IQVIA Holdings Inc. (IQV) Earnings Call Transcript & Summary

Hi, everyone. Welcome to today's live broadcast, The Silent Pandemic: Antimicrobial Resistance. My name is Andy Studna, Editor of Applied Clinical Trials, and I will be your host for today's event. We are pleased to bring you this webcast presented by Applied Clinical Trials and sponsored by IQVIA. I would like to share a statement from our sponsor. IQVIA is a leading global provider of advanced analytics, technology solutions and clinical research services to the life sciences industry. IQVIA creates intelligent connections to deliver powerful insights with speed and agility, enabling customers to accelerate the clinical development and commercialization of innovative medical treatments that improve health care outcome for patients. With approximately 82,000 employees, IQVIA conducts operations in more than 100 countries. Learn more at www.iqvia.com. We have a few important announcements before we begin. This webcast is designed to be interactive and we encourage you to ask questions during the event. [Operator Instructions] The slides will advance automatically during the event. And if you have any technical problems viewing or hearing this presentation, please click on the question mark Help widget in the top right of your presentation window. And with that, I would now like to introduce today's speakers. We are pleased to be joined today by Colin Brown, Sharon Hughes and Philippe Glaser. Furthermore, there has been a last-minute change to our events moderator, and Dr. Paul Turner will instead be taking over Jeff Spaeder's role in today's discussion. Paul Turner is a U.S. board-certified infectious disease physician and serves as the VP and Global Head of Medical Strategy for Infectious Diseases and Vaccines for IQVIA. Turner has provided medical and scientific adviser and safety physician services on multiple clinical trials in influenza treatment and vaccines, dengue vaccines, antimicrobial agents in severe pneumonia, chronic hepatitis B and C, West Nile virus vaccines, invasive fungal diseases, plague vaccine, anthrax vaccine, HIV and other indications. He has developed Phase I, II and III clinical trial protocols in IDV, including COVID-19 [ vaccine ] and treatment trials. Prior to his career in clinical trials, Turner was a clinical assistant professor at UCLA responsible for medical resident teaching in HIV care after spending 14 years in clinical practice in Los Angeles and head of a large HIV clinical and research practice. Colin Brown is an infectious disease and medical microbiology consultant working at UK Health Security Agency on a portfolio of clinical and emerging infection, antimicrobial resistance and global health. His time is currently split between treating patients with clinical infections, including high-consequence infectious diseases, at the Royal Free Hospital in London, working on domestic infection policy in health care-associated infection and antimicrobial resistance activities as Deputy Director of the HCAI/AMR Division and as Interim Director of Clinical and Emerging Infections. Sharon Hughes is a Senior Director of Therapeutic Strategy in Infectious Diseases and Vaccines with over 28 years of industry experience, spanning both research and solid disease forms development. She has a deep focus on respiratory infectious diseases and antimicrobial resistance. Hughes is a strategist with years of experience in complex studies, managing clinical trials and developing therapeutic strategies around infectious diseases. Philippe Glaser, Research Director at the Institut Pasteur, is heading the Ecology and Evolution of Antibiotic Resistance Unit. He is an expert in bacterial genomics and evolution of antibiotic resistance. He is well known for his genomic epidemiology studies of Group B Streptococcus both in humans and in animals. He has shown how the extensive use of tetracycline starting in the 1950s has been responsible for the replacement of the GBS population colonizing humans by few tetracycline-resistant clones and to the emergence of neonatal GBS infection in the 1960s through '70s, both in Europe and in the United States. Philippe is involved in multiple collaborations right now, including deciphering the evolution and antibiotic resistance of E.coli and K. pneumoniae, characterizing the transmission of beta-lactam resistant E.coli across farms, modeling of the transmission of antibiotic-resistant bacteria and co-coordinating the AMR axis of the Institut Pasteur strategic plan. Thank you all for joining us today, and Paul, if you would, please get us started.

Thank you very much, Andy. Hello, everyone, and welcome, and thank you for joining the IQVIA webinar on AMR: The Silent Pandemic. Apologies for my voice; I'm losing it a bit today. But I think we all know how important antimicrobial resistance has become over the past several years. There's been high morbidity, high mortality associated with -- directly caused by AMR. There's been a huge burden to health care systems and health care personnel throughout the world. And certainly, an increasing list of pathogens that are becoming resistant to our current antimicrobial arsenal, including Candida auris as one of the most recent ones to rear its ugly head. So it's been stated that the prospects of scientists developing new antibiotics as fast as bacteria become resistant is virtually nil or impossible at this time. So over the next 30 to 40 minutes, you'll hear from our panel of esteemed experts on the challenges we face in the veterinary, health and environmental communities, where this may take us if we don't up our game against AMR and whether we can control or alter the course of this silent pandemic. We will also explore IQVIA's offerings on AMR data collection and our commitment to AMR research as well. So again, thank you all for joining today. And with that, let me turn it over to Sharon Hughes. [Technical Difficulty]

Thank you. My name is Sharon Hughes. I'm a Senior Director of Therapeutic Strategy and focused in infectious disease and vaccines. And I'm going to focus just a few slides today just to give you a brief introduction on some of our points that we'd like to make today. And we want to continue having these conversations even after the webinar today. We can move into the next slide. So just a few points to make. These are really important and critical conversations to have. AMR spans not just bacteria but also fungi and viruses as well. However, the larger focus today is really on bacterial AMR. And it is the deadliest global public health challenge that we have, and that spans both in modern medicine, in scientific discovery, patient advocacy, even veterinary medicine. Approximately 1.3 million people died in 2019 just due to resistant bacterial pathogens. And some of the problems that we have around that is it's been very challenging to bring new antibiotics and medications to market. Within a year or so, patterns of resistance start to develop very quickly. And latest, in 2020, a study was done and some patterns of resistance are now seen in certain pathogens in as little as 11 days, which is staggering. Some of the challenges around controlling AMR are really antibiotic use and misuse, which we have seen, and we have certainly seen the guidelines around responsible antibiotic stewardship. But that may not be enough or it hasn't been enough, as we see that, that trend still continues. And some of the challenges are not only the appropriate use of antibiotics, which also includes length, duration and targeting the appropriate antibiotic for the targeted pathogen, but also around patient education and compliance, which we always see as a challenge. And then I would be remiss to not mention agricultural and veterinary medicine as well. And another challenge is not having seen a new class of antibiotics since 1962 being approved and coming into research as late as 1980. Another thing to challenge here is the world's economic burden. So as of 2022, it's USD 100 trillion of economic burden attached to AMR. And it takes around 10 to 15 years just to bring a new antibiotic to market. And these are very challenging, complex studies with high dollar values, at least USD 1 billion to bring a new medication to market. And that being said, these trends with AMR continue to plague us, and these conversations are so critical to have because the World Health Organization is now estimating that we could see upwards of 10 million deaths in 30 years and that is just staggering. Now if we move into the next slide, I just want to highlight some pieces of IQVIA's attention to this silent pandemic. And then I know that -- those of you that have joined today know IQVIA as a world-class CRO, full service. However, I want to highlight that we do play a role in advancing global public health. We've been a member of the Global Health Clinical Consortium since 2010. And we have worked with multilateral agencies and nongovernmental organizations, some of those icons you can see there that are, I'm sure, very familiar, as well as governments. And that's all in a goal of advancing public health and increasing equitable access to treatment. And some of the example projects are seen to the right-hand side there, and you can see that we also participated in the Fleming Fund, ASLM in 14 African countries, and that was evidence generation on antibiotic resistance. We've also participated in Operation Warp Speed with the COVID-19 global pandemic. So these are all pieces that IQVIA is very interested in, continuing to partner with clients as well as with NGOs to advance global public health. And with that being said, I'm going to hand this back over to Dr. Paul Turner and to the panelists for our discussion. Thank you very much.

Great. Thank you very much, Sharon. So I'd like to bring Philippe and Colin into the conversation here. And one of my biggest questions having been a practitioner many years ago and currently with IQVIA, why are we still in 2023 discussing AMR? Why haven't we been successful in eradicating antimicrobial resistance? Why is this still a worldwide problem? So I'd be interested in your thoughts on this, Philippe, and Colin.

So maybe I can start. And so just I think that, in fact, this is a Darwinian system. If you are using an antibiotic against bacteria, then you will select for resistant bacteria. So you can't avoid resistance. Even if it can take many years, like in the case of vancomycin to select for resistance, that will spread over. So we have to know the process of selection of antibiotic resistance and to limit it. And then we need to learn how bacteria are disseminating once they are resistant to, somehow to limit this dissemination, for example, in the hospital context, to avoid to have the bacteria in the community, because then they will disseminate much more broadly. But this we can't avoid resistance. So this is a principle, just we can limit it and to have it acceptable. The other point is that we have many antibiotics. So by using just and by somehow using different types of antibiotics, at the end, it's possible to cure the disease until we reach a point where we have bacteria that are resistant to all known antibiotics and maybe Colin you will complete?

Yes. I mean I think it's a very big question. There's kind of multiple factors. A, I think it's transmissibility. We know that a variety of resistance mechanisms transmits via plasmids so they exchange genetic material with other bacteria so on to resistance mechanisms and there's either an individual host or a hospital or other environment. It can spread its resistance across other different bacteria. And so it's not a straightforward as [indiscernible] saving a single patient with a single bacterium that [indiscernible] resistance and that kind of being the end of stopping the resistance from transmitting. There's a wide number of factors, including understanding who has got an infection, which is not an easy question as non-clinicians may think. Who's got the right type of infection that would benefit from an antibacterial, which is the right antibacterial to give and what are the side effects of giving any form of antibacterial in terms of changes of resistance profiles in the trillions and trillions of bacteria that exist within an individual? There are a large number of questions about how long do we give an antibiotic for? What happens when we get very resistant antibiotics, what is the best treatment options? And sometimes those are very limited and are often salvage regimens, which certainly the evidence base behind giving them is very limited and indeed, the therapeutic outcomes are unclear. As Sharon said, from a development point of view, novel antimicrobials are not that attractive an option compared to the next heart medication or cholesterol medication, where you can give it to millions and millions of people. And you want to give it to as many people as possible, which is the key thing, is that where we got beneficial outcomes from a large number of drugs. We want it to be circulated widely and for that benefit to be reached. Whereas there is the balance with novel antimicrobials, where if we get a new antibacterial, particularly a novel one that's got a completely different mechanism of action than any others, we want to give that to as restricted a group of people as possible to limit the likelihood of further resistance developing and that obviously is a sort of unattractive option for many people to want to invest in, and we can come on later on to talk about potential different kind of financing models from that. And then there's gross inequity across the world, globally, both with availability of drugs, availability of diagnostics and of the whole infrastructure that you need from taking a clinical sample, having a decent laboratory that is able to process it, getting reliable results that we can get out of the mix, so that we know what antibacterial to give in the right indication. And there's still considerable imbalance across the world in lots of countries where they are just essentially working blind on giving antibiotics, without knowing what their local epidemiological profile is and without knowing what their resistance rates are and that obviously compounds issues more and more. So I think there is no really easy answer as to why can we not control it. And I think what we need to do is look at what we can do to prevent the increase as the main thing that we can do and if we can have improvement so much the better.

So I appreciate that. All excellent points. And I totally agree that it's -- there are a number of factors that are involved in being able to control, at least control AMR, if not eradicate it, which appears not to be an option at this point. One of the other things I want to drill down a little bit more on is the fact that why aren't people getting this in the general sense? I mean those attending today's webinar, those of us on the panel, we certainly understand the great concerns that there are related to AMR. There are a lot of conferences out there, there are a lot of -- how to do this kind of publications that are coming from government regulatory agencies, WHO, CDC, certainly. But it seems that people are not getting the message, even to the point of local hospitals perhaps not, if you will, correctly implementing infection control practices. Why is that? Are we just overwhelmed by the amount of data, by the number of messages that are coming down about AMR? Is it like we've got too many other things to worry about in life, even as physicians, that we can't be bothered with this, if you will? I'm just curious as to Philippe and Colin, your thoughts about what is it? Is the message not getting across to people? Or are we starting to see that change in 2023?

So first of all, I think that still antibiotics are very efficient. So if you've got a urinary tract infection, then you take a pill of antibiotics and then you will, in most cases, getting -- feeling better and getting cured from the infection. So there are, of course, cases where you will -- the antibiotics will somehow not work and you need to take another one. You need to have diagnostic. You will have [indiscernible]. So for the people, they feel that antibiotics are still efficient. And the other point that I think -- and this, I discuss this with student, is that there is not a disease that is associated with antibiotics resistance. So this means that people are not -- it's more difficult for them to put a name and even, for example, malaria or tuberculosis, this is a name and a disease and a lot of people are dying from this. But antibiotics, this is many different types of disease. So it's a little bit maybe more complicated to explain what is the antibiotic resistance to the general public. And even -- and for example -- and also, I think that in these, during these, at least in France, for example, antibiotic resistance is not a very important topic during the medical studies, for example. They have some lectures on this, but there are many, many lectures. And so at the end, it's not also still a priority in the curriculum for medical doctors. So -- and all this maybe explain why it's not seen so, to be so important. And of course, there are some -- the hygienists people in the hospital will make some campaign to -- for the proper use of antibiotics and so on and they try to make the best, but it's difficult to communicate on this issue. And I think this is my experience from France, but it's maybe a bit similar in other countries.

So Colin, interested -- yes, in your....

Yes, I mean particularly with your point about why aren't we doing better in hospitals, I think there's a big question of what is the thing that we need to do better? Because the [indiscernible] was the IPC measures, is that -- historically, they've been done often as a bundled approach, whereby we do a lot of things at once. And teasing out which one of those has each individual effect is really quite challenging. And therefore, it means when you've got a problem, so when you see a rise in transmission of cases, it is difficult to know which thing you might tweak to have the greatest impact. Hand hygiene is obviously very important. Isolation of patients, very important. Different countries across the world have very different hospital architectures. In the U.K., I would say, compared to a lot of the European countries, I'm not sure about France actually, but certainly compared to the U.S., is less individual or 2 people side rooms. So a lot more of our patients are cared for in an open ward, where any type of infection control is just that much more challenging. Different types of bacteria transmit in different ways. Some are spread by skin, some are spread either through fecal routes and different bugs emerge at different times, they behave in different ways. Candida auris being a big concern recently, particularly in the U.S., but in fact globally, as the first fungus to behave like a hospital or health care-acquired infection, and it transmits very much like Staph aureus does, skin to skin, probably lives very easily in the environment in a dry format and can survive for long periods of time and then can sort of revitalize itself. And all of those require different approaches to sort of cleaning of skin, screens of different bits of kind of particularly multi-patient use equipment. And so I would say there's always evolving challenges. We use chlorhexidine to reduce transmission of bacterium on kind of people's skin and then we get chlorhexidine-resistant isolates, particularly as we've seen with MRSA, developing that becomes resistant to the measures that we use. So I think it's not a sort of, A, there's not an easy thing to go, well, we're not doing that effectively enough and we will -- we should do more of it; and B, we should be -- and it's also not a static thing. There's always new advances in the microbes that I think change our ability to be able to eradicate them. And I would say that we saw during COVID-19 pandemic, certainly in the U.K., I don't think replicated in many other countries, whereby we had peaks of health care associated infections that accompanied the COVID-19 with. I'm sure that was in part a just sort of overwhelming of the health system response and it was different people being treated for different types of conditions in areas that they wouldn't normally. So intensive care is spreading outside of traditional ICU environments and into general wards and being cared for by different cadres of staff perhaps who are unfamiliar with line care in the same way the intensivists or intensive care nurses will be used to. So I think the difficult thing, to answer your question, is that there's not a binary answer of like if only we did more of x, we would reduce health care associated infections more. And I think IPC historically has been a sort of a neglected area, and we really need to invest in a lot more research into looking both at novel methods of control and really identifying what are the key levers of what really might have of a game-changing nature of things. And also, it is a bit neglected in terms of its place on the curriculum and in people's minds.

Yes. Again, very good points. And I think particularly important related to research. When we think about research in AMR, we think about, again, new antibiotics, let's develop new antibiotics. But I think you're absolutely right, that research into how can we do a better job at the local level, at the local hospital level, outpatient clinics. I don't see that there's been a lot of research in that area as well. Again, something that seems to have been forgotten. It's a problem for the hospitals, let them deal with it. And I think that's really not the way to approach this. So thank you both for that. Very, very important points. So then again, this comes to what really is going to be the economic burden of AMR over the next several years? Is the economic burden directly related to the AMR rate, what will the future global impact be if we do not bring AMR under control? Philippe, I'll turn to you.

So I'm -- so first, first of all, I think the situation is very different from one country to another country. And it's -- and I think we have not yet discussed what is the burden of AMR in different countries and how variabilities and how -- it is not well known, what is really this burden in low-income countries and what will be the economic impact in this country. And this is, for example, in medium income countries like in India also, it's probably largely unknown what is the economic burden. And there are some estimates of this burden, but it's not so easy because you have to combine this with the estimate of infections -- burden linked to infections. So the real estimate is complicated, but it seems that it was very high, that it will also increase, just it's an increase in the hospital cost. And there was, Colin mentioned, but once you have some patients that are colonized by multidrug-resistant bacteria, for example, by carbapenem-resistant bacteria, then you need to isolate them. So there is a cost for the hospital, but there is also a cost for the patient because it will be more complicated to treat and to -- this patient, to handle him, and there will be also some psychological effect that will -- because he needs to be isolated, it will have the exam at the end of the day. For example, there are many things that are done to avoid transmission of the bacteria to other patients that will lead to some economical cost, but some other costs that are more difficult to quantify. So I think that to summarize just the -- so the antimicrobial resistance somehow multiplied by certain factors that need to be defined, the cost of infectious disease in general.

And Colin, anything to add to that?

Just to say, I mean it's significant. Some colleagues of ours were involved in the GRAM global burden of antimicrobial resistance report. They highlighted that there were over 3.6 million deaths each year associated with antimicrobial resistance. I think that was based on 2019 data. If you look at the burden of health care associated infection and AMR costs, individual kind of country studies go from negligible amounts up to $1 billion a year. Economic burden can be $20,000 per case to over $3 trillion in country GDP loss. So it's -- the numbers are big and they're only set to get bigger and bigger. And I think there's the incremental increase in kind of economic burden and costs. And then there's the sort of game-changing nature of what a totally drug-resistant world looks like, whereby it's not so much the individual -- even the cost, albeit they will be in the sort of in the billions or trillions in terms of loss [indiscernible]. So that will be very significant. But it's what does the world look like where you cannot do emergency colorectal surgery anymore because you've got such high levels of resistance that, that operation is highly risky. What does bone marrow transplant look like, where we know people are going to get Gram-negative -- by Gram-negative, I mean the sort of type of bacteria that live within our gut -- infections. And if those suddenly become untreatable, we may be in a position where we can't do complex immuno-suppressive therapies anymore, where people are likely to get infections that will render them useless because they will have a high mortality rate. So I think there's the economic cost which has been very significant. And then there's the world of what does the no-antibiotics look like, which I don't think any of us are quite there yet. And I do a daily clinical practice still, the rest, in public health and it is difficult when you have the first couple of conversations with your clinical colleagues certainly say, "Well, what's the next antibiotic that we can use?" And you go, "Well, there isn't one." And they go, "No, no, no, but we -- like that one you keep in the back shelf that you don't tell us about, what's that next one?" And you go, "There isn't one." And yes, we can come up with regimens of very high dose, looking at a combination of a couple of likely agents. But I think that's -- it's that shock value that people aren't yet completely seeing, but I think it's not far away, that is the -- that along with the economic impact are the 2 kind of big ticket items for the future.

So that sort of paints a bit of a bleak picture for medical care. So hopefully, we as a community and the world can alter that course, but it certainly is of concern that, that may be the outcome. And again, I want to just jump a little bit to how important is it to really involve the veterinary community, animals, antibiotic use in animals. There was a recent article suggesting that the use of sort of one of our hidden antibiotics, if you will, colistin, "last resort", is being used extensively in animal feed. And there's a big concern about that kind of approach. How can we stop that? How can we educate people that -- in animal care, that is going to lead to resistance to colistin, for example? So I'd be interested in your thoughts on that.

Okay. So in fact, this is very different from one country to another country. For example, so this colistin used as growth promoter for -- and it was used as a growth promoter because it was no more used in humans because it's a last resort antibiotic, but it's also toxic. So we try to avoid to use colistin in humans and this is just if it's the last choice. And that's why it was used in animal in the past because it was not used in human. But now we start to use it again and just because this is the only choice. And -- but in fact, antibiotics as a growth promoter is banned in Europe since 2006, I think. And also, there is really these -- there was not only also a prophylactic use of antibiotics was also quite massive in farms. And -- but they have reduced this consumption by -- both in France or in Germany or in the Netherlands and many countries, it has been reduced last 10 years by about 40%. So there is a strong reduction in antibiotic use in Europe in general. And this led to a reduction in antibiotic resistance. So we can observe that if you use less antibiotics in this kind of farming, then you will select less antibiotics in the animals and at the end, in the food also. So there is -- really, it is efficient. And so we have to recognize this. But there are also countries where there is much less reduction. But following the discovery of these mobile resistant genes for colistin and there was a ban in China to use. So it's forbidden to use colistin as a growth promoter also in China. So they are probably using other antibiotics, but they stopped using colistin. And this shows that 1 discovery can have an effect on political decision just to ban a product. And this was done in about 1 year following the publication of the discovery of these mobile resistant genes for colistin. So there is some hope, as you can see. There are some decisions that are taken. But still, for example, in the U.S., antibiotics are allowed to be used as growth promoter in -- I don't know if it's in all animals, but in some animals at least it is still allowed. So there is still some progress that needs to be made, but the second point is that it's not so easy to demonstrate the contribution of antibiotic resistance in animals, in the human sector. It's true that, for example, these resistant genes for colistin was probably and very likely selected in animals and then it spread to human bacteria and resistant genes could be disseminated from animals to humans. But also we observed that there is some host-specificity. So for example, for E.coli that is found both in humans and animals, these are mostly different clones that are found in animals and humans. So there is the transmission from animals to humans is not so frequent, but it's possible also that some rare events of transmission really to the emergence of new clones that are at risk for humans. So there is many possibilities of zoonotic potential of this drug-resistant bacteria. And also important is the mobility of resistant genes that could be selected in an animal somehow adapted isolates, but will jump to human-adapted isolates and then disseminate. So this is one -- important aspect is that the selection and dissemination of antibiotic resistant bacteria, it's a complicated process and it's not fully understood.

Great. And Colin, I don't know if you have anything to add to that at this time?

No, I mean I think that's very much what I was going to say. I think the animal sector has been very efficiently reducing, certainly in Europe, reducing antimicrobial consumption. We've also been -- we've also done the same in different kind of primary and secondary care settings within Europe in the human health sector as well. And there is the unknown about the interaction of the two. And that's not to say the reductions in animal food promotor kind of antibiotics or just kind of treatment use is inappropriate because what you may well be doing is preserving antibiotics that remain for animal husbandry and therefore have their own use, but that they do not necessarily affect that much in the human health population. We don't really have an understanding about the transmission between the different sectors, including the environment. And it may well be that there is a degree of transmissibility between say, the food sector animals, human health and the environment, that may well be that this is just humans to the environment to animals. We don't really, I think, have enough of an understanding from a one health perspective. And there is a lot of activity going on in developing one health initiatives to sort of link up all of the antimicrobial resistance, monitoring antimicrobial usage, parts of the different sectors into a combined approach. And I think we will know a lot more information in a number of years' time once we've done that in a standardized way across a number of countries, to be able to see if we decrease, for example, our quinolone use in the pig industry or in the chicken industry, does that have an impact on salmonellosis in the human population? And I think we -- there's certainly not the evidence that we have yet to really suggest that, but the better stewardship in each sector clearly is beneficial in its own right.

Great. Okay. Thank you for those points. Again, very timely. I want to switch a little bit and talk about the drug development industry. We've already touched on that it's extremely expensive to develop new antibiotics, $1 billion to $1.5 billion. Research has shown that if a company, a pharmaceutical company, emerging biopharma, if they have that amount of money, invest in antibiotic development, they pay out that much for running the clinical trials, but they may only see $50 million a year in return. So it's stacked against really developing of new drugs because of the significant cost. So related to that, again, for all panel members, Sharon, I want to bring you in as well, what can be done to either reduce the cost of antibiotic development? Speeding up the time line, because it often takes 10 to 15 years to develop antibiotics, what can we do to speed up the time line? Are there other sort of novel ways to do clinical trials? Can we look at AI, can we log into ChatGPT and get all the answers for AMR? What can we do from the standpoint of clinical research that either incentivize companies to do these trials? Or what can we do to suggest shorter time frames and better design, as we saw with COVID-19, where a lot of clinical trials were done sort of off the cuff and done in a very quick and in a relatively inexpensive way? So Sharon, I'd like your thoughts on that, if you wouldn't mind.

Sure. I can certainly add a little bit of color to the trials that have been done thus far in the last, say, 10 years. The dollar amounts associated with the trial development has been -- I think -- and I think it was Dr. Brown, I think you had mentioned, this is not going to be your first-line treatment. This is -- you're going into a smaller population. And it's usually immunocompromised, so looking at your HSCT population, also looking at say, VAP, ventilator-acquired pneumonia. And these are trials that are multiyear, they are very low recruitment rates and they are high dollar amount because of all of that being said. And some of them actually never really fully complete. If they look at efficacy, they'll pull the trial, because they are focused on that dollar amount and then you don't want to go too far. So the complexity related to the design of the trials and the focus population has contributed to that -- the return on investment not really being there because of so much tied into that development, to then turn around and have your product start to see patterns of resistance within a year. So I think that there should be some design, maybe some redesign in how we would go about going for these populations and maybe not focus in so much on some of the most difficult populations to test like HSCT and VAP, because they are going to be multiyear and very, very long trials with a lot of dollars attached to it in order to do that. And I think that utilizing what we have at IQVIA in terms of data mining to try to streamline those strategies to assist our clients, I think is going to be how we move some of those designs forward.

Okay. Great. And so Colin, let me jump to you. What about doing a subscription system. I understand the U.K. does that. Is that working? Is that a reasonable approach to perhaps, again, incentivizing companies to develop these drugs?

So it's in progress at the moment. So we had our first 2 and we're beginning to sort of tinkering around what the next piece looks like. So for those that don't know, it's been described by some as the Netflix model, where you kind of sign up to drugs on demand. I think the more appropriate way is a firefighter model in that you pay for a service, hoping that you never need it, but they're there, ready and available when you do. Is it working? I think we need to wait to see what everyone's feeling is at the end of the trial period. And so we're funding them for a number of years. And the metrics of success, because this is a novel program, I think will be a mixture of where were the drugs used, what was the sort of patient profile that were used and the clinical indication, what has it led to in terms of either kind of resistance profiles or improved clinical outcomes for the groups that they're used in. And most importantly, what do the manufacturers think that this model works. So ostensibly, it provides them with security of numbers. So rather than we're going to retain these drugs for use in 3 or 4 individuals a month, and therefore, the overall return on product is very limited compared to all the money value that Sharon has said that goes into trials, we will guarantee a certain return on investment. But I think we will see what the evaluation looks like in a number of years as to whether for all players it looks like it has been successful. But certainly, I think it's the -- it is at the very least 1 option of trying to get novel drugs into the market, and there are a number of companies that are interested in the first run and then indeed, the second round. So the -- I think there are other options available, Europe, for example, is looking at expanding patents as a possibility and maybe Philippe might talk about that. But I think the more of these different type of incentive models that we can get that don't rely purely on a per product usage might be better.

Okay. And Philippe, is anything happening in France that is similar to that, do you know?

I think it's a level of discussion still. But what I may add is that, in fact, 1 point is that it's very difficult to develop a novel antibiotic that is really -- for example, there is most of these -- some novel antibodies that are available are just targeting known targets and most of them are a combination of beta-lactam, with beta-lactam as inhibitors. And in fact, to have really another antibiotic that will target a novel target that will have no mechanism of resistance already known and so on. It is -- to my knowledge, there is none that are not close to be in the market. And so it's -- technically, it's very difficult. It is and especially for immunocompromised person, where you need to have a very efficient antibiotic that will be able to eradicate the bacteria. And this is technically and biologically, it's complicated before to be financially complicated to have it -- to have it could be prescribed to the patient. And so I think there is a need to have really a global thinking on how to get novel antibiotics that will be some are used as rarely as possible just in very few cases, as mentioned by Colin.

Right. So I totally agree with that. It's almost like a new antibody comes along, it's the new kid on the block, boy, I want to use that. But you're absolutely right, that's not the approach. It's something that needs to be put in the back there and reserved for when it's really needed, so...

The worst for the -- in some ways for the incentives for that, is that the more novel the therapeutic, the least it might be used. So if you were to have something with a completely new model -- mode of action that was unseen before, you're going to want to keep that one on the top, top shelf.

Absolutely. Totally agree with that. So thank you to the panelists for a great discussion. This has been very helpful, I think. But now we do have time for live questions from our audience. So let me hand it over to Andy to start giving us our questions.

Great. Thank you so much, Paul, and thank you to the panel as well for a great presentation and conversation. So before we officially get started on the Q&A, I would like to remind our audience how to submit the questions. [Operator Instructions] So one moment to get our first question in and then we'll kick off. So our first question is: How does IQVIA address the strategy planning for an AMR study where prevalence of a known or emergent resistant pathogen is key?

I can take that. Do you want me to take that, Paul? So thank you for that question. Very good question. We would utilize obviously our own data resources that we have. So the strategy is multifaceted. So we would look at everything from what is available globally, like WHO's GLASS, of course, to plan this in the right countries, but also looking at things like prescription intelligence, looking at density data, et cetera, but also the relationships that we have with our sites and with the networks that could -- that have the capabilities to perform studies like this, are going to be key in collecting like antibiogram data. Because as I said, these are usually multiyear studies and that's something that is usually updated on a yearly basis. There's a -- the local types of surveillance that we would use to identify if we need to make any changes or any shifts. So I would probably say that kind of looking at things, you have your global level, but also looking at things on a local level, site level, with the antibiogram data and collecting that and assessing that.

Great. Thank you, Sharon. Okay.

Okay. So our next question is: What is the role of molecular diagnostics in managing AMR? If there is a role, then what is needed to make sure these are included in clinical pathways?

So let me jump in on that a little bit first. Yes, so I think 1 thing we haven't had time to discuss is the role of testing at the bedside, if you will, or point of patient care. There are actually -- I mean as we all know right now, typically, it takes 2 to 3 days to get your resistant results, your MICs and so on, and that's really way too long, because during that time, you're doing empiric antibiotic therapy, right? So what is needed is a rapid turnaround time. There are a number of systems available right now that can turn around results in even 4 hours, for example. But the problem is that a lot of these are very expensive to use at a local hospital level including the need, for example, reagents throughout the year. It becomes very difficult for hospitals to be able to afford that kind of equipment and machinery. And a lot of these are -- there are a variety of different ways of doing these tests that are being looked at right now. But it's clear that the current solutions don't fit what we really need, because again, we need that something we can bring to the patient, plop it in a little box and it tells us within 2 to 3 hours. There's a recent paper looking at -- apologies, I don't remember the name, but something that has at least gone through 1 round of testing. It is not FDA or EMA, U.K. approved as far as I know, but it does give results within 4 hours. It does not require a lot of huge machinery or mass spectrometry, for example, to get those results. So we're still -- there's still a lot of work that needs to be done in looking at bedside if you will, or point-of-care testing, because that is really critical, I think, to helping change the -- what's happening with AMR. Philippe and Colin, I don't know if you have any other thoughts on that?

I mean I think it's -- the challenge, I think, as you highlight, is that we really want more diagnostic tests to be engaged in guiding antimicrobial therapy for both do we need to give it for a bacteria and what's the resistance profile that we need to think about when treating. But the greater the cost of the test, the more challenging that's going to be to implement at a global level. And I think that's a -- I completely agree the more tests that we can have the better, but ideally, we want ones that are also cheap. And that is the -- that's the Holy Grail.

That's the problem right now. Yes, especially for certain countries, low-to-middle income countries as well, where the resources are just not there. So definitely, we need an improvement in, again, bedside testing.

The 1 point, in the choice of the antibiotics, before to have the results of the diagnostic or without diagnostics, a probabilistic way to select the antibiotics, there is probably possibility for improvement. And to really, according to the symptoms to maybe to use some artificial intelligence, subsystems and things like that. So it's maybe places for improvement in selecting the right antibiotics. And we observed this, for example, there was -- there is a decreased use of the amoxicillin plus clavulanic acid that is replaced now by just using amoxicillin alone and with similar efficiency in most cases than this to avoid to use this combination, limit the selection for more resistant bacteria, for example. So this is how these antibiotics, some stewardship and to combine this with diagnostic is a good place for improvement. And you asked a question on awareness on anti-microbial resistance. And this is also -- that it has also a place here in the choice of the antibiotics.

Great. Okay. Thank you all. Okay, Andy?

Great. Our next question: Do you believe that the introduction of sanitizing wipes and/or gels has increased the amount of bacterial resistance and increased the infection rate amongst people?

So I would say that this is complicated because you have 2 effects when you are increasing this, because on 1 hand, the biocide might somehow select for resistant bacteria. But also, it will eliminate the bacteria. So it will, in most cases, reduce the transmission of resistant bacteria from 1 patient to another patient. So this means that the right use of this product will contribute at the end to a decreased transmission of drug-resistant bacteria. And the selection of resistant one, it should be -- we should take care on this, but it's beneficial to use is much higher than the burden that could be associated.

I would say with a caveat that if you do get development of resistance to various things, you -- unless you screen carefully, you may see selection pressures lead to novel clades that are resistant becoming predominant clades. And they sometimes may be associated with different antimicrobial resistance profiles. And we saw that with some of our QAC associated, quaternary ammonium compounds associated kind of resistance in MRSA. So it's not to say that you shouldn't do it. It's just that you need to monitor for the, the trends in implementation. And a lot of biocides on the skin are really quite irritant and are not easy to give in places like intensive care or the areas where you may want to suppress burden considerably. But used appropriately, perfectly reasonable.

Great. Thank you. Andy?

Our next question is: Have there been any significant advances in phage therapy? And any new products in development?

I think there is a lot of interest in phage therapy. There's a group here in Pasteur that is really trying to put science behind this phage therapy to understand how it works or how it will not work in a different contexts and how it is the need to have the immune response also together with phage to avoid rapid selection of resistance. And there is probably some specific application of phage therapy and there is room for phage therapy, but it will not by no means replace antibiotics, because you need to have to select the right phage to eliminate bacterial infection. So it will take some time to identify the right product. So of course, if you have a urinary tract infection, you need to treat immediately and you can't wait a couple of days before to select the right phage. So it will -- so there is -- probably there will be improvement to get it faster and to have more phage collection, but it is complicated. So for example, for the moment, it's still a kind of niche specific niche for phage therapy. And of course, like for antibiotics, it's very difficult to have trials. And what is done today is just to combine antibiotics with phages. So it's difficult to estimate what is the efficacy of the phage because it was used together with antibiotics. Maybe, Colin, you can complete?

Yes. I mean I think very similar. So our public health agency, maybe like the Institut Pasteur, has got a variety of work looking at phage therapy, particularly for chronic infections where antimicrobials have failed. There are complex regulatory environments for phage therapy. And Australia has a good example of the utility of those on a named patient basis. They're not yet, I don't believe, anywhere in reaching clinical care, but there are some encouraging outputs where they've been used individually, albeit sometimes with antibiotics that make these outcomes difficult to disentangle. But I think there's, at the very least, a sort of theoretical benefit and some individual case report benefit and there's a program of work to look to get that more widely used.

Great. Thank you very much for that. So Andy, I think we have time for 1 more question.

You got it. So our last question for today is: Can you please share examples of push-and-pull incentives?

So Philippe or Colin, I'll turn that over to you.

So we've done both. So if you look at MRSA reductions in the U.K., they very much were sort of push [ a bit ]. So unlike in the U.S., we don't have a big circulating community MRSA problem. So our MRSA historically was a hospital issue. And people didn't think it was easy to get rid of. It was just -- it was there, it was what were you going to do about it? We created rigorous targets for hospitals to meet and we implemented those with punitive measures for trusts -- trusted collection of our secondary care hospitals that are under 1 leadership that didn't meet the targets. So they're very much with the push approach. And we reduced, for example, in 1 big London hospital I used to work at, from 100 MRSA bacteria [indiscernible] a year down to 0 for 2 years. And that's because with bundles of care, line package care versus screening for MRSA, decolonization, targeted therapies, we were able to reduce those. We then tried it for Gram-negative infections in our current National Action Plan and it's been far less successful because those have been just far less amenable to those types of push therapies. Pull therapies are I think very much like the novel antimicrobial prescribing regimens that we have, where we're encouraging people to bring drugs to market on a bulk purchase basis rather than a per use basis. And we're trying to do that also with certain incentives to trusts if they achieve certain targets that they get benefits rather than they get fines or other punitive things for failing to meet targets.

Great. Thank you very much. Andy, I'll turn it over to you for wrap-up.

So as you said, with that, we will wrap up. I would like to thank the audience today for attending and for participating in today's event. I'd also like to thank our sponsor IQVIA for making today's webcast possible. We would like to ask everyone in the audience to participate in a brief survey and this survey will appear on your screen after the presentation has ended. You will receive an e-mail alerting you when this webcast will be available for replay. We invite you to forward that announcement to your colleagues who may have missed today's live event. We hope to see you all next time. Enjoy the rest of your day and goodbye.

Thank you, everybody.

Thank you.

Thanks very much.

All right. Take care.