Y-ECCO Interview Corner: Marc Ferrante

How did you end up as a doctor?

In my family there were no doctors except my oldest brother, who became a gastroenterologist specialising in oncology.  My personal intention at the time I chose medicine was to go to Africa with Médecins Sans Frontières. However, as I got older and got married, these dreams changed a bit. Despite that, I still have my love for Africa, and I am really hoping that Corona will be over soon, because I’ve promised myself and my kids that we will go to Africa and do a safari.

Marc Ferrante © ECCO

So how did it end up being IBD?

My brother Michel was a big influence on me. He actually died two years ago. He was eight years older than me, so he was clearly ahead of me in his career. I had some difficulties in my first year as a fellow with what I perceived to be the responsibilities of a fellow – I thought that I had to know everything already. In the end, I got talking with Gert van Assche – who coincidentally was a friend of my brother – and then Gert introduced me to Paul Rutgeerts and Séverine Vermeire. They recommended that I do a PhD because that would give me greater future options. So actually, it was a moment when I was really feeling bad that gave me these important opportunities. That is something I will never forget: that even in the moments when you really think you are not doing well, opportunities might come up. That is actually how it went for me. I don’t have any issues with sharing that. In fact, in my role as a coach to younger fellows, I often discuss with my students that it is normal to have moments where you question yourself, even your decision to become a medical doctor.

For me, it was during the more difficult times when I got in touch with Paul, Séverine and Gert; they believed in me and gave me the opportunity to do a PhD. Of course, once I was doing a PhD in IBD I got so enthusiastic that I didn’t want to shift to any other disease.

Have you have been at Leuven for all of your training?

Yes, that is quite usual in Belgium – you tend to stay within the one centre where you study. We Belgians don’t have the habit of moving about a lot – we have a saying that Belgians are born with a brick in their stomach, meaning that they build their own house and then they stay in that house forever. That’s actually sort of what happened with me. The idea with my post-doc was to travel and learn some new skills and techniques. Classically people travel to the United States or Canada, but my wife was not able to join me. She supported me by suggesting that I could go alone, but I did not want to do that. So, we looked for other positions that were available. It was around the time that Hans Clevers was coming up with his ideas of using organoids to investigate cancer. Paul Rutgeerts was visionary and thought organoids might be interesting for IBD as well. So, I went to Utrecht, which is only 1.5 hours away from where I live. Then I could be home every weekend and see my son, who was born around that time.

What effect did your post-doc have on your career?

In Leuven they have a policy, which I am in favour of, that if you are going to become part of the staff then you have to have something new to contribute, to go abroad, learn a specific technique and bring it back. That is how I ended up in Hans Clevers lab. This was a steep learning curve for me because I love to see patients and spending one year outside of the clinic was very tough. Also, the ambience was completely different. Although there was a friendly atmosphere, people did not want to reveal all their ideas for fear that others would take them, and this was completely novel to me. I think I can say I am an expert in organoids, but I am certainly not a basic scientist. Just by spending one year in a renowned basic science lab, you don’t become a basic scientist. Rather I regard myself as a clinician who has knowledge on some basic science topics such as organoids.

What are the applications of organoids in IBD?

I think we have to be realistic about the application of organoids in IBD. Of course, they can help us to look at the pathogenesis of IBD and a main advantage is that you have tissue from the patient him- or herself and you can expand the tissue, generating more than enough material to look into different experimental conditions. There might be a role for organoids in transplantation, but we are not there yet. Some mouse studies suggest that you can transplant organoids into a sick bowel. There are some human studies going on in Japan and we are awaiting those data. Of course, we want to do more with these organoids – not only adding microbiota, but also elements of the immune system because these are all interrelated in IBD. But this is not how a basic scientist likes to work – they will start with just one component and then go on to the second and then the third, studying each separately. In Leuven we are trying to set up a system where you have both the epithelial and immune cells of a specific patient as well as the microbiome combined in the same system.

You mentioned that you have a passion for Africa and you actually did some of your training in Africa. How did that influence you?

It is still influencing me today. It taught me that what you are doing in your own country may not be as logical or as normal as you think – that in other parts of the world people are dealing with different possibilities and having to look completely differently at the same problems. I stayed four months in South Africa (Soweto and Stellenbosch) and then had one month travelling, which was very nice – to see a part of the country. Of course, the health system is completely different. Also, later it was very rewarding to travel abroad to meet different people, to network, to influence perhaps in a minor way some part of their healthcare system or treatment of IBD. That is one of the reasons why I do like to travel a lot, although I know that this means that your ecological footprint is not that good, but you learn so much by meeting other people. Also, it gives an understanding that what we have here in Europe is not as bad as we sometimes say.

What are your other research projects?

My main topic at this moment is quality of care. We want to come up with better outcome and also process indicators – particularly linked to our electronic patient records so there is no need for any external programmes to evaluate the data. I am currently collaborating with several hospitals in Belgium where the idea is that we can complement our electronic patient records system to automatically generate up to 70 outcome indicators, not only in our centre but in other centres throughout Belgium. It is important to actually see what you are doing. For example, because of these systems I know that we vaccinate our patients, that we give calcium and vitamin D, and I know how much we use steroids. It’s not just what we believe we are doing with these data collection systems: we actually have the data to show we are doing it. In this way we can learn where we could still improve. To have these data automatically logged in a computer system that can track what you are doing and confront you with it is very helpful.

I am also interested in finding opportunities for combinations of biological therapies. In the IBD community, we have been saying for several years that we need these studies and I have been trying to set up a collaboration where we can run an investigator-initiated study of combination biologics. Unfortunately, the industry is not yet providing us with these data.

Finally, I am also working with the patient organisations on a current issue concerning lack of therapies. Many companies in Belgium have stopped the production of some drugs like cholestyramine or mesalamine enemas, and for some patients this is terrible. For patients who are used to using cholestyramine, to go back from three bowel movements a day to 20 has a huge impact on quality of life – it may mean they can’t work or have social contacts. And the only reason is economics: companies find that they can’t get a good price in Belgium anymore and that is why they can’t keep the drugs on the market. Also, because of the European free market, there are biological treatments which are cheaper in Belgium than in other countries. It has been suggested that wholesalers in Belgium sell their products abroad, meaning there is no longer sufficient drug available for the patients in Belgium though the local pharmacies. I am currently discussing that with the patients’ organisation as well as with the Belgian Ministry of Health and European parliamentarians to try to address these problems. Another issue which is very crucial to patients is that the COVID pandemic has resulted in all Belgian public toilets being closed. For an IBD patient that is terrible. If an IBD patient is coming to clinic in Leuven, travelling by car for say an hour, they normally know where all the toilets are on the way. Now those facilities are closed that journey is a bigger challenge. This is something that we as physicians need to think about – what that means for the patient.

You and I are both involved in the H2O project. Could you tell us a bit about that?

Yes, H2O stands for Health Outcomes Observatory. The health outcomes observatories are working to develop digital tools, including an app, for patients to report their health outcomes in a standardised way. The project will focus on setting up health outcomes observatories in four countries (Germany, Spain, the Netherlands and Austria). Later, if funding allows, the project will be rolled out to more sites across Europe. What we want to do is to put the patient more in the middle of what we are doing. Not to only look at the classical outcomes we have for clinical trials but to focus on patient-reported outcomes (PROs). We are already implementing some PROs in clinical trials such as the PRO-2 in Crohn’s Disease and Ulcerative Colitis, but there are likely many more outcome factors that we could ask our patients about and that may in the future become more important in deciding whether a product is valuable as a treatment. We strive for endoscopic remission and nowadays even for histological remission, but maybe we should strive for a patient who has an improvement in their PROs. So, the idea of the H2O project is to come up with a standard set of these PROs across different countries. This is also going to be developed not only across different geographical areas but also across different chronic diseases, namely IBD, diabetes and cancer. The idea would be that some of the H2O outcome measures we follow up will be more generic; for example, the quality of life scores would ideally be the same across these three disease groups. This aggregated data could also form the basis of research into new, innovative, evidence-based treatments. So, the first thing is to identify the outcome measures that we want to follow up and then to implement them. This will differ from country to country, but as I mentioned before, we would like then to link that to our electronic patient record system. Many companies come to us as physicians with a nice app that we can use to monitor our patients, to identify red flags, to detect whether there is a flare – but as long as this is not linked to the electronic patient record I am not a big fan, because eventually you will have to somehow transfer and link the data. In an ideal world, you would be able to import data automatically into the patient record and patients should be able to access that remotely.

This would be a huge advance, as you say, for use in clinical trials, but will this impact how IBD professionals and their patients communicate in the clinic? What are the implications for the H2O project there?

I would like to have a system where, before the patient enters the office, I already know in which direction the patient wants the consultation to go. We all know that we have very little time to see our patients and that if we ask the same questions to each individual patient, we are not doing a good job. Whereas if you take an IBD quality of life indicator like the IBD Disk, where there are several components in the assessment, you can see the scoring that the patient gives for each of the seven components using their app. If the patient has highlighted problems with fatigue, I can then ask directly about fatigue. Often the patient will bring up the problem at the end of the consultation, so it is a great advantage if you as the physician or nurse can bring it up directly and say ok, let’s talk about fatigue because I see based on your answer that it is quite important for you. I think in this way projects like H2O can help to individualise the patient contact. This seems quite logical, but unfortunately it is not always the way things happen. We sometimes already stand up when we ask if there is anything else the patient wants to ask, clearly showing the patient that we don’t have much time for their answer.

In addition, tools like that which H2O will develop allow you to see the evolution of the symptoms – perhaps with an easy-to-grasp visual to summarise trends over time. Of course, these systems need to be accessible with few clicks and to be very visible, not only for us but also for the patients. It is very important that the patient can see how he or she is doing and can compare more easily how they feel before and after starting a drug. That is also a question that one can ask of multi-refractory patients –“Which drug was best for you?” – but the patient has received so many drugs they can no longer remember the details. With one of these tools you can see easily how the patient reported previously with each drug.

What is the role of patients in the development of the H2O project?

They are in the front line; their ideas will be regarded as the most important ones. We will use the classic Delphi process to come up with the list of factors that we want to use, and patients are in the core panel and also in the focus groups and their opinions will be prioritised in generating the list of outcomes. Patients also need to be involved in defining what the value is for the patient in filling out these questionnaires: patients will do it once or twice in the clinic, but if they don’t clearly see an added value, they will stop doing it and that, of course, is not what we want – we want them to be consistently and repeatedly filling out these questionnaires. For us as physicians and scientists the benefit is that we can do science, set up trials or find out about these diseases, but the benefit to the patient has to be clear, too.

You mentioned that the H2O project goes across different disease areas. Is there potential in the project for increased collaboration or understanding across different chronic disease areas?

Well, you can always learn from each other. We already collaborate within the hospital, but sometimes you can work on something for a few years and then find out that someone else has been working on the same thing and may have come further. Think, for example, about wearables. Diabetes patients are used to wearable devices to follow their glycaemia, while we in IBD don’t use such wearable health devices – yet – but there may be types of wearables that are useful for us. To know not only the heart rate and the number of steps we did that day, but also more specific IBD applications could be a great advantage.

How were you involved in setting up Y-ECCO?

It was a joint idea – a lot of the credit goes to Gionata Fiorino, who was the first chair of Y-ECCO and came up with the idea. He came to me and I was very positive to the idea. It was not easy though. You start as young people with a lot of ambitious ideas, and you go and knock on the door of the established key opinion leaders and they are a bit suspicious of novel suggestions. But if you look at what Y-ECCO is nowadays, I think we should be very proud of what we did. Some people in ECCO at the time did not believe in this, but I think now we see only advantages – by stimulating the younger colleagues you will only increase the power of your organisation in the long term. Many Y-ECCO Committee Members have gone on to become members or chairs of other committees. You only reinforce your own organisation by giving opportunities to young people. I’m not only talking about Y-ECCO; here in Leuven, too, there are so many opportunities and that is one of the reasons I am so happy here. At some sites the professor wants to control everything and you just have to be satisfied with the little project you are allowed to do, whereas here in Leuven Paul Rutgeerts gave Séverine, Gert and also myself a lot of possibilities. Now this is what I in turn am trying to do. If you want to grow your team, you will not do that on your own. So, it is a very good thing that ECCO is giving younger people the opportunity to try to set up new things. And sometimes it will be too ambitious for sure, but that does not mean we cannot dream.

You moved on from Y-ECCO. Where did you go onto next?

After Y-ECCO I was not on a committee for one or two years, and that was strange. I like to think of ECCO as a family, and it’s strange when suddenly you are out of that family. I was used to getting all the e-mails and being aware of everything that was going on, so it was strange to be on the outside. But then I became part of ClinCom and then eventually the chair – and then 2 years ago I moved from ClinCom to SciCom.

What is the role for Y-ECCO in ClinCom?

During my time in ClinCom we worked to establish more collaboration with Y-ECCO. We really encourage Y-ECCOs to send in projects for review by ClinCom. ClinCom has a great network in the form of the National Study Group Meeting, so if you have a project that you want to do but don’t have enough patients in your own centre, you can present it at that forum and perhaps come up with a collaboration through that network.  We also collaborate with Y-ECCO on the literature review podcast and the yearly Y-ECCO/ClinCom Survey. There are probably many ideas for collaboration that I or we did not think of. You have to be prepared that if you have ten ideas then maybe only one of them will come to fruition – and if you are lucky enough to have that one idea, you should be very proud. One example is the Basic Science Workshop: this was a great initiative, but I think if we had come up with that originally, it would have been rejected. Now, however, it is a very successful meeting and all my PhD students want to get time off to attend, so Y-ECCO should be very proud of that.

What do you do when you are not working?

A good work–life balance is an issue for many of us, including me. Sometimes you go over the red line and realise you need to decrease a bit. My strategy for avoiding over-work is a classic one – I say no. But that is not always easy to do. If the question comes from one of your mentors it is more difficult to say no. Now that I am more established it is easier to say no, but as a young clinical scientist you think you have to say yes to everything in order to be regarded as someone that people want to work with in the future, but in reality it is good to be able to say no.

I go running three times a week – only 5k but it is a moment to refresh my head and look after my health. Recently I’ve decided that Wednesday evenings are my free evenings, so I don’t just come home and open my computer again; instead I try to sit and relax. But the main thing I like doing to relax is planning travel and holidays to areas that I do not know yet. Of course, with COVID this is more difficult, but usually I like to plan one year in advance where the next holiday will be and then I read and read to really get prepared. I like to plan my travels myself.

Apparently, you’re famed for creating quizzes for the lab retreats. Is that something you do?

Well, I was a Boy Scout and they say, once a Boy Scout, always a Boy Scout – I cannot be serious all the time, and team building is very important. This was something Paul Rutgeerts did not really believe in, but when I became part of the group, I thought it was important to have a lab retreat every year – all about team building and we also have quizzes and other things. They often call me the Boy Scout!

What’s in the future for you?

The biologics combination trial and creating a platform for discussions between our patients and the politicians is very important to me and I would like to establish those things. Although we at Leuven are regarded as an important centre in Europe, we need to make sure that we continue to be that, so we need to attract new people and give them opportunities to continue what we have done in the past  to make the lives of our patients better, not only though clinical work but also through translational basic science aspects of the work.

Note: The H2O project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 945345-2. This JU receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA and Trial Nation and JDRF.

This interview reflects the views of the speaker. The JU is not responsible for any use that may be made of the information contained.

Innovative Medicines Initiative www.imi.europa.eu, @IMI_JU

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