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Summary

This on-demand teaching session is relevant to medical professionals and will focus on pragmatic late-phase surgical trials. Hosts Will Glasgow and Dr James will introduce and discuss the key features of these trials and how they are used to take innovation to fruition, and with the help of Dr OJA, will share real world experiences of running large-scale trials in Nigeria and West Africa. The session will also discuss the strengths, weaknesses, and challenges of such trials, as well as the need for high-quality evidence for global adoption. At the end, the session will provide an opportunity for attendees to ask questions.

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Description

Join us for Module 5 of the GASOC Frugal Innovation Skill course! This module is in collaboration with the NIHR Global Health Research Unit on Global Surgery - GlobalSurg! Join us to learn how to develop skills in Global Surgery Research and how these can be used in frugal and innovative ways to increase the impact of research!

Module 5: Global surgical research skills with Dr James Glasbey and Prof Adesoji Ademuyiwa.

Learning objectives:

o   Describe different types of clinical research

o   Understand principles of global surgical trial design

o   Describe the evaluation pathway of innovation in global surgery

Please note this date and time is TBC and will be updated accordingly - we will also pos ton our social media feed and our mailing list once the final date and time is confirmed!

Learning objectives

Learning Objectives:

  1. Explain the role of pragmatic clinical trials in surgical innovation pathways.
  2. Compile evidence to support the safe and effective adoption of innovations.
  3. Examine the strengths and weaknesses of pragmatic clinical trials.
  4. Understand the challenges in running a large-scale trial.
  5. Recognize how trial results can impact real-world healthcare decisions.
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Computer generated transcript

Warning!
The following transcript was generated automatically from the content and has not been checked or corrected manually.

Good evening everyone. Thank you, er, so much for, for joining us on this um er this latest module of the Gas O Food Innovation Skills course. Um And for those of you that are, you know, watching us and play and play it back and catch up. I hope that you're enjoying it at your convenience. Um My name's Will, I'm the Gas o past president and um I'm helping coordinate the er session today. Um And er II just, I wanted to just give a little introduction to the session um real quick before we hand over to our amazing guest speakers. Um And for those of you that have been taking part in the other, in the other modules, um I think what we're trying to do with this frugal innovation skills course is to develop innovations in technology that's going to benefit patients all around the world, hopefully, er, especially those in low resource environments um and getting your innovation safely adopted into practice um requires evidence generation in healthcare. We have to make sure that everything we do is evidence based and um creating that evidence, generating that evidence is can be really challenging in any context. And having a really good understanding of the kind of skills and the pathway around how you get your innovation adopted into practice is um is absolutely essential. You have to make sure that you do things safely and effectively and you have to be able to persuade policymakers to pay for your innovation and use it um and to benefit the target population that you're trying to benefit. So it's really exciting to have this, this session around research skills and in particular, focusing on kind of the, the later stage of the innovation pathway. So once you've got your innovation, how do you get those late phase studies up and running and deliver to generate that effectiveness, data that you need and health economic space that you need to get your innovation safely and er safely funded and adopted. So, um yeah, it's, it's, it's, it's, it's gonna be a fantastic conversation. I can't wait to have, can't wait to listen to the speakers. And also towards the end, we're gonna have AQ and A. So if you do have any questions for the, the speakers, please do pop them in the chat. I'll do my best to get through them all at the end. Ok. Um And for, for those of you, for those of you that have colleagues that can't make it live, feel free to share the link at the end, it will be available on catch up uh shortly after the event today. So, yeah. So thanks again for coming and without further ado, I'm gonna stop talking. I'm gonna turn my camera off. I'm gonna hand right over to, uh, our first guest speaker, James, who's gonna introduce his topic and his colleague? Thanks. Thanks very much. Well, it's a pleasure to be here and thank you all for joining us on a Thursday evening. Um, I, my name is James. I'm a, um, N IR academic in Global Surgery at the University of Birmingham and a General Surgery registrar. Uh I'm delighted to be joined today um by, by so he's a treasured colleague and friend of mine. Uh we've worked with for, for many years together and um so please to introduce yourself. Thank you very much James. My name is OJ A, I'm a pediatric surgeon and I also lecture at the University of Lagos Nigeria. It's a pleasure to be here. Thank you. And we're very lucky to have. Um So really as a, as a key research leader around the world. So thank you very much for joining us um from a just today. Um So today we're gonna talk to you a little bit about um pragmatic late phase surgical trials. So, right down the far end of your innovation pathway, and we're going to talk to you about how pragmatic trials um can take your innovation from something that's safe and feasible. Hopefully, through the evidence you need to um to fuel global adoption. We'll talk a little bit about um theory and try and ask a address some kind of key questions about the strengths and weaknesses of pragmatic trials and perhaps a little view to the future. And so is gonna give us a, a real world experience of leading these big large scale trials in, in Nigeria and across West Africa. Hopefully fuel your thoughts for the for the future. If anyone hears any toddler screaming in the background, it's bedtime in the Glasgow household. So I apologize in advance. Uh So we've heard about a little bit about um us all already. So what we're hoping to do today is to run through these five objectives. So firstly, to talk to you about, um where do a pragmatic trial fit in this pathway of surgical innovation? Um Are they the only way to, to do research which is taken through to adoption? And, and what are the potential problems with these big chromatic trials? We're gonna share some thoughts um about why all trial evidence. So really high quality trial, um, evidence is not adopted across the the world in every operating theater. Although I have to say I don't have a full answer for that. And that's something which I think is a major research agenda for the next 10, 2500 years in, in global surgery, I suspect. And then we're going to address a little bit about what it's like to run a large clinical trial and share some thoughts about how the results of trials are seed in the real world. So we're really excited for this discussion today and we really do want to make it as interactive as possible. And so please do ask questions in the chat. And if you ask us as we're going along, we'll try and pause and answer to make it a bit more of a conversation. And so, and I will have a conversation too with, with will probably again at the end, we're not gonna focus too much on the nitty gritty theory, the sort of thing you'd get in a master's in clinical trials or, you know, research modules in university, but focus a bit more on lived experience and, and an oversight of, of where this fits and what sort of people you may need to involve in your project if you want to run large clinical trials in the future. So without further ado I'll hand over it to so to talk a little bit more about the N hr Global Surgery Unit and the Lagos hub. So thank you again, James and good evening everyone. Um Welcome to this webinar. So um like I said, I'm a pediatric surgeon and this is the hospital I work in the Lagos University Teaching Hospital, which is like 1000 bed hospital integrated. Um We treat all manner of patients from birth to um geriatrics next slide, please. So, um just to give a background to some of the amazing work we have done in our collaboration. Um A number of you might have heard about Global Search. So the idea started probably shortly before 2013, but I got to know about it in 2013. Um of some young men who feel that who have worked um with the decision of surgeons in training in the UK and feel that can be translated into a global network. And a couple of people around the world were contacted and I was lucky to be one of those contacted very early. And by 2016, we had our first meeting in Birmingham. And um we also had an observational study looking at over 10,000 patients from 58 countries in 3, 857 centers. And that study um showed that there was a lot of inequalities in mortality from emergency surgery. And it also showed that one of the commonest complications of surgery was surgical site infection. So in two years later, we did global search two looking at 12,000 patients um from 343 hospitals in 66 countries across the world. Um one of the largest and it also shows that surgical site infection was about three times higher in low income countries compared with high-income countries. Um We then took up the challenge to test interventions. Um as you know, um observational study usually will generate hypotheses that can then be tested by interventional study. So our first randomized controlled trial was published in the Lancet in 2 2021 randomizing close to 6000 patients from seven countries in 54 hospitals. And this trial showed that the use of cheaper alternatives of plain sutures and um, Povidone iodine do not have any deleterious effect on patients when compared with um, more expensive alternatives like, um, um, chlorhexidine. Pardon me? And, um, triglyceride, um, sutures. And this is quite important because in many low and middle income countries, um, surgery is born out of pocket. Then finally, um, we had the Cheetah trial also published in Lancet looking at 13,000 patients. And this is there any problem? I can't see these lights anymore. Hello. Hi, James. Um, uh, I think James was sharing his slides. Are they still sorry? Uh Can you still see me? You just, I can still see, I got the slides. Yeah, it just a error occurred. So, no worries. Ok, back to you. Thank you. Thank you so much. So, um, we were just talking about Twitter trial and, um, this is a very good example of how innovation could be tested. Um, the wh O recognizes that there is no, um, randomized controlled trial at all in the world to test change of gloves and instruments and their role in surgical site infection. And our group decided to take that up and we tested this intervention in a cluster randomized controlled trial. Um, in 81 clusters across seven countries. I were able to show significant reduction in surgical site infection just by this simple innovation that is very cost effective. Um Next slide, please. So our network is across seven countries um As you can see, and these are the leads in those countries at the moment. Um Our collaboration actually has close to 20,000 surgeons, anesthetist, medical students across close to 100 countries. Next slide, please. In addition to those. So the gentlemen on the top row were the first three I am aware of that started of Global Search. And then Michael presented today James and um dimet seems to be the backbone of people who have been able to impact um the network through early um conversion of our evidence into publications. And then um Martin is the lead of the NIH R group and has done quite a lot of work. So these are the faces behind much of the work that you see, including the COVID. So collaborating next slide, please. So I think there is a lot we're going to learn today um from James. So I'll hand over to James again before I come back. Thank you. Thanks. Thank you for an excellent introduction to the to the network, which really has grown substantially over the last 10 years. And there's now a kind of force of energy really in in surgical um innovation evaluation. And so something that um I find very um inspiring. Um so starting with these pragmatic clinical trials, what are they? Well, they're randomized clinical studies that compare at least two treatments or innovations. And what we're looking at with a pragmatic clinical trial is comparing something which is new and something which is stable. So it's not still under development, it's an established feasibility and safety profile. And what we do is compare that new thing to usual practice as close as possible to real life. So, um there's this thing which we call the pragmatic explanatory continuum. When you look at drug trials that are done in industry settings, and they tend to be what we call very explanatory. So they micromanage every little detail of the process, desperately trying to find an effect in a population who they think will benefit the most. And actually, that's not what we're interested in in pragmatic trials. What we want to know is that the innovations there we are testing are likely or whether or not they are likely to benefit a broad range of people across a broad range of settings. So with an explanatory trial, what we might have is 40 inclusion and exclusion criterias where only if or for 100 patients coming into a hospital undergoing surgery, perhaps one or two would be eligible for the study. What we aim to do in, in global surgery in, in our Pragmatic clinical trials network is to get, you know, 95% of patients into trials that are eligible. So our studies tend to include all major abdominal surgery, even including Cesarean section and a a and things in, in the Falcon trial, for example. So this is very inclusive. It means that we a broad range of patients and the evidence that we generate, we hope is very generalis from the um the best resourced hospitals. Um all the way to very small district and rural hospitals, which perhaps the less well resourced, we think that's very important for your evaluation of your new in, in innovations. When you get to the point where they are stable and you're happy with the safety and small studies and you know that they can be delivered and you ha you know exactly how they should be delivered. Um You get to that next step of of asking, should we roll this out worldwide? And when we design these pragmatic clinical trials, comparing something new versus usual practice, we tend to design these studies with one key primary outcome and that has to be co prioritized. So it's not a decision just for one researcher, it's something which is decided by a broad range of researchers and clinicians from across a multidisciplinary team and very importantly patients and members of the community. So that when we, when we design these trials, they um they answer questions which are relevant to patients and communities. Um There's a brilliant phrase that the NH I used um in their patient and community involvement work, which is nothing about us without us. So, patients, um we, we, we no longer can do research, which is designed to answer questions which are only important to clinicians. We have to do them in partnership with our patients and address things that are important to patients. So um if I were to give you one key suggestion, if you would like to, when the one of these um uh grants to help your innovation at the end of this program, it would be absolutely put patients at the forefront and think about how you're going to involve patients within the design and development and evaluation. Right from the start, I think that will make a very unique selling point for your project. So across the global study network, as so g highlighted, we, we've got this kind of pipeline of clinical trials now. So Falcon was our first kind of flagship trial where we designed the protocol and, and most trial protocols I've worked with in the past have probably been in about um 16 different trial development and management groups over the last 10 years. And um most of the protocols to these trials are upwards of 5100 pages in Global Surgery. Our trial protocols are somewhere between 2025 pages. They're very streamlined, very pragmatic and they really just look at what is the absolute things that we need to answer a question versus the things that might be nice to, to know. So it's a kind of lean frugal way of doing high quality multicenter research. And through that pipeline, we run the cheaper trial and then we've got other trials that are ongoing across peroperative uh cancer and wound infection. And we have several other trials which are using new designs and a new frontier in the future. Um So if you would like to learn from that experience, please, if you can take a look at our website and look at the protocols for these trials, they're a great resource to get you started. If you're thinking about designing AAA late phase trial viewer innovation. So where the pragmatic trials fit in this um of the the pipeline of innovation. So you might have seen this ideal framework before and if not, I really um encourage you to look at the ideal collaboration. A will who we met earlier. I think it is involved in er needing a new development of this for global surgery. I'm interested to see the results of that um in, in the coming months and years. The idea of the ideal framework is that historically, there's been no structured way to evaluate surgical innovation from conception through to long term follow up like post market surveillance would be the term from drug trials. And actually it is it it quite, there's quite sophisticated pathway um where things um can change quite a lot within a surgical technique from when it's first designed to when it's finally tested and implemented. And this pathway reflects that um differences in practice between surgeons and how a surgical innovation might evolve throughout lifespan. So ideal stands for idea development, expiration assessment, and long term. And each stage there's different guidance around how you should develop your study at at each of those, those points if you come up with a new surgical innovation. So again, I would highly suggest when it comes to designing a project at the end of this process, I would definitely map it to the ideal phase of the surgical innovation. And today, what we're looking at really is this a. So we, we, we've got, we've been past the idea stage and we've refined it in the um evaluation stage. Um And then we've kind of tested its early safety and feasibility and exploration. And what we do in pragmatic draws is is assess the innovation. So we can compare it against real world practice to know, is it actually effective for our patients? So that's what we're focusing on um today. Why do so? And II hate to steal words for why do, why do we look pragmatic trial as well if we're randomizing patients? So they have a um equal chance of receiving ie treatment. We have got study design which, which has the lowest risk of bias of any other study design when it's designed to high quality and to, to get very philosophical. Therefore, it's most likely to represent the truth as it were as to whether or not things work in real world practice. And whilst we do run these observational studies and, and probably, um somewhat er, elaborate on, on what their implications should be. They are, they always will be biased in comparison to something where a patient coming to the door has an equal chance of receiving one or another treatment. So neither um, the patient nor I nor anybody else would decide which treatment they get. And that's down entirely to this process in front of the medication. Um So that's very, very, very important. And a lot of the design tenets of randomized trials effectively try and protect the integrity of that randomization process. So the long discussions we have over weeks and months of la away to try and get the protocol right in a study really is to protect that process of randomization and reduce risk of bias. Um It means that if we've got these low bit studies that really does inform our discussion with patients, it means that we have integrity in the way that we can talk to them and we able to back our practice up with, with evidence. And because of all of those reasons, trials are most likely to influence practice. So practice being what surgeons are, this are the obstetricians or the healthcare workers do in hospitals and most likely to influence policy. And by policy, we mean what organizations and governments and NGO S um put out into the world to encourage changes in practice. And those two are not exactly aligned and often they can uh disagree or to some extent, um not, not kind of being cole at the same time. So we talked about a bit about these two examples and I think they were really, really strong examples and they showed two different types of innovation. And so these are stable innovations. And this was device innovations that we tested within the file control in the Lancer a couple of years ago. So one of them was the Clicky chlorhexidine sticks, um which you can brush up and down um where you're doing the uh the incisional, the incision in, in the abdomen. Um And you're supposed to do about 30 seconds of, of brushing with the sponge and it puts chlorhexidine over the wound and then you go to come, come around. And so you've covered the entire of your surgical site um versus bead, which is globally available and it's got a much, much lower um cost. Um However, in the rich guidelines at the moment, they still recommend using chlorhexidine. Um because of one study published in 2008, where half the authors um were from the company that made chlorhexidine and uh coated sutures, which effectively are sutures, which we can close the fascial sheath with in the abdomen. Um And they're coat it in an antiseptic which made sense that it would stop um bugs from being harbored within that um the suture material and hopefully reduce the risk of surgical site infection. What we found in this trial as so highlighted was that actually neither of these expensive innovations despite being adopted in global guidelines, um actually had any benefit from patients versus the much cheaper alternatives. So that was very important that these were not effective in real world practice and they're not cost effective. And actually in healthcare systems where patients have to pay for their own parts of the journey. And that is very unreasonable to ask them to do so for something that was not effective or cost effective. I like there was a study where this was not a device innovation and II encourage you to think about this when you come to the point of designing your innovations, this was a behavioral innovation. So, um at the point where people are about to close the fascial sheath in the abdomen just simply routinely changing your gloves and, and instruments at, at that point before you close the fascia. And this is something which I've seen done variably in different operating theaters. And often if you just have a bit of kind of paywall put on your gloves, you change at the end of the operation. But certainly I've, I've never worked anywhere where everybody routinely does this at the, every at the end of every operation. And this was the behavioral innovation that actually showed in this big trial of 13,000 patients to prevent one in seven surgical site infections. Something that simple. This to me was an amazing example of, of a frugal innovation that can benefit patients. Now, my question would be when you're next in an operating theater, does everybody change their gloves and instruments at the end of the operation? And if not, why not? I'd be interested to know. So how do we know if ther is pragmatic? Well, there is some tools that we can use to, to get a sense. I mean, in its purest sense, what you, what you want is it to be as close to possible as close to real life apart from the thing that you're testing. So every everything, everything else about the drug should be like real life. So patients should be effectively receiving standard care in that hospital or just this slightly altered um version of standard care with a new alteration to your pathway. There is this tool called Pre Tt, which is really interesting and this looks at each um component of a clinical trial design and you can rate the trial based on certain criteria on how close it is to the real world um for each of these kind of e design elements. Um It's encouraged that people use this when they are designing their studies to make them as pragmatic as possible. Um And there is a little bit of work ongoing about kind of post hoc and assessment of trials to say, oh, do you think we could have made that more pragmatic to make the recruitment better or to make it more generalis or make it um improve its adoption in the future? So think about if you are going to design a late phase trial um for your surgical innovation, taking a look at this proce diagram. Um So what are the kind of key things that your prognostic trial can give you your innovation? Well, to me, it's three things and one of them we've just added last year. So the first thing is you can find whether it's really effective in the real world. So will it be better in terms of your primary sector outcomes than what we're doing ready for patients? And that's probably the most important thing, isn't it? However, probably not to policymakers. Sadly, what they want to know is, is, is their bang for buck in the um in the money that they spend on, on healthcare. So if you're designing a, a pragmatic tro you have to think about cost effectiveness and, and your health economic analysis can be done um at the level of a hospital of a health system. Um So in the UK, we do kind of NHS budget um assessments, but whatever happens to speak to policymakers, you need to have a cost effectiveness analysis and what that usually is borne out as, as a as a price for a quality adjusted life year. So for one year of a good, healthy, healthy life, how much money is the healthcare system spending? And uh that sounds like a crazy thing to reduce it to. Um But policymakers that really is the the key question and different healthcare systems will have different cutoffs for what they're willing to spend on your surgical innovation. This is something really important to think of right at the start, if you have an ex um you know, a marginal benefit innovation, that's extraordinarily expensive. It is very unlikely to ever be cost effective if you have something which makes a small or a substantial benefit. Um And it's very, very low cost, it's very likely to be cost effective. The final thing that you might want to think about um particularly um at the moment, it is becoming increasingly important is the carbon effectiveness. And actually, to what extent is your innovation, greater or lower carbon than what has come before. And I think increasingly for policymakers, this will be at the tip of their tongues. And we've just designed a trial called um dragon which is rolling out in the, in the UK and hopefully globally in the next year or so, um which will have a co primary outcome of the carbon footprint um of reusable versus disposable gloves and gowns. So I definitely have an eye on carbon impact in your design. I know go out very well, with any judging panel. So why don't we do these big amazing pragmatic trials for every clinical question? Well, firstly, they're really bloody expensive. Um I think probably we have one of the most cost efficient platforms in the world to deliver surgical trials in our, in our child label surgery unit. Um, and it costs about 100 and 50,000 lbs per year of the trials running per trial to run one of these trials. So, um that is incredibly low cost for um, a fy trial, um, drug trials in the US, you're talking about, you know, 8 to $10 million a year um for um a similar study. Um So you have to think about whether, um therefore the thing that you're assessing has to be um important and to address an important question and not all innovations and not all research questions can or should be answered for this design. They take years to run. Um You know, we are doing things now in about two or three years in the Global Surgery Network, but some of our UK trials have taken 10 to 12 years and start to finish. And the question we ask ourselves is, is care still the same, is, is real world care still the same 10 years down the line has things shifted. Um So much that actually is the trial still by the time you finish it. And one problem we have in surgical innovation is this thing called Buxton's Law, which II always found fascinating and that's the kind of surgical innovation is always too early to be assessed in the trial until it's too late. And my, um, I guess robotic surgery kind of falls into that pathway now as it's being rolled out in many places around the world. Um, will there ever be more trials in robotic surgery? Uh I'm not sure it will. I think it's too late now. Um Interesting point. Um So the last um couple of points then I over the surgery, the we've done a trial. Um So what, so we ran this trial in the UK called um Rox, which was putting a biological mesh in when we closed the stomer site. Um and, and to try and reduce um incisional hernias of the stoc site and this happens for about 30% of patients. It's really common. Uh And we thought it was a really important question and lo and behold, it reduced the rate of stomy closure hernias by 30% at the end of the study. Six years, we were really excited and we published it in the lancet. We won the ideal prize for the best trial of the year. And we thought what is gonna happen to it after this? And we thought it would be like this. This is the lioness of the English ladies football team. They did very well at the Euros but didn't quite win it. And they're currently in their World Cup final at the moment. And everyone's very excited. So we thought we published the trial to be really excited and changed their practice around the world. And what we actually found was just a bit of, uh, no one, no one even really notice. And I don't think anyone in the UK or internationally really is routinely replacing these biological mass. And it's because of this thing called the evidence practice divide where actually it's not enough to have evidence alone to drive changes in, in practice. Um as a researcher, as you're doing, designing your study and thinking about um what you're going to do with um your, your evidence, you really half the work begins after you publish your, your trial, everything really is in pushing for implementation and, and promoting your work and trying to find um ways to talk to clinicians and to leverage, you know, policymakers um to, to actually realize differences in, in, in practice. And, and certainly what I find in surgery is that actually we're very conservative. Um We love the idea of innovation. We're very like excited by that. But actually when it comes to changing something you do for your patient, you do what you know, and you do what you've been taught to do. And that's because um you feel like any deviation uh may have a AAA difference in outcomes for the patient in front of you. So there's this difference between this um community from what, you know, from the literature versus what you should do for the patient in front of you. I've closed this, the, the, your skin in the same way for every patient that in the last, you know, eight years. And if anyone told me that another way would reduce wound infection, I think I find it really hard to change and it's the same with policymakers that, um, actually, uh, unless you speak in their language and it's something which is going to be politically important to them. And then actually, they probably don't care as much about um patient benefits. We do something uh So working on things to improve your impact right from the start with ways to talk to the press and patients and doing things like webinars and educational modules um is a really good way of kind of improving that we learn a lot from our COVID research work where we managed to get recommendations and lots of different news channels and, and and guidelines around the world. So I'll just leave you with it. I think um Richard Horton in 1987 he's the editor of the Lancer. And he said this thing about surgical research or comic opera. And he said that actually surgeons, they are, they're the clowns of the clinical world and they've done no proper research to inform their practice. And I think at that time, that was true. I think we are in a new era. And, and I think so you were one of the authors on a new editorial in the lancet saying that actually we're past that point now and I'd put it to you as an audience that our new comic opera is actually implementation. Actually, our new problem is that we have good evidence and we don't know how to implement it. And I wonder if we should think together about how we can improve the way that we adopt evidence around the world and look at kind of behavior change in the three states like Cheetah. And I would encourage you to think about when you're designing your innovation. If it, it has a good user experience and something which surgeons are likely to want to use and patients are likely to want to look at and use or interact with, then that sort of thing is gonna make a really big difference, these non tangible parts of a surgical condition. So I hope that's er forgive my um meetings and uh I hope, I hope that was useful. I'll um hand over to. So just talk a little bit about his uh real world er experience. OK. Thank you again. Um James. So um James has given us a background to some of the reasons and um the advantages of clinical trials, the next few slides is just to take you through how we started from the Comic Opera of Case Series to now becoming the um a center that has capacity to conduct clinical trials. And as we speak, we we have done three clinical trials, major clinical trials and we are still conducting some presently next slide please. So when we started, we started only with one hospital in Lagos. Lagos is um a state in Nigeria and has a population of about 30 million people. Nigeria as a country has a population of about 240 million. And now we have a network of hospitals of close to 30 hospitals. Um Many of them are teaching hospitals, but we also have some general hospitals spread all around the country next place, right. So before trial commencement, there are a lot of work that must be done. Um What we did in our own center was we had a research team um based on the interventions we wanted to test. At that time, we included people from g uh general surgery, urology, obstetric, and gynecology, and pediatrics. Um It could change depending on what um innovation you are trying to test. Then all our team members, we made it compulsory for them to be trained in ethics of using human subjects for research as well as good clinical practice for clinical trials. Um It's important that people who are going to be engaged in clinical trials have enough knowledge about the ethos of ensuring that patients are properly taken care of. Um their rights are not cramp upon just because of the research And so we made this compulsory and then there were lots of due diligence that was done between the hub and the University of Birmingham, looking at our research governance, clinical governance and financial governance. And again, this has actually um build capacity for us centers because some of the centers have never been involved in funded research before. And so this was an opportunity for them to actually develop research governance in those areas. Following this, we had um clinical trial agreement between the Hope and the University of Birmingham. Again, this is very, very important um because recently we received the um FDA equivalent in Nigeria and many of these documents that we just thought was um to fulfill all righteousness was scrutinized and they were impressed that all the I's were dotted and the T's were crossed. Then we also make sure that we recruited appropriate help staff and we involved both institutional and national ethics research committees before our trials begin. Um In Nigeria, there is a National Ethics policy that insists that once you are using more than three centers, you're most involved in National Ethics. So most of our studies, because the Multicenter we usually involve the National Health Research Ethics Committee. Next. So again, many of our trials involve um innovations um and investigative medicinal products. Um so we needed to involve the National Agency for Food Drug Administration and Control NAFDAC and their approval is very critical for us to have successful trial. Following this, we then have what we call a soft site incision visit, which is usually done online and that was PRE COVID. And then later we have the A S IV um in which there is physical visitation to our center. And this is also the same thing we do to our own sports within the country. And um we also have a contract between the hub and spoke institutions so that we are all on the same page concerning the trial. And then there is this concept of green light um in which a checklist is developed. And when all items have been met, all criteria eligibility criteria have been met, then a green light is issued for the commencement of recruitment of the first patient next place. Mhm Then during the trial recruitment, um we consent is usually gained at two levels. The consent for surgery is gained by the surgical team um who will be operating on the patient for the trial. The the surgical team could gain the consent or our research. Um staff, usually a nurse could also gain the consent for the trial. And in Nigeria, once you are 13 and above, there must be accent apart from the consent gained from the parents, we make sure that randomization was at the red line because we did not want to have too many patients who are randomized and did not end up being operated. But we feel that once the patient is at the red line. It's, it's almost as good as that surgery will be done. And we had very, very little um patients that had to exit the trial for any reason. Um, like not having their surgery done, then we fill the case report forms initially, usually with hard copy and then this is uploaded onto the red cap electronically follow up was on the wards before discharge and then after discharge, we really will review in clinic. But there was also another innovation in our first trial in which we tried to look at the validity of telephone follow up compared with in person follow up. And this came in and as this trial then extended into the COVID PE period and that evidence from telephone follow up showed that it was very, very, it was almost as good as um as an in-person follow up. And therefore we were able to do telephone follow up. We even developed that further to include video follow up. So these are some of the things that we did and we followed up at 30 days according to protocol. Um If there was any se ae these were reported across um along the protocol and along the line of report next slide, please. So during the trial recruitment, we make sure we continue to have meetings with our research teams quarterly. We had spoke visits and we monitored them um and gave feedback. We we did a lot of troubleshooting during those visits. And again, we conducted training for our data managers because one of the things about our trial is that the the inclusion criteria into analysis was very high. It was as high as 95% of the data points must have been entered. So we did a lot of training and capacity building for data manager on use of Red Car. And we also did the same thing for our financial reporting officers as well. Next slide, please, following um recruitment to the trial, we still continue to work. We needed to compile the list of authors um was at a meeting recently in Nigeria. And one of the things he said that cracked the audience was the fact that our goal as a community of researcher is to make sure that the least the pages of our authors is more than the pages of the manuscript itself. And as a matter of fact, our collaboration has a Guinness world record for that with 15,025 authors, you know, during the COVID um um pandemic. So we, we, we did a lot of work doing that. Then the statistical article plan was also um done usually after the trial and then a writing group is formed. And I'm I'm about to say that for our collaboration, there is inclusion of all those who have contributed one way or the other and all the herbs are well represented at every stage of implementation of conception of implementation and of the final write up, then it comes to publication. We are also involved in the choice of, of journals to publish in. And some of um our members from global health have led publications in very high impact journals through the collaboration. And I think that's a positive one for the impact of this collaboration in the career advancement of members of our network. And then we did, we do dissemination to stakeholders and we also had a number of press releases for some of our um research evidence um to be picked up by the public. Next slide, please. So we this was a dissemination at the decision of Surgeons of Nigeria conference held recently um in Nigeria. And this is also has been done in Ghana um last week and then in the Republic of Benin also in uh in West African Subregion. And it's also been replicated across all our hopes next place. We also recently were invited by the West African Journal of Medicine, which is the journal of the West African College of Surgeons and the West African College of Physicians um to write the editorial and we use that to disseminate some of the evidence that we have generated in uh um recent trial. Next please. Yeah, so we have quite a good spread across the world um in Africa, in the Americas, as well as in Asia. And some of our trials actually brought across the seven continents of the world next place. Uh It remains for me to say big thank you. And I hope we've not board you in the last one hour. I'll and over back to James. Thank you, James for inviting me again. Thank you so much. So, it's a pleasure to have you here and thank you for sharing um your, your rich experience and leadership of these trials over the last five years. Um So I wonder if we have any um questions um from the audience. Um Well, are you happy to start off? Yeah. Uh Thank you. Absolutely, James. Thank you, James. And so for that uh fascinating talk and for, for sharing your, your journey with us. Um You know, II yeah, I think it's true. It's inspiring um is underselling it, but it was, it's fantastic to see the work that you've done, especially against such um such challenges and such barriers. Um So congratulations and please keep it up. I look forward to seeing more results um from, from your group, you know, as you get them. Um So guys, um if er you do have any questions, this is a really good opportunity to speak to two of the leaders in this field in the whole world. So um please do post, I've got a list of um a load of questions that I don't think I'll get time to ask. So please do interrupt me, but I do have a few to start with. That's Ok, guys. So, um, I guess, uh, uh, pe people in the audience may have a, a range of experience of trials. Some of them may have never got involved in the trial before. Um, or, you know, they're just beginning their journey. So I just wondered if, er, www, we could take it in turns, we'll go with James first. If you could just share maybe your thoughts on, what would you advise someone about them making their first steps to getting involved in a trial, this kind of this kind of area of research, if, if James, you could give your, your sort of overview of that. And then, so you, I'd be great to hear your perspective as well. All right, thanks will. And yeah. So do you, do you wanna go class? All right, I can um I think it's um um very important that if you agree to have your first trial, you should have training. I think it cannot be overemphasized. Um Before we started, we had several trainings um in the ethics of research and clinical trials. We also had trainings in the um um the conduct, we are training in this specific protocol of that trial. So, um for example, um the, the recruitment um the of the patient, so the patient pathways who is supposed to be informed. Um So if, if it's a training, for example, I think the first thing is such a trainee should talk to someone who has done it before. Such a trainee should have um should equip himself or herself in um good clinical practice with such ethics. And then thirdly, I think it's important that in, in my, in my place, we see that one tree does not make a forest. So it's important that there is collaboration. There is no way you are going to be able to deliver a trial um all by yourself. So you need to speak to friends. Um People of like mind the hospital that will deliver the trial that they have the facilities and, and, and all that. And then I think it's also equally important, most trials as we heard from the, the talk that James gave um are quite capital intensive and it's unlikely that they are going to just give it to um a new bee, you know, somebody who has not done it before. So one of the things that I didn't have time to say was even though you went and um Anil and Fitzgerald started when we are going to go for the big grants, they have to bring in De Morton. So I think if you are going to do your four trial, you need a mentor and may be important to also bring someone who's done it before. And then finally, I think so that I don't say everything James still has a lot to say. Finally, I think um a group like Gas o is, is there to help, they will be able to link you with the persons you need and then you can, you may be able to get resources easily. So these what these these wide groups like go like global search like NIH R GSU. Uh And then you can tap into those experiences and le and lessen your own learning cough. I think I'll stop here and allow James to also come in. Thank you very much, William. Thanks. So brilliant insights and yeah, II didn't have a huge amount more to add. I guess. The first thing is, as you said, this is a to are a massive massive team game. It's a property sport and everyone brings something different to the table and there's different roles for people across all phases of training right across the m sparing team. And the trial teams include people from a huge range of disciplines. This is like running almost like start ups for each trial really. It's very, very um it's almost like entrepreneurship really. And so there is a role for everybody and of course, there is an opportunity cost of doing any project, research, innovation otherwise. And what I put to you is that if you're going to spend your precious time and energy doing a study, then getting involved in one of these big multicenter trials I think is probably the best use. If you're interested in patient benefit, then actually, this is the the best way of spending your and that time, if you want to put it aside for that, that's certainly what I believe and why I am involved in these. And, well, I continue to be hopefully for the rest of my career because I truly believe it can bring benefit for patients in terms of the practical elements of that. Um You would think that, um, there would be too many people, you know, too many people involved and there's going to be too much competition for studies. And the the opposite is actually true that actually these take a huge amount of human resource and human capital to run. And there is a, there is always a lack of enthusiastic people that are motivated at every site. Um And you have to have pioneers like so in a hospital that are pushing things forward, pushing things forward, pushing things forward every day, clocking in it and, and, and saying, what's the next step for the study? What's the next steps for the study? And that, that really, that energy is what runs these studies in each hospital and you can be that person um wherever you are in the world and, and actually looking uh locally to start off with at what studies are open in your center, getting yourself GCP trained it, like doing your basic surgical skills course before going to theater for the first time. If you walk up to a principal investigation in investigator for a study in your center. And you say I'm really interested in research. I would like to randomize patients. I've done GCP training and we have a course called Granule, which is about recruiting patients to trials. And it's available free on the NR hr website. It's called granule. And I've done my granule training. I've done my GCP training, how I'm gonna get involved. It's almost impossible for that person to say no. Um A a and, and um so II would start locally and find a research leader, a mentor or locally that's involved in these m um Multicenter studies. Uh And, and, and get stuck in, you can get involved at any stage. Um, so that's certainly been my, my experience so much. Both of you really, uh fascinating um, insights and answers and, um, guys, uh if you are interested in, you know, joining the, the global search team or getting more involved, you know, uh just, just Google them, they've got, you know, an amazing website, um, join their mailing list. Um It, it's always got really interesting things in there. So, um, and, and likewise, thank surgery for the plug for gas. Of course, er, many of you may be members of gas do but if you're not then it's um, free to be a member, sign up and, um, reach out to us, we've got a large committee, one of us will be able to put you in touch with someone who's involved in trials or maybe we're involved ourselves. Um, so, yeah, definitely. I hope that this, this, this module, this talk, uh, this, this evening has given people the inspiration to get started in trials and, um, and it'd be great to see, you know, some of the participants of this, this course being the future trialists, er, evaluating their innovations in a really robust way. Um, just, I'm just looking at time, I think we, we've got time for just one more, one more question if that's ok. Um, it's, it, er, I don't want to make it too big but I guess it's just saying that I'm, I'm gonna take moderators sort of advantage here and choose one that I've always kind of wanted to ask. Cos I don't really know the answer and I don't know that anyone necessarily really does. But, um, I think it's an interesting question. Um, how do we ensure that trials involve rural patients as much as possible in whichever setting that we're in? Um, have you, uh are there any kind of um, activities or mechanisms that you guys have used or come across or seen other teams use that have helped boost their participation from rural communities essentially in trials? So, so do you want to go in first again? Um, let me allow you to go first this time. Ok, thanks and see you say, say you have some more kind of li living experience that within Nigeria. Um But from, from my learning, the the first thing is that you have to involve patients and communities in your research design from the word go. So your whole trial has to be designed around their priorities. So we're designing a um a study at the moment in, in, in greener operating theaters that's going to be launching shortly. And actually, um I have to say that it, it, it's patients everywhere don't really seem to, they want a good quality operation. They don't necessarily think that much about the border of physical. I had a patient stay that did it later. And they said, well, can I just have it open because I don't want to use all the calmed up side. I thought it was really interesting because I don't think when you're a patient and you're facing adversity, actually, people just want a good operation. But what we learned from our community engagement and involvement around that green surgery trial um in, in, in, in India was that um actually patients, a member of the Publix are regularly facing flood damage and loss of crops and food hardship because of climate change. So actually saying we're designing a study which hopefully might reduce the risk of that happening in the future, made very much more appealing to patients than in that area. So I think co prioritizing topics designing the study. So it is well aligned with pathways that are not just applicable to big tertiary hospitals, but actually using inclusion criteria testing and innovations that can be adopted in any environment, I think is really, really key if you have something which is only going to be able to be afforded by big tertiary hospitals in any country, not rural settings, it's probably going to be pretty unappealing for surgeons and patients in those settings to look to test those. Um So I think, yeah, good, strong community engagement, involvement and find local pioneers and leaders. So our colleague Philip Alexander in India is a great example. He was involved just like so right from the beginning and he's pioneering our rural surgery trials network and really, he just absolutely loves research in this community and these kind of sentiments of working hard to improve things to patient benefit and I think people like, like that and, and, and so er really kind of help um showcase research and its um accessibility, er even in, in its r rural hospitals, I think that's really, really very important. Uh So what are your thoughts? Right. Thank you very much James. Um So the truth is um we are not there yet. I don't think we are there yet. Um I'm not sure we'll be there in 5, 10 years, but I think that we are thinking about it means it's a journey we must take. Um the reason I'm saying that is that in many lower middle-income countries, the rural areas, the access to safe surgery and anesthesia in rural areas is really very low and therefore, it will be difficult to then recruit patients except those who will come to urban areas where those facilities are. But let me amplify what James has said in our work. Um The C EI that's community engagement and involvement is a cornerstone work. Um that is that derives a different line of funding. So all our work as ac ei component and the idea is to improve uptake of surgical services and research in the community. So that's a step in the right direction. Like I said, we are not there, but we have already begun the journey. The second thing also is the rural surgical network and he alluded to that when he mentioned Philip Alexander Phillip works in rural India on the Himalayas and access is very, very tough, but it works in a um mission based hospital there and is bringing a team within our network um of rural surgeons. And we hope that when we are able to do this, we will be have better uptake um of um having rural patients in our trials. But like I said, um a lot still needs to be done, but that we are thinking of it means we'll probably get the answer one day. Thank you very much. Thank you both for that, that insight into a really sort of challenging, challenging topic. But um it's great to hear you speak about how you're leading the way in um in, you know, in advocating for uh rural population involvement in trials. It's really inspiring as you, as you said on that last point, it's um definitely, you know, the future and I think you are making progress in it. So, um so thank you so much guys. I think we're unfortunate. We're out of time. II II only got about a quarter of the way through my list of questions. Um So, uh so that's a shame, but it is still such a fascinating, fascinating conversation. I wanna thank James and Soja again, so much for giving up your time and um sharing your expertise. Um uh keep keep up the great work. And um and thank you to everyone who's, who's joined us this evening. Um Like I said, please feel free to share the link on social media and with your colleagues. Um People can watch it for free on catch up. Uh The next module will be in September um And we will be announcing plans for our hackathon where you can take part in designing your own innovation project and also apply for some funding to take it forward. So, really exciting time. Um We've got some people saying thank you for sharing your experience in the chat bar. So that's really great. So guys, I hope that you have a lovely rest of your day, wherever you are, whatever you've got to do or have a good rest if you are going to sleep. And um yeah, I'm gonna stop broadcasting now? Thanks very much, take care. Thank you very much. Thank you.