know on our end, we can absolutely serve global trials.

The way our system works and the way our delivery model works for sponsors is that the configuration of the study template, if you're using our eSource EDC solution is global. There's one template. You can have multiple language versions of that, but it's, no different than having a V one of V V1a V1b V1c You can push the different versions to the different sites around the world When the sites collect the data, and we will send that data, even if they're across different regions into one. Regional server in the United States, which is on an anonymized basis. So PHI never crosses geographic lines. And then, the sponsors can review that data pretty much in real-time across the globe.

So we've already set up the global infrastructure. It's already there. And so I think we have something already that's scalable and we can already service global trials today. But, hopefully, that addresses your question.

Yeah. And I guess that the next step would be to identify these local champions of these other solutions, basically, that can provide the other piece of the puzzle that you can connect and then work together.

Yeah. Yeah, absolutely. And it's hard. We have a lot of аdoption the United States among US sites, Australia, and obviously the English-speaking countries, but, it's obviously been harder for us to generate adoption in particularly non-English speaking countries and some countries with lower budgets because of our price points. So what we've had success with and we're rolling out is the concept of finding local sites and site networks that adopt our technology in a region. And then having them be essentially resellers for our technology. So we've had huge success with that model in Brazil, for instance, because we have an amazing partner in Brazil who's done a great job, servicing, other sites and site networks and, and the economics have to work with both parties.

But we definitely could see ourselves expanding through that model.

I wonder now, like in Europe, for example, you have these hospitals, these medical centers that are also a site.

So where do you see this is the future of sites?

I think. We're always going to have essentially 2 different kinds of sites in my mind. I kind of simplistically divide into AMCs and hospitals that are like AMCs and behavior that primarily focus on, their own patients versus, I would say private research sites, community physicians, and maybe smaller healthcare practices that are a little bit more nimble and entrepreneurial about this.

I think on the latter side with sites and, community physicians where we've had most of our early adoption, we're starting to get a lot of interest from EMCs. But in that latter group, I am definitely seeing a trend towards network consolidation just because there are tremendous efficiencies. And I think what's going to happen is that it's very hard for a small physician practice just to adopt research.

It's a very different workflow, right? This critical scale issue. It's hard to build up a study pipeline. And so I think what's going to happen is you're going to have the emergence of those networks that can partner with those physician practices and stand up research. So I think you're going to have both models for a while, and I think it depends on, for each trial, where the patient population is, right?

So, oncology, particularly late stage, is going to be skewed much more to the AMCs, maybe some of the rare diseases. But any indication or chronic disease that's more community-based, I mean, that's where the sites can really excel. So what I've seen when I looked at the data is if you look at the site selection it's almost bimodal it tends to be either AMC-centric or sort of site, small doctor-centric.

And do they require completely different solutions in your opinion?

I think the core solutions are very similar, but there are some differences in features, I think the big difference for the AMCs is that a lot of them are going to want some kind of integration with the EMR system. And that's going to be the next stage of our journey how do we really take research and integrate it with care at the provider level?

Um, yeah. And that's actually gonna be a big differentiator for CRIO, right? We all know EMR systems are opening up. Now there's a lot of EMR to EDC, like integrations and all of that, right? But think about an EDC. They can't have PHI, they're not a provider tool, right? So, the integrations are extremely limited, right?

It's just grabbing a data point and sending it in. We are a site-facing tool. We are a tool that, that is absolutely 100 percent free to use PHI. That's basically a private sort of site-facing workflow tool. And what we do is, we can take medical records, EMR data, and we can ingest that data, and then we can allow the principal investigator to curate that data, reconcile that data, review the data.

Do some kind of a workflow where there's a PI review of that data and curation before it goes into the official study record, where it then becomes visible to the sponsor, either directly through our application or through transmission to the sponsor-facing reviewer application. So that's a piece that's missing because it's very hard.

To just blindly insert EMR into data because it very rarely maps one to one almost always you're paying a principal investigator to curate and interpret the medical records, right? So I think what we do and what we bring to the table is the ability to give that investigative site that kind of research-oriented tool, right?

That can integrate freely with their EMR system and allow them to curate and reconcile. So the real data flow should be EMR to site eSource. And then to the sponsor system, it has to have, you can think of it as a pit stop or a middleware, I don't care what you call it, it has to have a stop within the site facing system.

I think that should be a requirement because you mentioned something that I'm not quite sure. I agree. You mentioned that medical records are more accessible now. I mean, they are, but I don't think that in the future they will be I mean, at least I'm not sure. Let's say 100 percent sure.

If you see different trends in different parts of the world in some countries, though, we were expecting more access to medical records. They actually Tightened like the regulations and it's becoming even harder to get access to these records So I wonder what will happen worldwide like even in the States I wonder if one day people will just go out and say hey I no longer want my record to be accessed and so on and so forth and probably What you're doing with this middle stop is some sort of an insurance that your record doesn't go to just someone But your doctor reviews that and only when they think that record Is actually that patient is, a patient that might benefit from.

Learning more about the trial, being qualified, going through a screening visit, and so on and so forth. Only then, they should go to the next final step, let's say sponsor or whoever.

So it makes sense to have this definitely. And I have one other question. You mentioned the communities, the community hospitals, and you mentioned that, it will be very hard for them to start like to become clinical researchers. Let's say centers. And I understand your rationale. Basically, on top of your head is how do I scale that as a business? How do I get more and more studies, et cetera, et cetera. But what about just being a community? I mean, is that even possible?

Do doctors think in that way? I'm not looking into building this as a business. I just want to make sure that my patients can also benefit from clinical trials.

Oh yeah, completely. Totally. Absolutely. And that's why if you are a physician and you have a core business in healthcare and a patient base, you don't need the same revenue hurdle, right, to have a clinical research business to be successful. It can be sort of ancillary and you can leverage a lot of those shared costs.

But it's still a hard capability to adopt. there's still a big learning curve, and I think there's a huge benefit to partnering with an operator. That's knowledgeable of the space. I can do the budgets and all of that. So that the 2 interests are aligned. And I know, at least in the United States there is a big push for diversity in trials, and we're not gonna get diversity in trials unless we bring new investigators.

And obviously, if the current investigator mix. We're servicing diversity, we wouldn't have a diversity shortfall, so we need to bring new investigators into the mix who have access to these populations, but many of them don't have the time or the resources to learn how to do research because it is complicated.

And that's where I think you can have that alliance between those service operators, who know how the clinical research component and partner with the physicians. So now the physicians will have to learn some basic GCP, but now they can focus on patient care and doing the PI oversight, that they sort of are trained to do.

But not have to worry about the administrative aspects of

Mm. And do you actually plan on expanding in that direction, or partnering at least with such operators? Actually, this is the site management organization more or less.

It. It is. It is. And there aren't clients naturally. And we're not a service business because for us to service our clients, we have to be neutral and not, be a competitor to them. But, as a company, we're very committed to this mission of diversity. And we think that our technology is uniquely suited to meet these diversity challenges in partnership with, the entrepreneurs, the operators, and the community physicians, and we can't replace the power of a locally embedded, highly empathetic, highly trusted P. I. Like that's gold, right? But we think our technology can be a part of that solution delivery. So we're very active in industry consortiums and groups with other stakeholders to make sure that our technology can evolve to meet those requirements.

That's great. And Raymond, I love that you're speaking about collaboration and partnership because that's something we lack in this industry. More transparency, more collaboration. So it's great that you're going after this, and I wish you good luck. And I hope that everyone who listens to this podcast and has some sort of solution can reach out to you.

And probably you can start thinking about this partnership. And you can tell them a little bit more about yourself. Plans for expansion. So thanks for sharing this. I have one last question Because I'm trying to collect different opinions about what is this one thing that can really change the success rate of clinical trials So if you can think of this one thing that can change clinical trials to make them more successful, what would that be?

So, of course, I'm going to say technology or site-facing technology, but I'm going to, I'm going to say, I think a really important component is the protocol design, making sure that the eligibility criteria are realistic.

Making sure that the protocol, both the eligibility, but also the burden on the site and the patient is realistic and basically being able to put yourself in the shoes of the patient and the investigator and say, how feasible is this?

How, realistic is this, I'm competing against other people's time. And what other times there are, what are the therapeutic regimens they can do. Is this compelling enough? So I think that sort of view and perspective and informing that protocol design. I think that's hugely important and totally underutilized.

Thank you for this answer, Raymond. And once again, good luck with what you're building. And, yeah, thank you once again for your time and answers.

Thank you very much.