cracking the code: delivering a world first in genomics ...€¦ · dr nirupa murugaesu -...

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Cracking the code: delivering a world first in genomics

Innovate Stage

6th September

1:15 PM - 2:15 PM

Speakers: Richard Erwin - Managing Director, Roche UK Professor Sir Malcolm Grant CBE - Chairman, NHS England

Professor Dame Sue Hill - Chief Scientific Officer, NHS England Professor John Mattick - CEO, Genomics England Dr Nirupa Murugaesu - Consultant in Medical Oncology, St George’s

Hospital Stage host: Dr Nikita Konani

Nikita:

Hello.

For those of you with me this afternoon we are moving on from something exciting and different to where we were.

It's called cracking the code.

We have a great panel for you, so I think we are going to enjoy this.

We know that it's the most disruptive healthcare out there, when we start thinking

about what that means, it's quite challenging, I am going to ask this group to take us through it and I will introduce our chair for the session and our first speaker.

Professor Malcolm Grant.

Malcolm:

Thank you very much, Niki, my role this afternoon is to introduce those who will be speaking to us, they are under 6-minute instructions so is will be rapid.

Then we will have detailed aspects of the new genomic medicine service.

We know that genomics is one of the big disruptive technologies that is going to

transform healthcare for the next 10 years and beyond. From October we are going to be rolling out the world's first national genomic medicine service.

It's going to build on the achievement of the 100,000 Genomes Project, it's great to have Professor John Mattick with us as the new CEO of Genomics England, it's been a ground-breaking partnership between Genomics England and NHS England.

mailto:[email protected]




So in this session we are going to focus on how we cement our partnerships.

I am going to introduce our first speaker, Professor Dame Sue Hill, who is the Chief Scientific Officer for NHS England and our lead on genomics.

Sue.

Sue:

Thank you very much, Sir Malcolm.

Good afternoon, everyone.

Welcome to this session as well from my perspective. So I am going to think about

the clinical context for delivering this new revolution in genomics within the NHS. Within the NHS we have a 60-year history of harnessing genomics and genetics which started before the start of the NHS.

It initially focussed on rare and inherited diseases and more recently moved into cancer.

Recognising that cancer is a strategic disease in itself.

The services in the NHS have been very rapid adopters of technology and most recently in the contribution to the 100,000 Genomes Project where 100,000

genomes will be sequenced from patients and their families with rare disease and with patients with cancer. And this NHS contribute to the 100,000 Genomes Project has established pathways for the implementation of genomic medicine in the NHS which provides a platform to incorporate genomics across clinical care and for the future and for now to deliver improved personalised treatments and interventions.

So recent years have seen a step change in the power and the potential of genomics.

This has been exemplified in the speed, the price and the availability of whole genome sequencing and that is essentially what the 100,000 Genomes Project has been about, it's about a proof of concept project to bring genome sequencing into

routine care to really understand how that technology can be utilised in the NHS for both clinical care purposes and through the partnership with Genomics England to drive the development and the curation of a national genomics resource for research

and for development. But this has only been possible by the step change in our computer power and also the data analyticals who analyse this enormous amount of data.

What we know is genomics is evolving rapidly, it's now tipping into a disruptive revolution and opening up a whole explosion of possibilities in terms of its application

in clinical care purposes and on the right-hand side of this slide I have illustrated that as we move forward we need to move from DNA into other elements that really help





us understand how DNA is translated for example into proteins that make up our body.

That is really important if we start, want to start to understand what drugs will be effective or not. But this is already delivering more precise diagnosis and

personalised care, but this will drive a new generation of predicative and preventative healthcare approaches and for example our ability to risk profile individuals within the NHS.

As Sir Malcolm said in his introduction, the NHS is already delivering the genomic

revolution, but from October, so within this financial year we will be rolling out the new NHS Genomic Medicine Service, this will be delivered in partnerships with Genomics England, particularly to access whole genome sequencing.

As part of the new NHS Genomic Medicine Service it will provide access to all genomic technologies and within this financial year we will be introducing whole

genome sequencing into routine care for some rare conditions and for cancers and over time this will be expanded.

In particular the improved access will drive better cancer diagnosis and better treatment as well as driving the innovation pathway from left to right as we annually evaluate all the emerging technologies.

Importantly every patient, as we go forward, will begin to receive the opportunity to participate in research and innovation, which will benefit individuals in terms of

opening up our clinical trial possibilities for them, but also through the partnership with industry, the potential for new treatments and innovations. But importantly by further building the research database it will build the evidence base for the NHS and

further drive the experience and so our whole future NHS Genomic Medicine Service is based around how we can drive up improved benefits over time for patients within the NHS.

So this National Genomic Data Resource will speed treatment development by partnering the NHS's real-world data that will be generated for interactions between

the NHS and between the genomic technology and all the other data that will be collected about their condition that has accumulated over their life course to enable us to collaborate with researchers and with industry.

So our challenge is how we make genomics the day-to-day business of the NHS.

Our current focus is on consolidating key services and the infrastructure to drive standardisation through driving standards and equality and also drive our financial sustainable position and the efficiency of those services. But what we have to do is establish and embed pathways to drive genomic mainstreaming in terms of the

application of those genomic technologies across all clinical specialities and from primary care right through to specialist and tertiary care.

What will enable this and make it part of the day-to-day business of the NHS will be the workforce developments that need to happen.





We need to look across a 10-20 year horizon and this is what the Topol Review is doing at the moment in terms of understanding how the total workforce has to change, not just the specialist workforce.

So, in concluding then, part of the work that we are focussing on at the moment is how we can deliver long-term value for NHS services.

The NHS long-term plan provides us with the opportunity to consider the genomics offer and how we can improve patient care, how we can drive a focus on predictive and preventative healthcare and how we can drive research and innovation by a

future driven by real world data. But importantly it will allow us to understand that the fundamental interrelationship with medicines in terms of how we optimise that 17 billion spend on medicines in the NHS, but also how we reduce our adverse drug interactions and also in our interactions with the pharmaceutical and industry

colleagues in understanding ideal cohorts for clinical effectiveness and for future discovery, given those cohort sighs will change as we start to characterise patients better.

So the future is here, the future is being supported and we will only see this growing over the next 5-10 years and we will be setting that out in the NHS long-term plan.

So thank you, Sir Malcolm.

Malcolm:

Thank you very much, Sue, for that exciting introduction and it really is an exciting time as we take forward this exciting new programme.

On that note, I would like to introduce Dr Nirupa Murugaesu, she is a consultant in medical oncology in St George's project and she is also Clinical Lead for Molecular Oncology, part of the 100,000 Genomes Project. Nirupa.

Nirupa:

Thank you.

So I will start by providing an overview of the clinical impact of the 5,700 reports that have been sent back to the NHS and highlight a specific case where participation in the project has had direct clinical impact for a patient.

So when we sequence these genomes we look at initially potentially actionable genes and there are 136, what this means is there a known molecular target in the gene and associated therapy.

If we look at that across the 5,700 tumours we can see that 50% of patients had a tumour with actionable mutations or potentially actionable mutations. The one in dark

blue indicates those were there is a known therapeutic target and a therapy and in light blue those were there is a potential gene and this means there is a tumour specific trial available for that patient and highlighted within the report.





So, but this is just really looking at single genes still and with the whole genome what we are able to do is look at, or within the report it's provided pangenomic markers. An example of this is tumour mutation burden.

Associated with this is a specific signature which indicates that there is it a problem

with the DNA or mismatch repair machinery, so if we look at, we get this information within the report from the whole genome sequence, so these two plots are called circus plots which many of you would have seen and go around from chromosome 1

all the way to chromosome 22 and X and Y. Those solid red and green bars indicate a large number of mutations that are present and this is actually a mismatch deficient tumour and you can look at the genomic landscape and see that the tumour associated or next to it looks very different which is one with normal mismatch repair.

So these are the sort of things we can begin to look at and within the report we

provide the circus plots but also quantify the number of mutations that are present.

In the dashed box are those tumours that have a high mutational burden and what

that means is these tumours are likely to be more immune-genic and they are the

tumours that are likely to respond better to immuno-therapies.

If we start to look at what trials are available, based on these biomarkers such as

tumour burden and abnormal mismatch repair, the green box indicates those

patients where a clinical trial would be available based on this biomarker. So, if we

come back to the specific case, this is a 42-year-old gentleman who presented with

weight loss and jaundice, went on to have an ultrasound which revealed a large liver

lesion, went on to have a sigmoid biopsy which confirmed a carcinoma.

He was found to have an MRAS mutation. He didn't within his diagnostic sample

have mismatched repair undertaken but had something sent off for the 100,000

Genomes Project. He went on to receive standard of care, combination

chemotherapy but unfortunately, he was found to have rising tumour marker.

At the same time his whole genome report was issued and there were a large

number of actionable mutations seen.

The ram mutation was confirmed.

The MS6 mutation was confirmed.

It could provide a risk and may explain why he presented at an early age and causes

a problem with the mis-match repair machinery and the plot there was consistent

with what we would expect.

This had clinical implications because as a result of this, he was referred to clinical

genetics.





This mutation was confirmed, validated and now his family have been tested. He

has children, so this has implications for them. Both in terms of testing but also for

subsequent and appropriate screening, but importantly for him, the red dashed line

up indicates where his tumour burden is, respective to other cancers that have been

sequenced.

Given he has a high burden, he is likely to respond to immunotherapy treatments

and has been referred for a trial.

So, in terms of considering the impact of whole genome sequencing, if you have a

small biopsy which is a few millimetres, part of it has to be sectioned for diagnosis, to

confirm the diagnosis, under the microscope by the pathologist, subsequently more

sections are taken to look at the protein and further sections are taken and DNA

taken to look at the three genes. And often, another test is undertaken to see

pharmacogenomic testing and essentially what the whole genome can you do is

provide all of that information, as well as the germline test within one single test and

so, hopefully this case highlights how participation in the project has directly

impacted on patient's clinical care. I would like to thank a number of people, so thank

you.

Malcolm:

Thank you.

It is wonderful to have a particular example of how it works in the case of an

individual patient.

So, thank you very much for explaining that.

We are very fortunate earlier this year to attract from Australia, as the new CEO of

Genomics England limited, Dr John Mattick, he was running an institute in Australia.

He has extensive expertise of genomics and is one of the world's leading genomic

scientists and has come to lead Genomics England, which is a private company but

owned entirely by the Department of Health and Social Care, so it is an intermediate

company between industry and the NHS. John.

John:

Thank you Sir Malcolm, great to be here, I want to talk about the future and start at

the destination and then work back to where we are now.





The destination is, and I think this is largely uncontroversial is that in the fullness of

time, the next ten years or beyond, patient genomic sequences will be standardly

incorporated not only into their medical records but into their healthcare.

We will be dealing with a situation where we will have information about people's not

only their acute conditions, in the sense of rare disease or cancer but also in terms of

their risk for cardiac, cardiovascular problems, cancer, etc and we will be moving

from a largely diagnostic and crisis managing health system to a largely prognostic

and health management health system which is going to issue challenges for us

all.

Now why whole genomic sequencing?

Well, there are two reasons, the first is that while 95%, give or take, of the

catastrophic mutations that occur in proteins that cause diseases like cystic fibrosis,

and hunting disorder, etc, occur in 1% of the genomic codes for proteins, the data is

clear that the 95% of the all variations in our genome that underpin our susceptibility

to complex diseases including cardiovascular risk, neuropsychiatric and neuro-

degenerative disorders and diabetes, etc, that occurs in the other 95% of the

genomes, and just using these sequences only gives you information on particular

conditions but not on the major diseases that affect our community and cause such

morbidity later in life.

The second reason, as Nirupa has explained, that you only have to do one test, one

test gives you all the information, and in the end, it won't matter why that test was

commissioned acutely, for a cancer or rare disease or whatever, that information can

then be mined for other sorts of information, including pharmacogenomic information

about adverse drug reactions and about the at least 30% of the prescriptions that are

useful because they metabolise so quickly you might as well not give them, as well

as incipient risk for cardiovascular disease, the latest figures from the Wellcome

Trust is showing on polygenic risk scores on non-coding genome we can predict risk

of heart disease and cardiovascular disorders higher than other familial disorders.

Where do we go from where we are?

Well, back to where we are now, I think I'm privileged to join this organisation, which

is leading the world because in the partnership with NHS England, this is the first

nation to actually imbue genomic testing more comprehensively as opposed to

traditional genetic testing into mainstream healthcare and we have to grow that.

The first cat off the rank here was rare diseases.





The thousands of mutations in proteins that cause serious, physical and or

intellectual disability and affect somewhere between 2 to 5% of all of our kids and in

fact, monogenic mutations will affect 10 to 12% at some point in our lives and cause

a hospitalisation event or the consequences of other diseases.

I think we are well on the way to enacting that into service and I think it'll become the

standard of care very quickly.

Giving that information back to the families, through their physicians, is

extraordinarily important because, it not only gives the families the answers they

desperately seek, it avoids, if done at the outset the diagnostic odyssey is traumatic,

in many cases visits to hundreds of specialists and 60% of that can be avoided by

whole genome sequencing.

It also gives information to treat options some of which are spectacular and if I had

more time I would show you pictures of twins who were in wheelchairs who couldn't

function properly when sequenced showed they had a metabolic disorder that

blocked the production of neurotransmitters and when that metabolic disorder was

fixed by dietary supplementation, these two individuals have graduated high school

and are running marathons and examples of little boys in intensive care who are

happy back at school because we understood the because of their problem.

That transforms families and the healthcare system because these individuals have

a lifetime cost in the order of at least £100,000 a year, often costs incurred outside

healthcare system in disability support, and lost income for parents.

So tremendous outcomes.

Cancer is the next important cat off the rank, and following on from Nirupa, within a

year of two it'll be standard to sequence the tumour because the data is that it is

transformational in terms of survival and outcomes and surprisingly cheaper than the

current standard of care, that's coming in from the United States. But we will segway

into using genomic information, irrespective of how it is collected as a standard part

of healthcare in terms of being able to avoid adverse drug reactions and avoiding

useless prescriptions, to advise patients they might be at elevated risk of

cardiovascular or cancer.

Don't worry, Sir but I do want you to turn up every six months for a check-up or take

a daily dose of statin that is will cost the NHS £12 a year.

A lot of those Damocles' sword sitting around genomes that could potentially hit us

later in life, can be mitigated by early warning.





I'm looking forward to the journey, we want to go from 100,000 genomes to the 55

million people in England and to the people across the nation. The question is what

we do with the next five years?

The answer is we are looking at that with the NHS at the moment and sequencing

other patient co-hearts with high medical value. People with chronic illness, for

example, and people at serious risk for cancer or heart disease because of family

history and perhaps trying a programme on replacing the Guthrie tests at birth with

more comprehensive tests on whole genome sequencing, thank you very much.

Malcolm:

Thank you very much.

This is all very exciting. And immensely progressive but industry has to take a step

because it can be a game changer for the pharmaceutical industry.

I'm delighted we have Richard Irwin, the general manager for Roche UK and I

though is passion ability about championing sustainable change in the industry. you

have a real challenge, Richard. We are giving you a real opportunity. Over to you.

Richard:

Good afternoon.

It's a great pleasure to join you and to try and give you our industry perspective on

where we go with personalised healthcare and what we truly believe to be innovative

healthcare.

Many of you will know the company Roche as being a leading provider of oncology

medicines worldwide you may not know we known a company called Flat Iron, a

leader for cancer patients in the US and a company called Foundation Medicine

which is one of the leading providers of next generation sequencing, in particular, in

the US for cancer patients. And what I'm here today to do is to talk to you about

predominantly collaboration and we have a strong collaboration with those two

companies, but our hope, through this week with Expo is to sell why we need

collaboration with the NHS, and why the NHS needs collaboration with us. And we

believe, together, we can make a massive difference to patients.

No matter how much we believe in our medicines, at this point in time, we believe

that actually we can change patient outcomes more with real world data and with

next generation sequencing, than we can with medicines and that's an incredible

admission for someone who works for the world's leading cancer medicine provider.





Please don't think we have any lack of belief in our future medicines but what I would

like to try and set out is how we expect to go about this, and make continual pleas for

collaboration with yourselves.

So, in terms of how cancer has worked in the past, and looking at the audience,

many of you are too young to realise this, but 30 years ago, cancer was easy. Every

single patient, whether it be with a breast tumour or a colorectal tumour was treated

in the same way.

What we have seen over the last 20 years was more and more go to personalised

medicines that looked at genetic mutations and overexpression of certain proteins

and for many of you in the clinical field, you will now be very, very used to HER-2

overexpression, EGR overexpression, alcove overexpression and know by looking at

those patients that have those overexpressions we can treat them with targeted

medicines and ensure you get both much higher response rates, much more durable

responses and actually avoid using medicines in those patients who are less likely to

respond. And that's been a major step forward in terms of our industry, but not alone

in collaboration with healthcare professionals and healthcare systems worldwide,

including the UK.

We stand at a unique point, hopefully in this country taking the lead - and I will come

back to talk about that in a couple of minutes, but we stand at a unique different point

in healthcare where we'll fundamental get to a situation where treatments will be

tailored for individual patients and their mutations. And you have seen some

announcements this week, but if we look at things like cancer vaccines for the future,

where you will take the patient's genetic profile, and make an individualised medicine

unique to that profile and treat them.

Our hope is that through doing this, you will lead to huge response rates in terms of

overall patient's see and efficacy but ideally extremely overall survival, I will not use

the C word but of course, cure will be the ultimate aim if we can ever get there and

it'll mark a step change and all of you, all of us will be touched by this change. But,

for us, it is all about patients and actionability.

We freely admit a lot about our collaboration with real world data and with genetic

profiling was first and foremost about enhancing our research and development and

that is the right thing to do, even though we are the number one R&D investor in our

sector, it is still right that we look at how we can be even more effective.But as we

move forward it is with patients at the centre, with, as I have said genomics testing,

next generation profiling and there will be multiple options within that so I am not

here to argue for only one, it will be about ensuring that every patient and world

leading hospitals and ultimately all hospitals are linked up so we have got genetic





profiling data, we have real world outcomes that we can track how those patients are

progressing and we can also track the toxicity for those patients.

When you combine that with health and enhanced pathology and again in

collaboration with healthcare systems we can change the world and give huge hope

to patients worldwide.

To finish, I just would say that our model and if you look at the left-hand side it is first

and foremost effective clinical trial participation and to give you an idea at this

moment in time we have about 11,000 patients on Roche clinical trials in the UK and

we only want to increase our commitment to that, but it is already the case that if

centres in any country want to be involved in phase 1, phase 2, or phase 3 research

it is now routine those patients will need to be genetically profiled and sequenced.

As we go around that will lead to much better diagnosis and actually ultimately better

prognosis, we believe and we have heard this, we can drive boast more effective

medicines but also less toxicities and we can drive improved access to therapies by

looking at real world data and fundamentally and eventually as an industry sector

implement outcome-based pricing where you only pay if a patient gets the sort of

response we would all hope for and then also we can monitor better the diseases

that these patients have.

This is not a dream, it is available right now, the two key points - it's about patients,

number one. Number two, nobody can do it alone, not big pharma, not the NHS, this

needs collaboration. I am not going to talk about the B word of Brexit, but through

industrial strategy the UK healthcare system in the UK has an opportunity to lead the

world in these things and I hope that we all take this as a prompt to take that, make a

massive difference to patients and have the UK leading the world. Thank you.

Malcolm:

So now we are going to have a few Q&As. I have the privilege of course of kicking

off. I want to pick up on Richard's presentation, really inspiring vision of where this might go.

We know that the pharmaceutical industrial industry has gone through a significant change from blockbuster drugs into the modern world.

How do you see that future that you describe affecting the economics of the pharmaceutical industry and if I may say the economics of our budget at NHS England?

Richard:





I think we should be really honest when we don't know things and we don't know the answer to that.

What we do know is that the days of medicines for mass populations are over, so if we look at cancer, the days when you are used in a broad type of tumour for all

patients will no longer occur. We are increasingly seeing our pipeline get very specific mutations, M track (?) Is a good example, we may only have a few hundred of those patients, and this is where we have to be really honest, we don't know how

we are going to basically test the whole UK population of patients with cancers and make sure we give them those tests of next generation sequencing, what we do know is if we do that, if we find patients that are mutated we know we will have more

effective medicines for patients with those mutations and I am not going to talk too much about cost effectiveness, but we do know where you got that much greater efficacy, these medicines will be better value for a country like the UK, so this is

again where we need collaboration in terms of working where the NHS on how that is going to work, but the future, if you look at pipelines of pharma companies is much more medicines, but for much, much less patients with very specific mutations.

Malcolm:


I will keep an eye out for hands in the audience.

They are going up, I am not going to carry on further.

Where are the microphones?

There is one over there. Several hands over there.

Could you please bring the microphone to the lady just there.


Could we observe the normal rule, please say who you are, where you are from and the question, please.

Floor:

Thanks very much for the fantastic presentations I am Ange Davis from the

University of Manchester, my interest is in educating healthcare scientists in Manchester.

As Sue will be well aware of, we have done fantastic work in this area over the last few years and also on the MSE and genomic medicine, my question is probably

directed to Sue which is where do you feel we are at in terms of workforce transformation and what is the kind of vision for realising this kind of revolution and transforming the workforce?

Sue:





Very good question. So that is the very question that the Topol Review and particularly the piece on genomics is looking at, but perhaps over a slightly longer

horizon given that what they are looking at in particular is how you influence prospective training pathways and for some, for doctors this can take 15 years.

In terms of the here and now, through the Health Education England Genomics Education Programme, you will be aware this has been targeting the workforce, segmented into three different areas, the first is the more general awareness-raising around the use of genomic information into clinical pathways.

The second is being very specific and you have already heard from Nirupa and also from Professor John Mattick that it's both important to develop the medical oncology and our surgical colleagues as it is other clinical specialities like cardiologists for example, that is the second tier, how start to embed it in specialities, but to date

where there have been genetic tests available, but they haven't always been utilised more fully to get the maximum potential for the patient. And the third area is to focus on that very specialist workforce, for example in clinical genetics or in bioinformatics as you have been leading in Manchester, that is the approach.

It's about delivering some just in time resources, some learning resources as well as having a framework for professionals in the NHS to access modules in MSC and genomic medicine, either for upskilling them or for giving them a qualification if they complete the whole framework.

I think there is a lot for us to do, but I think the workforce of the future will have to be

both agile and responsive and it won't just be for genomics it will be for many other areas such as the use of artificial intelligence and machine learning.

Malcolm:

We need many more graduates from your programme.

Floor:

Fantastic.

Thank, Sue, I feel personal quite passionate around and you touched on it is getting more genomics into the undergraduate curricula and hopefully that is something that will come out of the Topol Review.

Sue:

We are working on that, there are challenges with some of that, but let's say the

important thing is to recognise this field is moving at pace and what we wouldn't want to do is agree a curriculum that is out of date before it's implemented.

MALCOLM:

Gentleman there has the microphone over to you.





Floor:


My name is Parker Moss, I left the NHS as a CTO and I am now investing in health technology.

I was going to ask a similar question so I am going to have to switch questions but my first one is to Nirupa.

I would love to hear your views as an oncologist.

In a sense the two offerings from Genomics England and Roche are quite different and I am talking about cancer here, Genomics England you are looking at all 23,000 genes and I think the foundation one is looking at 300 and something genes but in

more than ten times the depth of coverage than Genomics England is looking at so I would love to know, they are two different approaches, which, as an oncologist do you think is most applicable to treatment of cancer?

That is my first question.

I have to ask as well, I would love, it's great to have you an stage, Richard, it's fantastic you are spending all of this cash on buying companies like Foundation and

developing this knowledge base in mutations and variants etc, do you think that data by you and your colleagues will be locked up in pharma companies or do you think there is a need for this data to move into the Commons so we can share knowledge between the biopharma industry players?

Malcolm:

Nirupa first.

Nirupa:

Thank you for that question.

It's an important question and one we are trying to address as part of the experimental arm within Genomics England, because ultimately we need to be making those cross comparisons, both within large panels, also comparing with whole exome, assessing what kind of depth is required to be accurately able to call,

specifically the example I gave which is of a wild-type mutation, so there is a number of those issues, I think also the other thing to be mindful is what are the new markers that are going to come on and what is the impact of having to adjust a panel and bolt

that on, because we know that that is not trivial either in terms of reestablishing, so these are the things that have been looked at in the research setting, but haven't had a formal comparison and that is one of our aims going forward.

The thing I want to just add is it's not just what panel and what depth, it's more important what happens upstream and that is how is the tissue handled in the first place as well because that will also impact.





Malcolm:

Richard around data.

Richard:

I am going to answer the first question as well, we should look at this as not being in

competition, what we all want is comprehensive profiling of patients and there will be multiple ways of doing this, all I would say is the key factor, we all know friends and family who are impacted by cancer, it's getting the results back quickly. You can't

wait for long periods, but anyway, as for the data sharing that is really straightforward.

There has to be data sharing and that is going to be both with patients, more specifically physician, but units that we work with there is no question about routine sharing of data, for instance what we will do in the UK is make sure that that data is

UK-based, so not based in San Francisco or whatever else, but I think we are working through the informatic,s challenges of this, but there must be sharing of data and everyone knows there is some sensitivities about moving data and therefore we

have to work with the UK and the same in every country to make sure that that data is hugely sensitive and kept in those countries but must be routinely shared.

Malcolm:

And also that the data is concentred for research purposes as well as clinical care. Do we have a microphone placed strategically.

Floor:

I work for a company who is a platform who work within the NHS and industry. My Professor is aimed at your, Professor John Mattick, you are mentioned you are aiming to get 55 million patients who have provided their genome sequence.

Genomic data is obviously highly sensitive so in a patient with advanced cancer or needs to have that profiling as an immediate need, I understand that, but for those

who are healthy or those who aren't in the healthcare system what is the proposition for them?

How are you going to get them to consent to share that data? What is the value proposition for a healthy population to have that genome sequence.

John:

Another very good question.

I think the journey ahead is to progressively introduce genomic information into the

healthcare setting, so that you are progressively showing value to the health system,

the health professionals, I won't call them patients, the people of the nation.





At the moment the approach to medicine is turn up and you are sick already for

some reason. What we can do now with genomic information is look under the hood

and anticipate risk and mitigate that risk in almost every circumstance.

So once the general practitioners, I think they are key to this, start to see the value of

having an information available as a decision support mechanism at the point of care

it will start to be used more routinely in healthcare for the patients. For example 7%

or more of the hospital admissions in this nation which is similar in Europe and

across the world are due to adverse drug reactions.

They can largely be avoided and in fact figures out of Liverpool are showing if we

had the whole nation sequenced we could use that information to avoid those

adverse drug reactions at the point of prescription that would save the NHS close to

£500 million a year.

So that avoids those problems those people. We can advise people of future risks or

current conditions, if you have familial hypercholesterolemia, 4 out of 5 are

undiagnosed, don't worry I want you to take one of these a day and you will be fine.

Look at this way if you don't do that you will have a 50% chance of having a heart

attack in your 50s.

So you start to explain the value proposition of people managing their own health

with their physician and the healthcare system.

This is not going to be done overnight, so we focus on areas of need and strategic

value as we go over the next decade or two, towards that objective. But I would just

make the assertion, because it really is unchallenged, although how to get there is

another issue, is that in the future world of precision medicines there will be two sorts

of information, baseline genomic information, under the hood and fragility, it'll tell you

which you drugs you should and shouldn't take and tell you what infections you are

likely to get if exposed and the real-time information largely coming out of the smart

devices, real-time physiological information, you putted those two things together

and you can imagine a future healthcare interaction where the GP gets an alert and

says - this patient is showing an elevation in blood pressure rise, which would be the

first warning size of this thing that the genomic analysis says they are at risk for, so

you might want to bring them in to address that.

You have to look at that proposition but first things first, let's deal with the most

pressing problems and take the public with us as we go.

The security issue, I will just say, we are fierce on, that our data is online, you have

to bring the queries to the data, we think it is a very secure system.





So, there are various levels of security in any data system, one is how the data is

fragmented and deidentified but the big one is access control.

I think I would be fair in saying that Genomics England is state-of-the-art in that

respect, because we, above all, as our chairman said, we cannot afford to lose the

trust of the public.

Malcolm:

Can I ask Sue about consenting within the NHS for genomics?

Sue:

At the moment within the NHS we don't necessarily consent all patients for a

genomic test.

That's within the NHS per se, rather than in their contribution as participants to

100,000 Genomes Project, but as we roll forward with the NHS Genomic Medicine

Service, we will introduce a new consent model, both consent for the use of data for

their clinical care and I think Richard made a really important point, which is, in terms

of getting enhanced information to drive a clinical decision, some of that data may

need to be shared to ensure that we move away from an where there is one clinical

decision point, to something informed by a bigger data set.

The second is offering every patient the opportunity to participate in research. And

that's important. And, so, that will be the future offer, both the offer for their clinical

care, and to enhance that, and research and innovation.

I wonder Malcolm if I may say a word about where we are in terms of predictive and

preventative health care, in terms of the whole genome sequence results being

returned in the 100,000 Genomes Project, we haven't had the opportunity to test

what are the additional or incidental findings that might drive that more risk-profile

approach and so our plan would be to introduce that, to understand what that means

in terms of the value proposition in health in a clearly evaluated way, so we can

make informed decisions about how we roll forward that approach within the NHS

and, in terms of what we are offering from October, there will be a more extensive

set of genomic tests and genomic technologies, up to the level of whole genomes,

but also a number of non-whole genome sequencing tests that will really drive

improvements, whether it's in cancer care or whether it's in our management of

where an inherited disease and some common diseases.

Malcolm:

Let's take another question.





Floor:

I'm a clinical programme director of one of the local genomic medical centres. My

question is - a lot of clinicians looking after cancer patients are not aware of our

genomic testing and those that are, don't have the commissioning currently to ensure

that we are able to embed this in their normal clinical practice. How do we make

sure commissioning becomes an enabler of this technology for our clinical users?

Malcolm:

For you, Sue.

Sue:

Thank you, Angela for that question.

You know, this is a complex issue and one that we are very aware of and that we are

working on at the moment.

I think having a national genomic test directory, for the first time, that sets out the

tests that should be available for all of our cancer patients, is a step in the right

direction.

The second is, as we look towards the future, is how can we in NHS England bring

all the levers we have got to bear to affect change and one will be through NHS

standard contracts, as we started to introduce with where providers should access

care through our genomic laboratory hubs and over time, it is what might we be able

to do, to look at how we unbundle tariffs, for example, or how we might introduce a

more centralised resource for testing, but none of that is, at the moment, there.

It's more work that needs to be done to determine this. And it will be something that

we are looking at in terms of the genomics offer as part of long-term plan.

Malcolm:

Thank you.

Gentleman at the front.

Floor:

I'm Tony Johnson, I'm a governor at Stockport Foundation Trust. I wanted inquire to

what extent the UK bio-bank plays a part in the provision of information that would

help this project?

Malcolm:





A very good question. John, I think for you.

John:

A terrific question.

We are very supportive of this, talking at the national genomics board, chaired by

Lord O'Shaughnessy, we are aware that we need to try to aggregate and integrate

all of the sequencing analysis across the country, this includes projects funded not

only by the UK bio-bank but by the Wellcome Trust and others.

At the moment, the situation is that if we do genome analysis for clinical purposes,

the patients, participants are offered us for consent to do research. We get double

value.

Clinical value now and in the future and also research value.

We are proposing and we have had a good reception so far, reciprocally, that studies

that are done at the UK bio-bank, primarily for research, the participants going

forward, we also ask if they would consent that that information be used in the right

circumstances for their clinical care, so we can actually get double value out of that

as well.

At the moment, the UK bio-bank has terrific research resource but those people are

going to have to be sequenced again as part of their clinical care, unless they are

consented in the beginning for that purpose. So, we are trying to move that along,

without wanting to trespass on the provenance of those agencies who use that for

whatever research purposes.

Malcolm:

Thank you.

I am, by coincidence a bio-bank subject.

I entered into that about 12 years ago.

I have not a clue what I consented to, given the lapse of time between now and then,

I look forward to learning more about it.

Thank you for the answer.

There was another hand up here.

Sorry, one there,





madam, please.

Then we will be drawing to a close.

Floor:

I'm from the PHG Foundation, policy unit about making science work for health. To

Professor Mattick, you mentioned the potential for whole genome sequences for new

borns as a potential to the new approach to the new born screening blood spot test.

I wondered if you had any sense of whether it would be confined for the indications

currently tested for or something you might expand to other indications as well?

John:

A good question.

I don't have a specific answer except to say yes.

There is no doubt probably at a generational level, this is the way that

comprehensive genomic information will be entered into healthcare. And not just in

this country but in others, every time I have talked about this, the first thing that

Prime Ministers or ministers for health say, they say we should sequence everybody

at birth.

I say that's true, we will get there but we have some soil to till first. So, first steps.

What we are proposing, is an experimental programme to look at the practicalities of

this.

We have been looking for volunteers but we will also be looking for areas where we

can actually get most value for doing so, rather than simply just doing it.

We have not worked through the filters that might be in place, it is a suggestion.

What we would like to be able to say and I'm not sure we can, it depends on cost

structures, that in five years' time, instead of the Guthrie test, which nearly every

parent consents to, that in five years' time, it'll be automatically whole genome

sequence and that will be the information that will be there to help that child through

their journey in life.

If I give you one quick example to show you the value of this, one of the most

common genetic disorders in our society is hemochromatosis. With fatigue and

lethargy.





We can actually tell with a new born, the mum will go to the primary care physician

and say - the baby looks beautiful but she has had blood iron overload, easy fixed, I

want you to bring her in for a treatment every six months and she will be a happy,

healthy and active little girl.

So, all that information will be available from birth to help parents and children to

grow up and navigate their health future in a far more informed way as we do at the

moment.

Sue:

Philippa, you will know, as many other people in the audience will, in this country,

any changes to the new-born screening programme has to go through the Screening

Committee and, therefore, any such change in terms of technology is also subject to

the same processes.

So, just so everyone is aware, there is a set of systems and processes laid down in

Public Health England for such changes.

John:

And there is a committee looking at this carefully established with us and the NHS.

And it includes representatives from across the system. Done properly.

Malcolm:

Time is drawing to a close.

I will ask any members of the panel what they disagree with from what everybody

else has said during the discussion?

If there are any final closing words they think we haven't covered.

Let's rapidly go along the line, Richard may we start with you?

Richard:

Who would I be to disagree with any of my esteemed colleagues on the panel. It is a

starting point of discussion with the NHS and offers huge hope for the future.

John:

I will disagree and agree with one thing.





I agree entirely that we need much more awareness in the medical fraternity and

during training about the importance of genetic information, whether it is in the renal

context or cardiovascular context, awareness needs to go up.

I'm not sure we need a lot of training in the bowels of this. It is just like getting a

pathologist report, a GP will get a genomic report and that will be top lined, this

individual probably has this disorder, recommend a blood test.

That's all they want.

I think we need an engine behind that has bio-mathematicians and analysts behind

it. I'm not suggesting every doctor needs to be a bio-mathematician. But at the point

of care, evidence-based.

Well curated, gold standard through NHS and Genomics England.

But we need to grow the bio-mathematicians, for that report to provide it to the GP.

John:

To provide that, yes, we do.

Malcolm:

Nirupa.

Nirupa:

From my involvement in the project, the main thing actually is, touching on Angela's

point, is to have that standardised care testing and processes available and you

actually realise what a disparity there is in terms of what testing is made available

and also, as the research and technology is evolving so rapidly, and it highlights that

we need to really think about and try and future plan, future-proof to what the

changes are likely to be, so that we can actually fully profile all cancer patients

upfront because, you know, I think many oncologists now, especially molecular

oncologists will see how this is beginning to impact on patient care.

Sue:

I certainly agree we have to enter new relationships both with researchers, but also

with industry and, particularly, industry and the pharmaceutical companies around

how we enter new relationships about drug pricing for the future with the access to

real world data and I couldn't resist saying, that Richard.





I think, Malcolm as you know only too well, as we look at the next five years and we

look at the investment strategy, as part of the ten-year plan, I think what is important

and what will drive how quickly we are able to offer whole genome sequencing will

be the price point, it is moment it is unaffordable and will break the bank.

That's part of our concerns for the future, what will we be able to deliver in terms of

improvements for patients, against the backdrop of what we can actually afford and

what is appropriate to deliver and what we can stop doing, because that is part of

what we have to consider in the NHS going forward, as

we adopt a more complex and comprehensive technology, what do we stop doing,

so that it makes it affordable and drives up enhanced benefits.

Malcolm:

Well thank you very much, Sue and on the last point, we know the technology is

constantly changing, Moor's Law has applied to sequencing in pretty sharp relief

over the period we have been involved in, we anticipate the price point of the

sequencing will continue to fall and become more mobile and portable but that's just

the beginning of the cost and the cost of curating the data and sending the samples,

etc, is going to continue to be a major sticking point.

But can I, on your behalf thank Richard, John, Nirupa, and Sue for a fascinating

insight into what is not just a potentially transformational technology but something

that is happening now and will drive through the NHS over the next few years.

Thank you all very much.

[APPLAUSE]


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