We are pleased to introduce the podcast series, Precision Neuroscience Reimaged: By Industry, for* Industry.
In the first episode of Precision Neuroscience Reimagined, Jane Twichen, Head, Clinical Trial Accelerator Unit & Senior Director, Global Clinical Operations, and Sarah Deeley, Senior Clinical Country Lead, at Biogen, joined Tina Marshall, Head of Commercial at Akrivia Health to discuss barriers in clinical trials and how to overcome them, why the UK is an attractive place for clinical trials, and what steps we need to take to make the UK a global hub for life sciences.
Tina Marshall: Biogen is a truly amazing and innovative organisation. They’ve been delivering therapies for neurological disorders for the past 40 years and are really looking at how to deliver innovations globally, particularly in the UK where the UK is hoping to become and is planning to be the global hub for life sciences.
We’re going to talk today to find out more about Jane and Sarah and also to see how real world data help with that challenge. I’m really thrilled to be here. I particularly love the strapline of this organisation:
“where science meets humanity.”
From my perspective, you can’t get better than that to tie the two together. So, thank you for coming today, and welcome.
What brought you to Biogen? Why are you here in this amazing organisation?
Jane Twitchen: I joined Biogen about nine years ago and it was a time that Biogen began expanding beyond just being a multiple sclerosis company. And I really like the fact that Biogen was trying to tackle some of the neurodegenerative diseases that we hear so commonly about Parkinson’s and Alzheimer’s, for example.
I also love the fact that at our UK site, we have an R&D centre, but we also have our UK commercial affiliate. And I think that not only creates a really nice culture but allows us to learn a lot between the two organisations.
Sarah Deeley: Yeah, so similar to Jane, I’ve been here almost nine years and it was really a personal drive that brought me to Biogen. Having family members that have suffered from both Parkinson’s disease and multiple sclerosis, albeit a number of years ago, and really seeing Biogen being the pioneer in neuroscience and being able to drive the science forwards, really attracted me to Biogen as a company. But also, the role here in the UK has so many amazing facilities and the company culture where science and innovation meet in terms of a perfect partnership.
Tina Marshall: I was going to say that the company culture actually does seem to be pretty amazing. As we were coming in and you could see the Women Innovation Network, the focus on the Mosaic network, it seems like an incredibly diverse environment to be in.
Sarah Deeley: Yes, absolutely. And I think although being a sort of large global biotechnology company, the nuances, and the individual sort of aspects that we have here on site are second to none. You sort of definitely named some of the most amazing ones here.
Jane Twitchen: I think we’re all encouraged to enrich that culture as well. There are so many events and collaborations that we can get involved with to support some of the things like the Women’s Innovation Network. We mentor at local schools and perform other community activities.
What are your roles at Biogen?
Jane Twitchen: So, my role now is that I head up something called the clinical trial accelerator unit. It was a role I moved into nearly exactly a year ago. And before that, I had been in clinical study leadership, so very much attached to our clinical trials and helping to move them forward. But through an initiative we started last year, we really examined our operating model for clinical trial delivery and we looked at how Biogen performed against our competitors and we thought we’ve got room to do more, we’ve got room to become better and hence we put the clinical trial accelerator unit together really with a focus on how can we move our portfolio forward with more agility, what can we do to get our drugs to patients faster.
Tina Marshall: In that role, are there any barriers for you to overcome?
Jane Twitchen: Plenty, I think is the honest answer. I mean if clinical research was easy, we’d all be doing it, we’d be doing it really quickly. I think we’ve got challenges still with some of the really tactical parts of clinical trials. So, when you start up a clinical trial, you start by finding a site and helping that site to activate. And both of those come with plentiful challenges. For years, one of the biggest problems for sites has been site contracting, and I don’t think that’s gone away. I think we still have lots of problems with site contracting. We’re learning, and we’re improving, but things like data privacy keep on changing, so we have to adapt and be ready to move forward. So definitely some of the tactical areas we’ve brought into the clinical trial accelerator unit to really make sure that we’re set up for success.
We’re learning, we’re not reinventing the wheel. And we’re really working with our Clinical Research Organisation partners to make sure we’re managing those processes effectively as possible. We also spend a lot of time trying to understand how we can make our studies easier for both the sites and the patients. And I think, in the industry, you often hear the word burden now, site burden, and patient burden. We were examining a study that was just about to have its protocol approved and realised that in order for a site to activate, it had over 40 hours of training required for the site to take before it could be ready to bring on patients. And you think these are busy research units, they’ll be participating in multiple trials, so having a compelling argument for them to complete 40 hours of training-
Tina Marshall: I mean might take a really long time to get that trial up and running.
Jane Twitchen: Absolutely. And that involves, it’s not 40 hours necessarily for the same person, but it will be different people in that team. It will be making sure they understand what they have to do, have access to the right systems, have time available to do it, and have support available. So, all of those infrastructure things, we try and look at ways of making them easier for the-
Tina Marshall: And this is everything that they’ll be doing around their day job.
Jane Twitchen: Exactly. I guess running for some clinical trial units, that’s part of their day job, but some of our trials are running acute care centres and that’s very much above their day job because their number one priority is looking after the patient.
Jane Twitchen: So, getting sites active is still a challenge, and making the studies as easy for them is still a challenge. Possibly one of the more interesting areas of challenge is getting better at feasibility. So if we’re better at feasibility, we can ensure that our sites are placed in the best locations and we can ensure that we’ve got a pool of patients ready to onboard to our trials when we’re ready for them. So feasibility has been a massive growth area for us over the last couple of years and it’s one we’re still looking to grow, still considering which data sources we use, how we work differently in different countries, what the patient journey looks like in different countries, and how we can understand that better. So that’s another area within my unit. We have our feasibility centre of excellence and we’re really looking to work with partners and grow our internal expertise in that space.
Tina Marshall: I mean, this is all about the right patient at the right time for the right trial, isn’t it? And Sarah, for your role, how does that affect you? Because you were on the ground working with the sites.
Sarah Deeley: Similar to Jane, I work in the global clinical operations organization in the clinical country and site management team. And I’m responsible for the UK and Ireland in terms of the strategic pipeline and the delivery and oversight of the entire pipeline at the local level. So, it’s working very closely with Jane and her colleagues and other individuals in the Global Clinical Operations organisation. And exactly as you said, it’s making sure that we have the right protocol at the right sites in the right country and to deliver for the right patients. So, we work across the life cycle of the clinical trial, really working with our key medical experts, and our patient organisations to make sure that we design a protocol that’s fit for purpose in terms of the conduct and then also further down the line.
And then also in terms of how we can deliver it and working very closely with Jane and her team members to make sure that we are conducting appropriate feasibility and teasing out issues right at the early stage and seeing how we can address them. And then working with our CRO partners and the delivery of the protocols at the local level and really teasing out all of the nuances and trying to address challenges upfront with the best one in the world and supporting the delivery along the way with the oversight.
Jane Twitchen: Because we’re a global organisation, we’ll start with a global protocol, and our medical team is often based in Boston in our headquarters. And that will mean we’ll design a protocol that will work really well in America, but there may be challenges with delivering that protocol in other parts of the world. And obviously, eventually, we want to bring our drugs and our treatments to other parts of the world, so we need to make sure we’ve got representative demographics. So, working with Sarah, we really try and understand what the difference in maybe a diagnosis route will be or what will be the difference in the standard of care, or how would concomitant medications change in different parts of the country. And that will allow us to tailor our protocols and make them fit for purpose and then hopefully overcome recruitment challenges further down the line.
Sarah Deeley: Absolutely. And thinking about the further downstream, as that’s another benefit of working here in the UK. As Jane mentioned, we have our affiliate colleagues. We work very closely with our value on access teams and our commercial teams to really understand what the commercial setting looks like. So, we make sure that we design the trial that’s fit for purpose in terms of the pricing and in terms of access for patients further down the line as well. So again, working with a sort of holistic view-
Tina Marshall: It’s a very different beast, isn’t it, the healthcare system in the UK- the data that’s available. From healthcare in the US compared to here.
Jane Twitchen: I also think our pipeline, obviously we’ve spoken about it being neuroscience, it’s really evolved just in the time that we’re here. So, I think one, there are elements of our pipeline that we’re trying to look for presymptomatic patients or pre-diagnosis patients and that brings a deeper layer of complexity. Because of course once the patient’s been diagnosed, they have a nice code next to them and we can go and find them without too much trouble.
Tina Marshall: And of course, in the UK we don’t like to diagnose them too soon, particularly for mental health and dementia.
Jane Twitchen: Absolutely. So, we’re thinking about what other signs or other signals could we be looking for. We have some other parts of our portfolio that are looking for really rare diseases or genetic subsets of common diseases, and that brings another layer of complexity too. So, we’ve had to expand our mindset and our thinking about how we perform feasibly in those circumstances. What other data do we need to use? So working with genomic data, working with EpiData as well as beginning to expand in the areas of real world data.
Tina Marshall: It’s really interesting to hear what you’re saying about the feasibility, the protocols that are being developed in the US, and then bringing them over to the UK.
What flexibility do you have actually in changing those protocols and adapting them for the UK?
Sarah Deeley: Well, I think that questions are sort of applicable to global organisations. Something that Biogen does extremely well is making sure that we do have that external engagement with both our regulatory authorities, as well as our key medical experts with a draft protocol so we can hopefully feedback as necessary. We get feedback and then the changes are discussed as necessary in terms of making sure that the protocol is fit for purpose globally and not US-centric. So that’s something that myself and my counterparts do, in terms of understanding whether the inclusion and exclusion are going to be able to identify the correct patients for that country. As well as study schedules and really teasing out nuances and identifying challenges at that very, very early stage.
Jane Twitchen: And as well as learning from the regulators and the key opinion leaders, we’re trying to listen more to the patients. This is an area that’s really grown, I think post-COVID or through the COVID experience. One, everybody knows more about clinical trials now and understands what a clinical trial is. But two, that’s really enhanced our wish to deliver flexibility to protocols. That’s hugely challenging. It’s particularly challenging in neuroscience where we often rely on rating scales as our endpoints. And there’s a huge difference between an observed interaction when you’re sitting next to me like this, then there could be through a screen or using a third party to perform that assessment.
So there are lots to get over and to learn from in that area, but we are trying to listen to our patients. We are trying to bring innovation to our study design to have flexible protocols that also allow change as the patient’s disease progression changes as well. So we might start working with a Parkinson’s patient when they are perfectly happy to come in and want to see their doctor, but as their disease progresses as they go throughout the study that opinion might change. How can we make sure the protocol adapts to them?
Tina Marshall: We’ve been hearing about how you’ve been adapting your protocols based on sites.
How is this working for patients? The landscape for patients and clinical trials has completely changed. Patients know so much more now and they want to know so much more. So what are you guys doing?
Sarah Deeley: We’re working very closely with the National Institute for Health and Care Research, the NIHR in the UK in organising patient advisory boards. These can take in terms of a number of objectives and it’s really bringing the patient voice into a much earlier stage of research, whether it’s reviewing certain documentation, or reviewing certain aspects of the protocol. But it’s making sure that we are designing protocols that are fit for purpose for the individual patient and that they will want to be able to partake in the study and it will be a positive experience for them because that’s what we want to make sure that we are generating clinical studies where patients do want to participate and they’re getting something out of it.
Jane Twitchen: We’re really trying to consider the patient in everything we do. And we’ve run a few internal initiatives recently in response to that. So one was really simple and I’m not sure why we didn’t think of it before, but it was to develop a patient glossary. So regardless of where we sit within Biogen, whether we’re a commercial member of the sales team, producing materials for a patient, whether we’re producing clinical trial materials, whether we’re adding text to our website, we should be using one voice, we should all be using the same terminology. We should make sure it’s not too medically or scientifically rich so anyone can pick it up and understand it and see that consistency between our materials.
We’ve just published the first version of that and hopefully, that’s going to be really well received by our patients. That’s one level of complexity if you like, something that we could work on quite rapidly. What’s a much longer journey for us is adjusting our protocol design to listen to patient feedback. And as you rightly said, Tina, we’ve got such an aware general public now post-COVID trials, and a lot of thought has gone into how can we make the delivery of clinical trials easier for the patient. I think in neuroscience that’s particularly challenging. We have a lot of reliance on our endpoints and rating scales and me observing you for example as a patient will be very different here sitting next to you than it would be if you were behind a TV screen or using a third party and observing you.
We’ve really got a few things we need to think through and work out there, but we’re trying to make our protocols more flexible in terms of delivery options. We’re trying to not require the patients to come into the clinic if they’re a population that doesn’t need to come into a clinic. Or the ultimate nirvana would be to design a protocol where the patient has choices and particularly choices, they go down their disease progression. For long-term neurodegeneration, I might be very happy if I’m an early Parkinson’s diagnosed patient to come in and meet with my doctor, but a few years down the line I might not be so happy and it might be easier for me to be seen in the home.
Tina Marshall: So this is, I mean, everything that I’m hearing, and the last few weeks, as an organisation we’ve spoken to a lot of companies. And word on the street is it’s difficult to recruit in the UK. Clinical trials are difficult, which means that there’s going to be a lack of investment from big pharma going into the UK.
Why is the UK such a difficult place to recruit? Why is it so challenging?
Sarah Deeley: Well, I think for a number of reasons and really just to put it in context with a few numbers, I think looking back to five years ago and then 17, 18 years ago, we’re seeing a decrease compared to now of about 40% of commercial clinical trials. And that’s clinical trials being started and patient enrollment. So that’s a significant decrease in terms of the availability of trials for patients. That’s what we’ve got to think about first and foremost. We saw a number of innovations and flexibilities introduced during COVID, which really supported highly efficient and innovative research from digital methods to regulatory flexibilities, et cetera.
However, unfortunately, the UK has not recovered compared to some of our other counterparts in Europe. And really it comes down to capacity within the NHS. We’re seeing that across the board right, from R&D departments to staff to specific research resources and facilities such as imaging and pharmacy. And it’s really being able to identify where the lack of capacity is and a number of bodies within the UK, the NIHR, NHS England, DHSC, as well as the ABPI. Have a number of initiatives out there in order to try and overcome these challenges, so we can increase the volume of research and get the research out to the patients once again.
Tina Marshall: So we recognize that the UK’s a challenging place, there’s no capacity. But why the UK? Why is it worth overcoming these challenges?
Sarah Deeley: I think what really comes down to what makes the UK an absolute sort of beacon in terms of life science research is the availability of the data. We have a national healthcare system, which is the largest in the world in terms of lifetime access right the way from birth through to death. And it’s access to these incredibly rich data sets, which makes the UK so attractive for conducting clinical research. We have phenomenal academic institutions interwoven within our national healthcare system, which we are able to access as an industry. We also have wonderful stakeholders in terms of the MHRA, HRA, NIHR, supporting the conduct of clinical research here in the UK. And really with the aim of becoming a life sciences super house and a superpower from a global standpoint.
Jane Twitchen: I was just going to add, I also think that we’ve got a really diverse patient population within quite a small geography as well. So like many pharmaceutical and biotech organisations at the moment, we want to make sure that we are recruiting from across section demographics. We don’t just want white Americans or white British males, we want all sorts of backgrounds. And I think in the US and in the UK, we have the opportunity to achieve that within the site networks that are already in place.
Tina Marshall: So then essentially if an organisation were to invest in a clinical trial in the UK, they would have a diverse population. They would have access to a wide range of data sets, but also because of the support from the government bodies, it would be a robust clinical trial as well.
Sarah Deeley: Absolutely. And I think it comes back to what Jane mentioned earlier in terms of making sure that we do appropriate feasibility so that we are placing our trials at the right sites in order to access those diverse populations that we are so readily available here in the UK and are such a benefit to the whole UK as a whole.
Tina Marshall: To the ecosystem.
Sarah Deeley: To the ecosystem. Exactly.
How can real world data help with the challenges that we have? Can it help?
Sarah Deeley: Absolutely. So I think again, it’s bringing it in so early on in the feasibility process, looking at real world data from a global perspective, but then taking, including it in our feasibility outreach, feasibility insights, and making sure that the real world data is fit for purpose from a protocol standpoint within inclusion, exclusion criteria. We can look at it in terms of enrollment modeling as well. Looking at it in terms of bio market insights. So again, it’s got a whole breadth of benefits and it’s making sure that we’re utilising it right at the early standpoint and then of course further down the line, making sure that we’re utilising it in terms of identifying the patients that we want to be enrolled in our clinical trial as well.
Jane Twitchen: I think it’s definitely got time and cost benefits. So from a time perspective, the more robust and accurate our feasibility, the more likely we’re going to have a sort of pre-identified patient population that we can move forward and recruit into our clinical trial.
Sarah Deeley: Much sooner.
Jane Twitchen: And I’m afraid the kind of saying, time is money, is very true in clinical research.
Tina Marshall: Well, you are also the acceleration unit.
Jane Twitchen: We are indeed, but the quicker we get the first patient in, the quicker we get the last patient out ultimately. So if we’re good at having our sites in the right place, identifying the patients. And taking a step further, there’s kind of theoretically identifying the patients. So in feasibility, everything will be anonymized. We’ll be saying:
“Where have we got the greatest areas of disease density? Where have we got patients who look like they’re going to match our recruitment criteria?”
And as Sarah explained, we can do our scenario modeling on those to try and define what our timelines going to be for our clinical trial, and how many sites we need for example, for our clinical trial. But where it gets even better is.
Tina Marshall: Absolutely. And it’s so important for us to manage that pathway very carefully as well. As we were talking about earlier, privacy first is a key standpoint for us, information governance. So the recontacting of patients, we do it through our healthcare organisations. And our healthcare organisations would reach out to our patients because we also want there to be a win. And so much of the work that we would do around the feasibility to support Biogen and organisations is a course on the data, but we also want to make sure that the sites have got the capability, that the patients are the right patients. And this is where working with healthcare organisations is absolutely key to that.
Jane Twitchen: I think it’s worth reflecting back on some of the talking points we shared earlier about why is the UK a really favorable environment to us, and the fact that we do have a joined-up healthcare system. So when we compare this kind of analysis that we are able to do in the UK now to with the US. In the US, we’d be working with insurance company data and that doesn’t give you the longitudinal view of the data that Sarah described earlier. So it’s rare to have that full picture because people will move from insurance company to insurance company.
So if they move job or move home or whatever. And so it’s more complex in terms of the data journey that you’re picking it from different places and having to put it together. So the simplicity of gaining that longitudinal data is a sort level easier or more straightforward in the UK environment too.
Sarah Deeley: Absolutely. And I think again, thinking about the UK healthcare system being so joined up through primary, secondary, and tertiary care, the nature of Biogen’s protocols and our pipeline dictates that we would normally conduct our clinical trials in secondary care hospitals within the specialist units. However, a number of our patients may reside in primary care. And again, that just highlights the importance and the benefit of being able to utilize real world data to identify them both from the early feasibility stage and then as Jane mentioned, the way through to potentially identifying them from an enrollment perspective. And that certainly is one of the unique aspects of the benefits of the UK healthcare system.
Tina Marshall: I remember when we first spoke Jane and we were talking, we were looking at heat maps of dementia and heat maps of the Akrivia patients, because of course we’re looking at that anonymised data set to start off with, aren’t we? Before we get through and we get through feasibility and of course then the process is to, contact patients with our healthcare organisations.
The UK has a mission to become a global hub for life sciences. What steps do you think we need to take to make this happen?
Jane Twitchen: I certainly think it’s about carrying on listening. Listening to the sites and listening to the patients. As we mentioned earlier, the sites have given us lots of feedback, but we haven’t been able to adapt to all of it yet. There are certainly things in terms of trial technology that we can do to make things easier. That training example I gave earlier I think is really key. So from the big picture perspective, as sponsors, I think we really need to listen and we need to respond. So we need to make our studies easier for the sites to run. We need to make our studies easier for the patients to participate in.
Sarah Deeley: Absolutely. And I think it’s also looking at the infrastructure. We have the expertise there in the NHS, the patients are there as well. However, we need to make research a priority and that certainly is something that the UK government is striving to do. We need to embed it within the NHS. We need to protect research time for our principal investigators, and all of the staff working on the studies. We also need to provide mechanisms to streamline clinical research. And going back to a point that Jane made earlier is making, for instance, contracting much more simplified, and much more unified across our nations. And again, there are lots of initiatives that are working to do this. It just needs to be done much quicker and with much sort holistic support from a government perspective.
Jane Twitchen: I think from the patient perspective as well, and we talked about it a little bit with the glossary, we have a massive opportunity now as we discussed post-COVID. Everybody knows what a clinical trial is. It’s been demystified a little bit, so we need to build on that momentum.
Tina Marshall: We do need to build on that momentum.
Jane Twitchen: And I think we’ve been really good and we’ve talked about the UK being a great kind of center for life science, and I certainly know my colleagues in translational biology and genomics have got great networks with the UK universities. But it’s leveraging it and it moving forward. So we’re starting early. We just need to carry on bringing it forward and bringing that data into our clinical trial work.
Tina Marshall: It’s really reassuring to see everybody on the same page, whether you’re a healthcare organisation, government agency, life sciences organisation, real world data.
Everybody’s on the same page and we’re all working toward the same goal to really drive value back into our healthcare organisations that can deliver value to our patients.
Jane Twitchen: I think that’s what really motivates us at Biogen. There are such a huge number of patients with unmet needs. Anything we can do to accelerate our clinical research and hopefully bring forward solutions to those unmet needs, and develop drugs that are going to help these patients, it’s such a positive step forward and when we really want to be part of the journey.
Sarah Deeley: And I think from a UK perspective is just making sure that we do continue to try and overcome these challenges, to build on that UK life sciences vision, to be the life sciences’ superpower. And I think there’s a huge amount of opportunity with a number of changes in the ecosystem and the environment and it’s making sure that we can bring these protocols and these trials to the patients, so they have the availability to access these medicines from an investigational form and then ultimately in a commercial form.
Tina Marshall: Thank you so much for your valuable insights. I really appreciate them and I’m sure that everybody else will as well. It’s really clear to me that patients are at the core of everything that we do. We need to make sure that we protect their privacy, but we also need to make sure that we’re able to bring clinical trials to them in the right way. And this is using our government organisations. This is making sure that the trials we bring into the UK are robust and protected and delivered ethically to a diverse population. Once we’re able to do that, then I’m sure we can ramp up the speed of medications to patients and obviously deliver better care for all.
For the first episode of Precision Neuroscience Reimagined, RWD, Patient-centricity and Clinical Trial Optimisation with Biogen, and more: https://precisionneurosciencereimagined.buzzsprout.com/2088238/11910368-rwd-patient-centricity-and-clinical-trial-optimisation-with-biogen