Tom Nichols

Embark on an enlightening expedition, as we navigate the vital intricacies of pharmacovigilance and risk management alongside Tom Nichols, zoologist turned PV aficionado and Director of Drive Phase PV. Tom regales us with his unexpected but inspiring foray into the world of drug safety, stemming from a keen interest in epidemiology. His captivating tales underscore the importance of PV in delivering life-saving therapies to market, particularly through his work with Clozapine, an anti-psychotic medication. This conversation is a testament to PV's dual role as both a guardian of public health and a strategic ally in expediting breakthrough medical treatments.

Tom then delves into the nuances of integrated clinical trial sponsorship and how this model encourages collaboration across the pharmaceutical landscape. Reflecting on my own career trajectory, he offer's a candid comparison of working within the close-knit fabric of clinical research versus the challenges posed by outsourcing, providing a glimpse into the dynamic nature of our industry.

As the journey concludes, Tom explores the landscape of future pharmacovigilance strategies, where the deployment of AI could revolutionize patient safety protocols, and the delicate balance between swift drug access and thorough post-market analysis is ever-present. Tom's insights, coupled with moments of passionate discourse, have been nothing short of invigorating. Join us for a conversation that promises not only to inform but to inspire a deeper appreciation of pharmacovigilance.

Transcript

Speaker 1 0:16

Welcome to another episode of Innovation and the Future of Pharma Convigilance, a podcast series brought to you by Trudiant Talks. I'm your host, Indi Alawalia, and I'm delighted to navigate the dynamic world of pharma provisions and risk management with you. A quick disclaimer first the opinions expressed in this episode are solely those of the individual guest and do not necessarily reflect the official views of Trudiant Consulting or their own company. We're all about fostering insightful conversations here at Trudiant Talks and we want you to know that any product, vendor or service mentioned does not imply an endorsement. If you're seeking professional advice for specific situations, we encourage you to go to our experts. Please remember this podcast content is meant for informational and educational purposes only. Now, that's out the way. Let's get back to the show. Today, we are privileged to have Tom Nichols, who is the director of Drive Phase PV, as our guest speaker. Tom, thank you for joining me. Thank you for having me, Indi. So, Tom, we always start with the traditional icebreaker in every single PV function, which is how did you get into PV?

Speaker 2 1:35

I have seen with everyone else. I said I grew up and dreamt as a young boy of working in drug safety.

Speaker 2 1:41

But the reality was I after university friends went off to start their careers and I stayed on for an extra year to do a Masters and so sort of come January time I thought I'd better start thinking about what I'm going to do next September and basically I spoke to all my friends from the same course and how they were enjoying their work and I thought, okay, medical information at Roche sounds quite good. Roche wouldn't have me. So I did start in medical information. I thought it seemed to tie, tie together what I kind of from my zoology and epidemiology background and you know deeply scientific and have a touch on the business side of things, I thought it sounded perfect. I started at a company called Merz Pharma and quickly found I really didn't like medical information. It was not for me. I kind of found it quite restrained. I didn't find it as as kind of intellectually stimulating as I've subsequently found, found drive, found fun, co vigilance and particularly having done just done a Masters in epidemiology as I, actually I want to really understand kind of how diseases spread. But I kind of actually decided, you know the side effects and adverse events are kind of very similar. Why are these things happening and and what populations are they happening in? So I kind of saw that was going to be. I thought that fairly quickly that was going to be my, my way out of MI, if you like. But I was going.

Speaker 2 3:24

Being at Merz kind of was a but you know, entirely by chance, you never know, you know the way you end up working. To start with it was kind of like the best place to start if you're going to start in pharmacovigilance. Because they had a product called clozapine. So for anyone who doesn't know, it's anti psychotic it was. You know, it's gold standard treatment for treatment, resistance schizophrenia. And it had been banned for a number of years because in I think somewhat 2% of the population who take it, it causes a complete collapse of the immune system and it was idiocycratic, so couldn't predict who it was going to to happen in and so it was withdrawn from market, is not being safe.

Speaker 2 4:13

But it had been brought back in a very controlled manner and I guess we'd call now to additional risk minimization measure. So you had the monitoring scheme. So there were three companies involved there was Merz, there was Novartis and I confess I forget the third company was. And so all patients on the on clozapine had to. Their consultant had to sign a disclaimer to say that they were aware of the risks and the patient was aware had been made aware of the risks. They had to have blood tests as frequently as every week when they first started to to be dispensed. If you didn't have a green blood result, that you neutrophils and were high enough that you would not get the drug dispensed. If you had, if you, if you got a granular cytosis, you would then entered onto a central database that all the companies, that all the ma h's had access to that you had to check before you signed someone up. So it was a really kind of a perfect example of what pharmacovigilance can do to bring a mark, a drug to market for patients who really need it, who otherwise couldn't. It's at a population level. You couldn't, you couldn't prescribe it, but if in this controlled manner.

Speaker 2 5:35

So I guess I started my career in PV with this idea of like it was. It was always kind of forefront of my mind that this is what PV can do. It wasn't a sitting at a desk processing cases with no idea, because you had to do it. You know we started in the industry. It was. Everyone talks about the evolution from not having it being told you have to have it accepting. It's a block from a guardian, from the regulators, to a commercial driver. Well, actually, I started my career somewhere where it was a commercial driver.

Speaker 2 6:12

Having said that, it was also quite interesting and kind of prescient for now, when we talk about the if we bring drugs to market earlier and more post marketing studies and risk minimization measures. It was entirely commercially unviable as far as I could tell. You were basically dealing with a generic product for which margins are tiny, for which there was a huge amount of infrastructure required and I don't think anyone was really making any money per packet on these things. So it's kind of thinking back. You know 17 years ago that this seems to be like an era we're entering now where there's going to be more. We need to get more drugs to patients. This is patient requirement more rare diseases, higher risk populations. What can we do to get the drugs to them quicker? What can we do to stop this or reduce this 15-year development cycle? It's going to be things like risk minimization, additional risk minimization as it is more intense monitoring, but that will come at quite literally a cost, and I think that's the kind of thing we can look back to to say, well, actually, what can we do to try and reduce that and rationalize what we do. So, yeah, it was a great place to kind of set the stall of. This is what PV can do, and not just it's something that happens.

Speaker 2 7:48

Having said that, it was one product and it was fairly, you know, there was not a lot outside. That company didn't have a huge amount. So I thought let's go and do a lot, get full exposure to the whole system with lots of products, and so I then moved to a company called Aero, which was a reasonable, small, medium-sized generics company headquartered in the UK, a couple of EU or European affiliates. We had someone in Canada as well and again, just by sort of coinciding a bit, there's a lot. I think there's been a lot of serendipity in my career of just being kind of right place at right time.

Speaker 2 8:35

Again, it was a great place to learn the full spectrum of pharmacovigilance. I had an absolute. The PV team had been built up by a fantastic head of the department who was growing it with the company. I was really, you know, really hammered home. The attention to detail that is ultimately everyone in PV is a bit kind of OCD with details and having to get things absolutely right and perfect. We've all got that tendency in us, I think. But it was again. Particularly, it was a really valuable lesson I learned throughout that I think after, on my second day, I sent a load of blank disks meaning to contain PSURs to regulators across Europe, and so that was a valuable lesson. To just check that you have properly burned files onto the DVD, so I was given a pass on that one, and then I think I think we developed into quite a decent PV professional, but probably not the wouldn't recommend for anyone else in their first, first couple of days at a job. But that was you know, and that was kind of a really quickly ended up being quite a fast growing company, both because of the number of products we had we had in it was there over the 2012 GVP modules and so that I was up to my, up to my eyeballs in SOPs and impact assessments and kind of really the face of pharmacovigilance in Europe changed.

Speaker 2 10:24

At that point of what was required, there was this you know, the great calls of you know and great expectations of harmonization, and before we know it, we're all going to be working exactly in step with each other and we're not going to have any more confusing two page checklists on where this literature case needs to be sent, depending on the status of the type of license you've got and where it's marked. We were just going to send it to you, gvp vigilance, and then we'd never have to think about anything. You know wouldn't have to think about that again. We could just write us that everything would be standardized. Unfortunately that's not quite worked out, but it was a great dream while we had it and it was a great thing. It was fantastic to kind of be implementing thousands of pages of regulations and building out a PV system. And we also there went through quite big acquisition from Watson Farmer to big US company. Well, it was a big US company. I guess I kind of lose track now of where these products and who we are. Then there was an merger with activists. Something happened with Teva after my year. It just suddenly it went from being quite a small company to hugely global.

Speaker 2 11:49

My first kind of experience of PV systems and large data migrations tens of thousands of rows of different product names, trying to get Excel spreadsheets, two other different types of PV systems all into Argus and again I thought, 13 years, sorry. Yeah, 12 years ago I thought PV migrations are going to be so much easier. Later in my career this is a pointless exercise to go through. I'll never have to think about this again. But again, it's amazing how little, ultimately, things haven't changed a huge amount there. So, yeah, I was at the Harrow for four and a half years.

Speaker 2 12:40

It was brilliant and I kind of I remember, when I started there, someone saying to me oh, give me a call when you want to learn about proper PV, because they were very much. They were a big pharma background. That's what they did, and I think I'd actually recommend a generic company. A smallish sized or medium sized generic company is actually a fantastic place to learn PV, because you can't just sit there and do your case processing and then pass it on to another team that you don't. It's you know. I think it was there. I kind of quite quickly read that I'm I like I'm nosy enough. I kind of want to be involved enough and understand how things fit together. So I think I can leave proper PV to other people just worrying about your one area. I just want to get involved with everything. So, yeah, I'd recommend generics as a great place to learn. You're still following all the GVPs. You probably got complex distribution agreements so you still get the same you know, still held to the same inspection standards. So, yeah, I thought that was, that was great. But having said that, I thought let's jump to the other end of the spectrum and go learn about clinical trials. And so I really did. I went to. I went to work for Cancer Research UK and worked in phase one and phase two studies there and had their PV team. So they've got this.

Speaker 2 14:11

The Center for Drug Development, now called the Drug Development Office when I started, has this little, this little department that most people don't know about. That. It basically it is. It is sponsor of its own clinical trials, taking de-prioritized products from big pharma or take it or products from smaller biotechs that need a kind of proof of concept, but takes the product, is entirely sponsor of everything, has everything in house CRAs, data management, pv, qa, everything. It's not a kind of it's sort of sits aside from the rest of their funding model of like it run, it runs everything. And again from those when we're back in the office.

Speaker 2 15:00

I was sat less than 20 feet from every function. So if you didn't know, if you didn't know clinical trials going into it, you certainly knew about it pretty quickly because you would overhear conversations. You could wander up to someone and say, well, actually, what does we're doing this with the safety database? What's the impact of that? On? On data management, what's what do the physician you know, what do the medics think of that? And you just had everyone in this small team working on 15 studies at a time, 10, 15 studies all the way through, for bench to bed to bedside, and it was. It was.

Speaker 2 15:40

It was a great, a real kind of great place to learn and as well as as well as it being small and that kind of aspect, every because of the kind of environment, it was everyone. You can work for a charity free because you want to be there. You know it's. Everyone has a you know, either a belief in what they're specifically what they're doing, or or just wants to be involved in charity. You know a charity's work for a bit. So it kind of led to a really good environment and kind of in, I'd Say, an environment and a culture is the hot dog that I think and I'd encourage every company to have and I'd like to think that Kind of have a drive phase as you know, take it that through dry phase as well of of people really caring about what they do and when wanting to and being conscientious and and being innovative and being and taking some risks, but in kind of an, an ethical framework. So they had the opportunity you know they're working with with Donate, you know donors money that you know we're not, they're not awash with with cash, so they do have to be Very careful about how it's spent and you know not spend where it shouldn't be and but on the other hand, because everyone's at a charity and almost by default wants to do everything ethically and right, there was that. But there was more of an opportunity to say, well, we should do this, because it should be done this way, because we believe it's done so, and you know they Front.

Speaker 2 17:14

I think just before I'd started, a few years before I'd started there, there was the Northwick Park, so TGMI scandal, the Elephant man trial, these and I can't remember the name of the report that came out of it now, but there was. There was a big report came out and a number of suggestions about how clinical trials should be run in the in the UK and the list of suggestions was kind of, if you looked at it now you would think it was crazy that anyone wasn't doing that. But actually it had very little impact on CDD because they were already doing these things because, say, look back, they seem, they looks like and they weren't the right thing to do. They just weren't necessarily Mandated by the regulator. It was kind of working within the spirit of the law rather than to the letter. You know things like.

Speaker 2 18:05

They always conducted their studies in Phase one units attached to a hospital, with, you know, an A&E department and everything, because that was what that was. By chance, northwick Park was attached to it. The phase one unit didn't have to be attached to emergency medical you know facilities. So it's things like. And so it gave again, gave me.

Speaker 2 18:25

This is of like, particularly around having gone through the GVPs changes and seen how the rules had gone like that to that. But that made me see as well, though actually, whatever rules and regs and legislation there might be, there's, you know there is a you can't just stop or you shouldn't just stop there. There's a lot of gray area in between and say the spirit versus the rule, and it was a kind of it was a good focus, say you can do really good Science, you can be bringing benefit to patients and you cannot be doing it on the absolute. You know that you can be doing it in the right way and that what you believe the right thing to do and really, as I've said, but we really be innovative.

Speaker 2 19:07

There was lots of work with transcelerate around, particularly around risk-based monitoring in studies, because we did have lived, we had limited numbers of CRAs and we were running more stuff. We needed to do it in a proportionate way, but that it was. That was a really big piece of work they did because it had benefit to everyone. Rather than just going up will introduce you, we'll do it in the way we think we can get away with. It was like no, we're gonna lead the way with. This is best practice of how you can do risk-based monitoring without Compromising patient safety.

Speaker 2 19:42

Say that was yeah, it's a, really it's a. It was a really, really interesting place to work. And Then I made my first, my first step and to onto the other side of things, onto the dark side of outsourcing and and CROs Scout. I'd been kind of I'd gone from one side to the other. I've gone generics, clinical trials, and I thought I like both, let's find a decent balance of it. And so I went to a Data-focused CRO called Quanticate, so it didn't really run the studies themselves but they're off the biostats data management and as well that had had pharma co vigilance, so headed up their PV team. Again, really interesting.

Speaker 2 20:31

Pyrenei. I've kind of every move I've kind of looked, been looking for something new and Broadly being pretty successful and kind of filling in gaps in where I had knowledge. So you know it was that was a particularly a hot time for off-shoring. So we, you know we established and and and grew a, an office and in India and trained up the team there and that was that was really kind of Interesting piece of work. You know well, it wasn't, it never stopped, wasn't just a piece of work properly over the years of of Training up a group and you kind of the because there was such a move towards it.

Speaker 2 21:09

But you talks a lot, there's a lot, there's a lot of cultural differences in the ways of working and things like globally, and particularly, I think these region and so working with to build up a team that you kind of you feel addresses kind of what's considered weak no, yes, sometimes weaknesses of and Of the offshoring model, and so well, actually you can do, you can do in exactly the same way as the UK, these you've empowered your team to, to make decisions, to not defer, you know, to question things, and Offshoring doesn't just have to be a we're sending out there, follow these instructions, send it back to the UK, the US, where decisions will be made and where the you know the, the big, the larger chunks of what could be. So it was an invaluable, invaluable piece of work there. Lots more database stuff. I think we realized that where we actually first met each other, I see you as in an, in an August pitch, I think.

Speaker 1 22:14

Yes, and these.

Navigating Regulatory Challenges in Pharma

Speaker 2 22:16

And again, that was an interesting period of project that Off again regs versus you know, requirements versus recommendations we were Can you to be our three had been such a hot topic for years of we need to be ready for it. We need it's gone live. It's gone live and I and as we're doing it's like we should be at you know Vanguard of this and we should be. We need a database upgrade anyway. Let's well, we'll get our three and we'll be ahead of the game. And we did that and we were. You know, we were, logistically, I think we were up and running with our three for clients March earlier than well, as I discovered, years earlier than others who were leaving for right until the last minute. But then you but then you find actually was that you know this, but it wasn't mandated. It was a best practice. It was quite clearly not a commercial driver for company it that our three was not a differentiator because you don't have to do it. Therefore, why do we? You know you have to have a particular kind of like who just wanted, who was particularly interested in In it being a project in itself. So I think that's you know, lot of the work that you guys are truly into with with tech it's kind of what and the integration of that. It's working with this small group of companies that really want to be at the forefront of things they don't have to do things, but they want to because they know it's coming and they can see the benefit of it and essentially, a best practice of the integration of these of these things, rather than it being a being mandatory. But yeah, I think that was so.

Speaker 2 24:11

Yeah, we worked on with Consecate, was here fairly soon. We worked clinical and and post marketing stuff there also for a couple of years, and then that's when drive phase happened. Thought, well, I've seen myself through all the phases, done a couple of years, done a couple of years. I see a road to think I know how things work, more business manner, and so set up drive phase Next month. We're, yeah, five a month away from six years of trading, which will be yeah, and I can't see. I can't see that I think I'm institutionalised now for my own company, why I couldn't go back to work for someone else, and what I really like now is that the ability to kind of work with most like as a as a consultant, you almost by definition when a company you need to want to consult and then, or once, a project team, they have bought into the change and neat and and what needs to be done, rather than there is a reason they are bringing you in because they need something changed and something done. So you kind of already have that engagement, that that drive to do to deliver something where, as often in house, if you know the day job can get in the way if things are broke, don't fix them. As a consultant, you're that other side of things are broke, new, we need to fix them. So it was keeps things interesting and, yeah, that's all Helping them was the friend helping them navigate the regulatory waters and the difficulties of being compliant, trying to predict where things are going.

Speaker 2 26:12

As I mentioned that GVPs in 2012, we thought we're going to be Harmonised. We thought we knew where we're going to stand and I don't think we're really much further along. I think there are a few years where it looks like we're moving in the right direction and now it seems like there's more and more exceptions, more and more kind of With DSUR, dsur, country specific annexes. You know do tend to think what's the point of having a standardized format for a DSUR. If you then have country specific annexes where everyone can say, oh, but we want it slightly different, it kind of it seems counterintuitive.

Speaker 2 26:58

I know we're particularly, depending on the way you look at it sort of exciting or frustrating period with, through Brexit and the like, with the MHRA global standing and I mean we all probably worry about the UK standing in everything at the moment that kind of watching and watching from the direction of travel that the MHRA takes in terms of what does it harmonize on, do we have lots of work being done with the FDA in health Canada, but we still, we are still part of Europe. If not, you know, if not part of it, if not politically, we're still Just over the channel and there are closest so and still normally work under most of the GVP. So where, where do they? Where do they start to hitch their wagon? Do they start to become, you know, try and become a leader and influence things and take countries, take other regulators along with them.

Speaker 2 28:02

I think we're kind of a yeah at the start of what could be quite an interesting few years. I mean, it certainly looks like the We've just had. We just had the MHRA symposium this week, couple days ago, as we called this, and it does sound like there's an awful lot of, I guess, talk of being proportionate, risk based and an attempt to reduce the burden on industry. Whether that's a primary driver to reduce the burden on industry or because the MHRA has been left in, you know, left with serious funding shortfalls because of Brexit and kind of needs to cut its cloth accordingly, we don't know, and we'll see how it, how it plays out. I mean, I do have and I think the June rain had said that really wants the MHRA to be an enabler of the industry and to be able to bring drugs to market quicker.

Pharmaceutical Companies and Drug Regulation

Speaker 1 29:03

To that, to that exact point. It's something that you mentioned earlier about bringing drugs to market and you were talking about. You know, the focus on, maybe rare diseases, etc. But how about lifestyle sort of drugs that are, quite frankly, making a lot of companies a lot of money right now? How is that how companies could mitigate this cost Problem? Because, if I take a step back, for instance, pfizer is a is a very good example. They made a lot of money off the covid vaccine and now they're in a situation where you know covid vaccines not selling as much. Where are they investing that money? Do they invest it in rare diseases or do they invest it in potentially more lifestyle drugs, which will obviously increase revenue, so that at least they can continue to do Research into some of the more rare drugs?

Speaker 2 30:17

So how could they change in focus of the companies or an ability to bring them to market? I mean, I think if you look at the novos going to be kind of the company to follow At the me know for the from the last year of those guys, that's, that's quite a good, good kind of product to jump on the bandwagon for. I'm going to get into it in terms of regulation and kind of strength of and what that actually does mean for the industry. I have some concerns that and in terms of the strength of, you know ultimately who is who is properly enforcing regulations. You know and you know?

Speaker 2 31:03

no, no, they have been. Was it get a two year ban from the AB PI for from breaking, you know, breaking some of their code of conduct? Ultimately, does that matter? Has that? You know just what's the scope, what was actually the deterrent for breaking the AB PI code of conduct? A two year, a two year ban versus sales and share price? That that flies up and I kind of feel that that you know.

Speaker 2 31:43

Similarly, with with PV, with these kind of lifestyle drugs that are, they are licensed for a very particular indication which is clearly being prescribed outside of. Well, actually, if something does happen with that, who is, who is, in short, who is keeping an eye on that? Who is enforcing that the PV is being proper, that the safety is being properly monitored, that different patient populations are and affecting that are being looked at? Benefit, risk and the different populate you know is okay, should this be limited to this population? Is it okay to open up? Where's where are the different benefit risks lining up?

Speaker 2 32:33

I remember from COVID when the cardiovascular, cardiovascular side effect I can't remember which one it was now came and which was actually, I think I remember, first spotted in Israel because they had a very particular I think it was a very particularly young cohort of people being vaccinated. But the, as part of the daily briefs that we were we were all getting, I thought there were some really good slides on benefit risk in each age group. So it was saying, obviously, is that a population level rather than an individual. It was saying, look, we are not. I think it was when they said that if you're under 30, you're not going to get AZ anymore. Because they showed like if you are under 30, your risk of getting of dying of COVID or getting seriously ill is tiny. The risk of getting this side effect is slightly larger. So it's not worth you having. Once you hit 30, you're in trouble with COVID, so it is worth it. So it was trying to explore the risk. I remember it was a really good graphic of the benefit.

Speaker 2 33:45

Risk is not static and so I think I'm always wary of when products are being used widely outside of their indication, their licensed indication. Who is ultimately responsible? Who is going to carry the can if something goes wrong? Most great drug scandals are not due to the drug being bad. It has gone through clinical trials, it has been licensed in a indication, in a population. For a reason the scandals always involve. It's been overused. It's been people. Companies, regulators have been aware of it but are kind of tied in knots of like Chuckle Brothers To you, to you. Everyone is responsible, but no one's responsible, and we see it in every kind of regulator. We've got in the UK the post office. We've got water pollution at the moment and everyone knows it's going on, but no one's truly responsible for fixing it. And the cost of fixing and I don't just mean the monetary to fix a pipe or whatever the structural cost of how society works is too is too big to fix it at that point.

Speaker 1 35:13

And how? How do you feel, then, with the changes? Circling back to the point where I diverge this conversation, how do the changes with MHRA and you know, obviously you were at symposium how do they make you feel as a PV professional?

Speaker 2 35:38

I think that they make me feel a bit I was going to say a bit nervous, but as a P I think possible. I think it does a disservice to PV in the UK, particularly because you know there's you know that's where I'm based and that's where the MHRA out, but I think they've done. There's been such good work done over. You know comms wise in PV and we're not. You know again, we're very details orientated. We're not very good at promotion and marketing and things of changing that story from. It's a tick box you've got to do. We'll stop you getting inspection findings to commercial driver.

Speaker 2 36:19

The number of audits that are done now because the fear of inspections has been just sort of implanted, regardless of whether actually the outcome and mid their remedial action is, is a problem.

Speaker 2 36:33

You know that they've done a really good job.

Speaker 2 36:35

There is more order to PV auditing done now than ever before and it primarily is driven most of it is driven by a fear of the regulators coming in and something and something coming at that, rather than commercial drivers.

Speaker 2 36:50

Obviously there are some you know some companies where PV and risk minimization measures are driving it and slightly different. So I feel it kind of a stepping back from that and saying we're going to you know there are going to be fewer inspections, that we actually expect less of less of you, so clinical trial proposals to ground board, don't worry about submitting individual suicide. You just need to have a proportionate safety system and do your own analysis and then your DSUR can just focus on on risks, rather than giving us listings and things. I think it pushes back to like oh well, actually, if we have to do less, we're going to do less, and if they're going to inspect less, we're going to have you know they're going to be, we're less likely to be seen. I think it rose back on what on what PV has accomplished as a function, has accomplished on its growth today. I think it undermines the ability then to be able to say we can get your drug to market quicker, because you certainly can't be doing that if you've got a minimal and minimal PV system.

Speaker 1 38:10

Do you think this moves away from putting the patient first?

Future Trends in Pharmacovigilance Strategy

Speaker 2 38:16

That. I think that's a particularly interesting question because, depending on let's, I'll take another tangent. If you look at sodium valproate which I think I wrote my first, I think when I set up my first blog about to try and show some insights, that's, the number of patients who have been affected by that is horrendous. And they've had the Cumberlidge report and it's looked and it's been going on for so long. Anyone who's in the industry is kind of new.

Speaker 2 38:53

It was tetrageneric anyway, but in terms of playing out in public in lots this week, what more should be done to restrict access and things like that? And then on the other side you have the patients who actually need it, who it is vital for their day-to-day functioning. So I think it in some ways reducing PV doesn't put the patient first because it puts them at more risk. But on the other hand, those who want earlier access, those who want to be able to take drug as individual, it's putting them. I think it's swinging from one kind of putting the patient. It's swinging from putting patient safety first, putting patient treatment first, I think. So, depending on what camp you're in and it could change from drug to drug you'll support some strict PV on some and reduction of access to it. But for another drug which you really need to go, I don't care. I want that. Don't worry about the PV.

Speaker 1 39:58

So surely the answer is post-market studies. No.

Speaker 2 40:03

I think that's going to be the way things are going to go. Well, it looks like they are. I think they're particularly interesting sessions at the MHA around their NIPASS inspections, really interesting about how much more labour-intensive they are as well and how long they're taking. I think it was something like 20 inspector days compared to nine for a standard PV inspection. But I think more post-authorisation studies then will need to lead to a kind of a fundamental shifting kind of, I guess, how things look after a drug's marketed, because it's shifting a lot of costs, there's a lot of additional oversight. It's a changing way of thinking about things, which I think it actually would be for the better, because there can be an element of once a drug's been approved, yeah, it's fine. I think it's a real bugbear of mine when people call phase one studies safety studies. Then we move on to efficacy it's proving that it's not catastrophically toxic, but it's not a safety study. It doesn't prove the safety, but there can be a thought that even once you've done phase one it's safe enough. So in post-authorisation studies that are going to be the way we go. But there's going to have to be a kind of whatever the horrendous cost of developing and bringing a drug to market is at the moment. There's going to have to be a. It's going to have to allow for an equal reduction in that development time to find it. Otherwise it's not going to be sustainable for either payers, whether in the states, insurance here, the NHS combination, in the EU, even something like sodium valprate.

Speaker 2 42:01

I said if the risk minimisation measure is, you have to get each patient to sign a form to say I've understood the risks I have. This has been explained to me. I know what it is, whether it be a form, a video, whatever. You get 10 minutes with your GP. You get a 10 minute slot in the UK to speak to your GP. About one thing it's not if more drugs come, have more of those risk minimisation measures, and particularly elderly patients, polypharmacy are they? The GPs are not going to be able to cope with having a patient have to have five different appointments over the course of the week to be informed about the drugs that they're about to be prescribed. The patients aren't going to be able to come in. So it's, I think, in terms of safety and that does look like a logical way to go, but I think again, the wider kind of health care system impacts need to be thought through Because, I mean, I don't know, trying to get an appointment with the GPs bad at the best of times.

Speaker 1 43:14

So, tom, thank you for the discussion today. There is a final question that I need to ask, and it's quite an. For me, it's quite an important one, and it's pretty simple really is what's next for PV?

Speaker 2 43:32

I wish I had a simple answer for it. I think I mean it's. I think it's a case of we continue to muddle along. It's I, if you'd asked me a few years ago, I've said harmonisation. I think what I think in reality, what looks like next for PV is decrease to harmonisation, more complexity introduced into our day to day work, and I mean it would be probably be remiss to not mention something about AI and the glory of that.

Speaker 2 44:09

But we almost made a whole episode not saying AI, well, I'm going to say I'm going to say I actually don't think at this stage, I don't think that is going to make an inherent difference to what we do. I think its uses certainly. You know where it's being taught. It's about pulling together the information. It's about being able to, it's having slightly cleverer ways of pulling stuff from your databases and together. But, as you know, that is not pharmacovigilance. That's the building blocks of what PV can achieve, of bringing clozapine back to the market, making sure that you know, making drugs available to populations they would not. That's what PV is. So I don't. I think the future is let's not get sidetracked by the tools, which the tools are, I'm sure will be great and are giving us great building blocks. But that's not ultimately what our job should be about. It's about how do we use that to benefit, you know, to benefit patients and bring and bring drugs safely to market.

Speaker 1 45:17

I think that's a very good answer and actually I was just thinking on that, on your answer Can the tools bring in? Can the tools being brought in, can they push PV into where it needs to be, which is you've mentioned it a few times which is to be looked upon as a commercially viable unit in itself, by maybe pushing it towards the early phases of a clinical trial, and to say that actually these tools could almost predict in some certain aspect of if this drug will be of benefit to a patient.

Speaker 2 46:09

Obviously there's lots of companies you're trying to do, you know, identify targets and what, and the next logical step of that is being able to prove actually how much quicker that or how much better those targets are. So I think it's the target. Finding the targets is the first step. With safety profile, yes, that can help. I think it would be. There's a lot of work you can do on your predicting your safety profile as it stands. The DIA has done a couple of great papers on helping to implement an FDA rule around aggregate reports sorry, aggregate safety review. That is that's possible to do now. You build up what your baseline is. You look at what you're anticipating to do. So, yes, ai and tools additional tools will be able to help speed that up. But I think it will be a sad state of affairs if we're having to wait for someone, when you can do that now, that companies would have to wait to have a shiny new toy to say, oh, yeah, we can do that and press a button. Companies can do that now and start to build things out.

Speaker 2 47:38

How many companies have a development risk management plan? You go, oh, we might do a development risk management plan. You'll know from phase. You can start planning from phase two of what you think you might need to do. By the time you get to market. You shouldn't be seeing, or you wouldn't expect to see, massive problems with completely unexpected safety problems. By the time you're getting towards the end of your phase three, you know where you're going to start and get a development risk management plan in place. Yes, I know there are providers doing tools to help put that together. Again, it's pulling together information you've already got. Yes, I agree with you that it could do that. I just think it's a bit sad that it's not done already, because it's almost like it's going to need those non-PV people with their more commercial and marketing-minded to say you should do this, guys, to get the company start. But maybe that is incumbent upon us to keep pushing that ourselves.

Speaker 1 48:51

Tom, it's been a fascinating conversation, as always, with you. Thank you very much for joining me today.

Speaker 2 48:59

Thank you, apologies for the bit ranty and soliloquy. It's been good summer. It's been good summer. It's been good summer.