23
Examination of witnesses
Dr Valerie Crolley and Professor Nick Turner.
Q216 The Chair: Welcome to the second session this morning. We have two witnesses. We are very pleased to have Dr Valerie Crolley, who is a medical oncology consultant at the Royal Free NHS Foundation Trust, and Professor Nick Turner, coming in online, who is director of clinical research and development at the Royal Marsden NHS Foundation Trust.
By way of introduction, could you each briefly set out your role, your NHS trust, and how your trust compares to other trusts? In this inquiry we are interested in the process of getting innovations into the NHS. Could you each describe perhaps one innovation: a test, an AI or software tool, or a new therapy that you have tried to adopt or scale within your trust? Did it succeed? Did it stall, and at what point in the process? So those are the challenges. Dr Crolley, would you like to start?
Dr Valerie Crolley: Thank you very much for this invitation to be here. I am a locum medical oncology consultant at the Royal Free NHS Foundation Trust. As is common these days, I work over two different hospital sites. I work at the Royal Free Hospital in Hampstead, looking after patients with colorectal cancer, and then I also work at North Middlesex University Hospital, and there I look after pan-GI cancer. I cover oesophageal cancer, gastric cancer, pancreas cancer, biliary tract cancer, small bowel cancer and colorectal cancer. I also cover cancer of unknown primary—so gizzards, basically.
I could not tell you the exact number of patients that the entire Royal Free Trust covers. It covers very different demographic backgrounds; anything from the highly affluent, leafy Hampstead area all the way to some areas of significant deprivation. We also have a significant number of patients who have English as a second language. I was at a conference the other day and heard that our hepato-pancreato-biliary cancer service covers, I think, 3.6 million patients. So we have a very large catchment area for some of the more uncommon cancers that we treat.
The Chair: Can you perhaps describe one innovation?
Dr Valerie Crolley: Probably the newest thing that has come into widespread clinical use is a protocol that we informally call the Matterhorn protocol. There was a phase 3 clinical trial that reported out at the ASCO conference last year. ASCO is a big international conference at the end of May or beginning of June every year. It is the biggest one, where all the biggest trials come out. A phase 3 trial reported there called Matterhorn.
The previous standard of care for oesophago-gastric cancer would be to give chemotherapy before surgery—a combination of chemotherapy called FLOT, which is a three-drug combo. You would give two months of that chemotherapy, do the operation and then you would give another two months of that chemotherapy combination. The idea behind Matterhorn was to still use that combination chemotherapy, but add immunotherapy to it. So we would give two months of immunotherapy with the chemotherapy, do the surgery, and then, after the surgery, do two months of chemotherapy with a year of immunotherapy.
The study was positive, and it showed that adding immunotherapy increased and improved long-term outcomes. That data came out at the beginning of June, say, in 2025. By November, or maybe December, of 2025, we had the expanded access programme open, meaning that it had not quite gone through the NICE approval process but we were able to give the immunotherapy with the chemotherapy to patients with oesophago-gastric cancer. Then, as of the beginning of May, just over a month ago now, it became licensed through NICE, so we can give it to all patients. Within a year, we have gone from positive clinical trial data to widespread clinical implementation, which is pretty much light speed for this sort of thing.
The Chair: Thank you, that is very interesting.
Professor Turner, over to you.
Professor Nick Turner: Thank you very much for inviting me today. I am a medical oncologist and I treat breast cancer. I am also the director of research and development at the Royal Marsden, and the director of our Biomedical Research Centre, which is the biomedical researcher devoted to cancer research in NHS England. As you may all know, the Royal Marsden is a very specialised trust that is solely devoted to the treatment of cancer. It is also very research-focused in collaboration with the Institute of Cancer Research. Among NHS trusts it is relatively unusual, compared to the bulk of foundation trusts.
You asked me to highlight one innovation. One innovation I will highlight is the recent approval of liquid biopsies for patients with metastatic breast cancer. If the committee is not familiar with them, liquid biopsies are a way of getting the same information we used to get from a tissue biopsy just from a blood test. Cancers shed their DNA into the bloodstream, and so blood tests can analyse this DNA and tell us which mutations are in the cancer, to direct therapy.
This concept of liquid biopsies was added to the national test directory approximately a year ago to select the optimum best therapy for patients with metastatic breast cancer. The reason for bringing this up is that there were some challenges in implementing this around the NHS. Because we had been doing lots of research in this area, we already had some infrastructure in place for taking these blood test, and so for us, it was relatively smooth to implement this into clinical practice at the Royal Marsden, but there were more general challenges throughout the NHS.
The Chair: Are you saying that it is not widely adopted in other trusts?
Professor Nick Turner: It is widely adopted now, but I did not know if you wanted me to refer to those comments now or later. Once it is in the genomic test directory it is then, available for all patients and all trusts in England. However, some of the mechanics—the pathway required to take these blood tests—required implementation. For example, the special blood tubes required are relatively expensive +and there was no mechanism in place to make these available through all the trusts in the NHS. Specialist centres such as ours were able to adopt it pretty much right away, but throughout the NHS this then required a lot of process to work out how to actually do this in practice. That delayed this becoming widely available by six months or perhaps even a year.
Q217 Lord Drayson: Exploring the barriers to the widespread adoption of innovation within the NHS is an area we are really trying to get to the bottom of. Witnesses have told us many times that, whereas the UK is very good at life sciences innovation and piloting new technologies, it often fails at spreading those proven innovations into routine use. From both of your perspectives within your respective trusts and your wider experience within the NHS, could you give us your views of what you think are the most important barriers to that more widespread, rapid and permanent adoption of innovations?
Dr Valerie Crolley: The biggest barrier, at least from my experience, is time. In order to bring in new innovations and to set up new drugs, new machines or new tests, you need people to have the time to set it up. Pharmacists need time to get the new drugs into your trust, and you need time to set up the protocols on the chemotherapy prescription systems. You need time to set up new tests and to get the equipment. It all takes a lot of time. The problem is that, at the moment, people in the NHS are pretty much working to their maximum time just to fulfil their clinical duties. In order to set up a new trial or even to implement the results of a new trial, somebody has to make extra time in their day or work outside of their time in order to make these things happen. That massively slows down the whole system.
I can give you an example from just this week. A colleague of mine is trying to set up a new phase 3 colorectal cancer study, looking at a new targeted drug in the first line for colorectal cancer. We are almost there, having done all the paperwork, but we have had to delay opening the study because the pharmacist who was meant to be helping us set this up does not have time to do so and has pulled out. That has delayed the entire set-up of the study. And this type of thing is not uncommon.
Professor Nick Turner: I mentioned in my previous response the pathways that need to be in place to allow adoption. I want to touch on another issue of moving from pilot phase into later adoption.
Pilot phases, especially where a new innovation has come from a university or a trust, are often done on in-house exemption—health institution exemption from UKCA or CE marking. This regulatory framework can add significant challenges to then rolling this out further because in-house exemption can only be in the legal entity that is doing the manufacturing. This can allow a pilot study to happen in the trust partnered with an institution, but then the barrier to taking that forward is relatively substantial.
There are funding mechanisms in place, of course, such as the NIHR i4i, but those are competitive and there certainly needs to be institutional support to help the applicants apply for them. The other approach is to spin out and seek UKCA marking, but this is a significant challenge for taking in-house developments and innovations forward.
Lord Drayson: That is really interesting. When you say spin out, do you mean the creation of a commercial vehicle of some kind to be able to begin the regulatory approval process for a CE or CA mark?
Professor Nick Turner: Yes, exactly that. It is often very challenging for a trust or an HEI to fund development all the way up to a CA mark, so the most common route would be to seek to spin out to industry, but doing that in-hose is a challenge. It is doable where it is an in vitro diagnostic and can be done in-house, and many genomic hubs have developed that as the way they do genomic testing in the NHS. But it is definitely a very common challenge for taking devices, innovations, AI or other tools forward.
Lord Drayson: That is a really helpful insight. We have heard a lot from witnesses about this so-called pilot-itis. It is interesting and good to see that the NHS is still actively clinically innovating, and that you have the ability to have those exemptions within an individual trust that enable you to try a new idea. But then there is that important step of getting it into a commercial route, which would allow wider regulatory approval.
Are there other barriers that you see that are adding to that pilot-itis? In other words, when a pilot ends within an individual trust, what happens to it? Is there someone who has responsibility within the trust for the procurement of the innovation? Let us say that this regulatory issue was not the barrier in this particular case. Who in the trust is responsible for taking the ball and running with it?
Professor Nick Turner: I am not an expert in procurement, so I apologise for my comments on this. Pilots are often funded by research funding, and then obviously that will largely end at the end of the pilot. There are mechanisms for ongoing research funding, of course, as we have already mentioned. If the innovation is ultimately going to be cost saving or if there are very clear benefits for patient care, the route for adopting that locally is clear. But if it is ultimately going to be costly to develop that innovation, it is often difficult for local trusts to identify a funding stream that will allow that innovation to go forward, whereas NICE is very much there to fund things that have the level of evidence that is required for UK CA marking across the country. It is simply the financial challenge that then hits when funding ends.
The Government provides very useful funding for this through biomedical research centres and applied research consortia, which are aimed at bridging this gap. But the reality is that it often comes down to available sources of funding.
Lord Drayson: I will push you a little further, just to understand. Let us imagine this innovation that has been invented, so to speak, by a particular clinician within your trust that does not require additional funding for its adoption, though it does require the rolling-out of that practice across the trust. Who is responsible for ensuring that the innovation is taken up in the trust? What is the role within an NHS trust where that responsibility is held?
Professor Nick Turner: Thank you very much for the question. I can give you the answer for the Royal Marsden but I am afraid that is very different from the rest of the NHS in general. Because the Marsden does so much research and innovation, it has a transformation team that is there to do exactly the transition you refer to. We have done multiple transitions on this, especially the adoption of robotics into cancer surgery. But we have a transformation team, and that would exist to a much lesser extent as you head into district general trusts, for example.
Dr Valerie Crolley: I do not think I have much more to add to Professor Turner’s remarks. I agree that funding, especially for an innovation that requires extra funding, is always going to be a challenge. I must admit I am also not an expert on procurement, and, when it comes to who would be in charge of new innovations at the Royal Free Trust, for example, I do not entirely know. To be fair, I have only been a consultant for a year, so I am probably not the best person to ask.
Lord Drayson: But as far as you are aware there is not a transformation team in the Royal Free?
Dr Valerie Crolley: If there is, I do not know about it. I cannot say that there is not, but it is certainly nothing that I personally have come across, though, I must admit.
Lord Drayson: Is it clear to you, as a consultant in the Royal Free, who is responsible for deciding to adopt innovation that has gone well at the pilot stage?
Dr Valerie Crolley: Again, as far as I am aware there is not any overarching committee. It would be a decision between us as consultants in any specific tumour site or tumour group that we, as a group, are going to introduce something novel between ourselves. For example, something we have done is introduce the use of aspirin for patients with a mutation called PIK3CA in patients who have had their tumours fully resected and had post-surgery chemotherapy. There is some evidence that giving long-term aspirin improves outcome and that is something we have decided to do locally as the MDT. As far as I am aware, that has not come from above, because aspirin is very cheap and very easy to prescribe, but we made a decision in our MDT that that is how we are going to treat patients going forward.
Lord Drayson: How would that innovation be spread across other trusts?
Dr Valerie Crolley: That is something that has come from the results of a major phase 3 clinical trial. All the trusts that work with patients with colorectal cancer have the same ability to see the evidence. It is not something that is going to require extra funding for the NHS, so it really is a local decision as to whether we think that the evidence is strong enough to give it to our patients. As far as I am aware there is no national guidance about it, but we decided that we think the evidence is strong enough to do this. I am sure other trusts, departments and colorectal teams have decided to do something similar.
Q218 Lord Patel: Sorry for interjecting, but Lord Drayson’s question and Professor Turner’s answer have dug up an important issue for me. Having a transformation team that is responsible for making sure that all innovations are embedded in every hospital seems to be a good idea. I wonder if Professor Turner might answer the second step. We could recommend that transformation teams exist in major hospitals, and not just for cancer, for innovations to be embedded, but it is, has he said, much more difficult in district general hospitals. How could transformation teams work with district general hospitals? Do you think it could be done?
Professor Nick Turner: I wonder if a hub-and-spoke type model might be the model there. This is often how NHS trusts and foundation trusts have expanded. The Royal Free Trust is the trust for many of the hospitals in the region, and so one could imagine a hub-and-spoke model, where there is a hub based in the more specialist hospital, the Royal Free, that could also be tasked with thinking about how the transformation happens in the smaller district general hospitals.
I will just come back to one comment that Dr Crolley raised earlier, which was the adoption of innovations. She brought up the fantastic example of aspirin, which is incredibly simple. The guidance that we have in the NHS is adopted over very long timescales. NICE guidance on the management of breast cancer, for example, is perhaps revised every five years. I wonder if another consideration, perhaps aligned to the question, would be whether we could consider more rapid guidance around that particular example in deciding which of those relatively more simple changes should be adopted widely across the NHS, rather than waiting for the updates of national NICE guidance on the timescale they occur?
Lord Patel: The transformative could be not just hospital based, but could be established by, say, integrated care boards that are then responsible for every hospital, small and big, to have all innovations embedded in all hospitals responsible to that ICB.
Professor Nick Turner: I agree that could be a very effective alternative model. Further discussion would need to be had about that, and I am not a sufficient expert to be able to really contribute.
The Chair: Dr Crolley, does that make sense to you?
Dr Valerie Crolley: It does. As Professor Turner says, I work in a very much hub-and-spoke system, the Royal Free being the hub and North Middlesex being the spoke. It does work, in a way. I mentioned the Matterhorn protocol, for example. I must admit that the Royal Free is very quick at implementing new drug treatments, at least in Gi cancers, at a trust-wide level in GI cancers. As soon as this expanded access programme became available, for example, we were not the earliest—I think the Royal Marsden beat us to it—but we were one of the first hospitals to get access to it as part of the expanded access programme, so as a trust it was relatively easy to set up.
The issue was then getting it available at North Middlesex, which is where I actually see patients with oesophago-gastric cancer. Obviously, it was straightforward that, as a trust, we had it available, but that is no good if our local hospital does not have the drug available and set up. It took a lot of polite shoving—I will call it that—to get it available at North Middlesex in a timely manner. We basically used the big argument that you cannot have one drug protocol available at a hub that is not available at a spoke—we could not let that slide. So even though the team at North Middlesex are fantastic but very stretched, they were able to get it done, but it did take a lot of shoving to get it all sorted.
Professor Turner mentioned the length of time between NHS reviews of new treatment. What I forgot to mention in my introduction is that I also do a lot of research in biliary tract cancer: cancer of the bile ducts and the gallbladder. I do a lot of translational bioinformatics research. I would say that in five years in biliary tract cancer we have gone from first-line chemotherapy and second-line chemotherapy to first-line chemotherapy and immunotherapy, and at least four different types of targeted therapies. If you are reviewing the guidelines only every five years, you will miss massive changes in different tumour types. Things need to be updated perhaps a more frequently than they are.
The Chair: Who is responsible for those guidelines?
Dr Valerie Crolley: At the moment—and I can speak only for the biliary tract cancer community—we are lucky, in that we are quite a large international community, with the European Network for the Study of Cholangiocarcinoma being a big European network. We work closely together to run big clinical trials internationally and then try to ensure that the results and the outcomes of these end up in clinical practice as soon as possible.
It is still basically reliant on us to push these things through as interested teams of clinicians, and to say, look, there is a study that looks very positive that this could make a massive difference, albeit to an admittedly reasonably small number of patients. Then there is charity work. AMMF is huge in the cholangiocarcinoma world and has helped to lobby and push this through. But the onus is mostly on us to push these things through quickly.
Professor Nick Turner: I wanted to comment on the guidelines. These guidelines that are done by NICE are incredibly important. They capture how patients should be treated for each tumour type across the whole portfolio, from screening through to advanced cancer treatment, and what type of scans one should consider doing. Therefore, if this is advised by NICE it needs to be adopted by the whole community. It is fundamentally important. But because it covers everything so broadly and the guidelines are changed perhaps every five years, considering how important changes might be adopted into guidance in a cycle that is not on five years is perhaps what both Dr Crolley and I are talking about.
Q219 Lord Drayson: You may have heard that we had the chief executive of NICE giving evidence to the committee just before you. We asked whether NICE had sufficient resources to keep up with the speed of innovation in medical science and medical technology, and your view is clearly that it is not keeping up. If five years is not the right cycle time, what do you think would be an appropriate cycle time for NICE guidance to be updated? Is it one year or two years? Give us some sense as to how far off is it in keeping up with the speed of innovation?
Professor Nick Turner: I cannot give a single answer to the question. There is a role for having the whole guidance reviewed on a scale of a few years. But I would advocate for living updates to be able to happen more rapidly, in between the larger cycle where you update the whole guidance for the whole treatment pathway. It would be inefficient to try to update that very regularly. But the ability to update when specific innovations have occurred in between the larger cycles would be very welcome and would help be a spur for adopting those innovations around the country.
The Chair: Does that chime with you, Dr Crolley?
Dr Valerie Crolley: I agree. It would be a massive amount of work to update entire pathways on a very frequent basis, but perhaps an annual mini review of particular updates would be perfectly reasonable and would keep the whole pipeline much more up to date than it currently is.
Lord Drayson: That is very helpful.
Q220 Lord Winston: I should perhaps declare an interest. I was a trustee of ICRF and involved with the merger with Cancer Research UK. Another interest is that I was research director at Hammersmith Hospital and had control of a budget of about £50 million at that time.
Do you not think that having a research director in a university hospital, such as the Royal Free or North Middlesex, would be a huge advantage to get some of the collaboration that you are talking about? We found it made a massive difference when we started to raise money for trials, for example. It seemed to be quite novel at the time. You have a medical director, why not a research director as well?
Dr Valerie Crolley: That would be a good idea to help bring research money into the trust and free up research funding so that you can get more clinicians to get funded research time. A massive issue at the moment is to get clinicians time to do research. Unless you happen to have an academic job, it is almost impossible to get time in your timetable and your paid rota to do any research. To have someone bring in the funding to allow that to happen would make a massive difference to us.
Lord Winston: Professor Turner, do you have anything to add to that?
Professor Nick Turner: Many trusts do have research directors, but maybe the question is more about empowering them to be able to drive forward change, if I heard the question correctly.
Lord Winston: That was exactly the question. Given the amount of research that is going on in the National Health Service, should it not be routine to have a research director in an NHS trust?
Professor Nick Turner: I agree completely. Part of the growth agenda is a 150-day target for getting trials open, which is to facilitate the driving forward of research, and exactly what you advocate for would be really useful in doing that.
Lord Winston: Would you go as far as to say that it might be a recommendation that this committee should consider when it reports to the Government?
Professor Nick Turner: I would imagine so, yes.
Dr Valerie Crolley: I agree.
Lord Winston: We have perhaps asked the questions in an order we did not really expect. One interesting issue is that working in a National Health Service trust that is predominantly a district general hospital, if you will, in many ways is totally different from being in a specialist hospital like the Hammersmith or the Royal Marsden. It seems to me that there are massive pressures in making connections between your oncological needs and the needs which go on in the general practice in a hospital. For example you may want to start chemotherapy for somebody, but there is no surgeon available to do the preliminary need, which is to make certain that you have things in the right situation.
Do you think that, in a broad sense, one of the problems in district general hospitals is that the massive amount of work and the huge variation in what you are responsible for as a hospital trust has a negative impact on getting rapid action in patients who have aggressive cancers, for example?
Dr Valerie Crolley: Working at a hospital such as the North Middlesex, which, as you said, is not a cancer-specific hospital, these days you cannot take oncology as a completely separate system on its own. Oncology patients require regular input from surgeons, or, in my case, gastroenterologists and hepatologists. There are other specialties who are always going to need to be involved in our patient care, so it is not enough just to say that we put a lot of money into the oncology service.
For example, if I have a patient who needs a biliary stent—quite common in patients I treat with cholangiocarcinoma—and they to wait one or two weeks for that, that is then going to delay the chemotherapy and treatment they get, and it is all going to cascade downwards from there. You need to take a holistic picture; you cannot just improve one isolated service at a time if you want to improve outcomes for patients overall.
I used to work at Bart’s, which is similar to the Royal Marsden, if not more extreme, in that there are basically only cancer services and cardiac services. If we wanted someone to get an endoscope, they had to physically go over to the Royal Free Hospital, which, if you know your geography, is a significant distance away. We had to take that into account when we were treating our patients and consider how we were going to get patients well enough to go over and come back for various investigations. You are right. You cannot take oncology just as oncology; you have to think of the bigger picture and related sub-specialties as well.
Q221 Lord Winston: One of the issues that we tend to forget is that there is such a thing as multi-morbidity, and in fact we see this particularly with the ageing patient. How does that work in your two trusts? I would be interested to hear how you manage that at the Royal Marsden, where you have people who may have morbidity which is associated but not causing the cancer.
Professor Nick Turner: I will come in on the first question, Lord Winston, before coming back to that one.
It is the cancer alliances that hold a lot of what you referred to, which is co-ordinating cancer pathways in a region. They have a very important role for cancer and working out how that role comes in other diseases is a very important question. The local cancer alliance in west London is Royal Marsden Partners and it works very well. We increasingly work with them on the challenge of hospital to community and how we can move work out of the hospital into the community in the future. They are ultimately responsible for cancer, in co-ordinating some aspects of the cancer pathway across the whole network, including the district general hospitals.
Multi-morbidity is a really increasingly important area. It is one where, as a specialist cancer hospital, the Royal Marsden is not ideally placed. In London, this is going to be a major focus of the Applied Research Consortium, and we will work very strongly with them. Locally we work a lot with Imperial, and the people at Imperial are very interested in multi-morbidity. This is going to be an increasingly important area for research.
If we are screening for cancer, we should increasingly be screening at the same time for lots of other diseases where early interventions are going to matter. Your question is an important one about how we move from disease silos to thinking more broadly for the future.
Dr Valerie Crolley: Multi-morbidity is definitely something that is becoming more and more of an issue. At the Royal Free Hospital, we cannot quite say that our average patient is over 80, but I imagine it is not far off, if you look at our patient cohort. We have patients in their 90s who are well enough that we are giving systemic anti-cancer therapy to, so we have to think about this.
In a way, we are also somewhat victims of our own success. It is not unusual to have patients who have had previous cancers who then do well and then develop another cancer, five to 10 years later, or even another cancer after that. We have several patients who have more than one cancer active at the same time; for example, to have colorectal cancer and prostate cancer is absolutely not unheard of. As more people are surviving cardiovascular illnesses and diabetic complications, they are living longer, and these patients are more likely to develop cancers. We have to take that into consideration when we have perhaps potentially cardiotoxic drugs—which is a common theme in breast cancer and colorectal cancer.
Clinical trials are getting a bit better at this, but all clinical trials have very strict inclusion and exclusion criteria: what comorbidities you can and cannot have to be on a major clinical trial. That generally excludes quite a few patients you would see in the wild, as it were, when drugs become available to the general public. That is becoming more and more of an issue, and that is why it is particularly important to have real-world data on new clinical drugs and interventions. When you are actually using this drug on a patient cohort that you see day-to-day, are you getting the same outcomes on perhaps less fit patients than you are on the slightly more selected and curated clinical trial cohort?
Q222 Lord Verjee: The inquiry has looked extensively at personalised or genomic medicine and AI as two areas where the UK could excel at innovation, in line with the Government’s ambitions outlined in their strategies, such as the 10-year health plan for England. Could you give us your views on both personalised medicine and AI for healthcare? What is their potential and what might limit their adoption? Dr Crolley.
Dr Valerie Crolley: That is a big question.
Lord Verjee: It is.
Dr Valerie Crolley: Maybe I will break it down into two sections. Personalised medicine, especially in oncology, is becoming more and more of a thing, and that is completely unavoidable. We have already gone from different tumour types needing different treatments to then different sub-types of different tumours needing different treatments. We are now at the stage where cancers with specific mutations require different treatments. For example, if a patient of mine presents with colorectal cancer that is incurable by surgery, I need to know up front whether they have a mutation in the gene called KRAS. If they do, I give them chemotherapy with one specific targeted drug; if they do not, I give them chemotherapy with a different targeted drug. That is something I need to know up front for an individual patient. There are more and more targets and more and more targeted therapy becoming available.
In my opinion, the next step, beyond finding new drug targets, is finding out why drugs do not work in patients. With primary treatment failure, where you give a patient a targeted drug and it does nothing, why, in that patient, did that drug not work? They have the mutation which the drug targets, but there is no effect. Then, later down the pathway, if this drug stops working in the future—perhaps a patient responds well to a drug and then six or 12 months later it stops working—what has changed in that patient’s tumour to make that drug stop working? Does this now mean that a different targeted drug might work better? If you change drugs and treatment, maybe the tumour will change again and go back to its original type, and maybe that original drug might work again. Being able to track different mutations in individual patients, and being able to track a wider variety of mutations in individual patients, is something that we are going to have to use more commonly.
We are already expanding the way that we are doing genetic testing. We used to do PCR individual gene tests for, say, three or four genes. Now, we are using much bigger panels of next generation sequencing, where many more genes—20 or 40—are detected at once. We might not, as clinicians, get the reports of all that, but that information is becoming more and more available.
A drug may not be available when the patient is initially diagnosed but becomes available a couple of years later. If you have not done the test for that drug at the beginning, you are going to have to do another biopsy and go through the whole testing process again. That takes a lot of time, effort and energy. If you do a wide panel at the beginning, that is a lot easier and more straightforward. You might then go into circulating DNA testing as patients progress their treatment, to find out what new mutations are being gained and lost, which might help you guide treatments on an individual basis. That is where oncology is heading.
Lord Verjee: Thank you. I know these are big questions, but what about AI adoption in the NHS?
Dr Valerie Crolley: Oh boy. I can think of perhaps three areas where AI adoption might make a big difference. The first is relatively straightforward, and that is AI scribing. A lot of my time in the clinic is spent seeing and speaking to patients and then writing notes afterwards. In the Royal Free Hospital, I am very lucky in that I have to document only once. I generate a letter and type out the information; it is on the electronic system and that letter is then automatically sent to the patient. So one documentation. At the North Middlesex Hospital, I have to document and duplicate. I have to document on our electronic patient system and then—luckily I have access to typing—re-document in a typing manner on to a separate system that then generates a letter to go out to the patient and is also documented in the patient notes. So two levels of documentation.
At my previous trust, where I worked as a registrar, in order to generate a letter I would have to document it on the electronic patient system, so there would be documentation of what I had done, and I would then have to verbally dictate a letter. That would then go off somewhere and, a few weeks later, I would get back a dictated letter that may or may not be accurate, depending on who did the dictation, sometimes rewrite said letter and then get that sent off to the patient and the GP. That could take weeks to months, depending on time.
I know there are some electronic dictation systems becoming available. I do not have access to them, but I know one of my colleagues does, and some of my colleagues at a different hospital do. But, at the moment, they are more text to speech rather than actual intelligence. What would be more helpful would be something that could, for example, automatically pull on to the notes the most recent CT scan report and pull on to the letter the histology report, without me having to look it up and look back and retype every time. That could filter out general rapport conversations— “How are you?”, “How was the holiday?”—that perhaps do not need to go in the letter, but information on diagnosis and treatment should. So we need a bit more intelligence and widespread documentation for clinics, ward rounds and discharge summaries, which is a big use of resident doctor’s time.
Another area for AI would be clinical trials and recruiting to clinical trials. Different hospitals tend to have slightly different clinical trials open for slightly different patient sub-groups or slightly different targeted treatments. If I have a patient who turns up in my clinic and I want to know what trials might be available, say, in London, apps are being developed for this but, at the moment, there is no single place that I can say, “What studies are open for this specific tumour type with this specific mutation?” There is no one place I can easily look up and find this information.
The way that we currently do this is by a UK-wide WhatsApp group, which is not the most efficient use of being able to do this. It would be great to have a database—and this is a problem, as someone would need to keep it up to date—where you could put in the information that you have a patient with this type of tumour, this mutation and these comorbidities, and ask what trials might be available to this patient. Even better would be something that could pull that automatically from electronic patient records—you would put in this information and something would ping to say, hey, UCLH has a trial for this patient, you should contact these people and consider recruiting to this study AI detection of clinical trial availability and recruitment would be massive.
One more point—this is something that someone brought up at a conference I was at the other week—would be virtual control groups for clinical trials. There are different phases of clinical trials, and the biggest, longes and most expensive phase is the phase 3 clinical trial. Basically, is this intervention that you know works from a positive phase 2 trial better than what we are currently doing? Better could mean extended life, less toxic or cheaper, but better than what we are doing.
At the moment, the gold standard would be to take two ideally identical patient groups, give half of them the intervention and for half of them do what you normally do. That requires very large numbers of patients—500,000, 600,000 or 700,000 easily, depending on the magnitude of change statistically you are looking at. It can be very difficult to recruit that number of patients, especially in something such as biliary tract cancer, which is relatively uncommon. If you are looking at a relatively uncommon mutation, just finding that number of patients is very difficult. Telling a patient in clinic, “I have this potentially fantastic new drug, but there is a 50% chance you are not getting it”, does not really go down well when you are trying to consent people—they get very annoyed with you at that.
The idea is that, instead of needing to recruit two large cohorts of patients, you would run only a phase 2 study, or recruit your new diagnostic interest and, instead of recruiting a direct comparison, recruit a virtual cohort of patients who have been treated with the current standard of care and use that as a comparison arm rather than recruiting a whole new comparison arm. That is obviously going to require a lot of statistical analysis to get into actual practice, but potentially that could make phase 3 studies a lot cheaper and easier to run.
Professor Nick Turner: I want to particularly touch on AI because, in many ways, the NHS has been leading on the adoption of genomic medicine into a healthcare system through Genomics England, the 100,000 Genome Project and the setting up of genomic laboratory hubs. We are very well placed for genomic personalised medicine. We are substantially less so in thinking about the future adoption of AI. Dr Crolley very eloquently talked about single instances where we might be able to use AI, but, especially as we look at the future of agentic AI coming in, we are not well placed.
The IT infrastructure is there in specialist centres such as the Marsden or the Royal Free, but a lot less so when we think of district general hospitals and smaller foundation trusts. You then have to consider how you are going to bring access to the kind of GPUs that are required to run these more advanced AI systems, and how you will safely adopt AI. These are areas that we are not strong in, across the country. It is an extremely important aspiration, but I see substantial challenges that will need thinking at the sort of innovation level we did in personalised medicine 10 years ago in the NHS. We have a real need for consideration of innovation here.
The Chair: Lord Patel, do you want to come in? We are running a bit short of time.
Lord Patel: I will come in after Lord Verjee finishes.
Lord Verjee: That is great. It is a big question and I appreciate your answers.
Q223 Lord Patel: I go back to what Professor Turner just said about implementation for not just generic AI but more specialised AI. Dr Crolley also commented on research issues and data research. Do you think the NHS should therefore work towards producing what some people might call sovereign AI for the NHS? That would then accommodate all the issues that you both mentioned, not just clinical issues but managerial and research issues.
Professor Nick Turner: That is an excellent and interesting question. Developing it entirely by ourselves as the NHS is perhaps unlikely to be the right model, given the scale of investment that is going into this in the private sector. But looking at how we could do something similar to what we did with genomic medicine would be really interesting.
Can we partner and use the organisation of the NHS to look at how we pilot and implement this in a healthcare system? That is something we are ideally well-placed to do, as Genomics England did and as setting up the genomic laboratory hubs did in personalised genomic medicine. Those are the real opportunities that we have, as the NHS.
Dr Valerie Crolley: I agree. In an ideal world, having a bespoke NHS AI would be fantastic, but, in reality, we still have trusts using paper notes. We do not necessarily have enough computers for everyone who needs them on a ward to be using them all at the same time, so there are significant barriers before we even get to something of that scale. But I agree that having something bespoke, perhaps developed in the private system but set up for the NHS, would be a fantastic idea, if we were to get to that stage.
The Chair: Lord Ranger has some questions related to this, but before we do that, Lord Drayson, do you want to come in?
Lord Drayson: Professor Turner, it was really helpful having that comparison with genomics. Of course, genomics is a life-sciences-specific technology and AI is a more general technology. If I remember correctly, the genomics revolution, going back 10 years, was championed by a small number of academic and medical leaders who were pioneering the space. Are there such academic leaders recognised within the community in the AI space?
Professor Nick Turner: Oh, there definitely are. In various centres across the country, we have real leaders in the application of AI into healthcare. If I have understood the question, it is about harnessing their expertise to identify the best way forward to find the answer to the previous question of whether the NHS should be trying to develop its own AI, or whether the scale of investment in general AI companies is such that we should be looking to partner with and adapt those in the best way for the NHS, across healthcare systems.
I feel that we are leading on the research side of this. I will not pick out specific examples of names, but we really have the opportunity to look at how we harness the expertise we have going forwards.
Dr Valerie Crolley: I agree. There are definitely some leading names who are very keen on pushing this forward and, even at not such a big-name level, plenty of on-the-ground clinicians who would be very interested in helping move this forward as well.
The Chair: Lord Ranger, we have covered quite a lot on IT, but you may have some more questions.
Q224 Lord Ranger of Northwood: Dr Crolley and Professor Turner, thank you very much. I believe you would probably be some of those people on the ground who would take part in helping shape what might come from the answers you have thoroughly given us.
We have discussed a bit the barriers to adoption, and things that have come up include the existing IT infrastructure, how data is spread across the organisational structure of the NHS and the use of compute. We have touched on specialists and people within the NHS who are doing great work, but how do you view the support that the NHS workforce is getting in adopting innovation that comes in? We hear a lot about the challenge of adoption. Dr Crolley, you mentioned that your usage of new technology can be cumbersome and clunky in how it comes in. Where does that support come from, and how can that be improved?
I will add another point. We have not really spoken about the role of the private sector here, whether that is the big firms or SMEs. How do you see those playing into the work that can be done to help support the delivery of this type of innovation, particularly around AI?
Professor Nick Turner: Thank you for the question. The answer I would give about the challenges can be very well illustrated by new cancer drugs that are approved by NICE. There are pockets of the country where they are then adopted very quickly and pockets where they are adopted much less quickly. Those are often in sites where an oncologist may visit once or twice a week, for example, and adopting new therapies or innovations that might require some change in how you deliver healthcare locally are then really difficult to take forward. If you have a new therapy that causes specific side effects that need the adoption of new working practices to manage those side effects, that can be a real barrier to adoption of that new therapy.
Some thinking about how to support those changes locally is what is needed to get that innovation across the country. That individual consultant is often working at absolute capacity on their clinical work and they just do not have the physical time to be able to drive forward the change that would be required to deliver that therapy locally. That is definitely a pathway challenge to adoption of innovations in the first part of your question.
Other than giving generic answers, I am not well placed to answer the second part of your question on the role of the private sector in adopting AI or innovations, other than to say that empowering the private sector to do this in the right way is very important.
Dr Valerie Crolley: I agree with Professor Turner. Just because something is available on NICE does not necessarily mean it is available locally.
For example, last year, I had a lady with a cholangiocarcinoma—cancer of the bile ducts—and we had to re-biopsy and re-send through Genomics England, but found that she had a particular alteration called an FGFR2 fusion. There was previously a drug licensed for this—this was in April last year—and a second drug had been licensed in September the year before that was basically better than the initial drug. We had found the patient, great, and found the mutation of interest, fantastic, but the problem was that the drug was not available at my trust. No one had needed to use it so no one had set it up. No one had access to it and no one had brought it in. I just could not wait that long to treat the patient. It had already taken a long time to get her diagnosed with this mutation, so I had to give her a drug that was technically less effective than the best effective drug available, and that had been available for some time, simply because no one had the time to set up a drug that was not immediately going to be used.
As I said at the beginning, there is a lack of time to be able to bring these things in before they are needed. People are trying to keep their heads above water and keep up with the most up-to-date things that are being used, but if you then find something that is more rare or unusual and find you need to use it, everyone is scrambling in the background to get things ready in time.
When it comes to the private work, I am unfortunately far too junior to be able to do any private work, so I cannot really comment on that. I am sorry.
Lord Ranger of Northwood: Dr Crolley, thank you for that example but it immediately raises the question of how you would flag a potential workaround to get that drug. Who is looking at the challenge of those processes that would be potentially blocking the use of the drug? Where would that sit?
Dr Valerie Crolley: This is something where perhaps a research director or a specific team, for example, would try to stay up to date with new drugs becoming available at NICE, and then make them at least potentially available at the trust when they are available at NICE, rather than there needing to be a direct demand from clinicians.
At the moment, or at least this is how my trust works, there needs to be an immediate demand from a clinician to get things rolling and moving and make something directly available. If you have a drug that perhaps is very important but not used that often, you may have a patient who comes up who needs that drug and who cannot wait 90 days for it to become available because that pathway from NICE approval to adoption has not been kick-started yet.
Lord Ranger of Northwood: Thank you very much. That is something we should look at.
Q225 Lord Willis of Knaresborough: We want to understand not only the barriers that Lord Ranger and others mentioned but what actually works. I wonder if each of you could tell us about a case where adoption succeeded, and explain what made the difference. Was it down to particular people, particular funding, programmes, particular structures within the NHS, particular networks, or something that could be replicated? Which areas of the innovation ecosystem would you point to as working well? We would like to put those ideas in our final report.
The Chair: You have answered some of Lord Willis’s questions, but is there anything else you want to add?
Dr Valerie Crolley: I have already mentioned Matterhorn and the addition of immunotherapy to perioperative chemotherapy for gastric cancer becoming available quite quickly. That has been a massive benefit in our world.
The other thing I have mentioned is the biliary tract community as a whole, and the European community, and our ability to push things forward through that combination. Those would be my best two examples, to be honest.
Professor Nick Turner: Once something is approved by NICE, it is about thinking about the challenges in adopting that into the healthcare system and what the fixes to those challenges are. Sometimes, it falls upon the pharmaceutical company to work out what the solution to those challenges might be. It would be very useful to think about a process that would think about those challenges and then communicate to the trust the best way to go about solving them.
Lord Patel: Before I ask the main question, Dr Crolley gave an example about identifying the mutation and there being a drug that is effective but is not yet approved by NICE and therefore is not available. Is it not true that you can make a request through your trust, and it is then up to the trust to have that drug available to the patient in rapid time? Is that not correct?
Dr Valerie Crolley: Sometimes, yes. If it is a single drug that is used for other indications that we know well and have direct ability to stock, that can happen quite quickly. For example, with Matterhorn, the immunotherapy in question is something we were using in lung cancer. We know the drug and we have it available, so that was very easy to bring in.
That does not always work. Last summer, there was a different clinical trial for colorectal cancer called BREAKWATER, for patients with a specific mutation in a gene called BRAF V600E. We can give BRAF-targeted drugs in the second line, and the idea with BREAKWATER was to bring this into the first line.
We had the results of this study available last summer, so we know that chemotherapy plus BRAF targeting and EGFR targeting drugs as a combination works well in the first line. This probably should be what we are doing. We do not have an expanded access programme available because, as well as the chemotherapy, it involves two targeted drugs from two different companies, and the two companies cannot quite agree with each other to make an expanded access scheme available. It has not yet gone through NICE approval either. So despite the fact that I have clinical evidence showing that, for these mutated patients, I should be giving this combination up front, I cannot do it, and I cannot get expanded access either. So it does not always work.
Professor Nick Turner: Until the drug is MHRA approved, it is essentially very difficult indeed. Fostering early access to medicine schemes is the best way to make this available until NICE has considered the drug scheme. That is one area where I would advocate for looking to foster the availability of medicines.
Q226 Lord Patel: That leads me on to my key question, which is focused on personalised medicine. Our inquiry focus is on AI, genomics and personalised medicine. We are looking to see what recommendations we can possibly make that are really strong to drive the agenda of AI, genomics and personalised medicine throughout the NHS.
In the very helpful discussion today, you have already thrown up two very important issues: the transformation team and the living updates for guidelines rather than a five-year wait. We also had Lord Winston’s question about a research director. Those are three good, important comments. I am seeking to hear from each of you three other important comments in the areas of AI, genomics and personalised medicine that may form the basis of our recommendation. I will start with you, Dr Crolley.
Dr Valerie Crolley: When it comes to genomics, we are still using sometimes quite limited genetic panel. In some tumour types, we are looking at only a couple of genes at a time. That becomes problematic, say, a few years later, when a new drug becomes available and we never actually looked at that gene the first time around.
We need to move to larger panels or something like whole exome sequencing and looking at more genes at a time. As we learn which genes are and are not important—not just genes of interest but other genes that affect genes of interest—and that knowledge becomes more widespread, we need to be looking for those at the outset, so that that information is available when it becomes clinically relevant.
I have already mentioned a couple of areas where I think AI could specifically become quite useful. Implementing those and ideas like those would make a big difference as well. Those are a few things I can think of that have not already been covered.
Professor Nick Turner: I am sorry if some of these are a little repetitive. The three I would select would be how we consider the pathway to adopting innovations and how that is supported after NICE approval. That requires additional support and perhaps funding, to think about how innovations are adopted.
It is very important for us to consider and support how devices that have been initially developed on in-house exemption can be adopted more widely across the NHS. We talked about the big drop-off that can happen after pilot, when something has been done on in-house exemption, and how we can reduce the barriers to adopting those across the NHS, which can be very cost-effective.
My final one around genomic medicine is a real ambitious push to think about how this can improve screening and, ultimately, attempts to move into prevention. We have implemented genomic medicine in cancer, and very much in advanced cancer, but how can we shift that ambition to improving screening for cancer and then onwards into identifying people at risk for prevention. That is the next phase of where we need to advocate that genomic medicine goes in cancer.
The Chair: Dr Crolley and Professor Turner, you have been incredibly informative. Thank you very much indeed for coming to give evidence; we appreciate it very much. Many thanks.
