Clinical Pharmacology and Therapeutics [Re-release] (25 Oct 2023)

SPEAKER_00 0:00

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SPEAKER_01 0:24

Hello and welcome to another episode of Told by the Trainees and Members Committee of the Royal College of Physicians of Edinburgh. My name is David Ryan, and I'm a Foundation Year 2 doctor based at St. George's Hospital in London. Today I'm delighted to be joined by Professor Emma Baker, Professor of Clinical Pharmacology at St George's Hospital in London, and Dr. DePander Gill, an NIHO funded clinical lecturer in clinical pharmacology, currently based also at St. George's Hospital. Thank you very much, Professor Baker and Dr. Gill, for joining us today. I guess for many of us, our exposure to pharmacology is usually limited to preclinical years at medical school, focusing more on theoretical aspects of the subject. And it may come as a surprise that there is a whole medical specialty devoted to clinical pharmacology and therapeutics. However, given the growing number and complexity of therapeutics and a significant proportion of DNHS budget that is devoted to medicine, the field of clinical pharmacology is becoming more and more important. So the aim of today's podcast is to introduce the specialty of clinical pharmacology and therapeutics to a general audience, but also give our listeners an insight into current developments and research in the field. So to kick us off, I'll start by asking Professor Baker, can you give us an idea a bit about your background and how you started your journey in clinical pharmacology?

SPEAKER_03 1:50

Thanks, David, and thanks very much for giving us a chance to talk to future trainees about what I think is the most fantastic specialty, clinical pharmacology and therapeutics. I never intended to be a clinical pharmacologist, probably like most of the trainees out there. I did my medical degree in Edinburgh, and then I was a jobbing NHS doctor who thought research was just for somebody else. And I got sucked into doing a PhD in molecular biology and spent some fascinating time in the lab cloning sodium channels and sequencing back a long time ago when you had to do all that by hand. And by the time I'd done that, I was both a doctor and a scientist. And I'd also was uh trained in the old days where you were really a generalist, you went around lots of different specialties. So by the time I'd done that, the perfect choice for me was clinical pharmacology and therapeutics that allowed me to combine my interest in science and making that count for patients with my interest in clinical practice. And I guess I should point out also have a strong third arm, which is that I also love education.

SPEAKER_01 2:57

Very good. And Professor Baker, why is clinical pharmacology, in your opinion, so important in today's world?

SPEAKER_03 3:05

Have you noticed what's getting us out of the COVID pandemic? Um, my I'm in utopia at the moment because every time I turn on the radio in the morning, I'm basically getting the clinical pharmacology news. Uh, we've got a new drug, a new vaccine. Uh, clinical pharmacology is probably important now more than ever before because we need to develop new drugs, test them, get them into patients. And it's clinical pharmacology is a specialty that both understands research and clinical trials and designing those to get the best out of our new drugs, but also understands how to implement them in practice. So, more important than ever before, and I guess again, education, helping people understand, for example, how to use the new drugs, bring in the new guidelines, help people to understand how to use the new vaccines.

SPEAKER_01 3:52

I think it's definitely providing a lot of light on what can be quite dark times. Dr. Gill, can you share with us a little bit about how you started your path in clinical pharmacology?

SPEAKER_02 4:01

Yeah, so I first moved into the specialty at ST1 level, David, and that was as an academic clinical fellow. Uh, I found myself in my foundation year spending a bit of time thinking about what I wanted to do next, what I enjoyed, uh, what I found interesting, stimulating, and most rewarding. I came to the opinion that clinical pharmacology represented a specialty that brought in all of my interests together into one package. There was an opportunity to perform clinical work, work with patients, but at the same time integrate that with research and really understand the mechanisms behind the medicines and the treatments we were offering our patients and combining that together so to not only optimize the care that we were offering at the time, but also think about future perspectives about research we could do to make that better. And it was putting these interests together that really engulfed me into pursuing this career.

SPEAKER_01 4:51

Professor Baker, if I just returned to yourself, could you kind of summarize you know the key areas of the specialty of clinical pharmacology? Because from what you said previously, it sounds like it has quite a broad rematch. So to kind of take it back to basics, what does a clinical pharmacologist do on a day-to-day basis?

SPEAKER_03 5:09

So I'll give you a strapline and then I'm going to give give you a tiny bit of history. So the strap line is that clinical pharmacology is the medical specialty that is making sure that patients get the best medicines through practice, education, research, and policy. There's a strapline, and if you'll bear with me just for a two-second potted history of clinical pharmacology, it started back in the 1950s approximately, uh, when uh all the new small molecule drugs were uh beginning to be discovered. And so it started as an experimental medicine specialty, putting molecules into people for the first time. Eventually, then there were starting to be emerging severe side effects, for example, the thalidomide disaster. And so clinical pharmacologists moved across to a new branch in regulation, making sure that medicines are safe. For example, uh, the chair of the Commission on Human Medicines is currently a clinical pharmacologist, Mania Pir Mohammed, and NICE in England was set up in part by a clinical pharmacologist called Mike Rawlins. Moving across from regulation, uh, in the 1980s and 90s, clinical pharmacology lost some visibility as a clinical specialty, but people then realised that no one prescribed very well. So clinical pharmacology then went into prescribing education, and clinical pharmacologists through the British Pharmacological Society are leading, for example, the prescribing safety assessment, which everyone listening to this podcast uh will know about, and they also teach a huge amount of prescribing and drugs in medical schools. And then finally, I get to what I call the age of enlightenment, uh, where clinical pharmacology is realizing its value to the NHS. For example, setting up new polypharmacy services, working in uh harmony with their pharmacy colleagues to do medicines optimization. So, for example, they might do that through clinics, through working in multidisciplinary teams across integrated care systems, which are primary and secondary care, for example. And I guess we've come full circle now because now, more than ever before, uh we've got NHS is delivering large-scale trials. So we're back to that. For example, clinical pharmacologists are leading some of the big um trial groups that we've seen emerging across the UK. So we're back to experimental medicine. I guess Depender would be a good person to tell you what a typical week is like as a clinical pharmacologist.

SPEAKER_01 7:30

So, yeah, Depender, could you share with us a little bit about your day-to-day?

SPEAKER_02 7:35

I I think one of the things I enjoy most about clinical pharmacology is the opportunity to do whatever you're interested in, whatever you enjoy, whatever you're passionate about. That really is my philosophy in life. If you if you're always doing things you enjoy, you're not working a day of your life, you're just having fun. Uh, and if I'm honest, that is actually how I see clinical pharmacology. It's all things I would enjoy doing for fun in my spare time. And so actually, getting up in the morning and and starting work for me is playtime. And that's how I see it. The the other really interesting thing is that uh, as Emma alluded to, not every single day is the same. They're all very different, and that is not even consistent across individuals. Any two clinical pharmacologists may have a completely different lifestyle, completely different routine, and yet still be clinical pharmacologists. And I think that's reflective of the diversity of not only the specialty, but what it reflects. This is all aspects of medicines and treatments for patients. Um, and so that that could vary across uh identifying drug targets, drug development, clinical trials, research, practice, hypertension, various specialty clinics, polypharmacy, medical education, prescribing, working with pharmacists, included uh improving services, and any combination of that and spread out through the week. So, actually, what is a typical week for a clinical pharmacologist is a very difficult question to answer because it'll vary tremendously based on what an individual's skills are and what they enjoy and what they'd like to do. I think that is, while it's a complexity, it's also a major strength of clinical pharmacology. There is the opportunity for people to do what they enjoy and really excel at that.

SPEAKER_03 9:06

I think while that's a massive strength of the specialty in that got one of the lowest burnout rates of any medical specialty, it can be seen as a little bit of a weakness because it's hard for people to really understand what they will be doing as a consultant. And so if you're not someone who can cope with that uncertainty, that might put you off. But um I just probably will caveat that with that there is um a strong clinical pharmacology curriculum, and that is um the new curriculum is about to roll out, and so the things you will be covering if you do clinical pharmacology as a specialty will be very much NHS work. You would accredit with general medicine, you would do uh cover things like adverse drug reactions, medicines management, polypharmacy and multimorbidity, you will probably have a therapeutic area of interest which will vary between trainee. So, for example, minus respiratory independence is sort of cardiovascular metabolic. Uh, you will also have in your curriculum the time to develop your ability to deliver education, prescribing education, and you will also have time in your curriculum for developing your skills in clinical trials and experimental medicine. So there is now a boilerplate, if you like, for what a NHS consultant looks like in clinical pharmacology and therapeutics that's much more tied down than it might have been in the old days, and that's really important for making sure that there are consultant jobs for people to roll through. And I would finish by saying there are no unemployed clinical pharmacologists.

SPEAKER_01 10:34

So diverse in nature, but quite well defined. A major theme that's coming out in our discussion is the focus on research. Maybe I'll start with uh Dr. Gill. Could you share with us um what research you have been involved uh with and what is your main focus of the research that you're doing?

SPEAKER_02 10:51

I'll I'll start by answering a slightly different question, David, if that's all right. And and I I guess it's what why why do I enjoy research, or why is this something that I want that I want to also work on it as part of my role? I'm generally a curious person. Uh I like to understand what we're doing. It's great to do it and to see the results and see the benefit, but I'm always searching for more to understand why things happen the way they happen and how we can use that data to do it better, to improve it, to find the next big thing and continually make progress. And I think that is for me the the essence of research, the this constant search, this curiosity to understand how things work, to get into the truth of the matter, to understand the nitty gritty of the mechanism, and then harness that to make developments. You know, it's there's no other feeling like working with patients to understand them as people, to help them get better when they're vulnerable. But it's part of that motivation to do it to be good at that job that also fuels the research because you you want to do it even better. Um, and it's great to maintain the optimum standard of care, but to improve that, you really have to work in research, I think, um in some respects. And so that that's what drew me towards research. The actual the details of the research I work in have evolved to some degree through through my career. But the the general theme has been this kind of this curiosity to understand the mechanisms. Um, to more directly answer your your question, most recently my my work focuses on harnessing genetic data uh to identify drug targets, to explore their mechanisms, their repurposing potential, their adverse consequences, particular patient groups where they may be most beneficial in particular patient groups where they may not work as well in, uh, and then using that to prioritize the design of clinical trials and drug targets. Uh, but similarly, to identify biomarkers for early stage clinical designs.

SPEAKER_01 12:37

Very good. And I know that you've done some work using using genetic data to predict response to some drugs in patients with COVID-19. Could you share some some of the details of that work with us?

SPEAKER_02 12:49

Yeah, so uh a classic example is the interleukin uh six receptor inhibitor. Um and this is actually a great example for genetics because it was speculated very early in the pandemic that this may be a viable drug target to reduce the severity of disease. And actually, it's possible to explore this using genetic data. We we go to the gene that copes with the interleukin six receptor, and we identify variants at that locus that strongly relate to biomarkers suggested interleukin six receptor signaling, biomarkers such as C reactive protein, fibrinogen, soluble interleukin 6 receptor, and identifying such variants, we can use them as proxies for the effect of interleukin 6 signaling. Now, if we go to some of the genome-wide association studies that predict the variants related to severity of variants that predict individuals to have a greater chance of getting severe disease, we find that these same variants that proxy or mimic the effects of interleukin-6 signaling were also associated with a lower risk of having severe disease. And this therefore represents genetic evidence that actually this is a viable drug target to reduce the severity. And actually, as it happens, clinical trials have gone on to demonstrate that in particular contexts and patient groups, indeed, this drug target can have protective effects. So this is one of the nice examples where actually the genetics came before the trial evidence and highlighted that this is a target that should be prioritized for further evaluation, thus improving the efficiency of developing effective treatments.

SPEAKER_03 14:12

That illustrates the spectrum of clinical pharmacology because there is dependa identifying it as a suitable drug target. We have clinical pharmacologists involved in setting up and delivering trials of these drugs, and then clinical pharmacologists in the NHS supporting development of guidelines and implementation in practice. So a beautiful illustration of the spectrum of clinical pharmacology.

SPEAKER_01 14:34

In particular, the ability to be able to turn around this study in light of the kind of current pandemic is really fascinating. Professor Baker, can you share with us a little bit about your research experience and uh research interests?

SPEAKER_03 14:49

Um yes, I what I've done in my research career is made the translational journey in that I started with my PhD in molecular biology. I was interested in iron channels and how uh surgeon channel abnormalities contributed to disease. So I started off in a molecular biology lab, cloning and expressing channels, and I then progressed to doing phenotype studies in patients with polymorphisms of the epithelial sodium channel and looking at how that related to hypertension. That was the old days when polymorphisms were the thing. And I then sort of moved on from there to look at the importance of sodium channels in the airway, and that led me into respiratory disease, and I developed a research program looking at transport in the airway, particularly around glucose and how that related to infection, and uh did some investigator-led studies and clinical trials. But that more recently, um, I have, if you like, repurposed back from my more respiratory field to really try and take clinical pharmacology forward. And so I've taken my experience of multimorbidity and translational research forward into investigating polypharmacy, which, as you know, is almost the irony of clinical pharmacology, is quite a lot of the time what we're trying to do is stop people prescribing too many drugs as much as we're trying to find new drugs to get people to prescribe them. And so, with polypharmacy, do you know, David, that the more drugs you take, the more likely you are to come to harm and the less likely you are to get benefits from your medicines? And so we've been uh moving more lately into healthcare innovation and how we can, as clinical pharmacologists, contribute to the whole workforce in uh improving the use of multiple medicines for patients, where this sort of falls outside one individual specialty. And of course, we're in a big team with our colleagues from geriatrics, from primary care, all our colleagues from pharmacy. Uh, but we think we have a specific role as clinical pharmacologists in, I guess, driving the academic some of the academic understanding of polypharmacy and also in providing specialist support for the whole workforce and doing it better.

SPEAKER_02 16:58

May I ask Professor Baker a follow-up question, actually? Professor Baker, I should I should disclose as one of my mentors and role models. And one of the things that's been most inspiring to learn from her is the role of education. How important is it to pass on our skills to train up the next generation of clinicians, healthcare professionals, and also clinical pharmacologists. So I think a really important topic to touch on is Professor Baker, what do you think is the role of education and specifically in clinical pharmacology?

SPEAKER_03 17:25

Wow, I mean, we're trying to put in uh 30 years of sort of thinking and understanding into 30 minutes of podcasts, so I better be quick. Um, I think education, I think it's a brilliant question, Defendant. I think education is absolutely vital and something that clinical pharmacology really can contribute to. It's in our curriculum. We're supposed to get good at it. But I think that in my experience, pharmacology and clinical pharmacology are not that extensively taught in the healthcare specialties, in medicine. I'm recently been involved in physicians' associate programme, in nursing. People who do know the drugs the best are the pharmacists. Um, and so there is a big role also in clinical pharmacology in making sure that what's that there is teaching and keep the profile of pharmacology up, but also make sure it's really relevant to practice. So, one of the things we've done in our group is develop what we call the top hundred drugs. They're not the drugs that you everything you have to know about pharmacology, but they're the drugs you're actually going to prescribe. I remember frustrations at myself as a medical student learning about all sorts of erudite pharmacology that I was then never ever going to use. And then focusing education on not just knowledge but skills because knowing what to do is completely different from actually doing it. So lots of simulated prescribing and doing it and improving rather than just being told what to do or listening to lots and lots of lectures. So those are some of the things we've developed for our medical students, and they extend through into practice where we have not only loads of uh doctor prescribers but also independent prescribers and helping us all perhaps through multidisciplinary team meetings and again simulated patient discussions, etc., to all get better at prescribing. I think it's a skill that takes 25 years to be good at. So I think that's just a tiny flavor of how important I think education is. Uh, and I think clinical pharmacology, that's one of the things I love doing is teaching. People who like teaching out there as a role for you in clinical pharmacology. You don't have to be a genetic, a brilliant genetic academic that depends.

SPEAKER_01 19:34

Moving on to as to where you see the future role of clinical pharmacologists, uh, Dr. Gill, what would excite you most about the future of clinical pharmacology?

SPEAKER_02 19:45

I think it's a really exciting time to be in clinical pharmacology, to be in healthcare, to be in research. Aside from the COVID pandemic, which has been devastating and a major challenge, I think the current era in the bigger scheme of things offers a lot of technological advances. It's only now we're seeing the availability of large-scale genetic data where we can really decipher the mechanisms and use that knowledge to unravel targets and pathways. Uh, I think that's also coupled uh technologically with the growth in artificial intelligence. And I and I think these two things, either together but separately, offer unprecedented opportunity for what we can do in healthcare. The wealth of data with the methods to robustly analyze them, to understand mechanistic pathways, targets, and interventions, I think is profound. And I see a lot of really exciting potential for that in the next five to ten years. So that's something that I'm particularly excited about. I think the other important area to mention is the scope of harnessing human potential, human resources. I think in in healthcare and research, we're really privileged to have an enthusiastic, passionate body of individuals that really love what they do and want to make a difference. And I think one of the keys for the future is to harness the full potential of those people, to get the best out of them, to make sure they're doing the things they enjoy and then they're loving their work. And I think only with that, the full potential of our of our workforce, coupled with all the technological advances and the opportunities that are available to us. I think that's what's most exciting about what we can achieve getting the most out of that together.

SPEAKER_01 21:20

Same question over to Professor Baker. What excites you about the future of clinical pharmacology?

SPEAKER_03 21:26

Oh, so much, David. Thank you. It's a good question. What excites me about the future of clinical pharmacology? I think that there is so much we could do as a specialty. Sometimes one of our biggest problems is trying to do too much. But I think the COVID pandemic has really focused, I guess, what we can do and what we should be doing for the NHS going forward. The first thing, of course, is the COVID pandemic has illustrated how important it is to have clinical pharmacologists in the conversation around drug development and research. We bring a unique perspective. And understanding of things like dose, of choosing the right participants, choosing the right outcome measures. So we bring in important perspectives to design clinical trials and should be part of the MDT to do that, which I think is exciting. There's also the restart and refresh of NHS services post-COVID, if you like. And that's a place where we have a really important role. We've now going to see much more working together between different sectors, including primary and secondary care. And we've also got all these people with multimorbidity out there who haven't had optimal care while we've all had to focus on the COVID pandemic. And so I think clinical pharmacology have potential to innovate and provide specialist support to clinical networks in caring for patients on multiple medicines. And that includes working with a fantastic body of colleagues in the primary care network, GPs and pharmacists. So I think there's some great things to do out there. And thirdly, education. We've now got a workforce that's excited about clinical trials and that is rapidly evolving new protocols and new ways of treating a disease like never before. So there's a you like a an opening, an opportunity to get people excited about things and using drugs better. So I think those are the three ways I see the specialty going forward. We have to focus because we're small, but there's still, as Defender says, plenty of scope for people to focus on the bits they enjoy.

SPEAKER_01 23:27

And a question for both of you again.

SPEAKER_03 23:38

Do it. My first advice. Take the plunge. The first thing I would say is find out more. So there is increasing information about the specialty, and one really good place to go for information is the British Pharmacological Society. They have pages for careers at all levels. We have a specialist registrar committee who will be really happy to find somebody for you to talk to. You could come to some of our specialty training national Zoom days afternoons if you like to find out and meet people and find out a bit more about the specialty. So find out more. Dependra and I, of course, would be very happy to buy email addresses if people want to contact us. We love talking about climb farmers, you can probably tell. So first thing is find out more. Don't be put off because you've never heard of it. Um, most of us who got into it weren't didn't start off as career clinical pharmacologists. Don't be put off by you might not like one bit or the other because there's so much scope to um do the bit that you like. I suppose the sort of third bit would be to be curious, be excited, be interested. Don't I keep saying don't, I don't mean to say don't. Do read around the new innovations, for example, for COVID. Look at clinical trials, look at guidelines and protocols, go and find out who in your hospital is responsible for medicines, find out what formulary committees you have in your area and go and find out about how medicines are managed, think about drugs, uh, do a wardround with a pharmacist. That's a completely different experience than doing one with a doctor. Find out how you could get involved in teaching about drugs. Loads of opportunities, for example, through the British Pharmacological Society. So I would say find out more, get a taste on it, think of it, consider it as a specialty because you can have a very long and happy career in clinical pharmacology.

SPEAKER_02 25:25

I completely echo that that sentiment. I I think the first thing I'd want to say is that every everybody should be considering clinical pharmacology as a specialty because, firstly, it's it's fantastic, and obviously I'm I'm biased because I love it, but there is there's something in clinical pharmacology for everybody, whatever your interests, whatever your passions, there's something there for you. Second thing I'd say is that um find out what it is you enjoy, find out what it is that you like doing for fun that gets you up in the morning, that gets you excited, that you're really passionate about, and then hone in on that and and really make the most of that opportunity because that's the thing that you'll be able to do naturally for fun. You'll you'll do it better than anybody else, and you'll you'll really thrive in that uh scenario. And then the third thing is seek advice from others, people who may have been through similar experiences before. There's a wealth of experience there. It's a real opportunity to use that experience to improve your own situation. So find out what you love doing, find out what you're passionate about, and then find somebody who's equally passionate about that same thing, who's had those that been through that path before, and seek their advice. And um, I think those three things are uh what I would advise for anybody considering uh a career in clinical pharmacology, which should be everybody's thank you.

SPEAKER_01 26:32

I think I think we'll need to put a uh disclaimer on the front of the podcast because we're all quite biased, but uh that's really really good advice, and thank you for those. Um and that brings our podcast to a conclusion. Uh thank you very much to Professor Baker and Dr. Bottkill for sharing their experience and expertise with us today. Uh it's definitely helped find a spotlight on the current faculty. So um, I think it's really great and exciting to hear uh both perspectives on the specialty and learn about the diverse role that clinical pharmacologists play in today's world. Um I hope you enjoyed listening to this podcast, which is brought to you today by the training and members committee of the Royal College of Physicians of Edinburgh. Uh, thank you.

SPEAKER_02 27:15

Thanks very much, David.

SPEAKER_03 27:16

Thank you, David.