Behind the Genes

Dr Helen Hanson, Kelly Kohut, Rochelle Gold and Amanda Pichini: How are genetic tests transforming cancer prevention?

On today's episode, our guests will be discussing the CanGene-CanVar programme. Funded by Cancer Research UK, the 5-year programme aims to create an interface between NHS clinical care and research that will expand genetic testing access for those with inherited cancers.

Our host Amanda Pichini, Clinical Lead for Genetic Counselling at Genomics England, is joined by Dr Helen Hanson, Consultant in cancer genetics at the Peninsular Regional Genetic Service, Kelly Kohut, Lead Genetic Counsellor at the South West Thames Centre for Genomics, and Rochelle Gold, Patient Representative on the CanGene-Canvar research programme and co-founder of BRCA Journey.

 

"There is also the possibility of finding out genetic information that’s familial or inherited, which could mean that the information is not only important for the person who is being treated for cancer at the current time but also as a next step informing relatives that they might have a higher chance of getting cancers in the future due to a genetic variant..."

 

You can download the transcript or read it below.

Amanda: Hello and welcome to The G Word.  My name is Amanda Pichini and I’m the Clinical Lead for Genetic Counselling at Genomics England.  We know that cancer is a very common disease.  About one in two people will develop cancer at some point in their lifetime.  Cancer is a disease of the genome involving many changes to a person’s genome over time as well as other factors.  Only a small proportion of all cancers are inherited, but this can have a significant impact for those families who have a much higher risk of cancer and options to reduce their risk.   

Today I’m delighted to be joined by Dr Helen Hanson, Consultant Clinical Geneticist; Kelly Kohut, Consultant Genetic Counsellor; and Rochelle Gold, Patient Representative and co-founder of BRCA Journey.  We’ll be discussing the CanGene-CanVar programme which aims to link NHS clinical care and research to expand access to genetic testing and care for people with inherited cancers.  Welcome, Rochelle, Helen and Kelly to The G Word.  Thank you for joining me today.  Let’s start with some introductions.  Rochelle, over to you? 

Rochelle: Hi, everyone.  I’m Rochelle and I’m one of the Patient Reps on the CanGene-CanVar research programme.  I also co-founded an organisation called BRCA Journey that helps to raise awareness of the BRCA genetic mutation amongst both clinicians and the community, and also supports people who might be at risk of the mutation or who are thinking about testing, all the way through to maybe having preventative treatment or preventative surgery.  We support those with that decisions.  We’re not genetic counsellors but we do basically talk to people about our experience and knowledge that we have of what it’s like as a patient to be someone living with the mutation.   

Amanda: Thank you.  Could you briefly tell us what BRCA is and how you came to be a patient? 

Rochelle: BRCA is a genetic mutation that puts people at greater risk of breast and ovarian cancer.  My mum had the mutation, in fact she had two of the mutations which is apparently quite rare.  She passed away from breast cancer and just before she passed away I found out that I had the genetic mutation as well.  I personally have had preventative surgery and reconstruction to prevent myself from getting breast and ovarian cancer.  I got involved in being a patient rep so that I can advocate for people who may have the mutation, but also make sure that as many people as possible can be tested and be aware that they have the mutation and have that power to have the knowledge to be able to do something about it should they so wish. 

Amanda: Thank you so much for sharing that with us.  Kelly, over to you? 

Kelly: Hello, everyone.  I’m Kelly Kohut, I’m the Lead Consultant Genetic Counsellor at the South West Thames Centre for Genomics, which is based at St George’s Hospital in London.  For many years I’ve been working in clinical practice in genetic counselling, seeing patients and their families regarding personal or family history of cancer, offering genetic testing where that’s available, and then giving the results and helping to refer people on for surveillance programmes and to discuss risk reducing options, and also help a lot with communication within families, sharing the information from the genetic test results.   

For the past few years, I’ve also been doing my own research as part of the CanGene-CanVar programme, funded by the charity Cancer Research UK.  This has involved partnering directly with patients and other expert stakeholders to co-design a patient website to support decision-making around the genetic chances of getting cancer in families.    

Amanda: Thank you.  And Helen? 

Helen: Hi, everyone.  I’m Helen Hanson, I’m a Consultant in Cancer Genetics.  I’m based at the Peninsular Regional Genetic Service which is in Exeter.  In my clinical practice I see patients who either have a cancer diagnosis to consider whether they may have an inherited susceptibility or people who maybe have a family history of cancer to try and determine if they are at risk due to their family history.  Like Kelly and Rochelle I’ve also been involved in the CanGene-CanVar programme for the last four years.  I’ve been involved in work package three of the programme which is developing clinical guidelines with the patients who have an inherited predisposition to cancer.  I was also fortunate enough to be given some funding to carry on with this work beyond the programme in the new NIHR Exeter Biomedical Research Centre.   

Also, I’m currently chair of the UK Cancer Genetics Group, who has an aim of improving the management of patients who have an inherited predisposition to cancer.  It’s been really great to work on all these different things and try and bring things together to try and improve care for patients who do have rare inherited genetic conditions predisposing to cancer.  

Amanda: Fantastic.  Thanks, everyone.  Kelly, I wondered if you could start us off by just explaining a little bit more about how genetics and genomics is relevant to cancer.  Especially inherited cancers, why is this an important thing to talk about? 

Kelly: The availability of genetic testing has been increasing steadily over the years.  Currently from pretty much anyone who’s been diagnosed with cancer there should be some awareness around the possible benefit of knowing the genetics behind the development of that cancer and whether any genetic or genomic testing might help to choose more personalised treatments or surgical options for that cancer that’s been diagnosed.  There is also the possibility of finding out genetic information that’s familial or inherited, which could mean that the information is not only important for the person who is being treated for cancer at the current time but also as a next step informing relatives that they might have a higher chance of getting cancers in the future due to a genetic variant and that they could ask their GP for referral to genetics to be offered genetic testing and to find out about their chances of getting cancer and the choices for how to manage that.   

Amanda: Thank you.  There are clearly some important things that someone would do differently when they know they have an inherited cancer.  Helen, how can we make sure that clinicians and patients and families know what do to in these situations? 

Helen: Following on from Kelly explaining the amount of genetic testing we can offer has really increased over the last five to ten years and we’re not in a position to offer many more patients genetic testing, it’s important that we also consider what to do with that information when we discover somebody does have a pathogenic variant or a mutation in a cancer predisposition gene.  There are over 100 different cancer predisposition genes described and actually having a variant in one these genes is rare.  It’s difficult and like other conditions in medicine due to their rarity to really understand how best to manage these patients.  But what’s very important is that we try to understand how best we can help patients manage their cancer risk based on the lifetime risk of cancer and the particular cancers that they can develop and ensure that patients across the country are all being given the same advice, the same information about their cancer risks.   

Through the CanGene-CanVar programme we’ve had a whole work package which is devoted to clinical guideline development where we’ve looked at a number of these genes and looked at the evidence that is available in terms of cancer risks, the utility of surveillance or early detection of cancers in that condition, and also whether risk-reducing surgery could be offered.  Really try to bring together groups of experts to discuss the evidence because for some genes it really is quite limited due to the rarity of the condition.  The overarching aim is really to develop guidance that is relevant and can be offered in our current clinical practice and is consistent to all patients who have a variant in one of these genes. 

Amanda: You mentioned that many of these inherited cancer conditions are very rare. Is there a need to look internationally or collaborate internationally?  How do you pull some of these things together when there’s so little information?   

Helen: We definitely have found it really helpful to have international collaborations.  Some of these conditions there may be very few patients in the UK who have this condition, so each individual clinician who works in cancer genetics may have only seen one or two patients with the condition than themselves and, therefore, collaborating with international colleagues has been very helpful and we have recently published some guidance for a condition BAP1 tumour predisposition syndrome which increases an individual’s lifetime risk of developing mesothelioma, which is a type of lung cancer, renal cancer and melanomas of the skin and eye.  This is a rare condition, but we worked with European colleagues to develop a set of guidelines advising what surveillance the patient should have, so looking to melanomas, looking for early detection of kidney cancers, so having that international collaboration has been really very helpful because in the UK there are so few cases per centre of individuals who have that condition.    

Amanda: That sounds really helpful.  Rochelle, we know that shared decision-making is so important in healthcare.  How can we make sure that the voices of patients are reflected within these guidelines that were developing and that it’s clear to them what needs to happen for their healthcare?    

Rochelle: I think it’s really important that patients are involved in the development of the guidelines, first of all, and actually within those guidelines there is stuff that talks about that, being about shared decision-making.  A lot of these guidelines are in a language that are quite a clinical language that is not necessarily accessible to patients themselves.  It’s really important that they’re part of the creation of them but also that there are things out there that enable people to understand what are these guidelines about, what do these guidelines actually mean in practice.  When you find out that you have a particular genetic mutation, of course, the first place you probably go is Google.  You find a hell of a lot of information and you find all sorts from different countries and different people and different organisations.  You’re like which is the thing I need to look at, which is the thing that actually tells me what’s going on, which is the thing that really helps me to understand what this actually means for me and what should happen to me?  What is the pathway for me, etc.   

I think we also need to recognise that people have different levels of health literacy as well.  I am someone who can probably navigate my way around a very complex system, which is the NHS, maybe better than other people.  But there are plenty of people out there who this is new people, this is a completely new thing that’s happened to them, a completely new thing to understand.  If you’re not used to being part of health systems and navigating your way around it, it can be quite scary.  What does mutation mean?  What does it mean for me?  What does it mean to my future?  What does it mean for my family?  All this information.  There needs to be something somewhere that talks about this, some sort of lay way and helps people to understand what this means for them and helps them to engage with it.  To some extent, that’s where my organisation was born from, that thing about having somebody who can just talk about it in normal words, in normal terms and normal views of what these guidelines actually do mean.  The fact is they are just guidelines, they don’t tell you this is what you do.  You’re this person, you’re in this circumstance, you do this, it doesn’t.  There’s some ambiguity there that needs to be navigated by the patient and they need support in order to do that. 

Amanda: That’s a great point.  Having previously worked as a genetic counsellor, also seeing patients with inherited cancer conditions, it really strikes you how individual each person’s journey and decisions are.  They’re thinking about all kinds of factors in their life or in their family’s life.  Navigating through that and understanding do I have surgery or do I have screening and how do I make decisions about this is based on my previous experiences and so many other factors.  Having access to different sources of support to help people navigate through that feels incredibly important.   

We’ve been talking a bit about inherited cancers in general, but you’re all here because you’re involved in the CanGene-CanVar programme.  Kelly, could you tell us a bit more about what that is and what he programme is aiming to achieve? 

Kelly: The CanGene-CanVar programme is a five year grant funded by Cancer Research UK.  It involves six different work packages, so lots of experts all around the UK have been allowed to have some dedicated time to work on specific areas where there hasn’t been enough resource put in in the past which has resulted in a real gap between the research and the current findings and actually using that information to benefit patients by bridging the gap and putting those research findings into clinical care.   

My programme is in work package four which is co-designing patient resources which are decision support interventions.  Basically, it’s a website and it can be printed as a booklet and it’s interactive and it’s up to date and it’s personalised to help convey the complicated information about genetic cancer conditions in a way that’s meaningful and patients can understand, and it helps them with their personalised shared decision-making.  The CanGene-CanVar programme is underpinned by the patient reference panel and they’ve been involved, including Rochelle and others, from the conception of the idea of the programme and all the way through with various different activities helping to look at documents as they’re developed, before their finalised, and giving input in focus groups and one-on-one and email conversations.  They’re called upon frequently to share their lived experience and say what’s important to them when they make decisions and that’s really helped to drive the direction of the research and inform the results before they’re published.    

Amanda: That sounds like a really helpful approach to developing something in a way that’s really working very closely with patients and participants.  Rochelle, it sounded like you were involved in that.  Can you tell us a bit about what that was like from your perspective? 

Rochelle: It’s really rewarding, it’s really motivating to be actually one of the patient reps in relation to this.  I don’t want to make my colleagues from the team blush, but it’s just such an inclusive environment where as a patient is really welcomed, really heard, it’s very much a partnership and that’s been really, really important and it makes you feel valued as a patient and actually the importance of the lived experience the patient view has really been prominent in this.  I would say that’s why it’s helped develop such a useful tool, the fact as a patient people are really valuing and taking into account our lived experience, our views, our understanding.  It’s been quite fun in some of the sessions.  There have been some good debates between us and some of the clinicians and it’s been really good and really useful.  I think some of the people who maybe haven’t encountered a patient panel before and engaged with patient’s lived experience have probably learn a lot from it because we are pretty empowered to use our voice in this.  It’s been a really great experience.  

Amanda: I’d love to dig into those debates a bit more.  Kelly, were there things that you changed in the decision aid as a result of some of those discussions or as a result of that input that maybe surprised you?  

Kelly: We have made changes based directly on what we’ve learned from the patients presenting their lived experiences.  They’ve been very open and honest with us.  Like Rochelle, I felt so privileged to be part of this real partnership with the patients.  As a genetic counsellor who had many years of experience in clinical practice before moving into this research role, I’ve been really surprised but also gratified by how much I’ve been able to learn from the patients in a different way because I am sort of taking a step back, I’m there as a researcher and not directly as a clinician looking after someone one-on-one in clinic and just thinking about their specific needs at that time.  But because I’m hearing from people from all different situations, different parts of the UK and other countries and maybe it’s 10/20 years since they had their genetic diagnosis are actually getting a bigger picture of their care needs that we might not have heard about as the clinicians on the ground because they might not be coming back to tell us.  If we haven’t opened the door to that conversation about their personal situation or who’s influencing them or what’s important to them when they make decisions, we just might not have learned about the thing they’re grappling with and they’ve gone off and maybe Googled, they’ve found a patient support group or something else to support them.   

In my research and in my interviews and the focus groups, all of the activities I’ve been learning about the gaps in care, what might be needed to address that.  The decision aid has not been yet ruled into clinical practice but we’re very keen to get it out there and everyone wants it and wants to use it.  We want to make sure that we’ve developed it in a robust patient-centred way as much as we can for us before we put it out.  It will always be updated and go through refinements, but hopefully in the New Year we will be able to let people start using it in the real world situation. 

Amanda: That’s great, I’m sure you’re looking forward to that. 

Helen: I was just going to add to that in terms of the guideline development we’ve had a number of consensus meetings where we’ve made decisions about guidelines, for example, genes that can be predisposed to ovarian cancer and we’ve included patients from the patient reference panel and from other patient groups in those consensus meetings.  Again, as Kelly said, that’s been so helpful because it’s really brought something to those discussions and it is a different perspective than when we see patients in clinic because often we’re seeing them at the point of genetic testing or maybe for their results, but actually that doesn’t give us that overview of the whole patient journey and the whole patient experience.  I think that has been really one of the benefits of this programme and Kelly has been really pioneering the co-design of patient information leaflets, decision aids with patients.  Rather than clinicians designing things for patients that we think that they will understand, it’s actually working with patients from the start to get things right the first time.  It’s been a really great part of this programme. 

Amanda: Rochelle, did you want to add something further here?  

Rochelle: Yes.  I think one of the sessions that we had as a patient and clinician and researcher session that really stood out for me was when we started looking at how do people make decisions. We had academics and researchers who’ve looked at how do people make decisions, talk about the knowledge base and the research base that we have about it.  As a larger group of patients we got together to discuss about how have we made decisions.  It was really interesting because I don’t think I’ve ever reflected on how I made the decision and what came from that in terms of what I did about having my mutation.  Hearing about how other people did as well, that session really does stick in my mind and actually I learnt a lot as a person about decision-making theory but also about myself and reflecting on how I make decisions.  So as a patient involved in this, it’s not always about what I bring to this but actually as a patient rep you get a lot from it, too.  I’ve learnt a lot from the colleagues that I’ve worked with. 

Amanda: That’s fantastic.  It’s really great to hear the careful thought that’s gone into this, a real excellent example that hopefully others can look to.  I think, Kelly, hasn’t your work won an award recently as well? 

Kelly: We as a whole team won an award from the academic health science network and the NHS Confederation, it’s called the Innovate Awards 2023.  This was for excellence in patient and public involvement in transformation and innovation.  Yes, it was a chance to showcase the really positive experience that we’ve had.  I think on all sides we’ve learnt a lot from each other and just to hope to inspire other researchers and clinicians to take this co-design approach with patients because we all benefit from it so much.  We think that the resources, the guidelines, everything that we develop will be better from the start if we work together throughout the project.   

We’re really hoping to encourage others to consider from the beginning of their idea about a research programme or clinical development to bring the patients in right at the start, because they can really help to guide where things go next and then throughout.  Even through to publications being on, committees, being co-chairs, presenting together at conferences, that can all help to really share the experience and the benefits that we get from the partnership. 

Amanda: That’s great, congratulations.  Coming back now to some of the aims of CanGene-CanVar and trying to bridge that gap, as you said, between research and clinical care, I guess that means there are some needs that still aren’t being met that are falling through that gap at the moment.  Helen, from your perspective what are some of those unmet needs that we currently have or areas that are still needing improvement?   

Helen: I think there’s still lots that we have to learn, particularly about individual risks for patients.  We might have patients who all have a pathogenic variant in a certain gene but their risks might be slightly different due to factors that can modify their risk.  Trying to understand some of those risks better so that we can really have much better informed discussions with patients about their lifetime cancer risks I think would be really helpful.  Work package one of the programme is really focussing on that and looking at some of the information we have through national registries and trying to understand risks for specific genes better, which will help our discussions with patients, and then we still need to understand, which is more outside the programme, more how surveillance, so early cancer detection through screenings such as mammograms or ultrasounds for different cancers can help detect cancers early. There’s still lots of information that we need to learn.   

I think Kelly’s decision aid which has been focussed on Lynch Syndrome, I think that can be translated across lots of other genetic conditions, because for each gene there is a different set of decisions.  For some of the genes that we developed clinical guidelines for we might be recommending slightly different management or for some of the genes we’ve recommended maybe a minimum and an extended level of surveillance, particularly for a gene called DICER1 where we’ve offered different options in childhood.  Decision aids would potentially help in some of those other genes building on the work that’s already been developed as part of the programme.  Although the programme is coming to an end in the next year, I think there’s still lots of work to be done in this area.  

Amanda: It really sounds like you’ve all been collectively improving how much this work is worthwhile, so that’s great to hear.  Rochelle, how about for you, are there areas that you would see as unmet needs or areas where we or research can improve to help patients and families with inherited cancers. 

Rochelle: Similar to some of the stuff that Helen was saying, knowing more about what happens when people have different types of treatment, different types of surveillance and monitoring and stuff like that, I think there are things that are evolving all the time.  I think in the end when you think about gaps, there’s nothing that’s going to be written down on paper that says if you have this, do this.  In the end, every single patient is an individual with individual circumstances.  I think until we actually know that if you do this, this happens and this happens, this is going to be your chances of survival if you go through this route.  Even then when you’ve got the chance of survival, that’s literally just a probability, it’s not a binary this will happen or that will happen.  There’s always going to be a need for discussion, there’s always going to be a need for these brilliant genetic counsellors that we have to talk us through some of those complex decisions that we have to make.  I think, yes, we’ll get more information, we’ll get more evidence, we’ll get more understanding of treatments that work best for different people, and we’ll get it out there and we absolutely do need to do that.   

Even when you have all the information you need, even if you made a solid decision, I mean, when I found out I had the mutation immediately I was like, right, that’s it, I’ll have preventative surgery after what happened to my mum.  It was an absolute no-brainer for me.  For other people it might not have been if they were at a different life stage.  I’d had my kids, I didn’t need my ovaries, I didn’t need my womb, it was pretty clear cut.  Even then when I was thinking about the different treatment and when to have that surgery, I got most of my information from bumping into somebody in the ladies’ toilets who has been through it before.  I think there’s always going to be a need in terms of being able to have those conversations to take in all the information you do that and make some sort of informed decision.  What came out of that decision-making workshop and all the other things that we did about probabilities, it’s all just a model.  It’s a model of what might happen.  The thing is, all of these models, they’re all wrong, they just help you maybe make a discussion or a decision that might be right.  You just never know.  I still don’t know if the decisions I made were the right decisions either.  There needs to be that space for people to consider their options, you’re never going to get the definitive answer.   

Amanda: An important message there.  We talk a lot about using digital tools to be able to do things better at scale, better ways to give information, but I think what you’re saying is we can’t replace certain elements of human connection, we can’t underestimate the value of that.  You made a really good point earlier as well about how so many of these decisions have uncertainty and it can be really difficult to navigate the complexities of a health system.  Perhaps even more challenging if you have struggles with health literacy or if you are an underserved group in some way or another.    

Kelly, I think you mentioned that some of your research has also touched on developing information for underserved groups.  Can you tell us a bit more about that? 

Kelly: We recognised that there are many underserved groups that are not represented in research, in literature, and applied for additional funding to do some specific targeted projects in the community.  There were a couple of examples I can mention.  One was inspired by colleagues at the Royal Marsden who made some videos about prostate screening and the had black men and their family members talking about this in a relaxed barber’s shop setting.  Through reaching out into the community I was connected with Lee Townsend from Macmillan who’s been making these barbershop videos around London for the last seven years.  He’s focussed on a number of topics like mental health, vaccination and cancer.  We connected and it was really about making that connection in the community, him as a trusted leader, and having formed partnerships with some of the barbers who opened up their barbershops for filming these sessions and went way beyond that.   

One of them has actually trained as a counsellor himself because he said men are coming for a haircut and actually they have a bald head, they don’t need the haircut, they’re coming actually for the chat.  Because it’s benefitting their mental health and they felt able to open up about topics that they wouldn’t talk about even at home with their family members or with their friends, such as symptoms of cancer, going for cancer screening or presenting for treatment if they were symptomatic.  It’s really powerful.  We’ve actually filmed six videos with black and minority ethnicity patients, talking about their cancer experience and they’ve really both helped others by setting an example that it’s okay to talk about these things.  Also, through the process an added benefit was helping themselves, so it was peer support.  When they came to the barbershop to film their stories, they didn’t need to stay for the whole time but they did stay for the three hours.  They said afterwards how helpful it was just to hear others in a similar situation sharing their stories.  One of them told me he’s got up on stage and shared his cancer journey and he’s been going to these patient groups and talking when he didn’t feel able to do that in the past.  It’s been a great project and we’re going to be adding the videos to the CanGene-CanVar patient decision aid website soon. 

Another thing that we’ve done in the diet and lifestyle section of the website where it talks about things that people might do to lower their chances of getting cancer have partnered with Professor Ranjit Manchanda who had some colleagues in India and made some infographics that specifically depict patients of a South Asian heritage and the types of foods that they might be choosing to give examples of how they might for example try to get more fibre in their diet to lower the chances of getting bowel cancer or trying to eat more fruits and vegetables or drink less alcohol.  It shows images of Indian patients.  What people have told me in my research, my interviews, focus groups, is they tend to go and try to search for something that means something to them, so they’re looking for someone like me.  One of the patients I filmed she said that she had breast cancer as a young black woman and she was only middle-aged women on the websites.  She thought why is this, do black women not get breast cancer or young women like me?  For her to share her story was very brave but also has the potential to help a lot of other people in the community.  

Amanda: That’s really powerful, so understanding those nuances in different cultures or communities or groups is just so crucial to really being able to also develop information or messages or provide care that’s going to really reach those people where they are, I guess. 

This has been a really fantastic conversation.  If we could end with a final question, it would be great to hear from your perspective just one thing that you’d like to see in the next five to ten years when it comes to care for inherited cancer susceptibility conditions.  Helen, let’s start with you? 

Helen: I think that in developing the guidelines one of the things that we’ve had to struggle or grapple with is a lack of evidence and the lack of the data that’s available for some of these conditions.  I’m really hoping that over the next five to ten years that we will see much more data on cancer risks and outcomes of surveillance progress for people who have an inherited predisposition.  Then we can utilise that information to be able to share with patients to enable them to make best decisions about their care.  There’s a number of initiatives that are currently underway thinking about how we might better collect data on patients with inherited cancer predisposition in the UK, through registries, so I am really hoping that we manage to get some useful data that we can then use in our discussions with patients going forward. 

Amanda: Thank you.  Kelly? 

Kelly: I think that over the next five to ten years as awareness and availability of genetic testing continues to increase, we know that there will be more and more families identified who have a higher genetic risk of getting certain cancers.  We can’t replace that personalised counselling that takes place, face-to-face or sometimes telephone and video appointments with a healthcare profession.  So there are more resources needed for the NHS to deliver this.  To compliment that, the patient website decision aid that we have co-designed is one way to help.  What patients tell us they would like, access to a central trusted source of information that’s up to date.  Importantly in genetics it’s very fastmoving, there’s a lot of research, guidelines are changing, and it’s very crucial to have information that’s correct and relevant for people, and also meaningful.  We can only do that by partnering together with patients and co-designing things rather than designing them and asking them afterwards if they’re useful.  It’s a partnership all the way through that we all benefit from.   

As I said earlier, it’s not a one-size-fits-all, decision-making is so personal and shared decision-making is recommended but we don’t always have enough time in clinic to really address all of the issues that the patient might not have even thought about themselves.  Having something like a patient-facing resource website booklet that they can look at in their own time, prepare for their questions that they really want to focus on in clinic, it might help give them the confidence to bring something up that they might not have otherwise.  It’s about a number of different ways of helping to support people.  We’ve identified that there are gaps in care that we could try to help address if we have more resource in future.  Those are my aspirations.  Thank you, Amanda.  

Amanda: Thank you.  And Rochelle, to you? 

Rochelle: I think for me I would like to have as many people as possible to understand or know about their genetic mutation status.  We know people don’t even know about the fact that they may have a genetic mutation that may make them more susceptible to cancers, and we know that even then if you do can you get access to testing to know whether you’ve got it or not.  That is the most important thing.  My mum, if she’d known that some of this was related, if she’d had that awareness that breast and ovarian cancer in your family was related to potential genetic risk, maybe she would have pushed harder to get testing and maybe she wouldn’t have been tested when it’s too late.  In the end, all this knowledge and empowering people with knowledge, whether that be about empowering people with the knowledge that they may have a genetic mutation, there’s a possibility of the genetic mutation, that these things are related and empowering people through the knowledge of knowing their genetic mutation status, all that is something that saves lives.  From my view, it undoubtedly probably has saved my life and so my hope for the future is that we can empower more people like me and we can save more lives.  

Amanda: Thank you for our guests today Dr Helen Hansen, Rochelle Gold and Kelly Kohut.  If you enjoyed today’s episode, we’d love your support.  Please subscribe to The G Word on your favourite podcast app and like, share and rate us wherever you listen.  I’ve been your host, Amanda Pichini.  This podcast was edited by Mark Kendrick at Ventoux Digital and produced by Naimah Callachand.  Thanks for listening.   

 

Rebecca Middleton, Professor Dame Sue Hill and Dr Rich Scott: Transforming the NHS with genomic testing

This year as we celebrated our 10-year annivesary, the NHS celebrated a significant milestone of 75 years. In this episode we reflect on our journey over the last 10 years, including the impact of embedding genomic testing into the NHS, how it all started with the 100,000 Genomes Project, and how patients have influenced the shape of the Genomic Medicine Service today.

Host Rebecca Middleton, Vice Chair of The Participant Panel at Genomics England is joined by Professor Dame Sue Hill, Chief Scientific Officer and Senior Responsible Officer for Genomics in the NHS, and Dr Rich Scott, Interim Chief Executive Officer for Genomics England in this special episode of the G Word.

 

"To date, we’ve had over 1,500 putative diagnostic variants returned to the NHS, so to our NHS genomic laboratory hubs, for further investigation, further discussion with clinical teams. About 80% of those have been returned to clinicians and therefore to patients to, for example, give them a diagnosis or to update the diagnosis that they’ve been given or make treatments available. That is a real positive benefit from that pipeline to individual patients."

 

Listen to the other episodes in our 10-year series:

• Shelley Simmonds, member of the Participant Panel at Genomics England, speaks to Louise Fish, CEO of Genetic Alliance UK, and Amanda Pichini, clinical lead for genetic counselling for Genomics England as they reflect on how the patient journey has changed over the last 10 years for those living with rare conditions.
• Dave McCormick, member of the Participant Panel at Genomics England is joined by Jenny Taylor, a valued member of our research community, and Professor Matt Brown, our Chief Scientific Officer, discussed the last decade of genomic research at Genomics England.

 

Transcript

You can read the transcript below or download it here: Transforming-the-NHS-with-genomic-testing.docx

 

Rebecca: Hello and welcome to the G Word. My name is Rebecca Middleton and I’m the Vice Chair of The Participant Panel at Genomics England. On today’s episode, I’m joined by Professor Dame Sue Hill, Chief Scientific Officer and Senior Responsible Officer for Genomics in the NHS, and Dr Rich Scott, Interim Chief Executive Officer for Genomics England. Today we’ll be reflecting on the last ten years of genomics, including the impact of embedding whole genome sequencing into the NHS, how it all started with the 100,000 Genomes Project, and how patients have influenced the shape of the Genomic Medicine Service today. If you’ve enjoyed today’s episode, we would love your support. Please like, share and rate us on wherever you listen to your podcasts.

Thank you, Sue and Rich, for joining me today as we look back at how genomics has developed in the NHS over the past decade and impacted tens of thousands of lives. It all started with the creation of Genomics England and it’s first groundbreaking initiative, the 100,000 Genomes Project, which sequenced around 85,000 NHS patients affected by rare conditions or cancers and led to groundbreaking insights and discoveries for so many families. I’m one of those rare condition patients and my genome sits in the National Genomics Research Library besides thousands of others. Along with the project, I’ve been on a journey over the past ten years and I’m still hopeful that through time and further scientific discovery, my family and many others will get the answers they need for the future.

Today is a chance to reflect back over the progress of the past ten years and to look forward about what’s next for genomics, for genomic science, the genomic service, and for the patients and families it impacts. Sue, welcome. If we can come to you first, and it’s a very big ask coming up, but can you briefly sum up your critical role in genomics over the past ten years and talk us through how you’ve shaped the service in the NHS to date?

Sue: My role in genomics in the NHS has actually been much longer than ten years, because particularly genetic services have been part of the NHS journey since it was formed in 1948. As Chief Scientific Officer for England, part of my responsibility since I was first in that post in the Department of Health at that time and now subsequently in NHS England, but still with a crosscutting health and social care role, genetics and genomic services actually sit under the remit of the Chief Scientific Officer for England. Shortly after the 100,000 Genomes Project was announced and that the NHS would be a major contributor to the 10,000 Genomes Project, I was asked to lead the NHS contribution to the 100,000 Genomes Project. My role has been both of leading the NHS contribution to the 100,000 Genomes Project, and then as Senior Responsible Officer for Genomics in the NHS in introducing the NHS Genomic Medicine Service to the NHS and its subsequent role in delivery and in supporting research and other initiatives.

Rebecca: Rich, over to you. Ten years ago I believe your role was very different and you were in clinic, so how has it changed over the past decade as genomics has embedded itself into the NHS?

Rich: That’s right. As you say, I’m a doctor by background and ten years ago I was consultant in clinical genetics at Great Ormond Street, where I still practice, I still do one clinic a month, but my role is primarily sat there meeting families with a child normally with some symptoms or some problems which people thought might be those of a rare condition and thinking about how we did that testing. At that time I was beginning to think about how we use in Great Ormond Street some of the newer technologies that were coming along. Using, for example, gene panels to help diagnose children who had epilepsy of early onset. Eight years ago, I joined Genomics England, where I could see the work of Genomics England and the partnership with NHS to deliver the 100,000 Genomes Project was something where at national scale we could do something, which at that stage I was just thinking about within one hospital setting. That’s really changed things for me in clinic, but also my role in that has changed. I joined Genomics England originally as the clinical lead for rare disease, so bringing that specialist clinical expertise to give advice on how we establish the rare disease component of the 100,000 Genomes Project.

More recently, in my role as Chief Medical Officer, I’m actually now as interim CEO thinking about how we’ve made that transition from the learning that we’ve gained through the 100,000 Genomes Project to working in partnership with the NHS and Sue and team to play our role in supporting their NHS Genomic Medicine Service. The next phase, if you like, or questions for us to make sure that we are still thinking in a forward looking way about how genomics can do what we believe it can do to be really there in the mainstream for everyone in terms of healthcare.

Rebecca: And it really has been quite a journey over these past ten years, moving from a research project with 100,000 Genomes Project to a live clinical service and all the challenges that that must bring. Sue, what are you most proud of, what are those challenges that you’ve had to overcome and how do you see genomics medicine service moving forwards so it can help even more families?

Sue: I think in answering your question, first of all, the Genomic Medicine Service is much broader than the whole genome sequence service that is delivered in partnership with Genomics England, and I’ll come back to that. In terms of what I’m most proud of, I think when we started the 100,000 Genomes Project there was a view that we shouldn’t involve the whole of the NHS in recruitment and in feedback to participants. I pushed really hard to have the whole of the NHS involved, recognising that if we were going to enter into a transformative project particularly for the use of cutting edge technologies by whole genome sequencing and the analytics that went alongside that, if we only started with a small number of centres we wouldn’t get the transformation that was required within a whole health system.

I’m really proud of the NHS contribution because the number of patients that were recruited over the period of time where we didn’t start active recruitment until 2013 and then we completed early in 2019, to deliver this from routine care in the NHS in terms of recruitment and then for feedback I think is something that is unsurpassed by many other research projects, let alone research initiatives in genomics across the world. So while this is a world leading project, it’s also I think a world leading contribution from the NHS from its routine care position.

I was also proud myself to be a participant in the 100,000 Genomes Project within the cancer arm of the project and being able to speak at different public events around the benefits of sharing data through the National Genomics Research Library, in that it’s a benefit that is much broader than you as an individual and has the potential to impact on thousands of people.

The other thing I’m most proud of is introducing the NHS Genomic Medicine Service because we still remain in the NHS world leading. Of course, a key part of that is that we have whole genome sequencing now available within routine care, within the NHS for patients with rare and inherited disease and cancer. Obviously not for all of those patients, but for the group of patients that fit within those broad-brush clinical groupings where there is the most need, but also the ability to deliver a diagnosis compared to what we could do from standard of care testing.

I think it’s those two halves for me with myself being a participant and being part of the NGRL right in the middle. Because, of course, from the NHS Genomic Medicine Service, which is what many other countries are grappling with, as soon as you introduce a whole genome sequencing service within a health system, how do you also continue to support research and continue to populate a research database that can be accessible, access is approved and in a safe data environment, how can you continue to support that?

Rebecca: Over to you now, Rich, on what you’re most proud of for yourself, but also for Genomics England and being the custodian of people’s data, that people have given their data through the 100,000 Genomes Project and they continue to give their data through the GMS. If you could pick up also on the research side, so the role that Genomics England has played in the development of the Genomics Medicine Service and the genomics within the NHS, but also in the wider ecosystem as well in terms of driving discovery and driving answers for the many families and for many patients out there who are still looking for those answers.

Rich: I think really there is one word that I come back to quite a lot which is the word together, where the journey that we’ve been on as Genomics England, me playing my role at Genomics England, but all of those involved across the ecosystem, that key partnership that we have with the NHS and with our participants, but also broader than that into the other people involved in delivering a live clinical service now that we support the whole genome element of. Also, collaborators in research, whether that’s in academia or industry, this is a team sport. What I’m proud of most is the impact that we’ve had together and recognising that when this journey started there was a real vision about the potential that genomics could bring in the coming years because of the changes that came. For example, the next generation sequencing technology, but also the changes in ability to hold and analyse data at scale. I think rightly no one would have pretended to know what the journey was.

I think the thing I’m most proud of is that we have navigated that together. In a way, we’ve continued to learn and we’ve learnt from the challenges that we have encountered, whether it’s through delivering the 100,000 Genomes Project or our work since, because there always will be challenges. The reason that we’re so proud of the impact that there has been is because we recognise it’s hard to do. I think that point particularly of linking healthcare and research is absolutely key. That’s something that we’re working with Sue and the teams across the NHS are absolutely committed to and recognising that this is an ongoing learning area. That means learning how we do every element of it, but it also means that marrying clinical care and research is absolutely critical to getting the best outcomes for the system as a whole and for participants/patients individually.

We’ve learnt how to set up a system that works in that way. We’ve worked through the consent models that patients in the NHS receiving routine care are comfortable with. The models of presenting data de-identified for researchers to use for purposes that those participants are comfortable within, as we call it, a trusted research environment, is a model that comes with challenges in terms of the data access for researchers but is one that is really broadly accepted and we can get to work at scale. I think it’s that ongoing learning and that we’ve now I think shaped an approach to genomics across clinical care and research which no one would say is perfect, but we definitely understand that we’ve learnt about a model that we can keep iterating on and, crucially, we’ll keep learning for participants present and future.

So that, as you say, Rebecca, one example of that situation is where families have had a test, whether that’s through 100,000 Genomes Project or more recently through the NHS Genomic Medicine Service, if today’s knowledge can’t find the answer in terms of a rare condition diagnosis, we know that one really important element of that research offer is that researchers will continue to look for answers. If something is found that is relevant, that can be fed back to the clinical laboratories to look at. If there is something that is clinically actionable, that can be reported.

Rebecca: Thank you, Rich. I suppose, Sue, we’ve had a decade of navigation, a decade of learning and a decade of adapting to really take us from the 100,000 Genomes Project to the NHS Genomics Medicine Service. There have been challenges along the way, no less we’ve had COVID to deal with, a global pandemic. What other challenges have you had to overcome to embed a workable world class service within the NHS, how have you navigated that with your partners such as Genomics England?

Sue: What’s been really important is actually understanding the challenges. I see the challenges more in the sense of the transformation that we need to drive rather than them actually being challenges. Some of the transformation that was driven through the 100,000 Genomes Project we’ve actually baked into the Genomic Medicine Service. For example, during the 100,000 Genomes Project we understood the importance of clinical leadership; particularly if genomics was going to be embedded across the NHS for patient benefit, then it would involve more clinical specialties than clinical genetics. Through the 100,000 Genomes Project, we really drove leadership and engagement across multiple clinical specialties.

We also drove this whole model that Rich talked about earlier about data sharing for broader benefit, and that benefit has then transferred over into the Genomic Medicine Service. We also recognise that if we were going to hold genome sequence a number of the processes, technical processes that happen within now our genomic laboratory hubs, needed to be standardised with quality and also external quality assurance at the core. That’s right from taking a sample from a patient, extracting DNA, the sequencing methodology, whatever that is, whether it’s whole genome sequencing of the type of testing within the NHS, so large gene panels, whole exome sequencing, or even smaller gene panels and other types of testing, that had to be consolidated and standardised. When results are returned we needed a standardised approach to results and interpretation. Across all of those areas if we’re trying to drive a national approach as we were in the 100,000 Genomes Project and we’re now in the Genomic Medicine Service is having an external quality assurance process that can look externally at each of those components that has been an important learning from the 100,000 Genomes Project into the Genomic Medicine Service.

A key other element of transformation, and I hope you’ll agree with this, Rebecca, was the involvement of members of the public and also participants. So right through the 100,000 Genomes Projects from Genomics England establishing The Participant Panel, through to the involvement of patients and public throughout the national programme for the 100,000 Genomes Project in NHS England, through to the genomic medicine centres that we created at that time, all of that has now been reproduced in the Genomic Medicine Service. So, patient and public involvement is a key part of the delivery mechanism.

Finally, we’ve had to change and continually adapt and develop the underpinning data and digital infrastructure in the NHS. Initially in the 100,000 Genomes Project we standardised the data that was collected for rare disease. We introduced the use of terms called human phenotype ontology system that enabled individual patients and their presenting characteristics to be classified; that’s continued on into the Genomic Medicine Service. But still more work to do in the 100,000 Genomes Project, we have to get multiple informatic systems to talk to one another. As we moved into the Genomic Medicine Service, we’ve both with Genomics England had to develop the analytical pipeline. We’ve had to develop a system that’s enabled whole genome sequencing, for example, to be ordered and then to be returned after sequencing and the semi-automatic analytical pipeline in Genomics England to generate a report that could then be looked at and interpreted in the genomic laboratory hubs and returned to patients.

What’s been a key part of that has also been the establishment of genomic multidisciplinary team meetings that came out of the 100,000 Genomes Project, but now is embedded into the Genomic Medicine Service. Of course, the difference between the 100,000 Genomes Project contribution and now in the genomic medicine service is to ensure there’s equity of access across the country in terms of the testing that is provided. A key part of the way in which the testing is offered is that introduction of the National Genomic Test Directory that sets out the standardised offer that will be funded by NHS England. That’s across where an inherited disease or cancers, as well as common diseases and some other pharmacogenomic applications.

The challenge always is standardisation, equity of access, and the infrastructure and leadership that makes this happen, together with developing a workforce that is genomically enabled so that it can spread out beyond that clinical genetics specialty into those multiple specialties to make sure that it’s embedded. So remain in terms of some of the challenges around making sure that we change clinical pathways where genomics means that we can do things much earlier on in a patient pathway and get a definitive result and intervene. This is particularly important in cancer, but it’s not just cancer, it’s also in rare disease.

Secondly, it’s about how do we develop the whole of the NHS workforce. We have 1.3 million people that are directly employed by the NHS. There are another 600 that actually are associated with the NHS through the contracts that they hold. It’s a huge task that we still have to undertake to make sure that genomics is available to all. There are two other elements, one we have to continue to take the public with us, and I think we’ve learnt from COVID that the public does understand now the importance of molecular tests. But there’s still more to do as we use genomic information more broadly across the NHS and to drive treatment decisions that might mean that a patient thought they were going to get one cancer drug but they’re going to get another because their genomic mutation says treatment B might be better for them than treatment A. We have and will continue to have a number of ethical issues that will arise as we consider whether it’s some of the research initiatives that are undertaken or whether it’s some of the decisions that might be made within the NHS Genomic Medicine Service or for the use of genomics.

That’s just a few, but it pulls it together from what we’ve learnt from the 100,000 into the GMS, what else the GMS is doing, and what some of the challenges are that remain.

Rebecca: And a great deal has been done. There are a number of key challenges ahead. As you say, it’s been a learning process, it’s been a navigation process, but it’s been driven by the people, by systems, by people, and they have played a critical role and will continue to play a critical role in ensuring the success going forward. I sit as the Vice Chair of Rare Conditions on The Participant Panel. Rich, if I can come to you next, how has the patient voice, how has The Participant Panel but the wider patient voice been heard and how are their view, their needs being reflected in addressing these four big sort of buckets of challenges and how are we learning these lessons going forward thinking of the new projects? For example, the newborn genome project, The Generation Study, could you give us some examples of how that learning is going forward and we’re learning from the past but preparing for the future?

Rich: I think it comes back to one of the really key words here is transparency and transparency in a number of ways. One of those is about the fact that this is a journey we’re all on together. So, one of the things that was there right from the beginning of the 100,000 Genomes Project before I arrived was putting participants absolutely at the centre of project and the design and then in time that came for us in Genomics England wider in terms of our organisational governance. Establishing The Participant Panel on which you’re a co-chair I think was really important for us early on to make sure that participants whose data it is we hold, it’s no one else’s data, it’s our participants’ data, are there driving and at the centre of the decision-making process, for example, through our Access Review Committee around who accesses the data. Participants sit on various of our governance groups and that’s a template which I think is one that people have seen in various fields as working really well. It’s one that Sue has touched on as being looked at and has provided useful input as to how patient and participant involvement has been set up in the Genomic Medicine Service.

I think recognising that much of this is us all collectively finding the right path forward is how we approach every question that we tackle. Sometimes that’s around really very practical questions. So, for example, Rebecca, you will know we often come to you guys about how we phrase a letter that might go out to participants, because recognising that from the inside of an organisation you see things one way but you might not recognise some of the nuances that are really important. Through to thinking about the really important questions around how we should set up access and safeguards around access that are there and, again, having participants sat on our Access Review Committee is crucial. And on to finding our way in new areas where the Newborn Genomes Programme I think is a really nice example where in many ways it’s quite similar to the 100,000 Genomes Project in that it’s a research study and it’s delivered in partnership with the NHS. It’s asking big questions around whether genomics can be used in a particular setting and if so, how could we use it? I think a really critical part of that and one that’s been, as you know, sat in a number of the different strands and in the overall governance for the programme, Rebecca, having participants guide us, whether those people who like yourself are already part of the national genomic research library or whether they’re people who might join the study themselves, or whether they’re people with a different perspective that is important to include, including that engagement work as well as just with the broader public as part of the study is absolutely crucial.

Before we even started the design of the study we set out with a public dialogue around attitudes to do with genome sequencing in newborns jointly with the National Screening Committee to understand where public views were to allow us to do a bit of a deep dive, not just a superficial vox pop view on what’s your attitude to a one-liner question, but really to work with people on understanding some of the nuances here. There’s a lot of nuance in most of the questions that we’re engaging with, and then through the programme into different elements, whether that’s designing the materials for consent or whether it’s understanding how to practically design the process for contacting families or feeding back findings as part of the study, making that part of the process rather than a separate endeavour I think is really crucial.

One of the words that I often hear people use when talking about challenging questions around how we make advantages in medicine is around explaining what people are doing. I actually think that’s a really interesting word which I don’t like. Most of the time this is about dialogue and it’s about discovering together what we are doing and it’s not people sit in with the best of intentions and with great expert knowledge in a closed room to decide what’s the best approach, which is often an easy way to think about how to design a research study, for example, but this needs to be an active process where there’s genuine dialogue and we learn and find our ways together.

Rebecca: Some great examples there, Rich, of how powerful the participant and the patient is in the designing future services for even more patient and participants going forward and ensuring how needs and views are reflected. But, Sue, it doesn’t just happen in Genomics England, there are patients and participants across the GMSAs as well, which is fantastic to see and I sit on the panel at the East GMSA as well. How important was that for you to establish that as part of establishing the Genomics Medicine Service? How important was that for you to ensure that the patient and participant view was there locally as well?

Sue: So, I think we learnt from the 100,000 Genomes Project about the importance of patients and participants being part of the research element of the 100,000 Genomes Project and how that was designed, how the different pathways were put in place. In NHS England the patient is at the centre of everything when we come to our services. In all of our major programmes we have patient representatives, patient for an ongoing discussion with patient groups. This was both building upon what we’d created together with the Genomics England Participant Panel in the 100,000 Genomes Project, but then making sure that it fitted with the new genomic medicine service infrastructure that NHS England commissioned from 2018 onwards. It was making it a key part of that, making sure that coproduction with patients and families and really having a temperature check on an ongoing basis about the experience of patients and families of the genomic medicine service that they were experiencing has been a key component of our infrastructure and how we’ve put the infrastructure together. I always think there is more we can do, there’s more we can do to monitor the experience particularly of services. That having been said, we will continue to drive forward the involvement of patients and families in the future iteration of services, whatever that might look like.

I think if you put patients and families at the centre, that actually helps you determine the type of services that need to be commissioned nationally, the type of concerns that people have of the service and the experience that’s feeding up, but it makes sure that patients and public representatives are part of all the important governance groups. For me, that’s where the conversation needs to happen, it needs to happen both at an individual service level but through all the levels of governance that actually govern a service that is commissioned by the NHS in England for the population that is being served. Even if we haven’t got it totally right, I hope that we’ve got it as a key component of all of the services and set out in commissioning specifications such that it’s a requirement as is having the technology in place to deliver a bunch of genomic tests.

Rebecca: Thank you, Sue. The Genomic Medicine Service is unique in the way that it provides a clinical outcome that is an answer for a patient, and also includes the option of joining the research library which supports further discovery. What are the benefits of this?

Sue: The positive benefit of having the National Genomic Research Library has been through the researchers, scientists who’ve been granted access to the data. To date, we’ve had over 1,500 putative diagnostic variants returned to the NHS, so to our NHS genomic laboratory hubs, for further investigation, further discussion with clinical teams. About 80% of those have been returned to clinicians and therefore to patients to, for example, give them a diagnosis or to update the diagnosis that they’ve been given or make treatments available. That is a real positive benefit from that pipeline to individual patients. But also the evidence that’s generated enables us to evolve the genomic test directory. It enables us to add to genes if new genes have been discovered to the test directory, changes in eligibility criteria, so it’s this continuous evolving learning system. From patients providing samples and their consent for their data to be used to the research library, to the feedback loop back into the NHS that influences both individual patient care, but also the type of tasks that get offered in the genomic medicine service overall.

In conjunction with Genomics England we have also been working on an NHS Genomic Medicine Service research collaborative that’s enabled us to look at the projects and initiatives that industry or other researchers would like to undertake, would like to have access to samples or to data, and to consider that on the basis of would this support the overall national endeavour in genomics, would it add to the National Genomic Research Library and create that learning system? Is it something that we need to do nationally rather than just locally in a research project? It’s making the infrastructure available for those research projects over and above the ones that are part of Genomics England spending review initiatives or NHS England’s Genomic Networks of Excellence. But enabling us to work with industry and researchers to support their research endeavours in a way that is contained and make sure that we create and continue to create and add to the National Genomics Research Library and this overall learnings infrastructure.

Rebecca: And Rich, anything further to add there?

Rich: I think that creation, that word, that learning infrastructure is the key thing there. I think the process that has taken us here where we’ve worked out how to integrate clinical care and research is so valuable, both for the individual patient and participant and also for the system as a whole, often making the choices that allow us to arrive in the direction actually all point together towards doing the same thing. It’s really constructing things around that central vision and I think that is so important.

Rebecca: Thank you so much. We’ve had a whistlestop tour of genomics over the past decade which and improved and informed the lives of thousands of patients and families. But to finish, let’s look forward. What is your one hope for the future of genomics within the NHS? Rich, perhaps we could start with you?

Sue: I think my wish is a relatively simple one, which is that we maintain this momentum that we’ve got and we’ve built together. We’re on a journey and it’s momentum towards genomics being absolutely part of the day-to-day, the mainstream of healthcare so that wherever you are in the country, whoever you are and often potentially without the clinical teams needing to feel they’re doing anything very genomicsy, if you like, genomics is there and bound into the routine care that one has to deliver. I think when we look and we compare ourselves to other countries, because of that link that we’ve made and that partnership between clinical care and research, we are in a really strong position. It’s therefore about maintaining that momentum and getting us to that place where genomics is just a routine part of everyone’s care.

Rebecca: And Sue, finally over to you, what is your one hope for the future?

Sue: What I’m looking for when we put the patient at the centre is that we adopt all of the genomic technologies that would really enable us both to diagnose a genomic cause for patients that of presenting symptoms, or to inform their more preventative or inform their treatment such that genomics becomes part of everyone’s pathway of care in the NHS, and that we really maintain the NHS Genomic Medicine Service as the most advanced service within the world and that it continues to work to populate a National Genomic Research Library with Genomics England such that patients can benefit from ongoing analysis and interpretation of their data. That we really become the leader across the world of this learning ecosystem and we give as many patients as possible a diagnosis and that we inform as many patients as possible treatment pathways. I believe we’re in the next wave of genomics following the discovery of DNA in 1953, and now it’s how do we make genomics available to everyone across where an inherited disease, across cancer, across common and acquired disease and in pharmacogenomics.

Rebecca: Thank you to our guests, Professor Dame Sue Hill and Dr Rich Scott, for joining me today. It’s been great to talk to you and understand the journey so far and what’s ahead for genomic healthcare. Happy 10th birthday, Genomics England, and happy 75th birthday, NHS. Here’s to the next decade of supporting patients and more scientific research and genomic discovery to drive home. If you’d like to hear more like this, please subscribe to the G Word on your favourite podcast app. I’ve been your host, Rebecca Middleton. This podcast was edited by Mark Kendrick at Ventoux Digital and produced by Naimah Callachand. Thank you for listening.

 

Amanda Pichini, Jonathan Roberts and Emma Walters: How can Genetic Counsellors improve care through research?

Genetic Counsellors play an important part in healthcare and research. This Genetic Counsellor Awareness Day we focus on the role genetic counsellors have in research, to help improve care for patients and families.

On this episode of the G Word, Amanda Pichini, Clinical Lead for Genetic Counselling at Genomics England, is joined by Emma Walters, member of the Participant Panel at Genomics England, and Jonathan Roberts, NHS Genetic Counsellor and Clinical Content Developer at Genomics England. Emma shares her personal story and our guests delve into the impact of not having access to genetic counselling. They explore how research priorities can be defined by bringing together both the genetic counsellors and what they're doing in their healthcare roles and the patients themselves and their experiences together.

Johnathan will also be talking to genetic counsellors throughout this episode from the recent World Congress on Genetic Counselling.

You can download the transcript here.

"I think another way in which research can really push that agenda forward is understanding who isn't accessing that [genetic] counselling. So when people get through the door and they experience genetic counselling, often that can be really valuable and they can suddenly start to make sense of all this testing, this family history. They can have a chance to talk about how they feel about it."

 

With special thanks and acknowledgements to World Congress on Genetic Counselling and Wellcome Connecting Science for their contribution to this podcast including Genetic Counsellors, Manisha Chauhan, Alison McEwen, Jared Warde-Jospeh, Nour Chanouha, Jehannine Austin and Kennedy Borle.

Dr Mie Rizig, Sir John Hardy, Candice King and Will Townley: Why is diversity in Parkinson’s research so important?

Unfortunately, please note you may be able to hear some background noise or static during some parts of the recording.

In this episode of the G Word, Candice King, Patient and Public Engagement Manager and Will Townley, Cohorts Manager who both work at the Diverse Data initiative at Genomics England, are joined by Dr Mie Rizig and Sir John Hardy, who both work at University College London (UCL).

This podcast delves into a new paper published by Mie and John in the Lancet Neurology. The paper describes a novel African ancestry Parkinson's disease genetic risk factor. Our guests discuss the need for diversity in genetic research, the key findings from their study, and opportunities for future research in Parkinson's disease.

 

You can read the full transcript here: Diversity-in-Parkinsons-research.docx

 

“The number of people [in genomic research studies] from a white background, Northern Europeans, is about 95%. The number of people from an African background is only 0.2%. This is a significant disparity. When [clinicians] want to translate this into clinical practice, [they] think about: How will be able to test those people sufficiently enough?”

 

The study was conducted by scientists from the UCL Queen Square Institute of Neurology, London, the National Institutes of Health, and the University of Lagos, Nigeria as part of the Global Parkinson's Genomic Program (GP2). GP2 is supported by the Aligning Science Across Parkinson's (ASAP) initiative and implemented by The Michael J. Fox Foundation for Parkinson's Research (MJFF). The paper mainly included cohorts from:

1. The Nigerian Parkinson Disease Research Network, which is part of the International Parkinson's Disease Genomics Consortium (IPDGC) Africa, a collaboration of cohorts across 12 countries to increase the scientific understanding of Parkinson's disease in Africans. IPDGC Africa is funded in part by MJFF.
2. The BLAAC PD study is a cross-sectional study that collects blood or saliva samples and clinical data from Black and African Americans. It is funded by ASAP and implemented by MJFF.
3. Most of the control participants were obtained from 23andMe, a personal genetics company that has assembled a sizable cohort of individuals who have consented to contribute their data for use in various research studies.

Vivienne Parry and David Bick: Which conditions will we look for initially in the Generation Study?

The Newborn Genomes Programme is delivering the Generation Study in partnership with the NHS. The study will explore the possibilities of whole genome sequencing in newborn babies, including to identify a wider range of rare genetic conditions current NHS newborn blood spot test. To do this, we have undertaken significant engagement work to identify the genetic conditions that should be looked for and fed back to families.

In this episode of the G Word, Vivienne Parry, Head of Public Engagement at Genomics England, speaks to David Bick, Principal Clinician for Newborn Genomes Programme at Genomics England. They discuss the process behind determining the provisional list of over 200 conditions caused by genetic changes in more than 500 different genes and how this list may change during the course of the study as new evidence emerges.

 

You can read the transcript here: Conditions-list-for-the-Generation-Study.docx

You can also find a short explainer video explaining the conditions list on our YouTube channel.

Dr Jack Bartram: Can genomics improve our understanding of childhood cancers?

In this episode of the G Word, Naimah Callachand, Head of Product Engagement and Growth at Genomics England, is joined by Dr Jack Bartram, consultant paediatric haematologist at Great Ormond Street Hospital (GOSH) for Children.

Dr Bartram leads on molecular diagnostics within the haematology department at GOSH and has expertise in minimal residual disease in acute lymphoblastic leukaemia. He is currently the clinical lead for haematological malignancy genomics in the NHSE North London genomic laboratory hub and has been responsible for the implementation of advanced genomics and whole genome sequencing into clinical practice at GOSH.

Approximately 2,000 children in the UK receive a childhood cancer diagnosis each year. However, childhood cancers account for a relatively small percentage (less than 1%) of all cancer diagnoses in the UK. This rarity has posed challenges in fully understanding the associated risk factors and underlying causes. In this podcast Dr Bartram discusses how genomics has emerged as a pivotal tool in enhancing our understanding, offering opportunities for precise diagnosis, personalised treatment, and improved screening methods for childhood cancer.

 

You can read the transcript here: Childhood-cancer-awareness.docx 

 

"If I look back on and if I reflect on the last three years, we can probably accurately say for at least a quarter of patients it's [genomics] given us additional information, which has either aided in diagnosis or like I'd say to help re-stratify a patient or potentially reveal a target for a therapy that we didn't know of before."

Will Macken, Nicky Whiffin, Charlotte Durkin and Jamie Ellingford: Early Career Researchers navigating the field of genomics

This week on the G Word, our host Will Macken, is joined by a panel of Early Career Researcher (ECR) representatives to discuss how ECRs can navigate and position themselves within the ever-changing field of genomic research.

Will is a clinician and researcher at the University College London Queen Square Institute of Neurology and Great Ormond Street Hospital. Will is also an ECR representative on the Genomics England Clinical Interpretation Partnership board. In this week's episode he's joined by:

• Nicky Whiffin, Associate Professor and Sir Henry Dale Fellow at the University of Oxford, and Quantitative Genomics representative on the Genomics England Clinical Interpretation Partnership board
• Charlotte Durkin, Head of Programme at the Medical Research Council, and
• Jamie Ellingford, Lead Genome Data Scientist for Rare Disease at Genomics England.

 

"There can be people that just pick up basic skills to analyse the dataset that's in front of them that they've spent months in the wet lab trying to generate. Through to people who are proper software engineers and will be writing unit tests to test every single line of that code. I don't think it really matters where you sit on that continuum as long as it works for you, and it aligns with your future career progressions and what you want to be in the future, essentially."

You can read the transcript here: Early-Career-Researchers.docx

You can find the information on resources, events and support for ECRs mentioned on this podcast on our website.

We've got free-to-attend monthly research seminars, and Research environment training sessions for those who have joined the Genomics England research community - find out more and register for our next sessions here.

Email us if you have any questions: gecip-help@genomicengland.co.uk.

Sarah Justine Kerruish, Hélène Guillaume Pabis, Emilia Molimpakis and Lois Gulliford: How can we overcome bias in healthtech?

In this episode of the G Word, Lois Gulliford, Legal Counsel at Genomics England, is joined by Sarah Justine Kerruish, Chief Strategy Officer at Kheiron Medical, Hélène Guillaume Pabis, Founder and CEO of Wild.AI and Emilia Molimpakis, CEO and Founder of thymia, to discuss how to tackle bias in healthtech.

With growing concerns about the safety of AI prompted by rapid technological advancements, a crucial question arises: how can we guarantee the equitable and unbiased utilisation of AI? Our guests delve into this issue and examine the importance of integrating diverse data sources.

You can read the transcript here: How-can-we-overcome-bias-in-healthtech.docx

 

"I think multimodal is the future, but we have a very special responsibility to be inclusive - to make sure that we are completely rigorous and robust in making sure that women and people from ethnic minorities are represented from the beginning and not as an afterthought."

 

Jamie Ellingford: Genomics 101 - What is a bioinformatician?

In this episode of our explainer podcasts, we’ve asked Jamie Ellingford, Lead Genome Data Scientist for Rare Disease at Genomics England, to explain what bioinformaticians do and how they're involved in the study of genomes, in less than 10 minutes.

You can also find a series of short videos explaining some of the common terms you might encounter about genomics on our YouTube channel.

You can read the transcript here: What-is-a-bioinformatician.docx

If you’ve got any questions, or have any other topics you’d like us to explain, feel free to contact us on info@genomicsengland.co.uk.

Dr Rich Scott and Professor Zornitza Stark: Genomic newborn screening for rare diseases – a review

In this episode of the G Word, Naimah Callachand, Head of Product Marketing at Genomics England, is joined by Dr Rich Scott, Chief Medical Officer and Deputy CEO at Genomics England, and Professor Zornitza Stark, clinical geneticist at the Victorian Clinical Genetic Services in Melbourne, to discuss their recent paper published in the Nature Review's Genetics journal on 'Genomic newborn screening for rare diseases'.

Rich and Zornitza discuss and compare newborn screening practices on a global scale, and delve into the benefits and challenges of incorporating genomic sequencing into newborn screening.

Read the full review paper here. 

You can read the transcript here: Genomic-newborn-screening-for-rare-diseases.docx

 

"We’re just also on the cusp of what feels like a really potential game-changing period in terms of the availability of treatments and interventions for rare conditions."