Spotlight on Professor Otavio Berwanger

In the latest instalment in their Spotlight Series, George Medicines profiles Professor Otavio Berwanger, Executive Director of the George Institute for Global Health UK and Chair in Clinical Trials at Imperial College London. This Q&A was first published on the George Medicines website and is reproduced here with kind permission.

1. What are the main priorities of The George Institute for Global Health?

Our mission is to improve the health of millions of people worldwide and key to that is reducing the burden of non-communicable diseases (NCDs) and injuries, which are responsible for over 70% of deaths globally. We have a particular focus on low- and middle-income countries, but we are also interested in under-privileged populations in high-income countries. We are focused on reducing the key causes of mortality and disability globally in key areas such as cardiovascular diseases, renal diseases, diabetes and hypertension, common injuries, stroke and dementia.

2. Tell us about your responsibilities as Executive Director of the George Institute for Global Health UK and how this complements your role as Chair in Clinical Trials at Imperial College London.

I wear two hats. One as Executive Director of the Institute in the UK and the other as Chair in Clinical Trials at Imperial College. As Executive Director, my main responsibility is supporting the Institute’s mission, which includes generating revenue and growth and establishing partnerships within the UK, with Imperial College being the main one, but we are also interested in establishing global partnerships. Currently the Institute runs projects in over 50 countries. For example, we are discussing collaborations in countries like the US, the Netherlands, India, China and countries in Latin America and Scandinavia. I am also responsible for managing our employees, which involves supporting HR, staff wellbeing, career growth as well as identifying and retaining talent.

When it comes to my academic work as Chair in Clinical Trials at Imperial College, my main goal is to find innovative and efficient ways to run trials. We are mainly interested in running global trials in a very efficient manner, and that includes innovative statistical methodology and digital technology to decentralise a trial. As a cardiologist, my aim is to deliver large-scale cardiovascular trials efficiently and we are doing this through networks in different countries. Through Imperial College, we have a very strong partnership with ICTU, the Imperial Clinical Trials Unit, who we can work with to deliver these trials.

3. You coordinate a network of several cardiovascular research sites in various countries, can you tell us more about this project?

I’ve done a couple of large-scale trials in partnership with different countries, and currently we are working with two types of networks. The first is a network of academic research organisations and is in partnership with ICTU, where we are identifying other academic groups who are interested in partnering to make a global network. In the second we are identifying groups who are interested in innovative and decentralised trial models using routinely collected data. We’ve identified groups in the UK, Scandinavia, the US, the Netherlands and Brazil with the idea to bring together all these groups and deliver these very large-scale innovative trials on a global level. As we go, we expect, and hope, that more and more countries will join our efforts. That is the idea – to have comprehensive projects with a global footprint.

4. George Medicines recently collaborated with Medisanté to enable remote blood pressure monitoring in a decentralised phase III trial of GMRx2, its lead combination candidate for hypertension. What do you see as the benefits of decentralised clinical trial models? Are these the future?

I would say decentralised trials are the future and the present. They are growing really fast. Even before COVID-19, there was a trend towards decentralised trials.

There are a number of benefits. The first is increased efficiency, which translates to reduced costs and shorter timelines. Instead of waiting 7-10 years for a trial, we will hopefully be able to do it in two-three years. I think the way in which traditional trials were being delivered, especially before the pandemic, was not sustainable. The costs were skyrocketing, there was competition for a lot of patients and a lot of inefficiencies.

Secondly, there will be gains in comfort and convenience for patients. There are some trials conducted in different countries where lots of patients need to travel miles to the research site but now they can do these from the comfort of their home. There is also an important consideration of the impact of clinical trials and their carbon footprint. In terms of the environment, traditional clinical trials are not sustainable.

Finally, some evidence suggests that decentralised trials have faster recruitment rates and better retention rates.

5. Given your extensive experience as a clinical trialist, what do you consider the biggest challenges currently facing clinical trials, both in the UK and globally?

If we kept on doing traditional trials there is a challenge of sustainability, because the costs are skyrocketing. There needs to be a shift in terms of the way we deliver trials because the most important stakeholders are the trial participants.

Usually, when we design trials we put together an executive committee, which includes academics and sometimes representatives of the sponsor. They meet with regulators, agree on some standards, and they design a trial protocol that defines primary and secondary outcomes, the inclusion criteria and the trials procedures. However, we forget to hear the patients’ voices. The most important stakeholders are not the trial’s Principal Investigator or the executive committee or the regulators – the most important stakeholders are the patients, and we need to make sure that they participate in the trial design, in the trial protocol, data interpretation and in the engagement. I think it will be a cultural challenge as it shifts from traditional trials towards the more innovative and decentralised trials.

6. ICTU is collaborating with George Medicines on its Phase III programme for GMRx2. As a cardiologist yourself, why do you think cardiovascular disease is still the leading cause of death worldwide, and how can we improve the treatment paradigm for hypertension?

It is the number one healthcare problem by far. It is true in all regions and social classes and both genders. There are several reasons for that. Our urban spaces are not healthy nor are our lifestyles. People don’t exercise, smoking is still a problem in several regions – including vaping which is a problem now among young people.

Another key issue stems from healthcare providers. There are gaps in what guidelines recommend and what people usually do in clinical practice. So even well-established evidence-based therapies like aspirin and statins are not applied correctly in clinical practice. Moreover, when doctors prescribe recommended therapies, patients don’t take them. In terms of hypertension, less than half of the patients take their pills correctly – so there is a huge problem of adherence to therapies. George Medicines’ single-pill, multi-mechanism, triple combination is a very important potential treatment because evidence from systematic reviews suggest that it could increase adherence to therapies and reduce therapeutic inertia. I am a big believer in single-pill combinations.

7. NCDs are responsible for 71% of global deaths annually and most of these are in low- and middle-income countries. How can we ensure that healthcare is accessible and affordable for all?

You need a multi-faceted approach. A key part has to do with societal change and community engagement. We need to engage communities and educate patients to take their treatments correctly, to have healthy habits. Another part of it is generating more evidence, so conducting more trials and finding effective therapeutics.

Secondly, the amount of investment in low- and middle-income countries is clearly not sufficient. There needs to be some commitment from governments to invest in preventing non-communicable diseases. In some low- and middle-income countries they are not aware that the number one killer is cardiovascular diseases. For example, women are aware of breast cancer, but for every woman who dies of breast cancer, 5-10 people die of stroke or heart failure.

8. What are you most proud of having accomplished in your career to date?

What I am most proud of is collaborating with different groups and different countries. We all learn from each other. Some of the most important papers I published were about meeting people and doing things together.

9. Finally, what can we find you doing outside of work?

I have something that is very dear to me; I am a guitar player – I play blues and classic rock and I collect vintage guitars. One of the reasons I accepted my job in London is because it is the most important city, historically, for classic rock and the homeland of some of my heroes such as Jimmy Page, Eric Clapton, Peter Green, Jeff Beck, and Mick Taylor. I am also a collector of rock n roll fine art.