The DPA has a lot of stakeholders. We include these stakeholders in our discussions so that we can stay on top of the new developments…
…our approach is to look at all these techniques and ask how we can leverage them and how can we use them to optimize digital pathology.
Interview with Esther Abels
President at The Digital Pathology Association. Chief Clinical and Regulatory Officer, Visiopharm
BIOSKETCH: Esther’s scientific career started in the pharmaceutical industry, however, a desire to not just cure disease but also manage it led her away from pharmaceutical development. Esther, intrigued by diagnostics, found herself working for Philips and on her very first day ended up at Pathology Visions, a major conference in the Digital Pathology landscape run by the DPA. Years on, Esther is now the President of that very same association along with also being the Chief Clinical and Regulatory Officer at Visiopharm.
Interview by Jonathon Tunstall – 14 Sep 2021
Published – 26 Sep 2022
JT – Esther, welcome to pathology news. You are Chief Clinical and regulatory officer at Visiopharm and also the current president of the digital pathology Association. Perhaps you can start by telling us a little bit about your background, how you came into the field of digital pathology, and your current position in the DPA.
EA – Thank you for having me here. I started my career in biomedical health science and also worked in the pharmaceutical industry. That is, in pharmaceutical strategic product teams, proof of concept, research and development, bridging these disciplines, and bringing products to different markets and into different geographies using clinical evidence. I expanded my knowledge gained during my education in health science, by collaborating with colleagues, medical doctors, regulators, nurses, researchers and scientist. This gave me a good understanding of the market landscape, including clinical needs and what were the regulatory legislative initiatives. I always questioned; how can I help there? Can I challenge the status quo to accelerate development, and what would this mean this for the product marketing strategy? What I noticed, is that I really enjoyed exploring, discovering and ultimately bringing new medicines to patients and making those medicines accessible to them. That meant asking the right questions through involving the patients and identifying whether the compounds would really bring benefit to them and to their well-being. This is my true ambition, to be able to really contribute to making lives better.
That ambition ranges from working to prevent diseases – because often that is a function of diagnosis – and of course, we need to treat the patient. I wanted to focus on curing and managing diseases, which means having an understanding of the disease and being able to make a diagnosis. For that reason, I transferred from the pharma industry to the medical device industry and joined Philips, where I was heading the Quality, Regulatory, Clinical, and Medical Affairs teams. We were striving to get our imaging devices on the market, especially focussing on the US to overcome the regulatory assessment made by the authorities that it was initially classified as a high-risk device. That situation later turned around fortunately, and it was reclassified as class two, i.e. a moderate risk device.
Interestingly, my first day, when I actually started in digital pathology, I remember that well, because I went to Pathology Visions. That was my first real day at Philips, and I really enjoyed it because there were many stakeholders present there at that conference. I got to see digital pathology from a lot of different angles including how you can help the patients. That is why I have enjoyed working with the DPA and working in digital pathology.
I later moved more into software and Pharma. That was with regards to focusing more on how we could use the hardware and the images to convert them into something more accessible and tangible that could really add something to life science and precision medicine. We started to work on algorithms to see if they could perhaps identify new pathogenic features to assist with diagnosis, or make better predictions, or provide a more accurate prognosis to guide patient treatments. That is how I ended up joining Visiopharm.
JT – It’s interesting that your first day in digital pathology was spent at Pathology Visions and now, here you are, the president of the Digital Pathology Association.
EA – I believe that Pathology Visions is broad, but at the same time, so specific, and that it manages to encompass so many views and multiple stakeholders. I really think that this is a powerful approach for digital pathology and one that is crucial to the evolution of the domain. I think you do need all of the stakeholders to be involved. That’s why I instantly really enjoyed it.
JT – I can think back to my own history when I started with Aperio in 2008, at that time, pathology visions was an Aperio customer meeting, to which Aperio invited other commercial companies. From memory, the DPA was formed in 2009 to separate the academic and commercial elements and to try and avoid conflicts of interest, and it’s probably fair to say that the DPA emerged naturally from the energy and impetus of those earlier Aperio meetings. Of course, we’ve come a long way since then, and I wonder whether you could comment on how you feel the breadth and scope of the organization have evolved since those early days.
EA – That’s a very good question and you have a good memory, because indeed, Aperio held those user group sessions and Dirk Soenksen of Aperio took charge of the meetings. Then in 2009, it was converted officially to the DPA, initially with a big focus on industry and pharma. We have seen organic growth over the years since with more and more histotechs and clinical pathologists joining the organization. We’ve also been through a phase where the pharma groups disappeared a little, but now they are returning. We also now see the biotech companies who are having to provide the assays and the biomarkers, and at the moment, they are becoming a substantial part of the membership. I think that is extremely important because within pathology itself you have many stakeholders; you have labs, lab directors and histotechs as well as the pathologists themselves. Digital pathology is also a financial project involving disciplines such as IT and many of those people are also users. The patients too are now becoming more tech-savvy and many are interested to see their images and understand what you can see and what you can determine. If you perform a kidney biopsy for example, the patient may ask, ‘what can you see, can I look at the image?’ so everything is changing. And that’s also the story of the DPA. In the early days, the organization was focused on industry, but it has grown organically along with the science and its applications, and I hope that we will continue to grow in the same way. Digital pathology will ultimately become a crucial element in the entire digital health system, and I believe that we should also look into expanding more and more into different areas and different elements. For example, getting more integrated with radiology.
JT – I’m interested that you mentioned pharma, which I do see as a really critical component of digital pathology, because the pharma researchers, particularly in discovery phase, were the early adopters of this technology. Prior to 2010, I remember that Aperio had multiple scanning system installed in all the major pharma companies at various global locations and in fact, back then, Aperio’s entire install base was in pharma. There is a lot of digital pathology going on in early drug discovery processes. So, I can I presume that it is part of the current strategy of the DPA to reengage with those groups in order to bring in both their experience and their scientific contributions?
EA – Absolutely. That is also my strong opinion and also that of the DPA. It’s important to bring precision medicine to patients and we see the emergence of more and more personalised medicine and targeted treatments. This is something that the community wants right now. So, coming back to your question, with regards to re-engaging with the pharma groups, Yes absolutely. They did a lot of the early research work with techniques such as fluorescence imaging, for example, and these methods are becoming important again and getting more and more attention alongside elements such as molecular pathology. Ultimately, we can get more data and link that to radiology, patient outcomes and patient-related outcomes to investigate response rates. We could find extra characteristics, extra features in the histology and phenotype of the patients and then link that back to genotyping and develop further tools for prediction. So yes, I think it’s really important to get the pharma researchers involved again and to revisit the work that has been done in that area.
Going back to pathology and what I think may be particularly important, is the wider use of spectral imaging and hyperplexing. It’s always been possible to switch your stains, by removing a stain from the tissue and starting again, but you can’t do that many times. Now we have multiplexing and hyper plexing linked to digital imaging and I think that opens up a whole new world which better targets treatments and may allow development of the treatment process.
JT – Well this is really such a big inflection point in the field right now. Certainly, we have seen in the past couple of years that COVID has really moved forward the adoption of digital pathology. However, we now have a lot of new image analysis algorithms coming to market and there is also renewed interest in a lot of allied technologies. You’ve mentioned some of those, such as spectral imaging, multiplexing and hyperplexing, but I am also thinking of techniques such as Raman spectroscopy, in vivo imaging etc, which could potentially be very important in a future which is centred on diagnostic imaging. So, perhaps you could comment on how you think the DPA is aligning itself to deal with these big changes in our industry?
Yeah, looking at digital pathology itself, there are of course, a lot of connections and opportunities that are being explored; and, as we discussed earlier, that means the DPA has a lot of stakeholders. We include many of these stakeholders in our discussions, (Abbey Norris our executive VP is an enormous support here) so that we can stay on top of the new developments. For example, we work with a lot of different societies and not only those focusing on digital pathology, but also in radiology imaging and imaging informatics. We’re also looking into and keeping track of what is happening with the latest research – for example in circulating tumour DNA and in the liquid biopsy field – and asking ourselves if we could do something with those techniques. There are certain techniques and certain elements which have been around for a while, but we also see that there are new applications, niche applications popping up all the time. Some of those are actually taking off but they’re not taking off in mainstream practice right now. So generally, our approach is just to look at all these techniques and ask how we can leverage them and how can we use them to optimize digital pathology. For example, there may be other types of algorithms out there that we can optimize. Most of the current algorithms are focused on decision support, but you can do so much more with algorithms. If we can link these to the right elements and the right technologies, we can use the data to optimize them. This is the way the DPA is working, taking it step by step and focusing on current needs in digital pathology. At the same time, we try to ensure that we have the right connections and that we work together with allied societies to optimize the techniques rather than working on the same things and duplicating effort.
JT – Of course, as we develop new methodologies for clinical practice, we also need to think about regulation and that is surely one of the biggest hurdles for all of this development. You mentioned decision support algorithms but if we are to move to a point where a diagnosis can be made via a combination of imaging technologies then the regulation needs to evolve at a similar pace. Do you see any change to the conservative nature of regulation around the clinical application of digital analysis? Do you perhaps foresee an opportunity to move to a form of generic regulation for the entire digital pathology industry?
EA – I believe that it will of course evolve. Thinking back to the DPA’s previous involvement with the FDA and the fact that whole slide imaging devices were moved from class three to class two, that was a big accomplishment. That’s what we are still doing in the DPA. We have a task force focusing on regulation & standards and we are closely collaborating with the FDA to understand their concerns and their needs, because of course we do have to obey the regulations that are in place. In addition, we need to understand their concerns and their current thinking in order to have professional conversations which addresse those concerns. So that is what we’re doing and what we’re striving for.
When we look at specific topics, such as for example, how could we change the algorithms, we may find automated detection devices that are already approved for radiology. We’re leveraging those examples with the FDA and other authorities are also using this same template. The regulations are of course evolving over time and as the amount of regulation becomes more substantial, then in this way, it also becomes more flexible. Most of the developments right now are in software. Hardware is crucial, but it is the software that is being developed at a fast pace. Regulation for hardware can exist over a long period of time, but in the world of software, the updates and the iterations happen very quickly, and verification and validation can also be done quickly. The regulation does need to keep up with this fast pace of development and that is what we see happening. That’s also why the FDA reached out to us, and I should highlight that we now have the Pathology Innovation Collaborative Community. That came about because The FDA asked whether we wanted to form a collaborative community so that they could engage with us. So, in fact, the FDA is ensuring that everybody is involved in giving their input in order to optimize the guidelines or regulations according to their current thinking. So yeah, I do believe that it will change. Things might move faster in the future, but we should not forget that the FDA is there because we do need regulatory oversight and we need to ensure that there will not be any malfunctions or safety issues associated with bringing a device to the market too quickly.
JT – Absolutely. The DPA clearly has a positive working relationship with the FDA and that is continuing but there are other world regulatory authorities as well. The FDA is just one of those. When you consider the number of global regulatory hurdles that a new device has to move through, it seems that we need to look at ways to expedite approvals in the future, maybe that is coming as you suggest and perhaps ultimately some form of balance will prevail.
That does lead me however into thoughts of how our science evolves in the future. I’m aware Esther that you are someone who can view this field simultaneously from both the academic and commercial perspectives. I wonder how you actually see the long-term picture of digital pathology as the digitization of pathology services inevitably becomes widespread and perhaps becomes the norm for both research and clinical laboratories. There are a number of questions I could ask here, but let me start by asking whether you think that all labs will ultimately have to digitize in order to remain competitive? what happens to labs that are just based on the older microscope technology?
EA – That it’s a very good question, I think at this moment, labs can continue as they are and don’t need to implement digital pathology. However, looking at the future, I do think that they will need to have some sort of digital pathology implemented. Does that mean going 100% digital? No, I don’t think so. That is because I think that a pathologist will always remain involved. In addition, you could also take the approach that you just scan a few slides, upload them to the cloud, let algorithms run and work on them, and then get a report back which is evaluated on site. That’s something to consider, rather than the other option, which is to move to an entire digital workflow. However, everybody has their own workflow, so the vendors need to adapt and customize the processes to their needs and there are a lot of things to consider if everything will become digital. I will also challenge this question by saying that we could look at it from the perspective of; can any hospital afford not to implement a component of digital health? That is because this is about more than just digital pathology. You need to look at all of the elements together and everything which is linked to the workflow and anything that can become part of the digital pathology process. It’s all connected.
JT – Yes, that’s right. Perhaps we may see two tiers of pathology service, one tier which is digital and then a second one that you pay less money for, which is a service based on traditional microscopy. In this case it takes a longer time to get the result. I don’t know, but perhaps that is a system which could develop. I’m also thinking however about the young pathologists of the future. Will new pathologists starting their careers in 10-15 years’ time, pathologists who have largely been trained on digital systems, will they be willing to work in a microscope-based environment? From the lab perspective you can only provide a service if you have the pathologists, if you have the labor and the skills available.
EA – That’s a great question. And, of course, I’m not a pathologist, but looking at the generations that are coming up. The next generation are really tech savvy. They’re all working digitally and they’re being brought up with notepads and in a world of tech-savvy computer science. That is why we see an uptake in our DPA education program on how to use digital images to make a diagnosis. So, certainly we can see that the next generation is really interested in digital pathology, and it may be that at some point, the microscope may not be needed anymore. When I’ve talked to some of our pathologist colleagues, Dr. A. Parwani and Dr. L. Pantanowitz for example, they’ve also mentioned that the next generation is totally different and has different expectations. Often during an interview, they will ask, ‘are you working with digital pathology?’
JT – Yeah, that’s an interesting trend, isn’t it? It may become very difficult to recruit into a microscope-based lab in the future. That could very easily happen, and we also have simultaneous developments in algorithmic analysis. How much of the workload do you think image analysis and AI will take away from pathologists in the future? Does the DPA have a view on the future role of the pathologist? Surely, this technology is going to completely alter the workload of pathologists and redefine their working day.
EA – Yeah, I do believe so. Right now, I don’t think that algorithms are yet having a big influence on the role of pathologists, because we only have a few algorithms available that they can use and those need a lot of human oversight. There are also the ethical aspects to consider, an algorithm cannot just take over. So, in the future, I think there may be a few or many areas that could change. When I say that, I’m not only thinking about decision support apps but also about everything else that is related to digital pathology. It could be that workloads remain the same, but the balance of workload shifts. I do think these changes will be on a large scale and we have to consider the entire healthcare industry, everything will change.
JT – So, we may see, for example, a future where the algorithms take over the more routine aspects of the workload, such as screening (we’re seeing that in prostate right now) or counting, for example. Then Ultimately digital pathology becomes a digital assistant for the pathologist.
EA – Exactly, and maybe also it has a role in automatically requesting additional staining based on the H&E slide even before the pathologist evaluates the entire case. Or perhaps in determining the quality of staining. That could be at the level of a single slide or it could say something about stain consistency throughout the entire process. Once the slide has been scanned, you could run algorithms to check on artefacts, or stain quality across the slide and then highlight areas of discrepancy. If the quality is consistent that could feed into the proficiency testing of your lab and perhaps could also help you in your validation studies. Within Pharma for example, when you observe a deviation in the quality of the staining (and this can be due to the stain itself, or due to some other part of the process) its key that you catch it. Otherwise, your response rate might be affected. In Pharma you could also leverage algorithms to identify clusters and new pathogenic features, and in toxicology studies. So, this is another way that algorithms could be used in routine practice as well as in Life Sciences. There are clearly both qualitative and quantitative benefits from this new technology.
JT – And of course, that would be a huge positive to fall out of the use of algorithms if they could be used to enforce consistent quality across the industry. These are certainly exciting times for our industry.
EA – Yeah, absolutely!
JT – We’ll leave it there Esther. Thank you for your time today.
