Why Diversity Matters in Obesity Clinical Trials

Key Takeaways

Why Representation in Obesity Trials Matters
The composition of clinical trial populations directly influences the safety, effectiveness, and real-world applicability of obesity treatments. Evidence from a recent systematic review published in The Lancet Diabetes & Endocrinology demonstrated how trial data underpin regulatory approval, reimbursement decisions, clinical guidelines, and ultimately care for people living with obesity.

Patterns of Over- and Under-Representation
Consistent over-representation of certain demographic groups – typically middle-aged, white participants – was observed, alongside under-representation of older adults, some minority ethnic groups, and individuals living with multiple diseases or conditions other than obesity. These patterns raise concerns regarding external validity and whether findings reflect the diversity of populations seen in routine obesity care across Europe.

Beyond BMI as a Sole Entry Criterion
Reliance on BMI thresholds as primary inclusion criteria remains common in obesity trials. While BMI offers a pragmatic screening tool, it does not capture body composition, disease severity, or functional impairment. Consideration of additional markers – such as waist circumference, body composition measures, and metabolic parameters – may better reflect clinical heterogeneity and disease complexity.

Implications for Obesity Pharmacotherapy
Limited population diversity has implications for dosing, safety profiles, treatment response, and long-term outcomes. Under-representation may obscure differential effects across age groups, ethnic backgrounds, and individuals living with multimorbidity, potentially reinforcing inequities in access to and benefit from treatment.

Regulatory, Policy, and Reimbursement Considerations
Because clinical trials inform approval and reimbursement frameworks, restricted diversity can influence which populations are prioritised or considered eligible for treatment. Transparent reporting of demographic characteristics and subgroup analyses is essential to support equitable policy and clinical decision-making.

Designing Future Research – A Role for Early-Career Professionals
Critical appraisal of inclusion criteria, recruitment strategies, and outcome measures is essential when designing future studies. Embedding diversity considerations at protocol stage – rather than retrospectively – strengthens the evidence base and improves alignment between research and real-world obesity care.

Paper Discussed
The analysis presented was based on: Alsaqaaby MS, Cooney S, le Roux CW, Pournaras DJ. Sex, race, and BMI in clinical trials of medications for obesity over the past three decades: a systematic review. The Lancet Diabetes & Endocrinology. 2024;12(6):414–421.

Future Directions and Next Steps

• Expand inclusion criteria beyond BMI alone to better capture the clinical heterogeneity of obesity as a chronic disease
• Improve transparency in reporting demographic and clinical characteristics in obesity trials
• Proactively recruit under-represented populations, including older adults and different ethnic groups
• Strengthen methodological training on equity-focused trial design
• Align research populations more closely with real-world obesity care to support equitable implementation

Summaries are AI-generated from meeting transcripts.

Transcripts are auto generated, if you spot an error, please email enquiries@easo.org

Speaker 1 • 00:00
Okay, welcome everyone. Good afternoon. Good evening from wherever you’re tuning in and welcome to the EASO Early Career Network Learning Hub webinar for February. Today we have a great hour ahead. We have our expert, Mr Dimitri Pornaras, who will be talking about why diversity matters in clinical trials. This is following on from an excellent systematic review recently published in Lancet Diabetes and Endocrinology. The Novri Nordisk Foundation has provided support for these activities, but it’s also important to say that they had no influence over the content. So my name is Matt Harris. I’m a bariatric surgery resident and PhD fellow at the University of Manchester in the UK, and also one of the EASO Early Career Network board members. As a reminder, this webinar is being recorded and will be available to Early Career Network members over the next few days. We have an hour today, so we’ll going up to 5pm UK time. We’ll hopefully have plenty of time for questions so please put your questions in the Q&A function at the bottom throughout the talk and at the end and we’ll have lots of time to discuss this with our expert Dimitri. I also want to highlight that ECM membership is free as these webinars and they have been excellent so please don’t hesitate to share this with your Early Career Network colleagues. So before we get started I’d like to hand over to Laura, one of the other board members at the ECN, who can give a quick update on upcoming events.

Speaker 2 • 01:30
Yes, very warm welcome from me as well. My name is Laura. I’m a postdoctoral researcher at Heidelberg University, and I’m just going to run you through some of the opportunities that are available to all ECN members. There’s also going to be a link that is shared in the chat where you can access all of these opportunities as well up different opportunities too. So first of all we have the European Congress on Obesity upcoming that’s going to be taking place from the 12th to the 15th of May 2026 in Istanbul. The abstract submission for that has now closed but the early registration is open until the 27th of February. At ECO there’s going to be several ECN activities that you can attend throughout the congress. So that includes networking events in our dedicated ECN lounge, so you can come meet us there in person. And there we will also have award sessions, so for example the ECN Best Thesis Award and the EASO Novo Nordisk Foundation New Investigator Awards, so make sure to mark that in your programs. Then aside from ECO we also have the regular ECN spotlight feature that I just wanted to remind you of. So that’s a feature that is shared across the EASO website and the social media where we highlight the work of ECN members to share to the wider obesity community. So if If you’re interested in featuring your work, you can get in touch with us. We also have an ECN WhatsApp group where we share quick updates, resources and networking across Europe. So we would be very delighted for you to join us in the WhatsApp group as well. And you can also find the link to join the WhatsApp group in the chat. So that’s it for me today and I’ll hand over back again to Matthew.

Speaker 1 • 03:37
Great, thanks Laura. I’m very excited we’re getting closer and closer to ECO. So without further ado it’s my pleasure to introduce our expert speaker Mr. Dimitri Pornaris who is an internationally recognized expert in obesity management and a bariatric surgeon in Bristol. Thank you very much.

Speaker 3 • 03:56
Well thank you Matt, thank you Laura and thank you to the ESO, thank you to all of you who joined today. I have to say nothing makes you feel older than when you get invited to the Early Career Network as a speaker. And I have to say it doesn’t take very long from the time I thought I was in the Early Career Network and suddenly I’m doing a talk to you. I’m going to talk to you a bit about how representation matters in Obesity Clinical Trials. This is my hospital in North Bristol NHS Trust, South Mid Hospital. There are not many sunny days of the year, but the one sunny day of the year we took a picture and you’re welcome to join us. We are part of the ESO Com network. We have had colleagues from all over Europe visiting as part of that scheme, but more importantly, always there for anyone who wants to collaborate or anyone who wants to come and learn with us, and more importantly, we can learn from you. And please reach out on social media. This is my conflict of interest. I work in a variety of different spaces around obesity care, bariatric surgery, medical devices, endoscopic treatments, pharmacotherapy. And I stand up for for multi-modal treatment of obesity. In fact, the term was was first coined by myself and Professor Kallaroo exactly a decade ago in an editorial in the Lancet. And that’s exactly what I deliver in my day to day basis. But I should also acknowledge that my most important of interest is that I am a full-time surgeon. I work in as a bariatric surgeon but also work as an upper GI and emergency GI surgeon so I see obesity outside the obesity clinic. I do on call for major trauma surgery in fact I’ve only stopped being on call not a very long time ago a few hours ago so I do see obesity outside my clinic and I should also declare the fact that I did my research about 18 years ago on a rather unknown molecule at the time called glucagon-like peptide 1. I now read about this in the national international news but I’m sure this has also had an impact on my views. But let’s go back to the question. So why does recent presentation matter in obesity clinical trials? So the short answer is it’s simply the right thing to do And we can stick to that and then we can, this can be the world’s shortest webinar, or I can give you a bit more information and discuss some of the thoughts and reflections around this and give you a longer answer, but also show you some of the data. And it’s always important to do the right thing, but the longer answer is that first of all, it’s biology. There is a lot of understanding around obesity, but there’s also a lot of gaps in our understanding. Obesity is a complex condition. It affects populations differently. Our tools to diagnose obesity, our tools to stage obesity, are challenging at the moment. They’re not exactly precise. And different treatments of obesity have different effect on populations. If you are not convinced about that, this is some of our work from many years ago. This was published about five years ago, but the work is over 20 years ago. This is the UK’s largest series of laparoscopic raw Y-gaseous bypass, still the most effective treatment for obese in terms of impact. Although the gap with pharmacotherapy is getting more and more narrow and we’re all very excited about this. But what I really want to show you here is that these are 2000 people operated over a 15 year period. As you can see our preoperative body mass index is higher than most series about BMR 50, gets down to 38 at 10 years. The follow up is always sketchy the further you go from the time of surgery. But what you see is some people do really well and some people do not so well at all. And that’s a biological phenomenon. There is heterogeneity of the population in terms of the baseline, in terms of the disease, and there is a heterogeneous response to treatment. So it’s all complex and therefore we need to understand the populations we’re treating. And if you’re not convinced about that, I’m just gonna explain the concept a little bit more. This is a slide that Professor Lee Kaplan from Harvard at the time and has shared with me. And it just says what happens with every intervention for obesity. And this is, and we use examples for that. For diet, we use low carbohydrate, and this is true data. And you can see that there is a normal distribution, of course, for drugs, the arachlidioid, the first generation of GLP-1 receptor agonists. And what you see is that with the more modern pharmacotherapy that curve is shifting towards your screen, right? But it’s still a curve. Some people do really well, some people do not so well, and that’s a biological phenomenon. There is heterogeneity. And that’s true for, this is the deuterogenal liner, the endoscopic device, and this is surgery, this is wrong Y-gaseous biobus at the time. And we can become more effective and we can shift that curve further to the right, but it’s always a curve. Having explained the biology, it’s also important to understand the external validity. So based on clinical trials, we change health policy. that happens at global scale and it’s important to recognize that that happens for all diseases. So if a new chemotherapy agent for cancer is studied in New York, as soon as it becomes effective in a clinical trial and more centers will happen, at some point it will change care globally. And we do this for obesity as well. So it is important that the populations that are being studied in those clinical trials are reflective of who we’re treating. And that is an academic issue, it’s a clinical issue as well and it’s a health policy issue. If we don’t use heterogeneous populations, if we don’t have inclusive designs in our study, we will exclude some people from getting exposed to the treatment and that means that safety signals will be missed. If a specific group of people, and of course we know this very well around women who are pregnant and of course we accommodate for that, but in specific groups of people who are, it’s perhaps different from pregnancy, but if we just exclude a group of people who may experience a specific response to those treatments and that is risky, that’s not captured in the clinical trials. We will expose a lot of people in the real life treatment down the line. That’s on the individuals affected, it will also have implications to everyone else because the treatment will stop being available. If we get a very high risk signal after the registration of the product, after the medication for example is being rolled out, that is a major issue and that can have implications that are really wide. And finally going back to the beginning of this argument, it’s the ethical thing to do. We have to be changing care based on high level, on high quality of clinical trials, but at the same time the populations need to be reflective of who we look after. I’ve explained to you how important it is, let’s look at the data and we did this for you. So we’ve all had a feel that some of the clinical trials are not really reflective of the of the inclusivity of the populations we look after. So we decided to do this work I did when I was working in Dublin, together with Carla Rui in St. Vincent’s Hospital and collaborated with colleagues at University College Dublin. So we looked at sex, race and BMO in clinical trials, all for registration purposes with the FDA. So these are the medications that were eventually made through FDA, or at least the studies were done for that reason. And we systematically reviewed that over 30 years. It was published in the last WDs in Econology about a year and a half ago. And I’ll start with the MinBMI. So as you can see at the top of your screen, this is the MinBMI 242 trials of medications for obesity. And what’s fascinating is that there is a lot of crowding around the BMR 35. What I really want you to show you is that this is a temporal, so the horizontal line is the temporal line. in 1998 and you go all the way to 2025 and you can see this hasn’t changed. And I want you to think about how obesity has changed in those years. So the person with BMR 35 today, they’re not considered to have very severe and complex obesity compared to the BMI 60 and 70 and 83 that I see in my clinic. And what was a BMI 35 in 1998? The epidemic’s evolving, I’ll get more into it, it’s important to recognize that this has not changed and it doesn’t reflect the actual burden of the disease. And if you split that between trials for type 2 diabetes and without type 2 diabetes sort of diagnosis involved in the population studied, you can see that there is some change of course in the studies for people with type 2 diabetes, the BMI can go a little bit I’m not going to talk about the participation of females and males in these studies. And again, you can see that this is the proportion of female participants. And as you can see, they are predominantly female. If you look at the top of that graph, you can see multiple studies where 100% of the population studied were female. And that is also a concern. Again, remember the biology, if we have people with exactly the same body mass index and exactly the same race, if we’re just measuring cardiovascular risk, what is the risk of an event, that’s a major cardiovascular event in males versus females? We do know that in males it will be higher, but we studied more females. And that’s important to recognize when we look at the validity of this work. Very interestingly, and again, it just shows that we as academics, we as clinicians, as everyone in the field adjusts to those phenomena. So if you are doing a study with cardiovascular outcomes, you tend to increase, to include more males. Why? Because you want to increase your statistical power. You want to detect more heart attacks, more strokes. And it’s easier to do that if you include males. But that is not true for all the other clinical trials we do where you’re not having a primary endpoint being cardiovascular or MACE. And finally, if you’re looking at race, at the top of the screen is the Caucasian participants and you can see that most studies, they’re predominantly Caucasian. And if you look at the blue dots, it’s the black participants and you can see that it’s a lot lower, it’s a minority. If you look at Hispanic participants, again, some studies have a higher participation, most studies have zero. And if you look at Asian participants, again, the vast majority of clinical trials have zero Asian participants in the people they studied. And if you look at other races and ethnicities, again, there is a similar picture. So some reflections on that. It doesn’t look great, but you can’t improve anything unless you measure it. And we need to start from that. And I would urge you that if you are doing any research in this field, and I can tell you as an editor, as a reviewer, I will always say you need to tell us what’s the population, you need to describe the population and you need to tell us those characteristics. And most people do, but it’s really important we do that so that we can actually try to improve this participation. We need to recognise the evolution of the epidemic. And that is something that has been very challenging to do. That concept of evolution of the epidemic is a bit more challenging unless you’re an epidemiologist, or it has been more challenging until five years ago, when we all had a cross course on evolution of epidemics, ’cause you all experienced an epidemic, the COVID-19 epidemic, the COVID-19 pandemic, at tragic events, a lot of life lost, a lot of lives destroyed, but there’s some lessons from it. And that is, and I just want you to remember, I want you to think how you treated COVID-19 in April 2020. How would you stage my disease if I told you that I have COVID-19 and I was, let’s say in Italy or even in the UK. And I had COVID-19 in May 2020, with most hospitals overwhelmed, most intensive care units full of people with COVID-19. And what would you say if I told you today that I’ve just done a test and I tested positive? You’d have a very different response. And it’s exactly that evolution. And it’s the same in obesity. So when the, let’s say the mean BMI has increased in any part of the world, you know, in 20 years, That means that those of us who have a BMI of 42 today are very different to those people who had a BMI of 42 in 1998. It’s important to recognize that. So that our data and our work remains valid in an epidemic that is evolving, that is not static. It’s very important to talk about accurate staging. And again, a lot of lessons can be learned from cancer. One of the reasons that it’s easier to do clinical trials in cancer is that we know that if we take people with T4 N2 M0 disease, we know exactly what the outcomes will be by staging them. And therefore we can do clinical trials on specific populations with a lot more accuracy. And our treatments are different. So you would treat, let’s say, an ideal bit of upper GI surgery. So I’ll just use stomach cancer, which is a condition most of you will be aware. So if I have T1 disease, you’ll do a very different operation or different treatment option. You’ll give me a much more sort of less invasive surgery if you can. And if I had T4 disease or T3 disease, and if I have metastatic disease, you’re actually gonna be less aggressive because you know you can’t cure me. So you will be non-curative. So you will try to maintain my quality of life. And we’re talking about palliation. And if I have T3 and T2 disease, you’ll give it the most aggressive treatment. So the risk benefit balance becomes very clear. In obesity, we don’t have that. Not only that, but I would argue that our treatments for obesity right now, we’re treating, it’s not that we’re treating T1 disease and T4 disease exactly the same way. I would argue that we treat pancreatic cancer and breast cancer exactly the same way. Because we don’t have the sophistication yet of those diagnostic and staging criteria that can help us deliver this kind of work. And finally, the lack of treatment target. So obesity is a chronic condition and it’s not really helpful to talk about in the same context as cancer because you either have it or you don’t have it. But let’s just think about obesity as hypertension, as a continuum, or as type 2 diabetes, as glycemic control. Now think of it, please tell me, and I would urge you to please bring this up in the Q&A if you have that, ’cause I’ve been looking for this answer for a very long time so please tell me if you can think of one disease where the treatment target depends on the baseline. So would you ever treat hypertension by saying you need to improve your hypertension, you need to improve your systolic blood pressure by 15%? Would you ever say that your glycemic control will improve by getting your A1c by 22%? We don’t say that, we have specific targets, very clear guidance on what the end point should be. Should be less than 120 or less than 140 or whatever it needs to be. Because we know that at that, at exactly that point, the risk benefit balance is favorable. And we do know that if we improve, we can reduce this systolic further, but people will start having car accidents and fainting and it’s also not very good for the brain if they get hypertensive. And the same about hypoglycemia, you know that we have a very good target and if we give people more hypoglycemia, that’s not really good, but if we do have a very high, glucose a very high A1c, that’s also not very good. But in obesity, we just say, yes, depends on where you start, we’ll give you 15% or 22%. So that is a massive challenge and we need to define a treatment target. We don’t have one right now and that is a major gap in our care, major gap in our understanding and therefore a major gap in healthcare policy. So the big question is, what can we do? What can the ECN do? What our colleagues, what can we all do? This is, ’cause sometimes this kind of questions and this kind of challenges feel as if we’re trying to boil the ocean. It’s just too big for us. And I would argue, absolutely not. And I’m going to get to the detail of what can we do, could each one of us do to improve on the current situation? And the only way is up, really, because as you’ve seen, the representation is not good at all at the moment. So the first thing is to acknowledge the limits of the current evidence base. It has to get better. And we need to accept it. And I’m not going to sit in front of you here and rubbish the current clinical trials. They’re amazing. The clinical trials in obesity care are incredible. We have studies, tens of thousands of people, 42 countries, 150, 180, 200 centers around the world, incredible clinical trials. And as someone who does, I can tell you as someone who does surgical trials, these numbers are just mind blowing. And the quality of them, because of the regulatory aspect of it, because of the academic robustness of them, really well-designed, amazing data, very rich data sets. But there is a limitation. We’re not studying the population, we’re treating every day. And we need to acknowledge that. And we need to acknowledge that in our guidelines, we need to acknowledge that at global health. Remember, obesity is not a disease that is only effective in the parts of the world where the studies are being performed. It affects the whole world. And the way we do guidelines, affects also, you know, they have a global impact. It’s important to recognize that. And by recognizing the gap, we can do something about it. And we can all start doing research in that field. And I can guarantee you that if you start working in this field, you’re likely to be very successful academically and you’re likely to be funded. We need to understand the biology better. And that involves, so it’s not just about doing better clinical trials. If you are listening right now and you’re doing a lot of basic research, a lot of lab-based research, that’s also really important to do that. because if we understand obesity at the molecular level better, if we understand what is different in terms of profile, for those of us who have a BMI of 33 that are going to get colorectal cancer when we’re 50, and those of us who will get a stroke when they’re 61, compared to those people who have a BMI of, again, the same BMI, but they’re gonna live a very long life, and they’ll still be hanging around with a 90 with high levels of function. There’s fundamental biological differences that we haven’t understood and we can’t predict right now. So if we get more precise about that risk, if we understand the heterogeneity better, but then we get precise about what makes different people behave differently, then we can treat them differently. There’s a lot to be done there. And then that will also help us finally have a therapeutic target that makes sense. It may even help us to have better diagnostic and staging criteria, because we don’t have them right now, and we debate about them. And the ESO, and I say this, has an incredible framework on diagnosing obesity and staging obesity. And you also know a different viewpoint from the Lancet Commission, again, about the diagnosis of obesity. But those documents and those viewpoints have highlighted exactly the need to improve from what we have now. They’ve started the discussion. But right now, my ability as a bariatric surgeon, someone who has done a PhD on GLP-1 to predict what’s going to happen to a patient in a SIN clinic with a BMR of 51 in two years is really worse than a coin because it’s not even 50% right. I have no way of predicting what’s going to happen and also have no way of predicting which one of my patients need treatment more because I cannot predict who’s going to get endometrial cancer, I cannot predict who’s going to get end-stage heart failure, who’s going to get chronic kidney disease, who’s going to die of a stroke or a heart attack. Our designs have to be inclusive, and that starts today. We just need to do studies that are more inclusive and they are representative of research, and that is not a passive process. So if I’m doing a study in Bristol and we do have a diverse population here, we have strong communities that are not represented in the study, they want to do something differently. I want you to understand the gaps. We’re talking about biological processes, but there is the interaction of the social processes. So a lot of our patients, perhaps, who could participate in research, they’re not. And they’re not perhaps because we need to translate our information leaflets in a different language. Perhaps there is no enough trust in research. So we need to reach out, we need to go to those clinics, we need to go and recruit in the community. We need to understand what the barriers are. Perhaps people don’t have enough time to come to the research appointments. need to make arrangements for this, perhaps pay some of the of the lost work that they have. We can’t just sit here and then in 10 years from now, keep counting how many people are involved in our studies and then and then keep demonstrating that our population studies exactly what I showed you today predominantly female, predominantly Caucasian with a BMR 34. So we have to change that. And we can do that by reaching out to those communities who are and they’re represented. I have to admit to you that when this piece of work came in, I went very heavy on our industry partners. I went to them and said, “You have to do something better than that. This is just not right.” And very often they engage with me, and I have to say, and I have to really acknowledge that, that very often said, “We understand that.” And in fact, a lot of organizations now, industry partners, they are doing clinical trials addressing that gap. the regulators are not doing that. So if you go to our regulators, whether it’s the FDA or the European Agency or the MHRA in the UK, they still use the same criteria they had in the 1990s. 5% weight loss, BMI, you know, low BMI, because obesity has not been recognized as a disease. It’s definitely not treated as a disease by regulators fully as yet. So there is this sort of risk aversion from exposing a lot of people to these medications that are mainly considered a lifestyle option as opposed to life-saving life-changing treatment and the responsibility lies again with us. So who are influenced? Who influences the regulators? We do. Scientists, clinicians, leaders. Who makes policy? You know again the scientific associations, the professional associations, clinicians, researchers, scientists. We do. So we need to engage with those organizations and change the narrative, change the direction of trouble. Funding. And again, funders need to focus on this research. For a lot of funders, obesity is considered a solved problem now. Well, it doesn’t feel like that in my clinic and definitely doesn’t feel like that as a citizen. But again, as citizens of this research community, of this after people living with obesity, who sits in those committees? We do. Funders are not, of course, they’re anonymous organisations. And very often, you know, I can say this, that very often, I disagree with some of those decisions. But there are clinicians involved, there are scientists involved, we need to influence those decisions so that research is a lot more inclusive, a lot more representative, therefore, a lot more valid, therefore, therefore, of a higher standard quality. Academia is the same again, the academic institutions is us, we influence those, and industry partners again, who do they ask when they want to know about those issues? They ask us. So a lot of us are consulting those organisations, a lot of us, and as we all, and I know I’m talking to colleagues who are in the early stages of their career, but before you know it industry partners will be asking for your opinion and you’ll be able to influence them. And finally, we can’t be doing research for a population we don’t talk to. So we need to engage with the population. So PPIE is not some sort of box text that yes, we know we have had some sort of involvement and engagement with the lived experience groups. We need to have deep discussions, we need to have deep collaboration, we need to engage with the community. They will tell us how to do this better. They will tell us how to reach the communities we’re not reaching. unlikely to understand how I need to recruit patients in the most undeserved part of my city by sitting in my university office or in my hospital office. I’m much more likely to understand what I need to do by engaging with the community and talking to them. They will tell me what to do, they will make it happen, but we need to engage better with those agencies, the PPI groups and of course the community. And the question is, when are going to do this? Well, if it’s not going to be us who’s going to do it, then I would question you, then who is it going to be? And if it’s not going to be now, then when? So this is from the economist from a few months ago. We live in this amazing era, the most exciting era in memory in terms of obesity care. And I’ve been in this field for two decades now. This is the most exciting time. We finally have amazing treatments. They’re safe, they’re effective, they influence cardiovascular risk, they make people’s lives better, they make people’s lives longer. It’s an incredible time. And this is demonstrated by the sort of parting of those medications and the sort of Swiss army kind of approach to these GLP-1 based drugs. It’s an amazing time. Now is the time to do this, so we can actually improve because the future is coming very fast and our treatments are getting better but my concern is that we’re still studying the wrong populations. So I’m going to start concluding and just bring all this together. So my take-home messages are so first of all current research does not yet reflect the people it’s supposed to serve and that’s a really important statement and we need to acknowledge that. We need better inclusivity because it will strengthen the evidence base and a stronger evidence-based means better clinical outcomes, better policy, better care for the individual. It’s back to the population again and the opportunity but also the responsibility is ours. I’m going to thank you for your attention. Please allow me to acknowledge my colleagues at North Bristol that allow me to do all this sort of work and collaborate with and my collaborators around the world in Dublin and in Sweden. And I’ll just close with a bit of another reflective note. This is the Concorde. This is the last time a Concorde ever flew. This is just over the Clifton Bridge. It’s just a couple of miles away from where I’m based now. It’s in Bristol. And you can see a lot of people are on the gorge waving because a lot of the design was here in Bristol. So if you’re ever in Bristol, you can visit the last Concorde ever landed just just around the corner from from where I work. And the point I’m trying to make is that there is a very fast pace of change. But it will never be this slow again. And the current treatments we have, although they’re amazing, they’re the worst treatments we will ever have from now on. The future looks really bright. Thank you very much for listening.

Speaker 1 • 33:04
Thank you so much, Dimitri. And a great message to finish on as well. So we have plenty of time for questions which is great and we already have quite a few and just whilst people are thinking of their questions please use the Q&A. I wanted to ask you a relatively leading question myself first if that’s all right. So you rightly talked about the importance of engaging with those with lived experience to help design research and clinical trials. Do you have any advice specifically to the Early Career Network researchers on any

Speaker 3 • 33:38
organisations that can help support? Absolutely, so reach out. There are European organisations, the ECPO is a great organisation, advocates for people living with obesity and then look regionally and locally depending on your country. These organisations are very well outspoken so you can easily find them because that’s what they do, they do advocacy most. And by getting to those advocacy organizations you can start the discussion. And in the UK we’re very lucky we have a group in Leeds which is the Obesity Voices which is a great organization to collaborate with and of course depending on the population you’re targeting you could have those discussions. It’s very important to understand the limitations of these organisations. And I have to acknowledge that I’ve been working with these organisations for more than a decade, and I have strong relationships with some of the individuals involved, just because we’ve collaborated for such a long time. But there is also a barrier about who participates in those organisations. And I would argue that the inclusivity of the people involved in these organisations is also very narrow because who has the time and who has the resources to be able to be involved in these organisations? So you already self-selected as someone who has the financial resources to give time and if you are a person living with obesity who’s unemployed, who’s struggling to provide for your family, it’s very unlikely that you will have the time to come to those meetings, the energy to advocate and the ability to engage with different sort of stakeholders. So it’s important to recognise that those organisations also have that challenge of becoming more inclusive and we should also work with them to improve that inclusivity. But it’s the place to start and it’s a place to start those discussions and it can only improve.

Speaker 1 • 35:43
Great. And following on from this, there’s a great question, actually. Could you share a specific case of PPIE that you were involved in in this context and how it shaped your work?

Speaker 3 • 35:56
Yeah, so I’ll tell you actually my first. So one of the first realisations of that, and I’ll take you back 17 years ago, and there’s a piece of there’s a paper with my name somewhere in a gynaecology journal, believe it or not. So we had some questions, so when I started working in bariatric surgery in 2007 in Taunton, we were giving people questionnaires that were quite generic, loads of questions about why do you have surgery, you know, it’s a lot of data. The key thing was that it was being delivered, not it was being given, not by the surgeon or the researcher. They were being given, it’s not even a research exercise, it was just a part of audit process. It was given by our bariatric nurse specialist. So a staff nurse, really well specialised, was just giving that and wasn’t even looking at it, was just putting it in the box. And at some point, I thought, you know, I’m just going to open that box and find out what happens. And the reason for that is that one of my patients admitted to me that said, look, I don’t care about weight loss, I just want to have a baby. I’m really not interested about the BMI. Now, if you look at her documented letters, he just wanted to have surgery because he wanted to use surgery as a tool because again people have been programmed to tell us what they think we want to hear because they live in the same stigmatized environment that we all live in and the beast is a highly stigmatized condition and imagine how much more stigmatized he was in 2007. So this lady she just said look we sort of built some reports said I’m not interested in any of this I just want to drop my BMI so I can have a baby. So based on that I went back and looked at all the questionnaires and we found that something like one in nine women of childbearing age, the main reason to have bariatric surgery at the time was to have a baby. And we published it in a gynecology journal because it was just a striking finding. So I just have a paper because someone told me what to look at. So if you like, and it was not a formalized PPIE. PPIE did not exist in 2007. I don’t remember PPIE being a thing in 2007 and if it was I didn’t know about it. But engaging with the community tells you what you need to do. Another aspect of it is that I was involved in a clinical trial, I’m not going to give details because it may affect individuals who may be involved, we’re trying to improve access to this clinical trial, engage with PPIE and PPIE said the language is terrible, I mean people will read this and they’ll say I’m not going to be part of that. And they were right. The language was just full of jargon, at times highly stigmatizing. Because it was copy and paste from a piece of work that was done years ago that went really well. And of course, the feel has changed. So using PPI is not, and we have to be very careful, this is not a tokenistic process. So a lot of funders right now, and a lot of academics and whatever review process will look at your PPI involvement. It’s not something you do and you say, fine, I’ve done it. I want to see what you got out of it. If you do it properly, you’re not getting a box ticked, you’re improving your quality of research, it opens your horizon and you’ll do much better research, you’ll be much more successful. So I would urge you to do, to engage with PPIE, not because it’s the right thing to do, it’s because it’s hugely beneficial.

Speaker 1 • 39:21
Yeah, thank you, it’s a great answer and thank you for sharing those examples. And sort of staying on a similar topic, do you think there has been a loss of trust from people who have been traditionally excluded from clinical trials, for example, people from different ethnic backgrounds, and how can that potentially be addressed for the future?

Speaker 3 • 39:42
That’s a very good question. I think the only way to know if that is correct is to actually ask the question, and that’s a really good study to do. So do some qualitative research and actually understand if those communities already feel betrayed. My suspicion, I don’t know that, and I should not be asking, you know, in a scientific forum, I’m going to give you a this is not science, but my suspicion is that that betrayal goes well beyond the participation in clinical trials and that goes into multiple other dimensions. However, the way forward is to address this head-on, is to acknowledge that and do something differently. So although there is no doubt, and I’m not proud of this piece of work that I’ve showed you demonstrating that actually those populations are not are not reflective of what solution. So I think if we engage with a community that is underrepresented and we start doing this work explaining why we want to do that, not tokenistically, it’s because we want to know that when some guideline comes in, it is reflective of the people I look after in Bristol or in Birmingham or in London or in Manchester or in Heidelberg or anywhere around the world. So we need to, or globally, you know, also to make sure it’s valid in, you know, in Mumbai, in Kenya, wherever, you know, it’s all over the world, you know, globally. So I think by explaining that, by being upfront, I think we can engage. I don’t, the concern here is that although it can feel demoralizing, is that we give up on that. I don’t think we have, I don’t think that’s an option. How can we continue to do that? So we just need to try harder, engage with those underrepresented populations, perhaps explain that the current state of affairs is not what we would like to do, but we will change it. And ask the question, what do these communities want us to do? My first question to PPI groups is, what should I do differently? How do you want me to improve this? I want to include more people from this subgroup of the population. Tell me how to do it. ask me to jump, I’ll say hi, not the other way around. And the risk, and I think we’re getting into very sensitive topics here, but I think it’s important to say that is that, and I say this as someone who is based in the UK, is that there is a risk of colonialism, of academic colonialism. So we’re going to come and show you how it’s being done. And that’s not good enough. I mean, that’s not acceptable. So we need to ask the population we want to study how we’re not going to tell them, I’m not going to go into a community that is underrepresented and tell them, look, I think I need to I’m going to do this. And then it’s going to work. It’s not you need to tell me how I’m going to make this work.

Speaker 1 • 42:36
Sure, thank you. And so following on from that, and another question from the audience. The systematic review you recently published was was interesting, and probably the the results were relatively expected that there was a real lack of diversity. And I know that other systematic reviews have of other obesity management like bariatric surgery, behavioral lifestyle intervention have been very much the same in terms of a lack of representation. But do you think that the, I guess, the popularity of obesity management medications are likely to improve inclusion of more diverse populations comorbidities in the future. And how are we going to address that in the future, the big, very heavily industry funded clinical trials?

Speaker 3 • 43:26
Yeah, so, so, so first of all, yes, it wasn’t expected finding, but nobody was expecting that scale. And as I say before, is when you start measuring the scale, you can start changing practice. And, and that also means you can improve on that. So if you don’t know what you’re aiming for, you’re never going to get there. So and that is true for bariatric surgery, I’m absolutely certain. In fact, bariatric surgery was even more challenging to get due to the cost of it and the social barriers to it and probably due for lifestyle modifications. In terms of the popularity of these medications, we’ll address some of that because we will get real world evidence on populations that are probably more enriched, one could assume. We don’t know that, but I would expect it. As those medications become more available globally, may be able to capture some of these data from real world evidence, but it’s not the same as clinical trials. So I still think we need to do both. I think we should not miss the opportunity to use real world evidence from more diverse populations. And I would love to see that in in parts of the world that we don’t have a lot of clinical trials and that involves parts of Asia, parts of Africa, you know, I’d love to see that. But at the same time, I think we can do the studies are industry funded because an FDA clinical approval study will always be industry funded. But there are two opportunities here. First of all to influence the industry and I think we can do that. And again, who does those clinical trials? We do. So when you know when there’s 17,000 people get included in the study, who actually includes those studies? It’s not the employees of a company, it’s people in this network. So we can change that and we can also influence this by influencing the design and finally influencing the regulators. And on top of that if that’s not good enough and it may not be good enough our academic studies can focus on exactly that. There’s no point in trying to get an effectiveness study right now on Caucasian women with BMR 33. So if you’re in a university and you’re trying to study people, don’t study this population, you’re not going to get better data than what we have from these amazing clinical trials. But perhaps you can do another study in a different population and and academically that will be interesting and it will change our, it will also learn how you recruit because that’s also very important. You’ll tell us, you’ll tell the rest of the world, you’ll tell the companies how to recruit in those clinical trials and you’re also going to give us insights

Speaker 1 • 45:52
we don’t have. Sure, thank you very much and another question from the audience, a little bit more specific around clinical trials, is given the heterogeneity of obesity is it clear that BMI is not an adequate gatekeeper for trial eligibility, how can we change this?

Speaker 3 • 46:13
Yes, I mean that’s a that’s a I mean the questions are getting more and more challenging and that’s great that’s what we’re here for. So absolutely, so BMI has its challenges and we know that it has its challenges at clinical level and at individual level and it has its advantages, you know if you measure my BMI, you know all participants, all attendees measure my BMI, you’re going to get a similar figure. And every time we try to change that, we get heterogeneity around the measurement of the same individual, which is also problematic. So I think replacing BMI with something else is very important, but we need to have something better. There’s no point in replacing BMI with something that’s not accurate. And I don’t think we have that. I think that we do have some great tools. I think some of the staging tools are really important. I’m a big fan of the Edmonton obesity staging score. I used it in my clinical practice. But to make it an endpoint for a clinical trial, I will need a lot more data than that. I need to know that someone with this at population level, someone with this score, if I reduce it, you know, I’ll be able to save someone’s life. And I don’t have that. So I think we need to do so. Yes, we need to change it. But that’s also a big statement. You know, right now, BMI is, I mean, there’s a lot of debates, but we don’t debate BMI very much. And it has its uses. But as I said earlier, we need the basic science to find, to understand the biology better, and then we need the clinical studies to find something that is better than BMI. And you know, it could be a variety of things. It could be a biomarker. We’re getting better biomarkers. It may not be a high weight, sort of, formula. It’s likely to be a biomarker. We just, you just look, you do a multiomic kind of test, and you know that if a specific molecular target, it’s got a little bit sort of a specific level, I’m going to get colorectal cancer with my BMR36, whilst my, you know, someone next to me with a BMR52, they’re going to live forever. So I think there are, this is where it’s going to go. So there’s a lot of work to be done. This is the beginning. This is not even, this is not the end. It’s not, this is the beginning of the beginning. Yeah, absolutely. It’s definitely something that we’ve

Speaker 1 • 48:24
we’ve been exploring and toying with within our group too. We’ve just had another question come in and please do keep asking questions, there’s still another 10 minutes to go. So you mentioned that industry often ask for input from obesity professionals. Could you share some examples of the kinds of things that industry are asking about for those who’ve never connected in these forums before?

Speaker 3 • 48:45
– Yeah, so the challenging thing is that I can’t tell you, I can’t give you details because the first thing you do when you engage with industry is you sign a non-disclosure, particularly for the really sort of can’t get research ’cause it’s commercially sensitive, of course. But the, so the, what I like to say to the, to this network is that, first of all, very often the ways to engage with industry is, and I can probably give you three minutes sort of talk on that, is that, first of all, talk to people. So you build the connections, understand that they’re not, you know, it’s not like we’re pure as clinicians or researchers and they’re the evil, because there is that sort of stigma out there. They’re just people with, you know, just like us who are doing a job and they, you know, they get differently sort of rewarded and differently sort of, they have different sort of day-to-day work, but actually they’re trying to make the world a better place by giving better care to people. So engage with them and understand how you can help them and what they need from you. And every time it’s something different. And very often it’s a question, it all starts, what’s the question they want to answer? The other ways of engaging is that through education, and there’s a lot of professional education. The, so, you know, you can teach with them, you can, there’s a lot of educational events. In fact, this educational event is unrestricted, but there are other events that are sponsored by industry. There are studies that you can get involved. And then again, you engage with them around the design of the study, the participation of the study, the delivery of those clinical trials. And finally, when you’re an expert in your field, is you can consult these organizations and advise them. You can take advisory roles. The most important thing is that you can’t really make a recipe about where you’re going to be. And I definitely, I mean, I did a PhD as a surgeon, GLP-1. I didn’t think that I was going to be working with industry at the time. But when those opportunities appear, it’s important to keep the conversation going and to be able to have an interaction where you learn a lot from them because there’s a lot of information they have and a lot of insight. And there’s some really smart people working in those organisations. And you can provide them what they need, which is the real life, what really happens in the street, what happens in your obesity clinic. So if you’re a dietician, a psychologist, an obesity doctor, what happens in your clinic? They can’t know that, you’re the expert in that. So that is the way to work together and therefore shape the future in a way that is positive for these organisations. They, you know, of course they, you know, they are accountable to shareholders, but also positive for us who are researchers and scientists and clinicians who just want to look after our patients better. – Sure. – I hope I’ve answered your question.

Speaker 1 • 51:32
– Yeah, definitely. Thank you very much. So we’ll begin to start wrapping up soon, I think, but I have a question for you and I’m sure Laura might as well. Right towards the start, talking about the importance of including diverse populations in a clinical trial, is there a balance to be had of setting your, I guess your expected inclusion as the broadest possible population you want to include everybody to maximise external validity, but taking into account that there’s going to be some additional uncertainty into how your recruitment’s going to go, what your intervention effect size is going to be and therefore your chance of having a successful trial. How, I guess, what’s your take on that and what’s your advice, I guess, as people and researchers who are going to be planning these sorts of clinical trials in

Speaker 3 • 52:26
the future? So you’re a methodologist, you’re a trial methodologist, and I’m not one of them, I have to say this with capital letters, we’ll help you with that. So absolutely, you want to have as little limitation to your population so you can have a successful trial. I think what we often see is that means that you end up recruiting Caucasian females with BMR 33. So every one of those studies started with an inclusive population, but it starts being not very inclusive at the end of it. So it needs to be an active process to ensure that your population that you’re trying to study, for example, so you know, depending, I’m not going to use examples, but if your population is, I don’t know, is of a certain profile, you know, you can’t have… So if you’re in Bristol, you can’t include Eskimos, because there are not that many in Bristol. But the people who are diverse here, and you’re not including them, that you can do something about it. And I would start your recruitment, so you can do something around block randomization, that’s another way of doing it, so make sure that people are properly randomized. But more importantly is trying to increase your diversity as an active process and that is actually qualitative rather than coditive. And then keep looking at your population and making sure that studying your population that you are recruiting and ensure and have a process that your population will remain diverse enough by the end of the study. So I think that is a strategy, there’s There’s not some statistical sort of shortcut here. It’s a strategy to have. And then you make the trial methodology work towards that objective, just like they always do. But you need to have that objective and you need to explain that to your trial methodologist, who may never heard of GLP1 receptor agonist or bariatric surgery. You need to explain what you’re trying to do and highlight, acknowledge the limitation of the current evidence base.

Speaker 1 • 54:24
– Sure. And probably final or penultimate question. we’ve just had another one come in. If you have been involved in writing or reviewing grant applications for trials, what are the kind of green flags that you might be looking for?

Speaker 3 • 54:39
If I knew them, I would be a lot more successful in my own grant applications, and I haven’t been. But I think that a true, a real acknowledgement of the issue and the real engagement with the issue and an honest and fair PPI engagement as opposed to tokenistic one. And you can read that from miles away. You don’t need to be, you can see straight away if someone just has a grant application and five days before the deadline sends it to a PPI so you can have a green tick versus someone who’s started a project with PPI from the start with a population, the patient at the center of it. You can see that from miles away. You may still not get funded, but you’re doing the right thing.

Speaker 1 • 55:29
Sure, great. And Laura, anything else to ask?

Speaker 2 • 55:36
I think we have another few minutes. And I’m going to tag on to the question that you’ve asked before as well. I’m really wondering a little bit more on the side of the research institutions what the barriers could be that we could tackle and improve though as early career researchers to be able to have more inclusive recruitment processes?

Speaker 3 • 56:01
Do you have any more discussion? So, you know, and again, I’ve been quite philosophical today, but you know, it’s the old, I think it’s all Confucius said that, that, you know, first they ignore you, then they laugh at you, then they want to fight and then you win. So you need to start with a I mean, we think that we kind of knew that. I mean, I’m surprised that my systematic review went that far, to be honest with you, because it hasn’t been done before. But most of our colleagues who are not in this field, who have no idea about that, to start the discussion, acknowledge it, and then start building on it and make it a priority, demonstrate to your institution that this is a huge opportunity to contribute meaningfully in the global evidence base. How many times do research institutions have that opportunity? How many times early career network researchers have the ability to do something so impactful at this stage of your career? So I would demonstrate that and start the discussion. It’s the first step to actually getting to where you want to go. Yeah, thank you so much. That’s a great point to conclude on.

Speaker 1 • 57:14
So I just wanted to say a huge thank you, Dimitri, for your time and expertise and for having such a an honest and excellent discussion over the past hour and hopefully, well I certainly have learned a lot and will take a lot of this into my practice. And wanted to also take the opportunity again to plug one of our partner organisations, the European Coalition for People Living with Obesity, and certainly to me how helpful they’ve been in shaping my research and if you are thinking about planning clinical trials they’re a really good organisation to reach out to and can point you in the right direction of the best practices. So yeah thank you again so much the webinar has been recorded and we will see everybody

Speaker 2 • 57:59
at next month’s webinar so thank you very much. Thank you everyone.