Jonathan Barratt

PhD, FRCPello

Professor Barratt’s research is focused on pathogenesis of IgA nephropathy and a range of areas across renal medicine including glomerular disease, multi-system renal disease and complications of chronic kidney disease, in particular renal associated anaemia. He is the IgA nephropathy Rare Disease Group lead for the UK National Registry of Rare Kidney Diseases and leads the Renal Research Group within the College of Life Sciences, University of Leicester. He also participates in other IgA nephrology  initiatives such as the International IgA Nephropathy Network and in workgroups identifying endpoints for clinical trials such as the FDA and ASN Kidney Health Initiative.

Professor Barratt has been Principal Investigator for international randomized controlled clinical trials in IgA nephropathy and has attended both the FDA and EMA as an expert witness for new therapies in IgA nephropathy. He is an Editorial Board member for Kidney International and the American Society of Nephrology Journals and co-chairs the UK Glomerulonephritis Clinical Study Group.

Will newly approved treatments such as Spartensan and Nefecon for IgA nephropathy make it harder to recruit patients for further research?

I do think there is a challenge coming in terms of new approved therapies and recruitment to clinical trials in the traditional format, and there is a lot of effort at the moment to keep patients in ongoing trials. The challenge now is very much concentrated in the US because these new drugs are approved first in the US and become available first to patients in the US. But of course, over time, more and more countries will have these drugs available which will bring an increasing challenge. We need to think about how we design and deliver clinical trials now that we have new therapies coming thick and fast in this disease.

And this is about educating clinicians. If they want to start patients on these new treatments—start them early, and then assess whether a patient should be eligible for a trial. What we don’t want, is for patients to start these new drugs halfway through a trial. We also need to educate our investigators that if they delay starting one of these new drugs by two or three months, it’s unlikely to negatively impact on the patient’s long-term outcome, but could have a major adverse effect on the integrity of the clinical trial.

So, it’s very much about educating the clinical trial teams, about the suitability for bringing someone into a clinical trial where there’s a placebo control, and it’s about working with the sponsors to ensure that we match the clinical trial design with what is changing in standard of care therapy. It’s going to be a slow transition and we need to make sure trial design in IgA nephropathy moves with the times.

What is research going to look like going forward for rare kidney diseases?

Undoubtedly the way we’re going to manage these diseases is with multiple therapies. We don’t have any trials of those combination therapies, and we need to be thinking about moving to trials of combination therapies in diseases like IgA nephropathy. That comes with challenges. But I think over the next three to five years we definitely need to explore different combinations of new drugs to gain the greatest benefit for our patients. What is clear is that many of the drugs currently in development for IgA nephropathy may also be useful in other forms of kidney disease and we need to explore what new indications there might be for these new therapies. Most sponsors do want to explore other indications for their drugs but are limited in their ability to deliver multiple simultaneous studies and so they have to, by necessity, deal with one indication at a time and then move on. That clearly delays the movement of a drug into different disease areas. But I’m sure that will come.

So, what is the potential future for new kidney therapies, particularly in regard to rare diseases such as IgA nephropathy?

We have a massive growth in clinical trials of complement inhibitors, and these are going to be relevant to a whole range of different inflammatory kidney diseases. We are currently also evaluating a new class of drugs that target B cell modulation by inhibiting BAFF and APRIL. I think these drugs are equally relevant in other antibody mediated kidney diseases. I’m sure once we start seeing some of the data in IgA nephropathy, we will see these drugs move into other areas, such as lupus nephritis, membranous nephropathy, ANCA-associated vasculitis—lots of opportunities.

There are already combination trials in progress looking at the combination of renin-angiotensin system blockade, SGLT-2 inhibition and endothelin receptor antagonism for treating chronic kidney disease. What we would like to see are trials of combination therapies targeting the immune system in IgA nephropathy.

Could you speak to the very real importance of a more global concept of diversity in clinical trials?

We need to be evaluating drugs in as diverse populations as possible. That’s because we need to understand how a drug works in populations with different genetic backgrounds and in different parts of the world. There are clearly differences in the way diseases behave in different populations. For example, in people of East and Southeast Asian origin, IgA nephropathy is more common and is more likely to put you on dialysis. We don’t understand why that is. There may also be environmental factors that can influence drug efficacy and drug safety.

We need to ensure we offer the opportunity for clinical trial involvement to all patient populations, including those disadvantaged populations in all parts of the world—women, children, people of different races, people at different levels of social deprivation. We need to work hard to ensure that we reach those populations, and that we are able to give them the information they need to feel safe and confident about being involved in research.

You mentioned giving patients the information they need to take part in a clinical trial. Can you share your thoughts on engaging patients?

Patient engagement starts from the very beginning—at the protocol stage—before the trial design is finalized. It’s about listening and understanding. Patients say things that as clinicians and researchers, we may not have thought about. They have a lot to offer in terms of talking through the type and frequency of procedures they’d be prepared to have as part of a clinical trial. They can review the information sheets that are given out to patients to make sure they are readable and understandable. They can help us learn what would make the trial easier for a patient—like frequency of visits, home nursing and sample collection. All of these things are really important in making sure that a trial is designed with the patient at the center of the process.

This is the responsibility of the entire clinical trial team including the sponsor, the CRO and the local site staff. I have experience of studies where this wasn’t really thought about, and I think they have suffered because of that.

How does it benefit you as a researcher to work with other Emerald Clinical scientific leaders and what are the long-term and cumulative effects to the world of renal research?

I think Emerald Clinical has a clear renal pedigree. They have established a global network of highly credible, highly experienced nephrologists with proven track records in the design and delivery of clinical trials in both common and rare kidney diseases. They’ve shown they can work collectively as a team, and that they can deliver clinical studies exactly as planned with high quality data. The network and relationships that Emerald Clinical has developed over the many years that they’ve been in the renal space has been integral to the success of the trials that they’ve been involved with.

What we have now is a global network of nephrologists who have delivered clinical trials and want to deliver more, and they know how to do it. Seeing these studies published in high profile publications—new drugs getting approved for our patients—justifies all the time and effort spent in delivering these clinical trials and really changes clinical practice for the better. This applies to the whole research team. Success breeds success, and sites have the confidence that they can deliver kidney studies.

What would be your one key message to the FDA and to pharma companies developing new treatments in this time of rapid change in the treatment paradigms for kidney disease?

To the FDA it would be to keep their innovative approach to assessing drug efficacy in rare kidney disease. They have been true trailblazers in facilitating drug development in rare kidney disease and they need to continue to challenge themselves to see whether the endpoints we are using at the moment can be refined. The FDA are engaging with nephrologists to explore opportunities so watch this space.

To pharmaceutical companies, I think the key message is to keep investing in kidney disease, and in particular rare kidney disease, and keep working with the experts to get the advice and guidance they need to make sure that their programs are a success.

The entire nephrology community is to be congratulated for stepping up to the challenge of delivering global trials in rare kidney disease. But we need to make sure that everyone understands that the job is not done. We have to continue to deliver these trials because we are going to need more therapies than we have at the moment to prevent kidney failure in our patients with rare kidney disease.

When you have the time, what do you do relax and refresh your mind?

Family time is important, and I like listening to music, especially blues, country and bluegrass. We’re going on our family holiday to Nashville this year with plans for the Ryman and the Grand Old Opry. And I like watching sport—rugby and football (the original, and best, version!).

Ralph Boccia

MD, FACP

Scientific Leadership Team, Oncology

Dr. Boccia is Medical Director of the Center for Cancer and Blood Disorders in Bethesda, Maryland, and Clinical Associate Professor of Medicine at Georgetown University in Washington, DC. He also serves as the Chief Medical Officer for the International Oncology Network (ION). He conducts research in exploring the latest advances in cancer treatment and offers individualized care to patients with focus on multi-modal treatment regimens.

What made you decide to become a doctor and choose oncology as a specialty?

I enjoyed science and knew that being a doctor would put me together with people. I really enjoyed everything I did between medical school and my residency — at first I thought I would be a cardiologist because I like procedures. But as a resident, you rotate through many specialities and every time I would think — okay THIS is what I’ll be. But when I got to the hematology oncology section at UCLA, there were such phenomenal teachers who inspired me — especially in the acute leukemia and bone marrow transplant units — I just fell in love with it and that’s how I chose it.

The reason I continue to like and enjoy oncology hematology is because it’s a very different relationship that you establish with your patients. Since it’s uncommon for oncology patients to go to their visits alone, you also typically establish a relationship with their families. So for me, it’s the ability to help people through a journey — whether it’s a curative journey or a palliative journey. It’s that aspect that really interests me — helping families understand what that journey is.

What is your main focus of interest?

My main focus of interest is clinical research because I’m dedicated to finding as many new, innovative, safe and effective drugs as possible for cancer patients. I don’t have a focus on any particular type of tumor — it’s more about striving to always have something else to offer patients who need or want something else — searching for as many options as possible for people.

We’re a community practice and, unlike a huge university, we have 50-60 clinical trials open at all times. I think our expertise is finding those innovative therapies. We get referred patients from big universities because we will find trials that they don’t have. There are lots of places that offer four or five trials, but here you can find something for many more cancer types. We have trials for solid tumors, hematologic tumors and supportive care drugs.

How was the experience at ASCO this year?

My first big conference was American Society of Hematology (ASH) in Atlanta, and then I went to ASCO. It was nice to be with people again because you can’t network virtually. It just doesn’t happen. Certainly the highlight was the Destiny-04-Breast study in patients with HER2-low Metastatic Breast Cancer —it’s the only time I’ve ever seen a standing ovation for a presentation and applause that went on for minutes. It almost brought tears to your eyes. That really took over the show.

On the colorectal trial that showed 100% remission — I agree that’s spectacular, but we certainly need more patients. 100% is great — you don’t see that in anything, so there’s definitely a good signal there. It’s an important study because we know that the upswing in younger patients presenting with colorectal cancer is alarming. It has changed my practice when I see a patient with iron-deficiency anemia, and unfortunately, that’s something that’s very common. Now if I see a patient who is close to 40 with this condition, I will be sending them for a colonoscopy. The guidelines have changed from 50 to 45 now because of all the younger patients we have identified with cancer — but I’m going down to 40 in my iron-deficient patients that are women. We don’t really know what is causing this. It could be dietary or environmental but we just don’t know.

What direction is oncology research going in now and in the near future?

Over time we have found more drivers of cancer in cases where mutations are the primary growth driver. Industry has done a great job of finding ways to inhibit that driving movement or finding a target that they can identify a drug to block. We’re now seeing many more different cancer types in any one organ system than we ever thought. Take for example lung cancer. Ten years ago it was non small cell and small cell lung cancer, and even though we knew there were different histologies within these cancers, it didn’t matter because we treated them all with exactly the same drugs.

Now we know that for non small cell lung cancer there are multiple different types of tumors and those all have a different biology. With so many different drugs that target those drivers, we have a relatively limited number of patients for each of these. So now we have to have multiple different types of clinical trials for any one tumor type because we’re finding that the therapies that we can offer each of these are very different than before and are now especially targeted.

Having drug development has brought us all these new innovations and allowed us to really individualize or “personalize” therapies for any one person. Two people who have colon cancer could have very different types of colon cancer in today’s way of assessing a person’s individualized cancer type, and therefore different therapies.

The main theme of ASCO was “Equitable Cancer Care for All”. What do you see happening to make that a reality?

I think people have to talk about it first and there is certainly a lot of chatter out there on this topic. In our own small way, we are doing something — working with South Carolina oncologist Dr. Kashyap Patel who is the CEO of Carolina Blood and Cancer Center and current president of the Community Oncology Alliance (COA). His special focus is on racial and ethnic disparities and end-of-life care and he has done a lot — from educating colleagues across the country about how inequitable medical care is for people of color, to work with ASCO, with medicare and also trying to introduce certain bills.

We’re working on implementing a plan with some large pharmaceutical companies and other partners to extend a couple of significant clinical trials in patients of color to try to gather more data. We’re also trying to recruit other sites to join us in this effort. We’re talking about large clinical trials in multiple sites. We know that certain types of cancers are more prevalent in certain ethnicities. Ethnicity does matter. So it’s important to include these populations in significant clinical trials.

What type of cancer networks are you currently involved in?

We have a small research program with ION — the International Oncology Network where I am Chief Medical Officer. And in our American Oncology Network, which is a partnership of community practices with about 35 sites across the country, we’re building out a research network with the Sarah Cannon Research Institute. Those are the ones I’m most involved in right now. And we are recruited by multiple CROs for all the trials we do. And before COVID I travelled 5-6 times a year to multiple steering committees for pharmaceutical companies during drug development. However, COVID shut a lot of that down. Most of my steering committee work is now for drug development in the US or either virtual. I do love to travel and to interact with my international colleagues. Those relationships stimulate a lot of discussion and a lot of collegiality.

With a clinical practice and all your research work, what do you do to relax and refresh your mind?

Especially over the last couple of years I’ve spent a lot of time with family. We have a daughter and a son — both of whom graduated from Georgetown. They are both close by at the moment so that’s nice. I play a little bit of golf — would love to play more — and in the wintertime we do a lot of skiing and snowboarding. In the summertime we like boating — cruising and visiting places in the Chesapeake Bay.

Chee Kay Cheung

MBChB, MRCP, PhD, FHEA

Dr. Cheung is a Consultant Nephrologist and Honorary Senior Lecturer, University of Leicester, UK. His PhD examined factors that contribute towards progressive kidney damage in IgA nephropathy (IgAN), and his current interests focus on clinical trials in this condition. He leads a number of investigator-initiated studies in collaboration with industry and academic partners, and has served as UK national chief investigator and principal investigator on multiple IgAN clinical trials. He leads specialist clinics in glomerular diseases and in vasculitis and lupus nephritis. He is a steering committee member and active member of several national working groups, including the UK IgAN rare diseases group and the UK glomerular diseases clinical studies group.

What made you choose to be a kidney specialist and researcher, and in particular in IgA nephropathy?

I was quite struck as a medical student when I saw a young person with a dramatic presentation of vasculitis affecting their kidneys and lungs, and it was when the nephrology team became involved and could start effective treatment that the patient started getting better. This sparked my initial interest in nephrology.

I have always been fascinated by autoimmune diseases and how the kidneys may be involved in diseases that also affect multiple organs. IgAN is really interesting, as it is a disease of the kidneys, but the primary issue occurs outside of the kidneys. The immunology behind it is fascinating.

Nephrology offers a unique and rewarding mix, where you look after acutely unwell patients and also those with chronic disease. It’s a privilege to be able to look after patients over the long-term through the course of their kidney disease — for example if they may need dialysis treatment or a kidney transplant. It’s a relationship where you are there with them through all the ups and downs.

You work as both a clinician and a researcher. Do you have a preference between academic and commercial work? Where do you prefer to put your energy and focus?

I think the two areas are very intertwined. Many of the commercially sponsored clinical trials I am involved with as an investigator and through Emerald Clinical are studying drugs that were underpinned by careful work and discoveries that took place at academic institutions. Equally, it would not be possible to translate these findings and bring new therapies into clinical practice by performing global multicenter clinical trials in rare diseases such as IgAN without the backing of pharmaceutical companies.

A current area of focus for me is in designing and conducting detailed investigator-initiated studies to examine the mechanisms of how novel drug treatments are working in patients. This has exciting potential to help us discover more about the underlying disease and better inform how we are going to use new treatments in the future.

What is the value that Emerald Clinical brings to a trial and that you bring to Emerald Clinical?

I really enjoy working with Emerald Clinical because I get an insight into clinical trials beyond my own site towards a regional and global level, as well as exposure to steering committees and input into protocol development and operational delivery. It has been a great learning opportunity. Emerald Clinical emphasizes the importance of the science behind a clinical trial. Its senior advisory board includes some of the most respected clinical trialists within nephrology who provide input all the way through a study — right from the idea of a trial through to protocol design to its actual delivery.

The scientific leadership model is a real strength. It forms a bridge between clinical academics and commercial trial delivery. Trials receive the benefit of a ready network of investigators and national leaders who are key opinion leaders within their country. I have the perspective of being both a practicing nephrologist and a principal investigator. I think this particular point of view is valuable when communicating with sponsors and the clinical operations teams to help provide an understanding of what may be happening at a site level.

What are the challenges for research in rare diseases such as IgA nephropathy and what has changed in research for rare diseases?

Rare diseases are often complex and affect very small populations. They are understood and treated by far fewer physicians. They require more innovative trial design, are often difficult to recruit to and may require novel endpoints. And funding is often difficult to find. Fortunately there has been an increased interest and desire to conduct trials and develop treatments for rare glomerular diseases such as IgA nephropathy.

A key driver for this has been the acceptance of surrogate endpoints of kidney outcomes such as proteinuria reduction or rate of change in kidney function by regulatory authorities including the US Food and Drug Administration and the European Medicines Agency for the accelerated approval of new therapies. This has provided the ability to conduct clinical trials at a much quicker rate than before, and has advanced the timeline to drug approval. We’ve recently seen two disease-specific treatments for IgAN receiving conditional approval due to these developments, with others hopefully to come soon.

This is a space where strong partnerships between academia and industry, as well as patient organizations, can expedite advances in the development, delivery and clinical approval of effective therapies.

You work to better connect with patients in the clinical trial arena. What are some examples of how you are accomplishing this?

In Leicester, we do a lot of work in collaboration with patient support groups such as the IgA Nephropathy Foundation. Early patient involvement when designing a clinical trial gives you very important insights into how acceptable a study protocol will be and helps define priorities for research. Our research group organizes an annual UK IgAN patient information day, and we post videos on YouTube, which has been great — many patients have approached us to join clinical trials after watching these.

How do you unwind and refresh your mind?

It can be quite a task to organize all the different areas of my work. I find it all very fulfilling and rewarding. But at the end of the day, I have two young children — and I have to stop work at a certain time and turn my focus to them. Spending time with my family in the evenings and on weekends is a great way to disconnect.

Mustafa Khasraw

MBCHB, MD, FRACP, FRCP

Scientific Leadership Team, Oncology

Dr. Khasraw’s is a neuro-oncologist, professor of medicine and Deputy Director of the Center for Cancer Immunotherapy at Duke University, USA. He is interested in translating research into new therapies and at Duke, is tasked with speeding up clinical research and translation for scientists across all departments and tumor sites. He leads several clinical and translational programs with significant laboratory collaborations and is the principal investigator on first-in-human Phase I immunotherapy clinical trials in solid tumors. His research interests include biomarker development and design of innovative clinical trials to improve outcomes for patients with primary and metastatic cancers of the central nervous systems.

What made you choose neuro-oncology as a specialty?

For me it was the science and the possibility to make a significant difference. I’ve always been fascinated by cancer biology, and I also like things that are more challenging and not straightforward. When I started training in oncology most of these advances we’ve seen over the last decade or so just did not exist — we had the old-fashioned chemotherapy and radiotherapy. So, there were many challenges and opportunities for research. And with brain tumors, compared to other cancers, outcomes for patients are so much worse. Therefore, the chance to contribute — to make a difference — is larger because the need is greater.

Part of making a difference is helping patients through their cancer journey and also working with advocacy and charity groups. Could you speak to these aspects of your work?

Patients go through a very difficult journey, and getting the correct information is not straightforward. It’s very common for patients to have a distorted understanding of reality. They may search online and come up with the wrong or bad information. Providing reliable information is very important. I’ve worked in patient advocacy groups to help make the complex landscape of cancer and available treatments more understandable in lay language in both the US and Australia.

I’ve served in the past as advisor for BCNA (the Breast Cancer Network Australia), the NeuroEndocrine Cancer Australia, formerly UNICORN, and several brain tumor societies, advocacy and funding organizations. I find that work very rewarding because you see how people are touched by just having someone answer their questions and give them the right information — it really makes a big difference.

I also work with patients’ families a great deal — especially with the cancers with a poor prognosis. You not only deal with the patient but with the entire family, the caregivers and everyone else involved. And you also work with your local teams and other providers.

You are quite involved in clinical trials and especially early-phase trials. Tell us about that work and your involvement.

I work at the interface between laboratory science and the clinical trials that take promising treatments to humans, and that’s where most of the interesting discoveries are made. You have the ability to examine biologic endpoints rather than just to answer the question “does the treatment work?”. You can look at whether the treatment gets to the tumor when it’s given — if the activity we’ve seen in the lab can be reproduced in humans — if there are any biologic markers you can measure in the blood or from the tumor samples after the patient receives the treatment. These “on-treatment” biopsies or neoadjuvant treatments or surgical window opportunity studies all allow examining specimens from patients to understand if the drug gets there, when it gets there and if it does what it’s supposed to be doing. Then you can identify the right amount of drug to be given to the patient. Sometimes you find that the drug doesn’t do what it was supposed to do. But you might also find something else interesting. So that’s all very satisfying to understand if the drug works, why it does — and if it doesn’t work, why it doesn’t.

How far have advancements in cancer treatment come?

There were many cancers that did not have effective treatments available in the past. But now we see diseases like malignant melanoma or non-small cell lung cancers that have evolved in a way that the classification is very different from before. Just identifying a disease based on the organ of origin is not enough anymore, because that doesn’t explain the biology. For example, not every lung cancer is the same. Some are driven by specific mutations. Some are caused by smoking. Others are not caused by smoking. The way these different types of lung cancer respond to treatment is also very different. And the same thing applies to almost all malignancies since we have learned to classify them based on the genetic makeup rather than just where they come from.

This helps us find more appropriate treatments for each of these subtypes. For some diseases, such as melanoma and non-small cell lung cancer, advancements have been made. But for others, like pancreatic cancer and glioblastoma and others in an unfortunately long list, we still don’t have effective treatments available. But we are learning more about that biology as well, which is encouraging — we are closer to the discovery of more effective treatments for these other diseases.

Have there been as many advancements in brain tumors as in other types of cancer, and if not, what is the reason?

There have not been and it’s complex — there are many reasons. One is that the brain has evolved to have a protective mechanism called the blood brain barrier and it filters toxins and prevents them from getting to the brain. Also, the immune system inside the brain is unique in keeping immune cells from easily getting to the brain — also for protection. In healthy people, that’s a good thing, because otherwise we would get brain inflammation. But if we want a therapy for brain tumors, we have to overcome those barriers and find a way to get immune cells and drug therapies past the barriers. There are many other reasons for the lack of advancement, but these are probably the two key explanations.

You’ve lived in many places. How has that impacted your work and what are the major differences in working and researching in these places?

I have lived in Australia, the UK, the Netherlands, Iraqi Kurdistan and of course the US. I guess it gives you a different perspective. We can always keep in mind that no place is perfect. Every environment has its own limitations, and having that perspective helps you to become more pragmatic, and in a way more efficient, in dealing with things. It helps you not to get frustrated easily. And because you’ve seen different aspects of clinical care or research, you expand your horizons and you may come up with better suggestions.

If you compare the different environments, I would say, for example, in the US there are more resources available for research, and there are also large numbers of patients, scientists and clinicians. But the healthcare system in the US is very problematic for many reasons. And there are equity issues and insurance. So that’s what I mean. There are advantages and disadvantages everywhere. No place is perfect.

What type of impact do you think Emerald Clinical’s scientific leadership model where you and other scientific leaders are involved so deeply in studies has on clinical trials?

You can’t really do those trials without scientific input. But it’s not just giving guidance and advice. When scientific leaders are deeply involved, they can stop things that don’t make sense before the trial starts — before the protocol is finalized. Even though a clinical trial protocol is a living document and constantly getting updated and amended, it’s much more important to get as much input as possible early on so that not only the scientific aspect is correct, but also the practical issues. Is the protocol possible from the clinic and the hospital and the patient’s point of view? If the practical aspects are not feasible, you will not get to the answer to your question.

But even though a clinical trial is about finding a new effective treatment, it’s also very important if that treatment doesn’t work to understand why and how we can make the next trial better.

What do you do to relax — refresh your mind?

Mainly I know that it’s important to keep a healthy work-life balance. I run and I cycle. I spend time with my two teenaged girls. I read a lot — things outside medicine and science. Recently I’ve gone back to the classics that I read when I was much younger. Something I read 20 years ago — it’s very different now. We all change with time. Right?

Herbert H. Loong

MBBS, PDipMDPath, MRCP (UK), FRCP Edin, FHKCP, FHKAM (Medicine)

Dr. Loong focuses on sarcoma medical oncology, neuro-oncology, thoracic oncology and experimental therapeutics (Phase I trials). Based in Hong Kong, he holds conjoint appointments of Clinical Associate Professor, Department of Clinical Oncology and Deputy Medical Director, Phase I Clinical Trials Centre, The Chinese University of Hong Kong. He is the current and founding convenor, the Prince of Wales Hospital Adult Sarcoma Multidisciplinary Team. He has conducted >50 oncology trials as Principal Investigator or Co-Investigator. Dr. Loong is a founding executive committee member of the Asia Pacific Oncology Drug Development Consortium and Chair-Elect, International Affairs Committee at ASCO.

Welcome to Emerald Clinical Dr. Loong. Could you tell us what made you decide to become a doctor and specialize in oncology?

It’s very timely you ask that because just recently doing interviews for medical school applicants for our university. I was looking at these youngsters graduating from high school and thinking about myself close to 20 years ago. I was always interested in science at school, yet I was also very involved in the humanities. And I chose medicine because I felt being a doctor was a good balance between the two. Medical Oncology was a natural progression because, although very scientific, it also involves a certain “art” of patient communication between the doctor, the patient and the family members. In Oncology we have the scientific backing, we have the knowledge, but how this is being presented to the patient is where the “art” meets science—being able to have that conversation of realistic expectations with patients while at the same time giving them a positive hope is a balance that is more of an art than a science.

You did your clinical fellowship in Canada before you returned to Hong Kong. Was there anything specific that you learned there that you were able to take to your work in Hong Kong?

I did all my training in Hong Kong but then I did a year’s Clinical Research Fellowship in Drug Development at the Princess Margaret Cancer Centre in Toronto, Canada, where I established a firm interest in clinical development of novel therapeutics, especially pertaining to sarcoma medical oncology and neuro-oncology. The purpose of going to Canada was to see what infrastructure is required to set up an early phase oncology trials center. The Princess Margaret is a well established cancer center in Toronto—probably the most eminent one in Canada and certainly one of the top five in North America, and they have a Phase I clinical trials unit which is very well organized.

During my year there, I gained the knowledge of how to set up a unit in terms of infrastructure, and I also had good exposure to clinical trials. Hong Kong has a healthcare infrastructure that is very similar to Canada, as our oncology care here is predominantly administered through public healthcare. So structurally, though the same, I was able to bring to Hong Kong the maturity and experience from Princess Margaret of running a unit that would be efficient as a trials center but would also benefit our patients.

Why do you feel that Hong Kong is an important contributor to the oncology research space?

Hong Kong is important because of its strategic location. Although we are a separate healthcare entity, we are a window to mainland China. And we have an enriched population of ethnic Chinese patients. As China is certainly a very big market for drug development, we can help accelerate the development of drugs in mainland China itself. And we have advantages in Hong Kong as well. Our public healthcare system is very mature and similar to Canada. Our professional language is English and all hospital records and notes are kept in English. We are also able to ship bio specimens and samples abroad. So as a bridge to mainland China, Hong Kong has a strategic position but we have certain advantages over mainland China in terms of getting clinical trials completed.

There’s also the fact that Asia is a large portion of the world’s population, and the epidemiology of cancer is different in Asian countries. For example, certain tumors are more common in Asia than other parts of the world, while others are less common—like melanomas which we don’t see as much of, and when we do, they are different from the melanomas in the West. There are other differences—environmental, behavioral and even ideological differences. So Hong Kong has a distinct advantage in conducting clinical trials involving Asian populations. In terms of treatment of very specific types of tumors with different genetic makeup—especially now that targeted therapies are becoming more relevant in the field, our access to, and experience with, this population certainly gives us a competitive edge.

What is the significance of the work that Emerald Clinical is doing in that region, and what’s exciting about that for you?

The significance is the fact that Emerald Clinical is an international organization, with deep roots in Australasia. It’s a young and dynamic clinical research organization, very supportive of growth within the Asia Pacific region but also of personal growth of those who work with them. So I am able to bring my expertise to the table, but I can also learn a lot because they are so dynamic. They’re open to discussion on how, as an organization, they can develop and on how each person complements the organization. It’s different compared to larger organizations where the infrastructure is often set in stone and change and innovation can take much more time.

Are you excited to be part of the Scientific Leadership team for Emerald Clinical and why?

I think it’s great that Emerald Clinical has expertise, not only in Oncology, but from all therapeutic areas in all parts of the world. As treatments for oncology become more complex, we need that expertise from other specialties. It’s important in determining long term side effects of our treatments—being able to engage with nephrologists or cardiovascular specialists will be extremely helpful in developing new treatment protocols and new drugs.

That’s the beauty of it for me, that when a clinical trial is conducted, there will be someone involved from the beginning who has actually dealt with patients and understands things, not only from the scientific side, but also from the patient side. Going back to what we discussed earlier about the balance between science and humanity—regardless of whether or not a drug is approved, knowing that the trial will have benefits when there’s a clinician coordinating things from the perspective of the day-to-day clinical care of patients. This helps give every clinical trial the potential to have results that can be embedded into clinical practice and benefit a wide range of patients.

Clinicians who are involved in patient care can affect trial protocols in a positive way. By knowing how patients will react to certain things, the protocol can be designed to maximize the potential for patients. By looking at the human side of trial protocols you end up with trials that are more successful—have greater patient compliance and retention—trials with more patients who are willing to take ownership of the trial. It’s a recipe for success, so I really enjoy the fact that with Emerald Clinical I will be able to bring my experience as a clinician into clinical trial process from the very beginning.

What is in the future for clinical trials and drug development?

Nowadays, because we have a better understanding of cancer itself, especially in targeted therapies, Phase I trials are more of an embodiment of both Phase I and Phase II. So aside from looking at the toxicities and the side effects of a drug, we are now also looking for clinical efficacy from the very beginning, such as being able to see some shrinkage of tumors or control of the disease. So, Phase I trials have become a lot more important and, more than ever, require very engaged investigators with clinical experience.

We also have to be ever more mindful that drug development is not only about obtaining regulatory approval, but rather it is a holistic approach of getting effective therapies to patients. Traditionally we do a trial, it is successful or not, and then we move on to the next drug, next trial. But I think, if we take a step back, going through all the hoops and hurdles in doing the clinical trial is not enough, because even when we prove that a particular drug is very useful there are often other barriers which may prevent a patient from having access to the drug. So in that way, we have not done the drug or the patients justice.

My interest is not only in doing the trials, but also what happens outside of the trials. For example, what can we do to make the regulatory approval process harmonized within the Asia Pacific Region? Often it’s the different regulatory authorities which have different rules and regulations that can keep us from moving forward efficiently. I am also interested in the aspect of health economics. Drugs are very expensive and we need a way to assess whether or not an effective drug is cost efficient. How do we run these analyses and determine the right information? It’s important because governments and healthcare regulatory authorities and insurance companies will look at the economics and will decide whether or not to allow the drugs to be registered or whether or not they will reimburse for them.

If we think a drug has a strong scientific rationale we should have a view at the beginning of a clinical trial about what is going to come next—address these points very early on, so that a drug that has a successful trial can actually find its way to patients more quickly.

Roberto Pecoits-Filho

MD, PhD, FACP, FASN

Dr. Roberto Pecoits-Filho is a key member of the Emerald Clinical Scientific Leadership Team. He is a Senior Research Scientist at Arbor Research Collaborative for Health, Ann Arbor, Michigan, and a full professor of Medicine at the Pontifical Catholic University of Paraná (PUCPR) in Brazil, where he is a practicing Nephrologist and Clinical Researcher. He is currently the Principal Investigator for CKDopps, a multinational observational study of practice patterns and outcomes. He is also the chair of the Education Working Group of the International Society.

Your journey to becoming a Scientific Leader at Emerald Clinical began at The George Institute for Global Health in Sydney. Could you tell us a little about how you got there and your experience?

I first heard about the George Institute from Vlado Perkovic when we met in international nephrology meetings. I was very interested in what this research organization was doing that was really impactful in the area of nephrology and in medicine in general. At the time I was working in the south of Brazil in a large academic institution and I felt that at that phase of my career, going to the George would help me to better think about what I wanted to do on my own.

First of all, you know Sydney is a great place — Australia is a great country. My family loved it. The experience was really great for us — we just fit in so easily. My son went to public high school in North Sydney and got with a group of guys who organized a football team. My wife had a great experience working in a place in North Sydney with refugees. It was something completely new for both of them.

For me, the experience was a very rich and interesting one at that time of my career. In a way the George is a think tank. It’s really about the people working there, not only at the Sydney offices but also in other countries where the George is present and active. The connections are incredible. And they are truly global. If you want to know who is the right person anywhere to talk to about a certain thing, they know who that person is.

The George is also very nicely organized. It has a great structure and is very professional and very efficient. Being there helps to really develop great skills in this area — learning how to set up observational studies and trials — because they understand how to design and implement these studies in any setting or region in the world. And the application of this skill can really change the reality of how research can impact practice and public health in different areas — not only in developed countries but also in very poor resource areas.

Another thing I took from the George that has become a part of my life is planning. It’s all about understanding, from the beginning, why it’s important to ask those particular questions and answers through a study or a trial — about how the information is going to be disseminated and implemented in practice so that you have in mind what you want at the end — something that could change the reality of a particular setting. The George is very good at choosing the best place to do the study and also structuring it right from beginning to end. And they are not afraid of challenges — of challenging the status quo and more traditional approaches to studies. Innovation in trials is taken very seriously by the George — introducing innovative ways from trial design to implementation and dissemination in post trial application. That’s a valuable quality that I now strive to carry with me in my own work.

What has your life and career looked like since you’ve left the George?

What I learned in the year at the George allowed me to go back to Brazil and introduce some of the George model to our own university clinical trial center, which is now thriving very nicely including in cooperation with the projects the George is doing in Latin America.

I have three main roles — at home in the U.S. I am a senior research scientist at the Arbor Research Collaborative for Health, a non-profit research organization working mainly on observational studies in nephrology. Then I spend about 20% of my time with my academic and clinical activities in the south of Brazil in Curitiba, and even during the pandemic I spent a significant amount of time in Brazil. Finally, wIth the experience and contacts I made at the George, I began my work with Emerald Clinical acting as a Scientific Leader for clinical trials in the U.S., Canada and Latin America. Being involved in the Emerald Clinical’s Scientific Leadership model is so important because it increases trial efficiency and quality and ensures that we reach the right sites, motivate investigators and bring the study to completion more efficiently.

Many things have happened in my life after my George experience to change the way I participate in clinical trials. I’ve gone from a position of site investigator and recruiting patients to a more proactive lead investigator in terms of proposing new studies and helping in study design, implementation and also searching for funding.

What challenges were there in moving from Brazil to the U.S.?

Mostly it was understanding the complex healthcare system in the U.S.. Brazil is a middle income country with low resources but universal healthcare through a public system. The U.S. is very different and it is so important to understand how care is delivered in order to know the best way you can benefit from your clinical research. One reason I moved to the U.S. is to have better conditions for research — an infrastructure that more adequately supports clinical research. It’s about organization, and some of the organizational skills I’ve learned both at the George and in the U.S. I can use in my projects in low resource settings, so that is a positive outcome.

What is your role in global clinical trials now?

Coming from my experience at the George is learning how to take advantage of all aspects of clinical research, study design and study models to navigate the discovery that needs to happen to change practice. I try to take full advantage of my opportunities in observational clinical research and how this can optimize intervention clinical trials — I am very interested in connecting these two with benefits going in both directions. Observational studies are a great source of inspiration that define targets for intervention, and clinical trials need validation of their findings in clinical practice settings. Also, understanding practice patterns usually helps in study design and study performance. It’s part of my world now to make the connections between different models of clinical research with a clear objective of really making a difference in bringing clinical science to become the real driver of changes in clinical practice.

The more you understand about a disease or a common practice in a different setting or region, the more you can actually design and perform a trial that would bring more pragmatic results — not only that the trial needs to be pragmatic but the design should include a good understanding of the real world through observational research to actually make the information that you generate from a clinical trial something that is more applicable to the real world.

I’m also interested in ensuring that the right sites are chosen for clinical trials. The typical way of approaching sites is very inefficient and based on information that is not very robust about performance — about real information about patient populations that would fit into a trial. Therefore, often you end up with a gap between what is promised or planned in the beginning and what is actually delivered. It’s about networking — about knowing the right people in different regions, collecting data about performance in previous trials and information on patient populations through observational research and through platforms that capture patient data. The trial community in general is making efforts to make these site choice improvements, but initiatives from the George are really going in that direction of understanding where the patients are, which sites are best qualified and connecting the right people that can work together to deliver studies very efficiently.

What is exciting to you about the current state of clinical research in nephrology?

We are in a great moment in many different areas of nephrology with a variety of initiatives from observational studies to new approaches to intervention trials. It’s really a privilege to live as a clinician scientist in an era like this — it was not this way ten years ago. Nephrology has been blessed in recent years with an active community of clinical trialists that have been advocating for more patient participation — for understanding the importance of patient voices and communicating with patients. Then there’s the movement of how clinical guidelines are actually aligning to the concept that the best clinical action in particular situations is to refer a patient to a clinical trial. KDIGO has actually included that recommendation in their recent guidelines for particular situations in glomerular disease. That’s an important development — where their recommendation is not drug X or drug Y but instead referring a patient to a clinical trial. As treatment continues to evolve, this option will hopefully become more embedded into clinical care.

We are seeing a very diverse scenario of breakthroughs and advances. There are advances in very simple things like an expansion of observational study initiatives like registries across the globe, for example some in Africa where no information was available before. There are global observational studies like the one that I lead from Arbor Research called CKDopps which is a multi-national perspective observational study collecting data about real practices in CKD and comparing practices in different countries and how they may be associated with different outcomes and generating some hypothesis for important interventions. There are new therapies like biologic drugs or cell therapy using modern technology that can dramatically change treatment for diabetic kidney disease and glomerular diseases.

We’re also seeing innovation that perhaps will provide solutions in areas that were difficult to tackle in the past — like a project at the George Institute to develop a device that can be used to provide dialysis at point of care in a very simple and cheap way that might improve the access to kidney replacement therapy in very low resource areas. It’s a great example of how global and collaborative initiatives can make a difference in problems that before were impossible to solve.

It’s exciting to be working in this time because my ultimate goal is to change clinical practice — to be a part of connecting research and science to really evolve the way patients are treated in day-to-day practice. In the end, this is why we do what we do.

Inna Kolesnyk

MD, PhD, Senior Medical Director

Inna has both clinical and research background in Internal Medicine & Nephrology. Located in the Netherlands, Inna is involved in many Emerald Clinical trials in chronic kidney disease, working predominantly in the EMEA region as Regional Scientific Lead. Her clinical research experience ranges from observational / registries studies in the field of end-stage kidney disease and renal replacement therapy, to Phases I-IV clinical trials in different types of chronic kidney disease, including Diabetic Nephropathy and various forms of Glomerulonephritis.

How did you come to choose the medical field as a profession?

In my case it has been a family thing – quite a few of my close relatives are in the medical field, but mainly I was influenced by my father, who is a professor of Nephrology. Because I grew up surrounded by family members and family friends as medical professionals, I was so exposed to the kind of people, the style of communication including (important!) the peculiar medical humor, that the choice was obvious in my case.

What are your workdays like?

It’s very different day to day and very much depends on the studies’ stages. I am typically working on multiple studies. Within the Scientific Leader (SL) projects, my primary role is direct communication with the National Leaders of the countries involved as well as with Emerald Clinical SL project team members. In addition, some interaction with the sponsor and clinical operations teams is usually required. I must know what is going on with all moving parts of the study so that I can offer support or guidance for any issue. There is typically quite a large group of people who need to be on the same page, and this requires regular internal and external calls with the latest updates from the field, etc.

As part of the SL service, we regularly deliver scientific webinars to update investigators on recent study developments and to give them the opportunity to share how the study is progressing at their sites. The personal involvement afforded by these webinars is critical in keeping everyone informed and engaged to study’s end.

How does your nephrology background fit into / enhance your current work?

It is crucial, because I know exactly what the study implies — what is the disease and type of patients we are targeting. This makes it much easier to communicate with clinicians and to bridge the gap between clinicians, the sponsor and the operational team. Very often these are different worlds and require a translation from one form of communication to another to ensure continuity. Classical CRO operational teams are very process and hierarchy oriented, whereas clinicians are pragmatic and patient-focused. Both are integral to the success of a study, but each needs to understand their counterpart clearly. I often see myself as a “translator” between the most important players in the study.

What has been your professional journey before arriving at Emerald Clinical?

I first got involved with the George Institute for Global Health when my family relocated from the Netherlands to Sydney. I had already decided that I wanted to stay on the clinical research side of nephrology, and when I learned about the work that George Institute was doing, I was really attracted to the fact that it was predominantly an academic organization run by research professors who were driven to answer the essential questions that could potentially improve lives of patients worldwide. I was also interested in their international orientation and involvement with global trials, both academic and commercial.

I started working as a nephrology research fellow for the Institute and simultaneously as a medical fellow for Emerald Clinical. Early on I got involved with the SL model in the landmark CREDENCE and SONAR studies, combining cross-functional roles — as medical monitor for the Asia-Pacific region, and supporting and leading the global SL team as APAC regional lead.

Emerald Clinical’s SL model puts investigators (both scientists and clinicians) in the driver’s seat of a clinical study — from protocol development to active study participation. This important communication layer connects all stakeholders, ensuring the best study governance.

You are one of the earliest people on Emerald Clinical team who started to implement the SL Model. Could you talk about the evolution of this model and your experience with it?

After being involved with many SL studies, it has become evident that the approach depends on the kind of trial and on the stage that we enter. For example, it’s very different when Scientific Leaders are brought in at startup and involved in the very early steps, than when the team gets involved in a study that has already been running. Different approaches are needed to deliver the best of the best results.

The ideal situation is having the model in place at the very beginning — involved in senior steering committees and academic boards — getting a very expert look into the protocol and collaborating on protocol development. This is what Emerald Clinical is known for — our relationships with the top scientists in the field. They add to the discussion of the study feasibility and alignment with current guidelines to determine how realistic it is going to be to meet the sponsor’s timelines and objectives. They also enhance the selection of the right sites for each participating country. This is the most crucial part of the SL model, especially in a global study. Without these steps, the recruitment for a study can be quite challenging. Many classic clinical trials that don’t involve the SL model will struggle to meet recruitment timelines and keep investigators engaged.

On-the-ground National Leaders are also crucial for local insight into the current situation in each country — from the hospitals and nephrology departments to study sites. The situations during these studies are very fluid, and having someone locally respected and knowledgeable on the ground can help determine if the study is moving ahead successfully or is a challenge in that location, and why.

What aspects of your work continue to excite you?

For me it is seeing the shift in the standard of care in CKD and all the new agents available. For example, the very important studies in SGLT2Is. It is very fulfilling to see they have led to a new standard of care for so many patients across the world. When you work on a global trial, and a couple of years later you see the results affecting so many, it is very rewarding. It’s the reason you do your job — to be an active participant in improving the quality of life and longevity of patients. That’s the motivation. We know that it still requires many more years to see the real impact of our research. So we move beyond the euphoria of one discovery to keep looking — there is always room for improvement. As investigators we maintain critical thinking, keep collaborating and look to the future.

What do you do to relax, unwind and refresh your mind?

For this purpose, I have a pure hedonistic approach: a nice meal with a glass of a good wine in great warm company, whether this is just my close family or group of friends. I love to cook, to travel, to talk and to listen. Add to this a nice view on a beautiful day – and I’m fully on board.

Dr. David Thomas

PhD, FRACP (Medical Oncology)

Professor Thomas’ research focus is on the application of genomic technologies to the understanding and management of cancer. He is the inaugural Director, Centre for Molecular Oncology, University of New South Wales; Head of the Genomic Cancer Medicine Laboratory, Garvan Institute of Medical Research; and CEO of Omico. He founded the Australasian Sarcoma Study Group and established Australia’s leading adolescent and young adult cancer unit at the Peter MacCallum Cancer Centre. Professor Thomas leads the International Sarcoma Kindred Study and led the first international study of denosumab in Giant Cell Tumor of bone, leading to FDA and TGA approval.

What inspired you to go into medicine, and specifically oncology and sarcomas?

As a young person I enjoyed reading and understanding about people and society, and I acquired a sense of responsibility. I started out studying arts at university because I loved reading English literature. But I soon came to the conclusion that it was one thing to read about people, and it’s another thing to actually help them — to be useful. So I went into medicine. I thought — and still think — it is necessary to consider how my career might have an impact on social well-being.

I became increasingly fascinated with humans from a physiological and pathophysiological perspective, and by my middle twenties, I decided to become a physician and to understand internal medicine as well as I could. During rotations, I particularly enjoyed my time in oncology and palliative care. I thought of cancer as a kind of crisis to which human beings have to react. To become an oncologist would allow me to participate — not merely be an observer — in those critical moments in people’s lives. I consider that to be a great privilege.

The next fascination was with molecular cell biology which led to a deep passion for biomedical research, and though I had little time to spare, I can visibly remember going into the basement and searching medical records for data that was relevant to the patients I was managing. I had a curiosity that led me to Harvard Medical School where a brilliant scientist called Phil Hinds challenged me to understand the role of a particular tumor suppressor in bone cancer. After working at the Peter McCallum Cancer Centre back in Australia, in 2008 I set up what is the largest sarcoma cohort worldwide that is now paying enormous dividends as genomics has developed to the point of influencing rational drug development.

Over the past 12-15 years I’ve been progressively setting up a national precision oncology structure in Australia — partly around the idea that in rare diseases like sarcomas, only molecular profiling is going to allow us to personalize treatments. Outside of that, the numbers are so low that it is unlikely that we will ever make any progress.

So that’s essentially the short version of the story of how I got where I am today.

In 2018 you established Omico, bringing together cancer centres, research institutes, governments, industry partners and patients to facilitate the delivery of genomic cancer medicine clinical trials to Australians. You are not only successful at manifesting your curiosities in a way that impacts human society, but you are also quite adept at getting funding — not only for Omico, but for other projects of yours as well. What is the secret?

What you’re describing is the twin drivers of any successful enterprise, especially in research. The first is to have an inexhaustible appetite for curiosity and a deep pleasure from satisfying that curiosity. But there’s no point in having curiosity unless you can create the resources to be able to satisfy it. So you acquire the skills that enable you to achieve those goals. That involves doing the right and good experiments and doing them effectively. But it also involves more systematic challenges like raising funds. And the secret to raising funds is to ask important questions that are unlikely to go away — will not become obsolete.

You have to think about the problems that society faces from a social, human perspective because that’s also the perspective of the funding agencies. What are the needs and the priorities of the health system itself? So in the case of Omico, we were offering a solution to an element of the health system that needs to be changed in order to realize the benefits that science has already delivered.

For example, in non small cell lung cancer, there are now at least 10 biomarkers for which there are very good drugs with proven efficacy. And yet in Australia we only recently gained routine access to the molecular profiling that will enable us to choose those drugs, and we don’t have access in a reimbursed way to all those drugs which actually produce the benefits.

The mission of Omico is to provide a no-cost access to molecular screening — looking at the DNA of cancer and other molecules — and to match people with rare, advanced, difficult-to-treat or early-onset cancers to existing treatments or clinical trials researching innovative new drugs. Essentially we are making hope meet possibilities. Omico is a unique structure of a government-backed not-for-profit collaboration between researchers, clinicians and industry partners.

Both our mission and our structure responded to a need in Australia’s healthcare system. Because we are a not-for-profit company, we can operate nationally at the patient interfaces. That’s important in Australia because we are actually eight separate states and territories with individual governments and healthcare systems — so that was an attractive proposition for the federal government when it came to funding us with 62 million $AUS. Omico offers a way to change the national healthcare system without having to work with eight separate systems individually.

The state government of New South Wales has also chipped in because it’s the hub of this national network. It saw its own interest in investing another $25 million. The rest has come from a variety of sources, including from industry itself, which is contributing not only dollars to make the program a reality, but also is committed to bringing in more trials into the country, which, of course, we also need to be able to treat patients.

We can also negotiate in a commercially realistic and nimble fashion with industry partners, which governments struggle to do. Omico has developed all sorts of very productive partnerships across a broad range in the pharmaceutical and biotech sectors that will enable us to deliver the trials — and therefore the treatments — that our patients need, and to do so in a way that, as a not-for-profit, still reflects the public interest.

So basically Omico is meeting both the economic and logistical challenges to unlocking the potential of precision oncology for cancer patients. In this era of biomarker-dependent drug development, novel and more efficient approaches to genomic profiling have the potential to revolutionize clinical trial access for both patients and clinicians. And working with CROs like Emerald Clinical can help overcome operational barriers faced by oncology trials and help clinicians and cancer centers target the right patients for the right trials.

We offered a solution to a problem that isn’t going away that bypassed some of the impediments the government faced and that was attractive. So when you ask the right questions — offer the right solution — you are most likely to get your resources.

How is Omico’s system of connecting the silos within the healthcare system working out?

There are now 10,000 people who have been through molecular screening, and we are currently preparing a paper on the first 3,000 of those patients. We can show that there’s an incredibly high frequency of these — more than one third — with good drug targets. This is a population that has little or no treatment option with a median survival of 8-10 months. For those screened patients who had access to their drug targets, survival was doubled to 18-20 months. So if we can just get access to the right drug targets for every patient screened, we will have a huge impact on the population as a whole.

You once said that research will generate light as well as heat. Could you elaborate on that concept?

Cancer at an individual level is the most common health-related tragedy that kills us in higher income countries today. The heat comes from the tragedy. But the light comes from the solution and the solution comes from science. Science sheds light on the nature of the problem and allows us to develop effective solutions that address the heat and pain of the tragedy.

Precision medicine, genomics and rational drug development are the solution to the tragedy of incurable cancers. And it’s not just limited to molecular therapeutics. It also relates to the use of genomics to understand why people get cancers and potentially to personalize risk management as well as personalized therapy. We’re in an era where we have the opportunity to implement solutions that will improve health outcomes for cancer patients. And that’s the light element to the heat.

Why is Australia the right place for cancer research?

Well, that’s easy. We have a first-rate healthcare system with the best five-year survival for cancer in the world at 70%. Our healthcare system delivers first-rate outcomes. And there are also very good tax incentives for doing clinical trials in Australia. Now, thanks to Omico, we have a population-scale molecular screening infrastructure that enables biomarker dependent drug development trials in a way that has not been possible previously. Those trials can happen, conservatively, twice as fast as would be possible without having a molecular screening infrastructure. And of course Australian data is widely accepted by both European and US drug agencies for regulatory filings.

We have only covered one-tenth of the projects you are involved in. With such a busy working life, what do you do to refresh your mind and relax?

I like playing chess. I’m an online chess addict. I’m not particularly good at it — I should make sure that’s clear — but I very much enjoy it. And I also enjoy playing classical guitar. My favorite composer is Bach. Also, we have a mountain cottage which I like to spend as much time at as I possibly can.

Hernán Trimarchi

MD, PHD, FACP, FASN

Dr. Trimarchi is Head of the Division of Nephrology and Renal Transplantation at the Hospital Británico de Buenos Aires and a member of the Steering Committee of the International IgA Nephropathy Network. He is involved in many clinical research protocols related to glomerular diseases and chronic kidney diseases as member of the advisory board and steering committee, as KOL or national coordinator. His research focuses on glomerular diseases, particularly in proteinuria and podocyturia, IgA nephropathy, FSGS and Fabry disease.

Why did you choose to become a nephrologist?

Early on I was working more in basic research and oncology, but I chose nephrology for both a scientific and a more personal reason. On the science side, nephrology makes you go through all the medical chapters of internal medicine. Kidneys set the basis of life for cells and therefore, the whole organism. The kidneys and the hormonal system play such a vital role in the equilibrium of salt and water in the body. They look to me like sensible computers.

And personally, it’s about the patients. When I started to see patients and began to understand how to really get in touch with them, it was the relationships and working as a team. Nephrology gives you the chance to work with patients and stand by them throughout the process — from the IC or out-patient, and if they progress, you take care of them during the challenging dialysis period. And finally, with the accomplishment of a kidney transplant, your patients gain independence and quality of health and life, and you continue to stand by them and take care of them for the future.

Also, since many kidney diseases are hereditary, you become the doctor for families — I have grandparents, parents and children from the same family and soon the next generation behind. They all know you and they trust you to help them. It’s a kind of relationship that goes beyond science and becomes more warm and compassionate. For me, the patient is the most important thing — these relationships have a place in my life. It doesn’t matter who is the person — they are coming to you because they need help.

How did the pandemic affect your practice and your patients?

You must realize that in Argentina, we were not allowed to walk outside our houses except to work. The pandemic was like a war — an invisible war — on all the world. We had to close our patient sections except for the critical things but we still had patients on dialysis. Patients were afraid they were going to die. Some of them got COVID, and we did lose some. It’s difficult when you lose even one patient.

In international groups we began to publish our experiences — what was working, what wasn’t — and with this sharing of information there were important contributions that helped all of us better deal with our patients. When someone far away would say, “I followed your suggestions and guides and got a good result,” then you know it is important to keep publishing. The scientific and medical community worked in a more unified and cooperative manner than ever.

The pandemic was a turning point for me. Personally it was humbling — that mankind cannot control everything. And in general, the pandemic exposed how the same resources are not available to all people. There are so many poor people in my country — in every country — that simply don’t have access to basic things like good nutrition, education and certainly not good medical care.

What are your thoughts on making progress to eliminate inequality in the area of clinical research?

I have to say that having a global team like Emerald Clinical has given me the chance to represent South America in the world of clinical research where we used to be absent. We now have trials coming through Argentina and Brazil and hopefully that will spread to Columbia and even Peru and Ecuador. We are trying to build a consortium of countries that we represent in this really poor area to bring well developed clinical trials so that these people can have the opportunity to participate. It’s important because diseases don’t behave the same in all people, which make them have quite different responses to drugs that have only been tested on Caucasian populations. If you were not born in the right place, you are not going to get the benefit of these developments.

So the fact that Emerald Clinical has given me a chance to bring high quality science to this country which has not been a part of the research before is really important and makes my patients really happy. They want to be a part of a process that belongs to the whole world and to have the chance to help future generations — that the drug trial they participate in today will make the drug available to everyone in ten years.

You have a very good recruitment record for clinical trials for rare kidney diseases. Is there a secret behind your success?

The secret is first of all you have to study — I started medical school when I was 17 and got the degree when I was 23 — during those years I studied a lot and even as a student I started to teach. So first, you have to study and work hard to learn how to deal with the diseases so that you are trusted — by patients and by colleagues. After 32 years of practicing medicine — 28 of those in only nephrology — I have dealt with many many patients from all parts of this large country of Argentina and I have had many referrals. And it’s relationships with patients and colleagues that make the difference. Your colleagues must trust you to send you patients. And you must know how to choose which patients are right for which trials.

You have to communicate with the patient from the start that in a randomized controlled trial they may get the drug and they may get nothing. You give the patient the option to say no, but you explain what is the aim of the trial and that you will be by their side during the whole duration — that the trial will offer them a chance for a more targeted, tailored, customized solution in contrast to the drugs they have now. And with these relationships, you build a family of patients who are enthusiastic to participate. You have to understand that clinical trials are not for everyone. It’s not just their illness that needs to be considered but also their emotional and psychological situation. It’s not just organs that determine how they will react to a trial.

What is the state of kidney research today?

This is a most exciting time for kidney research. Until now it’s all been cardiology and oncology — kidneys have been left out. But suddenly industry has realized that at least 10% of the people in the world have CKD and that it’s worth the investments in renal research. For me, this is a golden age because in the last 30 years I have not had the chance to assess one molecule. Now there are 10 molecules for just one entity and the competition is really high.

One of the great things about Emerald Clinical is that they are the link between the sponsors and what is going on in real life according to the doctors, so that is very compelling. It is actually very challenging to connect the right sponsor with the right drug to offer to the right doctors with the most patients who need the benefits of a particular drug — especially in the renal area with the rare or ultra-rare diseases — the forgotten diseases — which still count because there are patients and families waiting for something better.

Emerald Clinical is doing a great job of finding the right places for the right trials — places with an experienced staff — serious institutions with people who are really devoted and engaged. They are working to ensure that the money is being invested in a good way. Resources are limited. If you don’t do things right, that money is gone, and the chance for the protocol to finish is gone. It’s very challenging but it’s the only way to move forward in the world at this time.

So it seems that working with Emerald Clinical has been both personally and professionally rewarding?

Definitely. Emerald Clinical is very cosmopolitan — international — so I have the chance to interact with people from other parts of the world working in many trials. I may be speaking with teams from all over — it’s morning in Argentina and late night somewhere else but everyone is awake and available at any hour because there is something to be solved. Emerald Clinical has allowed me to be part of this clinical research movement that will not only benefit my site, but my country — my region and many people in this part of the world.

We’re interacting all over the world and it is like a family because all of the people know where they belong. They are identified with Emerald Clinical and are really responsible for what they are doing. It’s not that easy to have such a strong DNA in an international company — it can’t be taught to employees — and yet everyone is speaking the same language, which is responsibility, engagement, ethical, transparent, educated, polite, part of this family and of this mission. Each person on the team is important and each person on the team does their part. It is something very special about Emerald Clinical.

Lastly, as busy as you are, what do you do to unwind and relax.

I like to be in nature — to play sports — both things that I have begun to do much more since the pandemic. I am a writer and besides the medical publications, I have also published poetry and a history of Argentina’s favorite soccer team, Boca Juniors. I’ve collected stamps since I was a boy. I have my hobbies. And I love music — especially the Beatles. They take me back to primary school when the teachers used to play Yellow Submarine. The Beatles actually had a big influence on me. First, because they helped me to learn, speak and pronounce English which is so important in this field of clinical research. And also because they inspired me with how hard they worked — how they brought themselves up from nothing to changing music because they believed that what they wanted would come true — and that helped me to believe in myself.

Ari VanderWalde

MD, MPh, MBioeth, FACP

Dr. VanderWalde is the Vice Chair of the Precision Oncology Alliance as well as the Global Chair of Clinical Trials at Caris Life Sciences. An internationally recognized cancer researcher, Dr. VanderWalde was previously the Director of Research at West Cancer Center and Research Institute in Memphis, TN, where he is still a member of the research faculty. He held a dual appointment with the University of Tennessee Health Science Center as Associate Vice Chancellor of Clinical Research and Associate Professor in Hematology/Oncology. He has been a Senior Medical Director at Emerald Clinical since 2014. His primary research has been in melanoma, immunotherapy and targeted therapy including combinations of therapy and mechanisms of resistance.

What inspired you to have a medical career and more specifically to focus on oncology?

Everybody expects there to be an aha moment when you when you figure out what you want to do with your life. I’m not sure I had that moment, but I definitely had some inspirations. My dad is a pediatrician, and growing up we lived in a pretty tight community. On Saturdays, people would knock on the door, saying—my kid has an earache or stomachache or something like that. My dad would stop whatever he was doing and tend to whatever it was, so they didn’t have to go to urgent care or the emergency room. And I always remembered that—that my dad being a doctor wasn’t just something that he put down at the end of the day—it was something that was more infused in him. And that’s who he is even now at 75 and still in practice. I always admired that in him.

Why oncology? From the start I’ve always had one foot in science and one foot in patient care—and I’ve moved between those two since I was in medical school. I did a fellowship in oncology, got a degree in biomedical ethics and even a master’s in public health. And when I had to make a choice during my residency between primary care doctor or specialist, I wanted the more exciting path—a way to actually make a difference for patients. Listening to the attending physicians speak to patients about cancer, the idea of care just became really exciting for me, and it’s something that has kept its excitement throughout my career. And from the science point of view, if I hadn’t gone into oncology, I wouldn’t have been at the forefront of some of these amazing discoveries that have been made over the last 10–15 years. So, I’m really glad I made the decision.

You’ve treated cancer patients, done clinical research, been in academic settings, worked with big pharma—done it all. How has this broad exposure shaped your viewpoint?

There are definitely a lot of different ways to approach cancer. A lot of physicians and scientists don’t know much about the patients—they just hate cancer. And there are some doctors who love the patients but don’t really understand what happens in terms of cancer—they just know the drugs that work. As a scientist—a researcher—it would be easy to take the “I hate cancer” approach and not think about patients. But if you take care of patients with cancer, it teaches you that cancer doesn’t fit into a box—that people don’t fit into a box—that every person has a different journey and different priorities in terms of what they need—that it’s not as simple as giving them a drug to extend their life or make them feel better. You see the unfortunate side effects that many cancer treatments can have, and you try to calculate the risk and benefit ratio for all the therapies you use. Although scientists working in the lab with mice are the ones who have made all the major advances for cancer therapy, they don’t get this perspective.

Having a foot in both worlds has made me both a better scientist and a better physician. I think it’s important that my research career really started with looking into the patient experience. In my early days as a fellow at City of Hope, I focused on older adults with cancer—determining whether or not they were able to tolerate therapy. I think that was a good entryway into research—to be thinking about it from the patient’s perspective first and from the scientific perspective after.

So, with whatever I do, I need to be in the space where the patients and the science meet. And that can shift your outlook. For example, patients are not “cancer patients”— they are people who happen to have cancer. And neither having cancer nor being a patient defines them. I’ve focused on clinical research, which is the intersection of what happens to patients with new therapies or with new interventions. It’s based on what the individual patient is experiencing. Clinical research tells you that a drug that looks like it’s really good at killing cancer can also kill the patient. And it’s no good to be able to heal the body if you can’t also spare the soul.

You have spoken in the past about the process of clinical research in oncology—saying it is a labor of love that requires “stick-to-itiveness,” focus on one question at a time and real training. Having worked with big pharma can you speak to the process of taking a drug to approval—the pathways and challenges?

Rather than focus on the hardest part of drug development, which is in the lab and is basically a lottery, I’ll focus on the drugs that actually get into patients. Safety is really the most important thing that we end up defining. It’s also the most important thing—the thing that regulatory groups like the FDA end up looking at—and if it’s not approved by the FDA, you can’t give it to patients. So, safety is the biggest first step of drug development.

After we demonstrate an acceptable level of safety, which is its own science, we move into phase II trials with a larger group of patients and start looking at whether the drug is efficacious—actually works. And that’s hard to do. We’re still looking at safety and getting a broader sense of possible side effects. This is also where we see whether or not it’s worthwhile to go to a very broad group of patients. Clinical research can cost up to half a billion dollars, so we need a signal to continue forward.

The end piece is the phase III trial—the registrational trial—that compares the active agent or drug to either the best available second drug or to placebo if there’s nothing that is standard for those patients in that stage of their cancer. The purpose is to be able to demonstrate efficacy good enough to convince the regulators to approve that drug, and that is difficult. It’s expensive—costs of clinics, CROs, pre-filing and regulatory submissions, all the internal monitoring—and you’re going through this complicated process while you’re also racing two clocks.

The most important clock is this—for every minute it takes to get the drug that is showing it works onto the market, lives may be lost and cancers may have grown. In addition, the clock is racing because the patent on that drug expires at some point, and the drug company wants to move quickly. But you want to do things right—make sure you get meaningful endpoints that will determine whether or not the drug really works—is effective. It’s a real challenge. The hardest part of doing clinical research is the clinical research. One piece is not harder than the next. But making realistic timelines and sticking to them is extremely important.

How important is it in this complex process to have scientific leaders involved throughout the entire trial?

For every phase of a clinical trial, you need to have a doctor who takes care of patients with cancer actually looking at that trial. The drug company knows the drug better than anybody else in the world. They know if it’s going to work—they know why it should work. They do have doctors in the drug companies who are able to look at it, but it’s not the same as having a physician who is an expert in the cancer that is being treated to look at the protocol asking if the drug does what it needs to do for patients, and is it going to actually accrue patients in a timely manner.

It’s very important and something that Emerald Clinical really excels at—making sure that there’s a physician who looks at all of the protocols and is giving guidance. They ask the right questions along the way. What are they trying to do? Are they actually going to do it? Are they asking too many questions to get important answers, or are they asking one question they can get a definitive answer for? So having a clinical trialist who’s done this before—is a physician who has treated cancer patients and also has the perspective of a CRO to say if they can actually accrue the trial in the timeframe that is expected—is a real value that Emerald Clinical brings.

Give me a synopsis of what we’re going to see in cancer care in the next 5–10 years.

We’re going to start seeing more targeted therapy and also more immune therapy, which is recognizing that cancer is able to grow because it’s able to hide from the immune system. What we’ve developed in the last 10–15 years is a variety of different ways to be able to show the immune system—“Hey, look, there’s cancer here, you should start attacking it again”—and that’s been extremely effective. And there are alterations in cancer that actually can tell you whether immune therapy is more likely to work or not likely to work, just as it can be for targeted therapy.

We’re beginning to see new immune therapies that can be used in cancers that have not been that responsive to those we currently have. Those cancers are the ones we’re really going to find out about in the next few years. We’re also looking at tumor infiltrating lymphocytes (TILs) that have just been approved for melanoma, where we take tumors out, expand the number of T-cells that are able to be produced, and infuse those back into the patient. Those definitely work in melanoma. Emerald Clinical actually helped in the development of TILs.

I would say to a cancer patient—it’s important to realize that the overwhelming majority of people with cancer don’t have a death sentence hanging over their head. It used to be that there was a very high likelihood, even for an early-diagnosed cancer, the patient was potentially dying. But now, particularly if you have an early-stage cancer, don’t give up hope. There’s a lot that can potentially be done. Even with metastatic cancer, the goal is that patients live with cancer, not die of cancer—to make cancer a chronic disease for these patients. Don’t give up. There’s a therapy that’s going to potentially work, and if it stops working, we’ll move on to another therapy that hopefully will work for a time. And just keep going—taking the next step after the next step, because we’re discovering more and more every day.

How would you sum up the most impactful way to balance the patient-science equation?

I want to point out again that the intersection between patient care and clinical trials is very, very important. And it’s one of the reasons that I continue to do work with Emerald Clinical. I’ve done full drug development and molecular diagnosis and clinical trials—but Emerald Clinical is where the rubber meets the road. I can provide information about what the patient with cancer would benefit from—how the process of being in a clinical trial could potentially be meaningful for that patient. I can make sure that the trial is well designed and that the trial answers the questions that it wants to answer.

From a certain perspective, it’s an ethical question. You don’t want to do a clinical trial that wastes patients’ time and their gift to the scientific world. You want to make sure that when you do a clinical trial, it’s with a drug that is most likely to work, have a good side effect profile and going to answer the question that will get that drug to other people. If you don’t ensure these things, you’re wasting the sacrifices and gifts that those patients are giving. It’s really important when you’re developing a protocol to ensure that every perspective is being taken into account. And Emerald Clinical does an excellent job of that.

What do you do to refresh your mind, unwind, reset for the next challenge?

I’ve got four kids. Two are getting to college age, and that ends up being a lot of work and angst. My twins are in seventh grade, and their problems are the biggest that you could possibly have in the entire world. I don’t know that that necessarily resets my mind, but it certainly redirects it a little bit. One way I reset is a lot of traveling, both for work and for pleasure. It’s always great to be able to go see and interact with other people in this remote world we live in. And I really like to ski. Point me down a hill. I can usually get to the bottom still standing up.