In our third episode of Ask a Pathologist, our guests Staci J Kearney and Ciara Martin each share their top three tips for implementing digital pathology workflows. Listen now:
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As a biomedical professional with more than 10 years of experience, Staci Kearney has a passion for driving diagnostic, medical device, and pharmaceutical innovations to market for the advancement of patient care. She’s the Founder & President at Elevation Strategic Development, LLC.
Ciara Martin specializes in the commercialization of spatial biology workflows. For nearly a decade, she has focused on the development, validation, and implementation of biotechnology technologies, with a focus on digital pathology applications. She is a Principal Consultant, Clinical Biomarkers at Elevation Strategic Development.
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Transcript
Bianca Collings: Welcome to the Ask a Pathologist podcast. My name is Bianca Collings. I am the vice president of marketing for Lumea and I also sit on the executive board for the Digital Diagnostic Summit. And today we have a really amazing episode for you. It’s a hot topic. And speaking from the summit, the diagnostic summit, we created that event to give the industry a hands-on, step-by-step, really white glove experience on how to get started in digital pathology or how to break it down. It’s not just this academic high level. We really give our attendees the tools that they need so they can walk away and implement.
And so that is why I’m so excited to have our guests on this episode today.
We have Staci Kearney, who is the founder and president of Elevation Strategic Development and she’s going to tell you a little bit more about that in just a second. And we have her colleague, Ciara Martin, who specializes in the development, validation, and implementation of digital pathology workflows. And today we are going to just dive deep into the nuts and bolts of implementing digital pathology workflows. But before we do that, I would love Staci first for you to give us a little bit of background and how you got to where you were, and then Ciara, the same.
Staci Kearney: Yeah, absolutely. Thanks, Bianca. Really appreciate the opportunity to speak to your audience today. This is a topic both Ciara and I are very passionate about. We are committed to this field and this industry. And so enjoy getting to share our knowledge and experience with those who are interested in either entering into or expanding their experience in digital pathology. Actually, my background is that I got my PhD in immunology as my start. And when I was going through graduate school, really the emergence of biomarkers was happening.
We had a few examples in the HER2 and EGFR space, but PDL1 was starting to become very much talked about and I was focused on the utilization of the immune system and the pathways that could be used to combat cancer and for oncology treatments. And so I knew that I wanted to be a part of the storytelling and bringing life-saving treatments into patient care. And to me, I was looking for opportunities in grad school to go beyond the bench and understand how I could participate in the industry and took a course on regulatory affairs and wound up working towards a certificate and figured out that that was my sweet spot. That’s what I was passionate about.
This was the gateway to getting into the clinic where regulatory authorities and helping brilliant innovators tell their story, organize their data, and push that through the regulatory process. So my first out of grad school, I went into regulatory intelligence and it was some of the first exposure I had to the FDA starting to talk about biomarkers in a regulated fashion. They were having some town halls, things were starting to happen, and I realized I wanted to get involved in that scientific side of it. So one of my first movements was to begin working more on assays and biomarker development and landed at a company that did AI software development, or at the time, we were just image analysis.
We weren’t quite getting into AI yet. And we were using that in the CAP CLIA setting and developing that through pharma and looking at CDX applications or patient selection and building out the ability to bring digital pathology into a regulated IBD space, whether that was in the U.S. or Europe. And that’s how this blossomed and I realized then that this was growing. It was growing big and this industry needed some specialization in it to understand how do you, whether it’s through the LDT space or as an IBD, getting these tools into the hands of our pathologists to enhance patient care.
So I realized there was a need for that across so many companies. So that was the birth of Elevation. We are a regulatory, clinical, and quality services organization and we have a very high specialization in digital pathology and the development of these products, again, both in the laboratory setting, as well as for manufacturers. So it’s been a journey of luck and fortune, I would say, or fortunate circumstances that’s brought me here. And I’ve now been in the field coming close to 10 years, which is really hard to say. So it’s been a great journey. I think we wanna push it further though. We wanna see it expand and more adoption in the industry.
And so that’s what we do every day.
Bianca Collings: Well, absolutely. I love that it was almost a perfect storm for you.
And you were the perfect captain to get the ship through the storm and it is expanding. And you are not in this alone. You have quite a fine group of individuals that work by your side. And Ciara, I’d love to hear a little bit about your background and how you landed where you are.
Ciara Martin: Very, thank you. So my background is in toxicology. I got my Ph.D. in molecular toxicology from UCLA and I’ve approached, I kind of steered my career into this field as a technophile. I just love new technology and exploring it.
And so that’s kind of how I ended up here.
And that’s kind of the arc of the story of my career. So in graduate school, I was doing live imaging at the synapse and using genetically encoded reagents. And then I ended up kind of taking that experience and working with Staci at the image analysis vendor, and I was very fortunate and excited to lead an effort there to have a CLIA LDT validated and then implemented in a clinical trial with image analysis and IHC for patient selection. So that was a wild ride.
It was great and I’ve kind of been hooked ever since I’ve been focused on IVD and CDX development.
I’ve really been in the commercial space and in particular with spatial biology. So that requires the implementation of staining, you know, at benchtop or automated, and then acquisition, which can be quite complicated, complex. And then, and then once you have that image, how do you extract the data from that in a meaningful way and consistent across sites and studies and so forth? So that’s kind of where I’ve been and how I got here.
Bianca Collings: Oh, I love it. I resonate with the tech junkie part. That’s my background, but not the toxicology. So this is, I appreciate the expertise that both of you obviously have. And as we dive into this, the nuts and bolts of implementing digital pathology workflows, hoping that you’ll share each with us and we can rotate your top three, I’m sure there it’s, there’s a lot more than three – six, actually. So I’d love to hit on the top three.
And Staci, we’ll start with you.
Staci Kearney: Yeah, that’d be great.
So I think one of the places when, or areas where we get, for those coming into the field who are thinking, and COVID really did expand the interest or the curiosity about the ability to implement a digital workflow in a laboratory out of necessity, quite frankly, to keep our pathologists safe, healthy, and doing their job for their patients. And so then the question is, what is this? How is this regulated? What do I need to do? Like, where do I start from a regulatory perspective, meaning, or a compliance perspective? And, you know, the regulations for a laboratory to implement a digital workflow are still the CAP-CLIA environment here in the U.S. And so whether you’re CAP accredited or you’re CLIA certified or both, this is what you’re operating under. This is what you need to build your quality system under in order to support a digital workflow.
So the challenge of that and the reason why we get the question is because if you look at the CLIA regulations, you’re not going to find very much about implementing a scanner or validating a monitor. In fact, you won’t see anything. These regulations were written in 1988. They have not been updated since. So not a lot you’re going to learn there.
CAP has done some work. They have released some guidelines on this front, whether it’s validating a digital system for primary diagnosis. They have some information they’ve provided on AI software. You can find it on their website. But I think a lot of the work has actually happened by our pathologists in the field actually, and that the studies that are being put out and published in peer review journals are by pathologists implementing this in their laboratories, whether it is perhaps validation during COVID for a remote review, which under the CMS memorandum and enforcement policy, that is a possibility right now.
For pathologists, it’s an option as long as you are tied to your institutional CLIA lab or whether they’re validating AI software tools in their laboratory they’re going to use for clinical use. A lot of KOLs in this field are publishing sound, important studies on that front. So the work is actually being done by the industry itself in a lot of ways and staying ahead of the regulations. And we do have the opportunity, I think the digital pathology field right now lives and breathes in the LDT space. Meaning, if you look at the number of FDA-cleared or approved products we have, it’s somewhat limited based on what we actually see being used in the field. And that’s because pathologists and clinical laboratories are validating the use of these tools in their own laboratories.
And the innovation is definitely happening there. I think for manufacturers they’re working on it, they want to bring more tools as well. But yeah, so that’s actually where the information is coming from and the resources are really coming from at the moment, but really at your baseline, you’re being regulated under CLIA.
Bianca Collings: So – Okay, that’s fascinating. So it’s coming from within, it’s being regulated from CLIA. Before we move over to Ciara, I wanna ask one question cause you said it right at the beginning. When a pathologist considers going digital, is the first thought compliance and regulatory affairs? Is that the first, is that top of mind? Or is it, what do they shop for solutions first and then come here? I’m just, I’m curious about the order here.
Staci Kearney: Yeah, and I’d love to hear Ciara’s opinion on this because she’s the technophile. So I think probably they look for the platform first. Then, and Ciara I know can talk more in depth about this. Then it’s about which components do you need and how are you going to tie it together. Then we start talking about what does it mean to have compliance with those.
Bianca Collings: Sure, okay.
All right, well, let’s go from Ciara because I might have a follow-up to that.
Staci Kearney: Yeah.
Yes, I would completely agree.
That’s exactly what I was thinking. I think it’s…
It’s fairly rare, not just for pathologists, but any scientist in the translational space to think first about compliance and regulatory, and unless you came out of the regulatory space or have been burned before, maybe, but typically individuals who have this deep technical expertise, they’re gonna be thinking about how they’re, the scientific question, and how do I answer the scientific question, and the tools that enable you to do that. And if they’re a technophile, then maybe they’re thinking about how can I use this cool new tool I heard about, right, to answer, and maybe I can find a question for that.
Bianca Collings: Sure.
Ciara Martin: So I do think that individuals, pathologists in particular, yeah you do tend to start with the tools and that was that was kind of leading to one of the questions you had
Bianca Collings: Yeah we’re okay to go there yes for leading
Ciara Martin: Yeah so what the kind of typical question that we get which is what is the pathologist’s role in digital in the digital pathology workflow and in particular for AI applications and so to just step back if we think about the arc of digital pathology and everything that it encompasses as a workflow you’re starting with a slide and you’re going to stay in that slide and then the digital part really begins it’s the image acquisition where instead of sitting in front of a microscope you’re going to have a scanner that would be scanning the slide or a yes typically would be like a flatbed scanner but you could also have like an upright microscope sometimes there’s a lot there’s a lot of different solutions and then that slide is going to be digitized so then you’re going to have a digital image and that needs to be stored and then you’ll be able to need to recall that image so there’s lots of software solutions for doing that you know on the computer itself or in the cloud sharing and sharing across sites and being able to view those simultaneously with multiple individuals and assign tasks and things like that.
And then even beyond that, besides just viewing the images, then it becomes how do I annotate them so that I can remove regions that, you know, maybe there was a fold in the tissue or there was some necrosis or something happened that I don’t want. I just kind of want to ignore it, especially if I’m going to be bringing in AI algorithms to decipher where is the tumor in the sample and where are the cells, how many cells, how many cells are positive. These are the things that the pathologist is always there in guiding the entire process.
So particularly when it comes to annotations and QC of slide quality as well as QC of staining and then really for developing the algorithms that has to be done hand in hand with the expert who understands what is appropriate and what’s not appropriate and can then can determine, you know, the settings that are ideal, given that particular study so it’s really, there’s multiple steps to the workflow, the pathologist is, or histologists, they’re always there through the whole process and you’ll see, you’ll see different individuals come in and out right so when you’re in the beginning, you’re going to have a histologist and then maybe when you’re more in the data phase you may have a computational scientist, a data scientist, or translational scientists who would be working hand-in-hand with the pathologist to interpret the data.
Bianca Collings: No, it’s perfect. I love that you brought that up, that the pathologist, what, you know, what role exactly, right? What questions do they have and how they, how do they fit in the decision, especially the decision-making? And I’ve found that you know, you get the pathologist, you get them on board, you get them thinking and working through these things, then you can, it’s a lot easier to get upstream than it is to go from the top to go downstream to the pathologist and get them kicking and screaming.
Staci Kearney: And Bianca, I just thought I might just add, because I think it’s such an important point for pathologists who are thinking about coming, going digital, if you will. Um, you know, these workflows are really meant to enhance what the pathologist already does in their job, not to replace. And I think, because they are a critical component as a human in the loop, as we like to say in AI, that the quality of the outputs are driven by the pathologist reviewing this and determining that the device is functioning or the product is functioning properly. So it truly is an enhancement of the clinical workflow from the beginning. And so I think that’s an important point we try to stress to pathologists we’re talking to you about who might want to go into a digital workflow. There’s very little replacement. It’s usually just an enhancement.
Bianca Collings: That’s a good word, enhance. And actually, you said at the very beginning of the podcast,
Enhance versus replace, and to know that we, back to your first point, the information we’re getting, it’s from within. We are so dependent on these pathologists and using, you know, AI as an enhancement or a quality check or quality control and not, not at all, and at least in our frame of mind to replace. So, both of you are very, I love both the perspectives on the pathologist. Okay, give me another tip on the nuts and bolts of implementing digital pathology or a question that you are frequently asked, Staci.
Staci Kearney: Yeah, so I think, you know, we talked about that once you.
Once you bring a system into your laboratory, now what? And there are quite a few, you know because once it’s in your laboratory and the lab director is now responsible for the outputs of this tool in sign-off, as well as the pathologist, it does come under your quality system. And so I agree with Ciara. Everybody wants to think about the technology first. That’s more fun. But then here we are.
That is about quality because that’s what we do.
So, and I think the questions around, you know, each of those components that Ciara was talking about need to be validated in your system. So I think it’s really important that you may have components from different manufacturers even, but they have to be validated together as a system. So whether that’s the interface with your limbs, even, or it’s your monitor, your scanner, your viewer, your application, depending on how you’re going to use this in your reporting, those components need to be validated.
And again, think about that.
If you’re doing it within your laboratory on products that have not been FDA-cleared or approved yet, then that then falls under your standard analytical verification. You need to think about all of the components you would normally do for that. If you’re – now there are some FDA-cleared systems, then they have end-to-end versus different components. And again, if you’re using it in an unmodified way, then that falls under a verification at your lab.
I think it’s about also, you know, making sure that you understand that the full workflow is now incorporated into your system.
And the quality system needs to support an electronic system. I also will say not to forget about your privacy and security. So when you’re implementing a digital workflow, it’s likely at your institution, you’re going to be chatting with your IT folks now. There are HIPAA concerns as speaking from one regulation, but also just privacy and security in general at your institution that patient information needs to be protected.
And that confidential information. So I think it’s those different pieces that, in a digital space, particularly if data is moving in and out of the institution, you know, thinking about a VPN, for example, your IT departments can usually help you with that piece, but your quality management system and your processes need to address those components.
Bianca Collings: So with your group, do you consult on the type of security that they would need or do you provide, in-house, do you provide something like that for the companies that you consult with? Because that HIPAA and security piece is big because you are adding this digital component to what was prior, maybe, and mostly manual, except for your LIS, your LIMS, and your AHR, but…
Staci Kearney: Yeah, it’s a great question. So we actually, we do design quality systems to meet privacy and security regulations and standards. However, we are always very honest. We leave the IT expertise to those folks who specialize. We do have companies we know that can pressure test a system cybersecurity-wise, but that’s highly technical as you know, a lot of times if you’re at a large institution, you’ll already have the support you need, but if you’re at a smaller one, or you’re more individualized in how you’re implementing this, there are companies that can help with those types of examinations.
Bianca Collings: And at Elevation, you’ll point them in the right direction as part of that consulting.
Okay. All right.
So, Ciara, the next tip or question or most frequently asked question you get in the nuts and bolts of implementing digital pathology.
Ciara Martin: Yeah, I think one thing that we get a lot of is where do I start? Right?
Bianca Collings: Absolutely. Theoretically, it’s all wonderful. Okay. We know I’ve made it
Yeah. So where do we start?
Ciara Martin: Where do we start? So it is different for different individuals, right? If you’re the way that you approach it, if you’re a technophile, you’re like, I’m going to get all the instruments. I’m going to bring them in.
And then maybe others, it’s that we have others in our organization that we work with who are exposing us to these technologies and starting to introduce them. And then we’re adapting them as part of our everyday workflow.
So that is how you get there is a little bit different.
But if it’s something that you are exploring, then the typical, you know, things that I would advise would be going to the Summit. Like, I know you’re going to speak to – speaking to peers and individuals who specialize in that, right, who have experience with the software that you’re thinking about bringing in-house and the instruments you’re thinking about bringing in-house. And really leveraging your network to make sure that the tools are appropriate, and then reaching out to those companies and speaking to the application scientists and the experts and getting demos. So definitely that hands-on time is extremely valuable.
And then I would also add that it’s important to think about who’s going to be using this and in what setting, both in the near immediate use case, but then thinking over the lifespan of the technology, how long you think it will be leveraged then what is appropriate there? So do you need a RUO or a DX version of the software that is often offered, right? And one has more, DX has more compliance, but will limit your flexibility, right? And that’s true for stainers as well. It’s across the whole workflow, right? And so thinking what a pathologist may need may be different than what somebody who is in the discovery group needs. And are you going to be sharing the same instrumentation or not?
And so those are the types of things.
Having those discussions before the technology and systems are brought in-house will save a lot of headache down the road. So that would be what I typically tell those individuals.
Bianca Collings: Okay, so if this is one of the first questions you are asked and you hear, do you give recommendations, tools, software, or is it guiding them to what you said that it’s more peer, peer review, peer guidance? Do you have a set, if they can say, okay, here I am, this is my persona, this is what I want, you know, who we are. Do you, I’m just curious if it’s part of what you do.
Ciara Martin: I’ve done both, so in my role now, it’s different. I’ve worked for commercial organizations that sell particular solutions and of course, you’re going to advocate those solutions, but you never wanna sell anybody a doorstop either, right, because that doesn’t help anybody. So I think I’ve always been very transparent about when it’s an appropriate fit and when it’s not and then you know, in the role now, I can, I would always, I’m always going to tell somebody to reach out to colleagues who have first-hand experience. And then if I had first-hand experience, I’m happy to lend that to the individuals. Yeah.
Bianca Collings: Okay, fantastic. Okay, we have time for one more question, but I’m going to, I’m going to ask this one. And Ciara, I’m going to start with you. And unless Staci, of course you feel like this is more appropriate. Being a product developer, I am not a product developer, but having worked with them and trying to get a product out into the digital pathology market, we’re often criticized for taking a long time and
maybe you could pull back the curtain and tell us why. Why? Why do these things? And the other thing you mentioned earlier is there are a lot of tools out there. Not all of them are FDA-approved. In fact, that process, it’s so long. So you’re getting validation within. And even if I would say end-to-end FDA clearance on a certain piece of software, it seems like it’s more segmented that that’s an outlier to have an entire system. So I’m curious about your take on why. Why does this take so long to get things out? To go to market. A product enhancement.
Ciara Martin: I’ve definitely worked behind the curtain a lot with research and development and marketing teams to push these solutions out the door. And it is a harrowing effort. A lot of the time, you’re trying to…
balance the customer needs and the voice of the customer against the timeline, right? So I don’t necessarily think these are unique challenges to the field. I think it is, but perhaps why this comes up is that there are so many steps to this, you know. There are multiple steps to this workflow and each has its own unique complexity, right?
Tissue is complex. Science is complex. Staining with antibodies is very complex.
And then we love to ask these… really compelling questions that they are driving the science forward and they are changing our therapies, but you know, how are T cells interacting in the tumor versus in the stroma when I do XYZ versus 123, you know, it does get very exciting but very deep and expansive. So I guess that answers it at a high level.
Bianca Collings: And I would say it does, and I appreciate you. Can’t forget this. Yes, this is the technical world, technical world, digital, going to digital pathology. It’s moving towards that whole, you know, the tech side of business and other tech roles that I have had. If a customer base or the market is demanding changes in your product or something new, it’s the time to market, the runway isn’t long. Coming here, it’s so much longer because again, it’s the science complexities and the intricacies and the very almost sacred nature of what we’re handling and what we’re dealing with. So we have to remember that, right? When we’re not getting all the tech that we want at our fingertips.
Ciara Martin: Exactly. And there’s often not just one voice of the customer as well. So there are many customers who use these applications, like user personas is what you would say, right? So we’ve got the histologists, the pathologists, the translational scientists, you’ve got the computational biologists, then you’ve got the executive, right? And so, and it goes on and on and on, right? So when you’re trying to please everybody or get features in that are relevant to those different users, that also will extend your time to market unless your minimally viable product is only for one user persona.
Bianca Collings: Yeah, which is rare, right? And with these complex workflows. Okay, so last question for Staci. Future thinking, forward-thinking, you have a lot of insight on what’s going on in Europe and how that might affect the United States in digital pathology. Hold the curtain a little bit and tell us that. Tease it out because I know that we have
Staci and the Elevate Group, they’re coming to the Digital Diagnostics Summit and they will be a featured speaker and this is probably going to be one of the hot topics.
Staci Kearney: I think so, Bianca because I think it also gets to the question that Ciara was addressing about time to market and why does it take us so long. And I 100% agree with Ciara about the um, that you’ve got to figure out the science first and that is complicated.
Then if you look at the complexity of the system itself and the way that regulators look at that system, not just how the manufacturer looks at the system. There’s a lot of controls and a lot of regulations and a lot of requirements for a quality system to manufacture one of these devices in a regulated space. You have the benefit here in the US under the LDT concept to hold all of that control within your laboratory and do it under the CLIA regulations. Manufacturers who distribute their products are dealing with much larger regulations that they’re addressing. And that brings me to Europe from the perspective of the IVDR, which is the in vitro diagnostic regulation in Europe, was implemented this past May of 2022. So we’re coming up on a year. And what it did in actuality was limit almost entirely the scope of a laboratory-developed test in Europe to be almost non-existent.
And so, I think from that perspective, it’s, you now have a situation where you have to go through a regulated manufacturing process in order to do this and meet certain requirements that are larger.
So even in an LDT space, you have to meet what’s called annex one of the IVDR. This is a long list of requirements that are much longer than the five to seven you have to meet under the CLIA regulations. And not to say that CLIA and CAP do not provide sound quality management systems for clinical laboratories and the environment you operate in, but this is more speaking to manufacturing of these products.
That goes well beyond an analytical validation and kind of reagent QC.
So I think if we look at that and think about that environment and what’s happening in Europe and manufacturers now trying to work toward getting products on the market in a much – with many more requirements, it’s going to go slower. In addition to that, it’s in draft form in Europe but it’s called the Artificial Intelligence Act.
I think if you fall under the IVDR and you manufacture under the IVDR, you’re going to meet the requirements of the AI Act, or the AIA as they’re calling it for short. But if you are a user and you modify the product in any way, and it has artificial intelligence software in it, you now become the requirements of a manufacturer. So not entirely, but I just did paraphrase what we are seeing and how we’re interpreting it in the beginning. So should this proposal get pushed out there, users in Europe could inadvertently sometimes fall under this act. What I think is interesting about the space in general is, as I said in the beginning, digital pathology in the U.S. right now lives and breathes in the LDT space.
However, the FDA has not been shy about noting they don’t like the LDT concept and they are trying to undergo regulation. They put forward a bill called the Valid Act.
It was near passing this past fall, but under the Madufa renegotiation, it did fail.
And so now with sort of the chaos in Congress, it’s going to be tough to get it passed.
However, I think us in the industry who follow the regulatory landscape and intelligence will tell companies and laboratories, it’s likely not an if, but a when that what is occurring in Europe is likely to occur in the U.S. at some point. We will have a transition period like Europe, but if we’re watching what’s happening in Europe, the implementation has been a challenge. That’s just the reality, no matter how much you prepare. So while it’s down the road, as Ciara was noting, when you’re really thinking about the technologies you want to bring into your laboratory, I think it’s a good idea to start thinking about what’s going to happen in the U.S. think about this in the back of your head as to when it could come. Now, I think we’re years out, but these investments are important.
Bianca Collings: They are. And I say go in with eyes wide open and think about the long-term gain of this versus something now. And it’s really good for manufacturers to be on top of this. And so I am really grateful, especially just to have an organization like yours that you are on the front lines of all of it with the education and can help all of us in this industry because you’re right. If it’s going on in Europe, it’s said it’s not if, but when, and we want to be prepared.
I appreciate both of you coming on today. I cannot wait to get more later on this year.
I promise you this is going to probably be one of the hottest sessions that we have. And I imagine you’re going to be flooded with all sorts of questions. And who knows what between now and then what new information will come to light that you can share with us because we are moving very fast, ever, ever-evolving.
So again, thank you both, Ciara and Staci, from Elevation Strategic Development.
And just a little plug, Digital Diagnostic Summit.
You can register at digitaldiagnosticsummit.com. And that’s held in Park City, Utah later on this year. And again, we will have these lovely women with us. So thank you so much for coming today.
Staci Kearney: Thank you.
Ciara Martin: It was a pleasure.
Bianca Collings: All right. Take care. Thank you.
Tune in next month for our next podcast.
Thank you to the sponsors of our program, Lumea and the Digital Diagnostic Summit, our listeners, and our guests for making this possible and for your support.
